While most commercially insured patients with asthma have good disease control, some patients may not, according to a recent review of U.S. administrative claims data.

The results of the retrospective analysis, presented at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year, showed some patients with asthma had two or more refills for prescribed systemic corticosteroids (SCS) or short-acting beta agonists (SABA) within a period of 12 months.

“Frequent prescription of systemic corticosteroids and short-acting beta agonists is often indicative of poor asthma disease control,” Randall Brown, MD, MPH, pulmonologist and senior director of Global Respiratory Medical Affairs at Teva Pharmaceuticals in West Chester, Penn., said in a presentation at the meeting. “Understanding the extent of systemic steroid and SABA prescriptions among patients with asthma and the distribution of those prescriptions across disease severity can be useful in determining the degree of disease control.”

Global Initiative for Asthma (GINA) guidelines consider factors such as symptom control and risk of exacerbation when determining asthma severity, but uncontrolled asthma can still be difficult to assess. Dr. Brown and colleagues set out to determine the prevalence of uncontrolled asthma for patients in the IBM/Watson MarketScan U.S. claims database as well as the rate of uncontrolled asthma by GINA classification. In total, 597,955 patients who had an asthma diagnosis between 12 months before or up to 3 months after the index data of filling a SABA prescription were included for analysis. Patients were at least 12 years old with commercial insurance for at least 12 months, and had no other respiratory diseases other than asthma during the 12 months prior to the index date and during the study period.

The researchers then measured each patient’s 2018 GINA classification of asthma severity based on the number of SCS and SABA prescription claims made between January and December 2017. Overall, 54.3% patients were GINA Step 1, 14.6% were Step 2, 10.2% were Step 3, 19.8% were Step 4, and 1.1% were Step 5.

Dr. Brown and colleagues found that, regardless of GINA disease severity, 18.8% of patients filled two or more SCS prescriptions in 1 year, 27.4% filled three or more SABA prescriptions in 1 year, and 38.7% filled two or more SCS and/or three or more SABA prescriptions in 1 year. “[A] large proportion of these patients did not meet the GINA goal of disease control,” Dr. Brown said.

The researchers found 13% of patients with uncontrolled asthma categorized as GINA Step 1, 20% of patients categorized as GINA Step 2, 19% of patients who were GINA Step 3, 31% of patients who were GINA Step 4, and 54% of patients categorized as GINA Step 5 filled two or more two or more SCS prescriptions per year.

The proportion of patients with uncontrolled asthma who filled three or more SABA prescriptions per year included 19% in GINA Step 1, 29% in GINA Step 2, 35% in GINA Step 3, 44% in GINA Step 4, and 57% in GINA Step 5 groups. For patients who filled both two or more SCS and/or three or more SABA prescriptions per year, the proportion of patients with uncontrolled asthma by GINA category was 29% in GINA Step 1, 42% in GINA Step 2, 46% in GINA Step 3, 58% in GINA Step 4, and 76% of patients in GINA Step 5.

While “poor control was seen across all of the GINA disease severity classifications, the greatest proportion of uncontrolled disease was seen at the highest disease severity, which was also true when we used a stricter definition of uncontrolled disease,” Dr. Brown said. When the researchers applied stricter criteria for patients categorized as GINA Step 5, 39% of patients filled three or more SCS, 41% filled four or more SABA, and 60% filled three or more SCS and/or four or more SABA prescriptions over 12 months.

Dr. Brown said that the analysis “highlights the need for improved asthma management strategies within each of the asthma GINA classification steps.”

“While this population that was studied may be reflective of the wider insured U.S. population, the proportions of uncontrolled asthma may be even greater in non–commercially insured patients within the United States,” he said. “Updates to GINA guidelines incorporate recent consensus [and] recent scientific information and therapies, but many patients in the U.S. are not meeting the GINA goal of disease control. Newer paradigms for systemic corticosteroid-free asthma control as a target of disease ‘remission’ are becoming more commonplace. Such changes and goals may lead to improved asthma management strategies and advancement in treatment.”

This study was funded in part by Teva Branded Pharmaceutical Products R&D, which also provided funding for medical writing assistance from Ashfield MedComms. The authors report being employees of Teva Pharmaceuticals.

While most commercially insured patients with asthma have good disease control, some patients may not, according to a recent review of U.S. administrative claims data.

The results of the retrospective analysis, presented at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year, showed some patients with asthma had two or more refills for prescribed systemic corticosteroids (SCS) or short-acting beta agonists (SABA) within a period of 12 months.

“Frequent prescription of systemic corticosteroids and short-acting beta agonists is often indicative of poor asthma disease control,” Randall Brown, MD, MPH, pulmonologist and senior director of Global Respiratory Medical Affairs at Teva Pharmaceuticals in West Chester, Penn., said in a presentation at the meeting. “Understanding the extent of systemic steroid and SABA prescriptions among patients with asthma and the distribution of those prescriptions across disease severity can be useful in determining the degree of disease control.”

Global Initiative for Asthma (GINA) guidelines consider factors such as symptom control and risk of exacerbation when determining asthma severity, but uncontrolled asthma can still be difficult to assess. Dr. Brown and colleagues set out to determine the prevalence of uncontrolled asthma for patients in the IBM/Watson MarketScan U.S. claims database as well as the rate of uncontrolled asthma by GINA classification. In total, 597,955 patients who had an asthma diagnosis between 12 months before or up to 3 months after the index data of filling a SABA prescription were included for analysis. Patients were at least 12 years old with commercial insurance for at least 12 months, and had no other respiratory diseases other than asthma during the 12 months prior to the index date and during the study period.

The researchers then measured each patient’s 2018 GINA classification of asthma severity based on the number of SCS and SABA prescription claims made between January and December 2017. Overall, 54.3% patients were GINA Step 1, 14.6% were Step 2, 10.2% were Step 3, 19.8% were Step 4, and 1.1% were Step 5.

Dr. Brown and colleagues found that, regardless of GINA disease severity, 18.8% of patients filled two or more SCS prescriptions in 1 year, 27.4% filled three or more SABA prescriptions in 1 year, and 38.7% filled two or more SCS and/or three or more SABA prescriptions in 1 year. “[A] large proportion of these patients did not meet the GINA goal of disease control,” Dr. Brown said.

The researchers found 13% of patients with uncontrolled asthma categorized as GINA Step 1, 20% of patients categorized as GINA Step 2, 19% of patients who were GINA Step 3, 31% of patients who were GINA Step 4, and 54% of patients categorized as GINA Step 5 filled two or more two or more SCS prescriptions per year.

The proportion of patients with uncontrolled asthma who filled three or more SABA prescriptions per year included 19% in GINA Step 1, 29% in GINA Step 2, 35% in GINA Step 3, 44% in GINA Step 4, and 57% in GINA Step 5 groups. For patients who filled both two or more SCS and/or three or more SABA prescriptions per year, the proportion of patients with uncontrolled asthma by GINA category was 29% in GINA Step 1, 42% in GINA Step 2, 46% in GINA Step 3, 58% in GINA Step 4, and 76% of patients in GINA Step 5.

While “poor control was seen across all of the GINA disease severity classifications, the greatest proportion of uncontrolled disease was seen at the highest disease severity, which was also true when we used a stricter definition of uncontrolled disease,” Dr. Brown said. When the researchers applied stricter criteria for patients categorized as GINA Step 5, 39% of patients filled three or more SCS, 41% filled four or more SABA, and 60% filled three or more SCS and/or four or more SABA prescriptions over 12 months.

Dr. Brown said that the analysis “highlights the need for improved asthma management strategies within each of the asthma GINA classification steps.”

“While this population that was studied may be reflective of the wider insured U.S. population, the proportions of uncontrolled asthma may be even greater in non–commercially insured patients within the United States,” he said. “Updates to GINA guidelines incorporate recent consensus [and] recent scientific information and therapies, but many patients in the U.S. are not meeting the GINA goal of disease control. Newer paradigms for systemic corticosteroid-free asthma control as a target of disease ‘remission’ are becoming more commonplace. Such changes and goals may lead to improved asthma management strategies and advancement in treatment.”

This study was funded in part by Teva Branded Pharmaceutical Products R&D, which also provided funding for medical writing assistance from Ashfield MedComms. The authors report being employees of Teva Pharmaceuticals.

While most commercially insured patients with asthma have good disease control, some patients may not, according to a recent review of U.S. administrative claims data.

The results of the retrospective analysis, presented at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, held virtually this year, showed some patients with asthma had two or more refills for prescribed systemic corticosteroids (SCS) or short-acting beta agonists (SABA) within a period of 12 months.

“Frequent prescription of systemic corticosteroids and short-acting beta agonists is often indicative of poor asthma disease control,” Randall Brown, MD, MPH, pulmonologist and senior director of Global Respiratory Medical Affairs at Teva Pharmaceuticals in West Chester, Penn., said in a presentation at the meeting. “Understanding the extent of systemic steroid and SABA prescriptions among patients with asthma and the distribution of those prescriptions across disease severity can be useful in determining the degree of disease control.”

Global Initiative for Asthma (GINA) guidelines consider factors such as symptom control and risk of exacerbation when determining asthma severity, but uncontrolled asthma can still be difficult to assess. Dr. Brown and colleagues set out to determine the prevalence of uncontrolled asthma for patients in the IBM/Watson MarketScan U.S. claims database as well as the rate of uncontrolled asthma by GINA classification. In total, 597,955 patients who had an asthma diagnosis between 12 months before or up to 3 months after the index data of filling a SABA prescription were included for analysis. Patients were at least 12 years old with commercial insurance for at least 12 months, and had no other respiratory diseases other than asthma during the 12 months prior to the index date and during the study period.

The researchers then measured each patient’s 2018 GINA classification of asthma severity based on the number of SCS and SABA prescription claims made between January and December 2017. Overall, 54.3% patients were GINA Step 1, 14.6% were Step 2, 10.2% were Step 3, 19.8% were Step 4, and 1.1% were Step 5.

Dr. Brown and colleagues found that, regardless of GINA disease severity, 18.8% of patients filled two or more SCS prescriptions in 1 year, 27.4% filled three or more SABA prescriptions in 1 year, and 38.7% filled two or more SCS and/or three or more SABA prescriptions in 1 year. “[A] large proportion of these patients did not meet the GINA goal of disease control,” Dr. Brown said.

The researchers found 13% of patients with uncontrolled asthma categorized as GINA Step 1, 20% of patients categorized as GINA Step 2, 19% of patients who were GINA Step 3, 31% of patients who were GINA Step 4, and 54% of patients categorized as GINA Step 5 filled two or more two or more SCS prescriptions per year.

The proportion of patients with uncontrolled asthma who filled three or more SABA prescriptions per year included 19% in GINA Step 1, 29% in GINA Step 2, 35% in GINA Step 3, 44% in GINA Step 4, and 57% in GINA Step 5 groups. For patients who filled both two or more SCS and/or three or more SABA prescriptions per year, the proportion of patients with uncontrolled asthma by GINA category was 29% in GINA Step 1, 42% in GINA Step 2, 46% in GINA Step 3, 58% in GINA Step 4, and 76% of patients in GINA Step 5.

While “poor control was seen across all of the GINA disease severity classifications, the greatest proportion of uncontrolled disease was seen at the highest disease severity, which was also true when we used a stricter definition of uncontrolled disease,” Dr. Brown said. When the researchers applied stricter criteria for patients categorized as GINA Step 5, 39% of patients filled three or more SCS, 41% filled four or more SABA, and 60% filled three or more SCS and/or four or more SABA prescriptions over 12 months.

Dr. Brown said that the analysis “highlights the need for improved asthma management strategies within each of the asthma GINA classification steps.”

“While this population that was studied may be reflective of the wider insured U.S. population, the proportions of uncontrolled asthma may be even greater in non–commercially insured patients within the United States,” he said. “Updates to GINA guidelines incorporate recent consensus [and] recent scientific information and therapies, but many patients in the U.S. are not meeting the GINA goal of disease control. Newer paradigms for systemic corticosteroid-free asthma control as a target of disease ‘remission’ are becoming more commonplace. Such changes and goals may lead to improved asthma management strategies and advancement in treatment.”

This study was funded in part by Teva Branded Pharmaceutical Products R&D, which also provided funding for medical writing assistance from Ashfield MedComms. The authors report being employees of Teva Pharmaceuticals.

Wearing a mask to protect against transmission of COVID-19 does not decrease oxygen saturation, according to a new study.

Oxygen saturation did not decline in more than 200 mask-wearing individuals attending an asthma and allergy clinic, regardless of the type of mask they were wearing and how long they had been wearing the mask.

The study was presented in a late breaking poster session by Marisa Hodges, MD, University of Michigan, Ann Arbor, at the virtual annual meeting of the American Academy of Allergy, Asthma, and Immunology.

“In patients with or without asthma, wearing a mask does not decrease your oxygen level,” coauthor Alan P. Baptist, MD, MPH, director of the University of Michigan Comprehensive Asthma Program, said in an interview.

“Some of my asthma patients had called me requesting an exemption from wearing a mask because they feared that their oxygen intake may be affected, and that got me thinking,” said Malika Gupta, MD, assistant professor, division of allergy and immunology, University of Michigan, Ann Arbor, and the study’s lead investigator.

“We say masks are safe, but I couldn’t find any data to support that statement, and we wanted to provide them with evidence, so they could feel comfortable about wearing their masks,” Dr. Gupta added.

The study collected 223 surveys from adult and pediatric patients presenting to the University of Michigan Medicine Allergy Clinic between Sept. 10 and Oct. 23, 2020.

The patients were asked whether they had a diagnosis of asthma, their degree of perceived control if they did have asthma, the type of mask they were wearing, and how long they had been wearing it.

Investigators obtained resting pulse oximetry readings to measure oxygen saturation (SpO₂) from all study participants.

Forty percent of the participants were male, 46% reported having asthma, and 27% were age 19 years or younger.

Overall, the mean SpO₂ was 98% (range, 93%-100%) in both asthma and nonasthma groups.

The study also looked at SpO₂ with 3 different types of masks: fabric, surgical, and N95.

The mean SpO₂ for a fabric mask was 98% (119 patients), for a surgical mask it was also 98% (83 patients), and for the N95 mask it was 99% (3 patients).

Similar results were found with duration of mask use, with the mean SpO₂ 98% in those wearing a mask for 1 hour or less and 99% in those wearing a mask for 1 hour or longer.

People with asthma who reported they were well controlled showed similar mean SpO₂ levels (98%) compared with those who reported they were not well controlled (96.5%)

“No effect on oxygen saturation was noted in any patients, whether they had asthma or not, whether it was well controlled or not, and this was also true regardless of what masks they wore and how long they wore the masks for. So our data reinforce that wearing a mask, whether it be a surgical mask, cloth mask, or N95, is completely safe,” Dr. Baptist said.

“We know wearing a mask is an essential step we can all take to reduce the spread of COVID-19, and we hope these data will give peace of mind to individuals who fear that wearing a mask will adversely affect their oxygen levels,” Dr. Gupta added.

Leonard B. Bacharier, MD, professor of pediatrics and director of the Center for Pediatric Asthma, Monroe Carell Jr. Children’s Hospital at Vanderbilt University Medical Center, Nashville, Tenn., agreed with the investigators’ conclusions.

“The authors found no differences in oxygen saturations between asthmatic and nonasthmatic patients, nor was there a difference based upon mask use or type,” Dr. Bacharier, who was not part of the study, said in an interview.

“These findings provide reassurance that patients, including those with stable asthma, do not experience impaired oxygenation while wearing a mask.”

Dr. Hodges, Dr. Baptist, and Dr. Bacharier have disclosed no relevant financial relationships.

This article was updated 3/11/21.

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

Wearing a mask to protect against transmission of COVID-19 does not decrease oxygen saturation, according to a new study.

Oxygen saturation did not decline in more than 200 mask-wearing individuals attending an asthma and allergy clinic, regardless of the type of mask they were wearing and how long they had been wearing the mask.

The study was presented in a late breaking poster session by Marisa Hodges, MD, University of Michigan, Ann Arbor, at the virtual annual meeting of the American Academy of Allergy, Asthma, and Immunology.

“In patients with or without asthma, wearing a mask does not decrease your oxygen level,” coauthor Alan P. Baptist, MD, MPH, director of the University of Michigan Comprehensive Asthma Program, said in an interview.

“Some of my asthma patients had called me requesting an exemption from wearing a mask because they feared that their oxygen intake may be affected, and that got me thinking,” said Malika Gupta, MD, assistant professor, division of allergy and immunology, University of Michigan, Ann Arbor, and the study’s lead investigator.

“We say masks are safe, but I couldn’t find any data to support that statement, and we wanted to provide them with evidence, so they could feel comfortable about wearing their masks,” Dr. Gupta added.

The study collected 223 surveys from adult and pediatric patients presenting to the University of Michigan Medicine Allergy Clinic between Sept. 10 and Oct. 23, 2020.

The patients were asked whether they had a diagnosis of asthma, their degree of perceived control if they did have asthma, the type of mask they were wearing, and how long they had been wearing it.

Investigators obtained resting pulse oximetry readings to measure oxygen saturation (SpO₂) from all study participants.

Forty percent of the participants were male, 46% reported having asthma, and 27% were age 19 years or younger.

Overall, the mean SpO₂ was 98% (range, 93%-100%) in both asthma and nonasthma groups.

The study also looked at SpO₂ with 3 different types of masks: fabric, surgical, and N95.

The mean SpO₂ for a fabric mask was 98% (119 patients), for a surgical mask it was also 98% (83 patients), and for the N95 mask it was 99% (3 patients).

Similar results were found with duration of mask use, with the mean SpO₂ 98% in those wearing a mask for 1 hour or less and 99% in those wearing a mask for 1 hour or longer.

People with asthma who reported they were well controlled showed similar mean SpO₂ levels (98%) compared with those who reported they were not well controlled (96.5%)

“No effect on oxygen saturation was noted in any patients, whether they had asthma or not, whether it was well controlled or not, and this was also true regardless of what masks they wore and how long they wore the masks for. So our data reinforce that wearing a mask, whether it be a surgical mask, cloth mask, or N95, is completely safe,” Dr. Baptist said.

“We know wearing a mask is an essential step we can all take to reduce the spread of COVID-19, and we hope these data will give peace of mind to individuals who fear that wearing a mask will adversely affect their oxygen levels,” Dr. Gupta added.

Leonard B. Bacharier, MD, professor of pediatrics and director of the Center for Pediatric Asthma, Monroe Carell Jr. Children’s Hospital at Vanderbilt University Medical Center, Nashville, Tenn., agreed with the investigators’ conclusions.

“The authors found no differences in oxygen saturations between asthmatic and nonasthmatic patients, nor was there a difference based upon mask use or type,” Dr. Bacharier, who was not part of the study, said in an interview.

“These findings provide reassurance that patients, including those with stable asthma, do not experience impaired oxygenation while wearing a mask.”

Dr. Hodges, Dr. Baptist, and Dr. Bacharier have disclosed no relevant financial relationships.

This article was updated 3/11/21.

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

Wearing a mask to protect against transmission of COVID-19 does not decrease oxygen saturation, according to a new study.

Oxygen saturation did not decline in more than 200 mask-wearing individuals attending an asthma and allergy clinic, regardless of the type of mask they were wearing and how long they had been wearing the mask.

The study was presented in a late breaking poster session by Marisa Hodges, MD, University of Michigan, Ann Arbor, at the virtual annual meeting of the American Academy of Allergy, Asthma, and Immunology.

“In patients with or without asthma, wearing a mask does not decrease your oxygen level,” coauthor Alan P. Baptist, MD, MPH, director of the University of Michigan Comprehensive Asthma Program, said in an interview.

“Some of my asthma patients had called me requesting an exemption from wearing a mask because they feared that their oxygen intake may be affected, and that got me thinking,” said Malika Gupta, MD, assistant professor, division of allergy and immunology, University of Michigan, Ann Arbor, and the study’s lead investigator.

“We say masks are safe, but I couldn’t find any data to support that statement, and we wanted to provide them with evidence, so they could feel comfortable about wearing their masks,” Dr. Gupta added.

The study collected 223 surveys from adult and pediatric patients presenting to the University of Michigan Medicine Allergy Clinic between Sept. 10 and Oct. 23, 2020.

The patients were asked whether they had a diagnosis of asthma, their degree of perceived control if they did have asthma, the type of mask they were wearing, and how long they had been wearing it.

Investigators obtained resting pulse oximetry readings to measure oxygen saturation (SpO₂) from all study participants.

Forty percent of the participants were male, 46% reported having asthma, and 27% were age 19 years or younger.

Overall, the mean SpO₂ was 98% (range, 93%-100%) in both asthma and nonasthma groups.

The study also looked at SpO₂ with 3 different types of masks: fabric, surgical, and N95.

The mean SpO₂ for a fabric mask was 98% (119 patients), for a surgical mask it was also 98% (83 patients), and for the N95 mask it was 99% (3 patients).

Similar results were found with duration of mask use, with the mean SpO₂ 98% in those wearing a mask for 1 hour or less and 99% in those wearing a mask for 1 hour or longer.

People with asthma who reported they were well controlled showed similar mean SpO₂ levels (98%) compared with those who reported they were not well controlled (96.5%)

“No effect on oxygen saturation was noted in any patients, whether they had asthma or not, whether it was well controlled or not, and this was also true regardless of what masks they wore and how long they wore the masks for. So our data reinforce that wearing a mask, whether it be a surgical mask, cloth mask, or N95, is completely safe,” Dr. Baptist said.

“We know wearing a mask is an essential step we can all take to reduce the spread of COVID-19, and we hope these data will give peace of mind to individuals who fear that wearing a mask will adversely affect their oxygen levels,” Dr. Gupta added.

Leonard B. Bacharier, MD, professor of pediatrics and director of the Center for Pediatric Asthma, Monroe Carell Jr. Children’s Hospital at Vanderbilt University Medical Center, Nashville, Tenn., agreed with the investigators’ conclusions.

“The authors found no differences in oxygen saturations between asthmatic and nonasthmatic patients, nor was there a difference based upon mask use or type,” Dr. Bacharier, who was not part of the study, said in an interview.

“These findings provide reassurance that patients, including those with stable asthma, do not experience impaired oxygenation while wearing a mask.”

Dr. Hodges, Dr. Baptist, and Dr. Bacharier have disclosed no relevant financial relationships.

This article was updated 3/11/21.

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

And then there were three. The U.S. Food and Drug Administration (FDA) on Feb. 27 granted emergency use authorization (EUA) to the Ad26.COV2.S vaccine from Janssen/Johnson & Johnson (J&J) for people 18 and older after reviewing its safety and efficacy data.

More vaccine availability at a time of high demand and limited supply could help officials vaccinate more Americans, more quickly. In addition, the J&J vaccine offers one-dose convenience and storage at conventional refrigeration temperatures.

Initial reactions to the EUA for the J&J vaccine have been positive.

“The advantages of having a third vaccine, especially one that is a single shot and can be stored without special refrigeration requirements, will be a major contribution in getting the general public vaccinated sooner, both in the U.S. and around the world,” Phyllis Tien, MD, professor of medicine in the division of infectious diseases at the University of California, San Francisco, told Medscape Medical News.

“It’s great news. We have yet a third vaccine that is highly effective at preventing COVID, and even more effective at preventing severe COVID,” said Paul Goepfert, MD. It’s a “tremendous boon for our country and other countries as well.”

“This vaccine has also been shown to be effective against the B.1.351 strain that was first described in South Africa,” added Dr. Goepfert, director of the Alabama Vaccine Research Clinic and infectious disease specialist at the University of Alabama at Birmingham.

The EUA “is indeed exciting news,” Colleen Kraft, MD, associate chief medical officer at Emory University Hospital and associate professor at Emory University School of Medicine in Atlanta, said during a February 25 media briefing.

One recent concern centers on people aged 60 years and older. Documents the FDA released earlier this week suggest a lower efficacy, 42%, for the J&J immunization among people in this age group with certain relevant comorbidities. In contrast, without underlying conditions like heart disease or diabetes, efficacy in this cohort was 72%.

The more the merrier

The scope and urgency of the COVID-19 pandemic necessitates as many protective measures as possible, said Raj Shah, MD, geriatrician, and associate professor of family medicine and codirector of the Center for Community Health Equity at Rush University in Chicago.

“Trying to vaccinate as many individuals living in the United States to prevent the spread of COVID is such a big project that no one company or one vaccine was going to be able to ramp up fast enough on its own,” Dr. Shah told Medscape Medical News.“This has been the hope for us,” he added, “to get to multiple vaccines with slightly different properties that will provide more options.”

Experience with the J&J vaccine so far suggests reactions are less severe. “The nice thing about the Johnson and Johnson [vaccine] is that it definitely has less side effects,” Dr. Kraft said.

On the other hand, low-grade fever, chills, or fatigue after vaccination can be considered a positive because they can reflect how well the immune system is responding, she added.

One and done?

Single-dose administration could be more than a convenience — it could also help clinicians vaccinate members of underserved communities and rural locations, where returning for a second dose could be more difficult for some people.

“In a controlled setting, in a clinical trial, we do a lot to make sure people get all the treatment they need,” Dr. Shah said. “We’re not seeing it right now, but we’re always worried when we have more than one dose that has to be administered, that some people will drop off and not come back for the second vaccine.”

This group could include the needle-phobic, he added. “For them, having it done once alleviates a lot of the anxiety.”

Looking beyond the numbers

The phase 3 ENSEMBLE study of the J&J vaccine revealed a 72% efficacy for preventing moderate-to-severe COVID-19 among U.S. participants. In contrast, researchers reported 94% to 95% efficacy for the Pfizer/BioNTech and Moderna vaccines.

However, experts agreed that focusing solely on these numbers can miss more important points. For example, no participants who received the J&J vaccine in the phase 3 trial died from COVID-19-related illness. There were five such deaths in the placebo cohort.

“One of the things that these vaccines do very well is they minimize severe disease,” Dr. Kraft said. “As somebody that has spent an inordinate time in the hospital taking care of patients with severe disease from COVID, this is very much a welcome addition to our armamentarium to fight this virus.”

“If you can give something that prevents people from dying, that is a true path to normalcy,” Dr. Goepfert added.

More work to do

“The demand is strong from all groups right now. We just have to work on getting more vaccines out there,” Dr. Shah said.

“We are at a point in this country where we are getting better with the distribution of the vaccine,” he added, “but we are nowhere close to achieving that distribution of vaccines to get to everybody.”

Dr. Goepfert, Dr. Shah, and Dr. Kraft disclosed no relevant financial relationships. Dr. Tien received support from Johnson & Johnson to conduct the J&J COVID-19 vaccine trial in the San Francisco VA Health Care System.

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

And then there were three. The U.S. Food and Drug Administration (FDA) on Feb. 27 granted emergency use authorization (EUA) to the Ad26.COV2.S vaccine from Janssen/Johnson & Johnson (J&J) for people 18 and older after reviewing its safety and efficacy data.

More vaccine availability at a time of high demand and limited supply could help officials vaccinate more Americans, more quickly. In addition, the J&J vaccine offers one-dose convenience and storage at conventional refrigeration temperatures.

Initial reactions to the EUA for the J&J vaccine have been positive.

“The advantages of having a third vaccine, especially one that is a single shot and can be stored without special refrigeration requirements, will be a major contribution in getting the general public vaccinated sooner, both in the U.S. and around the world,” Phyllis Tien, MD, professor of medicine in the division of infectious diseases at the University of California, San Francisco, told Medscape Medical News.

“It’s great news. We have yet a third vaccine that is highly effective at preventing COVID, and even more effective at preventing severe COVID,” said Paul Goepfert, MD. It’s a “tremendous boon for our country and other countries as well.”

“This vaccine has also been shown to be effective against the B.1.351 strain that was first described in South Africa,” added Dr. Goepfert, director of the Alabama Vaccine Research Clinic and infectious disease specialist at the University of Alabama at Birmingham.

The EUA “is indeed exciting news,” Colleen Kraft, MD, associate chief medical officer at Emory University Hospital and associate professor at Emory University School of Medicine in Atlanta, said during a February 25 media briefing.

One recent concern centers on people aged 60 years and older. Documents the FDA released earlier this week suggest a lower efficacy, 42%, for the J&J immunization among people in this age group with certain relevant comorbidities. In contrast, without underlying conditions like heart disease or diabetes, efficacy in this cohort was 72%.

The more the merrier

The scope and urgency of the COVID-19 pandemic necessitates as many protective measures as possible, said Raj Shah, MD, geriatrician, and associate professor of family medicine and codirector of the Center for Community Health Equity at Rush University in Chicago.

“Trying to vaccinate as many individuals living in the United States to prevent the spread of COVID is such a big project that no one company or one vaccine was going to be able to ramp up fast enough on its own,” Dr. Shah told Medscape Medical News.“This has been the hope for us,” he added, “to get to multiple vaccines with slightly different properties that will provide more options.”

Experience with the J&J vaccine so far suggests reactions are less severe. “The nice thing about the Johnson and Johnson [vaccine] is that it definitely has less side effects,” Dr. Kraft said.

On the other hand, low-grade fever, chills, or fatigue after vaccination can be considered a positive because they can reflect how well the immune system is responding, she added.

One and done?

Single-dose administration could be more than a convenience — it could also help clinicians vaccinate members of underserved communities and rural locations, where returning for a second dose could be more difficult for some people.

“In a controlled setting, in a clinical trial, we do a lot to make sure people get all the treatment they need,” Dr. Shah said. “We’re not seeing it right now, but we’re always worried when we have more than one dose that has to be administered, that some people will drop off and not come back for the second vaccine.”

This group could include the needle-phobic, he added. “For them, having it done once alleviates a lot of the anxiety.”

Looking beyond the numbers

The phase 3 ENSEMBLE study of the J&J vaccine revealed a 72% efficacy for preventing moderate-to-severe COVID-19 among U.S. participants. In contrast, researchers reported 94% to 95% efficacy for the Pfizer/BioNTech and Moderna vaccines.

However, experts agreed that focusing solely on these numbers can miss more important points. For example, no participants who received the J&J vaccine in the phase 3 trial died from COVID-19-related illness. There were five such deaths in the placebo cohort.

“One of the things that these vaccines do very well is they minimize severe disease,” Dr. Kraft said. “As somebody that has spent an inordinate time in the hospital taking care of patients with severe disease from COVID, this is very much a welcome addition to our armamentarium to fight this virus.”

“If you can give something that prevents people from dying, that is a true path to normalcy,” Dr. Goepfert added.

More work to do

“The demand is strong from all groups right now. We just have to work on getting more vaccines out there,” Dr. Shah said.

“We are at a point in this country where we are getting better with the distribution of the vaccine,” he added, “but we are nowhere close to achieving that distribution of vaccines to get to everybody.”

Dr. Goepfert, Dr. Shah, and Dr. Kraft disclosed no relevant financial relationships. Dr. Tien received support from Johnson & Johnson to conduct the J&J COVID-19 vaccine trial in the San Francisco VA Health Care System.

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

And then there were three. The U.S. Food and Drug Administration (FDA) on Feb. 27 granted emergency use authorization (EUA) to the Ad26.COV2.S vaccine from Janssen/Johnson & Johnson (J&J) for people 18 and older after reviewing its safety and efficacy data.

More vaccine availability at a time of high demand and limited supply could help officials vaccinate more Americans, more quickly. In addition, the J&J vaccine offers one-dose convenience and storage at conventional refrigeration temperatures.

Initial reactions to the EUA for the J&J vaccine have been positive.

“The advantages of having a third vaccine, especially one that is a single shot and can be stored without special refrigeration requirements, will be a major contribution in getting the general public vaccinated sooner, both in the U.S. and around the world,” Phyllis Tien, MD, professor of medicine in the division of infectious diseases at the University of California, San Francisco, told Medscape Medical News.

“It’s great news. We have yet a third vaccine that is highly effective at preventing COVID, and even more effective at preventing severe COVID,” said Paul Goepfert, MD. It’s a “tremendous boon for our country and other countries as well.”

“This vaccine has also been shown to be effective against the B.1.351 strain that was first described in South Africa,” added Dr. Goepfert, director of the Alabama Vaccine Research Clinic and infectious disease specialist at the University of Alabama at Birmingham.

The EUA “is indeed exciting news,” Colleen Kraft, MD, associate chief medical officer at Emory University Hospital and associate professor at Emory University School of Medicine in Atlanta, said during a February 25 media briefing.

One recent concern centers on people aged 60 years and older. Documents the FDA released earlier this week suggest a lower efficacy, 42%, for the J&J immunization among people in this age group with certain relevant comorbidities. In contrast, without underlying conditions like heart disease or diabetes, efficacy in this cohort was 72%.

The more the merrier

The scope and urgency of the COVID-19 pandemic necessitates as many protective measures as possible, said Raj Shah, MD, geriatrician, and associate professor of family medicine and codirector of the Center for Community Health Equity at Rush University in Chicago.

“Trying to vaccinate as many individuals living in the United States to prevent the spread of COVID is such a big project that no one company or one vaccine was going to be able to ramp up fast enough on its own,” Dr. Shah told Medscape Medical News.“This has been the hope for us,” he added, “to get to multiple vaccines with slightly different properties that will provide more options.”

Experience with the J&J vaccine so far suggests reactions are less severe. “The nice thing about the Johnson and Johnson [vaccine] is that it definitely has less side effects,” Dr. Kraft said.

On the other hand, low-grade fever, chills, or fatigue after vaccination can be considered a positive because they can reflect how well the immune system is responding, she added.

One and done?

Single-dose administration could be more than a convenience — it could also help clinicians vaccinate members of underserved communities and rural locations, where returning for a second dose could be more difficult for some people.

“In a controlled setting, in a clinical trial, we do a lot to make sure people get all the treatment they need,” Dr. Shah said. “We’re not seeing it right now, but we’re always worried when we have more than one dose that has to be administered, that some people will drop off and not come back for the second vaccine.”

This group could include the needle-phobic, he added. “For them, having it done once alleviates a lot of the anxiety.”

Looking beyond the numbers

The phase 3 ENSEMBLE study of the J&J vaccine revealed a 72% efficacy for preventing moderate-to-severe COVID-19 among U.S. participants. In contrast, researchers reported 94% to 95% efficacy for the Pfizer/BioNTech and Moderna vaccines.

However, experts agreed that focusing solely on these numbers can miss more important points. For example, no participants who received the J&J vaccine in the phase 3 trial died from COVID-19-related illness. There were five such deaths in the placebo cohort.

“One of the things that these vaccines do very well is they minimize severe disease,” Dr. Kraft said. “As somebody that has spent an inordinate time in the hospital taking care of patients with severe disease from COVID, this is very much a welcome addition to our armamentarium to fight this virus.”

“If you can give something that prevents people from dying, that is a true path to normalcy,” Dr. Goepfert added.

More work to do

“The demand is strong from all groups right now. We just have to work on getting more vaccines out there,” Dr. Shah said.

“We are at a point in this country where we are getting better with the distribution of the vaccine,” he added, “but we are nowhere close to achieving that distribution of vaccines to get to everybody.”

Dr. Goepfert, Dr. Shah, and Dr. Kraft disclosed no relevant financial relationships. Dr. Tien received support from Johnson & Johnson to conduct the J&J COVID-19 vaccine trial in the San Francisco VA Health Care System.

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

An FDA advisory panel lent their support Feb. 26 to a rapid clearance for Janssen/Johnson & Johnson’s COVID-19 vaccine.

The Food and Drug Administration (FDA) is expected to quickly provide an emergency use authorization (EUA) for the vaccine following the recommendation by the panel. The FDA’s Vaccines and Related Biological Products Advisory Committee voted 22-0 on this question: Based on the totality of scientific evidence available, do the benefits of the Johnson & Johnson COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?

The Johnson & Johnson vaccine is expected to offer more convenient dosing and be easier to distribute than the two rival products already available in the United States. Janssen’s vaccine is intended to be given in a single dose. In December, the FDA granted EUAs for the Pfizer/BioNTech and Moderna COVID-19 vaccines, which are each two-dose regimens.

Johnson & Johnson’s vaccine can be stored for at least 3 months at normal refrigerator temperatures of 2°C to 8°C (36°F to 46°F). Its shipping and storage fits into the existing medical supply infrastructure, the company said in its briefing materials for the FDA advisory committee meeting. In contrast, Pfizer’s vaccine is stored in ultracold freezers at temperatures between -80°C and -60°C (-112°F and -76°F), according to the Centers for Disease Control and Prevention. Moderna’s vaccine may be stored in a freezer between -25°C and -15°C (-13°F and 5°F).

But FDA advisers focused more in their deliberations on concerns about Janssen’s vaccine, including emerging reports of allergic reactions.

The advisers also discussed how patients might respond to the widely reported gap between Johnson & Johnson’s topline efficacy rates compared with rivals. The company’s initial unveiling last month of key results for its vaccine caused an initial wave of disappointment, with its overall efficacy against moderate-to-severe COVID-19 28 days postvaccination first reported at about 66% globally. By contrast, results for the Pfizer and Moderna vaccines suggest they have efficacy rates of 95% and 94%.

But in concluding, the advisers spoke of the Janssen vaccine as a much-needed tool to address the COVID-19 pandemic. The death toll in the United States attributed to the virus has reached 501,414, according to the World Health Organization.

“Despite the concerns that were raised during the discussion. I think what we have to keep in mind is that we’re still in the midst of this deadly pandemic,” said FDA adviser Archana Chatterjee, MD, PhD, from Rosalind Franklin University. “There is a shortage of vaccines that are currently authorized, and I think authorization of this vaccine will help meet the needs at the moment.”

The FDA is not bound to accept the recommendations of its advisers, but it often does so.

Anaphylaxis case

FDA advisers raised only a few questions for Johnson & Johnson and FDA staff ahead of their vote. The committee’s deliberations were less contentious and heated than had been during its December reviews of the Pfizer and Moderna vaccines. In those meetings, the panel voted 17-4, with one abstention, in favor of Pfizer’s vaccine and  20-0, with one abstention, on the Moderna vaccine.

“We are very comfortable now with the procedure, as well as the vaccines,” said Arnold Monto, MD, after the Feb. 26 vote on the Janssen vaccine. Dr. Monto, from the University of Michigan School of Public Health in Ann Arbor, has served as the chairman of the FDA panel through its review of all three COVID-19 vaccines.

Among the issues noted in the deliberations was the emergence of a concern about anaphylaxis with the vaccine.

This serious allergic reaction has been seen in people who have taken the Pfizer and Moderna vaccines. Before the week of the panel meeting, though, there had not been reports of anaphylaxis with the Johnson & Johnson vaccine, said Macaya Douoguih, MD, MPH, head of clinical development and medical affairs for Janssen/ Johnson & Johnson’s vaccines division.

However, on February 24, Johnson & Johnson received preliminary reports about two cases of severe allergic reaction from an open-label study in South Africa, with one of these being anaphylaxis, Dr. Douoguih said. The company will continue to closely monitor for these events as outlined in their pharmacovigilance plan, Dr. Douoguih said.

Federal health officials have sought to make clinicians aware of the rare risk for anaphylaxis with COVID vaccines, while reminding the public that this reaction can be managed.

The FDA had Tom Shimabukuro, MD, MPH, MBA, from the CDC, give an update on postmarketing surveillance for the Pfizer and Moderna vaccines as part of the review of the Johnson & Johnson application. Dr. Shimabukuro and CDC colleagues published a report in JAMA on February 14 that looked at an anaphylaxis case reported connected with COVID vaccines between December 14, 2020, and January 18, 2021.

The CDC identified 66 case reports received that met Brighton Collaboration case definition criteria for anaphylaxis (levels 1, 2, or 3): 47 following Pfizer/BioNTech vaccine, for a reporting rate of 4.7 cases/million doses administered, and 19 following Moderna vaccine, for a reporting rate of 2.5 cases/million doses administered, Dr. Shimabukuro and CDC colleagues wrote.

The CDC has published materials to help clinicians prepare for the possibility of this rare event, Dr. Shimabukuro told the FDA advisers.

“The take-home message here is that these are rare events and anaphylaxis, although clinically serious, is treatable,” Dr. Shimabukuro said.

At the conclusion of the meeting, FDA panelist Patrick Moore, MD, MPH, from the University of Pittsburgh in Pennsylvania, stressed the need to convey to the public that the COVID vaccines appear so far to be safe. Many people earlier had doubts about how the FDA could both safely and quickly review the applications for EUAs for these products.

“As of February 26, things are looking good. That could change tomorrow,” Dr. Moore said. But “this whole EUA process does seem to have worked, despite my own personal concerns about it.”

No second-class vaccines

The Johnson & Johnson vaccine, known as Ad26.COV2.S, is composed of a recombinant, replication-incompetent human adenovirus type 26 (Ad26) vector. It’s intended to encode a stabilized form of SARS-CoV-2 spike (S) protein. The Pfizer and Moderna vaccines use a different mechanism. They rely on mRNA.

The FDA advisers also discussed how patients might respond to the widely reported gap between Janssen’s topline efficacy rates compared with rivals. They urged against people parsing study details too finely and seeking to pick and choose their shots.

“It’s important that people do not think that one vaccine is better than another,” said FDA adviser H. Cody Meissner, MD, from Tufts University School of Medicine in Boston.

Dr. Monto agreed, noting that many people in the United States are still waiting for their turn to get COVID vaccines because of the limited early supply.

Trying to game the system to get one vaccine instead of another would not be wise. “In this environment, whatever you can get, get,” Dr. Monto said.

During an open public hearing, Sarah Christopherson, policy advocacy director of the National Women’s Health Network, said that press reports are fueling a damaging impression in the public that there are “first and second-class” vaccines.

“That has the potential to exacerbate existing mistrust” in vaccines, she said. “Public health authorities must address these perceptions head on.”

She urged against attempts to compare the Janssen vaccine to others, noting the potential effects of emerging variants of the virus.

“It’s difficult to make an apples-to-apples comparison between vaccines,” she said.

Johnson & Johnson’s efficacy results, which are lower than those of the mRNA vaccines, may be a reflection of the ways in which SARS-Co-V-2 is mutating and thus becoming more of a threat, according to the company. A key study of the new vaccine, involving about 44,000 people, coincided with the emergence of new SARS-CoV-2 variants, which were emerging in some of the countries where the pivotal COV3001 study was being conducted, the company said.

At least 14 days after vaccination, the Johnson & Johnson COVID vaccine efficacy (95% confidence interval) was 72.0% (58.2, 81.7) in the United States, 68.1% (48.8, 80.7) in Brazil, and 64.0% (41.2, 78.7) in South Africa.

Weakened standards?

Several researchers called on the FDA to maintain a critical attitude when assessing Johnson & Johnson’s application for the EUA, warning of a potential for a permanent erosion of agency rules due to hasty action on COVID vaccines.

They raised concerns about the FDA demanding too little in terms of follow-up studies on COVID vaccines and with persisting murkiness resulting in attempts to determine how well these treatments work beyond the initial study period.

“I worry about FDA lowering its approval standards,” said Peter Doshi, PhD, from The BMJ and a faculty member at the University of Maryland School of Medicine in Baltimore, during an open public hearing at the meeting.

“There’s a real urgency to stand back right now and look at the forest here, as well as the trees, and I urge the committee to consider the effects FDA decisions may have on the entire regulatory approval process,” Dr. Doshi said.

Dr. Doshi asked why Johnson & Johnson did not seek a standard full approval — a biologics license application (BLA) — instead of aiming for the lower bar of an EUA. The FDA already has allowed wide distribution of the Pfizer/BioNTech and Moderna vaccines through EUAs. That removes the sense of urgency that FDA faced last year in his view.

The FDA’s June 2020 guidance on the development of COVID vaccines had asked drugmakers to plan on following participants in COVID vaccine trials for “ideally at least one to two years.” Yet people who got placebo in Moderna and Pfizer trials already are being vaccinated, Dr. Doshi said. And Johnson & Johnson said in its presentation to the FDA that if the Ad26.COV2.S vaccine were granted an EUA, the COV3001 study design would be amended to “facilitate cross-over of placebo participants in all participating countries to receive one dose of active study vaccine as fast as operationally feasible.”

“I’m nervous about the prospect of there never being a COVID vaccine that meets the FDA’s approval standard” for a BLA instead of the more limited EUA, Dr. Doshi said.

Diana Zuckerman, PhD, president of the nonprofit National Center for Health Research, noted that the FDA’s subsequent guidance tailored for EUAs for COVID vaccines “drastically shortened” the follow-up time to a median of 2 months. Dr. Zuckerman said that a crossover design would be “a reasonable compromise, but only if the placebo group has at least 6 months of data.” Dr. Zuckerman opened her remarks in the open public hearing by saying she had inherited Johnson & Johnson stock, so was speaking at the meeting against her own financial interest.

“As soon as a vaccine is authorized, we start losing the placebo group. If FDA lets that happen, that’s a huge loss for public health and a huge loss of information about how we can all stay safe,” Dr. Zuckerman said.



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

An FDA advisory panel lent their support Feb. 26 to a rapid clearance for Janssen/Johnson & Johnson’s COVID-19 vaccine.

The Food and Drug Administration (FDA) is expected to quickly provide an emergency use authorization (EUA) for the vaccine following the recommendation by the panel. The FDA’s Vaccines and Related Biological Products Advisory Committee voted 22-0 on this question: Based on the totality of scientific evidence available, do the benefits of the Johnson & Johnson COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?

The Johnson & Johnson vaccine is expected to offer more convenient dosing and be easier to distribute than the two rival products already available in the United States. Janssen’s vaccine is intended to be given in a single dose. In December, the FDA granted EUAs for the Pfizer/BioNTech and Moderna COVID-19 vaccines, which are each two-dose regimens.

Johnson & Johnson’s vaccine can be stored for at least 3 months at normal refrigerator temperatures of 2°C to 8°C (36°F to 46°F). Its shipping and storage fits into the existing medical supply infrastructure, the company said in its briefing materials for the FDA advisory committee meeting. In contrast, Pfizer’s vaccine is stored in ultracold freezers at temperatures between -80°C and -60°C (-112°F and -76°F), according to the Centers for Disease Control and Prevention. Moderna’s vaccine may be stored in a freezer between -25°C and -15°C (-13°F and 5°F).

But FDA advisers focused more in their deliberations on concerns about Janssen’s vaccine, including emerging reports of allergic reactions.

The advisers also discussed how patients might respond to the widely reported gap between Johnson & Johnson’s topline efficacy rates compared with rivals. The company’s initial unveiling last month of key results for its vaccine caused an initial wave of disappointment, with its overall efficacy against moderate-to-severe COVID-19 28 days postvaccination first reported at about 66% globally. By contrast, results for the Pfizer and Moderna vaccines suggest they have efficacy rates of 95% and 94%.

But in concluding, the advisers spoke of the Janssen vaccine as a much-needed tool to address the COVID-19 pandemic. The death toll in the United States attributed to the virus has reached 501,414, according to the World Health Organization.

“Despite the concerns that were raised during the discussion. I think what we have to keep in mind is that we’re still in the midst of this deadly pandemic,” said FDA adviser Archana Chatterjee, MD, PhD, from Rosalind Franklin University. “There is a shortage of vaccines that are currently authorized, and I think authorization of this vaccine will help meet the needs at the moment.”

The FDA is not bound to accept the recommendations of its advisers, but it often does so.

Anaphylaxis case

FDA advisers raised only a few questions for Johnson & Johnson and FDA staff ahead of their vote. The committee’s deliberations were less contentious and heated than had been during its December reviews of the Pfizer and Moderna vaccines. In those meetings, the panel voted 17-4, with one abstention, in favor of Pfizer’s vaccine and  20-0, with one abstention, on the Moderna vaccine.

“We are very comfortable now with the procedure, as well as the vaccines,” said Arnold Monto, MD, after the Feb. 26 vote on the Janssen vaccine. Dr. Monto, from the University of Michigan School of Public Health in Ann Arbor, has served as the chairman of the FDA panel through its review of all three COVID-19 vaccines.

Among the issues noted in the deliberations was the emergence of a concern about anaphylaxis with the vaccine.

This serious allergic reaction has been seen in people who have taken the Pfizer and Moderna vaccines. Before the week of the panel meeting, though, there had not been reports of anaphylaxis with the Johnson & Johnson vaccine, said Macaya Douoguih, MD, MPH, head of clinical development and medical affairs for Janssen/ Johnson & Johnson’s vaccines division.

However, on February 24, Johnson & Johnson received preliminary reports about two cases of severe allergic reaction from an open-label study in South Africa, with one of these being anaphylaxis, Dr. Douoguih said. The company will continue to closely monitor for these events as outlined in their pharmacovigilance plan, Dr. Douoguih said.

Federal health officials have sought to make clinicians aware of the rare risk for anaphylaxis with COVID vaccines, while reminding the public that this reaction can be managed.

The FDA had Tom Shimabukuro, MD, MPH, MBA, from the CDC, give an update on postmarketing surveillance for the Pfizer and Moderna vaccines as part of the review of the Johnson & Johnson application. Dr. Shimabukuro and CDC colleagues published a report in JAMA on February 14 that looked at an anaphylaxis case reported connected with COVID vaccines between December 14, 2020, and January 18, 2021.

The CDC identified 66 case reports received that met Brighton Collaboration case definition criteria for anaphylaxis (levels 1, 2, or 3): 47 following Pfizer/BioNTech vaccine, for a reporting rate of 4.7 cases/million doses administered, and 19 following Moderna vaccine, for a reporting rate of 2.5 cases/million doses administered, Dr. Shimabukuro and CDC colleagues wrote.

The CDC has published materials to help clinicians prepare for the possibility of this rare event, Dr. Shimabukuro told the FDA advisers.

“The take-home message here is that these are rare events and anaphylaxis, although clinically serious, is treatable,” Dr. Shimabukuro said.

At the conclusion of the meeting, FDA panelist Patrick Moore, MD, MPH, from the University of Pittsburgh in Pennsylvania, stressed the need to convey to the public that the COVID vaccines appear so far to be safe. Many people earlier had doubts about how the FDA could both safely and quickly review the applications for EUAs for these products.

“As of February 26, things are looking good. That could change tomorrow,” Dr. Moore said. But “this whole EUA process does seem to have worked, despite my own personal concerns about it.”

No second-class vaccines

The Johnson & Johnson vaccine, known as Ad26.COV2.S, is composed of a recombinant, replication-incompetent human adenovirus type 26 (Ad26) vector. It’s intended to encode a stabilized form of SARS-CoV-2 spike (S) protein. The Pfizer and Moderna vaccines use a different mechanism. They rely on mRNA.

The FDA advisers also discussed how patients might respond to the widely reported gap between Janssen’s topline efficacy rates compared with rivals. They urged against people parsing study details too finely and seeking to pick and choose their shots.

“It’s important that people do not think that one vaccine is better than another,” said FDA adviser H. Cody Meissner, MD, from Tufts University School of Medicine in Boston.

Dr. Monto agreed, noting that many people in the United States are still waiting for their turn to get COVID vaccines because of the limited early supply.

Trying to game the system to get one vaccine instead of another would not be wise. “In this environment, whatever you can get, get,” Dr. Monto said.

During an open public hearing, Sarah Christopherson, policy advocacy director of the National Women’s Health Network, said that press reports are fueling a damaging impression in the public that there are “first and second-class” vaccines.

“That has the potential to exacerbate existing mistrust” in vaccines, she said. “Public health authorities must address these perceptions head on.”

She urged against attempts to compare the Janssen vaccine to others, noting the potential effects of emerging variants of the virus.

“It’s difficult to make an apples-to-apples comparison between vaccines,” she said.

Johnson & Johnson’s efficacy results, which are lower than those of the mRNA vaccines, may be a reflection of the ways in which SARS-Co-V-2 is mutating and thus becoming more of a threat, according to the company. A key study of the new vaccine, involving about 44,000 people, coincided with the emergence of new SARS-CoV-2 variants, which were emerging in some of the countries where the pivotal COV3001 study was being conducted, the company said.

At least 14 days after vaccination, the Johnson & Johnson COVID vaccine efficacy (95% confidence interval) was 72.0% (58.2, 81.7) in the United States, 68.1% (48.8, 80.7) in Brazil, and 64.0% (41.2, 78.7) in South Africa.

Weakened standards?

Several researchers called on the FDA to maintain a critical attitude when assessing Johnson & Johnson’s application for the EUA, warning of a potential for a permanent erosion of agency rules due to hasty action on COVID vaccines.

They raised concerns about the FDA demanding too little in terms of follow-up studies on COVID vaccines and with persisting murkiness resulting in attempts to determine how well these treatments work beyond the initial study period.

“I worry about FDA lowering its approval standards,” said Peter Doshi, PhD, from The BMJ and a faculty member at the University of Maryland School of Medicine in Baltimore, during an open public hearing at the meeting.

“There’s a real urgency to stand back right now and look at the forest here, as well as the trees, and I urge the committee to consider the effects FDA decisions may have on the entire regulatory approval process,” Dr. Doshi said.

Dr. Doshi asked why Johnson & Johnson did not seek a standard full approval — a biologics license application (BLA) — instead of aiming for the lower bar of an EUA. The FDA already has allowed wide distribution of the Pfizer/BioNTech and Moderna vaccines through EUAs. That removes the sense of urgency that FDA faced last year in his view.

The FDA’s June 2020 guidance on the development of COVID vaccines had asked drugmakers to plan on following participants in COVID vaccine trials for “ideally at least one to two years.” Yet people who got placebo in Moderna and Pfizer trials already are being vaccinated, Dr. Doshi said. And Johnson & Johnson said in its presentation to the FDA that if the Ad26.COV2.S vaccine were granted an EUA, the COV3001 study design would be amended to “facilitate cross-over of placebo participants in all participating countries to receive one dose of active study vaccine as fast as operationally feasible.”

“I’m nervous about the prospect of there never being a COVID vaccine that meets the FDA’s approval standard” for a BLA instead of the more limited EUA, Dr. Doshi said.

Diana Zuckerman, PhD, president of the nonprofit National Center for Health Research, noted that the FDA’s subsequent guidance tailored for EUAs for COVID vaccines “drastically shortened” the follow-up time to a median of 2 months. Dr. Zuckerman said that a crossover design would be “a reasonable compromise, but only if the placebo group has at least 6 months of data.” Dr. Zuckerman opened her remarks in the open public hearing by saying she had inherited Johnson & Johnson stock, so was speaking at the meeting against her own financial interest.

“As soon as a vaccine is authorized, we start losing the placebo group. If FDA lets that happen, that’s a huge loss for public health and a huge loss of information about how we can all stay safe,” Dr. Zuckerman said.



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

An FDA advisory panel lent their support Feb. 26 to a rapid clearance for Janssen/Johnson & Johnson’s COVID-19 vaccine.

The Food and Drug Administration (FDA) is expected to quickly provide an emergency use authorization (EUA) for the vaccine following the recommendation by the panel. The FDA’s Vaccines and Related Biological Products Advisory Committee voted 22-0 on this question: Based on the totality of scientific evidence available, do the benefits of the Johnson & Johnson COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?

The Johnson & Johnson vaccine is expected to offer more convenient dosing and be easier to distribute than the two rival products already available in the United States. Janssen’s vaccine is intended to be given in a single dose. In December, the FDA granted EUAs for the Pfizer/BioNTech and Moderna COVID-19 vaccines, which are each two-dose regimens.

Johnson & Johnson’s vaccine can be stored for at least 3 months at normal refrigerator temperatures of 2°C to 8°C (36°F to 46°F). Its shipping and storage fits into the existing medical supply infrastructure, the company said in its briefing materials for the FDA advisory committee meeting. In contrast, Pfizer’s vaccine is stored in ultracold freezers at temperatures between -80°C and -60°C (-112°F and -76°F), according to the Centers for Disease Control and Prevention. Moderna’s vaccine may be stored in a freezer between -25°C and -15°C (-13°F and 5°F).

But FDA advisers focused more in their deliberations on concerns about Janssen’s vaccine, including emerging reports of allergic reactions.

The advisers also discussed how patients might respond to the widely reported gap between Johnson & Johnson’s topline efficacy rates compared with rivals. The company’s initial unveiling last month of key results for its vaccine caused an initial wave of disappointment, with its overall efficacy against moderate-to-severe COVID-19 28 days postvaccination first reported at about 66% globally. By contrast, results for the Pfizer and Moderna vaccines suggest they have efficacy rates of 95% and 94%.

But in concluding, the advisers spoke of the Janssen vaccine as a much-needed tool to address the COVID-19 pandemic. The death toll in the United States attributed to the virus has reached 501,414, according to the World Health Organization.

“Despite the concerns that were raised during the discussion. I think what we have to keep in mind is that we’re still in the midst of this deadly pandemic,” said FDA adviser Archana Chatterjee, MD, PhD, from Rosalind Franklin University. “There is a shortage of vaccines that are currently authorized, and I think authorization of this vaccine will help meet the needs at the moment.”

The FDA is not bound to accept the recommendations of its advisers, but it often does so.

Anaphylaxis case

FDA advisers raised only a few questions for Johnson & Johnson and FDA staff ahead of their vote. The committee’s deliberations were less contentious and heated than had been during its December reviews of the Pfizer and Moderna vaccines. In those meetings, the panel voted 17-4, with one abstention, in favor of Pfizer’s vaccine and  20-0, with one abstention, on the Moderna vaccine.

“We are very comfortable now with the procedure, as well as the vaccines,” said Arnold Monto, MD, after the Feb. 26 vote on the Janssen vaccine. Dr. Monto, from the University of Michigan School of Public Health in Ann Arbor, has served as the chairman of the FDA panel through its review of all three COVID-19 vaccines.

Among the issues noted in the deliberations was the emergence of a concern about anaphylaxis with the vaccine.

This serious allergic reaction has been seen in people who have taken the Pfizer and Moderna vaccines. Before the week of the panel meeting, though, there had not been reports of anaphylaxis with the Johnson & Johnson vaccine, said Macaya Douoguih, MD, MPH, head of clinical development and medical affairs for Janssen/ Johnson & Johnson’s vaccines division.

However, on February 24, Johnson & Johnson received preliminary reports about two cases of severe allergic reaction from an open-label study in South Africa, with one of these being anaphylaxis, Dr. Douoguih said. The company will continue to closely monitor for these events as outlined in their pharmacovigilance plan, Dr. Douoguih said.

Federal health officials have sought to make clinicians aware of the rare risk for anaphylaxis with COVID vaccines, while reminding the public that this reaction can be managed.

The FDA had Tom Shimabukuro, MD, MPH, MBA, from the CDC, give an update on postmarketing surveillance for the Pfizer and Moderna vaccines as part of the review of the Johnson & Johnson application. Dr. Shimabukuro and CDC colleagues published a report in JAMA on February 14 that looked at an anaphylaxis case reported connected with COVID vaccines between December 14, 2020, and January 18, 2021.

The CDC identified 66 case reports received that met Brighton Collaboration case definition criteria for anaphylaxis (levels 1, 2, or 3): 47 following Pfizer/BioNTech vaccine, for a reporting rate of 4.7 cases/million doses administered, and 19 following Moderna vaccine, for a reporting rate of 2.5 cases/million doses administered, Dr. Shimabukuro and CDC colleagues wrote.

The CDC has published materials to help clinicians prepare for the possibility of this rare event, Dr. Shimabukuro told the FDA advisers.

“The take-home message here is that these are rare events and anaphylaxis, although clinically serious, is treatable,” Dr. Shimabukuro said.

At the conclusion of the meeting, FDA panelist Patrick Moore, MD, MPH, from the University of Pittsburgh in Pennsylvania, stressed the need to convey to the public that the COVID vaccines appear so far to be safe. Many people earlier had doubts about how the FDA could both safely and quickly review the applications for EUAs for these products.

“As of February 26, things are looking good. That could change tomorrow,” Dr. Moore said. But “this whole EUA process does seem to have worked, despite my own personal concerns about it.”

No second-class vaccines

The Johnson & Johnson vaccine, known as Ad26.COV2.S, is composed of a recombinant, replication-incompetent human adenovirus type 26 (Ad26) vector. It’s intended to encode a stabilized form of SARS-CoV-2 spike (S) protein. The Pfizer and Moderna vaccines use a different mechanism. They rely on mRNA.

The FDA advisers also discussed how patients might respond to the widely reported gap between Janssen’s topline efficacy rates compared with rivals. They urged against people parsing study details too finely and seeking to pick and choose their shots.

“It’s important that people do not think that one vaccine is better than another,” said FDA adviser H. Cody Meissner, MD, from Tufts University School of Medicine in Boston.

Dr. Monto agreed, noting that many people in the United States are still waiting for their turn to get COVID vaccines because of the limited early supply.

Trying to game the system to get one vaccine instead of another would not be wise. “In this environment, whatever you can get, get,” Dr. Monto said.

During an open public hearing, Sarah Christopherson, policy advocacy director of the National Women’s Health Network, said that press reports are fueling a damaging impression in the public that there are “first and second-class” vaccines.

“That has the potential to exacerbate existing mistrust” in vaccines, she said. “Public health authorities must address these perceptions head on.”

She urged against attempts to compare the Janssen vaccine to others, noting the potential effects of emerging variants of the virus.

“It’s difficult to make an apples-to-apples comparison between vaccines,” she said.

Johnson & Johnson’s efficacy results, which are lower than those of the mRNA vaccines, may be a reflection of the ways in which SARS-Co-V-2 is mutating and thus becoming more of a threat, according to the company. A key study of the new vaccine, involving about 44,000 people, coincided with the emergence of new SARS-CoV-2 variants, which were emerging in some of the countries where the pivotal COV3001 study was being conducted, the company said.

At least 14 days after vaccination, the Johnson & Johnson COVID vaccine efficacy (95% confidence interval) was 72.0% (58.2, 81.7) in the United States, 68.1% (48.8, 80.7) in Brazil, and 64.0% (41.2, 78.7) in South Africa.

Weakened standards?

Several researchers called on the FDA to maintain a critical attitude when assessing Johnson & Johnson’s application for the EUA, warning of a potential for a permanent erosion of agency rules due to hasty action on COVID vaccines.

They raised concerns about the FDA demanding too little in terms of follow-up studies on COVID vaccines and with persisting murkiness resulting in attempts to determine how well these treatments work beyond the initial study period.

“I worry about FDA lowering its approval standards,” said Peter Doshi, PhD, from The BMJ and a faculty member at the University of Maryland School of Medicine in Baltimore, during an open public hearing at the meeting.

“There’s a real urgency to stand back right now and look at the forest here, as well as the trees, and I urge the committee to consider the effects FDA decisions may have on the entire regulatory approval process,” Dr. Doshi said.

Dr. Doshi asked why Johnson & Johnson did not seek a standard full approval — a biologics license application (BLA) — instead of aiming for the lower bar of an EUA. The FDA already has allowed wide distribution of the Pfizer/BioNTech and Moderna vaccines through EUAs. That removes the sense of urgency that FDA faced last year in his view.

The FDA’s June 2020 guidance on the development of COVID vaccines had asked drugmakers to plan on following participants in COVID vaccine trials for “ideally at least one to two years.” Yet people who got placebo in Moderna and Pfizer trials already are being vaccinated, Dr. Doshi said. And Johnson & Johnson said in its presentation to the FDA that if the Ad26.COV2.S vaccine were granted an EUA, the COV3001 study design would be amended to “facilitate cross-over of placebo participants in all participating countries to receive one dose of active study vaccine as fast as operationally feasible.”

“I’m nervous about the prospect of there never being a COVID vaccine that meets the FDA’s approval standard” for a BLA instead of the more limited EUA, Dr. Doshi said.

Diana Zuckerman, PhD, president of the nonprofit National Center for Health Research, noted that the FDA’s subsequent guidance tailored for EUAs for COVID vaccines “drastically shortened” the follow-up time to a median of 2 months. Dr. Zuckerman said that a crossover design would be “a reasonable compromise, but only if the placebo group has at least 6 months of data.” Dr. Zuckerman opened her remarks in the open public hearing by saying she had inherited Johnson & Johnson stock, so was speaking at the meeting against her own financial interest.

“As soon as a vaccine is authorized, we start losing the placebo group. If FDA lets that happen, that’s a huge loss for public health and a huge loss of information about how we can all stay safe,” Dr. Zuckerman said.



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

Posttraumatic stress disorder may occur in up to a third of patients who recover from severe COVID-19 infection, new research suggests.

A study of more than 300 patients who presented to the emergency department with the virus showed a 30.2% prevalence for PTSD 30-120 days after COVID recovery.

Factors linked to higher rates of PTSD included experiencing delirium or agitation during the acute COVID phase or having persistent medical symptoms after hospitalization. 

Additional diagnoses, such as depressive and hypomanic episodes and generalized anxiety disorder (GAD), were also present in some of the survivors.

“Previous coronavirus epidemics were associated with PTSD diagnoses in postillness stages, with meta-analytic findings indicating a prevalence of 32.2%,” write the investigators, led by Delfina Janiri, MD, department of psychiatry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome.

However, data focused specifically on COVID-19 have been “piecemeal,” they add.

The findings were published online Feb. 18 in a research letter in JAMA Psychiatry.
 

A traumatic event

From April to October 2020, the researchers assessed 381 consecutive patients (100% white; 56.4% men; mean age, 55.3 years) who presented to the ED and subsequently participated in a health check at the Fondazione Policlinico Universitario Agostino Gemelli.

The mean length of stay for the 309 patients hospitalized with severe COVID-19 was 18.4 days.

Results showed that 115 participants (30.2%) had PTSD, based on DSM-5 criteria, and 55.7% of the women had the disorder. Additional diagnoses found in the full patient population included:

• Depressive episodes (17.3%).
• GAD (7%).
• Hypomanic episodes (0.7%).
• Psychotic disorders (0.2%).

Patients with PTSD had higher rates than those without PTSD of a previous history of psychiatric disorders (34.8% vs. 20.7%; P = .003) and of delirium or agitation during hospitalization, as assessed with the Confusion Assessment Method (16.5% vs. 6.4%; P = .002).

In addition, 62.6% of those with PTSD had three or more persistent COVID-19 symptoms vs. 37.2% of their counterparts without PTSD (P < .001).

After logistic regression analyses, significant factors associated with a PTSD diagnosis were persistent medical symptoms (P = .002), delirium or agitation (P = .02), and being female (P = .02).

The investigators note that their results are “in line” with findings reported in research examining other traumatic events. This includes about 30% of Hurricane Katrina survivors who experienced PTSD, as did around 25% of survivors of the 2011 “Great Japan Earthquake and Tsunami.”

Study limitations cited include the “relatively small” size of the patient population, that it focused on only one participating center, and that it didn’t include a control group of non-COVID patients who reported to the ED.

“Further longitudinal studies are needed to tailor therapeutic interventions and prevention strategies,” the researchers write.

Dr. Janiri and four of the five other authors have disclosed no relevant financial relationships. The other author, Gabriele Sani, MD, reported having received personal fees from Angelini Spa, Janssen, and Lundbeck outside the submitted work.

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

Posttraumatic stress disorder may occur in up to a third of patients who recover from severe COVID-19 infection, new research suggests.

A study of more than 300 patients who presented to the emergency department with the virus showed a 30.2% prevalence for PTSD 30-120 days after COVID recovery.

Factors linked to higher rates of PTSD included experiencing delirium or agitation during the acute COVID phase or having persistent medical symptoms after hospitalization. 

Additional diagnoses, such as depressive and hypomanic episodes and generalized anxiety disorder (GAD), were also present in some of the survivors.

“Previous coronavirus epidemics were associated with PTSD diagnoses in postillness stages, with meta-analytic findings indicating a prevalence of 32.2%,” write the investigators, led by Delfina Janiri, MD, department of psychiatry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome.

However, data focused specifically on COVID-19 have been “piecemeal,” they add.

The findings were published online Feb. 18 in a research letter in JAMA Psychiatry.
 

A traumatic event

From April to October 2020, the researchers assessed 381 consecutive patients (100% white; 56.4% men; mean age, 55.3 years) who presented to the ED and subsequently participated in a health check at the Fondazione Policlinico Universitario Agostino Gemelli.

The mean length of stay for the 309 patients hospitalized with severe COVID-19 was 18.4 days.

Results showed that 115 participants (30.2%) had PTSD, based on DSM-5 criteria, and 55.7% of the women had the disorder. Additional diagnoses found in the full patient population included:

• Depressive episodes (17.3%).
• GAD (7%).
• Hypomanic episodes (0.7%).
• Psychotic disorders (0.2%).

Patients with PTSD had higher rates than those without PTSD of a previous history of psychiatric disorders (34.8% vs. 20.7%; P = .003) and of delirium or agitation during hospitalization, as assessed with the Confusion Assessment Method (16.5% vs. 6.4%; P = .002).

In addition, 62.6% of those with PTSD had three or more persistent COVID-19 symptoms vs. 37.2% of their counterparts without PTSD (P < .001).

After logistic regression analyses, significant factors associated with a PTSD diagnosis were persistent medical symptoms (P = .002), delirium or agitation (P = .02), and being female (P = .02).

The investigators note that their results are “in line” with findings reported in research examining other traumatic events. This includes about 30% of Hurricane Katrina survivors who experienced PTSD, as did around 25% of survivors of the 2011 “Great Japan Earthquake and Tsunami.”

Study limitations cited include the “relatively small” size of the patient population, that it focused on only one participating center, and that it didn’t include a control group of non-COVID patients who reported to the ED.

“Further longitudinal studies are needed to tailor therapeutic interventions and prevention strategies,” the researchers write.

Dr. Janiri and four of the five other authors have disclosed no relevant financial relationships. The other author, Gabriele Sani, MD, reported having received personal fees from Angelini Spa, Janssen, and Lundbeck outside the submitted work.

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

Posttraumatic stress disorder may occur in up to a third of patients who recover from severe COVID-19 infection, new research suggests.

A study of more than 300 patients who presented to the emergency department with the virus showed a 30.2% prevalence for PTSD 30-120 days after COVID recovery.

Factors linked to higher rates of PTSD included experiencing delirium or agitation during the acute COVID phase or having persistent medical symptoms after hospitalization. 

Additional diagnoses, such as depressive and hypomanic episodes and generalized anxiety disorder (GAD), were also present in some of the survivors.

“Previous coronavirus epidemics were associated with PTSD diagnoses in postillness stages, with meta-analytic findings indicating a prevalence of 32.2%,” write the investigators, led by Delfina Janiri, MD, department of psychiatry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome.

However, data focused specifically on COVID-19 have been “piecemeal,” they add.

The findings were published online Feb. 18 in a research letter in JAMA Psychiatry.
 

A traumatic event

From April to October 2020, the researchers assessed 381 consecutive patients (100% white; 56.4% men; mean age, 55.3 years) who presented to the ED and subsequently participated in a health check at the Fondazione Policlinico Universitario Agostino Gemelli.

The mean length of stay for the 309 patients hospitalized with severe COVID-19 was 18.4 days.

Results showed that 115 participants (30.2%) had PTSD, based on DSM-5 criteria, and 55.7% of the women had the disorder. Additional diagnoses found in the full patient population included:

• Depressive episodes (17.3%).
• GAD (7%).
• Hypomanic episodes (0.7%).
• Psychotic disorders (0.2%).

Patients with PTSD had higher rates than those without PTSD of a previous history of psychiatric disorders (34.8% vs. 20.7%; P = .003) and of delirium or agitation during hospitalization, as assessed with the Confusion Assessment Method (16.5% vs. 6.4%; P = .002).

In addition, 62.6% of those with PTSD had three or more persistent COVID-19 symptoms vs. 37.2% of their counterparts without PTSD (P < .001).

After logistic regression analyses, significant factors associated with a PTSD diagnosis were persistent medical symptoms (P = .002), delirium or agitation (P = .02), and being female (P = .02).

The investigators note that their results are “in line” with findings reported in research examining other traumatic events. This includes about 30% of Hurricane Katrina survivors who experienced PTSD, as did around 25% of survivors of the 2011 “Great Japan Earthquake and Tsunami.”

Study limitations cited include the “relatively small” size of the patient population, that it focused on only one participating center, and that it didn’t include a control group of non-COVID patients who reported to the ED.

“Further longitudinal studies are needed to tailor therapeutic interventions and prevention strategies,” the researchers write.

Dr. Janiri and four of the five other authors have disclosed no relevant financial relationships. The other author, Gabriele Sani, MD, reported having received personal fees from Angelini Spa, Janssen, and Lundbeck outside the submitted work.

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

To read a digital version of the print supplement, click here.

To gain a full understanding of the challenges faced by neurologists, headache specialists, and other clinicians when managing triggers that prompt migraine headache attacks, consider the case of Lola H, a 35-year-old woman with a history of recurrent headaches that was diagnosed 12 months earlier as migraine without aura. Lola is taking oral sumatriptan, 100 mg, for acute migraine episodes, which she reports experiencing 3 or 4 times a month. She also has up to 3 headaches a week that are less severe. Lola’s insurance carrier limits the number of sumatriptan tablets covered in a month, forcing her use the medication only when she has severe headaches. However, the rationing strategy adds stress to her life that could be contributing to additional headache episodes.

Lola raised this issue during a recent visit with her neurologist, at which time she also presented a lengthy list of things she felt were triggering her attacks: stress, her menstrual cycle, chocolate, the odor of gasoline, and the weather, among other potential causes. Regarding the weather, she reported experiencing headaches—sometimes severe—whenever barometric pressure drops. Lola told her clinician that she believes she has gained control of 2 triggers—chocolate and gasoline fumes—through avoidance. She no longer consumes chocolate and other sweets and relies on family members and friends to fill her automobile fuel tank. However, Lola said she cannot control other triggers and needs her clinician’s help. She insists on leaving the appointment with answers she feels satisfied with. More than anything, she wants to feel secure that she has enough medication to meet her needs. (We will reveal how Lola fared later in this article.)

Heterogeneity of triggers: A daunting challenge

Lola’s circumstances are not uncommon among the nearly 40 million migraine sufferers in the United States.¹ For clinicians seeking to better understand how potential triggers cause migraine attacks, it is important to appreciate the fine lines that exist between (1) perceived triggers, (2) their apparent frequency and strength, (3) patients’ efforts to control these factors, and (4) the distinction between real migraine triggers and premonitory symptoms. Moreover, recognizing how each of these 4 issues influence the patient’s experience enables the clinician to optimally manage individuals who experience migraine headache.

A diverse array of potential stimuli

Perhaps the most daunting challenge when trying to uncover what is triggering Lola’s and other migraine patients’ headaches is the realization that triggers and perceived triggers comprise a diverse array of potential stimuli. A meta-analysis of 85 studies conducted over a 60-year period and involving more than 27,000 participants revealed 420 unique headache triggers categorized to 1 of 15 categories.² Characterizing these triggers as vastly heterogenous is an understatement, considering that they include factors such as raising the arms overhead, sneezing, abstaining from coffee, using a low pillow, weekend sleep habits, use of shower gels, relaxing after stressful events, bus journeys, road stripes, and more.² The authors of the meta-analysis note that the variability observed likely is because of methodology differences among the studies included in their analysis. For this reason, the authors advised caution in interpreting the results.²

Nevertheless, the investigators concluded that (1) most of those who experience frequent headaches—including migraine sufferers—believe they have at least 1 trigger, and (2) stress is the trigger most frequently cited by patients, followed by sleep and environmental triggers.²

Perceived differences in trigger frequency and strength

Heterogeneity extends beyond the triggers and perceived triggers; incidence and strength also can vary greatly. In a cross-sectional observational study, 300 headache sufferers were asked to rate 33 triggers by frequency and potency.³ Triggers that were perceived to be encountered most days per month were air conditioning and caffeine (both 30 days). Red wine was perceived to be encountered least frequently (0 days). Importantly, interperson variability for frequency of encounter was significant—most ranges for each trigger spanned
15 days or more.³

Triggers that were perceived to increase the chance of a headache were stress (75%), missing a meal, and dehydration (both 60%). Nuts and salty food were least perceived to increase the likelihood of a headache (both 0%). Similar to frequency, perceptions about trigger strengths varied widely, with most ranges spreading by more than 50% for each trigger.³

The authors noted that the heterogeneity seen in frequency of encounters with triggers remained even when 2 patients had matching perceptions about the importance of the trigger in precipitating a headache. The fact that this was observed for nearly every perceived trigger is an important aspect of understanding trigger frequency at the patient-care level.³ Additionally, most headache sufferers do not believe that triggers are simply present or absent. Rather, they have diverse beliefs about the strength of perceived triggers.³ These broad differences among patients make it difficult to predict how an individual headache sufferer will rate triggers.³

The patient’s trigger belief system

Layered onto this challenge is the observation that many migraine sufferers use the so-called trigger belief system to create a safe and controlled environment to stave off headache attacks. Indeed, perception often dictates how headache triggers are experienced, and this adds to the complexity of managing these patients. This is borne out in 2 studies. One, involving more than 200 individuals, revealed that perceived control over and impact of headaches were related to headache severity.⁴ Another trial involving more than 300 patients seeking treatment for headache showed that participants who were confident they could avoid and better manage their headaches also believed that they could control factors impacting their headaches. Although this led to the use of positive coping strategies, it also triggered more anxiety.⁵

Trigger avoidance can also lead to reduced quality of life. Consider, for example, physical activity, which is recommended to prevent and manage migraine: As many as 8 in 10 migraine sufferers avoid physical activity because they fear triggering an episode.⁶ In a recent study, investigators examined the potential correlation between anxiety sensitivity and physical activity avoidance among 100 women with migraine. Participants completed an anonymous survey about migraine and avoiding physical activity. The survey included a tool that measured anxiety sensitivity. Migraine attacks in the previous 30 days were self-reported.⁶ Higher anxiety scores were linked with more frequent physical activity avoidance. Participants who cited physical concerns were nearly 8 times more likely to avoid vigorous physical activity. Those who mentioned cognitive concerns were more than 5 times more likely to avoid moderate physical activity.⁶ The authors noted that even though avoiding triggers often is recommended, in some situations it can lead to more migraines because of increased anxiety. For this reason, although avoidance is probably best for certain triggers that have true biologic onset mechanisms, triggers that work through anticipatory anxiety or fearful expectations might best be handled via gradual exposure and desensitization.⁶

Distinguishing between real triggers and premonitory symptoms

Once clinicians gain an understanding of these factors, they may consider themselves adequately prepared to optimally manage migraine sufferers. Yet, there is one more factor to consider: premonitory symptoms. Separating premonitory symptoms from actual migraine triggers gets the clinician closer to optimal management. Yet, it is not always easy to make the distinction.

Premonitory symptoms typically present 2 to 48 hours (or more) before migraine headache onset. Symptoms include changes in mood and activity, irritability, fatigue, food cravings, repetitive yawning, stiff neck, and photophobia. Because these symptoms can continue even past the premonitory stage, they often can be misinterpreted as actual migraine triggers.⁷ Premonitory symptoms have been found to accompany 30% to 80% of migraine attacks. Signs that often are confused with actual migraine triggers include neck pain, photophobia, and food cravings.⁸

Timing of symptoms: Potential clues

It is critical to understand the interval between a symptom and migraine onset, which can help determine whether it is an actual trigger, premonitory symptom, or other manifestation. For this, it helps to review the timeline of a migraine attack. The 4 phases of a migraine attack—premonitory/prodrome, aura, headache, and postdrome—are well known. According to the American Migraine Foundation, the 4 phases are marked by specific symptoms that typically—but not always—occur along a general timeline (Figure 1).⁹

Although this symptom timeline can help guide clinicians and migraine sufferers, it is important to understand that these phases do not always occur linearly, and there often is significant overlap, which can mislead both the clinician and patient.⁷

Common triggers

Stress: Stress is the most frequently self-reported migraine trigger, and numerous studies show a link between stress and migraine. However, retrospective and prospective diary studies have not been able to confirm a link between stressful days and acute migraine attacks. Moreover, although 1 study demonstrated that migraines were less likely to occur on holidays or days off, relaxation did not play a role. Fatigue was more common premigraine than mental exhaustion or insomnia, leading investigators to surmise it is a premonitory symptom and not a migraine cause.⁸ Further confounding is the finding that reduced stress from one day to the next is linked with migraine onset the next day, making it a possible predictor of a migraine attack because of the so-called letdown effect.¹⁰

Menstruation: Menstruation appears to be the most common migraine trigger in women. A large 3-month study showed an increase of migraine prevalence and persistence up to 96%. Additionally, diary studies demonstrate menstruation as a trigger, and in a population-based trial, more than half of female migraine sufferers reported an increased rate
of migraine. However, only 4% actually had a migraine during menstruation.^8,11

Diet: Studies that seek to find a link between specific foods and migraine are open to question because they do not have a placebo component, and it is difficult to tell the difference between premonitory food cravings and actual triggers. Moreover, in most patients food appears to be 1 of several contributors to migraine headache, and not the only factor.⁸ Fasting is among the most studied and consistent migraine triggers and seems to be more common during longer fasts. Dehydration is not thought to be a cause; rather, it could be because of hypoglycemia.⁸ A trial involving more than 3000 women revealed that those with migraine had a lower diet quality than their counterparts who did not experience migraine. Other smaller studies show benefit from low-fat vegan and ketogenic diets. Also, patients with irritable bowel syndrome and migraine might benefit from eliminating such foods that cause irritation to improve both migraine frequency and bowel symptoms.⁸

Weather: A few small studies have sought to evaluate the link between weather and migraines. One involving 77 individuals with migraine showed that slightly more than half were sensitive to at least 1 weather factor (i.e., barometric changes, lightning, temperature, and precipitation). Another involving 238 participants demonstrated a nonstatistically significant trend toward increased frequency of migraine attacks on days with high pressure, low wind speed, and increased sunshine, but they called the correlation questionable. A study of 90 individuals found lightning to be an independent risk factor for migraine.⁸

Sensory stimuli: Although visual, aural, olfactory, and other sensory stimuli have been shown to cause migraine in susceptible individuals and worsen migraine intensity, it is difficult to determine if these are true triggers or premonitory symptoms. Indeed, the discomfort thresholds of various sensory stimuli are lower in migraine sufferers.⁸ Odors are the most commonly reported triggers among all sensory stimuli. In 1 study, 7 in every 10 migraine sufferers reported that odors triggered their attack. Common offenders include perfumes, paint, gasoline, bleach, and rancid odors. Smoke and exhaust fumes were also found to be problematic.⁸

Best evidence on migraine triggers

A large retrospective survey looked at acute migraine trigger factors in 1750 individuals treated in a clinical practice. A detailed headache evaluation was conducted that included neurologic history, structured headache interview, and a neurologic exam.¹² More than three-fourths of patients experienced triggers. Approximately 6 in every 10 patients had between 4 and 9 triggers. Nearly one-fourth experienced 1 to 3 triggers.¹² As shown in Figure 2, the 5 triggers that occurred occasionally in at least  half of patients were stress (80%), hormone (65%), fasting (57%), weather (53%), and sleep disturbance (50%). The most common triggers, occurring very frequently, were hormone (33%) and stress (26%).¹²

Trials that use randomized and blinded exposure to possible triggers can—at face value—appear most useful. Potent compounds such as glyceryl trinitrite, prostaglandin I2 and E2, calcitonin-gene related peptide, and pituitary adenylate cyclase-activating polypeptide have been shown to be dependable triggers in the experimental setting. However, trial designs that do not closely mimic real-world experience lack usefulness in clinical practice. Moreover, studies of low intensity migraine triggers that are common in the real world—chocolate and aspartame, for instance—have produced mixed results.¹³ So-called N-of-1 studies—in which a single patient is repeatedly exposed in blinded fashion to a trigger or placebo—might be the best way to uncover actual triggers. However, migraine sufferers are, understandably, not interested in deliberately inducing an attack.¹³ 

This leaves results of diary studies as the most reflective of clinical practice. These evaluations limit the chance of bias that retrospective studies could carry and often provide a significant amount of real-world data that can be used to test hypotheses. Moreover, the advent of smartphone technology enables researchers to capture data in real time, which can help distinguish premonitory symptoms from actual triggers.¹³ A high-quality paper diary study (PAMINA) involving 327 individuals showed strong evidence that a migraine was likely to occur with the following factors: menstruation, muscle tension/neck pain, psychic tension, and sunshine that lasted 3 or more hours per day.¹⁴ 

Diary studies are also able to assess the ability of migraine sufferers to predict a headache. In an evaluation that used an electronic diary design, researchers looked at self-prediction through use of a single question asked daily: “How likely are you to have a headache today?” When participants reported at the beginning of a particular day that headache was “almost certain,” actual headache occurred more than 90% of the time on that day.¹³

Leveraging best evidence into best practices

The clinician–patient conversation

A clinician’s detective skills are put to the test when evaluating patients with migraine. Avoiding dead-ends and fruitless pursuits can spare providers and patients frustration and help patients avoid needless suffering. Yet, as noted, the list of potential triggers appears endless, duration and frequency are variable, patients often try to control their environment with mixed results, and it is difficult to tell the difference between actual triggers and premonitory symptoms.

Which brings us back to Lola H. She desperately wanted to leave her appointment with confidence that she had enough medication to meet her needs each month. She might have expected to go home with access to more medication, but she did not. Rather, she left her clinician’s office with a plan to reduce the number of monthly migraine episodes she experienced, enabling her to use medication as needed, rather than only when her attacks were severe.

Her clinician confirmed that avoiding gasoline odor would reduce the number of attacks. Eliminating chocolates and sweets might, but it is not known whether chocolate is a trigger. He suggested that she try allowing herself chocolate now and then, which would probably serve as a stress reducer. The net result would likely be no change in number of episodes, while allowing for a small improvement in quality of life.

Perhaps most striking, Lola left the appointment certain that her issue with lower barometric pressure was resolved because her clinician took the time to ask how she knew about the daily barometric pressure levels.

Her smartwatch, she told him. He strongly suggested that she delete the watch’s barometric pressure app, which she did on the spot. At her next appointment, Lola was happy to report that barometric pressure no longer played a significant role in her episodes. Moreover, the other strategies she and her clinician discussed have reduced the number of severe and less severe episodes. She no longer lives with the stress of pill-rationing and looks forward to enjoying a small amount of chocolate ice cream each weekend with her family.

Lola’s case demonstrates that in clinical practice the best way to elicit meaningful responses from migraine sufferers is to ask open-ended questions. Yet, clinicians often fail to do so. In a study evaluating communication strategies between clinicians and 60 long-term migraineurs (average 14 years) who experienced frequent headaches (average 5 per month), 90% of migraine-specific questions asked during an appointment were either close-ended or consisted of a short answer. Postvisit interviews with both clinicians and patients revealed these pairs misaligned on migraine frequency (55% of the time) and impairment (51%). One-third of patients were candidates to receive preventive medication, yet only 20% of them did so. Prevention was not discussed in half of the visits with patients who were candidates to receive preventive therapy but did not get it.¹⁰

A panel with extensive experience in migraine reviewed questions from migraine diaries and noted that migraine sufferers find value in capturing wide-ranging information about their condition, whereas clinicians prefer small amounts of data they perceive as relevant to managing migraine.¹⁵ It also is reported that the number of questions patients ask is inversely related to the amount of information a clinician gives.¹⁶

Recommended strategies

In his review article, Mamura reinforces the concept of open 2-way communication, which involves patients in their care more deeply and reinforces positive habits.⁸ It is important to be mindful that discussing triggers exclusively can be counterproductive and frustrating for patients, particularly if the conversation is about trigger avoidance. Patients might feel stigmatized by triggers, come away thinking nothing can be done to control them, and become more anxious about impending episodes.⁸ In fact, a better strategy could be to work with the patient to train their brain to become acclimated to certain triggers or premonitory symptoms, rather than avoiding them.¹⁷

Mamura provides a concise summary of 4 best-practice strategies.⁸ The first 2 should be factored into advice given to patients about migraine triggers and premonitory symptoms; the remaining 2 help frame the treatment approach:

1. Ask patients to keep a headache diary, which eliminates faulty recall and provides a clearer picture of migraine frequency and severity. Include symptoms and other important factors—missed time from work, canceled family activities, nausea and vomiting, etc. Journaling might uncover triggers that can be eliminated or acclimated to via behavior modification. It also can reveal to the patient that certain triggers might not be as useful in predicting migraine as originally thought.

2. Rather than trigger avoidance, suggest that patients concentrate on healthy lifestyle choices, including maintaining healthy weight, getting sufficient sleep, and exercising regularly. The latter has been shown in some studies to work better than preventive medications. Although a behavior change, such as acclimating to certain noises, is not thought to be a healthy lifestyle habit, it ends up being just that if it improves tolerance and reduces migraine episodes.

3. Recognize that many patients have a fear of experiencing a migraine between episodes. If observed in a patient, treat it aggressively. Left unmanaged, this condition could lead to chronic migraine and medication overuse. The right acute medication might be sufficient, but sometimes cognitive-behavioral therapy and biofeedback techniques could be necessary to address behavioral issues that might be interfering with successful treatment.

4. If attacks are frequent and making it difficult to identify distinctive triggers, consider preventive therapy. Patients might resist using preventive medications because they feel eliminating triggers is sufficient, or they might be concerned about medication cost and adverse effects. Eliminating a stressful event alone likely will not help, so it’s important to review with patients—using plain language—how preventive medication treats the underlying cause of migraine and decreases brain excitability, making the patient less prone to attacks.⁸

Emerging medications

New treatments offer increased options for the acute and preventive treatment of migraine attacks. New acute pharmacologic treatments include gepants and ditans. The gepants target calcitonin gene-related peptide (CGRP), a potent vasodilator and neurotransmitter. During migraine episodes, serum levels of CGRP increase as the peptide is released, modulating the transmission of nociceptive signals from peripheral trigeminal sensory afferents into the central trigeminal system.¹⁹ In clinical trials of acute migraine treatment, the gepants provided pain freedom at 2 hours in approximately 20% of attacks, pain relief at 2 hours in 58%, and freedom from the most bothersome symptom at 2 hours in 36% with significant benefit over placebo.^20,21 As these oral formulations became available in 2020, there are not enough data on potential long-term adverse events, particularly cardiovascular effects.¹⁸ However, the gepants are not associated with medication overuse headache and there is no contraindication to their use in patients with cardiovascular disease. These agents, currently available for oral administration, also show benefit as preventive agents and parenteral formulations are in development.  

Ditans target the serotonin 5HT-1F receptor. Triptans target this receptor as well as the 5HT-1B and 5HT-1D receptors. The 5HT-1B receptor action is responsible for constriction of cerebral and peripheral blood vessels that occurs with triptans. Thus, ditans are also options for treating patients with vascular disease. Lasmiditan, the only compound in this class thus far, yielded pain freedom in 2 hours in 31%, pain relief 2 hours in 64%, and relief of the most bothersome symptom at 2 hours in 41%.²² Lasmiditan crosses the blood-brain barrier. Thus, the most common side effects are dizziness, somnolence, and paresthesias, which are generally mild to moderate in severity. Based on driving simulation studies performed in the absence of migraine, patients should not drive within 8 hours of dosing.

Neuromodulation devices are effective options that avoid potential adverse events of systemic treatments. They include external trigeminal nerve stimulation, noninvasive vagus nerve stimulation, remote electrical neuromodulation, caloric vestibular stimulation, and single-pulse transcranial magnetic stimulation. Other treatments in development for the acute treatment of migraine include improved parenteral delivery systems and combination oral preparations of existing medications.

Monoclonal antibodies that block the CGRP ligand or its receptor were introduced in 2018, with 4 medications currently available. This is the first class of migraine medications specifically designed for migraine prevention. They are administered parenterally (subcutaneously or intravenously) either monthly or quarterly, depending on the medication.  The anti-CGRP monoclonal antibodies are indicated for the prevention of episodic and chronic migraine and are eliminated by proteolytic degradation, not involving the liver and reducing the potential for hepatotoxicity and drug-drug interactions.²³ A meta-analysis evaluated the subcutaneous formulations studied for chronic migraine, enrolling participants with at least 15 headache days monthly with migraine occurring on at least 8 of those days. In this cohort with a large disease burden, the pooled 50% responder rate 9-12 weeks after administration of the first dose was 37.4% and the 75% responder rate was 12.7%.²⁴ There was also improvement in the number of migraine days, number of days using acute treatment, and total headache hours. The most common side effects were injection site reactions and constipation, with post-marketing reports of hypertension in the compound targeting the CGRP receptor, with or without pre-existing hypertension.²⁵ The safety profile for use during pregnancy was not studied in any of the medications discussed in this section. 

Summary

Acute migraine headache is a significant management challenge for neurologists, headache specialists, and other clinicians involved in its treatment. Addressing potential migraine triggers can be a particularly overwhelming task because multiple components and factors play into the disorder. Perceived triggers; their frequency and strength; the effort by patients to control their environment; and the blurred line between real triggers and premonitory symptoms present the clinician with an amalgam of components that must be sorted through, defined, prioritized, and managed. Even though migraine symptoms generally appear along a 4-phase timeline, some symptoms stretch across multiple phases and not all symptoms play out in a linear fashion.

There are specific steps clinicians can take to simplify the process, optimize management, and improve patient outcomes and quality of life. Start by gaining an understanding of common triggers and the best evidence regarding triggers and premonitory symptoms. Use this evidence to modify your approach in practice, if necessary. Specifically:

• Improve the information you gather from patients by asking open-ended questions about their experience during a migraine headache, as well as the period between attacks.

• Rather than having patients tell you how many episodes they experience each month, try to elicit from them how many days per month they feel disabled.

• Ask your patients to keep a headache diary.

• Talk less about trigger avoidance and more about making healthy lifestyle choices.

• Address potential cephalgiaphobia via cognitive-behavioral therapy and biofeedback techniques.

• Consider managing frequent migraine attacks with preventive treatment, which now includes CGRP-targeted medications that are as effective as other agents but have fewer adverse effects and might avoid medication overuse headache.

Dr. Friedman reports being an Advisory Board member for Allergan, Biohaven Pharmaceuticals, Eli Lilly, Impel NeuroPharma, Invex, Lundbeck, Revance Therapeutics, Satsuma Pharmaceuticals, Teva Pharmaceuticals, Theranica, and Zosano Pharma. She has received grant support from Allergan, Eli Lilly, Merck, and Zosano Pharma. She is on the Medical Advisory Board for Spinal CSF Leak Foundation, HealthyWomen, and the Board of Directors of the Southern Headache Society. She currently sits on the Editorial Board of Neurology Reviews and has been a contributing author for MedLink Neurology and Medscape.

To read a digital version of the print supplement, click here.

To gain a full understanding of the challenges faced by neurologists, headache specialists, and other clinicians when managing triggers that prompt migraine headache attacks, consider the case of Lola H, a 35-year-old woman with a history of recurrent headaches that was diagnosed 12 months earlier as migraine without aura. Lola is taking oral sumatriptan, 100 mg, for acute migraine episodes, which she reports experiencing 3 or 4 times a month. She also has up to 3 headaches a week that are less severe. Lola’s insurance carrier limits the number of sumatriptan tablets covered in a month, forcing her use the medication only when she has severe headaches. However, the rationing strategy adds stress to her life that could be contributing to additional headache episodes.

Lola raised this issue during a recent visit with her neurologist, at which time she also presented a lengthy list of things she felt were triggering her attacks: stress, her menstrual cycle, chocolate, the odor of gasoline, and the weather, among other potential causes. Regarding the weather, she reported experiencing headaches—sometimes severe—whenever barometric pressure drops. Lola told her clinician that she believes she has gained control of 2 triggers—chocolate and gasoline fumes—through avoidance. She no longer consumes chocolate and other sweets and relies on family members and friends to fill her automobile fuel tank. However, Lola said she cannot control other triggers and needs her clinician’s help. She insists on leaving the appointment with answers she feels satisfied with. More than anything, she wants to feel secure that she has enough medication to meet her needs. (We will reveal how Lola fared later in this article.)

Heterogeneity of triggers: A daunting challenge

Lola’s circumstances are not uncommon among the nearly 40 million migraine sufferers in the United States.¹ For clinicians seeking to better understand how potential triggers cause migraine attacks, it is important to appreciate the fine lines that exist between (1) perceived triggers, (2) their apparent frequency and strength, (3) patients’ efforts to control these factors, and (4) the distinction between real migraine triggers and premonitory symptoms. Moreover, recognizing how each of these 4 issues influence the patient’s experience enables the clinician to optimally manage individuals who experience migraine headache.

A diverse array of potential stimuli

Perhaps the most daunting challenge when trying to uncover what is triggering Lola’s and other migraine patients’ headaches is the realization that triggers and perceived triggers comprise a diverse array of potential stimuli. A meta-analysis of 85 studies conducted over a 60-year period and involving more than 27,000 participants revealed 420 unique headache triggers categorized to 1 of 15 categories.² Characterizing these triggers as vastly heterogenous is an understatement, considering that they include factors such as raising the arms overhead, sneezing, abstaining from coffee, using a low pillow, weekend sleep habits, use of shower gels, relaxing after stressful events, bus journeys, road stripes, and more.² The authors of the meta-analysis note that the variability observed likely is because of methodology differences among the studies included in their analysis. For this reason, the authors advised caution in interpreting the results.²

Nevertheless, the investigators concluded that (1) most of those who experience frequent headaches—including migraine sufferers—believe they have at least 1 trigger, and (2) stress is the trigger most frequently cited by patients, followed by sleep and environmental triggers.²

Perceived differences in trigger frequency and strength

Heterogeneity extends beyond the triggers and perceived triggers; incidence and strength also can vary greatly. In a cross-sectional observational study, 300 headache sufferers were asked to rate 33 triggers by frequency and potency.³ Triggers that were perceived to be encountered most days per month were air conditioning and caffeine (both 30 days). Red wine was perceived to be encountered least frequently (0 days). Importantly, interperson variability for frequency of encounter was significant—most ranges for each trigger spanned
15 days or more.³

Triggers that were perceived to increase the chance of a headache were stress (75%), missing a meal, and dehydration (both 60%). Nuts and salty food were least perceived to increase the likelihood of a headache (both 0%). Similar to frequency, perceptions about trigger strengths varied widely, with most ranges spreading by more than 50% for each trigger.³

The authors noted that the heterogeneity seen in frequency of encounters with triggers remained even when 2 patients had matching perceptions about the importance of the trigger in precipitating a headache. The fact that this was observed for nearly every perceived trigger is an important aspect of understanding trigger frequency at the patient-care level.³ Additionally, most headache sufferers do not believe that triggers are simply present or absent. Rather, they have diverse beliefs about the strength of perceived triggers.³ These broad differences among patients make it difficult to predict how an individual headache sufferer will rate triggers.³

The patient’s trigger belief system

Layered onto this challenge is the observation that many migraine sufferers use the so-called trigger belief system to create a safe and controlled environment to stave off headache attacks. Indeed, perception often dictates how headache triggers are experienced, and this adds to the complexity of managing these patients. This is borne out in 2 studies. One, involving more than 200 individuals, revealed that perceived control over and impact of headaches were related to headache severity.⁴ Another trial involving more than 300 patients seeking treatment for headache showed that participants who were confident they could avoid and better manage their headaches also believed that they could control factors impacting their headaches. Although this led to the use of positive coping strategies, it also triggered more anxiety.⁵

Trigger avoidance can also lead to reduced quality of life. Consider, for example, physical activity, which is recommended to prevent and manage migraine: As many as 8 in 10 migraine sufferers avoid physical activity because they fear triggering an episode.⁶ In a recent study, investigators examined the potential correlation between anxiety sensitivity and physical activity avoidance among 100 women with migraine. Participants completed an anonymous survey about migraine and avoiding physical activity. The survey included a tool that measured anxiety sensitivity. Migraine attacks in the previous 30 days were self-reported.⁶ Higher anxiety scores were linked with more frequent physical activity avoidance. Participants who cited physical concerns were nearly 8 times more likely to avoid vigorous physical activity. Those who mentioned cognitive concerns were more than 5 times more likely to avoid moderate physical activity.⁶ The authors noted that even though avoiding triggers often is recommended, in some situations it can lead to more migraines because of increased anxiety. For this reason, although avoidance is probably best for certain triggers that have true biologic onset mechanisms, triggers that work through anticipatory anxiety or fearful expectations might best be handled via gradual exposure and desensitization.⁶

Distinguishing between real triggers and premonitory symptoms

Once clinicians gain an understanding of these factors, they may consider themselves adequately prepared to optimally manage migraine sufferers. Yet, there is one more factor to consider: premonitory symptoms. Separating premonitory symptoms from actual migraine triggers gets the clinician closer to optimal management. Yet, it is not always easy to make the distinction.

Premonitory symptoms typically present 2 to 48 hours (or more) before migraine headache onset. Symptoms include changes in mood and activity, irritability, fatigue, food cravings, repetitive yawning, stiff neck, and photophobia. Because these symptoms can continue even past the premonitory stage, they often can be misinterpreted as actual migraine triggers.⁷ Premonitory symptoms have been found to accompany 30% to 80% of migraine attacks. Signs that often are confused with actual migraine triggers include neck pain, photophobia, and food cravings.⁸

Timing of symptoms: Potential clues

It is critical to understand the interval between a symptom and migraine onset, which can help determine whether it is an actual trigger, premonitory symptom, or other manifestation. For this, it helps to review the timeline of a migraine attack. The 4 phases of a migraine attack—premonitory/prodrome, aura, headache, and postdrome—are well known. According to the American Migraine Foundation, the 4 phases are marked by specific symptoms that typically—but not always—occur along a general timeline (Figure 1).⁹

Although this symptom timeline can help guide clinicians and migraine sufferers, it is important to understand that these phases do not always occur linearly, and there often is significant overlap, which can mislead both the clinician and patient.⁷

Common triggers

Stress: Stress is the most frequently self-reported migraine trigger, and numerous studies show a link between stress and migraine. However, retrospective and prospective diary studies have not been able to confirm a link between stressful days and acute migraine attacks. Moreover, although 1 study demonstrated that migraines were less likely to occur on holidays or days off, relaxation did not play a role. Fatigue was more common premigraine than mental exhaustion or insomnia, leading investigators to surmise it is a premonitory symptom and not a migraine cause.⁸ Further confounding is the finding that reduced stress from one day to the next is linked with migraine onset the next day, making it a possible predictor of a migraine attack because of the so-called letdown effect.¹⁰

Menstruation: Menstruation appears to be the most common migraine trigger in women. A large 3-month study showed an increase of migraine prevalence and persistence up to 96%. Additionally, diary studies demonstrate menstruation as a trigger, and in a population-based trial, more than half of female migraine sufferers reported an increased rate
of migraine. However, only 4% actually had a migraine during menstruation.^8,11

Diet: Studies that seek to find a link between specific foods and migraine are open to question because they do not have a placebo component, and it is difficult to tell the difference between premonitory food cravings and actual triggers. Moreover, in most patients food appears to be 1 of several contributors to migraine headache, and not the only factor.⁸ Fasting is among the most studied and consistent migraine triggers and seems to be more common during longer fasts. Dehydration is not thought to be a cause; rather, it could be because of hypoglycemia.⁸ A trial involving more than 3000 women revealed that those with migraine had a lower diet quality than their counterparts who did not experience migraine. Other smaller studies show benefit from low-fat vegan and ketogenic diets. Also, patients with irritable bowel syndrome and migraine might benefit from eliminating such foods that cause irritation to improve both migraine frequency and bowel symptoms.⁸

Weather: A few small studies have sought to evaluate the link between weather and migraines. One involving 77 individuals with migraine showed that slightly more than half were sensitive to at least 1 weather factor (i.e., barometric changes, lightning, temperature, and precipitation). Another involving 238 participants demonstrated a nonstatistically significant trend toward increased frequency of migraine attacks on days with high pressure, low wind speed, and increased sunshine, but they called the correlation questionable. A study of 90 individuals found lightning to be an independent risk factor for migraine.⁸

Sensory stimuli: Although visual, aural, olfactory, and other sensory stimuli have been shown to cause migraine in susceptible individuals and worsen migraine intensity, it is difficult to determine if these are true triggers or premonitory symptoms. Indeed, the discomfort thresholds of various sensory stimuli are lower in migraine sufferers.⁸ Odors are the most commonly reported triggers among all sensory stimuli. In 1 study, 7 in every 10 migraine sufferers reported that odors triggered their attack. Common offenders include perfumes, paint, gasoline, bleach, and rancid odors. Smoke and exhaust fumes were also found to be problematic.⁸

Best evidence on migraine triggers

A large retrospective survey looked at acute migraine trigger factors in 1750 individuals treated in a clinical practice. A detailed headache evaluation was conducted that included neurologic history, structured headache interview, and a neurologic exam.¹² More than three-fourths of patients experienced triggers. Approximately 6 in every 10 patients had between 4 and 9 triggers. Nearly one-fourth experienced 1 to 3 triggers.¹² As shown in Figure 2, the 5 triggers that occurred occasionally in at least  half of patients were stress (80%), hormone (65%), fasting (57%), weather (53%), and sleep disturbance (50%). The most common triggers, occurring very frequently, were hormone (33%) and stress (26%).¹²

Trials that use randomized and blinded exposure to possible triggers can—at face value—appear most useful. Potent compounds such as glyceryl trinitrite, prostaglandin I2 and E2, calcitonin-gene related peptide, and pituitary adenylate cyclase-activating polypeptide have been shown to be dependable triggers in the experimental setting. However, trial designs that do not closely mimic real-world experience lack usefulness in clinical practice. Moreover, studies of low intensity migraine triggers that are common in the real world—chocolate and aspartame, for instance—have produced mixed results.¹³ So-called N-of-1 studies—in which a single patient is repeatedly exposed in blinded fashion to a trigger or placebo—might be the best way to uncover actual triggers. However, migraine sufferers are, understandably, not interested in deliberately inducing an attack.¹³ 

This leaves results of diary studies as the most reflective of clinical practice. These evaluations limit the chance of bias that retrospective studies could carry and often provide a significant amount of real-world data that can be used to test hypotheses. Moreover, the advent of smartphone technology enables researchers to capture data in real time, which can help distinguish premonitory symptoms from actual triggers.¹³ A high-quality paper diary study (PAMINA) involving 327 individuals showed strong evidence that a migraine was likely to occur with the following factors: menstruation, muscle tension/neck pain, psychic tension, and sunshine that lasted 3 or more hours per day.¹⁴ 

Diary studies are also able to assess the ability of migraine sufferers to predict a headache. In an evaluation that used an electronic diary design, researchers looked at self-prediction through use of a single question asked daily: “How likely are you to have a headache today?” When participants reported at the beginning of a particular day that headache was “almost certain,” actual headache occurred more than 90% of the time on that day.¹³

Leveraging best evidence into best practices

The clinician–patient conversation

A clinician’s detective skills are put to the test when evaluating patients with migraine. Avoiding dead-ends and fruitless pursuits can spare providers and patients frustration and help patients avoid needless suffering. Yet, as noted, the list of potential triggers appears endless, duration and frequency are variable, patients often try to control their environment with mixed results, and it is difficult to tell the difference between actual triggers and premonitory symptoms.

Which brings us back to Lola H. She desperately wanted to leave her appointment with confidence that she had enough medication to meet her needs each month. She might have expected to go home with access to more medication, but she did not. Rather, she left her clinician’s office with a plan to reduce the number of monthly migraine episodes she experienced, enabling her to use medication as needed, rather than only when her attacks were severe.

Her clinician confirmed that avoiding gasoline odor would reduce the number of attacks. Eliminating chocolates and sweets might, but it is not known whether chocolate is a trigger. He suggested that she try allowing herself chocolate now and then, which would probably serve as a stress reducer. The net result would likely be no change in number of episodes, while allowing for a small improvement in quality of life.

Perhaps most striking, Lola left the appointment certain that her issue with lower barometric pressure was resolved because her clinician took the time to ask how she knew about the daily barometric pressure levels.

Her smartwatch, she told him. He strongly suggested that she delete the watch’s barometric pressure app, which she did on the spot. At her next appointment, Lola was happy to report that barometric pressure no longer played a significant role in her episodes. Moreover, the other strategies she and her clinician discussed have reduced the number of severe and less severe episodes. She no longer lives with the stress of pill-rationing and looks forward to enjoying a small amount of chocolate ice cream each weekend with her family.

Lola’s case demonstrates that in clinical practice the best way to elicit meaningful responses from migraine sufferers is to ask open-ended questions. Yet, clinicians often fail to do so. In a study evaluating communication strategies between clinicians and 60 long-term migraineurs (average 14 years) who experienced frequent headaches (average 5 per month), 90% of migraine-specific questions asked during an appointment were either close-ended or consisted of a short answer. Postvisit interviews with both clinicians and patients revealed these pairs misaligned on migraine frequency (55% of the time) and impairment (51%). One-third of patients were candidates to receive preventive medication, yet only 20% of them did so. Prevention was not discussed in half of the visits with patients who were candidates to receive preventive therapy but did not get it.¹⁰

A panel with extensive experience in migraine reviewed questions from migraine diaries and noted that migraine sufferers find value in capturing wide-ranging information about their condition, whereas clinicians prefer small amounts of data they perceive as relevant to managing migraine.¹⁵ It also is reported that the number of questions patients ask is inversely related to the amount of information a clinician gives.¹⁶

Recommended strategies

In his review article, Mamura reinforces the concept of open 2-way communication, which involves patients in their care more deeply and reinforces positive habits.⁸ It is important to be mindful that discussing triggers exclusively can be counterproductive and frustrating for patients, particularly if the conversation is about trigger avoidance. Patients might feel stigmatized by triggers, come away thinking nothing can be done to control them, and become more anxious about impending episodes.⁸ In fact, a better strategy could be to work with the patient to train their brain to become acclimated to certain triggers or premonitory symptoms, rather than avoiding them.¹⁷

Mamura provides a concise summary of 4 best-practice strategies.⁸ The first 2 should be factored into advice given to patients about migraine triggers and premonitory symptoms; the remaining 2 help frame the treatment approach:

1. Ask patients to keep a headache diary, which eliminates faulty recall and provides a clearer picture of migraine frequency and severity. Include symptoms and other important factors—missed time from work, canceled family activities, nausea and vomiting, etc. Journaling might uncover triggers that can be eliminated or acclimated to via behavior modification. It also can reveal to the patient that certain triggers might not be as useful in predicting migraine as originally thought.

2. Rather than trigger avoidance, suggest that patients concentrate on healthy lifestyle choices, including maintaining healthy weight, getting sufficient sleep, and exercising regularly. The latter has been shown in some studies to work better than preventive medications. Although a behavior change, such as acclimating to certain noises, is not thought to be a healthy lifestyle habit, it ends up being just that if it improves tolerance and reduces migraine episodes.

3. Recognize that many patients have a fear of experiencing a migraine between episodes. If observed in a patient, treat it aggressively. Left unmanaged, this condition could lead to chronic migraine and medication overuse. The right acute medication might be sufficient, but sometimes cognitive-behavioral therapy and biofeedback techniques could be necessary to address behavioral issues that might be interfering with successful treatment.

4. If attacks are frequent and making it difficult to identify distinctive triggers, consider preventive therapy. Patients might resist using preventive medications because they feel eliminating triggers is sufficient, or they might be concerned about medication cost and adverse effects. Eliminating a stressful event alone likely will not help, so it’s important to review with patients—using plain language—how preventive medication treats the underlying cause of migraine and decreases brain excitability, making the patient less prone to attacks.⁸

Emerging medications

New treatments offer increased options for the acute and preventive treatment of migraine attacks. New acute pharmacologic treatments include gepants and ditans. The gepants target calcitonin gene-related peptide (CGRP), a potent vasodilator and neurotransmitter. During migraine episodes, serum levels of CGRP increase as the peptide is released, modulating the transmission of nociceptive signals from peripheral trigeminal sensory afferents into the central trigeminal system.¹⁹ In clinical trials of acute migraine treatment, the gepants provided pain freedom at 2 hours in approximately 20% of attacks, pain relief at 2 hours in 58%, and freedom from the most bothersome symptom at 2 hours in 36% with significant benefit over placebo.^20,21 As these oral formulations became available in 2020, there are not enough data on potential long-term adverse events, particularly cardiovascular effects.¹⁸ However, the gepants are not associated with medication overuse headache and there is no contraindication to their use in patients with cardiovascular disease. These agents, currently available for oral administration, also show benefit as preventive agents and parenteral formulations are in development.  

Ditans target the serotonin 5HT-1F receptor. Triptans target this receptor as well as the 5HT-1B and 5HT-1D receptors. The 5HT-1B receptor action is responsible for constriction of cerebral and peripheral blood vessels that occurs with triptans. Thus, ditans are also options for treating patients with vascular disease. Lasmiditan, the only compound in this class thus far, yielded pain freedom in 2 hours in 31%, pain relief 2 hours in 64%, and relief of the most bothersome symptom at 2 hours in 41%.²² Lasmiditan crosses the blood-brain barrier. Thus, the most common side effects are dizziness, somnolence, and paresthesias, which are generally mild to moderate in severity. Based on driving simulation studies performed in the absence of migraine, patients should not drive within 8 hours of dosing.

Neuromodulation devices are effective options that avoid potential adverse events of systemic treatments. They include external trigeminal nerve stimulation, noninvasive vagus nerve stimulation, remote electrical neuromodulation, caloric vestibular stimulation, and single-pulse transcranial magnetic stimulation. Other treatments in development for the acute treatment of migraine include improved parenteral delivery systems and combination oral preparations of existing medications.

Monoclonal antibodies that block the CGRP ligand or its receptor were introduced in 2018, with 4 medications currently available. This is the first class of migraine medications specifically designed for migraine prevention. They are administered parenterally (subcutaneously or intravenously) either monthly or quarterly, depending on the medication.  The anti-CGRP monoclonal antibodies are indicated for the prevention of episodic and chronic migraine and are eliminated by proteolytic degradation, not involving the liver and reducing the potential for hepatotoxicity and drug-drug interactions.²³ A meta-analysis evaluated the subcutaneous formulations studied for chronic migraine, enrolling participants with at least 15 headache days monthly with migraine occurring on at least 8 of those days. In this cohort with a large disease burden, the pooled 50% responder rate 9-12 weeks after administration of the first dose was 37.4% and the 75% responder rate was 12.7%.²⁴ There was also improvement in the number of migraine days, number of days using acute treatment, and total headache hours. The most common side effects were injection site reactions and constipation, with post-marketing reports of hypertension in the compound targeting the CGRP receptor, with or without pre-existing hypertension.²⁵ The safety profile for use during pregnancy was not studied in any of the medications discussed in this section. 

Summary

Acute migraine headache is a significant management challenge for neurologists, headache specialists, and other clinicians involved in its treatment. Addressing potential migraine triggers can be a particularly overwhelming task because multiple components and factors play into the disorder. Perceived triggers; their frequency and strength; the effort by patients to control their environment; and the blurred line between real triggers and premonitory symptoms present the clinician with an amalgam of components that must be sorted through, defined, prioritized, and managed. Even though migraine symptoms generally appear along a 4-phase timeline, some symptoms stretch across multiple phases and not all symptoms play out in a linear fashion.

There are specific steps clinicians can take to simplify the process, optimize management, and improve patient outcomes and quality of life. Start by gaining an understanding of common triggers and the best evidence regarding triggers and premonitory symptoms. Use this evidence to modify your approach in practice, if necessary. Specifically:

• Improve the information you gather from patients by asking open-ended questions about their experience during a migraine headache, as well as the period between attacks.

• Rather than having patients tell you how many episodes they experience each month, try to elicit from them how many days per month they feel disabled.

• Ask your patients to keep a headache diary.

• Talk less about trigger avoidance and more about making healthy lifestyle choices.

• Address potential cephalgiaphobia via cognitive-behavioral therapy and biofeedback techniques.

• Consider managing frequent migraine attacks with preventive treatment, which now includes CGRP-targeted medications that are as effective as other agents but have fewer adverse effects and might avoid medication overuse headache.

Dr. Friedman reports being an Advisory Board member for Allergan, Biohaven Pharmaceuticals, Eli Lilly, Impel NeuroPharma, Invex, Lundbeck, Revance Therapeutics, Satsuma Pharmaceuticals, Teva Pharmaceuticals, Theranica, and Zosano Pharma. She has received grant support from Allergan, Eli Lilly, Merck, and Zosano Pharma. She is on the Medical Advisory Board for Spinal CSF Leak Foundation, HealthyWomen, and the Board of Directors of the Southern Headache Society. She currently sits on the Editorial Board of Neurology Reviews and has been a contributing author for MedLink Neurology and Medscape.

To read a digital version of the print supplement, click here.

To gain a full understanding of the challenges faced by neurologists, headache specialists, and other clinicians when managing triggers that prompt migraine headache attacks, consider the case of Lola H, a 35-year-old woman with a history of recurrent headaches that was diagnosed 12 months earlier as migraine without aura. Lola is taking oral sumatriptan, 100 mg, for acute migraine episodes, which she reports experiencing 3 or 4 times a month. She also has up to 3 headaches a week that are less severe. Lola’s insurance carrier limits the number of sumatriptan tablets covered in a month, forcing her use the medication only when she has severe headaches. However, the rationing strategy adds stress to her life that could be contributing to additional headache episodes.

Lola raised this issue during a recent visit with her neurologist, at which time she also presented a lengthy list of things she felt were triggering her attacks: stress, her menstrual cycle, chocolate, the odor of gasoline, and the weather, among other potential causes. Regarding the weather, she reported experiencing headaches—sometimes severe—whenever barometric pressure drops. Lola told her clinician that she believes she has gained control of 2 triggers—chocolate and gasoline fumes—through avoidance. She no longer consumes chocolate and other sweets and relies on family members and friends to fill her automobile fuel tank. However, Lola said she cannot control other triggers and needs her clinician’s help. She insists on leaving the appointment with answers she feels satisfied with. More than anything, she wants to feel secure that she has enough medication to meet her needs. (We will reveal how Lola fared later in this article.)

Heterogeneity of triggers: A daunting challenge

Lola’s circumstances are not uncommon among the nearly 40 million migraine sufferers in the United States.¹ For clinicians seeking to better understand how potential triggers cause migraine attacks, it is important to appreciate the fine lines that exist between (1) perceived triggers, (2) their apparent frequency and strength, (3) patients’ efforts to control these factors, and (4) the distinction between real migraine triggers and premonitory symptoms. Moreover, recognizing how each of these 4 issues influence the patient’s experience enables the clinician to optimally manage individuals who experience migraine headache.

A diverse array of potential stimuli

Perhaps the most daunting challenge when trying to uncover what is triggering Lola’s and other migraine patients’ headaches is the realization that triggers and perceived triggers comprise a diverse array of potential stimuli. A meta-analysis of 85 studies conducted over a 60-year period and involving more than 27,000 participants revealed 420 unique headache triggers categorized to 1 of 15 categories.² Characterizing these triggers as vastly heterogenous is an understatement, considering that they include factors such as raising the arms overhead, sneezing, abstaining from coffee, using a low pillow, weekend sleep habits, use of shower gels, relaxing after stressful events, bus journeys, road stripes, and more.² The authors of the meta-analysis note that the variability observed likely is because of methodology differences among the studies included in their analysis. For this reason, the authors advised caution in interpreting the results.²

Nevertheless, the investigators concluded that (1) most of those who experience frequent headaches—including migraine sufferers—believe they have at least 1 trigger, and (2) stress is the trigger most frequently cited by patients, followed by sleep and environmental triggers.²

Perceived differences in trigger frequency and strength

Heterogeneity extends beyond the triggers and perceived triggers; incidence and strength also can vary greatly. In a cross-sectional observational study, 300 headache sufferers were asked to rate 33 triggers by frequency and potency.³ Triggers that were perceived to be encountered most days per month were air conditioning and caffeine (both 30 days). Red wine was perceived to be encountered least frequently (0 days). Importantly, interperson variability for frequency of encounter was significant—most ranges for each trigger spanned
15 days or more.³

Triggers that were perceived to increase the chance of a headache were stress (75%), missing a meal, and dehydration (both 60%). Nuts and salty food were least perceived to increase the likelihood of a headache (both 0%). Similar to frequency, perceptions about trigger strengths varied widely, with most ranges spreading by more than 50% for each trigger.³

The authors noted that the heterogeneity seen in frequency of encounters with triggers remained even when 2 patients had matching perceptions about the importance of the trigger in precipitating a headache. The fact that this was observed for nearly every perceived trigger is an important aspect of understanding trigger frequency at the patient-care level.³ Additionally, most headache sufferers do not believe that triggers are simply present or absent. Rather, they have diverse beliefs about the strength of perceived triggers.³ These broad differences among patients make it difficult to predict how an individual headache sufferer will rate triggers.³

The patient’s trigger belief system

Layered onto this challenge is the observation that many migraine sufferers use the so-called trigger belief system to create a safe and controlled environment to stave off headache attacks. Indeed, perception often dictates how headache triggers are experienced, and this adds to the complexity of managing these patients. This is borne out in 2 studies. One, involving more than 200 individuals, revealed that perceived control over and impact of headaches were related to headache severity.⁴ Another trial involving more than 300 patients seeking treatment for headache showed that participants who were confident they could avoid and better manage their headaches also believed that they could control factors impacting their headaches. Although this led to the use of positive coping strategies, it also triggered more anxiety.⁵

Trigger avoidance can also lead to reduced quality of life. Consider, for example, physical activity, which is recommended to prevent and manage migraine: As many as 8 in 10 migraine sufferers avoid physical activity because they fear triggering an episode.⁶ In a recent study, investigators examined the potential correlation between anxiety sensitivity and physical activity avoidance among 100 women with migraine. Participants completed an anonymous survey about migraine and avoiding physical activity. The survey included a tool that measured anxiety sensitivity. Migraine attacks in the previous 30 days were self-reported.⁶ Higher anxiety scores were linked with more frequent physical activity avoidance. Participants who cited physical concerns were nearly 8 times more likely to avoid vigorous physical activity. Those who mentioned cognitive concerns were more than 5 times more likely to avoid moderate physical activity.⁶ The authors noted that even though avoiding triggers often is recommended, in some situations it can lead to more migraines because of increased anxiety. For this reason, although avoidance is probably best for certain triggers that have true biologic onset mechanisms, triggers that work through anticipatory anxiety or fearful expectations might best be handled via gradual exposure and desensitization.⁶

Distinguishing between real triggers and premonitory symptoms

Once clinicians gain an understanding of these factors, they may consider themselves adequately prepared to optimally manage migraine sufferers. Yet, there is one more factor to consider: premonitory symptoms. Separating premonitory symptoms from actual migraine triggers gets the clinician closer to optimal management. Yet, it is not always easy to make the distinction.

Premonitory symptoms typically present 2 to 48 hours (or more) before migraine headache onset. Symptoms include changes in mood and activity, irritability, fatigue, food cravings, repetitive yawning, stiff neck, and photophobia. Because these symptoms can continue even past the premonitory stage, they often can be misinterpreted as actual migraine triggers.⁷ Premonitory symptoms have been found to accompany 30% to 80% of migraine attacks. Signs that often are confused with actual migraine triggers include neck pain, photophobia, and food cravings.⁸

Timing of symptoms: Potential clues

It is critical to understand the interval between a symptom and migraine onset, which can help determine whether it is an actual trigger, premonitory symptom, or other manifestation. For this, it helps to review the timeline of a migraine attack. The 4 phases of a migraine attack—premonitory/prodrome, aura, headache, and postdrome—are well known. According to the American Migraine Foundation, the 4 phases are marked by specific symptoms that typically—but not always—occur along a general timeline (Figure 1).⁹

Although this symptom timeline can help guide clinicians and migraine sufferers, it is important to understand that these phases do not always occur linearly, and there often is significant overlap, which can mislead both the clinician and patient.⁷

Common triggers

Stress: Stress is the most frequently self-reported migraine trigger, and numerous studies show a link between stress and migraine. However, retrospective and prospective diary studies have not been able to confirm a link between stressful days and acute migraine attacks. Moreover, although 1 study demonstrated that migraines were less likely to occur on holidays or days off, relaxation did not play a role. Fatigue was more common premigraine than mental exhaustion or insomnia, leading investigators to surmise it is a premonitory symptom and not a migraine cause.⁸ Further confounding is the finding that reduced stress from one day to the next is linked with migraine onset the next day, making it a possible predictor of a migraine attack because of the so-called letdown effect.¹⁰

Menstruation: Menstruation appears to be the most common migraine trigger in women. A large 3-month study showed an increase of migraine prevalence and persistence up to 96%. Additionally, diary studies demonstrate menstruation as a trigger, and in a population-based trial, more than half of female migraine sufferers reported an increased rate
of migraine. However, only 4% actually had a migraine during menstruation.^8,11

Diet: Studies that seek to find a link between specific foods and migraine are open to question because they do not have a placebo component, and it is difficult to tell the difference between premonitory food cravings and actual triggers. Moreover, in most patients food appears to be 1 of several contributors to migraine headache, and not the only factor.⁸ Fasting is among the most studied and consistent migraine triggers and seems to be more common during longer fasts. Dehydration is not thought to be a cause; rather, it could be because of hypoglycemia.⁸ A trial involving more than 3000 women revealed that those with migraine had a lower diet quality than their counterparts who did not experience migraine. Other smaller studies show benefit from low-fat vegan and ketogenic diets. Also, patients with irritable bowel syndrome and migraine might benefit from eliminating such foods that cause irritation to improve both migraine frequency and bowel symptoms.⁸

Weather: A few small studies have sought to evaluate the link between weather and migraines. One involving 77 individuals with migraine showed that slightly more than half were sensitive to at least 1 weather factor (i.e., barometric changes, lightning, temperature, and precipitation). Another involving 238 participants demonstrated a nonstatistically significant trend toward increased frequency of migraine attacks on days with high pressure, low wind speed, and increased sunshine, but they called the correlation questionable. A study of 90 individuals found lightning to be an independent risk factor for migraine.⁸

Sensory stimuli: Although visual, aural, olfactory, and other sensory stimuli have been shown to cause migraine in susceptible individuals and worsen migraine intensity, it is difficult to determine if these are true triggers or premonitory symptoms. Indeed, the discomfort thresholds of various sensory stimuli are lower in migraine sufferers.⁸ Odors are the most commonly reported triggers among all sensory stimuli. In 1 study, 7 in every 10 migraine sufferers reported that odors triggered their attack. Common offenders include perfumes, paint, gasoline, bleach, and rancid odors. Smoke and exhaust fumes were also found to be problematic.⁸

Best evidence on migraine triggers

A large retrospective survey looked at acute migraine trigger factors in 1750 individuals treated in a clinical practice. A detailed headache evaluation was conducted that included neurologic history, structured headache interview, and a neurologic exam.¹² More than three-fourths of patients experienced triggers. Approximately 6 in every 10 patients had between 4 and 9 triggers. Nearly one-fourth experienced 1 to 3 triggers.¹² As shown in Figure 2, the 5 triggers that occurred occasionally in at least  half of patients were stress (80%), hormone (65%), fasting (57%), weather (53%), and sleep disturbance (50%). The most common triggers, occurring very frequently, were hormone (33%) and stress (26%).¹²

Trials that use randomized and blinded exposure to possible triggers can—at face value—appear most useful. Potent compounds such as glyceryl trinitrite, prostaglandin I2 and E2, calcitonin-gene related peptide, and pituitary adenylate cyclase-activating polypeptide have been shown to be dependable triggers in the experimental setting. However, trial designs that do not closely mimic real-world experience lack usefulness in clinical practice. Moreover, studies of low intensity migraine triggers that are common in the real world—chocolate and aspartame, for instance—have produced mixed results.¹³ So-called N-of-1 studies—in which a single patient is repeatedly exposed in blinded fashion to a trigger or placebo—might be the best way to uncover actual triggers. However, migraine sufferers are, understandably, not interested in deliberately inducing an attack.¹³ 

This leaves results of diary studies as the most reflective of clinical practice. These evaluations limit the chance of bias that retrospective studies could carry and often provide a significant amount of real-world data that can be used to test hypotheses. Moreover, the advent of smartphone technology enables researchers to capture data in real time, which can help distinguish premonitory symptoms from actual triggers.¹³ A high-quality paper diary study (PAMINA) involving 327 individuals showed strong evidence that a migraine was likely to occur with the following factors: menstruation, muscle tension/neck pain, psychic tension, and sunshine that lasted 3 or more hours per day.¹⁴ 

Diary studies are also able to assess the ability of migraine sufferers to predict a headache. In an evaluation that used an electronic diary design, researchers looked at self-prediction through use of a single question asked daily: “How likely are you to have a headache today?” When participants reported at the beginning of a particular day that headache was “almost certain,” actual headache occurred more than 90% of the time on that day.¹³

Leveraging best evidence into best practices

The clinician–patient conversation

A clinician’s detective skills are put to the test when evaluating patients with migraine. Avoiding dead-ends and fruitless pursuits can spare providers and patients frustration and help patients avoid needless suffering. Yet, as noted, the list of potential triggers appears endless, duration and frequency are variable, patients often try to control their environment with mixed results, and it is difficult to tell the difference between actual triggers and premonitory symptoms.

Which brings us back to Lola H. She desperately wanted to leave her appointment with confidence that she had enough medication to meet her needs each month. She might have expected to go home with access to more medication, but she did not. Rather, she left her clinician’s office with a plan to reduce the number of monthly migraine episodes she experienced, enabling her to use medication as needed, rather than only when her attacks were severe.

Her clinician confirmed that avoiding gasoline odor would reduce the number of attacks. Eliminating chocolates and sweets might, but it is not known whether chocolate is a trigger. He suggested that she try allowing herself chocolate now and then, which would probably serve as a stress reducer. The net result would likely be no change in number of episodes, while allowing for a small improvement in quality of life.

Perhaps most striking, Lola left the appointment certain that her issue with lower barometric pressure was resolved because her clinician took the time to ask how she knew about the daily barometric pressure levels.

Her smartwatch, she told him. He strongly suggested that she delete the watch’s barometric pressure app, which she did on the spot. At her next appointment, Lola was happy to report that barometric pressure no longer played a significant role in her episodes. Moreover, the other strategies she and her clinician discussed have reduced the number of severe and less severe episodes. She no longer lives with the stress of pill-rationing and looks forward to enjoying a small amount of chocolate ice cream each weekend with her family.

Lola’s case demonstrates that in clinical practice the best way to elicit meaningful responses from migraine sufferers is to ask open-ended questions. Yet, clinicians often fail to do so. In a study evaluating communication strategies between clinicians and 60 long-term migraineurs (average 14 years) who experienced frequent headaches (average 5 per month), 90% of migraine-specific questions asked during an appointment were either close-ended or consisted of a short answer. Postvisit interviews with both clinicians and patients revealed these pairs misaligned on migraine frequency (55% of the time) and impairment (51%). One-third of patients were candidates to receive preventive medication, yet only 20% of them did so. Prevention was not discussed in half of the visits with patients who were candidates to receive preventive therapy but did not get it.¹⁰

A panel with extensive experience in migraine reviewed questions from migraine diaries and noted that migraine sufferers find value in capturing wide-ranging information about their condition, whereas clinicians prefer small amounts of data they perceive as relevant to managing migraine.¹⁵ It also is reported that the number of questions patients ask is inversely related to the amount of information a clinician gives.¹⁶

Recommended strategies

In his review article, Mamura reinforces the concept of open 2-way communication, which involves patients in their care more deeply and reinforces positive habits.⁸ It is important to be mindful that discussing triggers exclusively can be counterproductive and frustrating for patients, particularly if the conversation is about trigger avoidance. Patients might feel stigmatized by triggers, come away thinking nothing can be done to control them, and become more anxious about impending episodes.⁸ In fact, a better strategy could be to work with the patient to train their brain to become acclimated to certain triggers or premonitory symptoms, rather than avoiding them.¹⁷

Mamura provides a concise summary of 4 best-practice strategies.⁸ The first 2 should be factored into advice given to patients about migraine triggers and premonitory symptoms; the remaining 2 help frame the treatment approach:

1. Ask patients to keep a headache diary, which eliminates faulty recall and provides a clearer picture of migraine frequency and severity. Include symptoms and other important factors—missed time from work, canceled family activities, nausea and vomiting, etc. Journaling might uncover triggers that can be eliminated or acclimated to via behavior modification. It also can reveal to the patient that certain triggers might not be as useful in predicting migraine as originally thought.

2. Rather than trigger avoidance, suggest that patients concentrate on healthy lifestyle choices, including maintaining healthy weight, getting sufficient sleep, and exercising regularly. The latter has been shown in some studies to work better than preventive medications. Although a behavior change, such as acclimating to certain noises, is not thought to be a healthy lifestyle habit, it ends up being just that if it improves tolerance and reduces migraine episodes.

3. Recognize that many patients have a fear of experiencing a migraine between episodes. If observed in a patient, treat it aggressively. Left unmanaged, this condition could lead to chronic migraine and medication overuse. The right acute medication might be sufficient, but sometimes cognitive-behavioral therapy and biofeedback techniques could be necessary to address behavioral issues that might be interfering with successful treatment.

4. If attacks are frequent and making it difficult to identify distinctive triggers, consider preventive therapy. Patients might resist using preventive medications because they feel eliminating triggers is sufficient, or they might be concerned about medication cost and adverse effects. Eliminating a stressful event alone likely will not help, so it’s important to review with patients—using plain language—how preventive medication treats the underlying cause of migraine and decreases brain excitability, making the patient less prone to attacks.⁸

Emerging medications

New treatments offer increased options for the acute and preventive treatment of migraine attacks. New acute pharmacologic treatments include gepants and ditans. The gepants target calcitonin gene-related peptide (CGRP), a potent vasodilator and neurotransmitter. During migraine episodes, serum levels of CGRP increase as the peptide is released, modulating the transmission of nociceptive signals from peripheral trigeminal sensory afferents into the central trigeminal system.¹⁹ In clinical trials of acute migraine treatment, the gepants provided pain freedom at 2 hours in approximately 20% of attacks, pain relief at 2 hours in 58%, and freedom from the most bothersome symptom at 2 hours in 36% with significant benefit over placebo.^20,21 As these oral formulations became available in 2020, there are not enough data on potential long-term adverse events, particularly cardiovascular effects.¹⁸ However, the gepants are not associated with medication overuse headache and there is no contraindication to their use in patients with cardiovascular disease. These agents, currently available for oral administration, also show benefit as preventive agents and parenteral formulations are in development.  

Ditans target the serotonin 5HT-1F receptor. Triptans target this receptor as well as the 5HT-1B and 5HT-1D receptors. The 5HT-1B receptor action is responsible for constriction of cerebral and peripheral blood vessels that occurs with triptans. Thus, ditans are also options for treating patients with vascular disease. Lasmiditan, the only compound in this class thus far, yielded pain freedom in 2 hours in 31%, pain relief 2 hours in 64%, and relief of the most bothersome symptom at 2 hours in 41%.²² Lasmiditan crosses the blood-brain barrier. Thus, the most common side effects are dizziness, somnolence, and paresthesias, which are generally mild to moderate in severity. Based on driving simulation studies performed in the absence of migraine, patients should not drive within 8 hours of dosing.

Neuromodulation devices are effective options that avoid potential adverse events of systemic treatments. They include external trigeminal nerve stimulation, noninvasive vagus nerve stimulation, remote electrical neuromodulation, caloric vestibular stimulation, and single-pulse transcranial magnetic stimulation. Other treatments in development for the acute treatment of migraine include improved parenteral delivery systems and combination oral preparations of existing medications.

Monoclonal antibodies that block the CGRP ligand or its receptor were introduced in 2018, with 4 medications currently available. This is the first class of migraine medications specifically designed for migraine prevention. They are administered parenterally (subcutaneously or intravenously) either monthly or quarterly, depending on the medication.  The anti-CGRP monoclonal antibodies are indicated for the prevention of episodic and chronic migraine and are eliminated by proteolytic degradation, not involving the liver and reducing the potential for hepatotoxicity and drug-drug interactions.²³ A meta-analysis evaluated the subcutaneous formulations studied for chronic migraine, enrolling participants with at least 15 headache days monthly with migraine occurring on at least 8 of those days. In this cohort with a large disease burden, the pooled 50% responder rate 9-12 weeks after administration of the first dose was 37.4% and the 75% responder rate was 12.7%.²⁴ There was also improvement in the number of migraine days, number of days using acute treatment, and total headache hours. The most common side effects were injection site reactions and constipation, with post-marketing reports of hypertension in the compound targeting the CGRP receptor, with or without pre-existing hypertension.²⁵ The safety profile for use during pregnancy was not studied in any of the medications discussed in this section. 

Summary

Acute migraine headache is a significant management challenge for neurologists, headache specialists, and other clinicians involved in its treatment. Addressing potential migraine triggers can be a particularly overwhelming task because multiple components and factors play into the disorder. Perceived triggers; their frequency and strength; the effort by patients to control their environment; and the blurred line between real triggers and premonitory symptoms present the clinician with an amalgam of components that must be sorted through, defined, prioritized, and managed. Even though migraine symptoms generally appear along a 4-phase timeline, some symptoms stretch across multiple phases and not all symptoms play out in a linear fashion.

There are specific steps clinicians can take to simplify the process, optimize management, and improve patient outcomes and quality of life. Start by gaining an understanding of common triggers and the best evidence regarding triggers and premonitory symptoms. Use this evidence to modify your approach in practice, if necessary. Specifically:

• Improve the information you gather from patients by asking open-ended questions about their experience during a migraine headache, as well as the period between attacks.

• Rather than having patients tell you how many episodes they experience each month, try to elicit from them how many days per month they feel disabled.

• Ask your patients to keep a headache diary.

• Talk less about trigger avoidance and more about making healthy lifestyle choices.

• Address potential cephalgiaphobia via cognitive-behavioral therapy and biofeedback techniques.

• Consider managing frequent migraine attacks with preventive treatment, which now includes CGRP-targeted medications that are as effective as other agents but have fewer adverse effects and might avoid medication overuse headache.

Dr. Friedman reports being an Advisory Board member for Allergan, Biohaven Pharmaceuticals, Eli Lilly, Impel NeuroPharma, Invex, Lundbeck, Revance Therapeutics, Satsuma Pharmaceuticals, Teva Pharmaceuticals, Theranica, and Zosano Pharma. She has received grant support from Allergan, Eli Lilly, Merck, and Zosano Pharma. She is on the Medical Advisory Board for Spinal CSF Leak Foundation, HealthyWomen, and the Board of Directors of the Southern Headache Society. She currently sits on the Editorial Board of Neurology Reviews and has been a contributing author for MedLink Neurology and Medscape.

Patients with metastatic breast cancer (MBC) face an elevated risk of severe illness or dying from COVID-19. Given the slow rollout of the Moderna and Pfizer COVID vaccines and new, more infectious viral variants circulating in the United States, oncologists will face a challenging balancing act for the foreseeable future: sustaining patients› MBC care while safeguarding them from COVID. The scale leans heavily toward continuing treatment, experts say.

“If we stop treatment for metastatic breast cancer, death will occur quickly,” Fatima F. Cardoso, MD, director of the breast unit at Champalimaud Clinical Centre in Lisbon, Portugal, stated this past August in a Medscape perspective.

Joanne Mortimer, MD, director of Women’s Cancer Programs at City of Hope, a comprehensive cancer center near Los Angeles, expressed a similar sentiment. “Having MBC is worse than getting COVID,” she told Medscape. “We can’t stop treating patients with MBC because of concerns of exposure.”

But maintaining treatment does not mean business as usual. Oncologists have had to modify their pre-pandemic practices to some degree, and that degree largely depends on local COVID conditions.

“Weighing the risk of treatment with the risk of contracting the virus means that many places have carried on treating metastatic breast cancer in a more thoughtful, careful way,” said Jill Dietz, MD, president of the American Society of Breast Surgeons. “That means focusing on high-value treatments for patients with the goal of maximizing their outcomes and quality of life while limiting in-person visits and potentially unnecessary elements of care.”

To guide this more careful approach, Dr. Dietz and colleagues from the recently formed COVID-19 Pandemic Breast Cancer Consortium published recommendations in April 2020 to account for different disease types and severities. These recommendations align closely with those from Cardoso and colleagues in Europe, also published last April.

Although issued early in the pandemic when there was greater uncertainty about viral transmission, adverse outcomes, and treatment for COVID-19, these recommendations still hold almost a year later.

“The framework has proven to be timeless in that it can help institutions where they are in the pandemic,” Dr. Dietz said.

The recommendations at play

For MBC, in particular, Dr. Dietz and colleagues focused on patients who need systemic care but whose treatment can be modified to keep them home more. The modifications include prescribing oral agents such as capecitabine, vinorelbine, and cyclophosphamide to minimize visits to the hospital or infusion suite.

To limit adverse events associated with these oral drugs, Dr. Dietz and colleagues also recommended reducing the dose when possible. For instance, research shows that lowering the dose of the CDK4/6 inhibitor palbociclib in patients with HR+/HER2-negative MBC does not diminish efficacy.

When oral agents are not an option, Dr. Dietz and colleagues suggested stretching out the intervals for chemotherapy infusions or injections. Data show that trastuzumab and pertuzumab injections for metastatic HER2-positive tumors «may reasonably be administered at longer intervals,» such as 4 weeks instead of 3 weeks.

The extent to which oncologists have applied these recommendations hinges on two factors: the local severity of COVID-19 cases and institution-specific policies.

For some oncologists, the pandemic has largely left treatment decisions untouched. “COVID-19 has only minimally impacted my practice,” said Rita Nanda, MD, director of the Breast Oncology Program and associate professor of medicine at University of Chicago Medicine.

Dr. Nanda recalled her concerns in the early days of the pandemic. As the nation watched COVID cases surge across New York City, Chicagoans prepared for the worst, fashioning the McCormick Place Convention Center into a field hospital for COVID patients.

“But fortunately, we were never overwhelmed at the University of Chicago and never needed to use the convention center,” Dr. Nanda said. “We did not have to alter or limit the type of therapy patients with MBC could receive.”

The main changes described by Dr. Nanda at the University of Chicago have centered around limiting the flow of traffic within the infusion suite or hospital by implementing prescreening checks to catch patients with COVID symptoms, keeping waiting rooms empty and infusion centers socially distanced, and having patients come in for appointments solo. The university’s home phlebotomy service also came in handy. Implemented before the pandemic, this service allowed patients with MBC to get their labs done at home before coming in for treatment.

“Overall, with social distancing, mask wearing, and limiting who comes in to the clinic, we have been able to keep patients and staff safe without altering treatment-specific decisions,” Dr. Nanda said.

Streamlining the foot traffic in the cancer center also worked well for Lisa A. Carey, MD, chief of the Division of Hematology/Oncology and deputy director of clinical sciences at University of North Carolina-Chapel Hill. “The truth is, oncological principles of care are still in place,” said Dr. Carey, the Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research. “COVID hasn’t altered those; it has only thrown a little wrench in how we deliver that care.”

Kelly McCann, MD, PhD, a hematologist/oncologist in the Department of Medicine at the David Geffen School of Medicine, University of California, Los Angeles, has had to walk a tighter rope to protect her patients with MBC, as COVID cases began to soar in LA county last fall.

To keep patients with MBC home more, Dr. McCann said many chose oral cytotoxic chemotherapies over infusional therapies. Some patients with HER2-positive MBC, for instance, opted for the oral combination neratinib + capecitabine over a trastuzumab-deruxtecan infusion, and others with triple-negative tumors chose capecitabine over a taxane.

At City of Hope, Mortimer has had a different experience of LA county’s COVID surge. Because the center only treats patients with cancer, “we have not had huge numbers of patients with COVID or had to significantly modify our practice outside of screening patients who come in and doing fewer scans compared to pre-COVID,” she said. With these precautions, “we have had no internal transmission of COVID within our institution.”

Still, patients with MBC have gotten COVID, and treating both illnesses does complicate decision-making. In some cases, Mortimer has postponed cancer treatment for patients who can delay for a few weeks while they recover from COVID. But patients who need to continue MBC treatment receive care in a separate unit, and Mortimer considers prescribing Eli Lilly’s recently approved antibody therapy bamlanivimab to treat COVID symptoms. “For each situation, we can always page our infectious disease experts to address any concerns or questions,” Dr. Mortimer said.

The MBC and COVID toll

The biggest hurdle for patients with MBC has been less about treatment decisions and more about handling the psychological toll of the pandemic, according to Charles Shapiro, MD, medical oncologist, Icahn School of Medicine at Mount Sinai in New York City.

“These are my personal observations, but I’ve seen how much more stressful it is to have metastatic breast cancer during the pandemic,” said Dr. Shapiro, who worries that fear of COVID may fuel or exacerbate patients’ depression and anxiety. “Patients can’t have family and friends by their side during infusions or appointments, and many feel isolated because of the risk of exposure.”

Because most patients with MBC still need in-person care such as exams, blood draws, or chemotherapy infusions, Dr. McCann has found that many of her patients “are afraid to come to a medical center and have been delaying appointments, imaging, and procedures.”

The psychological toll of treating breast cancer during the pandemic has touched oncologists as well. A recent survey found that burnout scores were significantly higher among physicians whose patients experienced delays in care, including chemotherapy or specialty consultations.

Getting patients vaccinated will improve protection and hopefully lessen fears surrounding COVID infection and transmission. Preliminary recommendations from the National Comprehensive Cancer Network›s COVID-19 Vaccination Advisory Committee state that patients with cancer «should be prioritized for vaccination.»

Dr. McCann agreed. “I’ve recommended COVID-19 vaccination to all of my patients with MBC,” she said. But because a lot of these therapies suppress the immune system to some degree, “I’ll recommend a period of time for vaccination in which the immune system is expected to have recovered, such as in the days prior to a dose of chemotherapy.”

Overall, according to Dr. Carey, institutional responses to treating MBC during the pandemic have been very similar: The key has been that “no one is keeping secrets,” she said. “Our global oncology community is sharing and adopting best practices. Our focus has been doing right by our patients.”

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

Patients with metastatic breast cancer (MBC) face an elevated risk of severe illness or dying from COVID-19. Given the slow rollout of the Moderna and Pfizer COVID vaccines and new, more infectious viral variants circulating in the United States, oncologists will face a challenging balancing act for the foreseeable future: sustaining patients› MBC care while safeguarding them from COVID. The scale leans heavily toward continuing treatment, experts say.

“If we stop treatment for metastatic breast cancer, death will occur quickly,” Fatima F. Cardoso, MD, director of the breast unit at Champalimaud Clinical Centre in Lisbon, Portugal, stated this past August in a Medscape perspective.

Joanne Mortimer, MD, director of Women’s Cancer Programs at City of Hope, a comprehensive cancer center near Los Angeles, expressed a similar sentiment. “Having MBC is worse than getting COVID,” she told Medscape. “We can’t stop treating patients with MBC because of concerns of exposure.”

But maintaining treatment does not mean business as usual. Oncologists have had to modify their pre-pandemic practices to some degree, and that degree largely depends on local COVID conditions.

“Weighing the risk of treatment with the risk of contracting the virus means that many places have carried on treating metastatic breast cancer in a more thoughtful, careful way,” said Jill Dietz, MD, president of the American Society of Breast Surgeons. “That means focusing on high-value treatments for patients with the goal of maximizing their outcomes and quality of life while limiting in-person visits and potentially unnecessary elements of care.”

To guide this more careful approach, Dr. Dietz and colleagues from the recently formed COVID-19 Pandemic Breast Cancer Consortium published recommendations in April 2020 to account for different disease types and severities. These recommendations align closely with those from Cardoso and colleagues in Europe, also published last April.

Although issued early in the pandemic when there was greater uncertainty about viral transmission, adverse outcomes, and treatment for COVID-19, these recommendations still hold almost a year later.

“The framework has proven to be timeless in that it can help institutions where they are in the pandemic,” Dr. Dietz said.

The recommendations at play

For MBC, in particular, Dr. Dietz and colleagues focused on patients who need systemic care but whose treatment can be modified to keep them home more. The modifications include prescribing oral agents such as capecitabine, vinorelbine, and cyclophosphamide to minimize visits to the hospital or infusion suite.

To limit adverse events associated with these oral drugs, Dr. Dietz and colleagues also recommended reducing the dose when possible. For instance, research shows that lowering the dose of the CDK4/6 inhibitor palbociclib in patients with HR+/HER2-negative MBC does not diminish efficacy.

When oral agents are not an option, Dr. Dietz and colleagues suggested stretching out the intervals for chemotherapy infusions or injections. Data show that trastuzumab and pertuzumab injections for metastatic HER2-positive tumors «may reasonably be administered at longer intervals,» such as 4 weeks instead of 3 weeks.

The extent to which oncologists have applied these recommendations hinges on two factors: the local severity of COVID-19 cases and institution-specific policies.

For some oncologists, the pandemic has largely left treatment decisions untouched. “COVID-19 has only minimally impacted my practice,” said Rita Nanda, MD, director of the Breast Oncology Program and associate professor of medicine at University of Chicago Medicine.

Dr. Nanda recalled her concerns in the early days of the pandemic. As the nation watched COVID cases surge across New York City, Chicagoans prepared for the worst, fashioning the McCormick Place Convention Center into a field hospital for COVID patients.

“But fortunately, we were never overwhelmed at the University of Chicago and never needed to use the convention center,” Dr. Nanda said. “We did not have to alter or limit the type of therapy patients with MBC could receive.”

The main changes described by Dr. Nanda at the University of Chicago have centered around limiting the flow of traffic within the infusion suite or hospital by implementing prescreening checks to catch patients with COVID symptoms, keeping waiting rooms empty and infusion centers socially distanced, and having patients come in for appointments solo. The university’s home phlebotomy service also came in handy. Implemented before the pandemic, this service allowed patients with MBC to get their labs done at home before coming in for treatment.

“Overall, with social distancing, mask wearing, and limiting who comes in to the clinic, we have been able to keep patients and staff safe without altering treatment-specific decisions,” Dr. Nanda said.

Streamlining the foot traffic in the cancer center also worked well for Lisa A. Carey, MD, chief of the Division of Hematology/Oncology and deputy director of clinical sciences at University of North Carolina-Chapel Hill. “The truth is, oncological principles of care are still in place,” said Dr. Carey, the Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research. “COVID hasn’t altered those; it has only thrown a little wrench in how we deliver that care.”

Kelly McCann, MD, PhD, a hematologist/oncologist in the Department of Medicine at the David Geffen School of Medicine, University of California, Los Angeles, has had to walk a tighter rope to protect her patients with MBC, as COVID cases began to soar in LA county last fall.

To keep patients with MBC home more, Dr. McCann said many chose oral cytotoxic chemotherapies over infusional therapies. Some patients with HER2-positive MBC, for instance, opted for the oral combination neratinib + capecitabine over a trastuzumab-deruxtecan infusion, and others with triple-negative tumors chose capecitabine over a taxane.

At City of Hope, Mortimer has had a different experience of LA county’s COVID surge. Because the center only treats patients with cancer, “we have not had huge numbers of patients with COVID or had to significantly modify our practice outside of screening patients who come in and doing fewer scans compared to pre-COVID,” she said. With these precautions, “we have had no internal transmission of COVID within our institution.”

Still, patients with MBC have gotten COVID, and treating both illnesses does complicate decision-making. In some cases, Mortimer has postponed cancer treatment for patients who can delay for a few weeks while they recover from COVID. But patients who need to continue MBC treatment receive care in a separate unit, and Mortimer considers prescribing Eli Lilly’s recently approved antibody therapy bamlanivimab to treat COVID symptoms. “For each situation, we can always page our infectious disease experts to address any concerns or questions,” Dr. Mortimer said.

The MBC and COVID toll

The biggest hurdle for patients with MBC has been less about treatment decisions and more about handling the psychological toll of the pandemic, according to Charles Shapiro, MD, medical oncologist, Icahn School of Medicine at Mount Sinai in New York City.

“These are my personal observations, but I’ve seen how much more stressful it is to have metastatic breast cancer during the pandemic,” said Dr. Shapiro, who worries that fear of COVID may fuel or exacerbate patients’ depression and anxiety. “Patients can’t have family and friends by their side during infusions or appointments, and many feel isolated because of the risk of exposure.”

Because most patients with MBC still need in-person care such as exams, blood draws, or chemotherapy infusions, Dr. McCann has found that many of her patients “are afraid to come to a medical center and have been delaying appointments, imaging, and procedures.”

The psychological toll of treating breast cancer during the pandemic has touched oncologists as well. A recent survey found that burnout scores were significantly higher among physicians whose patients experienced delays in care, including chemotherapy or specialty consultations.

Getting patients vaccinated will improve protection and hopefully lessen fears surrounding COVID infection and transmission. Preliminary recommendations from the National Comprehensive Cancer Network›s COVID-19 Vaccination Advisory Committee state that patients with cancer «should be prioritized for vaccination.»

Dr. McCann agreed. “I’ve recommended COVID-19 vaccination to all of my patients with MBC,” she said. But because a lot of these therapies suppress the immune system to some degree, “I’ll recommend a period of time for vaccination in which the immune system is expected to have recovered, such as in the days prior to a dose of chemotherapy.”

Overall, according to Dr. Carey, institutional responses to treating MBC during the pandemic have been very similar: The key has been that “no one is keeping secrets,” she said. “Our global oncology community is sharing and adopting best practices. Our focus has been doing right by our patients.”

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

Patients with metastatic breast cancer (MBC) face an elevated risk of severe illness or dying from COVID-19. Given the slow rollout of the Moderna and Pfizer COVID vaccines and new, more infectious viral variants circulating in the United States, oncologists will face a challenging balancing act for the foreseeable future: sustaining patients› MBC care while safeguarding them from COVID. The scale leans heavily toward continuing treatment, experts say.

“If we stop treatment for metastatic breast cancer, death will occur quickly,” Fatima F. Cardoso, MD, director of the breast unit at Champalimaud Clinical Centre in Lisbon, Portugal, stated this past August in a Medscape perspective.

Joanne Mortimer, MD, director of Women’s Cancer Programs at City of Hope, a comprehensive cancer center near Los Angeles, expressed a similar sentiment. “Having MBC is worse than getting COVID,” she told Medscape. “We can’t stop treating patients with MBC because of concerns of exposure.”

But maintaining treatment does not mean business as usual. Oncologists have had to modify their pre-pandemic practices to some degree, and that degree largely depends on local COVID conditions.

“Weighing the risk of treatment with the risk of contracting the virus means that many places have carried on treating metastatic breast cancer in a more thoughtful, careful way,” said Jill Dietz, MD, president of the American Society of Breast Surgeons. “That means focusing on high-value treatments for patients with the goal of maximizing their outcomes and quality of life while limiting in-person visits and potentially unnecessary elements of care.”

To guide this more careful approach, Dr. Dietz and colleagues from the recently formed COVID-19 Pandemic Breast Cancer Consortium published recommendations in April 2020 to account for different disease types and severities. These recommendations align closely with those from Cardoso and colleagues in Europe, also published last April.

Although issued early in the pandemic when there was greater uncertainty about viral transmission, adverse outcomes, and treatment for COVID-19, these recommendations still hold almost a year later.

“The framework has proven to be timeless in that it can help institutions where they are in the pandemic,” Dr. Dietz said.

The recommendations at play

For MBC, in particular, Dr. Dietz and colleagues focused on patients who need systemic care but whose treatment can be modified to keep them home more. The modifications include prescribing oral agents such as capecitabine, vinorelbine, and cyclophosphamide to minimize visits to the hospital or infusion suite.

To limit adverse events associated with these oral drugs, Dr. Dietz and colleagues also recommended reducing the dose when possible. For instance, research shows that lowering the dose of the CDK4/6 inhibitor palbociclib in patients with HR+/HER2-negative MBC does not diminish efficacy.

When oral agents are not an option, Dr. Dietz and colleagues suggested stretching out the intervals for chemotherapy infusions or injections. Data show that trastuzumab and pertuzumab injections for metastatic HER2-positive tumors «may reasonably be administered at longer intervals,» such as 4 weeks instead of 3 weeks.

The extent to which oncologists have applied these recommendations hinges on two factors: the local severity of COVID-19 cases and institution-specific policies.

For some oncologists, the pandemic has largely left treatment decisions untouched. “COVID-19 has only minimally impacted my practice,” said Rita Nanda, MD, director of the Breast Oncology Program and associate professor of medicine at University of Chicago Medicine.

Dr. Nanda recalled her concerns in the early days of the pandemic. As the nation watched COVID cases surge across New York City, Chicagoans prepared for the worst, fashioning the McCormick Place Convention Center into a field hospital for COVID patients.

“But fortunately, we were never overwhelmed at the University of Chicago and never needed to use the convention center,” Dr. Nanda said. “We did not have to alter or limit the type of therapy patients with MBC could receive.”

The main changes described by Dr. Nanda at the University of Chicago have centered around limiting the flow of traffic within the infusion suite or hospital by implementing prescreening checks to catch patients with COVID symptoms, keeping waiting rooms empty and infusion centers socially distanced, and having patients come in for appointments solo. The university’s home phlebotomy service also came in handy. Implemented before the pandemic, this service allowed patients with MBC to get their labs done at home before coming in for treatment.

“Overall, with social distancing, mask wearing, and limiting who comes in to the clinic, we have been able to keep patients and staff safe without altering treatment-specific decisions,” Dr. Nanda said.

Streamlining the foot traffic in the cancer center also worked well for Lisa A. Carey, MD, chief of the Division of Hematology/Oncology and deputy director of clinical sciences at University of North Carolina-Chapel Hill. “The truth is, oncological principles of care are still in place,” said Dr. Carey, the Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research. “COVID hasn’t altered those; it has only thrown a little wrench in how we deliver that care.”

Kelly McCann, MD, PhD, a hematologist/oncologist in the Department of Medicine at the David Geffen School of Medicine, University of California, Los Angeles, has had to walk a tighter rope to protect her patients with MBC, as COVID cases began to soar in LA county last fall.

To keep patients with MBC home more, Dr. McCann said many chose oral cytotoxic chemotherapies over infusional therapies. Some patients with HER2-positive MBC, for instance, opted for the oral combination neratinib + capecitabine over a trastuzumab-deruxtecan infusion, and others with triple-negative tumors chose capecitabine over a taxane.

At City of Hope, Mortimer has had a different experience of LA county’s COVID surge. Because the center only treats patients with cancer, “we have not had huge numbers of patients with COVID or had to significantly modify our practice outside of screening patients who come in and doing fewer scans compared to pre-COVID,” she said. With these precautions, “we have had no internal transmission of COVID within our institution.”

Still, patients with MBC have gotten COVID, and treating both illnesses does complicate decision-making. In some cases, Mortimer has postponed cancer treatment for patients who can delay for a few weeks while they recover from COVID. But patients who need to continue MBC treatment receive care in a separate unit, and Mortimer considers prescribing Eli Lilly’s recently approved antibody therapy bamlanivimab to treat COVID symptoms. “For each situation, we can always page our infectious disease experts to address any concerns or questions,” Dr. Mortimer said.

The MBC and COVID toll

The biggest hurdle for patients with MBC has been less about treatment decisions and more about handling the psychological toll of the pandemic, according to Charles Shapiro, MD, medical oncologist, Icahn School of Medicine at Mount Sinai in New York City.

“These are my personal observations, but I’ve seen how much more stressful it is to have metastatic breast cancer during the pandemic,” said Dr. Shapiro, who worries that fear of COVID may fuel or exacerbate patients’ depression and anxiety. “Patients can’t have family and friends by their side during infusions or appointments, and many feel isolated because of the risk of exposure.”

Because most patients with MBC still need in-person care such as exams, blood draws, or chemotherapy infusions, Dr. McCann has found that many of her patients “are afraid to come to a medical center and have been delaying appointments, imaging, and procedures.”

The psychological toll of treating breast cancer during the pandemic has touched oncologists as well. A recent survey found that burnout scores were significantly higher among physicians whose patients experienced delays in care, including chemotherapy or specialty consultations.

Getting patients vaccinated will improve protection and hopefully lessen fears surrounding COVID infection and transmission. Preliminary recommendations from the National Comprehensive Cancer Network›s COVID-19 Vaccination Advisory Committee state that patients with cancer «should be prioritized for vaccination.»

Dr. McCann agreed. “I’ve recommended COVID-19 vaccination to all of my patients with MBC,” she said. But because a lot of these therapies suppress the immune system to some degree, “I’ll recommend a period of time for vaccination in which the immune system is expected to have recovered, such as in the days prior to a dose of chemotherapy.”

Overall, according to Dr. Carey, institutional responses to treating MBC during the pandemic have been very similar: The key has been that “no one is keeping secrets,” she said. “Our global oncology community is sharing and adopting best practices. Our focus has been doing right by our patients.”

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

Neoadjuvant chemoradiation plus esophagectomy can be performed safely in well-selected older patients with locally advanced esophageal or esophagogastric junction cancer, according to a review 282 patients treated from 2004 through 2019 at Ochsner Medical Center, New Orleans.

Although guidelines recommend curative-intent neoadjuvant chemoradiation (NACR) followed by surgical resection, it’s been demonstrated in several studies that “older patients with potentially curable stage II and III disease are often not considered” for the approach out of concern that they will not tolerate it, said investigators led by W. Peter Sawyer, MD, a surgery resident at Ochsner.

Outcomes, however, were comparable in the study when 188 patients aged younger than 70 years were compared with 94 patients aged 70 years or older, including 4 who were over 80 years old. “Patients 70 years and older should be evaluated for optimal curative therapy including neoadjuvant chemoradiotherapy and surgical resection,” the investigators concluded.

The patients had NACR followed by esophagectomy mostly for stage 2 disease. The average age was 59 years in the younger group and 74 years in the older group.

Older patients had a higher prevalence of cardiac, vascular, and pulmonary comorbidities and were more likely to have postoperative atrial arrhythmia and urinary retention.

However, there were no statistically significant differences in hospital length of stay (about 10 days in both groups), operative mortality (4.3% in the older group versus 3.8% in the younger group), or the incidence of postoperative grade 3 or higher complications (27.7% older versus 38.3% younger). Age-adjusted survival was 44.8% at 5 years among patients 70 years and older versus 39% among younger patients.

Comorbidity scores, clinically positive nodes, and clinical T3 tumors predicted worse survival on multivariate analysis, but age did not.

“Age itself doesn’t represent a contraindication to aggressive treatment. It is the patient’s comorbidities and functional status which are more important to predict the risk of complications after esophagectomy,” said Daniela Molena, MD, director of the esophageal surgery program at Memorial Sloan Kettering Cancer Center, New York, when asked for a comment.

The team noted that the results “reflect careful patient selection as well as thorough preoperative evaluation and preparation.” Patients with unstable or severe chronic heart disease, moderate to severe chronic liver disease, or severe chronic pulmonary disease were ineligible for surgery. Eligible patients had cardiac stress testing and were strongly encouraged to begin daily exercise. Nutritional deficiencies were addressed before surgery.

The Ochsner team is one of several in recent years that have pushed back on age limits for aggressive esophageal cancer treatment.

A British team, for example, reviewed 992 transthoracic esophagectomies, including 330 in patients 70 years or older, and found lower in-hospital mortality and pulmonary and cardiac morbidity for older patients than previously reported.

They concluded that “age should not be a discriminating factor when determining the treatment strategy for patients presenting with curative esophageal cancer.”

Even so, undertreatment remains “a big problem for elderly patients, and since the median age at diagnoses is 68 years, this is a problem for a large portion of patients with esophageal cancer,” Dr. Molena said.

“Patients can be cured of this disease” with aggressive treatment, but “unfortunately, patients often are not evaluated by a surgeon or referred to a high-volume center and are discouraged from undergoing surgery after an apparent good response to chemoradiation,” partly because esophagectomy has “unfairly gained a bad reputation over the years,” she said.

“There are clear data that outcomes of esophagectomy are very good at high volume centers with minimally invasive techniques and the ability to promptly identify and treat complications,” Dr. Molena said.

Overall, 52% of patients aged 70 years or older with stage II and III disease underwent NACR plus surgery at Ochsner, suggesting that “optimal, curative intent triple modality therapy [chemo, radiation, and esophagectomy] can be used successfully in a sizable segment of the elderly population,” the investigators said.

Treatment has changed significantly at Ochsner since the start of the review period in 2004, including a shift away from a fluorouracil and cisplatin doublet in favor of carboplatin and paclitaxel, which is less toxic, and greater use of minimally invasive surgery. The proportion of people 70 years or older undergoing triple modality treatment has been steadily increasing.

There was no outside funding. Investigator disclosures weren’t reported. Dr. Molena had no relevant disclosures.
 

[email protected]

Neoadjuvant chemoradiation plus esophagectomy can be performed safely in well-selected older patients with locally advanced esophageal or esophagogastric junction cancer, according to a review 282 patients treated from 2004 through 2019 at Ochsner Medical Center, New Orleans.

Although guidelines recommend curative-intent neoadjuvant chemoradiation (NACR) followed by surgical resection, it’s been demonstrated in several studies that “older patients with potentially curable stage II and III disease are often not considered” for the approach out of concern that they will not tolerate it, said investigators led by W. Peter Sawyer, MD, a surgery resident at Ochsner.

Outcomes, however, were comparable in the study when 188 patients aged younger than 70 years were compared with 94 patients aged 70 years or older, including 4 who were over 80 years old. “Patients 70 years and older should be evaluated for optimal curative therapy including neoadjuvant chemoradiotherapy and surgical resection,” the investigators concluded.

The patients had NACR followed by esophagectomy mostly for stage 2 disease. The average age was 59 years in the younger group and 74 years in the older group.

Older patients had a higher prevalence of cardiac, vascular, and pulmonary comorbidities and were more likely to have postoperative atrial arrhythmia and urinary retention.

However, there were no statistically significant differences in hospital length of stay (about 10 days in both groups), operative mortality (4.3% in the older group versus 3.8% in the younger group), or the incidence of postoperative grade 3 or higher complications (27.7% older versus 38.3% younger). Age-adjusted survival was 44.8% at 5 years among patients 70 years and older versus 39% among younger patients.

Comorbidity scores, clinically positive nodes, and clinical T3 tumors predicted worse survival on multivariate analysis, but age did not.

“Age itself doesn’t represent a contraindication to aggressive treatment. It is the patient’s comorbidities and functional status which are more important to predict the risk of complications after esophagectomy,” said Daniela Molena, MD, director of the esophageal surgery program at Memorial Sloan Kettering Cancer Center, New York, when asked for a comment.

The team noted that the results “reflect careful patient selection as well as thorough preoperative evaluation and preparation.” Patients with unstable or severe chronic heart disease, moderate to severe chronic liver disease, or severe chronic pulmonary disease were ineligible for surgery. Eligible patients had cardiac stress testing and were strongly encouraged to begin daily exercise. Nutritional deficiencies were addressed before surgery.

The Ochsner team is one of several in recent years that have pushed back on age limits for aggressive esophageal cancer treatment.

A British team, for example, reviewed 992 transthoracic esophagectomies, including 330 in patients 70 years or older, and found lower in-hospital mortality and pulmonary and cardiac morbidity for older patients than previously reported.

They concluded that “age should not be a discriminating factor when determining the treatment strategy for patients presenting with curative esophageal cancer.”

Even so, undertreatment remains “a big problem for elderly patients, and since the median age at diagnoses is 68 years, this is a problem for a large portion of patients with esophageal cancer,” Dr. Molena said.

“Patients can be cured of this disease” with aggressive treatment, but “unfortunately, patients often are not evaluated by a surgeon or referred to a high-volume center and are discouraged from undergoing surgery after an apparent good response to chemoradiation,” partly because esophagectomy has “unfairly gained a bad reputation over the years,” she said.

“There are clear data that outcomes of esophagectomy are very good at high volume centers with minimally invasive techniques and the ability to promptly identify and treat complications,” Dr. Molena said.

Overall, 52% of patients aged 70 years or older with stage II and III disease underwent NACR plus surgery at Ochsner, suggesting that “optimal, curative intent triple modality therapy [chemo, radiation, and esophagectomy] can be used successfully in a sizable segment of the elderly population,” the investigators said.

Treatment has changed significantly at Ochsner since the start of the review period in 2004, including a shift away from a fluorouracil and cisplatin doublet in favor of carboplatin and paclitaxel, which is less toxic, and greater use of minimally invasive surgery. The proportion of people 70 years or older undergoing triple modality treatment has been steadily increasing.

There was no outside funding. Investigator disclosures weren’t reported. Dr. Molena had no relevant disclosures.
 

[email protected]

Neoadjuvant chemoradiation plus esophagectomy can be performed safely in well-selected older patients with locally advanced esophageal or esophagogastric junction cancer, according to a review 282 patients treated from 2004 through 2019 at Ochsner Medical Center, New Orleans.

Although guidelines recommend curative-intent neoadjuvant chemoradiation (NACR) followed by surgical resection, it’s been demonstrated in several studies that “older patients with potentially curable stage II and III disease are often not considered” for the approach out of concern that they will not tolerate it, said investigators led by W. Peter Sawyer, MD, a surgery resident at Ochsner.

Outcomes, however, were comparable in the study when 188 patients aged younger than 70 years were compared with 94 patients aged 70 years or older, including 4 who were over 80 years old. “Patients 70 years and older should be evaluated for optimal curative therapy including neoadjuvant chemoradiotherapy and surgical resection,” the investigators concluded.

The patients had NACR followed by esophagectomy mostly for stage 2 disease. The average age was 59 years in the younger group and 74 years in the older group.

Older patients had a higher prevalence of cardiac, vascular, and pulmonary comorbidities and were more likely to have postoperative atrial arrhythmia and urinary retention.

However, there were no statistically significant differences in hospital length of stay (about 10 days in both groups), operative mortality (4.3% in the older group versus 3.8% in the younger group), or the incidence of postoperative grade 3 or higher complications (27.7% older versus 38.3% younger). Age-adjusted survival was 44.8% at 5 years among patients 70 years and older versus 39% among younger patients.

Comorbidity scores, clinically positive nodes, and clinical T3 tumors predicted worse survival on multivariate analysis, but age did not.

“Age itself doesn’t represent a contraindication to aggressive treatment. It is the patient’s comorbidities and functional status which are more important to predict the risk of complications after esophagectomy,” said Daniela Molena, MD, director of the esophageal surgery program at Memorial Sloan Kettering Cancer Center, New York, when asked for a comment.

The team noted that the results “reflect careful patient selection as well as thorough preoperative evaluation and preparation.” Patients with unstable or severe chronic heart disease, moderate to severe chronic liver disease, or severe chronic pulmonary disease were ineligible for surgery. Eligible patients had cardiac stress testing and were strongly encouraged to begin daily exercise. Nutritional deficiencies were addressed before surgery.

The Ochsner team is one of several in recent years that have pushed back on age limits for aggressive esophageal cancer treatment.

A British team, for example, reviewed 992 transthoracic esophagectomies, including 330 in patients 70 years or older, and found lower in-hospital mortality and pulmonary and cardiac morbidity for older patients than previously reported.

They concluded that “age should not be a discriminating factor when determining the treatment strategy for patients presenting with curative esophageal cancer.”

Even so, undertreatment remains “a big problem for elderly patients, and since the median age at diagnoses is 68 years, this is a problem for a large portion of patients with esophageal cancer,” Dr. Molena said.

“Patients can be cured of this disease” with aggressive treatment, but “unfortunately, patients often are not evaluated by a surgeon or referred to a high-volume center and are discouraged from undergoing surgery after an apparent good response to chemoradiation,” partly because esophagectomy has “unfairly gained a bad reputation over the years,” she said.

“There are clear data that outcomes of esophagectomy are very good at high volume centers with minimally invasive techniques and the ability to promptly identify and treat complications,” Dr. Molena said.

Overall, 52% of patients aged 70 years or older with stage II and III disease underwent NACR plus surgery at Ochsner, suggesting that “optimal, curative intent triple modality therapy [chemo, radiation, and esophagectomy] can be used successfully in a sizable segment of the elderly population,” the investigators said.

Treatment has changed significantly at Ochsner since the start of the review period in 2004, including a shift away from a fluorouracil and cisplatin doublet in favor of carboplatin and paclitaxel, which is less toxic, and greater use of minimally invasive surgery. The proportion of people 70 years or older undergoing triple modality treatment has been steadily increasing.

There was no outside funding. Investigator disclosures weren’t reported. Dr. Molena had no relevant disclosures.
 

[email protected]

Globally, some 700,000 people die from antibiotic-resistant infections ever year; by 2050, that number could be 10 million, according to the United Nations. To find new ways to fight pathogenic microorganisms, scientists are looking to Crispr, the gene-editing tool, according to the New York Times.

“Crispr is a specialized region of DNA that creates what amount to genetic scissors – enzymes that allow the cell (or a scientist) to precisely edit other DNA or its sister molecule, RNA…Crispr was originally discovered in bacteria, where it helps keep track of past injury. When a virus attacks, the bacterium stores small chunks of the viral genome within its own DNA. This helps the bacterium recognize viral infections when they occur again. Then, using Crispr-associated enzymes, it can disarm the virus and prevent the infection from spreading…today researchers are looking to Crispr to edit bacteria and viruses that infect humans and create new treatments.”

In a recent study, researchers successfully used a Crispr-associated enzyme called Cas9 to eliminate a species of Salmonella. They programmed the Cas9 to view the bacterium as the enemy and forced Salmonella to make lethal cuts to its own genome.

Some companies are now exploring Crispr-based antibiotics that might be delivered through viruses engineered so that they cannot reproduce or cause infections themselves, to name just one approach.

“Now researchers face the challenge of demonstrating that Crispr antibacterial and antiviral drugs are effective in living animals and in humans, not just in the lab, and that they will be cheaper than conventional therapies.”
 

Reference

1. Sheikh K. Is Crispr the Next Antibiotic? The New York Times. Oct 28, 2019.

https://www.nytimes.com/2019/10/28/health/crispr-genetics-antibiotic-resistance.html. Accessed Dec 3, 2019.

Globally, some 700,000 people die from antibiotic-resistant infections ever year; by 2050, that number could be 10 million, according to the United Nations. To find new ways to fight pathogenic microorganisms, scientists are looking to Crispr, the gene-editing tool, according to the New York Times.

“Crispr is a specialized region of DNA that creates what amount to genetic scissors – enzymes that allow the cell (or a scientist) to precisely edit other DNA or its sister molecule, RNA…Crispr was originally discovered in bacteria, where it helps keep track of past injury. When a virus attacks, the bacterium stores small chunks of the viral genome within its own DNA. This helps the bacterium recognize viral infections when they occur again. Then, using Crispr-associated enzymes, it can disarm the virus and prevent the infection from spreading…today researchers are looking to Crispr to edit bacteria and viruses that infect humans and create new treatments.”

In a recent study, researchers successfully used a Crispr-associated enzyme called Cas9 to eliminate a species of Salmonella. They programmed the Cas9 to view the bacterium as the enemy and forced Salmonella to make lethal cuts to its own genome.

Some companies are now exploring Crispr-based antibiotics that might be delivered through viruses engineered so that they cannot reproduce or cause infections themselves, to name just one approach.

“Now researchers face the challenge of demonstrating that Crispr antibacterial and antiviral drugs are effective in living animals and in humans, not just in the lab, and that they will be cheaper than conventional therapies.”
 

Reference

1. Sheikh K. Is Crispr the Next Antibiotic? The New York Times. Oct 28, 2019.

https://www.nytimes.com/2019/10/28/health/crispr-genetics-antibiotic-resistance.html. Accessed Dec 3, 2019.

Globally, some 700,000 people die from antibiotic-resistant infections ever year; by 2050, that number could be 10 million, according to the United Nations. To find new ways to fight pathogenic microorganisms, scientists are looking to Crispr, the gene-editing tool, according to the New York Times.

“Crispr is a specialized region of DNA that creates what amount to genetic scissors – enzymes that allow the cell (or a scientist) to precisely edit other DNA or its sister molecule, RNA…Crispr was originally discovered in bacteria, where it helps keep track of past injury. When a virus attacks, the bacterium stores small chunks of the viral genome within its own DNA. This helps the bacterium recognize viral infections when they occur again. Then, using Crispr-associated enzymes, it can disarm the virus and prevent the infection from spreading…today researchers are looking to Crispr to edit bacteria and viruses that infect humans and create new treatments.”

In a recent study, researchers successfully used a Crispr-associated enzyme called Cas9 to eliminate a species of Salmonella. They programmed the Cas9 to view the bacterium as the enemy and forced Salmonella to make lethal cuts to its own genome.

Some companies are now exploring Crispr-based antibiotics that might be delivered through viruses engineered so that they cannot reproduce or cause infections themselves, to name just one approach.

“Now researchers face the challenge of demonstrating that Crispr antibacterial and antiviral drugs are effective in living animals and in humans, not just in the lab, and that they will be cheaper than conventional therapies.”
 

Reference

1. Sheikh K. Is Crispr the Next Antibiotic? The New York Times. Oct 28, 2019.

https://www.nytimes.com/2019/10/28/health/crispr-genetics-antibiotic-resistance.html. Accessed Dec 3, 2019.

The pandemic has affected reproductive health because of barriers to contraception access, potentially increasing unwanted pregnancies, reported Tracy Kuo Lin, PhD, of the University of California, San Francisco, and associates.

During the pandemic, women have experienced an increased desire to avoid pregnancy, and when that desire is coupled with loss of income, accessing contraception becomes more difficult, Dr. Lin and colleagues observed in a cross-sectional survey published in the journal Contraception.

The study aimed to quantify the effect of COVID-19 on women’s economic status and reproductive health decisions related to childbearing and pregnancy. Women aged 18-49 who resided in the U.S. were targeted via Facebook and Instagram advertisements from May 16 to June 16, 2020. In all, 554 racially diverse respondents from 43 states were selected: 41% aged 18-24, 37% aged 25-34, and 23% aged 35-49.
 

Income losses affect nearly half of respondents

In determining risk of unwanted pregnancy, the researchers considered the influence of COVID-19 on a number of factors related to economic well-being as well as respondents’ sexual activity, intimate partner violence, overall desire for pregnancy, and access to contraception as issues affecting their interest in becoming pregnant and their ability to access medical care and contraception. Overall, 46% experienced a reduction in income, 43% reported no change, and 10% experienced an increase in income.

Difficulty in being able to afford food, transportation, and housing doubled among respondents from 8% to 16% as a result of the pandemic. The study authors cited education, race/ethnicity, federal poverty level, and change in income as predictors of inability to provide for these basic needs.

A total of 83% of respondents reported having sex within the past month; 54% of those had sex with someone they lived with, compared with 29% who had sex with someone they did not live with. The pandemic had no impact on sexual desire for 37% of respondents, compared with 32% who experienced a decrease in desire, and 29% who experienced more desire for sex. The presence of shelter-in-place orders had no effect on frequency of or desire for sex. Among the respondents, 4% noted intimate partner violence, which increased slightly from 3% before the pandemic.

Among respondents using contraception, the study authors noted that 17% reported greater difficulty accessing birth control during the pandemic compared with 4% who felt access had become easier. Of those citing increased difficulties, 9% noted increasing challenges getting to a pharmacy, 4% were less able to afford birth control, 3% said it had become harder to obtain a prescription, and 1% cited difficulties having long-acting reversible contraceptives removed.

Despite the pandemic’s overall impact on quality of life, 41% of respondents reported a stronger desire to become pregnant, compared with 25% who had a reduced desire, and 34% whose interest in pregnancy was unchanged by the pandemic.

More than one-third of respondents (37%) admitted that COVID-19 contributed to their fears of becoming pregnant while 13% indicated their fear of pregnancy stemmed from concerns over being able to afford the cost of having a child. Not surprisingly, the decrease in desire for pregnancy was twice as high in those who reported they were unable to afford food, transportation, and/or housing compared with those who saw no change in their ability to afford basic needs.

“In these uncertain economic times, it is of utmost importance to create policies that will ensure access to and comprehensive coverage of core sexual and reproductive health services,” Dr. Lin and colleagues urged. “By doing so, we safeguard people’s ability to make decisions that support their reproductive health goals.”
 

Will COVID-19 drive needed practice and policy changes?

“This study highlights the economic and reproductive health toll of COVID-19 and the pressing need for improved contraception access,” Eve Espey, MD, MPH, said in an interview.

“Ob.gyns. and other practitioners can use this information to consider evidence-based practice changes that incorporate telemedicine visits, extended refills on contraceptive methods, and a focus on postpartum and postabortion initiation of contraception,” noted Dr. Espey, of the University of New Mexico, Albuquerque. For women who are experiencing economic hardship, consulting with state-based programs that offer pharmacy access and online access to contraceptives may offer a reasonable alternative, she added.

The study was funded by the University of California, San Francisco’s National Center of Excellence in Women’s Health. Dr. Lin received funding from Lazarex Cancer Foundation. The remaining authors had no conflicts of interest and reported no disclosures.

The pandemic has affected reproductive health because of barriers to contraception access, potentially increasing unwanted pregnancies, reported Tracy Kuo Lin, PhD, of the University of California, San Francisco, and associates.

During the pandemic, women have experienced an increased desire to avoid pregnancy, and when that desire is coupled with loss of income, accessing contraception becomes more difficult, Dr. Lin and colleagues observed in a cross-sectional survey published in the journal Contraception.

The study aimed to quantify the effect of COVID-19 on women’s economic status and reproductive health decisions related to childbearing and pregnancy. Women aged 18-49 who resided in the U.S. were targeted via Facebook and Instagram advertisements from May 16 to June 16, 2020. In all, 554 racially diverse respondents from 43 states were selected: 41% aged 18-24, 37% aged 25-34, and 23% aged 35-49.
 

Income losses affect nearly half of respondents

In determining risk of unwanted pregnancy, the researchers considered the influence of COVID-19 on a number of factors related to economic well-being as well as respondents’ sexual activity, intimate partner violence, overall desire for pregnancy, and access to contraception as issues affecting their interest in becoming pregnant and their ability to access medical care and contraception. Overall, 46% experienced a reduction in income, 43% reported no change, and 10% experienced an increase in income.

Difficulty in being able to afford food, transportation, and housing doubled among respondents from 8% to 16% as a result of the pandemic. The study authors cited education, race/ethnicity, federal poverty level, and change in income as predictors of inability to provide for these basic needs.

A total of 83% of respondents reported having sex within the past month; 54% of those had sex with someone they lived with, compared with 29% who had sex with someone they did not live with. The pandemic had no impact on sexual desire for 37% of respondents, compared with 32% who experienced a decrease in desire, and 29% who experienced more desire for sex. The presence of shelter-in-place orders had no effect on frequency of or desire for sex. Among the respondents, 4% noted intimate partner violence, which increased slightly from 3% before the pandemic.

Among respondents using contraception, the study authors noted that 17% reported greater difficulty accessing birth control during the pandemic compared with 4% who felt access had become easier. Of those citing increased difficulties, 9% noted increasing challenges getting to a pharmacy, 4% were less able to afford birth control, 3% said it had become harder to obtain a prescription, and 1% cited difficulties having long-acting reversible contraceptives removed.

Despite the pandemic’s overall impact on quality of life, 41% of respondents reported a stronger desire to become pregnant, compared with 25% who had a reduced desire, and 34% whose interest in pregnancy was unchanged by the pandemic.

More than one-third of respondents (37%) admitted that COVID-19 contributed to their fears of becoming pregnant while 13% indicated their fear of pregnancy stemmed from concerns over being able to afford the cost of having a child. Not surprisingly, the decrease in desire for pregnancy was twice as high in those who reported they were unable to afford food, transportation, and/or housing compared with those who saw no change in their ability to afford basic needs.

“In these uncertain economic times, it is of utmost importance to create policies that will ensure access to and comprehensive coverage of core sexual and reproductive health services,” Dr. Lin and colleagues urged. “By doing so, we safeguard people’s ability to make decisions that support their reproductive health goals.”
 

Will COVID-19 drive needed practice and policy changes?

“This study highlights the economic and reproductive health toll of COVID-19 and the pressing need for improved contraception access,” Eve Espey, MD, MPH, said in an interview.

“Ob.gyns. and other practitioners can use this information to consider evidence-based practice changes that incorporate telemedicine visits, extended refills on contraceptive methods, and a focus on postpartum and postabortion initiation of contraception,” noted Dr. Espey, of the University of New Mexico, Albuquerque. For women who are experiencing economic hardship, consulting with state-based programs that offer pharmacy access and online access to contraceptives may offer a reasonable alternative, she added.

The study was funded by the University of California, San Francisco’s National Center of Excellence in Women’s Health. Dr. Lin received funding from Lazarex Cancer Foundation. The remaining authors had no conflicts of interest and reported no disclosures.

The pandemic has affected reproductive health because of barriers to contraception access, potentially increasing unwanted pregnancies, reported Tracy Kuo Lin, PhD, of the University of California, San Francisco, and associates.

During the pandemic, women have experienced an increased desire to avoid pregnancy, and when that desire is coupled with loss of income, accessing contraception becomes more difficult, Dr. Lin and colleagues observed in a cross-sectional survey published in the journal Contraception.

The study aimed to quantify the effect of COVID-19 on women’s economic status and reproductive health decisions related to childbearing and pregnancy. Women aged 18-49 who resided in the U.S. were targeted via Facebook and Instagram advertisements from May 16 to June 16, 2020. In all, 554 racially diverse respondents from 43 states were selected: 41% aged 18-24, 37% aged 25-34, and 23% aged 35-49.
 

Income losses affect nearly half of respondents

In determining risk of unwanted pregnancy, the researchers considered the influence of COVID-19 on a number of factors related to economic well-being as well as respondents’ sexual activity, intimate partner violence, overall desire for pregnancy, and access to contraception as issues affecting their interest in becoming pregnant and their ability to access medical care and contraception. Overall, 46% experienced a reduction in income, 43% reported no change, and 10% experienced an increase in income.

Difficulty in being able to afford food, transportation, and housing doubled among respondents from 8% to 16% as a result of the pandemic. The study authors cited education, race/ethnicity, federal poverty level, and change in income as predictors of inability to provide for these basic needs.

A total of 83% of respondents reported having sex within the past month; 54% of those had sex with someone they lived with, compared with 29% who had sex with someone they did not live with. The pandemic had no impact on sexual desire for 37% of respondents, compared with 32% who experienced a decrease in desire, and 29% who experienced more desire for sex. The presence of shelter-in-place orders had no effect on frequency of or desire for sex. Among the respondents, 4% noted intimate partner violence, which increased slightly from 3% before the pandemic.

Among respondents using contraception, the study authors noted that 17% reported greater difficulty accessing birth control during the pandemic compared with 4% who felt access had become easier. Of those citing increased difficulties, 9% noted increasing challenges getting to a pharmacy, 4% were less able to afford birth control, 3% said it had become harder to obtain a prescription, and 1% cited difficulties having long-acting reversible contraceptives removed.

Despite the pandemic’s overall impact on quality of life, 41% of respondents reported a stronger desire to become pregnant, compared with 25% who had a reduced desire, and 34% whose interest in pregnancy was unchanged by the pandemic.

More than one-third of respondents (37%) admitted that COVID-19 contributed to their fears of becoming pregnant while 13% indicated their fear of pregnancy stemmed from concerns over being able to afford the cost of having a child. Not surprisingly, the decrease in desire for pregnancy was twice as high in those who reported they were unable to afford food, transportation, and/or housing compared with those who saw no change in their ability to afford basic needs.

“In these uncertain economic times, it is of utmost importance to create policies that will ensure access to and comprehensive coverage of core sexual and reproductive health services,” Dr. Lin and colleagues urged. “By doing so, we safeguard people’s ability to make decisions that support their reproductive health goals.”
 

Will COVID-19 drive needed practice and policy changes?

“This study highlights the economic and reproductive health toll of COVID-19 and the pressing need for improved contraception access,” Eve Espey, MD, MPH, said in an interview.

“Ob.gyns. and other practitioners can use this information to consider evidence-based practice changes that incorporate telemedicine visits, extended refills on contraceptive methods, and a focus on postpartum and postabortion initiation of contraception,” noted Dr. Espey, of the University of New Mexico, Albuquerque. For women who are experiencing economic hardship, consulting with state-based programs that offer pharmacy access and online access to contraceptives may offer a reasonable alternative, she added.

The study was funded by the University of California, San Francisco’s National Center of Excellence in Women’s Health. Dr. Lin received funding from Lazarex Cancer Foundation. The remaining authors had no conflicts of interest and reported no disclosures.