Journal of Clinical Outcomes Management

French investigators are warning about using acetaminophen in patients with cancer who are taking immune checkpoint blockers.

The team found a strong association between the use of acetaminophen and a decreased response to immune checkpoint inhibitors in a study of three clinical cohorts involving more than 600 patients with advanced cancer.

Patients who took acetaminophen at the start of immunotherapy – with acetaminophen exposure confirmed by plasma testing – were found to have worse overall survival and progression-free survival than patients who did not take the analgesic. Multivariate analysis confirmed the association independent of other prognostic factors. “It is unlikely that our data are the result of bias or unmeasured confounding,” the authors comment.

The findings “present a compelling case for caution” in using acetaminophen in patients with cancer who are receiving immune checkpoint blockers, senior investigator Antoine Italiano, MD, PhD, a medical oncologist at the University of Bordeaux (France), and colleagues concluded.

The study was presented at the annual meeting of the American Society of Clinical Oncology and published simultaneously in Annals of Oncology.

“Patients with advanced cancer taking [acetaminophen] during immunotherapy experience worse clinical outcomes, which suggests that [acetaminophen] decreases T cell–mediated antitumor immunity,” the authors comment.

They also report bench research and blood studies in four healthy volunteers, which showed an up-regulation of immunosuppressive regulatory T cells (Tregs) with acetaminophen, and other findings that together suggest that acetaminophen undermines the antitumor immune processes by which checkpoint inhibitors work.
 

Reconsider acetaminophen pretreatment

After hearing Dr. Italiano present the results at the meeting, a Polish oncologist in the audience said he was concerned that his clinic premedicates with acetaminophen before immune checkpoint blockade and wanted to know if they should stop doing it.

“I don’t think inducing Tregs ... in cancer patients is a good approach. I do a lot of clinical trials,” and “I do not understand why in several cases sponsors required mandatory premedication with acetaminophen. I think ... we should reconsider this approach,” Dr. Italiano said.

There’s precedence for the findings. Acetaminophen – also known as paracetamol – has been shown in some studies to limit immune cell proliferation, T-cell–dependent antibody response, and viral clearance, among other things. After a randomized trial showing blunted responses to vaccines in individuals who were taking acetaminophen, the World Health Organization recommended in 2015 against concurrent use of acetaminophen with vaccines.

Steroids, antibiotics, and proton pump inhibitors have also recently been shown to worsen outcomes with pembrolizumab, noted invited discussant, Margaret Gatti-Mays, MD, a medical oncologist at Ohio State University, Columbus.

“We are starting to understand that ... commonly used medications may have a larger impact on the efficacy and toxicity of immune checkpoint blockade than historically seen with chemotherapy,” she said.

However, she expressed some uncertainty over the French findings, as she was concerned that even the multivariate analysis didn’t completely rule out that acetaminophen users had worse disease to begin with and so would be expected to have worse outcomes.

She was also unsure of how much acetaminophen is too much.

Acetaminophen has a half-life of around 3 hours or less, where the immune checkpoint inhibitors have a half-life of around 20 days or more.

Given that, Dr. Gatti-Mays wondered whether “a single dose of acetaminophen [is] enough to derail the benefit of checkpoint inhibition? Does exposure need to be continuous?”

She allowed that acetaminophen use may turn out to be one more of the many patient-level factors emerging lately – such as chronic stress, diet, body flora, and physiological age, among others – that might help explain why checkpoint inhibition works in only about 20% of eligible patients with cancer.
 

Study details

Dr. Italiano and his team analyzed plasma samples from 297 participants in the CheckMate 025 trial of nivolumab for renal cancer; 34 participants in the BIP study into actionable molecular alterations in cancer; and 297 participants in the PREMIS immune-related adverse events study. The patients in these last two studies had a variety of cancers and were taking various agents.

All 628 patients were on checkpoint inhibitors. The investigators divided them according to who had acetaminophen or its metabolite acetaminophen glucuronide in their plasma when they started checkpoint inhibition and those who did not.

In CheckMate 025, overall survival was significantly worse among participants who had detectable acetaminophen or its metabolite in plasma (hazard ratio, 0.67; P = .004).

None of the acetaminophen-positive participants in the BIP study responded to checkpoint blockade, compared with almost 30% of those who were negative. Acetaminophen-positive participants also trended toward worse progression-free survival (median, 1.87 vs. 4.72 months) and overall survival (median, 7.87 vs. 16.56 months).

In PREMIS, progression-free survival was a median of 2.63 months in the acetaminophen group versus 5.03 months in negative participants (P = .009); median overall survival was 8.43 months versus 14.93 months, respectively (P < .0001).

A multivariate analysis was performed in PREMIS. Acetaminophen exposure was associated with both progression-free survival (hazard ratio, 1.43; P =.015) and overall survival (HR, 1.78; P =.006) independently of performance status, liver metastases, bone metastases, number of metastases sites, tumor type, number of previous lines of treatment, steroid/antibiotic use, lactate dehydrogenase levels, and other factors.

There was no funding for the work. Dr. Italiano is a consultant for AstraZeneca, Bayer, Chugai, Deciphera, Merck, Parthenon, Roche, and Springworks, He also has grants from AstraZeneca, Bayer, Bristol-Myers Squibb, Merck, MSD, Novartis, Pharmamar, and Roche. Two authors work for Explicyte and one works for Amgen. Dr. Gatti-Mays is a consultant for Seattle Genetics.

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

French investigators are warning about using acetaminophen in patients with cancer who are taking immune checkpoint blockers.

The team found a strong association between the use of acetaminophen and a decreased response to immune checkpoint inhibitors in a study of three clinical cohorts involving more than 600 patients with advanced cancer.

Patients who took acetaminophen at the start of immunotherapy – with acetaminophen exposure confirmed by plasma testing – were found to have worse overall survival and progression-free survival than patients who did not take the analgesic. Multivariate analysis confirmed the association independent of other prognostic factors. “It is unlikely that our data are the result of bias or unmeasured confounding,” the authors comment.

The findings “present a compelling case for caution” in using acetaminophen in patients with cancer who are receiving immune checkpoint blockers, senior investigator Antoine Italiano, MD, PhD, a medical oncologist at the University of Bordeaux (France), and colleagues concluded.

The study was presented at the annual meeting of the American Society of Clinical Oncology and published simultaneously in Annals of Oncology.

“Patients with advanced cancer taking [acetaminophen] during immunotherapy experience worse clinical outcomes, which suggests that [acetaminophen] decreases T cell–mediated antitumor immunity,” the authors comment.

They also report bench research and blood studies in four healthy volunteers, which showed an up-regulation of immunosuppressive regulatory T cells (Tregs) with acetaminophen, and other findings that together suggest that acetaminophen undermines the antitumor immune processes by which checkpoint inhibitors work.
 

Reconsider acetaminophen pretreatment

After hearing Dr. Italiano present the results at the meeting, a Polish oncologist in the audience said he was concerned that his clinic premedicates with acetaminophen before immune checkpoint blockade and wanted to know if they should stop doing it.

“I don’t think inducing Tregs ... in cancer patients is a good approach. I do a lot of clinical trials,” and “I do not understand why in several cases sponsors required mandatory premedication with acetaminophen. I think ... we should reconsider this approach,” Dr. Italiano said.

There’s precedence for the findings. Acetaminophen – also known as paracetamol – has been shown in some studies to limit immune cell proliferation, T-cell–dependent antibody response, and viral clearance, among other things. After a randomized trial showing blunted responses to vaccines in individuals who were taking acetaminophen, the World Health Organization recommended in 2015 against concurrent use of acetaminophen with vaccines.

Steroids, antibiotics, and proton pump inhibitors have also recently been shown to worsen outcomes with pembrolizumab, noted invited discussant, Margaret Gatti-Mays, MD, a medical oncologist at Ohio State University, Columbus.

“We are starting to understand that ... commonly used medications may have a larger impact on the efficacy and toxicity of immune checkpoint blockade than historically seen with chemotherapy,” she said.

However, she expressed some uncertainty over the French findings, as she was concerned that even the multivariate analysis didn’t completely rule out that acetaminophen users had worse disease to begin with and so would be expected to have worse outcomes.

She was also unsure of how much acetaminophen is too much.

Acetaminophen has a half-life of around 3 hours or less, where the immune checkpoint inhibitors have a half-life of around 20 days or more.

Given that, Dr. Gatti-Mays wondered whether “a single dose of acetaminophen [is] enough to derail the benefit of checkpoint inhibition? Does exposure need to be continuous?”

She allowed that acetaminophen use may turn out to be one more of the many patient-level factors emerging lately – such as chronic stress, diet, body flora, and physiological age, among others – that might help explain why checkpoint inhibition works in only about 20% of eligible patients with cancer.
 

Study details

Dr. Italiano and his team analyzed plasma samples from 297 participants in the CheckMate 025 trial of nivolumab for renal cancer; 34 participants in the BIP study into actionable molecular alterations in cancer; and 297 participants in the PREMIS immune-related adverse events study. The patients in these last two studies had a variety of cancers and were taking various agents.

All 628 patients were on checkpoint inhibitors. The investigators divided them according to who had acetaminophen or its metabolite acetaminophen glucuronide in their plasma when they started checkpoint inhibition and those who did not.

In CheckMate 025, overall survival was significantly worse among participants who had detectable acetaminophen or its metabolite in plasma (hazard ratio, 0.67; P = .004).

None of the acetaminophen-positive participants in the BIP study responded to checkpoint blockade, compared with almost 30% of those who were negative. Acetaminophen-positive participants also trended toward worse progression-free survival (median, 1.87 vs. 4.72 months) and overall survival (median, 7.87 vs. 16.56 months).

In PREMIS, progression-free survival was a median of 2.63 months in the acetaminophen group versus 5.03 months in negative participants (P = .009); median overall survival was 8.43 months versus 14.93 months, respectively (P < .0001).

A multivariate analysis was performed in PREMIS. Acetaminophen exposure was associated with both progression-free survival (hazard ratio, 1.43; P =.015) and overall survival (HR, 1.78; P =.006) independently of performance status, liver metastases, bone metastases, number of metastases sites, tumor type, number of previous lines of treatment, steroid/antibiotic use, lactate dehydrogenase levels, and other factors.

There was no funding for the work. Dr. Italiano is a consultant for AstraZeneca, Bayer, Chugai, Deciphera, Merck, Parthenon, Roche, and Springworks, He also has grants from AstraZeneca, Bayer, Bristol-Myers Squibb, Merck, MSD, Novartis, Pharmamar, and Roche. Two authors work for Explicyte and one works for Amgen. Dr. Gatti-Mays is a consultant for Seattle Genetics.

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

French investigators are warning about using acetaminophen in patients with cancer who are taking immune checkpoint blockers.

The team found a strong association between the use of acetaminophen and a decreased response to immune checkpoint inhibitors in a study of three clinical cohorts involving more than 600 patients with advanced cancer.

Patients who took acetaminophen at the start of immunotherapy – with acetaminophen exposure confirmed by plasma testing – were found to have worse overall survival and progression-free survival than patients who did not take the analgesic. Multivariate analysis confirmed the association independent of other prognostic factors. “It is unlikely that our data are the result of bias or unmeasured confounding,” the authors comment.

The findings “present a compelling case for caution” in using acetaminophen in patients with cancer who are receiving immune checkpoint blockers, senior investigator Antoine Italiano, MD, PhD, a medical oncologist at the University of Bordeaux (France), and colleagues concluded.

The study was presented at the annual meeting of the American Society of Clinical Oncology and published simultaneously in Annals of Oncology.

“Patients with advanced cancer taking [acetaminophen] during immunotherapy experience worse clinical outcomes, which suggests that [acetaminophen] decreases T cell–mediated antitumor immunity,” the authors comment.

They also report bench research and blood studies in four healthy volunteers, which showed an up-regulation of immunosuppressive regulatory T cells (Tregs) with acetaminophen, and other findings that together suggest that acetaminophen undermines the antitumor immune processes by which checkpoint inhibitors work.
 

Reconsider acetaminophen pretreatment

After hearing Dr. Italiano present the results at the meeting, a Polish oncologist in the audience said he was concerned that his clinic premedicates with acetaminophen before immune checkpoint blockade and wanted to know if they should stop doing it.

“I don’t think inducing Tregs ... in cancer patients is a good approach. I do a lot of clinical trials,” and “I do not understand why in several cases sponsors required mandatory premedication with acetaminophen. I think ... we should reconsider this approach,” Dr. Italiano said.

There’s precedence for the findings. Acetaminophen – also known as paracetamol – has been shown in some studies to limit immune cell proliferation, T-cell–dependent antibody response, and viral clearance, among other things. After a randomized trial showing blunted responses to vaccines in individuals who were taking acetaminophen, the World Health Organization recommended in 2015 against concurrent use of acetaminophen with vaccines.

Steroids, antibiotics, and proton pump inhibitors have also recently been shown to worsen outcomes with pembrolizumab, noted invited discussant, Margaret Gatti-Mays, MD, a medical oncologist at Ohio State University, Columbus.

“We are starting to understand that ... commonly used medications may have a larger impact on the efficacy and toxicity of immune checkpoint blockade than historically seen with chemotherapy,” she said.

However, she expressed some uncertainty over the French findings, as she was concerned that even the multivariate analysis didn’t completely rule out that acetaminophen users had worse disease to begin with and so would be expected to have worse outcomes.

She was also unsure of how much acetaminophen is too much.

Acetaminophen has a half-life of around 3 hours or less, where the immune checkpoint inhibitors have a half-life of around 20 days or more.

Given that, Dr. Gatti-Mays wondered whether “a single dose of acetaminophen [is] enough to derail the benefit of checkpoint inhibition? Does exposure need to be continuous?”

She allowed that acetaminophen use may turn out to be one more of the many patient-level factors emerging lately – such as chronic stress, diet, body flora, and physiological age, among others – that might help explain why checkpoint inhibition works in only about 20% of eligible patients with cancer.
 

Study details

Dr. Italiano and his team analyzed plasma samples from 297 participants in the CheckMate 025 trial of nivolumab for renal cancer; 34 participants in the BIP study into actionable molecular alterations in cancer; and 297 participants in the PREMIS immune-related adverse events study. The patients in these last two studies had a variety of cancers and were taking various agents.

All 628 patients were on checkpoint inhibitors. The investigators divided them according to who had acetaminophen or its metabolite acetaminophen glucuronide in their plasma when they started checkpoint inhibition and those who did not.

In CheckMate 025, overall survival was significantly worse among participants who had detectable acetaminophen or its metabolite in plasma (hazard ratio, 0.67; P = .004).

None of the acetaminophen-positive participants in the BIP study responded to checkpoint blockade, compared with almost 30% of those who were negative. Acetaminophen-positive participants also trended toward worse progression-free survival (median, 1.87 vs. 4.72 months) and overall survival (median, 7.87 vs. 16.56 months).

In PREMIS, progression-free survival was a median of 2.63 months in the acetaminophen group versus 5.03 months in negative participants (P = .009); median overall survival was 8.43 months versus 14.93 months, respectively (P < .0001).

A multivariate analysis was performed in PREMIS. Acetaminophen exposure was associated with both progression-free survival (hazard ratio, 1.43; P =.015) and overall survival (HR, 1.78; P =.006) independently of performance status, liver metastases, bone metastases, number of metastases sites, tumor type, number of previous lines of treatment, steroid/antibiotic use, lactate dehydrogenase levels, and other factors.

There was no funding for the work. Dr. Italiano is a consultant for AstraZeneca, Bayer, Chugai, Deciphera, Merck, Parthenon, Roche, and Springworks, He also has grants from AstraZeneca, Bayer, Bristol-Myers Squibb, Merck, MSD, Novartis, Pharmamar, and Roche. Two authors work for Explicyte and one works for Amgen. Dr. Gatti-Mays is a consultant for Seattle Genetics.

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

Moderate to severe sleep disturbances and severe fatigue affect up to 40% of patients with long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC). Such disturbances are especially common among Black people, new research shows.

The “high” prevalence of moderate to severe sleep disturbances is “alarming,” study investigator Cinthya Pena Orbea, MD, sleep specialist at the Cleveland Clinic, said in an interview.

The findings were presented at the annual meeting of the Associated Professional Sleep Societies.

Dr. Pena and colleagues analyzed data on 962 patients with PASC seen at the Cleveland Clinic ReCOVer Clinic between February 2021 and April 2022.

More than two-thirds of patients (67.2%) reported at least moderate fatigue, while 21.8% reported severe fatigue, Dr. Pena reported.

In addition, 41.3% reported at least moderate sleep disturbances, while 8% of patients reported severe sleep disturbances, including insomnia, “which may impair quality of life,” Dr. Pena said.

Obesity, mood disorders, and Black race emerged as contributors to problems with sleep and fatigue after COVID.

Notably, after adjusting for demographics, Black race conferred threefold higher odds of moderate to severe sleep disturbances.

“We don’t know why this is, and one of our next steps is to better understand race-specific determinants of sleep disturbances after COVID and create targeted interventions,” Dr. Pena said.

How long after COVID the fatigue and sleep problems last “remains uncertain,” Dr. Pena acknowledged. However, in her clinical experience with therapy, patients’ sleep and fatigue may improve after 6 or 8 months.

Ruth Benca, MD, PhD, cochair of the Alliance for Sleep, is not surprised by the Cleveland Clinic findings.

“Sleep disturbances and fatigue are part of the sequelae of COVID,” Dr. Benca, who was not involved in the study, said in an interview.

“We know that people who have had COVID have more trouble sleeping afterwards. There is the COVID insomnia created in all of us just out of our worries, fears, isolation, and stress. And then there’s an actual impact of having the infection itself on worsening sleep,” said Dr. Benca, with Wake Forest University and Atrium Health Wake Forest Baptist, both in Winston-Salem, N.C.

The study had no specific funding. The authors have disclosed no relevant financial relationships. Dr. Benca is a consultant for Idorsia Pharmaceuticals.

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

Moderate to severe sleep disturbances and severe fatigue affect up to 40% of patients with long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC). Such disturbances are especially common among Black people, new research shows.

The “high” prevalence of moderate to severe sleep disturbances is “alarming,” study investigator Cinthya Pena Orbea, MD, sleep specialist at the Cleveland Clinic, said in an interview.

The findings were presented at the annual meeting of the Associated Professional Sleep Societies.

Dr. Pena and colleagues analyzed data on 962 patients with PASC seen at the Cleveland Clinic ReCOVer Clinic between February 2021 and April 2022.

More than two-thirds of patients (67.2%) reported at least moderate fatigue, while 21.8% reported severe fatigue, Dr. Pena reported.

In addition, 41.3% reported at least moderate sleep disturbances, while 8% of patients reported severe sleep disturbances, including insomnia, “which may impair quality of life,” Dr. Pena said.

Obesity, mood disorders, and Black race emerged as contributors to problems with sleep and fatigue after COVID.

Notably, after adjusting for demographics, Black race conferred threefold higher odds of moderate to severe sleep disturbances.

“We don’t know why this is, and one of our next steps is to better understand race-specific determinants of sleep disturbances after COVID and create targeted interventions,” Dr. Pena said.

How long after COVID the fatigue and sleep problems last “remains uncertain,” Dr. Pena acknowledged. However, in her clinical experience with therapy, patients’ sleep and fatigue may improve after 6 or 8 months.

Ruth Benca, MD, PhD, cochair of the Alliance for Sleep, is not surprised by the Cleveland Clinic findings.

“Sleep disturbances and fatigue are part of the sequelae of COVID,” Dr. Benca, who was not involved in the study, said in an interview.

“We know that people who have had COVID have more trouble sleeping afterwards. There is the COVID insomnia created in all of us just out of our worries, fears, isolation, and stress. And then there’s an actual impact of having the infection itself on worsening sleep,” said Dr. Benca, with Wake Forest University and Atrium Health Wake Forest Baptist, both in Winston-Salem, N.C.

The study had no specific funding. The authors have disclosed no relevant financial relationships. Dr. Benca is a consultant for Idorsia Pharmaceuticals.

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

Moderate to severe sleep disturbances and severe fatigue affect up to 40% of patients with long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC). Such disturbances are especially common among Black people, new research shows.

The “high” prevalence of moderate to severe sleep disturbances is “alarming,” study investigator Cinthya Pena Orbea, MD, sleep specialist at the Cleveland Clinic, said in an interview.

The findings were presented at the annual meeting of the Associated Professional Sleep Societies.

Dr. Pena and colleagues analyzed data on 962 patients with PASC seen at the Cleveland Clinic ReCOVer Clinic between February 2021 and April 2022.

More than two-thirds of patients (67.2%) reported at least moderate fatigue, while 21.8% reported severe fatigue, Dr. Pena reported.

In addition, 41.3% reported at least moderate sleep disturbances, while 8% of patients reported severe sleep disturbances, including insomnia, “which may impair quality of life,” Dr. Pena said.

Obesity, mood disorders, and Black race emerged as contributors to problems with sleep and fatigue after COVID.

Notably, after adjusting for demographics, Black race conferred threefold higher odds of moderate to severe sleep disturbances.

“We don’t know why this is, and one of our next steps is to better understand race-specific determinants of sleep disturbances after COVID and create targeted interventions,” Dr. Pena said.

How long after COVID the fatigue and sleep problems last “remains uncertain,” Dr. Pena acknowledged. However, in her clinical experience with therapy, patients’ sleep and fatigue may improve after 6 or 8 months.

Ruth Benca, MD, PhD, cochair of the Alliance for Sleep, is not surprised by the Cleveland Clinic findings.

“Sleep disturbances and fatigue are part of the sequelae of COVID,” Dr. Benca, who was not involved in the study, said in an interview.

“We know that people who have had COVID have more trouble sleeping afterwards. There is the COVID insomnia created in all of us just out of our worries, fears, isolation, and stress. And then there’s an actual impact of having the infection itself on worsening sleep,” said Dr. Benca, with Wake Forest University and Atrium Health Wake Forest Baptist, both in Winston-Salem, N.C.

The study had no specific funding. The authors have disclosed no relevant financial relationships. Dr. Benca is a consultant for Idorsia Pharmaceuticals.

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

If you have bacteria in your urine but don’t have symptoms of a urinary tract infection (UTI), such as burning or frequent urination, you probably don’t need antibiotics. So why did you get that prescription?

The Infectious Diseases Society of America recommends against antibiotics in this scenario, with exceptions for patients who are pregnant or undergoing certain urologic procedures.

Antibiotics for asymptomatic bacteriuria (ASB) generally do not help; are costly; and can cause side effects, Clostridioides difficile infection, and antibiotic resistance.

Still, antibiotic treatment for asymptomatic bacteriuria remains common, despite guidelines.

And when researchers recently surveyed 551 primary care clinicians to see which ones would inappropriately prescribe antibiotics for a positive urine culture, the answer was most of them: 71%.

“Regardless of years in practice, training background, or professional degree, most clinicians indicated that they would prescribe antibiotics for asymptomatic bacteriuria,” the researchers reported in JAMA Network Open.

Some groups of clinicians seemed especially likely to prescribe antibiotics unnecessarily.

“Medical maximizers” – clinicians who prefer treatment even when its value is ambiguous – and family medicine clinicians were more likely to prescribe antibiotics in response to a hypothetical case.

What to do for Mr. Williams?

To examine clinician attitudes and characteristics associated with prescribing antibiotics for asymptomatic bacteriuria, Dr. Baghdadi and his colleagues analyzed survey responses from 490 physicians and 61 advanced practice clinicians.

Study participants completed tests that measure numeracy, risk-taking preferences, burnout, and tendency to maximize care. They were presented with four hypothetical clinical scenarios, including a case of asymptomatic bacteriuria: “Mr. Williams, a 65-year-old man, comes to the office for follow-up of his osteoarthritis. He has noted foul-smelling urine and no pain or difficulty with urination. A urine dipstick shows trace blood. He has no particular preference for testing and wants your advice.”

Clinicians who had been in practice for at least 10 years were more likely to prescribe antibiotics (82%) to “Mr. Williams” than were those with 3-9 years in practice (73%) or less than 3 years in practice (64%).

Breaking a habit

Some prescribers may know not to treat asymptomatic bacteriuria but mistakenly consider certain findings to be symptoms of UTI.

Bradley Langford, PharmD, an antimicrobial stewardship expert with Public Health Ontario, said in his experience, most clinicians who say they know not to treat ASB incorrectly believe that cloudy urine, altered cognition, and other nonspecific symptoms indicate a UTI.

“The fact that most clinicians would treat ASB suggests that there is still a lot of work to do to improve antimicrobial stewardship, particularly outside of the hospital setting,” Dr. Langford told this news organization.

Avoiding unnecessary antibiotics is important not just because of the lack of benefit, but also because of the potential harms, said Dr. Langford. He has created a list of rebuttals for commonly given reasons for testing and treating asymptomatic bacteriuria.

“Using antibiotics for ASB can counterintuitively increase the risk for symptomatic UTI due to the disruption of protective local microflora, allowing for the growth of more pathogenic/resistant organisms,” he said.

One approach to addressing the problem: Don’t test urine in the first place if patients are asymptomatic. Virtual learning sessions have been shown to reduce urine culturing and urinary antibiotic prescribing in long-term care homes, Dr. Langford noted.

Updated training for health care professionals from the outset may also be key, and the lower rate of prescribing intent among resident physicians is reassuring, he said.
 

A role for patients

Patients could also help decrease the inappropriate use of antibiotics.

“Be clear with your doctor about your expectations for the health care interaction, including whether you are expecting to receive antibiotics,” Dr. Baghdadi said. “Your doctor may assume you contacted them because you wanted a prescription. If you are not expecting antibiotics, you should feel free to say so. And if you are asymptomatic, you may not need antibiotics, even if the urine culture is positive.”

The study was funded by a grant from the National Institutes of Health, and Dr. Baghdadi received grant support from the University of Maryland, Baltimore Institute for Clinical and Translational Research. Coauthors disclosed government grants and ties to Memorial Sloan Kettering Cancer Center, Vedanta Biosciences, Opentrons, and Fimbrion. Dr. Langford reported no relevant financial conflicts of interest.

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

If you have bacteria in your urine but don’t have symptoms of a urinary tract infection (UTI), such as burning or frequent urination, you probably don’t need antibiotics. So why did you get that prescription?

The Infectious Diseases Society of America recommends against antibiotics in this scenario, with exceptions for patients who are pregnant or undergoing certain urologic procedures.

Antibiotics for asymptomatic bacteriuria (ASB) generally do not help; are costly; and can cause side effects, Clostridioides difficile infection, and antibiotic resistance.

Still, antibiotic treatment for asymptomatic bacteriuria remains common, despite guidelines.

And when researchers recently surveyed 551 primary care clinicians to see which ones would inappropriately prescribe antibiotics for a positive urine culture, the answer was most of them: 71%.

“Regardless of years in practice, training background, or professional degree, most clinicians indicated that they would prescribe antibiotics for asymptomatic bacteriuria,” the researchers reported in JAMA Network Open.

Some groups of clinicians seemed especially likely to prescribe antibiotics unnecessarily.

“Medical maximizers” – clinicians who prefer treatment even when its value is ambiguous – and family medicine clinicians were more likely to prescribe antibiotics in response to a hypothetical case.

What to do for Mr. Williams?

To examine clinician attitudes and characteristics associated with prescribing antibiotics for asymptomatic bacteriuria, Dr. Baghdadi and his colleagues analyzed survey responses from 490 physicians and 61 advanced practice clinicians.

Study participants completed tests that measure numeracy, risk-taking preferences, burnout, and tendency to maximize care. They were presented with four hypothetical clinical scenarios, including a case of asymptomatic bacteriuria: “Mr. Williams, a 65-year-old man, comes to the office for follow-up of his osteoarthritis. He has noted foul-smelling urine and no pain or difficulty with urination. A urine dipstick shows trace blood. He has no particular preference for testing and wants your advice.”

Clinicians who had been in practice for at least 10 years were more likely to prescribe antibiotics (82%) to “Mr. Williams” than were those with 3-9 years in practice (73%) or less than 3 years in practice (64%).

Breaking a habit

Some prescribers may know not to treat asymptomatic bacteriuria but mistakenly consider certain findings to be symptoms of UTI.

Bradley Langford, PharmD, an antimicrobial stewardship expert with Public Health Ontario, said in his experience, most clinicians who say they know not to treat ASB incorrectly believe that cloudy urine, altered cognition, and other nonspecific symptoms indicate a UTI.

“The fact that most clinicians would treat ASB suggests that there is still a lot of work to do to improve antimicrobial stewardship, particularly outside of the hospital setting,” Dr. Langford told this news organization.

Avoiding unnecessary antibiotics is important not just because of the lack of benefit, but also because of the potential harms, said Dr. Langford. He has created a list of rebuttals for commonly given reasons for testing and treating asymptomatic bacteriuria.

“Using antibiotics for ASB can counterintuitively increase the risk for symptomatic UTI due to the disruption of protective local microflora, allowing for the growth of more pathogenic/resistant organisms,” he said.

One approach to addressing the problem: Don’t test urine in the first place if patients are asymptomatic. Virtual learning sessions have been shown to reduce urine culturing and urinary antibiotic prescribing in long-term care homes, Dr. Langford noted.

Updated training for health care professionals from the outset may also be key, and the lower rate of prescribing intent among resident physicians is reassuring, he said.
 

A role for patients

Patients could also help decrease the inappropriate use of antibiotics.

“Be clear with your doctor about your expectations for the health care interaction, including whether you are expecting to receive antibiotics,” Dr. Baghdadi said. “Your doctor may assume you contacted them because you wanted a prescription. If you are not expecting antibiotics, you should feel free to say so. And if you are asymptomatic, you may not need antibiotics, even if the urine culture is positive.”

The study was funded by a grant from the National Institutes of Health, and Dr. Baghdadi received grant support from the University of Maryland, Baltimore Institute for Clinical and Translational Research. Coauthors disclosed government grants and ties to Memorial Sloan Kettering Cancer Center, Vedanta Biosciences, Opentrons, and Fimbrion. Dr. Langford reported no relevant financial conflicts of interest.

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

If you have bacteria in your urine but don’t have symptoms of a urinary tract infection (UTI), such as burning or frequent urination, you probably don’t need antibiotics. So why did you get that prescription?

The Infectious Diseases Society of America recommends against antibiotics in this scenario, with exceptions for patients who are pregnant or undergoing certain urologic procedures.

Antibiotics for asymptomatic bacteriuria (ASB) generally do not help; are costly; and can cause side effects, Clostridioides difficile infection, and antibiotic resistance.

Still, antibiotic treatment for asymptomatic bacteriuria remains common, despite guidelines.

And when researchers recently surveyed 551 primary care clinicians to see which ones would inappropriately prescribe antibiotics for a positive urine culture, the answer was most of them: 71%.

“Regardless of years in practice, training background, or professional degree, most clinicians indicated that they would prescribe antibiotics for asymptomatic bacteriuria,” the researchers reported in JAMA Network Open.

Some groups of clinicians seemed especially likely to prescribe antibiotics unnecessarily.

“Medical maximizers” – clinicians who prefer treatment even when its value is ambiguous – and family medicine clinicians were more likely to prescribe antibiotics in response to a hypothetical case.

What to do for Mr. Williams?

To examine clinician attitudes and characteristics associated with prescribing antibiotics for asymptomatic bacteriuria, Dr. Baghdadi and his colleagues analyzed survey responses from 490 physicians and 61 advanced practice clinicians.

Study participants completed tests that measure numeracy, risk-taking preferences, burnout, and tendency to maximize care. They were presented with four hypothetical clinical scenarios, including a case of asymptomatic bacteriuria: “Mr. Williams, a 65-year-old man, comes to the office for follow-up of his osteoarthritis. He has noted foul-smelling urine and no pain or difficulty with urination. A urine dipstick shows trace blood. He has no particular preference for testing and wants your advice.”

Clinicians who had been in practice for at least 10 years were more likely to prescribe antibiotics (82%) to “Mr. Williams” than were those with 3-9 years in practice (73%) or less than 3 years in practice (64%).

Breaking a habit

Some prescribers may know not to treat asymptomatic bacteriuria but mistakenly consider certain findings to be symptoms of UTI.

Bradley Langford, PharmD, an antimicrobial stewardship expert with Public Health Ontario, said in his experience, most clinicians who say they know not to treat ASB incorrectly believe that cloudy urine, altered cognition, and other nonspecific symptoms indicate a UTI.

“The fact that most clinicians would treat ASB suggests that there is still a lot of work to do to improve antimicrobial stewardship, particularly outside of the hospital setting,” Dr. Langford told this news organization.

Avoiding unnecessary antibiotics is important not just because of the lack of benefit, but also because of the potential harms, said Dr. Langford. He has created a list of rebuttals for commonly given reasons for testing and treating asymptomatic bacteriuria.

“Using antibiotics for ASB can counterintuitively increase the risk for symptomatic UTI due to the disruption of protective local microflora, allowing for the growth of more pathogenic/resistant organisms,” he said.

One approach to addressing the problem: Don’t test urine in the first place if patients are asymptomatic. Virtual learning sessions have been shown to reduce urine culturing and urinary antibiotic prescribing in long-term care homes, Dr. Langford noted.

Updated training for health care professionals from the outset may also be key, and the lower rate of prescribing intent among resident physicians is reassuring, he said.
 

A role for patients

Patients could also help decrease the inappropriate use of antibiotics.

“Be clear with your doctor about your expectations for the health care interaction, including whether you are expecting to receive antibiotics,” Dr. Baghdadi said. “Your doctor may assume you contacted them because you wanted a prescription. If you are not expecting antibiotics, you should feel free to say so. And if you are asymptomatic, you may not need antibiotics, even if the urine culture is positive.”

The study was funded by a grant from the National Institutes of Health, and Dr. Baghdadi received grant support from the University of Maryland, Baltimore Institute for Clinical and Translational Research. Coauthors disclosed government grants and ties to Memorial Sloan Kettering Cancer Center, Vedanta Biosciences, Opentrons, and Fimbrion. Dr. Langford reported no relevant financial conflicts of interest.

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

A federal advisory panel strongly supported a bid for Novavax to win U.S. emergency authorization for its COVID-19 vaccine, which is based on a more traditional, protein-based approach than the cutting-edge technology used in mRNA-based shots.

The Vaccines and Related Biological Products Advisory Committee of the Food and Drug Administration voted almost unanimously June 7 in favor of Novavax’s two-dose COVID-19 vaccine for those 18 or older – despite some concerns over rare events of myocarditis and pericarditis.

The tally was 21 “yes” votes, without any “no” votes, but one abstention from a panelist who then offered a largely positive take on this vaccine.

Panelist Bruce Gellin, MD, explained at the end of the meeting that he would have cast a conditional vote in favor of the Novavax vaccine, called NVX-CoV2373, had that been an option. Dr. Gellin, chief of global public health strategy for the Rockefeller Foundation and a vaccine expert, said he didn’t want his abstention to be considered as signaling opposition to the Novavax shot.

Instead, he said, he expects FDA officials will gather more data and evidence about the Novavax vaccine, especially in relation to certain manufacturing issues, before making its decision on the company’s application.

Earlier in the day, a top FDA vaccine reviewer, Doran Fink, MD, PhD, noted that there were important manufacturing differences between the Novavax vaccine supply used in different projects, complicating efforts to assess the company’s application for emergency use authorization (EUA).

But Dr. Fink noted that the FDA staff already had made a convincing case in its briefing document, with enough evidence for an initial conditional clearance to be found in available data.

The FDA is not bound to follow the suggestions of its advisory committees but it often does.
 

Using the ‘bully pulpit’

At the beginning of the meeting, Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said he was seizing the “bully pulpit” in addressing the need to persuade more people in the United States to take shots against COVID-19.

About 67% of people in the United States aged 18 and older are fully vaccinated, but only about 50% of those in this group have had a first booster, according to the Centers for Disease Control and Prevention.

The two-dose mRNA vaccines from Pfizer and Moderna have been the subject of intense misinformation campaigns on social media, despite efforts by the FDA and other public health officials to convey the message about their strong benefit-risk profile. The FDA in May limited the authorized use of Johnson & Johnson’s single-dose COVID-19 shot, which is based on a different technology, because of concerns about rare and potentially life-threatening blood clots.

Novavax has been described as a more traditional vaccine – a protein subunit shot similar to one people have long received for protection against influenza, pertussis (whooping cough), diphtheria, and tetanus.

“Having a protein-based alternative may be more comfortable for some in terms of their acceptance of vaccines,” Dr. Marks said. “We do have a problem with vaccine uptake that is very serious in the United States. And anything we can do to get people more comfortable to be able to accept these potentially life-saving medical products is something that we feel we are compelled to do.”

Dr. Marks offered these remarks in answer to an FDA panelist’s question about the need to consider an EUA for yet another vaccine.

EUAs are special clearances the FDA can grant in connection with public health emergencies such as the pandemic. The FDA used EUAs for the initial December 2020 clearances of the Pfizer-BioNTech and Moderna vaccines. It has since granted normal approvals for both of these mRNA-based vaccines, based on larger bodies of evidence gathered and submitted by their developers.

During the meeting, the FDA panelists in general appeared comfortable with the idea of granting another EUA for a vaccine. There was agreement that the shot appeared to work in key tests, although these were done before the rise of the Omicron variant.

In a key test, known as study 301, the Novavax vaccine was judged to be 90.4% effective. In the study, 17 of the 17,272 people who got the Novavax vaccine developed COVID-19, compared with 79 of the 8,385 in the placebo group.

Panelists expressed disappointment with the lack of information about how the shot would work now.

“We’re looking at the efficacy against strains that don’t exist any longer,” said panelist Eric J. Rubin, MD, PhD, a Harvard professor and editor of the New England Journal of Medicine.

Still, Dr. Rubin added that he agreed with the argument the FDA’s Dr. Marks had made earlier for an EUA for the Novavax vaccine.

“If there really is a population of patients who are willing to take this and not willing to take the existing vaccines, I think it’s pretty compelling,” Dr. Rubin said.

Other FDA panelists were skeptical of this argument. Jay Portnoy, MD, who was listed on the FDA roster as the panel’s consumer representative, said he has close friends who are vaccine skeptics.

“Their hesitancy is more ideological than technological,” said Dr. Portnoy of Children’s Mercy Hospital, Kansas City, Mo. “So I really doubt that this vaccine is going to crack that nut, but perhaps some individuals would get this when they wouldn’t get the other ones.”
 

Myocarditis, pericarditis

The Novavax vaccine is already authorized in other countries, including Canada. Novavax in February announced that it had begun shipping its first doses of the vaccine to European Union member states. The vaccine can be moved through existing vaccine supply and cold chain channels instead of requiring complex new delivery procedures.

That could prove an advantage in time, said FDA panelist Michael Nelson, MD, PhD, of the University of Virginia, Charlottesville.

“Who knows even with supply chain challenges down the road, it will be nice to have options going forward,” Dr. Nelson said. 

As with other COVID-19 vaccines, clinicians and researchers are still working to understand the potential risk for inflammation of heart muscle and nearby tissue with vaccination. Most patients with myocarditis or pericarditis who sought medical care for these conditions responded well to medicine and rest and felt better quickly, the CDC says on its website. They usually return to their normal daily activities after their symptoms improve.

At the June 7 meeting, Dr. Nelson said there may be cases of myocarditis that go undetected.

“Our signals are those who get admitted to the emergency room and the hospital,” he said. “I’m quite convinced that there are others who are experiencing cardiac events of lesser severity that are worthy of being studied, both from mechanistic and outcomes standpoints. So we have a lot of work to do.”

In looking at results for an initial pool of 40,000 people who received the Novavax vaccine, there were five reported cases of myocarditis or pericarditis developing within 20 days of people getting the shot, the FDA staff said in its presentation on safety.

In a briefing document released ahead of the advisory committee meeting, the FDA staff flagged this number of cases in a relatively small database as a concern, noting it “could be higher than reported during postauthorization use of mRNA COVID-19 vaccines (for which no cases were identified in preauthorization evaluation).”

Novavax officials took a somewhat unusual step of responding in public. The Gaithersburg, Md.–based company on June 3 issued a statement saying researchers had come to “expect to see natural background events of myocarditis in any sufficiently large database, and that young males are at higher risk.”

The data from the company’s placebo-controlled studies show that, overall, in its clinical development program, the rate of myocarditis was balanced between the vaccine and placebo arms (0.007% and 0.005%), Novavax said.

At the June 7 meeting, FDA panelists including Dr. Nelson, and Paul A. Offit, MD, of Children’s Hospital of Philadelphia, urged continued study to try to determine whether and how the vaccines could trigger myocarditis. Investments made now in pursuing these questions related to COVID-19 shots may pay off later, Dr. Offit said.

“We can use that knowledge to make safer vaccines for a disease that is going to be with us for decades, if not longer,” he said.

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

A federal advisory panel strongly supported a bid for Novavax to win U.S. emergency authorization for its COVID-19 vaccine, which is based on a more traditional, protein-based approach than the cutting-edge technology used in mRNA-based shots.

The Vaccines and Related Biological Products Advisory Committee of the Food and Drug Administration voted almost unanimously June 7 in favor of Novavax’s two-dose COVID-19 vaccine for those 18 or older – despite some concerns over rare events of myocarditis and pericarditis.

The tally was 21 “yes” votes, without any “no” votes, but one abstention from a panelist who then offered a largely positive take on this vaccine.

Panelist Bruce Gellin, MD, explained at the end of the meeting that he would have cast a conditional vote in favor of the Novavax vaccine, called NVX-CoV2373, had that been an option. Dr. Gellin, chief of global public health strategy for the Rockefeller Foundation and a vaccine expert, said he didn’t want his abstention to be considered as signaling opposition to the Novavax shot.

Instead, he said, he expects FDA officials will gather more data and evidence about the Novavax vaccine, especially in relation to certain manufacturing issues, before making its decision on the company’s application.

Earlier in the day, a top FDA vaccine reviewer, Doran Fink, MD, PhD, noted that there were important manufacturing differences between the Novavax vaccine supply used in different projects, complicating efforts to assess the company’s application for emergency use authorization (EUA).

But Dr. Fink noted that the FDA staff already had made a convincing case in its briefing document, with enough evidence for an initial conditional clearance to be found in available data.

The FDA is not bound to follow the suggestions of its advisory committees but it often does.
 

Using the ‘bully pulpit’

At the beginning of the meeting, Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said he was seizing the “bully pulpit” in addressing the need to persuade more people in the United States to take shots against COVID-19.

About 67% of people in the United States aged 18 and older are fully vaccinated, but only about 50% of those in this group have had a first booster, according to the Centers for Disease Control and Prevention.

The two-dose mRNA vaccines from Pfizer and Moderna have been the subject of intense misinformation campaigns on social media, despite efforts by the FDA and other public health officials to convey the message about their strong benefit-risk profile. The FDA in May limited the authorized use of Johnson & Johnson’s single-dose COVID-19 shot, which is based on a different technology, because of concerns about rare and potentially life-threatening blood clots.

Novavax has been described as a more traditional vaccine – a protein subunit shot similar to one people have long received for protection against influenza, pertussis (whooping cough), diphtheria, and tetanus.

“Having a protein-based alternative may be more comfortable for some in terms of their acceptance of vaccines,” Dr. Marks said. “We do have a problem with vaccine uptake that is very serious in the United States. And anything we can do to get people more comfortable to be able to accept these potentially life-saving medical products is something that we feel we are compelled to do.”

Dr. Marks offered these remarks in answer to an FDA panelist’s question about the need to consider an EUA for yet another vaccine.

EUAs are special clearances the FDA can grant in connection with public health emergencies such as the pandemic. The FDA used EUAs for the initial December 2020 clearances of the Pfizer-BioNTech and Moderna vaccines. It has since granted normal approvals for both of these mRNA-based vaccines, based on larger bodies of evidence gathered and submitted by their developers.

During the meeting, the FDA panelists in general appeared comfortable with the idea of granting another EUA for a vaccine. There was agreement that the shot appeared to work in key tests, although these were done before the rise of the Omicron variant.

In a key test, known as study 301, the Novavax vaccine was judged to be 90.4% effective. In the study, 17 of the 17,272 people who got the Novavax vaccine developed COVID-19, compared with 79 of the 8,385 in the placebo group.

Panelists expressed disappointment with the lack of information about how the shot would work now.

“We’re looking at the efficacy against strains that don’t exist any longer,” said panelist Eric J. Rubin, MD, PhD, a Harvard professor and editor of the New England Journal of Medicine.

Still, Dr. Rubin added that he agreed with the argument the FDA’s Dr. Marks had made earlier for an EUA for the Novavax vaccine.

“If there really is a population of patients who are willing to take this and not willing to take the existing vaccines, I think it’s pretty compelling,” Dr. Rubin said.

Other FDA panelists were skeptical of this argument. Jay Portnoy, MD, who was listed on the FDA roster as the panel’s consumer representative, said he has close friends who are vaccine skeptics.

“Their hesitancy is more ideological than technological,” said Dr. Portnoy of Children’s Mercy Hospital, Kansas City, Mo. “So I really doubt that this vaccine is going to crack that nut, but perhaps some individuals would get this when they wouldn’t get the other ones.”
 

Myocarditis, pericarditis

The Novavax vaccine is already authorized in other countries, including Canada. Novavax in February announced that it had begun shipping its first doses of the vaccine to European Union member states. The vaccine can be moved through existing vaccine supply and cold chain channels instead of requiring complex new delivery procedures.

That could prove an advantage in time, said FDA panelist Michael Nelson, MD, PhD, of the University of Virginia, Charlottesville.

“Who knows even with supply chain challenges down the road, it will be nice to have options going forward,” Dr. Nelson said. 

As with other COVID-19 vaccines, clinicians and researchers are still working to understand the potential risk for inflammation of heart muscle and nearby tissue with vaccination. Most patients with myocarditis or pericarditis who sought medical care for these conditions responded well to medicine and rest and felt better quickly, the CDC says on its website. They usually return to their normal daily activities after their symptoms improve.

At the June 7 meeting, Dr. Nelson said there may be cases of myocarditis that go undetected.

“Our signals are those who get admitted to the emergency room and the hospital,” he said. “I’m quite convinced that there are others who are experiencing cardiac events of lesser severity that are worthy of being studied, both from mechanistic and outcomes standpoints. So we have a lot of work to do.”

In looking at results for an initial pool of 40,000 people who received the Novavax vaccine, there were five reported cases of myocarditis or pericarditis developing within 20 days of people getting the shot, the FDA staff said in its presentation on safety.

In a briefing document released ahead of the advisory committee meeting, the FDA staff flagged this number of cases in a relatively small database as a concern, noting it “could be higher than reported during postauthorization use of mRNA COVID-19 vaccines (for which no cases were identified in preauthorization evaluation).”

Novavax officials took a somewhat unusual step of responding in public. The Gaithersburg, Md.–based company on June 3 issued a statement saying researchers had come to “expect to see natural background events of myocarditis in any sufficiently large database, and that young males are at higher risk.”

The data from the company’s placebo-controlled studies show that, overall, in its clinical development program, the rate of myocarditis was balanced between the vaccine and placebo arms (0.007% and 0.005%), Novavax said.

At the June 7 meeting, FDA panelists including Dr. Nelson, and Paul A. Offit, MD, of Children’s Hospital of Philadelphia, urged continued study to try to determine whether and how the vaccines could trigger myocarditis. Investments made now in pursuing these questions related to COVID-19 shots may pay off later, Dr. Offit said.

“We can use that knowledge to make safer vaccines for a disease that is going to be with us for decades, if not longer,” he said.

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

A federal advisory panel strongly supported a bid for Novavax to win U.S. emergency authorization for its COVID-19 vaccine, which is based on a more traditional, protein-based approach than the cutting-edge technology used in mRNA-based shots.

The Vaccines and Related Biological Products Advisory Committee of the Food and Drug Administration voted almost unanimously June 7 in favor of Novavax’s two-dose COVID-19 vaccine for those 18 or older – despite some concerns over rare events of myocarditis and pericarditis.

The tally was 21 “yes” votes, without any “no” votes, but one abstention from a panelist who then offered a largely positive take on this vaccine.

Panelist Bruce Gellin, MD, explained at the end of the meeting that he would have cast a conditional vote in favor of the Novavax vaccine, called NVX-CoV2373, had that been an option. Dr. Gellin, chief of global public health strategy for the Rockefeller Foundation and a vaccine expert, said he didn’t want his abstention to be considered as signaling opposition to the Novavax shot.

Instead, he said, he expects FDA officials will gather more data and evidence about the Novavax vaccine, especially in relation to certain manufacturing issues, before making its decision on the company’s application.

Earlier in the day, a top FDA vaccine reviewer, Doran Fink, MD, PhD, noted that there were important manufacturing differences between the Novavax vaccine supply used in different projects, complicating efforts to assess the company’s application for emergency use authorization (EUA).

But Dr. Fink noted that the FDA staff already had made a convincing case in its briefing document, with enough evidence for an initial conditional clearance to be found in available data.

The FDA is not bound to follow the suggestions of its advisory committees but it often does.
 

Using the ‘bully pulpit’

At the beginning of the meeting, Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said he was seizing the “bully pulpit” in addressing the need to persuade more people in the United States to take shots against COVID-19.

About 67% of people in the United States aged 18 and older are fully vaccinated, but only about 50% of those in this group have had a first booster, according to the Centers for Disease Control and Prevention.

The two-dose mRNA vaccines from Pfizer and Moderna have been the subject of intense misinformation campaigns on social media, despite efforts by the FDA and other public health officials to convey the message about their strong benefit-risk profile. The FDA in May limited the authorized use of Johnson & Johnson’s single-dose COVID-19 shot, which is based on a different technology, because of concerns about rare and potentially life-threatening blood clots.

Novavax has been described as a more traditional vaccine – a protein subunit shot similar to one people have long received for protection against influenza, pertussis (whooping cough), diphtheria, and tetanus.

“Having a protein-based alternative may be more comfortable for some in terms of their acceptance of vaccines,” Dr. Marks said. “We do have a problem with vaccine uptake that is very serious in the United States. And anything we can do to get people more comfortable to be able to accept these potentially life-saving medical products is something that we feel we are compelled to do.”

Dr. Marks offered these remarks in answer to an FDA panelist’s question about the need to consider an EUA for yet another vaccine.

EUAs are special clearances the FDA can grant in connection with public health emergencies such as the pandemic. The FDA used EUAs for the initial December 2020 clearances of the Pfizer-BioNTech and Moderna vaccines. It has since granted normal approvals for both of these mRNA-based vaccines, based on larger bodies of evidence gathered and submitted by their developers.

During the meeting, the FDA panelists in general appeared comfortable with the idea of granting another EUA for a vaccine. There was agreement that the shot appeared to work in key tests, although these were done before the rise of the Omicron variant.

In a key test, known as study 301, the Novavax vaccine was judged to be 90.4% effective. In the study, 17 of the 17,272 people who got the Novavax vaccine developed COVID-19, compared with 79 of the 8,385 in the placebo group.

Panelists expressed disappointment with the lack of information about how the shot would work now.

“We’re looking at the efficacy against strains that don’t exist any longer,” said panelist Eric J. Rubin, MD, PhD, a Harvard professor and editor of the New England Journal of Medicine.

Still, Dr. Rubin added that he agreed with the argument the FDA’s Dr. Marks had made earlier for an EUA for the Novavax vaccine.

“If there really is a population of patients who are willing to take this and not willing to take the existing vaccines, I think it’s pretty compelling,” Dr. Rubin said.

Other FDA panelists were skeptical of this argument. Jay Portnoy, MD, who was listed on the FDA roster as the panel’s consumer representative, said he has close friends who are vaccine skeptics.

“Their hesitancy is more ideological than technological,” said Dr. Portnoy of Children’s Mercy Hospital, Kansas City, Mo. “So I really doubt that this vaccine is going to crack that nut, but perhaps some individuals would get this when they wouldn’t get the other ones.”
 

Myocarditis, pericarditis

The Novavax vaccine is already authorized in other countries, including Canada. Novavax in February announced that it had begun shipping its first doses of the vaccine to European Union member states. The vaccine can be moved through existing vaccine supply and cold chain channels instead of requiring complex new delivery procedures.

That could prove an advantage in time, said FDA panelist Michael Nelson, MD, PhD, of the University of Virginia, Charlottesville.

“Who knows even with supply chain challenges down the road, it will be nice to have options going forward,” Dr. Nelson said. 

As with other COVID-19 vaccines, clinicians and researchers are still working to understand the potential risk for inflammation of heart muscle and nearby tissue with vaccination. Most patients with myocarditis or pericarditis who sought medical care for these conditions responded well to medicine and rest and felt better quickly, the CDC says on its website. They usually return to their normal daily activities after their symptoms improve.

At the June 7 meeting, Dr. Nelson said there may be cases of myocarditis that go undetected.

“Our signals are those who get admitted to the emergency room and the hospital,” he said. “I’m quite convinced that there are others who are experiencing cardiac events of lesser severity that are worthy of being studied, both from mechanistic and outcomes standpoints. So we have a lot of work to do.”

In looking at results for an initial pool of 40,000 people who received the Novavax vaccine, there were five reported cases of myocarditis or pericarditis developing within 20 days of people getting the shot, the FDA staff said in its presentation on safety.

In a briefing document released ahead of the advisory committee meeting, the FDA staff flagged this number of cases in a relatively small database as a concern, noting it “could be higher than reported during postauthorization use of mRNA COVID-19 vaccines (for which no cases were identified in preauthorization evaluation).”

Novavax officials took a somewhat unusual step of responding in public. The Gaithersburg, Md.–based company on June 3 issued a statement saying researchers had come to “expect to see natural background events of myocarditis in any sufficiently large database, and that young males are at higher risk.”

The data from the company’s placebo-controlled studies show that, overall, in its clinical development program, the rate of myocarditis was balanced between the vaccine and placebo arms (0.007% and 0.005%), Novavax said.

At the June 7 meeting, FDA panelists including Dr. Nelson, and Paul A. Offit, MD, of Children’s Hospital of Philadelphia, urged continued study to try to determine whether and how the vaccines could trigger myocarditis. Investments made now in pursuing these questions related to COVID-19 shots may pay off later, Dr. Offit said.

“We can use that knowledge to make safer vaccines for a disease that is going to be with us for decades, if not longer,” he said.

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

The first decline in COVID-19 cases among children since early April may have been holiday related, but the shortened week also brought news about vaccination for the youngest children.

The Food and Drug Administration has accepted Pfizer’s application for a COVID-19 vaccine for children under age 5, so vaccination could begin as early as June 21, according to White House COVID-19 response coordinator Ashish Jha, MD.

“We know that many, many parents are eager to vaccinate their youngest kids and it’s important to do this right,” Dr. Jha said at a White House press briefing June 2. “We expect that vaccinations will begin in earnest as early as June 21 and really roll on throughout that week.”

Decline may just be underreporting

Over on the incidence side of the pandemic, the total number of cases reported for the week of May 27 to June 2 was about 87,000, a drop of 22% from May 20-26 and the first decline after 7 straight weeks of increases. “Testing and reporting may have been affected by the holiday weekend [since] states may change their reporting schedules, which may cause irregularities in trends,” the American Academy of Pediatrics and the Children’s Hospital association said in their latest COVID report.

The decline in new cases was not spread uniformly across the four major regions of the United States. The count actually went up in the West for the week of May 27 to June 2, while the South saw the largest decline. The Midwest and Northeast, meanwhile, saw new cases drop for the second straight week, the AAP and CHA said.

The cumulative number of COVID-19 cases in children was up to 13.45 million as of June 2, with children representing 18.9% of all cases since the start of the pandemic, according to the two organizations. The Centers for Disease Control and Prevention reported figures of 13.14 million and 17.5% on June 6.

The AAP/CHA estimates, however, are based on state data that have become increasingly hard to obtain and subject to inconsistency. “Shortages of COVID-19 tests during surges and the increasing use of COVID-19 home tests likely affect the undercounting of COVID-19 cases,” they noted, and “at times when COVID-19 transmission is low, states might reduce the frequency information is updated.”
 

Vaccinations held steady over the holiday

The ongoing vaccination effort in children aged 5 years and older did not show a Memorial Day drop-off, as initial vaccinations held at 43,000 in 5- to 11-year-olds and at 27,000 in 12- to 17-year-olds for a second consecutive week. That number has ranged from 34,000 to 70,000 for the younger children and from 25,000 to 47,000 for the older group since mid-March, the AAP said in a separate weekly report.

Despite weekly vaccine initiations that have been roughly double those of the older children for months, the 5- to 11-year-olds are still only at 36.0% coverage with at least one dose, compared with 69.5% for the 12- to-17-year-olds. Full vaccination for the two age groups comes in at 29.3% and 59.6%, respectively, as of June 6, according to the CDC’s COVID Data Tracker.
 

The first decline in COVID-19 cases among children since early April may have been holiday related, but the shortened week also brought news about vaccination for the youngest children.

The Food and Drug Administration has accepted Pfizer’s application for a COVID-19 vaccine for children under age 5, so vaccination could begin as early as June 21, according to White House COVID-19 response coordinator Ashish Jha, MD.

“We know that many, many parents are eager to vaccinate their youngest kids and it’s important to do this right,” Dr. Jha said at a White House press briefing June 2. “We expect that vaccinations will begin in earnest as early as June 21 and really roll on throughout that week.”

Decline may just be underreporting

Over on the incidence side of the pandemic, the total number of cases reported for the week of May 27 to June 2 was about 87,000, a drop of 22% from May 20-26 and the first decline after 7 straight weeks of increases. “Testing and reporting may have been affected by the holiday weekend [since] states may change their reporting schedules, which may cause irregularities in trends,” the American Academy of Pediatrics and the Children’s Hospital association said in their latest COVID report.

The decline in new cases was not spread uniformly across the four major regions of the United States. The count actually went up in the West for the week of May 27 to June 2, while the South saw the largest decline. The Midwest and Northeast, meanwhile, saw new cases drop for the second straight week, the AAP and CHA said.

The cumulative number of COVID-19 cases in children was up to 13.45 million as of June 2, with children representing 18.9% of all cases since the start of the pandemic, according to the two organizations. The Centers for Disease Control and Prevention reported figures of 13.14 million and 17.5% on June 6.

The AAP/CHA estimates, however, are based on state data that have become increasingly hard to obtain and subject to inconsistency. “Shortages of COVID-19 tests during surges and the increasing use of COVID-19 home tests likely affect the undercounting of COVID-19 cases,” they noted, and “at times when COVID-19 transmission is low, states might reduce the frequency information is updated.”
 

Vaccinations held steady over the holiday

The ongoing vaccination effort in children aged 5 years and older did not show a Memorial Day drop-off, as initial vaccinations held at 43,000 in 5- to 11-year-olds and at 27,000 in 12- to 17-year-olds for a second consecutive week. That number has ranged from 34,000 to 70,000 for the younger children and from 25,000 to 47,000 for the older group since mid-March, the AAP said in a separate weekly report.

Despite weekly vaccine initiations that have been roughly double those of the older children for months, the 5- to 11-year-olds are still only at 36.0% coverage with at least one dose, compared with 69.5% for the 12- to-17-year-olds. Full vaccination for the two age groups comes in at 29.3% and 59.6%, respectively, as of June 6, according to the CDC’s COVID Data Tracker.
 

The first decline in COVID-19 cases among children since early April may have been holiday related, but the shortened week also brought news about vaccination for the youngest children.

The Food and Drug Administration has accepted Pfizer’s application for a COVID-19 vaccine for children under age 5, so vaccination could begin as early as June 21, according to White House COVID-19 response coordinator Ashish Jha, MD.

“We know that many, many parents are eager to vaccinate their youngest kids and it’s important to do this right,” Dr. Jha said at a White House press briefing June 2. “We expect that vaccinations will begin in earnest as early as June 21 and really roll on throughout that week.”

Decline may just be underreporting

Over on the incidence side of the pandemic, the total number of cases reported for the week of May 27 to June 2 was about 87,000, a drop of 22% from May 20-26 and the first decline after 7 straight weeks of increases. “Testing and reporting may have been affected by the holiday weekend [since] states may change their reporting schedules, which may cause irregularities in trends,” the American Academy of Pediatrics and the Children’s Hospital association said in their latest COVID report.

The decline in new cases was not spread uniformly across the four major regions of the United States. The count actually went up in the West for the week of May 27 to June 2, while the South saw the largest decline. The Midwest and Northeast, meanwhile, saw new cases drop for the second straight week, the AAP and CHA said.

The cumulative number of COVID-19 cases in children was up to 13.45 million as of June 2, with children representing 18.9% of all cases since the start of the pandemic, according to the two organizations. The Centers for Disease Control and Prevention reported figures of 13.14 million and 17.5% on June 6.

The AAP/CHA estimates, however, are based on state data that have become increasingly hard to obtain and subject to inconsistency. “Shortages of COVID-19 tests during surges and the increasing use of COVID-19 home tests likely affect the undercounting of COVID-19 cases,” they noted, and “at times when COVID-19 transmission is low, states might reduce the frequency information is updated.”
 

Vaccinations held steady over the holiday

The ongoing vaccination effort in children aged 5 years and older did not show a Memorial Day drop-off, as initial vaccinations held at 43,000 in 5- to 11-year-olds and at 27,000 in 12- to 17-year-olds for a second consecutive week. That number has ranged from 34,000 to 70,000 for the younger children and from 25,000 to 47,000 for the older group since mid-March, the AAP said in a separate weekly report.

Despite weekly vaccine initiations that have been roughly double those of the older children for months, the 5- to 11-year-olds are still only at 36.0% coverage with at least one dose, compared with 69.5% for the 12- to-17-year-olds. Full vaccination for the two age groups comes in at 29.3% and 59.6%, respectively, as of June 6, according to the CDC’s COVID Data Tracker.
 

Spending more time doing light-intensity activities and less time being sedentary was associated with a reduced risk for first stroke in a population-based study of middle aged and older adults.

The study also found relatively short periods of moderate to vigorous exercise were associated with reduced stroke risk.

“Our results suggest there are a number of ways to reduce stroke risk simply by moving about,” said lead author Steven P. Hooker, PhD, San Diego State University. “This could be with short periods of moderate to vigorous activity each day, longer periods of light activity, or just sedentary for shorter periods of time. All these things can make a difference.”

Dr. Hooker explained that, while it has been found previously that moderate to vigorous exercise reduces stroke risk, this study gives more information on light-intensity activities and sedentary behavior and the risk of stroke.

“Our results suggest that you don’t have to be a chronic exerciser to reduce stroke risk. Replacing sedentary time with light-intensity activity will be beneficial. Just go for a short walk, get up from your desk and move around the house at regular intervals. That can help to reduce stroke risk,” Dr. Hooker said.  

“Our message is basically to sit less and move more,” he added.  

The study was published online in JAMA Network Open.

The study involved 7,607 U.S. individuals without a history of stroke, with oversampling from the southeastern “Stroke Belt,” who were participating in the REGARDS cohort study.

The participants wore an accelerometer to measure physical activity and sedentary behavior for 7 consecutive days. The mean age of the individuals was 63 years; 54% were female, 32% were Black.

Over a mean follow-up of 7.4 years, 286 incident stroke cases occurred.

Results showed that increased levels of physical activity were associated with reduced risk of stroke.

For moderate to vigorous activity, compared with participants in the lowest tertile, those in the highest tertile of total daily time in moderate to vigorous activity had a 43% lower risk of stroke.

In the current study, the amount of moderate to vigorous activity associated with a significant reduction in stroke risk was approximately 25 minutes per day (3 hours per week).

Dr. Hooker noted that moderate to vigorous activity included things such as brisk walking, jogging, bike riding, swimming, or playing tennis or soccer. “Doing such activities for just 25 minutes per day reduced risk of stroke by 43%. This is very doable. Just commuting to work by bicycle would cover you here,” he said.

In terms of light-intensity activity, individuals who did 4-5 hours of light activities each day had a 26% reduced risk for first stroke, compared with those doing less than 3 hours of such light activities.

Dr. Hooker explained that examples of light activity included household chores, such as vacuuming, washing dishes, or going for a gentle stroll. “These activities do not require heaving breathing, increased heart rate or breaking into a sweat. They are activities of daily living and relatively easy to engage in.”

But he pointed out that the 4-5 hours of light activity every day linked to a reduction in stroke risk may be more difficult to achieve than the 25 minutes of moderate to vigorous activity, saying: “You have to have some intentionality here.”
 

Long bouts of sedentary time are harmful

The study also showed that sedentary time was associated with a higher risk for stroke.

The authors noted that time spent in sedentary behavior is of interest because most adults spend most of their awake time being physically inactive.

They report that participants in the highest tertile of sedentary time (more than 13 hours/day) exhibited a 44% increase in risk of stroke, compared with those in the lowest tertile (less than 11 hours/day), and the association remained significant when adjusted for several covariates, including moderate to vigorous activity.

“Even when controlling for the amount of other physical activity, sedentary behavior is still highly associated with risk of stroke. So even if you are active, long bouts of sedentary behavior are harmful,” Dr. Hooker commented.

They also found that longer bouts of sedentary time (more than 17 minutes at a time) were associated with a 54% higher risk of stroke than shorter bouts (less than 8 minutes).

“This suggests that breaking up periods of sedentary behavior into shorter bouts would be beneficial,” Dr. Hooker said.

“If you are going to spend the evening on the couch watching television, try to stand up and walk around every few minutes. Same for if you are sitting at a computer all day – try having a standing workstation, or at least take regular breaks to walk around,” he added.

This research was supported by grants from the National Institute of Neurological Disorders and Stroke and the National Institute on Aging. Additional funding was provided by an unrestricted grant from the Coca-Cola Company. The authors report no disclosures.

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

Spending more time doing light-intensity activities and less time being sedentary was associated with a reduced risk for first stroke in a population-based study of middle aged and older adults.

The study also found relatively short periods of moderate to vigorous exercise were associated with reduced stroke risk.

“Our results suggest there are a number of ways to reduce stroke risk simply by moving about,” said lead author Steven P. Hooker, PhD, San Diego State University. “This could be with short periods of moderate to vigorous activity each day, longer periods of light activity, or just sedentary for shorter periods of time. All these things can make a difference.”

Dr. Hooker explained that, while it has been found previously that moderate to vigorous exercise reduces stroke risk, this study gives more information on light-intensity activities and sedentary behavior and the risk of stroke.

“Our results suggest that you don’t have to be a chronic exerciser to reduce stroke risk. Replacing sedentary time with light-intensity activity will be beneficial. Just go for a short walk, get up from your desk and move around the house at regular intervals. That can help to reduce stroke risk,” Dr. Hooker said.  

“Our message is basically to sit less and move more,” he added.  

The study was published online in JAMA Network Open.

The study involved 7,607 U.S. individuals without a history of stroke, with oversampling from the southeastern “Stroke Belt,” who were participating in the REGARDS cohort study.

The participants wore an accelerometer to measure physical activity and sedentary behavior for 7 consecutive days. The mean age of the individuals was 63 years; 54% were female, 32% were Black.

Over a mean follow-up of 7.4 years, 286 incident stroke cases occurred.

Results showed that increased levels of physical activity were associated with reduced risk of stroke.

For moderate to vigorous activity, compared with participants in the lowest tertile, those in the highest tertile of total daily time in moderate to vigorous activity had a 43% lower risk of stroke.

In the current study, the amount of moderate to vigorous activity associated with a significant reduction in stroke risk was approximately 25 minutes per day (3 hours per week).

Dr. Hooker noted that moderate to vigorous activity included things such as brisk walking, jogging, bike riding, swimming, or playing tennis or soccer. “Doing such activities for just 25 minutes per day reduced risk of stroke by 43%. This is very doable. Just commuting to work by bicycle would cover you here,” he said.

In terms of light-intensity activity, individuals who did 4-5 hours of light activities each day had a 26% reduced risk for first stroke, compared with those doing less than 3 hours of such light activities.

Dr. Hooker explained that examples of light activity included household chores, such as vacuuming, washing dishes, or going for a gentle stroll. “These activities do not require heaving breathing, increased heart rate or breaking into a sweat. They are activities of daily living and relatively easy to engage in.”

But he pointed out that the 4-5 hours of light activity every day linked to a reduction in stroke risk may be more difficult to achieve than the 25 minutes of moderate to vigorous activity, saying: “You have to have some intentionality here.”
 

Long bouts of sedentary time are harmful

The study also showed that sedentary time was associated with a higher risk for stroke.

The authors noted that time spent in sedentary behavior is of interest because most adults spend most of their awake time being physically inactive.

They report that participants in the highest tertile of sedentary time (more than 13 hours/day) exhibited a 44% increase in risk of stroke, compared with those in the lowest tertile (less than 11 hours/day), and the association remained significant when adjusted for several covariates, including moderate to vigorous activity.

“Even when controlling for the amount of other physical activity, sedentary behavior is still highly associated with risk of stroke. So even if you are active, long bouts of sedentary behavior are harmful,” Dr. Hooker commented.

They also found that longer bouts of sedentary time (more than 17 minutes at a time) were associated with a 54% higher risk of stroke than shorter bouts (less than 8 minutes).

“This suggests that breaking up periods of sedentary behavior into shorter bouts would be beneficial,” Dr. Hooker said.

“If you are going to spend the evening on the couch watching television, try to stand up and walk around every few minutes. Same for if you are sitting at a computer all day – try having a standing workstation, or at least take regular breaks to walk around,” he added.

This research was supported by grants from the National Institute of Neurological Disorders and Stroke and the National Institute on Aging. Additional funding was provided by an unrestricted grant from the Coca-Cola Company. The authors report no disclosures.

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

Spending more time doing light-intensity activities and less time being sedentary was associated with a reduced risk for first stroke in a population-based study of middle aged and older adults.

The study also found relatively short periods of moderate to vigorous exercise were associated with reduced stroke risk.

“Our results suggest there are a number of ways to reduce stroke risk simply by moving about,” said lead author Steven P. Hooker, PhD, San Diego State University. “This could be with short periods of moderate to vigorous activity each day, longer periods of light activity, or just sedentary for shorter periods of time. All these things can make a difference.”

Dr. Hooker explained that, while it has been found previously that moderate to vigorous exercise reduces stroke risk, this study gives more information on light-intensity activities and sedentary behavior and the risk of stroke.

“Our results suggest that you don’t have to be a chronic exerciser to reduce stroke risk. Replacing sedentary time with light-intensity activity will be beneficial. Just go for a short walk, get up from your desk and move around the house at regular intervals. That can help to reduce stroke risk,” Dr. Hooker said.  

“Our message is basically to sit less and move more,” he added.  

The study was published online in JAMA Network Open.

The study involved 7,607 U.S. individuals without a history of stroke, with oversampling from the southeastern “Stroke Belt,” who were participating in the REGARDS cohort study.

The participants wore an accelerometer to measure physical activity and sedentary behavior for 7 consecutive days. The mean age of the individuals was 63 years; 54% were female, 32% were Black.

Over a mean follow-up of 7.4 years, 286 incident stroke cases occurred.

Results showed that increased levels of physical activity were associated with reduced risk of stroke.

For moderate to vigorous activity, compared with participants in the lowest tertile, those in the highest tertile of total daily time in moderate to vigorous activity had a 43% lower risk of stroke.

In the current study, the amount of moderate to vigorous activity associated with a significant reduction in stroke risk was approximately 25 minutes per day (3 hours per week).

Dr. Hooker noted that moderate to vigorous activity included things such as brisk walking, jogging, bike riding, swimming, or playing tennis or soccer. “Doing such activities for just 25 minutes per day reduced risk of stroke by 43%. This is very doable. Just commuting to work by bicycle would cover you here,” he said.

In terms of light-intensity activity, individuals who did 4-5 hours of light activities each day had a 26% reduced risk for first stroke, compared with those doing less than 3 hours of such light activities.

Dr. Hooker explained that examples of light activity included household chores, such as vacuuming, washing dishes, or going for a gentle stroll. “These activities do not require heaving breathing, increased heart rate or breaking into a sweat. They are activities of daily living and relatively easy to engage in.”

But he pointed out that the 4-5 hours of light activity every day linked to a reduction in stroke risk may be more difficult to achieve than the 25 minutes of moderate to vigorous activity, saying: “You have to have some intentionality here.”
 

Long bouts of sedentary time are harmful

The study also showed that sedentary time was associated with a higher risk for stroke.

The authors noted that time spent in sedentary behavior is of interest because most adults spend most of their awake time being physically inactive.

They report that participants in the highest tertile of sedentary time (more than 13 hours/day) exhibited a 44% increase in risk of stroke, compared with those in the lowest tertile (less than 11 hours/day), and the association remained significant when adjusted for several covariates, including moderate to vigorous activity.

“Even when controlling for the amount of other physical activity, sedentary behavior is still highly associated with risk of stroke. So even if you are active, long bouts of sedentary behavior are harmful,” Dr. Hooker commented.

They also found that longer bouts of sedentary time (more than 17 minutes at a time) were associated with a 54% higher risk of stroke than shorter bouts (less than 8 minutes).

“This suggests that breaking up periods of sedentary behavior into shorter bouts would be beneficial,” Dr. Hooker said.

“If you are going to spend the evening on the couch watching television, try to stand up and walk around every few minutes. Same for if you are sitting at a computer all day – try having a standing workstation, or at least take regular breaks to walk around,” he added.

This research was supported by grants from the National Institute of Neurological Disorders and Stroke and the National Institute on Aging. Additional funding was provided by an unrestricted grant from the Coca-Cola Company. The authors report no disclosures.

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

Doctors were significantly less likely to order colorectal cancer screening with the at-home test Cologuard (Exact Sciences) for Black patients and were more likely to order the test for Asian patients, new evidence reveals.

Investigators retrospectively studied 557,156 patients in the Mayo Clinic health system from 2012 to 2022. They found that Cologuard was ordered for 8.7% of Black patients, compared to 11.9% of White patients and 13.1% of Asian patients.

Both minority groups were less likely than White patients to undergo a follow-up colonoscopy within 1 year of Cologuard testing. Cologuard tests the stool for blood and DNA markers associated with colorectal cancer.

Although the researchers did not examine the reasons driving the disparities, lead investigator Ahmed Ouni, MD, told this news organization that “it could be patient preferences ... or there could be some bias as providers ourselves in how we present the data to patients.”

Dr. Ouni presented the findings on May 22 at the annual Digestive Disease Week^® (DDW), held in person in San Diego and virtually.
 

Breakdown by physician specialty

“We looked at the specialty of physicians ordering these because we wanted to see where the disparity was coming from, if there was a disparity,” said Dr. Ouni, a gastroenterologist at Mayo Clinic, Jacksonville, Florida.

Just over half (51%) of the patients received care from family medicine physicians, 27% received care from internists, and 22% were seen by gastroenterologists.

Family physicians ordered Cologuard testing for 8.7% of Black patients, compared with 16.1% of White patients, a significant difference (P < .001). Internists ordered the test for 10.5% of Black patients and 11.1% of White patients (P <  .001). Gastroenterologists ordered Cologuard screening for 2.4% of Black patients and 3.2% of White patients (P = .009).

Gastroenterologists were 47% more likely to order Cologuard for Asian patients, and internists were 16% more likely to order it for this population than for White patients. However, the findings were not statistically significant for the overall cohort of Asian patients when the researchers adjusted for age and sex (P = 0.52).

Black patients were 25% less likely to have a follow-up colonoscopy within 1 year of undergoing a Cologuard test (odds ratio, 0.75; 95% confidence interval, 0.60-0.94), and Asian patients were 35% less likely (OR, 0.65; 95% CI, 0.52-0.82).
 

Ongoing and future research

Of the total study population, only 2.9% self-identified as Black; according to the 2020 U.S. Census, 12.4% of the population of the United States are Black persons.

When asked about the relatively low proportion of Black persons in the study, Dr. Ouni replied that the investigators are partnering with a Black physician group in the Jacksonville, Fla., area to expand the study to a more diverse population.

Additional plans include assessing how many positive Cologuard test results led to follow-up colonoscopies.

The investigators are also working with family physicians at the Mayo Clinic to examine how physicians explain colorectal cancer screening options to patients and are studying patient preferences regarding screening options, which include Cologuard, fecal immunochemical test (FIT)/fecal occult blood testing, CT colonography, and colonoscopy.

“We’re analyzing the data by ZIP code to see if this could be related to finances,” Dr. Ouni added. “So, if you’re Black or White and more financially impoverished, how does that affect how you view Cologuard and colorectal cancer screening?”
 

Some unanswered questions

“Overall this study supports other studies of a disparity in colorectal cancer screening for African Americans,” John M. Carethers, MD, told this news organization when asked to comment. “This is known for FIT and colonoscopy, and Cologuard, which is a genetic test in addition to FIT, appears to be in that same realm.”

“Noninvasive tests will have a role to reach populations who may not readily have access to colonoscopy,” said Dr. Carethers, John G. Searle Professor and chair of the department of internal medicine and professor of human genetics at the University of Michigan, Ann Arbor. “The key here is if the test is positive, it needs to be followed up with a colonoscopy.”

Dr. Carethers added that the study raises some unanswered questions; for example, does the cost difference between testing options make a difference?

“FIT is under $20, but Cologuard is generally $300 or more,” he said. What percentage of the study population were offered other options, such as FIT? How does insurance status affect screening in different populations?”

“The findings should be taken in context of what other screening options were offered to or elected by patients,” agreed Gregory S. Cooper, MD, professor of medicine and population and quantitative health sciences at Case Western Reserve University and a gastroenterologist at University Hospitals Cleveland Medical Center.

According to guidelines, patients can be offered a menu of options, including FIT, colonoscopy, and Cologuard, Dr. Cooper said in an interview.

“If more African Americans elected colonoscopy, for example, the findings may balance out,” said Dr. Cooper, who was not affiliated with the study. “It would also be of interest to know if the racial differences changed over time. With the pandemic, the use of noninvasive options, such as Cologuard, have increased.”

“I will note that specifically for colonoscopy in the United States, the disparity gap had been closing from about 15% to 18% 20 years ago to about 3% in 2020 pre-COVID,” Dr. Carethers added. “I am fearful that COVID may have led to a widening of that gap again as we get more data.”

“It is important that noninvasive tests for screening be a part of the portfolio of offerings to patients, as about 35% of eligible at-risk persons who need to be screened are not screened in the United States,” Dr. Carethers said.

The study was not industry sponsored. Dr. Ouni and Dr. Carethers report no relevant financial relationships. Dr. Cooper has received consulting fees from Exact Sciences.

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

Doctors were significantly less likely to order colorectal cancer screening with the at-home test Cologuard (Exact Sciences) for Black patients and were more likely to order the test for Asian patients, new evidence reveals.

Investigators retrospectively studied 557,156 patients in the Mayo Clinic health system from 2012 to 2022. They found that Cologuard was ordered for 8.7% of Black patients, compared to 11.9% of White patients and 13.1% of Asian patients.

Both minority groups were less likely than White patients to undergo a follow-up colonoscopy within 1 year of Cologuard testing. Cologuard tests the stool for blood and DNA markers associated with colorectal cancer.

Although the researchers did not examine the reasons driving the disparities, lead investigator Ahmed Ouni, MD, told this news organization that “it could be patient preferences ... or there could be some bias as providers ourselves in how we present the data to patients.”

Dr. Ouni presented the findings on May 22 at the annual Digestive Disease Week^® (DDW), held in person in San Diego and virtually.
 

Breakdown by physician specialty

“We looked at the specialty of physicians ordering these because we wanted to see where the disparity was coming from, if there was a disparity,” said Dr. Ouni, a gastroenterologist at Mayo Clinic, Jacksonville, Florida.

Just over half (51%) of the patients received care from family medicine physicians, 27% received care from internists, and 22% were seen by gastroenterologists.

Family physicians ordered Cologuard testing for 8.7% of Black patients, compared with 16.1% of White patients, a significant difference (P < .001). Internists ordered the test for 10.5% of Black patients and 11.1% of White patients (P <  .001). Gastroenterologists ordered Cologuard screening for 2.4% of Black patients and 3.2% of White patients (P = .009).

Gastroenterologists were 47% more likely to order Cologuard for Asian patients, and internists were 16% more likely to order it for this population than for White patients. However, the findings were not statistically significant for the overall cohort of Asian patients when the researchers adjusted for age and sex (P = 0.52).

Black patients were 25% less likely to have a follow-up colonoscopy within 1 year of undergoing a Cologuard test (odds ratio, 0.75; 95% confidence interval, 0.60-0.94), and Asian patients were 35% less likely (OR, 0.65; 95% CI, 0.52-0.82).
 

Ongoing and future research

Of the total study population, only 2.9% self-identified as Black; according to the 2020 U.S. Census, 12.4% of the population of the United States are Black persons.

When asked about the relatively low proportion of Black persons in the study, Dr. Ouni replied that the investigators are partnering with a Black physician group in the Jacksonville, Fla., area to expand the study to a more diverse population.

Additional plans include assessing how many positive Cologuard test results led to follow-up colonoscopies.

The investigators are also working with family physicians at the Mayo Clinic to examine how physicians explain colorectal cancer screening options to patients and are studying patient preferences regarding screening options, which include Cologuard, fecal immunochemical test (FIT)/fecal occult blood testing, CT colonography, and colonoscopy.

“We’re analyzing the data by ZIP code to see if this could be related to finances,” Dr. Ouni added. “So, if you’re Black or White and more financially impoverished, how does that affect how you view Cologuard and colorectal cancer screening?”
 

Some unanswered questions

“Overall this study supports other studies of a disparity in colorectal cancer screening for African Americans,” John M. Carethers, MD, told this news organization when asked to comment. “This is known for FIT and colonoscopy, and Cologuard, which is a genetic test in addition to FIT, appears to be in that same realm.”

“Noninvasive tests will have a role to reach populations who may not readily have access to colonoscopy,” said Dr. Carethers, John G. Searle Professor and chair of the department of internal medicine and professor of human genetics at the University of Michigan, Ann Arbor. “The key here is if the test is positive, it needs to be followed up with a colonoscopy.”

Dr. Carethers added that the study raises some unanswered questions; for example, does the cost difference between testing options make a difference?

“FIT is under $20, but Cologuard is generally $300 or more,” he said. What percentage of the study population were offered other options, such as FIT? How does insurance status affect screening in different populations?”

“The findings should be taken in context of what other screening options were offered to or elected by patients,” agreed Gregory S. Cooper, MD, professor of medicine and population and quantitative health sciences at Case Western Reserve University and a gastroenterologist at University Hospitals Cleveland Medical Center.

According to guidelines, patients can be offered a menu of options, including FIT, colonoscopy, and Cologuard, Dr. Cooper said in an interview.

“If more African Americans elected colonoscopy, for example, the findings may balance out,” said Dr. Cooper, who was not affiliated with the study. “It would also be of interest to know if the racial differences changed over time. With the pandemic, the use of noninvasive options, such as Cologuard, have increased.”

“I will note that specifically for colonoscopy in the United States, the disparity gap had been closing from about 15% to 18% 20 years ago to about 3% in 2020 pre-COVID,” Dr. Carethers added. “I am fearful that COVID may have led to a widening of that gap again as we get more data.”

“It is important that noninvasive tests for screening be a part of the portfolio of offerings to patients, as about 35% of eligible at-risk persons who need to be screened are not screened in the United States,” Dr. Carethers said.

The study was not industry sponsored. Dr. Ouni and Dr. Carethers report no relevant financial relationships. Dr. Cooper has received consulting fees from Exact Sciences.

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

Doctors were significantly less likely to order colorectal cancer screening with the at-home test Cologuard (Exact Sciences) for Black patients and were more likely to order the test for Asian patients, new evidence reveals.

Investigators retrospectively studied 557,156 patients in the Mayo Clinic health system from 2012 to 2022. They found that Cologuard was ordered for 8.7% of Black patients, compared to 11.9% of White patients and 13.1% of Asian patients.

Both minority groups were less likely than White patients to undergo a follow-up colonoscopy within 1 year of Cologuard testing. Cologuard tests the stool for blood and DNA markers associated with colorectal cancer.

Although the researchers did not examine the reasons driving the disparities, lead investigator Ahmed Ouni, MD, told this news organization that “it could be patient preferences ... or there could be some bias as providers ourselves in how we present the data to patients.”

Dr. Ouni presented the findings on May 22 at the annual Digestive Disease Week^® (DDW), held in person in San Diego and virtually.
 

Breakdown by physician specialty

“We looked at the specialty of physicians ordering these because we wanted to see where the disparity was coming from, if there was a disparity,” said Dr. Ouni, a gastroenterologist at Mayo Clinic, Jacksonville, Florida.

Just over half (51%) of the patients received care from family medicine physicians, 27% received care from internists, and 22% were seen by gastroenterologists.

Family physicians ordered Cologuard testing for 8.7% of Black patients, compared with 16.1% of White patients, a significant difference (P < .001). Internists ordered the test for 10.5% of Black patients and 11.1% of White patients (P <  .001). Gastroenterologists ordered Cologuard screening for 2.4% of Black patients and 3.2% of White patients (P = .009).

Gastroenterologists were 47% more likely to order Cologuard for Asian patients, and internists were 16% more likely to order it for this population than for White patients. However, the findings were not statistically significant for the overall cohort of Asian patients when the researchers adjusted for age and sex (P = 0.52).

Black patients were 25% less likely to have a follow-up colonoscopy within 1 year of undergoing a Cologuard test (odds ratio, 0.75; 95% confidence interval, 0.60-0.94), and Asian patients were 35% less likely (OR, 0.65; 95% CI, 0.52-0.82).
 

Ongoing and future research

Of the total study population, only 2.9% self-identified as Black; according to the 2020 U.S. Census, 12.4% of the population of the United States are Black persons.

When asked about the relatively low proportion of Black persons in the study, Dr. Ouni replied that the investigators are partnering with a Black physician group in the Jacksonville, Fla., area to expand the study to a more diverse population.

Additional plans include assessing how many positive Cologuard test results led to follow-up colonoscopies.

The investigators are also working with family physicians at the Mayo Clinic to examine how physicians explain colorectal cancer screening options to patients and are studying patient preferences regarding screening options, which include Cologuard, fecal immunochemical test (FIT)/fecal occult blood testing, CT colonography, and colonoscopy.

“We’re analyzing the data by ZIP code to see if this could be related to finances,” Dr. Ouni added. “So, if you’re Black or White and more financially impoverished, how does that affect how you view Cologuard and colorectal cancer screening?”
 

Some unanswered questions

“Overall this study supports other studies of a disparity in colorectal cancer screening for African Americans,” John M. Carethers, MD, told this news organization when asked to comment. “This is known for FIT and colonoscopy, and Cologuard, which is a genetic test in addition to FIT, appears to be in that same realm.”

“Noninvasive tests will have a role to reach populations who may not readily have access to colonoscopy,” said Dr. Carethers, John G. Searle Professor and chair of the department of internal medicine and professor of human genetics at the University of Michigan, Ann Arbor. “The key here is if the test is positive, it needs to be followed up with a colonoscopy.”

Dr. Carethers added that the study raises some unanswered questions; for example, does the cost difference between testing options make a difference?

“FIT is under $20, but Cologuard is generally $300 or more,” he said. What percentage of the study population were offered other options, such as FIT? How does insurance status affect screening in different populations?”

“The findings should be taken in context of what other screening options were offered to or elected by patients,” agreed Gregory S. Cooper, MD, professor of medicine and population and quantitative health sciences at Case Western Reserve University and a gastroenterologist at University Hospitals Cleveland Medical Center.

According to guidelines, patients can be offered a menu of options, including FIT, colonoscopy, and Cologuard, Dr. Cooper said in an interview.

“If more African Americans elected colonoscopy, for example, the findings may balance out,” said Dr. Cooper, who was not affiliated with the study. “It would also be of interest to know if the racial differences changed over time. With the pandemic, the use of noninvasive options, such as Cologuard, have increased.”

“I will note that specifically for colonoscopy in the United States, the disparity gap had been closing from about 15% to 18% 20 years ago to about 3% in 2020 pre-COVID,” Dr. Carethers added. “I am fearful that COVID may have led to a widening of that gap again as we get more data.”

“It is important that noninvasive tests for screening be a part of the portfolio of offerings to patients, as about 35% of eligible at-risk persons who need to be screened are not screened in the United States,” Dr. Carethers said.

The study was not industry sponsored. Dr. Ouni and Dr. Carethers report no relevant financial relationships. Dr. Cooper has received consulting fees from Exact Sciences.

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

COPENHAGEN – Most patients with immune-mediated inflammatory diseases (IMID) should not be considered at high risk for severe COVID-19 breakthrough infections, but those on anti-CD20 therapy are the exception, data from a large prospective, cohort study show.

“Overall, the data are reassuring, with conventional risk factors, such as age, and comorbidities seeming to be more important regarding risk of severe COVID-19 breakthrough infections than rheumatic disease or immunosuppressant medication,” said Laura Boekel, MD, from Amsterdam UMC, who presented the study at the annual European Congress of Rheumatology.

peterschreiber_media/iStock/Getty Images

But, she added, there was an exception for anti-CD20 therapy. “This is especially relevant for patients with conventional risk factors that might accumulate, and rheumatologists might want to consider alternative treatment options if possible. It is important to inform patients about the risks of anti-CD20.”

Another study, presented during the same session at the congress by Rebecca Hasseli, MD, from the University of Giessen (Germany) saw no deaths and no COVID-19 related complications in a cohort of triple-vaccinated patients with inflammatory rheumatic diseases, despite a higher median age and a higher rate of comorbidities compared to double-vaccinated and unvaccinated cohorts.

Ingrid Jyssum, MD, from Diakonhjemmet Hospital, Oslo, who presented results of the Nor-vaC study investigating the impact of different DMARDs on the immunogenicity of a third COVID-19 vaccine dose, welcomed the research by Dr. Boekel and Dr. Hasseli.

“The findings of Hasseli are interesting in the light of our data on serological response after the third dose, with a lack of breakthrough infections after three doses corresponding well to the robust antibody response that we found in our cohort,” she remarked. “This is very reassuring for our patients. Our own work together with the findings of Hasseli and Boekel demonstrate that additional vaccine doses are important to keep this population well protected against severe COVID-19 infections.”

The Nor-vaC study was conducted with a cohort of 1,100 patients with inflammatory joint and bowel diseases. “These patients had attenuated antibody responses after two vaccine doses; however, we found that a third vaccine dose brought the humoral response in patients up to the antibody levels that healthy controls had after two doses,” said Dr. Jyssum. “In addition, we found that the decline in antibodies after the third dose was less than the decline seen after the second dose. Importantly, the third dose was safe in our patients, with no new safety issues.”
 

Breakthrough infections and immunosuppressants

“Like the rest of the world, we were wondering if our patients were at increased risk of COVID-19, and if the immunosuppressants used by these patients influenced their risk,” said Dr. Boekel.

The researchers compared both the incidence and severity of COVID-19 breakthrough infections with the SARS-CoV-2 Delta variant in a population of fully vaccinated IMID patients taking immunosuppressants and controls (IMID patients not taking immunosuppressants and healthy controls).

Two large ongoing, prospective, multicenter cohort studies provided pooled data collected between February and December 2021 using digital questionnaires, standardized electronic case record forms, and medical files.

Finger-prick tests were used to collect blood samples that were analyzed after vaccination against SARS-CoV-2 for anti–receptor-binding domain (RBD) antibodies, and antinucleocapsid antibodies to identify asymptomatic breakthrough infections. Any associations between antibodies and the incidence of breakthrough infections were generated, and results were adjusted for sex, cardiovascular disease, chronic pulmonary disease, obesity, and vaccine type.

The analysis included 3,207 IMID patients taking immunosuppressants, and 1,810 controls (985 IMID patients not on immunosuppressants and 825 healthy controls).

Initially, Dr. Boekel and her colleagues looked at incidence of infections and hospitalizations prior to vaccination, and then after vaccination, which was the main aim of the study.

Prior to vaccination, hospitalization risk for COVID-19 was somewhat higher for IMID patients overall compared with controls, reported Dr. Boekel. “But those treated with anti-CD20 therapy, demonstrated much greater risk for severe disease.”

After the SARS-CoV-2 vaccination campaign began, the researchers then looked at how immunosuppressants influenced humoral response to SARS-CoV-2 vaccination.

“Anti-CD20 therapy showed the greatest impact on humoral immune response after SARS-CoV-2 vaccination,” said Dr. Boekel. Other immunosuppressant drugs had variable effects on humoral and cellular immunity. 

Once they had established that immunosuppressant drugs impaired immune responses to SARS-CoV-2 vaccination, the researchers wanted to determine if this affected clinical outcomes. Blood samples taken 28 days after the second vaccination enabled Dr. Boekel and her colleagues to see if antibody production was associated with breakthrough infections.   

Breakthrough infections were seen in 5% of patients on immunosuppressants, 5% of patients not on immunosuppressants, and 4% of healthy controls. Also, asymptomatic COVID-19 breakthrough cases were comparable between IMID patients taking immunosuppressants and controls, at 10% in each group.

“We saw that the incidence [of getting COVID-19] was comparable between groups, independent of whether they were receiving immunosuppressants or not, or healthy controls. However, if they developed antibodies against the two vaccinations the chance of getting infected was lower,” reported Dr. Boekel.

Hospitalization (severe disease) rates were also comparable between groups. “Patients with rheumatic diseases, even when treated with immunosuppressants were not at increased risk of severe disease from Delta breakthrough infections,” added the researcher. “Cases that were hospitalized were mainly elderly and those with comorbidities, for example cardiovascular disease and cardiopulmonary disease.”

Hospital admissions were 5.4% in patients on immunosuppressants, 5.7% in those not on immunosuppressants, and 6% in health controls.

However, once again, there was one exception, Dr. Boekel stressed. “Patients treated with anti-CD20 therapy were at increased risk of severe disease and hospitalization.”

Omicron variant has a different transmissibility than Delta, so the researchers continued the study looking at the Omicron variant. The data “were mostly reassuring,” said Dr. Boekel. “As expected, hospitalization rates decreased overall, with the exception of patients on anti-CD20 therapy where, despite overall reduced pathogenicity, patients remain at increased risk.”

She said that they were awaiting long-term data so the data reflect only short-term immunity against Omicron. “However, we included many elderly and patients with comorbidities, so this made the analysis very sensitive to detect severe cases,” she added.

Breakthrough infection among double- and triple-vaccinated patients

A lower rate of COVID-19 related complications and deaths were seen in patients who were triple-vaccinated against SARS-CoV-2, than in double-vaccinated or unvaccinated patients, despite the former having more comorbidities and use of rituximab (Rituxan), said Dr. Hasseli.

“These data support the recommendation of booster vaccination to reduce COVID-19-related mortality in patients with inflammatory rheumatic diseases [IRDs],” she said.

“A small number of COVID-19 cases were seen in patients with IRD after vaccinations, and in a few cases, hospitalizations were required. Breakthrough infections were mostly seen in patients on B-cell depletion therapy,” she added.

Dr. Hasseli and her colleagues looked at the characteristics and outcomes of SARS-CoV-2 breakthrough infections among double- and triple-vaccinated patients with IRD.

“We wanted to understand if patients with IRD are protected in the same way as the general population following vaccination, given that these patients receive drugs that might impair the immune response,” she explained.

Data for analysis were drawn from the German COVID-19-IRD registry covering February 2021 and January 2022, and patients who were double- or triple- vaccinated against COVID-19 either 14 days or more prior to a SARS-CoV-2 infection were included. Type of IRD, vaccine, immunomodulation, comorbidities, and outcome of the infection were compared with 737 unvaccinated IRD patients with COVID-19. Those with prior COVID-19 were excluded.

Cases were stratified by vaccinations status: unvaccinated (1,388 patients, median age 57 years); double vaccinated (462, 56 years) and triple vaccinated (301, 53 years). Body mass index was similar across groups (25-26 kg/m²), and time between SARS-CoV-2 infection and last vaccination was 156 days in double-vaccinated patients, and 62 days in triple-vaccinated patients.

Patients had rheumatoid arthritis in 44.7% and 44.4% of unvaccinated and double-vaccinated patients respectively, but fewer triple-vaccinated patients had RA (37.2%). Triple vaccination was seen in 32.2% of patients with spondyloarthritis, 16.6% connective tissue diseases, 5.3% other vasculitis, and 3.3% ANCA-associated vasculitis. Of triple-vaccinated patients, 26.2% were treated with tumor necrosis factor-alpha (TNF-alpha) inhibitors, and 6.3% with rituximab, while 5.3% were not on immunomodulation. At least 25% were treated with glucocorticoids, reported Dr. Hasseli.

“Arterial hypertension and diabetes, that might be risk factors for COVID-19, were less frequently reported in triple-vaccinated patients. More patients in the double-vaccinated group [42.9%] than the triple-vaccinated [23.8%] reported absence of relevant comorbidities,” she said.

COVID-19 related complications were less often reported in double- and triple-vaccinated groups with hospitalizations at 9.5% and 4.3% in double and triple-vaccinated people respectively.

Dr. Boekel and Dr. Hasseli report no relevant conflicts of interest.

COPENHAGEN – Most patients with immune-mediated inflammatory diseases (IMID) should not be considered at high risk for severe COVID-19 breakthrough infections, but those on anti-CD20 therapy are the exception, data from a large prospective, cohort study show.

“Overall, the data are reassuring, with conventional risk factors, such as age, and comorbidities seeming to be more important regarding risk of severe COVID-19 breakthrough infections than rheumatic disease or immunosuppressant medication,” said Laura Boekel, MD, from Amsterdam UMC, who presented the study at the annual European Congress of Rheumatology.

peterschreiber_media/iStock/Getty Images

But, she added, there was an exception for anti-CD20 therapy. “This is especially relevant for patients with conventional risk factors that might accumulate, and rheumatologists might want to consider alternative treatment options if possible. It is important to inform patients about the risks of anti-CD20.”

Another study, presented during the same session at the congress by Rebecca Hasseli, MD, from the University of Giessen (Germany) saw no deaths and no COVID-19 related complications in a cohort of triple-vaccinated patients with inflammatory rheumatic diseases, despite a higher median age and a higher rate of comorbidities compared to double-vaccinated and unvaccinated cohorts.

Ingrid Jyssum, MD, from Diakonhjemmet Hospital, Oslo, who presented results of the Nor-vaC study investigating the impact of different DMARDs on the immunogenicity of a third COVID-19 vaccine dose, welcomed the research by Dr. Boekel and Dr. Hasseli.

“The findings of Hasseli are interesting in the light of our data on serological response after the third dose, with a lack of breakthrough infections after three doses corresponding well to the robust antibody response that we found in our cohort,” she remarked. “This is very reassuring for our patients. Our own work together with the findings of Hasseli and Boekel demonstrate that additional vaccine doses are important to keep this population well protected against severe COVID-19 infections.”

The Nor-vaC study was conducted with a cohort of 1,100 patients with inflammatory joint and bowel diseases. “These patients had attenuated antibody responses after two vaccine doses; however, we found that a third vaccine dose brought the humoral response in patients up to the antibody levels that healthy controls had after two doses,” said Dr. Jyssum. “In addition, we found that the decline in antibodies after the third dose was less than the decline seen after the second dose. Importantly, the third dose was safe in our patients, with no new safety issues.”
 

Breakthrough infections and immunosuppressants

“Like the rest of the world, we were wondering if our patients were at increased risk of COVID-19, and if the immunosuppressants used by these patients influenced their risk,” said Dr. Boekel.

The researchers compared both the incidence and severity of COVID-19 breakthrough infections with the SARS-CoV-2 Delta variant in a population of fully vaccinated IMID patients taking immunosuppressants and controls (IMID patients not taking immunosuppressants and healthy controls).

Two large ongoing, prospective, multicenter cohort studies provided pooled data collected between February and December 2021 using digital questionnaires, standardized electronic case record forms, and medical files.

Finger-prick tests were used to collect blood samples that were analyzed after vaccination against SARS-CoV-2 for anti–receptor-binding domain (RBD) antibodies, and antinucleocapsid antibodies to identify asymptomatic breakthrough infections. Any associations between antibodies and the incidence of breakthrough infections were generated, and results were adjusted for sex, cardiovascular disease, chronic pulmonary disease, obesity, and vaccine type.

The analysis included 3,207 IMID patients taking immunosuppressants, and 1,810 controls (985 IMID patients not on immunosuppressants and 825 healthy controls).

Initially, Dr. Boekel and her colleagues looked at incidence of infections and hospitalizations prior to vaccination, and then after vaccination, which was the main aim of the study.

Prior to vaccination, hospitalization risk for COVID-19 was somewhat higher for IMID patients overall compared with controls, reported Dr. Boekel. “But those treated with anti-CD20 therapy, demonstrated much greater risk for severe disease.”

After the SARS-CoV-2 vaccination campaign began, the researchers then looked at how immunosuppressants influenced humoral response to SARS-CoV-2 vaccination.

“Anti-CD20 therapy showed the greatest impact on humoral immune response after SARS-CoV-2 vaccination,” said Dr. Boekel. Other immunosuppressant drugs had variable effects on humoral and cellular immunity. 

Once they had established that immunosuppressant drugs impaired immune responses to SARS-CoV-2 vaccination, the researchers wanted to determine if this affected clinical outcomes. Blood samples taken 28 days after the second vaccination enabled Dr. Boekel and her colleagues to see if antibody production was associated with breakthrough infections.   

Breakthrough infections were seen in 5% of patients on immunosuppressants, 5% of patients not on immunosuppressants, and 4% of healthy controls. Also, asymptomatic COVID-19 breakthrough cases were comparable between IMID patients taking immunosuppressants and controls, at 10% in each group.

“We saw that the incidence [of getting COVID-19] was comparable between groups, independent of whether they were receiving immunosuppressants or not, or healthy controls. However, if they developed antibodies against the two vaccinations the chance of getting infected was lower,” reported Dr. Boekel.

Hospitalization (severe disease) rates were also comparable between groups. “Patients with rheumatic diseases, even when treated with immunosuppressants were not at increased risk of severe disease from Delta breakthrough infections,” added the researcher. “Cases that were hospitalized were mainly elderly and those with comorbidities, for example cardiovascular disease and cardiopulmonary disease.”

Hospital admissions were 5.4% in patients on immunosuppressants, 5.7% in those not on immunosuppressants, and 6% in health controls.

However, once again, there was one exception, Dr. Boekel stressed. “Patients treated with anti-CD20 therapy were at increased risk of severe disease and hospitalization.”

Omicron variant has a different transmissibility than Delta, so the researchers continued the study looking at the Omicron variant. The data “were mostly reassuring,” said Dr. Boekel. “As expected, hospitalization rates decreased overall, with the exception of patients on anti-CD20 therapy where, despite overall reduced pathogenicity, patients remain at increased risk.”

She said that they were awaiting long-term data so the data reflect only short-term immunity against Omicron. “However, we included many elderly and patients with comorbidities, so this made the analysis very sensitive to detect severe cases,” she added.

Breakthrough infection among double- and triple-vaccinated patients

A lower rate of COVID-19 related complications and deaths were seen in patients who were triple-vaccinated against SARS-CoV-2, than in double-vaccinated or unvaccinated patients, despite the former having more comorbidities and use of rituximab (Rituxan), said Dr. Hasseli.

“These data support the recommendation of booster vaccination to reduce COVID-19-related mortality in patients with inflammatory rheumatic diseases [IRDs],” she said.

“A small number of COVID-19 cases were seen in patients with IRD after vaccinations, and in a few cases, hospitalizations were required. Breakthrough infections were mostly seen in patients on B-cell depletion therapy,” she added.

Dr. Hasseli and her colleagues looked at the characteristics and outcomes of SARS-CoV-2 breakthrough infections among double- and triple-vaccinated patients with IRD.

“We wanted to understand if patients with IRD are protected in the same way as the general population following vaccination, given that these patients receive drugs that might impair the immune response,” she explained.

Data for analysis were drawn from the German COVID-19-IRD registry covering February 2021 and January 2022, and patients who were double- or triple- vaccinated against COVID-19 either 14 days or more prior to a SARS-CoV-2 infection were included. Type of IRD, vaccine, immunomodulation, comorbidities, and outcome of the infection were compared with 737 unvaccinated IRD patients with COVID-19. Those with prior COVID-19 were excluded.

Cases were stratified by vaccinations status: unvaccinated (1,388 patients, median age 57 years); double vaccinated (462, 56 years) and triple vaccinated (301, 53 years). Body mass index was similar across groups (25-26 kg/m²), and time between SARS-CoV-2 infection and last vaccination was 156 days in double-vaccinated patients, and 62 days in triple-vaccinated patients.

Patients had rheumatoid arthritis in 44.7% and 44.4% of unvaccinated and double-vaccinated patients respectively, but fewer triple-vaccinated patients had RA (37.2%). Triple vaccination was seen in 32.2% of patients with spondyloarthritis, 16.6% connective tissue diseases, 5.3% other vasculitis, and 3.3% ANCA-associated vasculitis. Of triple-vaccinated patients, 26.2% were treated with tumor necrosis factor-alpha (TNF-alpha) inhibitors, and 6.3% with rituximab, while 5.3% were not on immunomodulation. At least 25% were treated with glucocorticoids, reported Dr. Hasseli.

“Arterial hypertension and diabetes, that might be risk factors for COVID-19, were less frequently reported in triple-vaccinated patients. More patients in the double-vaccinated group [42.9%] than the triple-vaccinated [23.8%] reported absence of relevant comorbidities,” she said.

COVID-19 related complications were less often reported in double- and triple-vaccinated groups with hospitalizations at 9.5% and 4.3% in double and triple-vaccinated people respectively.

Dr. Boekel and Dr. Hasseli report no relevant conflicts of interest.

COPENHAGEN – Most patients with immune-mediated inflammatory diseases (IMID) should not be considered at high risk for severe COVID-19 breakthrough infections, but those on anti-CD20 therapy are the exception, data from a large prospective, cohort study show.

“Overall, the data are reassuring, with conventional risk factors, such as age, and comorbidities seeming to be more important regarding risk of severe COVID-19 breakthrough infections than rheumatic disease or immunosuppressant medication,” said Laura Boekel, MD, from Amsterdam UMC, who presented the study at the annual European Congress of Rheumatology.

peterschreiber_media/iStock/Getty Images

But, she added, there was an exception for anti-CD20 therapy. “This is especially relevant for patients with conventional risk factors that might accumulate, and rheumatologists might want to consider alternative treatment options if possible. It is important to inform patients about the risks of anti-CD20.”

Another study, presented during the same session at the congress by Rebecca Hasseli, MD, from the University of Giessen (Germany) saw no deaths and no COVID-19 related complications in a cohort of triple-vaccinated patients with inflammatory rheumatic diseases, despite a higher median age and a higher rate of comorbidities compared to double-vaccinated and unvaccinated cohorts.

Ingrid Jyssum, MD, from Diakonhjemmet Hospital, Oslo, who presented results of the Nor-vaC study investigating the impact of different DMARDs on the immunogenicity of a third COVID-19 vaccine dose, welcomed the research by Dr. Boekel and Dr. Hasseli.

“The findings of Hasseli are interesting in the light of our data on serological response after the third dose, with a lack of breakthrough infections after three doses corresponding well to the robust antibody response that we found in our cohort,” she remarked. “This is very reassuring for our patients. Our own work together with the findings of Hasseli and Boekel demonstrate that additional vaccine doses are important to keep this population well protected against severe COVID-19 infections.”

The Nor-vaC study was conducted with a cohort of 1,100 patients with inflammatory joint and bowel diseases. “These patients had attenuated antibody responses after two vaccine doses; however, we found that a third vaccine dose brought the humoral response in patients up to the antibody levels that healthy controls had after two doses,” said Dr. Jyssum. “In addition, we found that the decline in antibodies after the third dose was less than the decline seen after the second dose. Importantly, the third dose was safe in our patients, with no new safety issues.”
 

Breakthrough infections and immunosuppressants

“Like the rest of the world, we were wondering if our patients were at increased risk of COVID-19, and if the immunosuppressants used by these patients influenced their risk,” said Dr. Boekel.

The researchers compared both the incidence and severity of COVID-19 breakthrough infections with the SARS-CoV-2 Delta variant in a population of fully vaccinated IMID patients taking immunosuppressants and controls (IMID patients not taking immunosuppressants and healthy controls).

Two large ongoing, prospective, multicenter cohort studies provided pooled data collected between February and December 2021 using digital questionnaires, standardized electronic case record forms, and medical files.

Finger-prick tests were used to collect blood samples that were analyzed after vaccination against SARS-CoV-2 for anti–receptor-binding domain (RBD) antibodies, and antinucleocapsid antibodies to identify asymptomatic breakthrough infections. Any associations between antibodies and the incidence of breakthrough infections were generated, and results were adjusted for sex, cardiovascular disease, chronic pulmonary disease, obesity, and vaccine type.

The analysis included 3,207 IMID patients taking immunosuppressants, and 1,810 controls (985 IMID patients not on immunosuppressants and 825 healthy controls).

Initially, Dr. Boekel and her colleagues looked at incidence of infections and hospitalizations prior to vaccination, and then after vaccination, which was the main aim of the study.

Prior to vaccination, hospitalization risk for COVID-19 was somewhat higher for IMID patients overall compared with controls, reported Dr. Boekel. “But those treated with anti-CD20 therapy, demonstrated much greater risk for severe disease.”

After the SARS-CoV-2 vaccination campaign began, the researchers then looked at how immunosuppressants influenced humoral response to SARS-CoV-2 vaccination.

“Anti-CD20 therapy showed the greatest impact on humoral immune response after SARS-CoV-2 vaccination,” said Dr. Boekel. Other immunosuppressant drugs had variable effects on humoral and cellular immunity. 

Once they had established that immunosuppressant drugs impaired immune responses to SARS-CoV-2 vaccination, the researchers wanted to determine if this affected clinical outcomes. Blood samples taken 28 days after the second vaccination enabled Dr. Boekel and her colleagues to see if antibody production was associated with breakthrough infections.   

Breakthrough infections were seen in 5% of patients on immunosuppressants, 5% of patients not on immunosuppressants, and 4% of healthy controls. Also, asymptomatic COVID-19 breakthrough cases were comparable between IMID patients taking immunosuppressants and controls, at 10% in each group.

“We saw that the incidence [of getting COVID-19] was comparable between groups, independent of whether they were receiving immunosuppressants or not, or healthy controls. However, if they developed antibodies against the two vaccinations the chance of getting infected was lower,” reported Dr. Boekel.

Hospitalization (severe disease) rates were also comparable between groups. “Patients with rheumatic diseases, even when treated with immunosuppressants were not at increased risk of severe disease from Delta breakthrough infections,” added the researcher. “Cases that were hospitalized were mainly elderly and those with comorbidities, for example cardiovascular disease and cardiopulmonary disease.”

Hospital admissions were 5.4% in patients on immunosuppressants, 5.7% in those not on immunosuppressants, and 6% in health controls.

However, once again, there was one exception, Dr. Boekel stressed. “Patients treated with anti-CD20 therapy were at increased risk of severe disease and hospitalization.”

Omicron variant has a different transmissibility than Delta, so the researchers continued the study looking at the Omicron variant. The data “were mostly reassuring,” said Dr. Boekel. “As expected, hospitalization rates decreased overall, with the exception of patients on anti-CD20 therapy where, despite overall reduced pathogenicity, patients remain at increased risk.”

She said that they were awaiting long-term data so the data reflect only short-term immunity against Omicron. “However, we included many elderly and patients with comorbidities, so this made the analysis very sensitive to detect severe cases,” she added.

Breakthrough infection among double- and triple-vaccinated patients

A lower rate of COVID-19 related complications and deaths were seen in patients who were triple-vaccinated against SARS-CoV-2, than in double-vaccinated or unvaccinated patients, despite the former having more comorbidities and use of rituximab (Rituxan), said Dr. Hasseli.

“These data support the recommendation of booster vaccination to reduce COVID-19-related mortality in patients with inflammatory rheumatic diseases [IRDs],” she said.

“A small number of COVID-19 cases were seen in patients with IRD after vaccinations, and in a few cases, hospitalizations were required. Breakthrough infections were mostly seen in patients on B-cell depletion therapy,” she added.

Dr. Hasseli and her colleagues looked at the characteristics and outcomes of SARS-CoV-2 breakthrough infections among double- and triple-vaccinated patients with IRD.

“We wanted to understand if patients with IRD are protected in the same way as the general population following vaccination, given that these patients receive drugs that might impair the immune response,” she explained.

Data for analysis were drawn from the German COVID-19-IRD registry covering February 2021 and January 2022, and patients who were double- or triple- vaccinated against COVID-19 either 14 days or more prior to a SARS-CoV-2 infection were included. Type of IRD, vaccine, immunomodulation, comorbidities, and outcome of the infection were compared with 737 unvaccinated IRD patients with COVID-19. Those with prior COVID-19 were excluded.

Cases were stratified by vaccinations status: unvaccinated (1,388 patients, median age 57 years); double vaccinated (462, 56 years) and triple vaccinated (301, 53 years). Body mass index was similar across groups (25-26 kg/m²), and time between SARS-CoV-2 infection and last vaccination was 156 days in double-vaccinated patients, and 62 days in triple-vaccinated patients.

Patients had rheumatoid arthritis in 44.7% and 44.4% of unvaccinated and double-vaccinated patients respectively, but fewer triple-vaccinated patients had RA (37.2%). Triple vaccination was seen in 32.2% of patients with spondyloarthritis, 16.6% connective tissue diseases, 5.3% other vasculitis, and 3.3% ANCA-associated vasculitis. Of triple-vaccinated patients, 26.2% were treated with tumor necrosis factor-alpha (TNF-alpha) inhibitors, and 6.3% with rituximab, while 5.3% were not on immunomodulation. At least 25% were treated with glucocorticoids, reported Dr. Hasseli.

“Arterial hypertension and diabetes, that might be risk factors for COVID-19, were less frequently reported in triple-vaccinated patients. More patients in the double-vaccinated group [42.9%] than the triple-vaccinated [23.8%] reported absence of relevant comorbidities,” she said.

COVID-19 related complications were less often reported in double- and triple-vaccinated groups with hospitalizations at 9.5% and 4.3% in double and triple-vaccinated people respectively.

Dr. Boekel and Dr. Hasseli report no relevant conflicts of interest.

Among an estimated 87% of people with HIV (PWH) whose condition has been diagnosed, roughly 66% have received medication. But only half are retained in care, leaving substantial risk for viral rebound and further HIV transmission.

A variety of factors contribute to falling out of care (OOC), a primary reason why a team from the Centers for Disease Control and Prevention reviewed over three decades of studies with the goal of identifying best practices for re-engagement.

The research, which was published  in the journal AIDS, underscores the need for more customized strategies, rather than a one-size-fits-all approach, especially for historically underserved communities.

“Many study participants across the studies included in this review represented communities who have the largest challenges with remaining in care,” Darrel H. Higa, PhD, MSW, lead study author and a behavioral scientist at the CDC in Atlanta, told this news organization.

For example, “Some face barriers that may limit their access to care ... including not having health insurance or being unable to pay for doctor visits or medication, HIV-related stigma, racism, homophobia, transphobia, health literacy, and a lack of providers who specialize in HIV care,” he said.

Other challenges relate to personal barriers, such as competing priorities (for example, work or childcare), substance use, mental health disorders, transportation problems, or a lack of social support.

Even with improvements that address some of these barriers, such as expanded access to health care insurance and broader provision of medical care and HIV medications through the national Ryan White program, structural challenges and social barriers persist.
 

Better versus best practices

In their analysis, the CDC team expanded the scope of prior reviews by including literature published between 2000 and 2020 and further conducted meta-analyses to assess the effectiveness of five common, non mutually exclusive interventions:

• patient navigation
• appointment help/alerts
• psychosocial support
• transportation/appointment reminders
• data-to-care HIV care outcomes (using health department surveillance data and/or patient health records to identify and re-engage OOC PWH)

The majority of the 26,154 participants in 39 included studies (incorporating 42 unique interventions) were male (71%) and Black (64%); the most common time frame for OOC was between 6 and 12 months, but some studies used a time frame of 3-4 months, and others more than 12 months.

Definitions for re-engagement and retention were likewise inconsistent across studies but most commonly involved having an HIV medical visit or viral load test record between 2 and 6 months (re-engagement), and ≥ 1 medical visits in each 6-month period a minimum of 60 days apart for a period of over 2 years (retention).

This is notable, as it points to the role played – at least in part – by the care fragmentation inherent in the United States health care system. Without national indicators or thresholds for clinical outcomes, services are unlikely to reach scale.

“You can’t expect retention in care until you have a close to seamless, less fragmented safety net in the United States,” said Mary Jane Rotheram-Borus, PhD, distinguished professor of clinical psychology and director of the Global Center for Children and Families at the Semel Institute for Neuroscience and Human Behavior at the University of California, Los Angeles. (Dr. Rotheram-Borus authored an accompanying editorial but was not involved in the study.)

Nevertheless, review findings highlighted that overall, the five interventions appeared to improve care re-engagement (odds ratio = 1.79, 95% confidence interval, 1.36-2.36), care retention (OR = 2.01; 95% CI, 1.64-2.46), and viral suppression (OR = 2.50; 95% CI, 1.87-2.24).

Overall, the five strategies were associated with optimal re-engagement and retention in care. In addition, four of them were associated with viral suppression for PWH who were OOC during the study time frame. The one exception was data-to-care, for which the evidence supporting an association with viral suppression was unclear.

Because of the similarities between patient navigation and transportation/appointment accompaniment, the researchers also compared PWH who received combined strategies to those who did not.

“The findings suggest that patient navigation services that often include helping with transportation to appointments or accompanying PWH to appointments may be more effective compared to interventions without the combination,” explained Dr. Higa, “especially for communities with the largest challenges remaining in care.”

He added that, moving forward, many of the same strategies that help re-engage out-of-care PWH may be useful for retention. These include co-locating services, outreach, mental health services, clinical care models, telemedicine, and financial incentives.

Despite its financial investments toward ending the HIV epidemic, the United States arguably still has a long way to go to improve retention and care.

Still, Dr. Rotheram-Borus underscores the silver lining.

“The breakthroughs in medication are substantial,” she said, pointing to her own research, which has shown that at least 60% of newly infected, poor, LGBTQ+ young people up to age 24 have been linked to care and are adherent enough to be virally suppressed.

For PWH who are out of care, perhaps treatment advances – including long-acting injectables – may ultimately fill in the gaps.

Dr. Higa and Dr. Rotherum-Borus report no relevant financial relationships.

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

Among an estimated 87% of people with HIV (PWH) whose condition has been diagnosed, roughly 66% have received medication. But only half are retained in care, leaving substantial risk for viral rebound and further HIV transmission.

A variety of factors contribute to falling out of care (OOC), a primary reason why a team from the Centers for Disease Control and Prevention reviewed over three decades of studies with the goal of identifying best practices for re-engagement.

The research, which was published  in the journal AIDS, underscores the need for more customized strategies, rather than a one-size-fits-all approach, especially for historically underserved communities.

“Many study participants across the studies included in this review represented communities who have the largest challenges with remaining in care,” Darrel H. Higa, PhD, MSW, lead study author and a behavioral scientist at the CDC in Atlanta, told this news organization.

For example, “Some face barriers that may limit their access to care ... including not having health insurance or being unable to pay for doctor visits or medication, HIV-related stigma, racism, homophobia, transphobia, health literacy, and a lack of providers who specialize in HIV care,” he said.

Other challenges relate to personal barriers, such as competing priorities (for example, work or childcare), substance use, mental health disorders, transportation problems, or a lack of social support.

Even with improvements that address some of these barriers, such as expanded access to health care insurance and broader provision of medical care and HIV medications through the national Ryan White program, structural challenges and social barriers persist.
 

Better versus best practices

In their analysis, the CDC team expanded the scope of prior reviews by including literature published between 2000 and 2020 and further conducted meta-analyses to assess the effectiveness of five common, non mutually exclusive interventions:

• patient navigation
• appointment help/alerts
• psychosocial support
• transportation/appointment reminders
• data-to-care HIV care outcomes (using health department surveillance data and/or patient health records to identify and re-engage OOC PWH)

The majority of the 26,154 participants in 39 included studies (incorporating 42 unique interventions) were male (71%) and Black (64%); the most common time frame for OOC was between 6 and 12 months, but some studies used a time frame of 3-4 months, and others more than 12 months.

Definitions for re-engagement and retention were likewise inconsistent across studies but most commonly involved having an HIV medical visit or viral load test record between 2 and 6 months (re-engagement), and ≥ 1 medical visits in each 6-month period a minimum of 60 days apart for a period of over 2 years (retention).

This is notable, as it points to the role played – at least in part – by the care fragmentation inherent in the United States health care system. Without national indicators or thresholds for clinical outcomes, services are unlikely to reach scale.

“You can’t expect retention in care until you have a close to seamless, less fragmented safety net in the United States,” said Mary Jane Rotheram-Borus, PhD, distinguished professor of clinical psychology and director of the Global Center for Children and Families at the Semel Institute for Neuroscience and Human Behavior at the University of California, Los Angeles. (Dr. Rotheram-Borus authored an accompanying editorial but was not involved in the study.)

Nevertheless, review findings highlighted that overall, the five interventions appeared to improve care re-engagement (odds ratio = 1.79, 95% confidence interval, 1.36-2.36), care retention (OR = 2.01; 95% CI, 1.64-2.46), and viral suppression (OR = 2.50; 95% CI, 1.87-2.24).

Overall, the five strategies were associated with optimal re-engagement and retention in care. In addition, four of them were associated with viral suppression for PWH who were OOC during the study time frame. The one exception was data-to-care, for which the evidence supporting an association with viral suppression was unclear.

Because of the similarities between patient navigation and transportation/appointment accompaniment, the researchers also compared PWH who received combined strategies to those who did not.

“The findings suggest that patient navigation services that often include helping with transportation to appointments or accompanying PWH to appointments may be more effective compared to interventions without the combination,” explained Dr. Higa, “especially for communities with the largest challenges remaining in care.”

He added that, moving forward, many of the same strategies that help re-engage out-of-care PWH may be useful for retention. These include co-locating services, outreach, mental health services, clinical care models, telemedicine, and financial incentives.

Despite its financial investments toward ending the HIV epidemic, the United States arguably still has a long way to go to improve retention and care.

Still, Dr. Rotheram-Borus underscores the silver lining.

“The breakthroughs in medication are substantial,” she said, pointing to her own research, which has shown that at least 60% of newly infected, poor, LGBTQ+ young people up to age 24 have been linked to care and are adherent enough to be virally suppressed.

For PWH who are out of care, perhaps treatment advances – including long-acting injectables – may ultimately fill in the gaps.

Dr. Higa and Dr. Rotherum-Borus report no relevant financial relationships.

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

Among an estimated 87% of people with HIV (PWH) whose condition has been diagnosed, roughly 66% have received medication. But only half are retained in care, leaving substantial risk for viral rebound and further HIV transmission.

A variety of factors contribute to falling out of care (OOC), a primary reason why a team from the Centers for Disease Control and Prevention reviewed over three decades of studies with the goal of identifying best practices for re-engagement.

The research, which was published  in the journal AIDS, underscores the need for more customized strategies, rather than a one-size-fits-all approach, especially for historically underserved communities.

“Many study participants across the studies included in this review represented communities who have the largest challenges with remaining in care,” Darrel H. Higa, PhD, MSW, lead study author and a behavioral scientist at the CDC in Atlanta, told this news organization.

For example, “Some face barriers that may limit their access to care ... including not having health insurance or being unable to pay for doctor visits or medication, HIV-related stigma, racism, homophobia, transphobia, health literacy, and a lack of providers who specialize in HIV care,” he said.

Other challenges relate to personal barriers, such as competing priorities (for example, work or childcare), substance use, mental health disorders, transportation problems, or a lack of social support.

Even with improvements that address some of these barriers, such as expanded access to health care insurance and broader provision of medical care and HIV medications through the national Ryan White program, structural challenges and social barriers persist.
 

Better versus best practices

In their analysis, the CDC team expanded the scope of prior reviews by including literature published between 2000 and 2020 and further conducted meta-analyses to assess the effectiveness of five common, non mutually exclusive interventions:

• patient navigation
• appointment help/alerts
• psychosocial support
• transportation/appointment reminders
• data-to-care HIV care outcomes (using health department surveillance data and/or patient health records to identify and re-engage OOC PWH)

The majority of the 26,154 participants in 39 included studies (incorporating 42 unique interventions) were male (71%) and Black (64%); the most common time frame for OOC was between 6 and 12 months, but some studies used a time frame of 3-4 months, and others more than 12 months.

Definitions for re-engagement and retention were likewise inconsistent across studies but most commonly involved having an HIV medical visit or viral load test record between 2 and 6 months (re-engagement), and ≥ 1 medical visits in each 6-month period a minimum of 60 days apart for a period of over 2 years (retention).

This is notable, as it points to the role played – at least in part – by the care fragmentation inherent in the United States health care system. Without national indicators or thresholds for clinical outcomes, services are unlikely to reach scale.

“You can’t expect retention in care until you have a close to seamless, less fragmented safety net in the United States,” said Mary Jane Rotheram-Borus, PhD, distinguished professor of clinical psychology and director of the Global Center for Children and Families at the Semel Institute for Neuroscience and Human Behavior at the University of California, Los Angeles. (Dr. Rotheram-Borus authored an accompanying editorial but was not involved in the study.)

Nevertheless, review findings highlighted that overall, the five interventions appeared to improve care re-engagement (odds ratio = 1.79, 95% confidence interval, 1.36-2.36), care retention (OR = 2.01; 95% CI, 1.64-2.46), and viral suppression (OR = 2.50; 95% CI, 1.87-2.24).

Overall, the five strategies were associated with optimal re-engagement and retention in care. In addition, four of them were associated with viral suppression for PWH who were OOC during the study time frame. The one exception was data-to-care, for which the evidence supporting an association with viral suppression was unclear.

Because of the similarities between patient navigation and transportation/appointment accompaniment, the researchers also compared PWH who received combined strategies to those who did not.

“The findings suggest that patient navigation services that often include helping with transportation to appointments or accompanying PWH to appointments may be more effective compared to interventions without the combination,” explained Dr. Higa, “especially for communities with the largest challenges remaining in care.”

He added that, moving forward, many of the same strategies that help re-engage out-of-care PWH may be useful for retention. These include co-locating services, outreach, mental health services, clinical care models, telemedicine, and financial incentives.

Despite its financial investments toward ending the HIV epidemic, the United States arguably still has a long way to go to improve retention and care.

Still, Dr. Rotheram-Borus underscores the silver lining.

“The breakthroughs in medication are substantial,” she said, pointing to her own research, which has shown that at least 60% of newly infected, poor, LGBTQ+ young people up to age 24 have been linked to care and are adherent enough to be virally suppressed.

For PWH who are out of care, perhaps treatment advances – including long-acting injectables – may ultimately fill in the gaps.

Dr. Higa and Dr. Rotherum-Borus report no relevant financial relationships.

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

A novel approach that involves sensors, artificial intelligence, and real-time individualized lifestyle guidance from an app and live coaches led to a high rate of remission of type 2 diabetes in a new study.

Specifically, among 199 patients with type 2 diabetes in India who received the app-delivered lifestyle guidance developed by Twin Health, Mountain View, Calif., mean hemoglobin A1c dropped from 9.0% to 5.7% at 6 months.

This is “huge,” Paramesh Shamanna, MD, told a press briefing at the annual scientific sessions of the American Diabetes Association. The research was presented as three posters by the group at the meeting.

Patients were a mean age of 43 and had diabetes for a mean of 3.7 years and up to 8 years.

An “unprecedented” 84% of patients had remission of diabetes at 6 months, Dr. Shamanna, medical director at Twin Health, noted.

Diabetes remission was defined according to the 2021 joint consensus statement from the ADA and other organizations as an A1c less than 6.5% without the use of diabetes medications for at least 3 months.

Importantly, patients’ time in range (percentage of time spent in target blood glucose range) increased from 53% to 81%, Dr. Shamanna pointed out. On average, patients’ waist circumference decreased by 10 cm (3.9 inches) and their weight dropped from 79 kg (approximately 174 lb) to 68 kg (150 lb).

These results are driven by “the continuous individualized and precise guidance regarding nutrition, activity, and sleep,” Dr. Shamanna said in an interview.
 

Remission is not reversal or cure ...

“Remission” from type 2 diabetes is not “reversal” or a “cure,” Robert A. Gabbay, MD, PhD, chief scientific and medical officer of the ADA, stressed to the press. Just like cancer, diabetes can return after remission

Therefore, it is important to follow the lifestyle guidance. Patients may still be at risk for diabetes complications after diabetes remission, so it’s also important to continue to be screened for eye disease, nerve damage, and lipid levels.

However, “remission can be made to last,” Dr. Shamanna said, by continuing to follow the lifestyle advice and getting back on track after a relapse.

“We’re in a different time right now,” Lisa Shah, MD, chief medical officer, Twin Health, noted. “This is very different from management of blood glucose to a certain number.”

This study shows that “remission [from type 2 diabetes] is possible. How you achieve it can be precise for you.”

The program is designed to consider the health and happiness of the patient, added Shashank R. Joshi, MD, chief scientist, Twin Health. “We want remission to be complication free. These findings give patients hope.”

“It’s exciting now that we can really start thinking about remission as an option for people with [type 2] diabetes, and that just provides such incredible hope for all of those living with [type 2] diabetes,” Dr. Gabbay said in an interview.
 

How the intervention works

The Twin Precision Treatment (TPT) intervention integrates multiple data – glucose values from a continuous glucose monitor (CGM); heart rate, activity, and sleep time from a fitness tracker; blood pressure values from a blood pressure cuff; food intake from the patient’s food log; and weight and body fat data from a smart scale – and provides the patient with precise, individualized nutrition and health guidance.

The four most critical sensors are the CGM, the fitness tracker, the smart scale, and the blood pressure cuff, Dr. Shah explained. The system gathers thousands of signals combined with patient self-reported data including mood or anxiety.

The CGM is used to build the initial nutrition guidance during the first 30 days. Once a patient is in remission, he or she can just keep the fitness tracker and smart scale.

The coaches who are part of this program include dietitians who are trained to provide compassionate patient education and help patients avoid diabetes relapse, and they are overseen by a licensed provider.

The program does not restrict calories. “It is not a diet,” Dr. Shah stressed.

The algorithm makes mini adjustments to the food a person is already eating to improve nutrition, Dr. Joshi explained. “This is personalized medicine at its best.” Patients eat food that they like and are guided to make small changes to get glucose under control and avoid glucose spikes.

The program is designed to safely deescalate diabetes medications as A1c decreases, Dr. Shamanna added.

U.S. clinical trial, health insurance coverage

The 1-year results of the current trial are expected in August, and the trial will continue for 2-=5 years, Dr. Shamanna said.

The company has started a clinical trial in the United States, with 5-year results expected in 2027.

“Currently, in the United States, we are partnering with self-insured employers and select health plans that offer [Twin Precision Treatment ] as an available benefit for their members,” Dr. Shah said. It “is suitable for most members living with type 2 diabetes, with rare exclusion situations.”

The study was funded by Twin Health. Dr. Shamanna, Dr. Shah, and Dr. Joshi are employees of Twin Health.

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

A novel approach that involves sensors, artificial intelligence, and real-time individualized lifestyle guidance from an app and live coaches led to a high rate of remission of type 2 diabetes in a new study.

Specifically, among 199 patients with type 2 diabetes in India who received the app-delivered lifestyle guidance developed by Twin Health, Mountain View, Calif., mean hemoglobin A1c dropped from 9.0% to 5.7% at 6 months.

This is “huge,” Paramesh Shamanna, MD, told a press briefing at the annual scientific sessions of the American Diabetes Association. The research was presented as three posters by the group at the meeting.

Patients were a mean age of 43 and had diabetes for a mean of 3.7 years and up to 8 years.

An “unprecedented” 84% of patients had remission of diabetes at 6 months, Dr. Shamanna, medical director at Twin Health, noted.

Diabetes remission was defined according to the 2021 joint consensus statement from the ADA and other organizations as an A1c less than 6.5% without the use of diabetes medications for at least 3 months.

Importantly, patients’ time in range (percentage of time spent in target blood glucose range) increased from 53% to 81%, Dr. Shamanna pointed out. On average, patients’ waist circumference decreased by 10 cm (3.9 inches) and their weight dropped from 79 kg (approximately 174 lb) to 68 kg (150 lb).

These results are driven by “the continuous individualized and precise guidance regarding nutrition, activity, and sleep,” Dr. Shamanna said in an interview.
 

Remission is not reversal or cure ...

“Remission” from type 2 diabetes is not “reversal” or a “cure,” Robert A. Gabbay, MD, PhD, chief scientific and medical officer of the ADA, stressed to the press. Just like cancer, diabetes can return after remission

Therefore, it is important to follow the lifestyle guidance. Patients may still be at risk for diabetes complications after diabetes remission, so it’s also important to continue to be screened for eye disease, nerve damage, and lipid levels.

However, “remission can be made to last,” Dr. Shamanna said, by continuing to follow the lifestyle advice and getting back on track after a relapse.

“We’re in a different time right now,” Lisa Shah, MD, chief medical officer, Twin Health, noted. “This is very different from management of blood glucose to a certain number.”

This study shows that “remission [from type 2 diabetes] is possible. How you achieve it can be precise for you.”

The program is designed to consider the health and happiness of the patient, added Shashank R. Joshi, MD, chief scientist, Twin Health. “We want remission to be complication free. These findings give patients hope.”

“It’s exciting now that we can really start thinking about remission as an option for people with [type 2] diabetes, and that just provides such incredible hope for all of those living with [type 2] diabetes,” Dr. Gabbay said in an interview.
 

How the intervention works

The Twin Precision Treatment (TPT) intervention integrates multiple data – glucose values from a continuous glucose monitor (CGM); heart rate, activity, and sleep time from a fitness tracker; blood pressure values from a blood pressure cuff; food intake from the patient’s food log; and weight and body fat data from a smart scale – and provides the patient with precise, individualized nutrition and health guidance.

The four most critical sensors are the CGM, the fitness tracker, the smart scale, and the blood pressure cuff, Dr. Shah explained. The system gathers thousands of signals combined with patient self-reported data including mood or anxiety.

The CGM is used to build the initial nutrition guidance during the first 30 days. Once a patient is in remission, he or she can just keep the fitness tracker and smart scale.

The coaches who are part of this program include dietitians who are trained to provide compassionate patient education and help patients avoid diabetes relapse, and they are overseen by a licensed provider.

The program does not restrict calories. “It is not a diet,” Dr. Shah stressed.

The algorithm makes mini adjustments to the food a person is already eating to improve nutrition, Dr. Joshi explained. “This is personalized medicine at its best.” Patients eat food that they like and are guided to make small changes to get glucose under control and avoid glucose spikes.

The program is designed to safely deescalate diabetes medications as A1c decreases, Dr. Shamanna added.

U.S. clinical trial, health insurance coverage

The 1-year results of the current trial are expected in August, and the trial will continue for 2-=5 years, Dr. Shamanna said.

The company has started a clinical trial in the United States, with 5-year results expected in 2027.

“Currently, in the United States, we are partnering with self-insured employers and select health plans that offer [Twin Precision Treatment ] as an available benefit for their members,” Dr. Shah said. It “is suitable for most members living with type 2 diabetes, with rare exclusion situations.”

The study was funded by Twin Health. Dr. Shamanna, Dr. Shah, and Dr. Joshi are employees of Twin Health.

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

A novel approach that involves sensors, artificial intelligence, and real-time individualized lifestyle guidance from an app and live coaches led to a high rate of remission of type 2 diabetes in a new study.

Specifically, among 199 patients with type 2 diabetes in India who received the app-delivered lifestyle guidance developed by Twin Health, Mountain View, Calif., mean hemoglobin A1c dropped from 9.0% to 5.7% at 6 months.

This is “huge,” Paramesh Shamanna, MD, told a press briefing at the annual scientific sessions of the American Diabetes Association. The research was presented as three posters by the group at the meeting.

Patients were a mean age of 43 and had diabetes for a mean of 3.7 years and up to 8 years.

An “unprecedented” 84% of patients had remission of diabetes at 6 months, Dr. Shamanna, medical director at Twin Health, noted.

Diabetes remission was defined according to the 2021 joint consensus statement from the ADA and other organizations as an A1c less than 6.5% without the use of diabetes medications for at least 3 months.

Importantly, patients’ time in range (percentage of time spent in target blood glucose range) increased from 53% to 81%, Dr. Shamanna pointed out. On average, patients’ waist circumference decreased by 10 cm (3.9 inches) and their weight dropped from 79 kg (approximately 174 lb) to 68 kg (150 lb).

These results are driven by “the continuous individualized and precise guidance regarding nutrition, activity, and sleep,” Dr. Shamanna said in an interview.
 

Remission is not reversal or cure ...

“Remission” from type 2 diabetes is not “reversal” or a “cure,” Robert A. Gabbay, MD, PhD, chief scientific and medical officer of the ADA, stressed to the press. Just like cancer, diabetes can return after remission

Therefore, it is important to follow the lifestyle guidance. Patients may still be at risk for diabetes complications after diabetes remission, so it’s also important to continue to be screened for eye disease, nerve damage, and lipid levels.

However, “remission can be made to last,” Dr. Shamanna said, by continuing to follow the lifestyle advice and getting back on track after a relapse.

“We’re in a different time right now,” Lisa Shah, MD, chief medical officer, Twin Health, noted. “This is very different from management of blood glucose to a certain number.”

This study shows that “remission [from type 2 diabetes] is possible. How you achieve it can be precise for you.”

The program is designed to consider the health and happiness of the patient, added Shashank R. Joshi, MD, chief scientist, Twin Health. “We want remission to be complication free. These findings give patients hope.”

“It’s exciting now that we can really start thinking about remission as an option for people with [type 2] diabetes, and that just provides such incredible hope for all of those living with [type 2] diabetes,” Dr. Gabbay said in an interview.
 

How the intervention works

The Twin Precision Treatment (TPT) intervention integrates multiple data – glucose values from a continuous glucose monitor (CGM); heart rate, activity, and sleep time from a fitness tracker; blood pressure values from a blood pressure cuff; food intake from the patient’s food log; and weight and body fat data from a smart scale – and provides the patient with precise, individualized nutrition and health guidance.

The four most critical sensors are the CGM, the fitness tracker, the smart scale, and the blood pressure cuff, Dr. Shah explained. The system gathers thousands of signals combined with patient self-reported data including mood or anxiety.

The CGM is used to build the initial nutrition guidance during the first 30 days. Once a patient is in remission, he or she can just keep the fitness tracker and smart scale.

The coaches who are part of this program include dietitians who are trained to provide compassionate patient education and help patients avoid diabetes relapse, and they are overseen by a licensed provider.

The program does not restrict calories. “It is not a diet,” Dr. Shah stressed.

The algorithm makes mini adjustments to the food a person is already eating to improve nutrition, Dr. Joshi explained. “This is personalized medicine at its best.” Patients eat food that they like and are guided to make small changes to get glucose under control and avoid glucose spikes.

The program is designed to safely deescalate diabetes medications as A1c decreases, Dr. Shamanna added.

U.S. clinical trial, health insurance coverage

The 1-year results of the current trial are expected in August, and the trial will continue for 2-=5 years, Dr. Shamanna said.

The company has started a clinical trial in the United States, with 5-year results expected in 2027.

“Currently, in the United States, we are partnering with self-insured employers and select health plans that offer [Twin Precision Treatment ] as an available benefit for their members,” Dr. Shah said. It “is suitable for most members living with type 2 diabetes, with rare exclusion situations.”

The study was funded by Twin Health. Dr. Shamanna, Dr. Shah, and Dr. Joshi are employees of Twin Health.

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