Clinician Reviews

TOPLINE:

Adolescents with atopic dermatitis (AD) experience bullying significantly more often than their peers without AD.

METHODOLOGY:

• Adolescents with AD have reported appearance-based bullying.
• To evaluate the association between AD and the prevalence and frequency of bullying, researchers analyzed cross-sectional data from adult caregivers of U.S. adolescents aged 12-17 years who participated in the 2021 National Health Interview Survey.
• Logistic regression and ordinal logistic regression were used to compare the prevalence of experiencing one or more bullying encounters during the previous 12 months and the frequency of bullying between adolescents with and those without AD.

TAKEAWAY:

• A total of 3,207 adolescents were included in the analysis. The mean age of the participants was 14.5 years, and 11.9% currently had AD. The prevalence of experiencing bullying was significantly higher among adolescents with AD, compared with those without AD (33.2% vs. 19%; P < .001), as was the prevalence of cyberbullying (9.1% vs. 5.8%; P = .04).
• Following adjustment for demographics and atopic comorbidities, adolescents with AD were at increased odds of bullying, compared with their peers without AD (adjusted odds ratio, 1.99; 95% confidence interval, 1.45-2.73).
• Following adjustment for demographics, adolescents with AD were also at increased odds of cyberbullying, compared with their peers without AD (AOR, 1.65; 95% CI, 1.04-2.62), but no association was observed following adjustment for atopic comorbidities (AOR, 1.27; 95% CI, 0.82-1.96).
• Following ordinal logistic regression that was adjusted for demographics and atopic comorbidities, adolescents with AD were at greater odds of being bullied at a higher frequency, compared with their peers without AD (AOR, 1.97; 95% CI, 1.44-2.68).

IN PRACTICE:

“Larger, future studies using clinical AD diagnoses and adolescent self-report can advance understanding of bullying and AD,” the researchers wrote. “Clinicians, families, and schools should address and monitor bullying among adolescents.”

SOURCE:

Howa Yeung, MD, of the department of dermatology at Emory University School of Medicine, Atlanta, led the research. The study was published online  in JAMA Dermatology.

LIMITATIONS:

Limitations include the study’s cross-sectional design. In addition, the investigators could not directly attribute bullying to skin-specific findings, and it was a caregiver report.

DISCLOSURES:

The study was supported by grants from the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One of the authors, Joy Wan, MD, received grants from Pfizer and personal fees from Janssen and Sun Pharmaceuticals outside of the submitted work.

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

TOPLINE:

Adolescents with atopic dermatitis (AD) experience bullying significantly more often than their peers without AD.

METHODOLOGY:

• Adolescents with AD have reported appearance-based bullying.
• To evaluate the association between AD and the prevalence and frequency of bullying, researchers analyzed cross-sectional data from adult caregivers of U.S. adolescents aged 12-17 years who participated in the 2021 National Health Interview Survey.
• Logistic regression and ordinal logistic regression were used to compare the prevalence of experiencing one or more bullying encounters during the previous 12 months and the frequency of bullying between adolescents with and those without AD.

TAKEAWAY:

• A total of 3,207 adolescents were included in the analysis. The mean age of the participants was 14.5 years, and 11.9% currently had AD. The prevalence of experiencing bullying was significantly higher among adolescents with AD, compared with those without AD (33.2% vs. 19%; P < .001), as was the prevalence of cyberbullying (9.1% vs. 5.8%; P = .04).
• Following adjustment for demographics and atopic comorbidities, adolescents with AD were at increased odds of bullying, compared with their peers without AD (adjusted odds ratio, 1.99; 95% confidence interval, 1.45-2.73).
• Following adjustment for demographics, adolescents with AD were also at increased odds of cyberbullying, compared with their peers without AD (AOR, 1.65; 95% CI, 1.04-2.62), but no association was observed following adjustment for atopic comorbidities (AOR, 1.27; 95% CI, 0.82-1.96).
• Following ordinal logistic regression that was adjusted for demographics and atopic comorbidities, adolescents with AD were at greater odds of being bullied at a higher frequency, compared with their peers without AD (AOR, 1.97; 95% CI, 1.44-2.68).

IN PRACTICE:

“Larger, future studies using clinical AD diagnoses and adolescent self-report can advance understanding of bullying and AD,” the researchers wrote. “Clinicians, families, and schools should address and monitor bullying among adolescents.”

SOURCE:

Howa Yeung, MD, of the department of dermatology at Emory University School of Medicine, Atlanta, led the research. The study was published online  in JAMA Dermatology.

LIMITATIONS:

Limitations include the study’s cross-sectional design. In addition, the investigators could not directly attribute bullying to skin-specific findings, and it was a caregiver report.

DISCLOSURES:

The study was supported by grants from the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One of the authors, Joy Wan, MD, received grants from Pfizer and personal fees from Janssen and Sun Pharmaceuticals outside of the submitted work.

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

TOPLINE:

Adolescents with atopic dermatitis (AD) experience bullying significantly more often than their peers without AD.

METHODOLOGY:

• Adolescents with AD have reported appearance-based bullying.
• To evaluate the association between AD and the prevalence and frequency of bullying, researchers analyzed cross-sectional data from adult caregivers of U.S. adolescents aged 12-17 years who participated in the 2021 National Health Interview Survey.
• Logistic regression and ordinal logistic regression were used to compare the prevalence of experiencing one or more bullying encounters during the previous 12 months and the frequency of bullying between adolescents with and those without AD.

TAKEAWAY:

• A total of 3,207 adolescents were included in the analysis. The mean age of the participants was 14.5 years, and 11.9% currently had AD. The prevalence of experiencing bullying was significantly higher among adolescents with AD, compared with those without AD (33.2% vs. 19%; P < .001), as was the prevalence of cyberbullying (9.1% vs. 5.8%; P = .04).
• Following adjustment for demographics and atopic comorbidities, adolescents with AD were at increased odds of bullying, compared with their peers without AD (adjusted odds ratio, 1.99; 95% confidence interval, 1.45-2.73).
• Following adjustment for demographics, adolescents with AD were also at increased odds of cyberbullying, compared with their peers without AD (AOR, 1.65; 95% CI, 1.04-2.62), but no association was observed following adjustment for atopic comorbidities (AOR, 1.27; 95% CI, 0.82-1.96).
• Following ordinal logistic regression that was adjusted for demographics and atopic comorbidities, adolescents with AD were at greater odds of being bullied at a higher frequency, compared with their peers without AD (AOR, 1.97; 95% CI, 1.44-2.68).

IN PRACTICE:

“Larger, future studies using clinical AD diagnoses and adolescent self-report can advance understanding of bullying and AD,” the researchers wrote. “Clinicians, families, and schools should address and monitor bullying among adolescents.”

SOURCE:

Howa Yeung, MD, of the department of dermatology at Emory University School of Medicine, Atlanta, led the research. The study was published online  in JAMA Dermatology.

LIMITATIONS:

Limitations include the study’s cross-sectional design. In addition, the investigators could not directly attribute bullying to skin-specific findings, and it was a caregiver report.

DISCLOSURES:

The study was supported by grants from the National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. One of the authors, Joy Wan, MD, received grants from Pfizer and personal fees from Janssen and Sun Pharmaceuticals outside of the submitted work.

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

A very long time ago, when I ran clinical labs, one of the most ordered tests was the “sed rate” (aka ESR, the erythrocyte sedimentation rate). Easy, quick, and low cost, with high sensitivity but very low specificity. If the sed rate was normal, the patient probably did not have an infectious or inflammatory disease. If it was elevated, they probably did, but no telling what. Later, the C-reactive protein (CRP) test came into common use. Same general inferences: If the CRP was low, the patient was unlikely to have an inflammatory process; if high, they were sick, but we didn’t know what with.

Could the heart rate variability (HRV) score come to be thought of similarly? Much as the sed rate and CRP are sensitivity indicators of infectious or inflammatory diseases, might the HRV score be a sensitivity indicator for nervous system (central and autonomic) and cardiovascular (especially heart rhythm) malfunctions?

A substantial and relatively old body of heart rhythm literature ties HRV alterations to posttraumatic stress disorder, physician occupational stress, sleep disorders, depression, autonomic nervous system derangements, various cardiac arrhythmias, fatigue, overexertion, medications, and age itself.

More than 100 million Americans are now believed to use smartwatches or personal fitness monitors. Some 30%-40% of these devices measure HRV. So what? Credible research about this huge mass of accumulating data from “wearables” is lacking.
 

What is HRV?

HRV is the variation in time between each heartbeat, in milliseconds. HRV is influenced by the autonomic nervous system, perhaps reflecting sympathetic-parasympathetic balance. Some devices measure HRV 24/7. My Fitbit Inspire 2 reports only nighttime measures during 3 hours of sustained sleep. Most trackers report averages; some calculate the root mean squares; others calculate standard deviations. All fitness trackers warn not to use the data for medical purposes.

Normal values (reference ranges) for HRV begin at an average of 100 msec in the first decade of life and decline by approximately 10 msec per decade lived. At age 30-40, the average is 70 msec; age 60-70, it’s 40 msec; and at age 90-100, it’s 10 msec.

As a long-time lab guy, I used to teach proper use of lab tests. Fitness trackers are “lab tests” of a sort. We taught never to do a lab test unless you know what you are going to do with the result, no matter what it is. We also taught “never do anything just because you can.” Curiosity, we know, is a frequent driver of lab test ordering.

That underlying philosophy gives me a hard time when it comes to wearables. I have been enamored of watching my step count, active zone minutes, resting heart rate, active heart rate, various sleep scores, and breathing rate (and, of course, a manually entered early morning daily body weight) for several years. I even check my “readiness score” (a calculation using resting heart rate, recent sleep, recent active zone minutes, and perhaps HRV) each morning and adjust my behaviors accordingly.
 

Why monitor HRV?

But what should we do with HRV scores? Ignore them? Try to understand them, perhaps as a screening tool? Or monitor HRV for consistency or change? “Monitoring” is a proper and common use of lab tests.

Some say we should improve the HRV score by managing stress, getting regular exercise, eating a healthy diet, getting enough sleep, and not smoking or consuming excess alcohol. Duh! I do all of that anyway.

The claims that HRV is a “simple but powerful tool that can be used to track overall health and well-being” might turn out to be true. Proper study and sharing of data will enable that determination.

To advance understanding, I offer an n-of-1, a real-world personal anecdote about HRV.

I did not request the HRV function on my Fitbit Inspire 2. It simply appeared, and I ignored it for some time.

A year or two ago, I started noticing my HRV score every morning. Initially, I did not like to see my “low” score, until I learned that the reference range was dramatically affected by age and I was in my late 80s at the time. The vast majority of my HRV readings were in the range of 17 msec to 27 msec.

Last week, I was administered the new Moderna COVID-19 Spikevax vaccine and the old folks’ influenza vaccine simultaneously. In my case, side effects from each vaccine have been modest in the past, but I never previously had both administered at the same time. My immune response was, shall we say, robust. Chills, muscle aches, headache, fatigue, deltoid swelling, fitful sleep, and increased resting heart rate.

My nightly average HRV had been running between 17 msec and 35 msec for many months. WHOA! After the shots, my overnight HRV score plummeted from 24 msec to 10 msec, my lowest ever. Instant worry. The next day, it rebounded to 28 msec, and it has been in the high teens or low 20s since then.

Off to PubMed. A recent study of HRV on the second and 10th days after administering the Pfizer mRNA vaccine to 75 healthy volunteers found that the HRV on day 2 was dramatically lower than prevaccination levels and by day 10, it had returned to prevaccination levels. Some comfort there.

Another review article has reported a rapid fall and rapid rebound of HRV after COVID-19 vaccination. A 2010 report demonstrated a significant but not dramatic short-term lowering of HRV after influenza A vaccination and correlated it with CRP changes.

Some believe that the decline in HRV after vaccination reflects an increased immune response and sympathetic nervous activity.

I don’t plan to receive my flu and COVID vaccines on the same day again.

So, I went back to review what happened to my HRV when I had COVID in 2023. My HRV was 14 msec and 12 msec on the first 2 days of symptoms, and then returned to the 20 msec range.

I received the RSV vaccine this year without adverse effects, and my HRV scores were 29 msec, 33 msec, and 32 msec on the first 3 days after vaccination. Finally, after receiving a pneumococcal vaccine in 2023, I had no adverse effects, and my HRV scores on the 5 days after vaccination were indeterminate: 19 msec, 14 msec, 18 msec, 13 msec, and 17 msec.

Of course, correlation is not causation. Cause and effect remain undetermined. But I find these observations interesting for a potentially useful screening test.

George D. Lundberg, MD, is the Editor in Chief of Cancer Commons.

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

A very long time ago, when I ran clinical labs, one of the most ordered tests was the “sed rate” (aka ESR, the erythrocyte sedimentation rate). Easy, quick, and low cost, with high sensitivity but very low specificity. If the sed rate was normal, the patient probably did not have an infectious or inflammatory disease. If it was elevated, they probably did, but no telling what. Later, the C-reactive protein (CRP) test came into common use. Same general inferences: If the CRP was low, the patient was unlikely to have an inflammatory process; if high, they were sick, but we didn’t know what with.

Could the heart rate variability (HRV) score come to be thought of similarly? Much as the sed rate and CRP are sensitivity indicators of infectious or inflammatory diseases, might the HRV score be a sensitivity indicator for nervous system (central and autonomic) and cardiovascular (especially heart rhythm) malfunctions?

A substantial and relatively old body of heart rhythm literature ties HRV alterations to posttraumatic stress disorder, physician occupational stress, sleep disorders, depression, autonomic nervous system derangements, various cardiac arrhythmias, fatigue, overexertion, medications, and age itself.

More than 100 million Americans are now believed to use smartwatches or personal fitness monitors. Some 30%-40% of these devices measure HRV. So what? Credible research about this huge mass of accumulating data from “wearables” is lacking.
 

What is HRV?

HRV is the variation in time between each heartbeat, in milliseconds. HRV is influenced by the autonomic nervous system, perhaps reflecting sympathetic-parasympathetic balance. Some devices measure HRV 24/7. My Fitbit Inspire 2 reports only nighttime measures during 3 hours of sustained sleep. Most trackers report averages; some calculate the root mean squares; others calculate standard deviations. All fitness trackers warn not to use the data for medical purposes.

Normal values (reference ranges) for HRV begin at an average of 100 msec in the first decade of life and decline by approximately 10 msec per decade lived. At age 30-40, the average is 70 msec; age 60-70, it’s 40 msec; and at age 90-100, it’s 10 msec.

As a long-time lab guy, I used to teach proper use of lab tests. Fitness trackers are “lab tests” of a sort. We taught never to do a lab test unless you know what you are going to do with the result, no matter what it is. We also taught “never do anything just because you can.” Curiosity, we know, is a frequent driver of lab test ordering.

That underlying philosophy gives me a hard time when it comes to wearables. I have been enamored of watching my step count, active zone minutes, resting heart rate, active heart rate, various sleep scores, and breathing rate (and, of course, a manually entered early morning daily body weight) for several years. I even check my “readiness score” (a calculation using resting heart rate, recent sleep, recent active zone minutes, and perhaps HRV) each morning and adjust my behaviors accordingly.
 

Why monitor HRV?

But what should we do with HRV scores? Ignore them? Try to understand them, perhaps as a screening tool? Or monitor HRV for consistency or change? “Monitoring” is a proper and common use of lab tests.

Some say we should improve the HRV score by managing stress, getting regular exercise, eating a healthy diet, getting enough sleep, and not smoking or consuming excess alcohol. Duh! I do all of that anyway.

The claims that HRV is a “simple but powerful tool that can be used to track overall health and well-being” might turn out to be true. Proper study and sharing of data will enable that determination.

To advance understanding, I offer an n-of-1, a real-world personal anecdote about HRV.

I did not request the HRV function on my Fitbit Inspire 2. It simply appeared, and I ignored it for some time.

A year or two ago, I started noticing my HRV score every morning. Initially, I did not like to see my “low” score, until I learned that the reference range was dramatically affected by age and I was in my late 80s at the time. The vast majority of my HRV readings were in the range of 17 msec to 27 msec.

Last week, I was administered the new Moderna COVID-19 Spikevax vaccine and the old folks’ influenza vaccine simultaneously. In my case, side effects from each vaccine have been modest in the past, but I never previously had both administered at the same time. My immune response was, shall we say, robust. Chills, muscle aches, headache, fatigue, deltoid swelling, fitful sleep, and increased resting heart rate.

My nightly average HRV had been running between 17 msec and 35 msec for many months. WHOA! After the shots, my overnight HRV score plummeted from 24 msec to 10 msec, my lowest ever. Instant worry. The next day, it rebounded to 28 msec, and it has been in the high teens or low 20s since then.

Off to PubMed. A recent study of HRV on the second and 10th days after administering the Pfizer mRNA vaccine to 75 healthy volunteers found that the HRV on day 2 was dramatically lower than prevaccination levels and by day 10, it had returned to prevaccination levels. Some comfort there.

Another review article has reported a rapid fall and rapid rebound of HRV after COVID-19 vaccination. A 2010 report demonstrated a significant but not dramatic short-term lowering of HRV after influenza A vaccination and correlated it with CRP changes.

Some believe that the decline in HRV after vaccination reflects an increased immune response and sympathetic nervous activity.

I don’t plan to receive my flu and COVID vaccines on the same day again.

So, I went back to review what happened to my HRV when I had COVID in 2023. My HRV was 14 msec and 12 msec on the first 2 days of symptoms, and then returned to the 20 msec range.

I received the RSV vaccine this year without adverse effects, and my HRV scores were 29 msec, 33 msec, and 32 msec on the first 3 days after vaccination. Finally, after receiving a pneumococcal vaccine in 2023, I had no adverse effects, and my HRV scores on the 5 days after vaccination were indeterminate: 19 msec, 14 msec, 18 msec, 13 msec, and 17 msec.

Of course, correlation is not causation. Cause and effect remain undetermined. But I find these observations interesting for a potentially useful screening test.

George D. Lundberg, MD, is the Editor in Chief of Cancer Commons.

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

A very long time ago, when I ran clinical labs, one of the most ordered tests was the “sed rate” (aka ESR, the erythrocyte sedimentation rate). Easy, quick, and low cost, with high sensitivity but very low specificity. If the sed rate was normal, the patient probably did not have an infectious or inflammatory disease. If it was elevated, they probably did, but no telling what. Later, the C-reactive protein (CRP) test came into common use. Same general inferences: If the CRP was low, the patient was unlikely to have an inflammatory process; if high, they were sick, but we didn’t know what with.

Could the heart rate variability (HRV) score come to be thought of similarly? Much as the sed rate and CRP are sensitivity indicators of infectious or inflammatory diseases, might the HRV score be a sensitivity indicator for nervous system (central and autonomic) and cardiovascular (especially heart rhythm) malfunctions?

A substantial and relatively old body of heart rhythm literature ties HRV alterations to posttraumatic stress disorder, physician occupational stress, sleep disorders, depression, autonomic nervous system derangements, various cardiac arrhythmias, fatigue, overexertion, medications, and age itself.

More than 100 million Americans are now believed to use smartwatches or personal fitness monitors. Some 30%-40% of these devices measure HRV. So what? Credible research about this huge mass of accumulating data from “wearables” is lacking.
 

What is HRV?

HRV is the variation in time between each heartbeat, in milliseconds. HRV is influenced by the autonomic nervous system, perhaps reflecting sympathetic-parasympathetic balance. Some devices measure HRV 24/7. My Fitbit Inspire 2 reports only nighttime measures during 3 hours of sustained sleep. Most trackers report averages; some calculate the root mean squares; others calculate standard deviations. All fitness trackers warn not to use the data for medical purposes.

Normal values (reference ranges) for HRV begin at an average of 100 msec in the first decade of life and decline by approximately 10 msec per decade lived. At age 30-40, the average is 70 msec; age 60-70, it’s 40 msec; and at age 90-100, it’s 10 msec.

As a long-time lab guy, I used to teach proper use of lab tests. Fitness trackers are “lab tests” of a sort. We taught never to do a lab test unless you know what you are going to do with the result, no matter what it is. We also taught “never do anything just because you can.” Curiosity, we know, is a frequent driver of lab test ordering.

That underlying philosophy gives me a hard time when it comes to wearables. I have been enamored of watching my step count, active zone minutes, resting heart rate, active heart rate, various sleep scores, and breathing rate (and, of course, a manually entered early morning daily body weight) for several years. I even check my “readiness score” (a calculation using resting heart rate, recent sleep, recent active zone minutes, and perhaps HRV) each morning and adjust my behaviors accordingly.
 

Why monitor HRV?

But what should we do with HRV scores? Ignore them? Try to understand them, perhaps as a screening tool? Or monitor HRV for consistency or change? “Monitoring” is a proper and common use of lab tests.

Some say we should improve the HRV score by managing stress, getting regular exercise, eating a healthy diet, getting enough sleep, and not smoking or consuming excess alcohol. Duh! I do all of that anyway.

The claims that HRV is a “simple but powerful tool that can be used to track overall health and well-being” might turn out to be true. Proper study and sharing of data will enable that determination.

To advance understanding, I offer an n-of-1, a real-world personal anecdote about HRV.

I did not request the HRV function on my Fitbit Inspire 2. It simply appeared, and I ignored it for some time.

A year or two ago, I started noticing my HRV score every morning. Initially, I did not like to see my “low” score, until I learned that the reference range was dramatically affected by age and I was in my late 80s at the time. The vast majority of my HRV readings were in the range of 17 msec to 27 msec.

Last week, I was administered the new Moderna COVID-19 Spikevax vaccine and the old folks’ influenza vaccine simultaneously. In my case, side effects from each vaccine have been modest in the past, but I never previously had both administered at the same time. My immune response was, shall we say, robust. Chills, muscle aches, headache, fatigue, deltoid swelling, fitful sleep, and increased resting heart rate.

My nightly average HRV had been running between 17 msec and 35 msec for many months. WHOA! After the shots, my overnight HRV score plummeted from 24 msec to 10 msec, my lowest ever. Instant worry. The next day, it rebounded to 28 msec, and it has been in the high teens or low 20s since then.

Off to PubMed. A recent study of HRV on the second and 10th days after administering the Pfizer mRNA vaccine to 75 healthy volunteers found that the HRV on day 2 was dramatically lower than prevaccination levels and by day 10, it had returned to prevaccination levels. Some comfort there.

Another review article has reported a rapid fall and rapid rebound of HRV after COVID-19 vaccination. A 2010 report demonstrated a significant but not dramatic short-term lowering of HRV after influenza A vaccination and correlated it with CRP changes.

Some believe that the decline in HRV after vaccination reflects an increased immune response and sympathetic nervous activity.

I don’t plan to receive my flu and COVID vaccines on the same day again.

So, I went back to review what happened to my HRV when I had COVID in 2023. My HRV was 14 msec and 12 msec on the first 2 days of symptoms, and then returned to the 20 msec range.

I received the RSV vaccine this year without adverse effects, and my HRV scores were 29 msec, 33 msec, and 32 msec on the first 3 days after vaccination. Finally, after receiving a pneumococcal vaccine in 2023, I had no adverse effects, and my HRV scores on the 5 days after vaccination were indeterminate: 19 msec, 14 msec, 18 msec, 13 msec, and 17 msec.

Of course, correlation is not causation. Cause and effect remain undetermined. But I find these observations interesting for a potentially useful screening test.

George D. Lundberg, MD, is the Editor in Chief of Cancer Commons.

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

It’s upper respiratory infection (URI) season. The following is a clinical scenario drawn from my own practice. I’ll tell you what I plan to do, but I’m most interested in crowdsourcing a response from all of you to collectively determine best practice. So please answer the polling questions and contribute your thoughts in the comments, whether you agree or disagree with me.

The patient

The patient is a 69-year-old woman with a 3-day history of cough, nasal congestion, malaise, tactile fever, and poor appetite. She has no sick contacts. She denies dyspnea, presyncope, and chest pain. She has tried guaifenesin and ibuprofen for her symptoms, which helped a little.

She is up to date on immunizations, including four doses of COVID-19 vaccine and the influenza vaccine, which she received 2 months ago.

The patient has a history of heart failure with reduced ejection fraction, coronary artery disease, hypertension, chronic kidney disease stage 3aA2, obesity, and osteoarthritis. Current medications include atorvastatin, losartan, metoprolol, and aspirin.

Her weight is stable at 212 lb, and her vital signs today are:

• Temperature: 37.5° C
• Pulse: 60 beats/min
• Blood pressure: 150/88 mm Hg
• Respiration rate: 14 breaths/min
• SpO₂: 93% on room air

What information is most critical before deciding on management?

Your peers chose: 

• The patient’s history of viral URIs

 14%

 

• Whether her cough is productive and the color of the sputum

 38%

 

• How well this season’s flu vaccine matches circulating influenza viruses

 8%

 

• Local epidemiology of major viral pathogens (e.g., SARS-CoV-2, influenza, RSV)

 40%
 

Dr. Vega’s take

To provide the best care for our patients when they are threatened with multiple viral upper respiratory pathogens, it is imperative that clinicians have some idea regarding the epidemiology of viral infections, with as much local data as possible. This knowledge will help direct appropriate testing and treatment.

Modern viral molecular testing platforms are highly accurate, but they are not infallible. Small flaws in specificity and sensitivity of testing are magnified when community viral circulation is low. In a U.K. study conducted during a period of low COVID-19 prevalence, the positive predictive value of reverse-transcriptase polymerase chain reaction (RT-PCR) testing was just 16%. Although the negative predictive value was much higher, the false-positive rate of testing was still 0.5%. The authors of the study describe important potential consequences of false-positive results, such as being temporarily removed from an organ transplant list and unnecessary contact tracing.
 

Testing and treatment

Your county public health department maintains a website describing local activity of SARS-CoV-2 and influenza. Both viruses are in heavy circulation now.

What is the next best step in this patient’s management?

Your peers chose: 

• Treat empirically with ritonavir-boosted nirmatrelvir

 7%

 

• Treat empirically with oseltamivir or baloxavir

 14%

 

• Perform lab-based multiplex RT-PCR testing and wait to treat on the basis of results

 34%

 

• Perform rapid nucleic acid amplification testing (NAAT) and treat on the basis of results

 45%

Every practice has different resources and should use the best means available to treat patients. Ideally, this patient would undergo rapid NAAT with results available within 30 minutes. Test results will help guide not only treatment decisions but also infection-control measures.

The Infectious Diseases Society of America has provided updates for testing for URIs since the onset of the COVID-19 pandemic. Both laboratory-based and point-of-care rapid NAATs are recommended for testing. Rapid NAATs have been demonstrated to have a sensitivity of 96% and specificity of 100% in the detection of SARS-CoV-2. Obviously, they also offer a highly efficient means to make treatment and isolation decisions.

There are multiple platforms for molecular testing available. Laboratory-based platforms can test for dozens of potential pathogens, including bacteria. Rapid NAATs often have the ability to test for SARS-CoV-2, influenza, and respiratory syncytial virus (RSV). This functionality is important, because these infections generally are difficult to discriminate on the basis of clinical information alone.

The IDSA clearly recognizes the challenges of trying to manage cases of URI. For example, they state that testing of the anterior nares (AN) or oropharynx (OP) is acceptable, even though testing from the nasopharynx offers increased sensitivity. However, testing at the AN/OP allows for patient self-collection of samples, which is also recommended as an option by the IDSA. In an analysis of six cohort studies, the pooled sensitivity of patient-collected nasopharyngeal samples from the AN/OP was 88%, whereas the respective value for samples taken by health care providers was 95%.

The U.S. Centers for Disease Control and Prevention also provides recommendations for the management of patients with acute upper respiratory illness. Patients who are sick enough to be hospitalized should be tested at least for SARS-CoV-2 and influenza using molecular assays. Outpatients should be tested for SARS-CoV-2 with either molecular or antigen testing, and influenza testing should be offered if the findings will change decisions regarding treatment or isolation. Practically speaking, the recommendations for influenza testing mean that most individuals should be tested, including patients at high risk for complications of influenza and those who might have exposure to individuals at high risk.

Treatment of COVID-19 should only be provided in cases of a positive test within 5 days of symptom onset. However, clinicians may treat patients with anti-influenza medications presumptively if test results are not immediately available and the patient has worsening symptoms or is in a group at high risk for complications.

What are some of the challenges that you have faced during the COVID-19 pandemic regarding the management of patients with acute URIs? What have you found in terms of solutions, and where do gaps in quality of care persist? Please add your comments. I will review and circle back with a response. Thank you!

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

It’s upper respiratory infection (URI) season. The following is a clinical scenario drawn from my own practice. I’ll tell you what I plan to do, but I’m most interested in crowdsourcing a response from all of you to collectively determine best practice. So please answer the polling questions and contribute your thoughts in the comments, whether you agree or disagree with me.

The patient

The patient is a 69-year-old woman with a 3-day history of cough, nasal congestion, malaise, tactile fever, and poor appetite. She has no sick contacts. She denies dyspnea, presyncope, and chest pain. She has tried guaifenesin and ibuprofen for her symptoms, which helped a little.

She is up to date on immunizations, including four doses of COVID-19 vaccine and the influenza vaccine, which she received 2 months ago.

The patient has a history of heart failure with reduced ejection fraction, coronary artery disease, hypertension, chronic kidney disease stage 3aA2, obesity, and osteoarthritis. Current medications include atorvastatin, losartan, metoprolol, and aspirin.

Her weight is stable at 212 lb, and her vital signs today are:

• Temperature: 37.5° C
• Pulse: 60 beats/min
• Blood pressure: 150/88 mm Hg
• Respiration rate: 14 breaths/min
• SpO₂: 93% on room air

What information is most critical before deciding on management?

Your peers chose: 

• The patient’s history of viral URIs

 14%

 

• Whether her cough is productive and the color of the sputum

 38%

 

• How well this season’s flu vaccine matches circulating influenza viruses

 8%

 

• Local epidemiology of major viral pathogens (e.g., SARS-CoV-2, influenza, RSV)

 40%
 

Dr. Vega’s take

To provide the best care for our patients when they are threatened with multiple viral upper respiratory pathogens, it is imperative that clinicians have some idea regarding the epidemiology of viral infections, with as much local data as possible. This knowledge will help direct appropriate testing and treatment.

Modern viral molecular testing platforms are highly accurate, but they are not infallible. Small flaws in specificity and sensitivity of testing are magnified when community viral circulation is low. In a U.K. study conducted during a period of low COVID-19 prevalence, the positive predictive value of reverse-transcriptase polymerase chain reaction (RT-PCR) testing was just 16%. Although the negative predictive value was much higher, the false-positive rate of testing was still 0.5%. The authors of the study describe important potential consequences of false-positive results, such as being temporarily removed from an organ transplant list and unnecessary contact tracing.
 

Testing and treatment

Your county public health department maintains a website describing local activity of SARS-CoV-2 and influenza. Both viruses are in heavy circulation now.

What is the next best step in this patient’s management?

Your peers chose: 

• Treat empirically with ritonavir-boosted nirmatrelvir

 7%

 

• Treat empirically with oseltamivir or baloxavir

 14%

 

• Perform lab-based multiplex RT-PCR testing and wait to treat on the basis of results

 34%

 

• Perform rapid nucleic acid amplification testing (NAAT) and treat on the basis of results

 45%

Every practice has different resources and should use the best means available to treat patients. Ideally, this patient would undergo rapid NAAT with results available within 30 minutes. Test results will help guide not only treatment decisions but also infection-control measures.

The Infectious Diseases Society of America has provided updates for testing for URIs since the onset of the COVID-19 pandemic. Both laboratory-based and point-of-care rapid NAATs are recommended for testing. Rapid NAATs have been demonstrated to have a sensitivity of 96% and specificity of 100% in the detection of SARS-CoV-2. Obviously, they also offer a highly efficient means to make treatment and isolation decisions.

There are multiple platforms for molecular testing available. Laboratory-based platforms can test for dozens of potential pathogens, including bacteria. Rapid NAATs often have the ability to test for SARS-CoV-2, influenza, and respiratory syncytial virus (RSV). This functionality is important, because these infections generally are difficult to discriminate on the basis of clinical information alone.

The IDSA clearly recognizes the challenges of trying to manage cases of URI. For example, they state that testing of the anterior nares (AN) or oropharynx (OP) is acceptable, even though testing from the nasopharynx offers increased sensitivity. However, testing at the AN/OP allows for patient self-collection of samples, which is also recommended as an option by the IDSA. In an analysis of six cohort studies, the pooled sensitivity of patient-collected nasopharyngeal samples from the AN/OP was 88%, whereas the respective value for samples taken by health care providers was 95%.

The U.S. Centers for Disease Control and Prevention also provides recommendations for the management of patients with acute upper respiratory illness. Patients who are sick enough to be hospitalized should be tested at least for SARS-CoV-2 and influenza using molecular assays. Outpatients should be tested for SARS-CoV-2 with either molecular or antigen testing, and influenza testing should be offered if the findings will change decisions regarding treatment or isolation. Practically speaking, the recommendations for influenza testing mean that most individuals should be tested, including patients at high risk for complications of influenza and those who might have exposure to individuals at high risk.

Treatment of COVID-19 should only be provided in cases of a positive test within 5 days of symptom onset. However, clinicians may treat patients with anti-influenza medications presumptively if test results are not immediately available and the patient has worsening symptoms or is in a group at high risk for complications.

What are some of the challenges that you have faced during the COVID-19 pandemic regarding the management of patients with acute URIs? What have you found in terms of solutions, and where do gaps in quality of care persist? Please add your comments. I will review and circle back with a response. Thank you!

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

It’s upper respiratory infection (URI) season. The following is a clinical scenario drawn from my own practice. I’ll tell you what I plan to do, but I’m most interested in crowdsourcing a response from all of you to collectively determine best practice. So please answer the polling questions and contribute your thoughts in the comments, whether you agree or disagree with me.

The patient

The patient is a 69-year-old woman with a 3-day history of cough, nasal congestion, malaise, tactile fever, and poor appetite. She has no sick contacts. She denies dyspnea, presyncope, and chest pain. She has tried guaifenesin and ibuprofen for her symptoms, which helped a little.

She is up to date on immunizations, including four doses of COVID-19 vaccine and the influenza vaccine, which she received 2 months ago.

The patient has a history of heart failure with reduced ejection fraction, coronary artery disease, hypertension, chronic kidney disease stage 3aA2, obesity, and osteoarthritis. Current medications include atorvastatin, losartan, metoprolol, and aspirin.

Her weight is stable at 212 lb, and her vital signs today are:

• Temperature: 37.5° C
• Pulse: 60 beats/min
• Blood pressure: 150/88 mm Hg
• Respiration rate: 14 breaths/min
• SpO₂: 93% on room air

What information is most critical before deciding on management?

Your peers chose: 

• The patient’s history of viral URIs

 14%

 

• Whether her cough is productive and the color of the sputum

 38%

 

• How well this season’s flu vaccine matches circulating influenza viruses

 8%

 

• Local epidemiology of major viral pathogens (e.g., SARS-CoV-2, influenza, RSV)

 40%
 

Dr. Vega’s take

To provide the best care for our patients when they are threatened with multiple viral upper respiratory pathogens, it is imperative that clinicians have some idea regarding the epidemiology of viral infections, with as much local data as possible. This knowledge will help direct appropriate testing and treatment.

Modern viral molecular testing platforms are highly accurate, but they are not infallible. Small flaws in specificity and sensitivity of testing are magnified when community viral circulation is low. In a U.K. study conducted during a period of low COVID-19 prevalence, the positive predictive value of reverse-transcriptase polymerase chain reaction (RT-PCR) testing was just 16%. Although the negative predictive value was much higher, the false-positive rate of testing was still 0.5%. The authors of the study describe important potential consequences of false-positive results, such as being temporarily removed from an organ transplant list and unnecessary contact tracing.
 

Testing and treatment

Your county public health department maintains a website describing local activity of SARS-CoV-2 and influenza. Both viruses are in heavy circulation now.

What is the next best step in this patient’s management?

Your peers chose: 

• Treat empirically with ritonavir-boosted nirmatrelvir

 7%

 

• Treat empirically with oseltamivir or baloxavir

 14%

 

• Perform lab-based multiplex RT-PCR testing and wait to treat on the basis of results

 34%

 

• Perform rapid nucleic acid amplification testing (NAAT) and treat on the basis of results

 45%

Every practice has different resources and should use the best means available to treat patients. Ideally, this patient would undergo rapid NAAT with results available within 30 minutes. Test results will help guide not only treatment decisions but also infection-control measures.

The Infectious Diseases Society of America has provided updates for testing for URIs since the onset of the COVID-19 pandemic. Both laboratory-based and point-of-care rapid NAATs are recommended for testing. Rapid NAATs have been demonstrated to have a sensitivity of 96% and specificity of 100% in the detection of SARS-CoV-2. Obviously, they also offer a highly efficient means to make treatment and isolation decisions.

There are multiple platforms for molecular testing available. Laboratory-based platforms can test for dozens of potential pathogens, including bacteria. Rapid NAATs often have the ability to test for SARS-CoV-2, influenza, and respiratory syncytial virus (RSV). This functionality is important, because these infections generally are difficult to discriminate on the basis of clinical information alone.

The IDSA clearly recognizes the challenges of trying to manage cases of URI. For example, they state that testing of the anterior nares (AN) or oropharynx (OP) is acceptable, even though testing from the nasopharynx offers increased sensitivity. However, testing at the AN/OP allows for patient self-collection of samples, which is also recommended as an option by the IDSA. In an analysis of six cohort studies, the pooled sensitivity of patient-collected nasopharyngeal samples from the AN/OP was 88%, whereas the respective value for samples taken by health care providers was 95%.

The U.S. Centers for Disease Control and Prevention also provides recommendations for the management of patients with acute upper respiratory illness. Patients who are sick enough to be hospitalized should be tested at least for SARS-CoV-2 and influenza using molecular assays. Outpatients should be tested for SARS-CoV-2 with either molecular or antigen testing, and influenza testing should be offered if the findings will change decisions regarding treatment or isolation. Practically speaking, the recommendations for influenza testing mean that most individuals should be tested, including patients at high risk for complications of influenza and those who might have exposure to individuals at high risk.

Treatment of COVID-19 should only be provided in cases of a positive test within 5 days of symptom onset. However, clinicians may treat patients with anti-influenza medications presumptively if test results are not immediately available and the patient has worsening symptoms or is in a group at high risk for complications.

What are some of the challenges that you have faced during the COVID-19 pandemic regarding the management of patients with acute URIs? What have you found in terms of solutions, and where do gaps in quality of care persist? Please add your comments. I will review and circle back with a response. Thank you!

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

TOPLINE:

Intensive antihypertensive treatment provides the same benefit with regard to cardiovascular disease (CVD) and all-cause mortality regardless of the presence or absence of orthostatic or standing hypotension, new research shows.

METHODOLOGY:

• In response to ongoing concern about the benefits of intensive versus standard blood pressure treatment for adults with orthostatic hypotension (OH), researchers conducted a meta-analysis of individual patient data from nine randomized clinical trials to see whether the benefit of antihypertensive treatment was diminished for patients who had OH at baseline. Benefit was defined as a reduction in nonfatal CVD events and all-cause mortality.
• The included trials assessed BP pharmacologic treatment (more intensive BP goal or active agent) and had data on OH.

TAKEAWAY:

• The nine trials included 29,235 participants (mean age, 69 years; 48% women) who were followed for a median of 4 years; 9% had OH and 5% had standing hypotension at baseline.
• Having OH at baseline was significantly associated with the composite of CVD or all-cause mortality (hazard ratio, 1.14; 95% confidence interval, 1.04-1.26) and with all-cause mortality (HR, 1.24; 95% CI, 1.09-1.41). The same was true for baseline standing hypotension (composite outcome: HR, 1.39; 95% CI, 1.24-1.57; all-cause mortality: HR, 1.38; 95% CI, 1.14-1.66).
• More intensive BP treatment or active therapy significantly and similarly lowered risk of CVD or all-cause mortality among adults who did not have OH at baseline (HR, 0.81; 95% CI, 0.76-0.86) as well as those with OH at baseline (HR, 0.83; 95% CI, 0.70-1.00).
• More intensive BP treatment or active therapy also significantly lowered risk of CVD or all-cause mortality among those without baseline standing hypotension (HR, 0.80; 95% CI, 0.75-0.85) and nonsignificantly lowered the risk among those with baseline standing hypotension (HR, 0.94; 95% CI, 0.75-1.18).

IN PRACTICE:

“These findings suggest that orthostatic hypotension alone (that is, without symptoms) and standing hypotension measured prior to intensification of BP treatment should not deter adoption of more intensive BP treatment in adults with hypertension,” the authors conclude.

The findings should “reassure clinicians that patients with OH (and perhaps standing hypotension) will derive the full expected benefits from antihypertensive therapy,” add the authors of an accompanying editorial. “This also applies to patients treated to lower BP goals, albeit with less certainty.”

SOURCE:

The study, with first author Stephen Juraschek, MD, PhD, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, and the accompanying editorial were published online in JAMA.

LIMITATIONS:

In the hypertension trials that were included in the analysis, the study populations differed, as did BP measurement procedures, interventions, duration, and CVD outcome ascertainment processes and definitions. Some trials excluded adults with low standing systolic BP, limiting the number of participants with standing hypotension. OH was determined on the basis of a seated-to-standing protocol; supine-to-standing protocols are more sensitive and may not be interchangeable. Medications used in the trials may not reflect current medicine practice, or the trials may not have included agents thought to be more likely to affect OH and falls.

DISCLOSURES:

The study had no specific funding. Dr. Juraschek has disclosed no relevant financial relationships.

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

TOPLINE:

Intensive antihypertensive treatment provides the same benefit with regard to cardiovascular disease (CVD) and all-cause mortality regardless of the presence or absence of orthostatic or standing hypotension, new research shows.

METHODOLOGY:

• In response to ongoing concern about the benefits of intensive versus standard blood pressure treatment for adults with orthostatic hypotension (OH), researchers conducted a meta-analysis of individual patient data from nine randomized clinical trials to see whether the benefit of antihypertensive treatment was diminished for patients who had OH at baseline. Benefit was defined as a reduction in nonfatal CVD events and all-cause mortality.
• The included trials assessed BP pharmacologic treatment (more intensive BP goal or active agent) and had data on OH.

TAKEAWAY:

• The nine trials included 29,235 participants (mean age, 69 years; 48% women) who were followed for a median of 4 years; 9% had OH and 5% had standing hypotension at baseline.
• Having OH at baseline was significantly associated with the composite of CVD or all-cause mortality (hazard ratio, 1.14; 95% confidence interval, 1.04-1.26) and with all-cause mortality (HR, 1.24; 95% CI, 1.09-1.41). The same was true for baseline standing hypotension (composite outcome: HR, 1.39; 95% CI, 1.24-1.57; all-cause mortality: HR, 1.38; 95% CI, 1.14-1.66).
• More intensive BP treatment or active therapy significantly and similarly lowered risk of CVD or all-cause mortality among adults who did not have OH at baseline (HR, 0.81; 95% CI, 0.76-0.86) as well as those with OH at baseline (HR, 0.83; 95% CI, 0.70-1.00).
• More intensive BP treatment or active therapy also significantly lowered risk of CVD or all-cause mortality among those without baseline standing hypotension (HR, 0.80; 95% CI, 0.75-0.85) and nonsignificantly lowered the risk among those with baseline standing hypotension (HR, 0.94; 95% CI, 0.75-1.18).

IN PRACTICE:

“These findings suggest that orthostatic hypotension alone (that is, without symptoms) and standing hypotension measured prior to intensification of BP treatment should not deter adoption of more intensive BP treatment in adults with hypertension,” the authors conclude.

The findings should “reassure clinicians that patients with OH (and perhaps standing hypotension) will derive the full expected benefits from antihypertensive therapy,” add the authors of an accompanying editorial. “This also applies to patients treated to lower BP goals, albeit with less certainty.”

SOURCE:

The study, with first author Stephen Juraschek, MD, PhD, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, and the accompanying editorial were published online in JAMA.

LIMITATIONS:

In the hypertension trials that were included in the analysis, the study populations differed, as did BP measurement procedures, interventions, duration, and CVD outcome ascertainment processes and definitions. Some trials excluded adults with low standing systolic BP, limiting the number of participants with standing hypotension. OH was determined on the basis of a seated-to-standing protocol; supine-to-standing protocols are more sensitive and may not be interchangeable. Medications used in the trials may not reflect current medicine practice, or the trials may not have included agents thought to be more likely to affect OH and falls.

DISCLOSURES:

The study had no specific funding. Dr. Juraschek has disclosed no relevant financial relationships.

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

TOPLINE:

Intensive antihypertensive treatment provides the same benefit with regard to cardiovascular disease (CVD) and all-cause mortality regardless of the presence or absence of orthostatic or standing hypotension, new research shows.

METHODOLOGY:

• In response to ongoing concern about the benefits of intensive versus standard blood pressure treatment for adults with orthostatic hypotension (OH), researchers conducted a meta-analysis of individual patient data from nine randomized clinical trials to see whether the benefit of antihypertensive treatment was diminished for patients who had OH at baseline. Benefit was defined as a reduction in nonfatal CVD events and all-cause mortality.
• The included trials assessed BP pharmacologic treatment (more intensive BP goal or active agent) and had data on OH.

TAKEAWAY:

• The nine trials included 29,235 participants (mean age, 69 years; 48% women) who were followed for a median of 4 years; 9% had OH and 5% had standing hypotension at baseline.
• Having OH at baseline was significantly associated with the composite of CVD or all-cause mortality (hazard ratio, 1.14; 95% confidence interval, 1.04-1.26) and with all-cause mortality (HR, 1.24; 95% CI, 1.09-1.41). The same was true for baseline standing hypotension (composite outcome: HR, 1.39; 95% CI, 1.24-1.57; all-cause mortality: HR, 1.38; 95% CI, 1.14-1.66).
• More intensive BP treatment or active therapy significantly and similarly lowered risk of CVD or all-cause mortality among adults who did not have OH at baseline (HR, 0.81; 95% CI, 0.76-0.86) as well as those with OH at baseline (HR, 0.83; 95% CI, 0.70-1.00).
• More intensive BP treatment or active therapy also significantly lowered risk of CVD or all-cause mortality among those without baseline standing hypotension (HR, 0.80; 95% CI, 0.75-0.85) and nonsignificantly lowered the risk among those with baseline standing hypotension (HR, 0.94; 95% CI, 0.75-1.18).

IN PRACTICE:

“These findings suggest that orthostatic hypotension alone (that is, without symptoms) and standing hypotension measured prior to intensification of BP treatment should not deter adoption of more intensive BP treatment in adults with hypertension,” the authors conclude.

The findings should “reassure clinicians that patients with OH (and perhaps standing hypotension) will derive the full expected benefits from antihypertensive therapy,” add the authors of an accompanying editorial. “This also applies to patients treated to lower BP goals, albeit with less certainty.”

SOURCE:

The study, with first author Stephen Juraschek, MD, PhD, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, and the accompanying editorial were published online in JAMA.

LIMITATIONS:

In the hypertension trials that were included in the analysis, the study populations differed, as did BP measurement procedures, interventions, duration, and CVD outcome ascertainment processes and definitions. Some trials excluded adults with low standing systolic BP, limiting the number of participants with standing hypotension. OH was determined on the basis of a seated-to-standing protocol; supine-to-standing protocols are more sensitive and may not be interchangeable. Medications used in the trials may not reflect current medicine practice, or the trials may not have included agents thought to be more likely to affect OH and falls.

DISCLOSURES:

The study had no specific funding. Dr. Juraschek has disclosed no relevant financial relationships.

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

Which conditions are caused by infection? Though it may seem like an amateur concern in the era of advanced microscopy, some culprits evade conventional methods of detection. Large medical databases hold the power to unlock answers. 

A recent study from Sweden and Denmark meticulously traced the lives and medical histories of nearly one million men and women in those countries who had received blood transfusions over nearly five decades. Some of these patients later experienced brain bleeds. The inescapable question: Could a virus found in some donor blood have caused the hemorrhages?

Traditionally, brain bleeds have been thought to strike at random. But the new study, published in JAMA, points toward an infection that causes or, at the very least, is linked to the condition. The researchers used a large databank to make the discovery. 

“As health data becomes more available and easier to analyze, we’ll see all kinds of cases like this,” said Jingcheng Zhao, MD, of the clinical epidemiology division of Sweden’s Karolinska Institutet in Solna and lead author of the study.

Scientists say the field of medical research is on the cusp of a revolution as immense health databases guide discovery and improve clinical care. 

“If you can aggregate data, you have the statistical power to identify associations,” said David R. Crosslin, PhD, professor in the division of biomedical informatics and genomics at Tulane University in New Orleans. “It opens up the world for understanding diseases.”

With access to the large database, Dr. Zhao and his team found that some blood donors later experienced brain bleeds. And it turned out that the recipients of blood from those same donors carried the highest risk of experiencing a brain bleed later in life. Meanwhile, patients whose donors remained bleed-free had the lowest risk.
 

Not so fast in the United States

In Nordic countries, all hospitals, clinics, and pharmacies report data on diagnoses and health care visits to the government, tracking that began with paper and pen in the 1960s. But the United States health care system is too fragmented to replicate such efforts, with several brands of electronic medical records operating across different systems. Data sharing across institutions is minimal. 

Most comparable health data in the United States comes from reimbursement information collected by the Centers for Medicare & Medicaid Services on government-sponsored insurance programs.

“We would need all the health care systems in the country to operate within the same IT system or use the same data model,” said Euan Ashley, MD, PhD, professor of genomics at Stanford (Calif.) University. “It’s an exciting prospect. But I think [the United States] is one of the last countries where it’ll happen.”

States, meanwhile, collect health data on specific areas like sexually transmitted infection cases and rates. Other states have registries, like the Connecticut Tumor Registry, which was established in 1941 and is the oldest population-based cancer registry in the world.

But all of these efforts are ad hoc, and no equivalent exists for heart disease and other conditions.

Health data companies have recently entered the U.S. data industry mainly through partnerships with health systems and insurance companies, using deidentified information from patient charts.

The large databases have yielded important findings that randomized clinical trials simply cannot, according to Dr. Ashley.

For instance, a study found that a heavily-lauded immunotherapy treatment did not provide meaningful outcomes for patients aged 75 years or older, but it did for younger patients.

This sort of analysis might enable clinicians to administer treatments based on how effective they are for patients with particular demographics, according to Cary Gross, MD, professor at Yale University in New Haven, Conn.

“From a bedside standpoint, these large databases can identify who benefits from what,” Dr. Gross said. “Precision medicine is not just about genetic tailoring.” These large datasets also provide insight into genetic and environmental variables that contribute to disease. 

For instance, the UK Biobank has more than 500,000 participants paired with their medical records and scans of their body and brain. Researchers perform cognitive tests on participants and extract DNA from blood samples over their lifetime, allowing examination of interactions between risk factors. 

A similar but much smaller-scale effort underway in the United States, called the All of Us Research Program, has enrolled more than 650,000 people, less than one-third the size of the UK Biobank by relative populations. The goal of the program is to provide insights into prevention and treatment of chronic disease among a diverse set of at least one million participants. The database includes information on sexual orientation, which is a fairly new datapoint collected by researchers in an effort to study health outcomes and inequities among the LGBTQ+ community.

Dr. Crosslin and his colleagues are writing a grant proposal to use the All of Us database to identify genetic risks for preeclampsia. People with certain genetic profiles may be predisposed to the life-threatening condition, and researchers may discover that lifestyle changes could decrease risk, Dr. Crosslin said. 
 

Changes in the United States

The COVID-19 pandemic exposed the lack of centralized data in the United States because a majority of research on the virus has been conducted abroad in countries with national health care systems and these large databases. 

The U.S. gap spurred a group of researchers to create the National Institutes of Health–funded National COVID Cohort Collaborative (N3C), a project that gathers medical records from millions of patients across health systems and provides access to research teams investigating a wide spectrum of topics, such as optimal timing for ventilator use.

But until government or private health systems develop a way to share and regulate health data ethically and efficiently, significant limits will persist on what large-scale databases can do, Dr. Gross said. 

“At the federal level, we need to ensure this health information is made available for public health researchers so we don’t create these private fiefdoms of data,” Dr. Gross said. “Things have to be transparent. I think our country needs to take a step back and think about what we’re doing with our health data and how we can make sure it’s being managed ethically.”

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

Which conditions are caused by infection? Though it may seem like an amateur concern in the era of advanced microscopy, some culprits evade conventional methods of detection. Large medical databases hold the power to unlock answers. 

A recent study from Sweden and Denmark meticulously traced the lives and medical histories of nearly one million men and women in those countries who had received blood transfusions over nearly five decades. Some of these patients later experienced brain bleeds. The inescapable question: Could a virus found in some donor blood have caused the hemorrhages?

Traditionally, brain bleeds have been thought to strike at random. But the new study, published in JAMA, points toward an infection that causes or, at the very least, is linked to the condition. The researchers used a large databank to make the discovery. 

“As health data becomes more available and easier to analyze, we’ll see all kinds of cases like this,” said Jingcheng Zhao, MD, of the clinical epidemiology division of Sweden’s Karolinska Institutet in Solna and lead author of the study.

Scientists say the field of medical research is on the cusp of a revolution as immense health databases guide discovery and improve clinical care. 

“If you can aggregate data, you have the statistical power to identify associations,” said David R. Crosslin, PhD, professor in the division of biomedical informatics and genomics at Tulane University in New Orleans. “It opens up the world for understanding diseases.”

With access to the large database, Dr. Zhao and his team found that some blood donors later experienced brain bleeds. And it turned out that the recipients of blood from those same donors carried the highest risk of experiencing a brain bleed later in life. Meanwhile, patients whose donors remained bleed-free had the lowest risk.
 

Not so fast in the United States

In Nordic countries, all hospitals, clinics, and pharmacies report data on diagnoses and health care visits to the government, tracking that began with paper and pen in the 1960s. But the United States health care system is too fragmented to replicate such efforts, with several brands of electronic medical records operating across different systems. Data sharing across institutions is minimal. 

Most comparable health data in the United States comes from reimbursement information collected by the Centers for Medicare & Medicaid Services on government-sponsored insurance programs.

“We would need all the health care systems in the country to operate within the same IT system or use the same data model,” said Euan Ashley, MD, PhD, professor of genomics at Stanford (Calif.) University. “It’s an exciting prospect. But I think [the United States] is one of the last countries where it’ll happen.”

States, meanwhile, collect health data on specific areas like sexually transmitted infection cases and rates. Other states have registries, like the Connecticut Tumor Registry, which was established in 1941 and is the oldest population-based cancer registry in the world.

But all of these efforts are ad hoc, and no equivalent exists for heart disease and other conditions.

Health data companies have recently entered the U.S. data industry mainly through partnerships with health systems and insurance companies, using deidentified information from patient charts.

The large databases have yielded important findings that randomized clinical trials simply cannot, according to Dr. Ashley.

For instance, a study found that a heavily-lauded immunotherapy treatment did not provide meaningful outcomes for patients aged 75 years or older, but it did for younger patients.

This sort of analysis might enable clinicians to administer treatments based on how effective they are for patients with particular demographics, according to Cary Gross, MD, professor at Yale University in New Haven, Conn.

“From a bedside standpoint, these large databases can identify who benefits from what,” Dr. Gross said. “Precision medicine is not just about genetic tailoring.” These large datasets also provide insight into genetic and environmental variables that contribute to disease. 

For instance, the UK Biobank has more than 500,000 participants paired with their medical records and scans of their body and brain. Researchers perform cognitive tests on participants and extract DNA from blood samples over their lifetime, allowing examination of interactions between risk factors. 

A similar but much smaller-scale effort underway in the United States, called the All of Us Research Program, has enrolled more than 650,000 people, less than one-third the size of the UK Biobank by relative populations. The goal of the program is to provide insights into prevention and treatment of chronic disease among a diverse set of at least one million participants. The database includes information on sexual orientation, which is a fairly new datapoint collected by researchers in an effort to study health outcomes and inequities among the LGBTQ+ community.

Dr. Crosslin and his colleagues are writing a grant proposal to use the All of Us database to identify genetic risks for preeclampsia. People with certain genetic profiles may be predisposed to the life-threatening condition, and researchers may discover that lifestyle changes could decrease risk, Dr. Crosslin said. 
 

Changes in the United States

The COVID-19 pandemic exposed the lack of centralized data in the United States because a majority of research on the virus has been conducted abroad in countries with national health care systems and these large databases. 

The U.S. gap spurred a group of researchers to create the National Institutes of Health–funded National COVID Cohort Collaborative (N3C), a project that gathers medical records from millions of patients across health systems and provides access to research teams investigating a wide spectrum of topics, such as optimal timing for ventilator use.

But until government or private health systems develop a way to share and regulate health data ethically and efficiently, significant limits will persist on what large-scale databases can do, Dr. Gross said. 

“At the federal level, we need to ensure this health information is made available for public health researchers so we don’t create these private fiefdoms of data,” Dr. Gross said. “Things have to be transparent. I think our country needs to take a step back and think about what we’re doing with our health data and how we can make sure it’s being managed ethically.”

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

Which conditions are caused by infection? Though it may seem like an amateur concern in the era of advanced microscopy, some culprits evade conventional methods of detection. Large medical databases hold the power to unlock answers. 

A recent study from Sweden and Denmark meticulously traced the lives and medical histories of nearly one million men and women in those countries who had received blood transfusions over nearly five decades. Some of these patients later experienced brain bleeds. The inescapable question: Could a virus found in some donor blood have caused the hemorrhages?

Traditionally, brain bleeds have been thought to strike at random. But the new study, published in JAMA, points toward an infection that causes or, at the very least, is linked to the condition. The researchers used a large databank to make the discovery. 

“As health data becomes more available and easier to analyze, we’ll see all kinds of cases like this,” said Jingcheng Zhao, MD, of the clinical epidemiology division of Sweden’s Karolinska Institutet in Solna and lead author of the study.

Scientists say the field of medical research is on the cusp of a revolution as immense health databases guide discovery and improve clinical care. 

“If you can aggregate data, you have the statistical power to identify associations,” said David R. Crosslin, PhD, professor in the division of biomedical informatics and genomics at Tulane University in New Orleans. “It opens up the world for understanding diseases.”

With access to the large database, Dr. Zhao and his team found that some blood donors later experienced brain bleeds. And it turned out that the recipients of blood from those same donors carried the highest risk of experiencing a brain bleed later in life. Meanwhile, patients whose donors remained bleed-free had the lowest risk.
 

Not so fast in the United States

In Nordic countries, all hospitals, clinics, and pharmacies report data on diagnoses and health care visits to the government, tracking that began with paper and pen in the 1960s. But the United States health care system is too fragmented to replicate such efforts, with several brands of electronic medical records operating across different systems. Data sharing across institutions is minimal. 

Most comparable health data in the United States comes from reimbursement information collected by the Centers for Medicare & Medicaid Services on government-sponsored insurance programs.

“We would need all the health care systems in the country to operate within the same IT system or use the same data model,” said Euan Ashley, MD, PhD, professor of genomics at Stanford (Calif.) University. “It’s an exciting prospect. But I think [the United States] is one of the last countries where it’ll happen.”

States, meanwhile, collect health data on specific areas like sexually transmitted infection cases and rates. Other states have registries, like the Connecticut Tumor Registry, which was established in 1941 and is the oldest population-based cancer registry in the world.

But all of these efforts are ad hoc, and no equivalent exists for heart disease and other conditions.

Health data companies have recently entered the U.S. data industry mainly through partnerships with health systems and insurance companies, using deidentified information from patient charts.

The large databases have yielded important findings that randomized clinical trials simply cannot, according to Dr. Ashley.

For instance, a study found that a heavily-lauded immunotherapy treatment did not provide meaningful outcomes for patients aged 75 years or older, but it did for younger patients.

This sort of analysis might enable clinicians to administer treatments based on how effective they are for patients with particular demographics, according to Cary Gross, MD, professor at Yale University in New Haven, Conn.

“From a bedside standpoint, these large databases can identify who benefits from what,” Dr. Gross said. “Precision medicine is not just about genetic tailoring.” These large datasets also provide insight into genetic and environmental variables that contribute to disease. 

For instance, the UK Biobank has more than 500,000 participants paired with their medical records and scans of their body and brain. Researchers perform cognitive tests on participants and extract DNA from blood samples over their lifetime, allowing examination of interactions between risk factors. 

A similar but much smaller-scale effort underway in the United States, called the All of Us Research Program, has enrolled more than 650,000 people, less than one-third the size of the UK Biobank by relative populations. The goal of the program is to provide insights into prevention and treatment of chronic disease among a diverse set of at least one million participants. The database includes information on sexual orientation, which is a fairly new datapoint collected by researchers in an effort to study health outcomes and inequities among the LGBTQ+ community.

Dr. Crosslin and his colleagues are writing a grant proposal to use the All of Us database to identify genetic risks for preeclampsia. People with certain genetic profiles may be predisposed to the life-threatening condition, and researchers may discover that lifestyle changes could decrease risk, Dr. Crosslin said. 
 

Changes in the United States

The COVID-19 pandemic exposed the lack of centralized data in the United States because a majority of research on the virus has been conducted abroad in countries with national health care systems and these large databases. 

The U.S. gap spurred a group of researchers to create the National Institutes of Health–funded National COVID Cohort Collaborative (N3C), a project that gathers medical records from millions of patients across health systems and provides access to research teams investigating a wide spectrum of topics, such as optimal timing for ventilator use.

But until government or private health systems develop a way to share and regulate health data ethically and efficiently, significant limits will persist on what large-scale databases can do, Dr. Gross said. 

“At the federal level, we need to ensure this health information is made available for public health researchers so we don’t create these private fiefdoms of data,” Dr. Gross said. “Things have to be transparent. I think our country needs to take a step back and think about what we’re doing with our health data and how we can make sure it’s being managed ethically.”

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

VANCOUVER – Patients who undergo either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy are at an increased risk of fracture, compared with patients with obesity who do not undergo surgery, according to a new analysis of a predominantly male group of U.S. veterans.

Previous studies involving premenopausal women have found a risk of bone mineral density loss and fracture with bariatric surgery, but little was known about the risk among men. Research has also shown an increase in risk after RYGB, but there is less information on risks associated with sleeve gastrectomy, though it is now the most common surgery for weight loss.

Bone density loss after bariatric surgery has been shown to be significant, according to Eileen H. Koh, MD. “It’s quite a lot of bone loss, quickly,” said Dr. Koh, a graduated fellow from the endocrinology program at the University of California, San Francisco, who is moving to the University of Washington, Seattle.

Those observations generally come from studies of younger women. The purpose of the new study “was to see if we see the same risk of fracture in veterans who are older men, so kind of the opposite of the typical bariatric patient,” said Dr. Koh, who presented the research at the annual meeting of the American Society for Bone and Mineral Research.

The researchers analyzed data from 8,299 U.S. veterans who underwent sleeve gastrectomy (41%), RYGB (51%), adjustable gastric banding (4%), or an unspecified bariatric procedure (4%) between 2000 and 2020. They were matched with 24,877 individuals with obesity who did not undergo surgery. The investigators excluded individuals who were at high risk of fracture because of another condition, such as organ transplantation or dialysis. Men made up 70% of both surgical and nonsurgical groups. The mean age was 52 years for both, and 89% and 88% were not Hispanic or Latino, respectively. The proportion of White individuals was 72% and 64%, and the proportion of Black individuals was 18% and 24%.

After adjustment for demographic variables and comorbidities, bariatric surgery was associated with a 68% increased risk of fracture (hazard ratio, 1.68; 95% confidence interval, 1.57-1.80), including hip fractures (HR, 2.42; 95% CI, 1.98-2.97), spine (HR, 1.82; 95% CI, 1.61-2.06), radius/ulna (HR, 2.38; 95% CI, 2.05-2.77), humerus (HR, 1.56; 95% CI, 1.28-1.89), pelvis (HR, 2.41; 95% CI, 1.68-3.46), and tibia/fibula/ankle (HR, 1.50; 95% CI, 1.33-1.69). Increased fracture risk was associated with RYGB (HR, 1.93; 95% CI, 1.75-2.12) and sleeve gastrectomy (HR, 1.50; 95% CI, 1.33-1.69) but not adjustable gastric banding.

Compared with sleeve gastrectomy, adjustable gastric banding was associated with a decreased risk of fracture (HR, 0.64; 95% CI, 0.49-0.84; P = .0012).

The study’s predominantly male population is important because men also get osteoporosis and are frequently overlooked, according to Anne Schafer, MD, who was the lead author of the study. “Even after they fracture, men are sometimes less likely to get care to prevent the next fracture. We’ve shown here that especially men who are on the older side, who go through surgical weight loss, do have a higher risk of fracture compared to those who are similarly obese but have not had the operation,” said Dr. Schafer, a professor of medicine at the University of California, San Francisco, and chief of endocrinology and metabolism at the San Francisco VA Medical Center.

There are limited data on fracture risk after sleeve gastrectomy. “I think this is one of the first times that I’ve been able to demonstrate that there was a higher risk of fracture with sleeve gastrectomy in comparison with nonsurgical cohorts. Of course, it’s necessary to confirm these findings in further studies, but it’s interesting,” said Julien Paccou, MD, who attended the poster session and was asked for comment. His group’s study of a French population showed an increased fracture risk associated with RYGB but not sleeve gastrectomy. Another study found a reduction of fracture risk associated with sleeve gastrectomy and no difference between RYGB and nonsurgical matched control patients in a Medicare population.

In fact, there is a belief that fracture risk may be lower with sleeve gastrectomy, according to Dr. Schafer. “It’s part of why it’s so popular,” she said.

The reasons for increased fracture risk following surgical weight loss remains unknown, according to Dr. Paccou, but they could include mechanical unloading, loss of lean mass, and hormone and nutrition changes. “There are many, many factors,” said Dr. Paccou, a professor of rheumatology at Hospital Roger Salengro in Lille, France.

The study’s findings of increased risk of fracture after sleeve gastrectomy may be an argument against malabsorption because the procedure shouldn’t affect nutrient absorption. It suggests that other factors are at play. “It’s not the only reason,” Dr. Schafer said.

There are recommendations for postbariatric surgery care to optimize bone health, such as protein intake and calcium and vitamin D targets, along with lifestyle factors. “Despite all those [efforts], we still know that bone loss occurs,” Dr. Koh said. In fact, the group is conducting a study funded by Amgen of the use of denosumab (Prolia) for the prevention of high-turnover bone loss after RYGB and sleeve gastrectomy.

Dr. Schafer has received research support from Bone Health Technologies and Amgen. Dr. Koh and Dr. Paccou have disclosed no relevant financial relationships.

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

VANCOUVER – Patients who undergo either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy are at an increased risk of fracture, compared with patients with obesity who do not undergo surgery, according to a new analysis of a predominantly male group of U.S. veterans.

Previous studies involving premenopausal women have found a risk of bone mineral density loss and fracture with bariatric surgery, but little was known about the risk among men. Research has also shown an increase in risk after RYGB, but there is less information on risks associated with sleeve gastrectomy, though it is now the most common surgery for weight loss.

Bone density loss after bariatric surgery has been shown to be significant, according to Eileen H. Koh, MD. “It’s quite a lot of bone loss, quickly,” said Dr. Koh, a graduated fellow from the endocrinology program at the University of California, San Francisco, who is moving to the University of Washington, Seattle.

Those observations generally come from studies of younger women. The purpose of the new study “was to see if we see the same risk of fracture in veterans who are older men, so kind of the opposite of the typical bariatric patient,” said Dr. Koh, who presented the research at the annual meeting of the American Society for Bone and Mineral Research.

The researchers analyzed data from 8,299 U.S. veterans who underwent sleeve gastrectomy (41%), RYGB (51%), adjustable gastric banding (4%), or an unspecified bariatric procedure (4%) between 2000 and 2020. They were matched with 24,877 individuals with obesity who did not undergo surgery. The investigators excluded individuals who were at high risk of fracture because of another condition, such as organ transplantation or dialysis. Men made up 70% of both surgical and nonsurgical groups. The mean age was 52 years for both, and 89% and 88% were not Hispanic or Latino, respectively. The proportion of White individuals was 72% and 64%, and the proportion of Black individuals was 18% and 24%.

After adjustment for demographic variables and comorbidities, bariatric surgery was associated with a 68% increased risk of fracture (hazard ratio, 1.68; 95% confidence interval, 1.57-1.80), including hip fractures (HR, 2.42; 95% CI, 1.98-2.97), spine (HR, 1.82; 95% CI, 1.61-2.06), radius/ulna (HR, 2.38; 95% CI, 2.05-2.77), humerus (HR, 1.56; 95% CI, 1.28-1.89), pelvis (HR, 2.41; 95% CI, 1.68-3.46), and tibia/fibula/ankle (HR, 1.50; 95% CI, 1.33-1.69). Increased fracture risk was associated with RYGB (HR, 1.93; 95% CI, 1.75-2.12) and sleeve gastrectomy (HR, 1.50; 95% CI, 1.33-1.69) but not adjustable gastric banding.

Compared with sleeve gastrectomy, adjustable gastric banding was associated with a decreased risk of fracture (HR, 0.64; 95% CI, 0.49-0.84; P = .0012).

The study’s predominantly male population is important because men also get osteoporosis and are frequently overlooked, according to Anne Schafer, MD, who was the lead author of the study. “Even after they fracture, men are sometimes less likely to get care to prevent the next fracture. We’ve shown here that especially men who are on the older side, who go through surgical weight loss, do have a higher risk of fracture compared to those who are similarly obese but have not had the operation,” said Dr. Schafer, a professor of medicine at the University of California, San Francisco, and chief of endocrinology and metabolism at the San Francisco VA Medical Center.

There are limited data on fracture risk after sleeve gastrectomy. “I think this is one of the first times that I’ve been able to demonstrate that there was a higher risk of fracture with sleeve gastrectomy in comparison with nonsurgical cohorts. Of course, it’s necessary to confirm these findings in further studies, but it’s interesting,” said Julien Paccou, MD, who attended the poster session and was asked for comment. His group’s study of a French population showed an increased fracture risk associated with RYGB but not sleeve gastrectomy. Another study found a reduction of fracture risk associated with sleeve gastrectomy and no difference between RYGB and nonsurgical matched control patients in a Medicare population.

In fact, there is a belief that fracture risk may be lower with sleeve gastrectomy, according to Dr. Schafer. “It’s part of why it’s so popular,” she said.

The reasons for increased fracture risk following surgical weight loss remains unknown, according to Dr. Paccou, but they could include mechanical unloading, loss of lean mass, and hormone and nutrition changes. “There are many, many factors,” said Dr. Paccou, a professor of rheumatology at Hospital Roger Salengro in Lille, France.

The study’s findings of increased risk of fracture after sleeve gastrectomy may be an argument against malabsorption because the procedure shouldn’t affect nutrient absorption. It suggests that other factors are at play. “It’s not the only reason,” Dr. Schafer said.

There are recommendations for postbariatric surgery care to optimize bone health, such as protein intake and calcium and vitamin D targets, along with lifestyle factors. “Despite all those [efforts], we still know that bone loss occurs,” Dr. Koh said. In fact, the group is conducting a study funded by Amgen of the use of denosumab (Prolia) for the prevention of high-turnover bone loss after RYGB and sleeve gastrectomy.

Dr. Schafer has received research support from Bone Health Technologies and Amgen. Dr. Koh and Dr. Paccou have disclosed no relevant financial relationships.

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

VANCOUVER – Patients who undergo either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy are at an increased risk of fracture, compared with patients with obesity who do not undergo surgery, according to a new analysis of a predominantly male group of U.S. veterans.

Previous studies involving premenopausal women have found a risk of bone mineral density loss and fracture with bariatric surgery, but little was known about the risk among men. Research has also shown an increase in risk after RYGB, but there is less information on risks associated with sleeve gastrectomy, though it is now the most common surgery for weight loss.

Bone density loss after bariatric surgery has been shown to be significant, according to Eileen H. Koh, MD. “It’s quite a lot of bone loss, quickly,” said Dr. Koh, a graduated fellow from the endocrinology program at the University of California, San Francisco, who is moving to the University of Washington, Seattle.

Those observations generally come from studies of younger women. The purpose of the new study “was to see if we see the same risk of fracture in veterans who are older men, so kind of the opposite of the typical bariatric patient,” said Dr. Koh, who presented the research at the annual meeting of the American Society for Bone and Mineral Research.

The researchers analyzed data from 8,299 U.S. veterans who underwent sleeve gastrectomy (41%), RYGB (51%), adjustable gastric banding (4%), or an unspecified bariatric procedure (4%) between 2000 and 2020. They were matched with 24,877 individuals with obesity who did not undergo surgery. The investigators excluded individuals who were at high risk of fracture because of another condition, such as organ transplantation or dialysis. Men made up 70% of both surgical and nonsurgical groups. The mean age was 52 years for both, and 89% and 88% were not Hispanic or Latino, respectively. The proportion of White individuals was 72% and 64%, and the proportion of Black individuals was 18% and 24%.

After adjustment for demographic variables and comorbidities, bariatric surgery was associated with a 68% increased risk of fracture (hazard ratio, 1.68; 95% confidence interval, 1.57-1.80), including hip fractures (HR, 2.42; 95% CI, 1.98-2.97), spine (HR, 1.82; 95% CI, 1.61-2.06), radius/ulna (HR, 2.38; 95% CI, 2.05-2.77), humerus (HR, 1.56; 95% CI, 1.28-1.89), pelvis (HR, 2.41; 95% CI, 1.68-3.46), and tibia/fibula/ankle (HR, 1.50; 95% CI, 1.33-1.69). Increased fracture risk was associated with RYGB (HR, 1.93; 95% CI, 1.75-2.12) and sleeve gastrectomy (HR, 1.50; 95% CI, 1.33-1.69) but not adjustable gastric banding.

Compared with sleeve gastrectomy, adjustable gastric banding was associated with a decreased risk of fracture (HR, 0.64; 95% CI, 0.49-0.84; P = .0012).

The study’s predominantly male population is important because men also get osteoporosis and are frequently overlooked, according to Anne Schafer, MD, who was the lead author of the study. “Even after they fracture, men are sometimes less likely to get care to prevent the next fracture. We’ve shown here that especially men who are on the older side, who go through surgical weight loss, do have a higher risk of fracture compared to those who are similarly obese but have not had the operation,” said Dr. Schafer, a professor of medicine at the University of California, San Francisco, and chief of endocrinology and metabolism at the San Francisco VA Medical Center.

There are limited data on fracture risk after sleeve gastrectomy. “I think this is one of the first times that I’ve been able to demonstrate that there was a higher risk of fracture with sleeve gastrectomy in comparison with nonsurgical cohorts. Of course, it’s necessary to confirm these findings in further studies, but it’s interesting,” said Julien Paccou, MD, who attended the poster session and was asked for comment. His group’s study of a French population showed an increased fracture risk associated with RYGB but not sleeve gastrectomy. Another study found a reduction of fracture risk associated with sleeve gastrectomy and no difference between RYGB and nonsurgical matched control patients in a Medicare population.

In fact, there is a belief that fracture risk may be lower with sleeve gastrectomy, according to Dr. Schafer. “It’s part of why it’s so popular,” she said.

The reasons for increased fracture risk following surgical weight loss remains unknown, according to Dr. Paccou, but they could include mechanical unloading, loss of lean mass, and hormone and nutrition changes. “There are many, many factors,” said Dr. Paccou, a professor of rheumatology at Hospital Roger Salengro in Lille, France.

The study’s findings of increased risk of fracture after sleeve gastrectomy may be an argument against malabsorption because the procedure shouldn’t affect nutrient absorption. It suggests that other factors are at play. “It’s not the only reason,” Dr. Schafer said.

There are recommendations for postbariatric surgery care to optimize bone health, such as protein intake and calcium and vitamin D targets, along with lifestyle factors. “Despite all those [efforts], we still know that bone loss occurs,” Dr. Koh said. In fact, the group is conducting a study funded by Amgen of the use of denosumab (Prolia) for the prevention of high-turnover bone loss after RYGB and sleeve gastrectomy.

Dr. Schafer has received research support from Bone Health Technologies and Amgen. Dr. Koh and Dr. Paccou have disclosed no relevant financial relationships.

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

VANCOUVER – The use of tricyclic antidepressants (TCAs) conferred the highest risk for a new, first-time clinical fracture in people with type 2 diabetes with overweight or obesity, independent of any prevalent neuropathy, according to findings from an analysis of a large, randomized clinical trial.

Although the findings are suggestive, they don’t definitively pin blame on TCAs, said Rachel Elam, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research. “I think that there’s not enough information to conclude that tricyclic antidepressants directly lead to fractures, but I think it opens the door [to] something we should look into more. Is it being mediated by a better predictor, or is it the medication itself? I think it’s more hypothesis generating,” said Dr. Elam, an assistant professor of medicine in the division of rheumatology at the Medical College of Georgia, Augusta.

Patients with type 2 diabetes are known to be at increased risk of fracture, but prediction tools tend to underestimate this risk, Dr. Elam said. “Type 2 diabetes–specific clinical risk factors may be helpful for finding out fracture risk in this population,” Dr. Elam said during her talk.

Glycemic control is one candidate risk factor because advanced glycation end products are linked to reduced bone strength. Other factors include antidiabetic medication use, neuropathy, and microvascular disease, which has been linked to increased cortical porosity.

The study examined a somewhat younger population than previous surveys, having drawn from the Look AHEAD-C clinical trial, which examined the effects of an intensive lifestyle intervention on type 2 diabetes. Look AHEAD-C included 4,697 participants aged 45-75 from 16 U.S. clinical sites. Participants had a body mass index of 25.0 kg/m² or higher and hemoglobin A1c levels of 11% or below.

Dr. Elam cited the database’s inclusion of factors like A1c levels, renal parameters, and diabetic neuropathy. “It gave us a really good population to look at those risk factors” in a large group of people with type 2 diabetes, she said.

Over a median follow-up of 16.6 years, there were 649 participants with incident first clinical fracture(s). Statistically significant factors predicting fracture risk included TCA use (hazard ratio, 2.24; 95% confidence interval, 1.14-4.43), female gender (HR, 2.20; 95% CI, 1.83-2.66), insulin use (HR, 1.26; 95% CI, 1.02-1.57), increases in A1c level (per 1% increase: HR, 1.12; 95% CI, 1.04-1.20), age (HR, 1.02; 95% CI, 1.01-1.04), other or mixed race/ethnicity (HR, 0.68; 95% CI, 0.52-0.87), Hispanic White race/ethnicity (HR, 0.60; 95% CI, 0.39-0.91), non-Hispanic Black race/ethnicity (HR, 0.35; 95% CI, 0.26-0.47), and estrogen use (HR, 0.65; 95% CI, 0.44-0.98).

During the Q&A session following the presentation, Elsa Strotmeyer, PhD, commented that TCAs have been linked to central nervous system pathways in falls in other populations. “It’s a very nice study. It’s important to look at the diabetes complications related to the fracture risk, but I thought that they should have emphasized some more of the diabetes complications being related to fracture rather than these tricyclic antidepressants, because that is not a unique factor to that population,” said Dr. Strotmeyer, who is an associate professor of epidemiology at the University of Pittsburgh.

Instead, she noted a different strength of the study. “The study population is important because they’re a relatively young population with type 2 diabetes, compared to many studies [that] have been published in older populations. Showing similar things that we found in older populations was the unique piece and the important piece of this study,” Dr. Strotmeyer said.

Ultimately, the model wasn’t sufficient to be used as a fall risk predictor, but it should inform future work, according to Dr. Elam. “I think it does lay some new groundwork that when we’re looking forward, it may [help in building] other models to better predict fracture risk in type 2 diabetes. Things that would be important to include [in future models] would be medication use, such as tricyclic antidepressants,” and to make sure we include glycemic control, A1c, and insulin medication.

The study was independently funded. Dr. Elam and Dr. Strotmeyer report no relevant financial relationships.

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

VANCOUVER – The use of tricyclic antidepressants (TCAs) conferred the highest risk for a new, first-time clinical fracture in people with type 2 diabetes with overweight or obesity, independent of any prevalent neuropathy, according to findings from an analysis of a large, randomized clinical trial.

Although the findings are suggestive, they don’t definitively pin blame on TCAs, said Rachel Elam, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research. “I think that there’s not enough information to conclude that tricyclic antidepressants directly lead to fractures, but I think it opens the door [to] something we should look into more. Is it being mediated by a better predictor, or is it the medication itself? I think it’s more hypothesis generating,” said Dr. Elam, an assistant professor of medicine in the division of rheumatology at the Medical College of Georgia, Augusta.

Patients with type 2 diabetes are known to be at increased risk of fracture, but prediction tools tend to underestimate this risk, Dr. Elam said. “Type 2 diabetes–specific clinical risk factors may be helpful for finding out fracture risk in this population,” Dr. Elam said during her talk.

Glycemic control is one candidate risk factor because advanced glycation end products are linked to reduced bone strength. Other factors include antidiabetic medication use, neuropathy, and microvascular disease, which has been linked to increased cortical porosity.

The study examined a somewhat younger population than previous surveys, having drawn from the Look AHEAD-C clinical trial, which examined the effects of an intensive lifestyle intervention on type 2 diabetes. Look AHEAD-C included 4,697 participants aged 45-75 from 16 U.S. clinical sites. Participants had a body mass index of 25.0 kg/m² or higher and hemoglobin A1c levels of 11% or below.

Dr. Elam cited the database’s inclusion of factors like A1c levels, renal parameters, and diabetic neuropathy. “It gave us a really good population to look at those risk factors” in a large group of people with type 2 diabetes, she said.

Over a median follow-up of 16.6 years, there were 649 participants with incident first clinical fracture(s). Statistically significant factors predicting fracture risk included TCA use (hazard ratio, 2.24; 95% confidence interval, 1.14-4.43), female gender (HR, 2.20; 95% CI, 1.83-2.66), insulin use (HR, 1.26; 95% CI, 1.02-1.57), increases in A1c level (per 1% increase: HR, 1.12; 95% CI, 1.04-1.20), age (HR, 1.02; 95% CI, 1.01-1.04), other or mixed race/ethnicity (HR, 0.68; 95% CI, 0.52-0.87), Hispanic White race/ethnicity (HR, 0.60; 95% CI, 0.39-0.91), non-Hispanic Black race/ethnicity (HR, 0.35; 95% CI, 0.26-0.47), and estrogen use (HR, 0.65; 95% CI, 0.44-0.98).

During the Q&A session following the presentation, Elsa Strotmeyer, PhD, commented that TCAs have been linked to central nervous system pathways in falls in other populations. “It’s a very nice study. It’s important to look at the diabetes complications related to the fracture risk, but I thought that they should have emphasized some more of the diabetes complications being related to fracture rather than these tricyclic antidepressants, because that is not a unique factor to that population,” said Dr. Strotmeyer, who is an associate professor of epidemiology at the University of Pittsburgh.

Instead, she noted a different strength of the study. “The study population is important because they’re a relatively young population with type 2 diabetes, compared to many studies [that] have been published in older populations. Showing similar things that we found in older populations was the unique piece and the important piece of this study,” Dr. Strotmeyer said.

Ultimately, the model wasn’t sufficient to be used as a fall risk predictor, but it should inform future work, according to Dr. Elam. “I think it does lay some new groundwork that when we’re looking forward, it may [help in building] other models to better predict fracture risk in type 2 diabetes. Things that would be important to include [in future models] would be medication use, such as tricyclic antidepressants,” and to make sure we include glycemic control, A1c, and insulin medication.

The study was independently funded. Dr. Elam and Dr. Strotmeyer report no relevant financial relationships.

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

VANCOUVER – The use of tricyclic antidepressants (TCAs) conferred the highest risk for a new, first-time clinical fracture in people with type 2 diabetes with overweight or obesity, independent of any prevalent neuropathy, according to findings from an analysis of a large, randomized clinical trial.

Although the findings are suggestive, they don’t definitively pin blame on TCAs, said Rachel Elam, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research. “I think that there’s not enough information to conclude that tricyclic antidepressants directly lead to fractures, but I think it opens the door [to] something we should look into more. Is it being mediated by a better predictor, or is it the medication itself? I think it’s more hypothesis generating,” said Dr. Elam, an assistant professor of medicine in the division of rheumatology at the Medical College of Georgia, Augusta.

Patients with type 2 diabetes are known to be at increased risk of fracture, but prediction tools tend to underestimate this risk, Dr. Elam said. “Type 2 diabetes–specific clinical risk factors may be helpful for finding out fracture risk in this population,” Dr. Elam said during her talk.

Glycemic control is one candidate risk factor because advanced glycation end products are linked to reduced bone strength. Other factors include antidiabetic medication use, neuropathy, and microvascular disease, which has been linked to increased cortical porosity.

The study examined a somewhat younger population than previous surveys, having drawn from the Look AHEAD-C clinical trial, which examined the effects of an intensive lifestyle intervention on type 2 diabetes. Look AHEAD-C included 4,697 participants aged 45-75 from 16 U.S. clinical sites. Participants had a body mass index of 25.0 kg/m² or higher and hemoglobin A1c levels of 11% or below.

Dr. Elam cited the database’s inclusion of factors like A1c levels, renal parameters, and diabetic neuropathy. “It gave us a really good population to look at those risk factors” in a large group of people with type 2 diabetes, she said.

Over a median follow-up of 16.6 years, there were 649 participants with incident first clinical fracture(s). Statistically significant factors predicting fracture risk included TCA use (hazard ratio, 2.24; 95% confidence interval, 1.14-4.43), female gender (HR, 2.20; 95% CI, 1.83-2.66), insulin use (HR, 1.26; 95% CI, 1.02-1.57), increases in A1c level (per 1% increase: HR, 1.12; 95% CI, 1.04-1.20), age (HR, 1.02; 95% CI, 1.01-1.04), other or mixed race/ethnicity (HR, 0.68; 95% CI, 0.52-0.87), Hispanic White race/ethnicity (HR, 0.60; 95% CI, 0.39-0.91), non-Hispanic Black race/ethnicity (HR, 0.35; 95% CI, 0.26-0.47), and estrogen use (HR, 0.65; 95% CI, 0.44-0.98).

During the Q&A session following the presentation, Elsa Strotmeyer, PhD, commented that TCAs have been linked to central nervous system pathways in falls in other populations. “It’s a very nice study. It’s important to look at the diabetes complications related to the fracture risk, but I thought that they should have emphasized some more of the diabetes complications being related to fracture rather than these tricyclic antidepressants, because that is not a unique factor to that population,” said Dr. Strotmeyer, who is an associate professor of epidemiology at the University of Pittsburgh.

Instead, she noted a different strength of the study. “The study population is important because they’re a relatively young population with type 2 diabetes, compared to many studies [that] have been published in older populations. Showing similar things that we found in older populations was the unique piece and the important piece of this study,” Dr. Strotmeyer said.

Ultimately, the model wasn’t sufficient to be used as a fall risk predictor, but it should inform future work, according to Dr. Elam. “I think it does lay some new groundwork that when we’re looking forward, it may [help in building] other models to better predict fracture risk in type 2 diabetes. Things that would be important to include [in future models] would be medication use, such as tricyclic antidepressants,” and to make sure we include glycemic control, A1c, and insulin medication.

The study was independently funded. Dr. Elam and Dr. Strotmeyer report no relevant financial relationships.

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

The Food and Drug Administration has approved a topical combination of 1.2% clindamycin phosphate, 0.15% adapalene, and 3.1% benzoyl peroxide for the treatment of acne vulgaris in patients aged 12 years and older, according to a press release from the manufacturer.

The combination of an antibiotic, a retinoid, and an antibacterial in a gel formulation will be marketed as Cabtreo, and is expected to be available in the first quarter of 2024, according to Ortho Dermatologics.

The treatment was evaluated in a pair of phase 3 multicenter, randomized, controlled trials of 363 patients with moderate to severe acne, according to the company. Approximately 50% of patients across both studies met the primary endpoint of treatment success after 12 weeks of daily use, compared with 24.9% and 20.4% of placebo patients on vehicle in studies 1 and 2, respectively. Treatment success in both studies was defined as a reduction of at least two grades from baseline on the Evaluator’s Global Severity Score (EGSS) with scores of clear (0) or almost clear (1), and absolute change from baseline in both inflammatory and noninflammatory lesions. Patients were evaluated at 2, 4, 8, and 12 weeks.

Patients in the treatment groups for both studies had significantly greater absolute mean reductions in both inflammatory and noninflammatory lesions from baseline to week 12, compared with those in the vehicle group. The mean reductions with the treatment vs. vehicle were 75.7% vs. 59.6% and 72.7% vs. 47.6% for inflammatory and noninflammatory lesions, respectively, in study 1, and 80.1% vs. 56.2% and 73.3% vs. 49.0% for inflammatory and noninflammatory lesions, respectively, in study 2.

The most common adverse events were erythema, application-site reactions, pain, irritation, exfoliation, and dermatitis, all of which were more common in the treatment groups vs. the placebo groups.

The Food and Drug Administration has approved a topical combination of 1.2% clindamycin phosphate, 0.15% adapalene, and 3.1% benzoyl peroxide for the treatment of acne vulgaris in patients aged 12 years and older, according to a press release from the manufacturer.

The combination of an antibiotic, a retinoid, and an antibacterial in a gel formulation will be marketed as Cabtreo, and is expected to be available in the first quarter of 2024, according to Ortho Dermatologics.

The treatment was evaluated in a pair of phase 3 multicenter, randomized, controlled trials of 363 patients with moderate to severe acne, according to the company. Approximately 50% of patients across both studies met the primary endpoint of treatment success after 12 weeks of daily use, compared with 24.9% and 20.4% of placebo patients on vehicle in studies 1 and 2, respectively. Treatment success in both studies was defined as a reduction of at least two grades from baseline on the Evaluator’s Global Severity Score (EGSS) with scores of clear (0) or almost clear (1), and absolute change from baseline in both inflammatory and noninflammatory lesions. Patients were evaluated at 2, 4, 8, and 12 weeks.

Patients in the treatment groups for both studies had significantly greater absolute mean reductions in both inflammatory and noninflammatory lesions from baseline to week 12, compared with those in the vehicle group. The mean reductions with the treatment vs. vehicle were 75.7% vs. 59.6% and 72.7% vs. 47.6% for inflammatory and noninflammatory lesions, respectively, in study 1, and 80.1% vs. 56.2% and 73.3% vs. 49.0% for inflammatory and noninflammatory lesions, respectively, in study 2.

The most common adverse events were erythema, application-site reactions, pain, irritation, exfoliation, and dermatitis, all of which were more common in the treatment groups vs. the placebo groups.

The Food and Drug Administration has approved a topical combination of 1.2% clindamycin phosphate, 0.15% adapalene, and 3.1% benzoyl peroxide for the treatment of acne vulgaris in patients aged 12 years and older, according to a press release from the manufacturer.

The combination of an antibiotic, a retinoid, and an antibacterial in a gel formulation will be marketed as Cabtreo, and is expected to be available in the first quarter of 2024, according to Ortho Dermatologics.

The treatment was evaluated in a pair of phase 3 multicenter, randomized, controlled trials of 363 patients with moderate to severe acne, according to the company. Approximately 50% of patients across both studies met the primary endpoint of treatment success after 12 weeks of daily use, compared with 24.9% and 20.4% of placebo patients on vehicle in studies 1 and 2, respectively. Treatment success in both studies was defined as a reduction of at least two grades from baseline on the Evaluator’s Global Severity Score (EGSS) with scores of clear (0) or almost clear (1), and absolute change from baseline in both inflammatory and noninflammatory lesions. Patients were evaluated at 2, 4, 8, and 12 weeks.

Patients in the treatment groups for both studies had significantly greater absolute mean reductions in both inflammatory and noninflammatory lesions from baseline to week 12, compared with those in the vehicle group. The mean reductions with the treatment vs. vehicle were 75.7% vs. 59.6% and 72.7% vs. 47.6% for inflammatory and noninflammatory lesions, respectively, in study 1, and 80.1% vs. 56.2% and 73.3% vs. 49.0% for inflammatory and noninflammatory lesions, respectively, in study 2.

The most common adverse events were erythema, application-site reactions, pain, irritation, exfoliation, and dermatitis, all of which were more common in the treatment groups vs. the placebo groups.

New evidence shows for the first time that the virus that causes COVID directly infects atherosclerotic plaques in the coronary arteries, producing a persistent inflammatory response.

The findings may not only explain the link between COVID and the increased risk of cardiovascular events but mark a starting point for new therapeutic approaches.

“Our study shows there is persistence of viral debris in the artery,” senior investigator Chiara Giannarelli, MD, associate professor of medicine and pathology at NYU Langone Health, New York, said in an interview. “There is an important inflammatory response. We can now look at ways to control this inflammation,” she said.

Dr. Giannarelli says COVID is more than a respiratory virus and that it can affect the whole body. “Our study shows a remarkable ability of the virus to hijack the immune system,” she points out. “Our findings may explain how that happens.”

Dr. Giannarelli says it’s important for doctors and patients to be aware of an increased cardiovascular risk after a SARS-CoV-2 infection and to pay extra attention to traditional risk factors, such as blood pressure and cholesterol.

“This study showing that severe acute respiratory syndrome coronavirus directly infects coronary artery plaques, producing inflammatory substances, really joins the dots and helps our understanding on why we’re seeing so much heart disease in COVID patients,” Peter Hotez, MD, professor of molecular virology and microbiology at Baylor College of Medicine, Houston, said in an interview.

Asked whether this direct infection of vascular plaques was unique to SARS-CoV-2 or whether this may also occur with other viruses, both Dr. Giannarelli and Dr. Hotez said they believe this may be a specific COVID effect.

“I wouldn’t say it is likely that other viruses infect coronary arteries in this way, but I suppose it is possible,” Dr. Giannarelli said.

Dr. Hotez pointed out that other viruses can cause inflammation in the heart, such as myocarditis. “But I can’t think of another virus that stimulates the sequence of events in coronary artery inflammation like we’re seeing here.”

Dr. Giannarelli noted that influenza is also associated with an increased risk of cardiovascular events, but there has been no evidence to date that it directly affects coronary arteries.

Dr. Hotez added that the increased risk of cardiovascular events with influenza has also been reported to be prolonged after the acute infection. “These new findings with SARS-CoV-2 could stimulate a redoubling of efforts to look at this possibility with influenza,” he suggested.
 

Heart disease after COVID

In a recent article published online in Nature Cardiovascular Research, Dr. Giannarelli and colleagues analyzed human autopsy tissue samples from coronary arterial walls of patients who had died from COVID in the early stages of the pandemic in New York.

They found an accumulation of viral RNA in atherosclerotic plaques in the coronary arteries, which was particularly concentrated in lipid-rich macrophage foam cells present within the plaques.

“Our data conclusively demonstrate that severe acute respiratory syndrome coronavirus is capable of infecting and replicating in macrophages within the coronary vasculature,” the researchers report.

The virus preferentially replicates in foam cells, in comparison with other macrophages, they add, suggesting that these cells might act as a reservoir of viral debris in atherosclerotic plaque.

“We have shown that the virus is targeting lipid-rich macrophages in atherosclerotic lesions. This is the first time this has been shown, and we think this is a very important finding,” Dr. Giannarelli said in an interview.

“We also found that the virus persists in these foam cells that could be responsible for long-term, low-grade inflammation in the vasculature that could contribute to the long-term cardiovascular manifestations in patients who have recovered from COVID,” she said.
 

Viral reservoirs

Macrophages residing in vascular tissue can undergo self-renewal and can remain in the tissue for many years, the investigators point out. They suggest that these macrophages may act as viral reservoirs of SARS-CoV-2 RNA in atherosclerotic plaques.

Using an ex vivo model, the researchers also found that atherosclerotic tissue could be directly infected by the virus. And just as was seen in cultured macrophages and foam cells, infection of vascular tissue triggered an inflammatory response. That response induced the secretion of key proatherogenic cytokines, such as interleukin-6 and interleukin-1 beta, which have been implicated in the pathogenesis of atherosclerosis and in an increased risk of cardiovascular events.

“Considering that plaque inflammation promotes disease progression and contributes to plaque rupture, our results provide a molecular basis for how infection of coronary lesions can contribute to the acute cardiovascular manifestations of COVID-19, such as myocardial infarction,” the researchers report.

Another interesting finding was a higher accumulation of viral RNA in the coronary vasculature of the three patients with acute ischemic cardiovascular manifestations, which they say adds to evidence that infection may increase cardiovascular risk.

Dr. Giannarelli points out that the patients in their study died in New York early in the pandemic, before vaccines were available. “They were unvaccinated and likely had little immunity against initial viral strains.”

Dr. Hotez says that when COVID-19 first emerged, many in the medical and scientific communities thought it would closely resemble the original SARS viral infection, which was primarily a respiratory pathogen.

“But it became pretty clear early on this virus was causing a lot of cardiovascular and thromboembolic disease,” he says. “This study provides an insight into the mechanisms involved here.”
 

Affecting more than lungs

Dr. Hotez pointed out that a recent study reported a 5% increase in cardiovascular deaths during the years 2020-2022, compared with before the pandemic.

“Those peaks of cardiovascular deaths corresponded with specific waves of COVID – the first happening at the time of the initial wave with the original virus and second during the Delta wave. So, there’s no question that this virus is contributing to excess cardiovascular mortality, and this paper appears to explain the mechanism.”

Dr. Hotez pointed out that the new findings suggest the cardiovascular risk may be prolonged well after the acute infection resolves.

“In long COVID, a lot of people focus on the neurological effects – brain fog and depression. But cardiac insufficiency and other cardiovascular events can also be considered another element of long COVID,” he said.

Dr. Giannarelli says her group is now studying whether patients with long COVID have virus in their coronary arteries. She points out that the current studies were a result of a team effort between experts in cardiovascular disease and virology and infectious disease. “We need to collaborate more like this to understand better the impact of viral infection in patients and the clinical manifestations,” she said.

Dr. Hotez says he believes these new findings will have implications for the future.

“COVID hasn’t gone away. The numbers have been going up again steadily in the U.S. in the last few months. There are still a significant number of hospitalizations,” he said.

While it would be unwieldy to ask for a cardiology consult for every COVID patient, he acknowledged, “there is probably a subset of people – possibly those of older age and who have had a severe case of COVID – who we suspect are now going to be more prone to cardiovascular disease because of having COVID.

“We should be vigilant in looking for cardiovascular disease in these patients,” Dr. Hotez said, “and perhaps be a bit more aggressive about controlling their cardiovascular risk factors.”

The study was funded by the U.S. National Institutes of Health, the American Heart Association, and the Chan Zuckerberg Initiative.

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

New evidence shows for the first time that the virus that causes COVID directly infects atherosclerotic plaques in the coronary arteries, producing a persistent inflammatory response.

The findings may not only explain the link between COVID and the increased risk of cardiovascular events but mark a starting point for new therapeutic approaches.

“Our study shows there is persistence of viral debris in the artery,” senior investigator Chiara Giannarelli, MD, associate professor of medicine and pathology at NYU Langone Health, New York, said in an interview. “There is an important inflammatory response. We can now look at ways to control this inflammation,” she said.

Dr. Giannarelli says COVID is more than a respiratory virus and that it can affect the whole body. “Our study shows a remarkable ability of the virus to hijack the immune system,” she points out. “Our findings may explain how that happens.”

Dr. Giannarelli says it’s important for doctors and patients to be aware of an increased cardiovascular risk after a SARS-CoV-2 infection and to pay extra attention to traditional risk factors, such as blood pressure and cholesterol.

“This study showing that severe acute respiratory syndrome coronavirus directly infects coronary artery plaques, producing inflammatory substances, really joins the dots and helps our understanding on why we’re seeing so much heart disease in COVID patients,” Peter Hotez, MD, professor of molecular virology and microbiology at Baylor College of Medicine, Houston, said in an interview.

Asked whether this direct infection of vascular plaques was unique to SARS-CoV-2 or whether this may also occur with other viruses, both Dr. Giannarelli and Dr. Hotez said they believe this may be a specific COVID effect.

“I wouldn’t say it is likely that other viruses infect coronary arteries in this way, but I suppose it is possible,” Dr. Giannarelli said.

Dr. Hotez pointed out that other viruses can cause inflammation in the heart, such as myocarditis. “But I can’t think of another virus that stimulates the sequence of events in coronary artery inflammation like we’re seeing here.”

Dr. Giannarelli noted that influenza is also associated with an increased risk of cardiovascular events, but there has been no evidence to date that it directly affects coronary arteries.

Dr. Hotez added that the increased risk of cardiovascular events with influenza has also been reported to be prolonged after the acute infection. “These new findings with SARS-CoV-2 could stimulate a redoubling of efforts to look at this possibility with influenza,” he suggested.
 

Heart disease after COVID

In a recent article published online in Nature Cardiovascular Research, Dr. Giannarelli and colleagues analyzed human autopsy tissue samples from coronary arterial walls of patients who had died from COVID in the early stages of the pandemic in New York.

They found an accumulation of viral RNA in atherosclerotic plaques in the coronary arteries, which was particularly concentrated in lipid-rich macrophage foam cells present within the plaques.

“Our data conclusively demonstrate that severe acute respiratory syndrome coronavirus is capable of infecting and replicating in macrophages within the coronary vasculature,” the researchers report.

The virus preferentially replicates in foam cells, in comparison with other macrophages, they add, suggesting that these cells might act as a reservoir of viral debris in atherosclerotic plaque.

“We have shown that the virus is targeting lipid-rich macrophages in atherosclerotic lesions. This is the first time this has been shown, and we think this is a very important finding,” Dr. Giannarelli said in an interview.

“We also found that the virus persists in these foam cells that could be responsible for long-term, low-grade inflammation in the vasculature that could contribute to the long-term cardiovascular manifestations in patients who have recovered from COVID,” she said.
 

Viral reservoirs

Macrophages residing in vascular tissue can undergo self-renewal and can remain in the tissue for many years, the investigators point out. They suggest that these macrophages may act as viral reservoirs of SARS-CoV-2 RNA in atherosclerotic plaques.

Using an ex vivo model, the researchers also found that atherosclerotic tissue could be directly infected by the virus. And just as was seen in cultured macrophages and foam cells, infection of vascular tissue triggered an inflammatory response. That response induced the secretion of key proatherogenic cytokines, such as interleukin-6 and interleukin-1 beta, which have been implicated in the pathogenesis of atherosclerosis and in an increased risk of cardiovascular events.

“Considering that plaque inflammation promotes disease progression and contributes to plaque rupture, our results provide a molecular basis for how infection of coronary lesions can contribute to the acute cardiovascular manifestations of COVID-19, such as myocardial infarction,” the researchers report.

Another interesting finding was a higher accumulation of viral RNA in the coronary vasculature of the three patients with acute ischemic cardiovascular manifestations, which they say adds to evidence that infection may increase cardiovascular risk.

Dr. Giannarelli points out that the patients in their study died in New York early in the pandemic, before vaccines were available. “They were unvaccinated and likely had little immunity against initial viral strains.”

Dr. Hotez says that when COVID-19 first emerged, many in the medical and scientific communities thought it would closely resemble the original SARS viral infection, which was primarily a respiratory pathogen.

“But it became pretty clear early on this virus was causing a lot of cardiovascular and thromboembolic disease,” he says. “This study provides an insight into the mechanisms involved here.”
 

Affecting more than lungs

Dr. Hotez pointed out that a recent study reported a 5% increase in cardiovascular deaths during the years 2020-2022, compared with before the pandemic.

“Those peaks of cardiovascular deaths corresponded with specific waves of COVID – the first happening at the time of the initial wave with the original virus and second during the Delta wave. So, there’s no question that this virus is contributing to excess cardiovascular mortality, and this paper appears to explain the mechanism.”

Dr. Hotez pointed out that the new findings suggest the cardiovascular risk may be prolonged well after the acute infection resolves.

“In long COVID, a lot of people focus on the neurological effects – brain fog and depression. But cardiac insufficiency and other cardiovascular events can also be considered another element of long COVID,” he said.

Dr. Giannarelli says her group is now studying whether patients with long COVID have virus in their coronary arteries. She points out that the current studies were a result of a team effort between experts in cardiovascular disease and virology and infectious disease. “We need to collaborate more like this to understand better the impact of viral infection in patients and the clinical manifestations,” she said.

Dr. Hotez says he believes these new findings will have implications for the future.

“COVID hasn’t gone away. The numbers have been going up again steadily in the U.S. in the last few months. There are still a significant number of hospitalizations,” he said.

While it would be unwieldy to ask for a cardiology consult for every COVID patient, he acknowledged, “there is probably a subset of people – possibly those of older age and who have had a severe case of COVID – who we suspect are now going to be more prone to cardiovascular disease because of having COVID.

“We should be vigilant in looking for cardiovascular disease in these patients,” Dr. Hotez said, “and perhaps be a bit more aggressive about controlling their cardiovascular risk factors.”

The study was funded by the U.S. National Institutes of Health, the American Heart Association, and the Chan Zuckerberg Initiative.

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

New evidence shows for the first time that the virus that causes COVID directly infects atherosclerotic plaques in the coronary arteries, producing a persistent inflammatory response.

The findings may not only explain the link between COVID and the increased risk of cardiovascular events but mark a starting point for new therapeutic approaches.

“Our study shows there is persistence of viral debris in the artery,” senior investigator Chiara Giannarelli, MD, associate professor of medicine and pathology at NYU Langone Health, New York, said in an interview. “There is an important inflammatory response. We can now look at ways to control this inflammation,” she said.

Dr. Giannarelli says COVID is more than a respiratory virus and that it can affect the whole body. “Our study shows a remarkable ability of the virus to hijack the immune system,” she points out. “Our findings may explain how that happens.”

Dr. Giannarelli says it’s important for doctors and patients to be aware of an increased cardiovascular risk after a SARS-CoV-2 infection and to pay extra attention to traditional risk factors, such as blood pressure and cholesterol.

“This study showing that severe acute respiratory syndrome coronavirus directly infects coronary artery plaques, producing inflammatory substances, really joins the dots and helps our understanding on why we’re seeing so much heart disease in COVID patients,” Peter Hotez, MD, professor of molecular virology and microbiology at Baylor College of Medicine, Houston, said in an interview.

Asked whether this direct infection of vascular plaques was unique to SARS-CoV-2 or whether this may also occur with other viruses, both Dr. Giannarelli and Dr. Hotez said they believe this may be a specific COVID effect.

“I wouldn’t say it is likely that other viruses infect coronary arteries in this way, but I suppose it is possible,” Dr. Giannarelli said.

Dr. Hotez pointed out that other viruses can cause inflammation in the heart, such as myocarditis. “But I can’t think of another virus that stimulates the sequence of events in coronary artery inflammation like we’re seeing here.”

Dr. Giannarelli noted that influenza is also associated with an increased risk of cardiovascular events, but there has been no evidence to date that it directly affects coronary arteries.

Dr. Hotez added that the increased risk of cardiovascular events with influenza has also been reported to be prolonged after the acute infection. “These new findings with SARS-CoV-2 could stimulate a redoubling of efforts to look at this possibility with influenza,” he suggested.
 

Heart disease after COVID

In a recent article published online in Nature Cardiovascular Research, Dr. Giannarelli and colleagues analyzed human autopsy tissue samples from coronary arterial walls of patients who had died from COVID in the early stages of the pandemic in New York.

They found an accumulation of viral RNA in atherosclerotic plaques in the coronary arteries, which was particularly concentrated in lipid-rich macrophage foam cells present within the plaques.

“Our data conclusively demonstrate that severe acute respiratory syndrome coronavirus is capable of infecting and replicating in macrophages within the coronary vasculature,” the researchers report.

The virus preferentially replicates in foam cells, in comparison with other macrophages, they add, suggesting that these cells might act as a reservoir of viral debris in atherosclerotic plaque.

“We have shown that the virus is targeting lipid-rich macrophages in atherosclerotic lesions. This is the first time this has been shown, and we think this is a very important finding,” Dr. Giannarelli said in an interview.

“We also found that the virus persists in these foam cells that could be responsible for long-term, low-grade inflammation in the vasculature that could contribute to the long-term cardiovascular manifestations in patients who have recovered from COVID,” she said.
 

Viral reservoirs

Macrophages residing in vascular tissue can undergo self-renewal and can remain in the tissue for many years, the investigators point out. They suggest that these macrophages may act as viral reservoirs of SARS-CoV-2 RNA in atherosclerotic plaques.

Using an ex vivo model, the researchers also found that atherosclerotic tissue could be directly infected by the virus. And just as was seen in cultured macrophages and foam cells, infection of vascular tissue triggered an inflammatory response. That response induced the secretion of key proatherogenic cytokines, such as interleukin-6 and interleukin-1 beta, which have been implicated in the pathogenesis of atherosclerosis and in an increased risk of cardiovascular events.

“Considering that plaque inflammation promotes disease progression and contributes to plaque rupture, our results provide a molecular basis for how infection of coronary lesions can contribute to the acute cardiovascular manifestations of COVID-19, such as myocardial infarction,” the researchers report.

Another interesting finding was a higher accumulation of viral RNA in the coronary vasculature of the three patients with acute ischemic cardiovascular manifestations, which they say adds to evidence that infection may increase cardiovascular risk.

Dr. Giannarelli points out that the patients in their study died in New York early in the pandemic, before vaccines were available. “They were unvaccinated and likely had little immunity against initial viral strains.”

Dr. Hotez says that when COVID-19 first emerged, many in the medical and scientific communities thought it would closely resemble the original SARS viral infection, which was primarily a respiratory pathogen.

“But it became pretty clear early on this virus was causing a lot of cardiovascular and thromboembolic disease,” he says. “This study provides an insight into the mechanisms involved here.”
 

Affecting more than lungs

Dr. Hotez pointed out that a recent study reported a 5% increase in cardiovascular deaths during the years 2020-2022, compared with before the pandemic.

“Those peaks of cardiovascular deaths corresponded with specific waves of COVID – the first happening at the time of the initial wave with the original virus and second during the Delta wave. So, there’s no question that this virus is contributing to excess cardiovascular mortality, and this paper appears to explain the mechanism.”

Dr. Hotez pointed out that the new findings suggest the cardiovascular risk may be prolonged well after the acute infection resolves.

“In long COVID, a lot of people focus on the neurological effects – brain fog and depression. But cardiac insufficiency and other cardiovascular events can also be considered another element of long COVID,” he said.

Dr. Giannarelli says her group is now studying whether patients with long COVID have virus in their coronary arteries. She points out that the current studies were a result of a team effort between experts in cardiovascular disease and virology and infectious disease. “We need to collaborate more like this to understand better the impact of viral infection in patients and the clinical manifestations,” she said.

Dr. Hotez says he believes these new findings will have implications for the future.

“COVID hasn’t gone away. The numbers have been going up again steadily in the U.S. in the last few months. There are still a significant number of hospitalizations,” he said.

While it would be unwieldy to ask for a cardiology consult for every COVID patient, he acknowledged, “there is probably a subset of people – possibly those of older age and who have had a severe case of COVID – who we suspect are now going to be more prone to cardiovascular disease because of having COVID.

“We should be vigilant in looking for cardiovascular disease in these patients,” Dr. Hotez said, “and perhaps be a bit more aggressive about controlling their cardiovascular risk factors.”

The study was funded by the U.S. National Institutes of Health, the American Heart Association, and the Chan Zuckerberg Initiative.

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

BERLIN – A novel regulatory T cell–stimulating therapy appears to significantly improve atopic dermatitis in patients with moderate to severe disease and may even benefit quality of life, suggest results from a phase 1b trial.

The research was presented at the annual congress of the European Academy of Dermatology and Venereology.

More than 40 patients were randomly assigned to receive one of two dosages of a highly selective recombinant interleukin (IL)-2 conjugate, rezpegaldesleukin, or placebo for 12 weeks, after which responders were observed out to 48 weeks. The higher dosage was associated with significant improvements in Eczema Area and Severity Index (EASI) and Body Surface Area (BSA) scores, which were maintained over the course of the study, as well as trends for improved patient-reported outcomes.

“This is the first study to demonstrate the therapeutic potential of rezpegaldesleukin,” said presenter Jonathan Silverberg, MD, PhD, MPH, professor of dermatology and director of clinical research at George Washington University, Washington. He added, “These may be some of the most compelling data to date for the field, proving that, at a high level, if you causally increase regulator T cells, you will take down inflammation and improve a disease state.

“For me, this is proof of concept for so many things, and it gets me very excited.”

Dr. Silverberg noted that with the response maintained out to 48 weeks, despite stopping therapy at week 12, the “hope” with the approach of inducing regulator T cells “is that we could induce tolerance and that we could have some potential for disease modification.”

He continued, “Maybe I daren’t use the word ‘cure,’ but can we at least get to something that is truly remitted, where they can stop the drug and maintain that response?”

Dr. Silverberg said rezpegaldesleukin is now being evaluated in a phase 2b study for moderate to severe atopic dermatitis, and a phase 2b trial for alopecia areata is in development.

Tiago dos Reis Matos, MD, PhD, MSc, Amsterdam University Medical Centers, who was not involved in the study, told this news organization that “recombinant human interleukin-2 is an original therapy.”

Instead of blocking or inhibiting inflammation, it stimulates the patient’s immune system to “restore a healthy balance.”

He explained that it “stimulates regulatory T cells, which can be seen as the Peace Corps of the immune system, responsible for maintaining the equilibrium and avoiding uncontrolled inflammation.”

At the meeting, Dr. Silverberg told the audience that although they are the “beneficiaries of riches of new advances” in atopic dermatitis, “still, many observational studies have shown that the majority of patients do not achieve adequate control by the end of their induction periods and clinical trials, in the real world,” with currently available treatments.

Moreover, “there are challenges that come up with any of the different therapies,” he said, with adverse effects an important issue. For example, biologic therapies are associated with conjunctivitis, facial erythema, and arthralgia, and there are boxed warnings for Janus kinase inhibitors.

Dr. Silverberg continued, “Even patients with a favorable response can experience a loss of disease control when they come off therapy.” Consequently, “new strategies are certainly welcome that could potentially induce both deep and potentially therapy-free remission.”

To those ends, he explained that regulatory T cells play a central role in immune homeostasis but have not been “therapeutically relevant until very recently,” when it was posited that increasing their function can “induce that homeostasis, to normalize the inflammatory cascades” seen in a range of conditions, including atopic dermatitis.

Rezpegaldesleukin has high selectivity for regulatory T cells, without causing activation of effector T cells, and has been shown to increase cell numbers in a dose-dependent manner that is sustained for up to 30 days.

The current study involved patients aged 18-70 years with moderate to severe atopic dermatitis and a history of inadequate responses or intolerance to topical medications, and an EASI score ≥ 16.

Participants were randomly assigned to receive subcutaneous rezpegaldesleukin 12 mcg/kg or 24 mcg/kg or placebo every 2 weeks for 12 weeks. They then discontinued treatment and were followed up until week 19, when responders, defined as having a reduction in EASI score ≥ 50%, continued follow-up out to week 48.

Seventeen patients were randomized to higher-dose rezpegaldesleukin, whereas 16 received the lower dose and 10 were assigned to placebo. Dr. Silverberg said that the three groups were “fairly well balanced,” with “fairly good representation” across age, race, and ethnicity groups.

The mean baseline EASI score was between 21.9 and 23.7, and the Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) suggested that there was an even split between moderate and severe atopic dermatitis, although the higher-dose rezpegaldesleukin group had more patients with moderate disease.

By week 12, rezpegaldesleukin was associated with significantly greater improvements in EASI scores vs. placebo. Patients on the higher dose had a mean 83% improvement over baseline vs. 65% with the lower dose and 47% with placebo (P = .002 for the higher dose vs. placebo).

Crucially, these differences were maintained up to week 48 in patients, particularly in the higher-dose group.

There was also a nonsignificant increase in the proportion of patients who achieved a reduction in EASI scores ≥ 75% over baseline with the active drug: 41% at week 12 with higher-dose rezpegaldesleukin, 25% with the lower dose, and 20% with placebo. Again, the benefit was maintained up to week 48.

The mean improvement in BSA score from baseline with rezpegaldesleukin was significantly greater than that seen with placebo, at 72% with the higher dose, 55% with the lower dose, and 36% with placebo (P = .0158 for the higher dose vs. placebo).

Although improvements in vIGA-AD scores over baseline with rezpegaldesleukin were not substantial at week 12, by week 48 there was a marked difference between higher-dose rezpegaldesleukin and placebo, with 40.0% of patients responding to the drug vs. 0% in the latter group.

A similar pattern was seen for the Itch Numeric Rating Scale, in which 55.6% of patients treated with higher-dose rezpegaldesleukin responding by week 48, compared with 0% of those who received placebo.

Greater improvements in the Dermatology Life Quality Index (DLQI) and Patient Oriented Eczema Measure (POEM) over baseline with higher-dose rezpegaldesleukin vs. plain placebo were also noted, despite a strong response in the latter group.

Dr. Silverberg reported that all treatment-emergent adverse effects in the two rezpegaldesleukin treatment arms were mild to moderate, with no severe or serious events observed.

The most common adverse events were mild to moderate injection-site reactions, seen in 75.0% of the lower-dose rezpegaldesleukin group and 58.8% the of higher-dose group. There were no cases of conjunctivitis.

The study was sponsored by Eli Lilly and Company in collaboration with Nektar Therapeutics.

Dr. Silverberg declares relationships with AbbVie, Alamar, Aldena, Amgen, AOBiome, Arcutis, Arena, Asana, ASLAN, BioMX, Biosion, Bodewell, Boehringer-Ingelheim, Bristol-Myers Squibb, Cara, Castle Biosciences, Celgene, Connect Biopharma, CorEvitas, Dermavant, DermTech, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, LEO Pharma, Nektar, Novartis, Optum, Pfizer, RAPT, Recludix, Regeneron, Sanofi-Genzyme, Shaperon, Target RWE, Union, and UpToDate.

A version of this article appeared on Medscape.com.

BERLIN – A novel regulatory T cell–stimulating therapy appears to significantly improve atopic dermatitis in patients with moderate to severe disease and may even benefit quality of life, suggest results from a phase 1b trial.

The research was presented at the annual congress of the European Academy of Dermatology and Venereology.

More than 40 patients were randomly assigned to receive one of two dosages of a highly selective recombinant interleukin (IL)-2 conjugate, rezpegaldesleukin, or placebo for 12 weeks, after which responders were observed out to 48 weeks. The higher dosage was associated with significant improvements in Eczema Area and Severity Index (EASI) and Body Surface Area (BSA) scores, which were maintained over the course of the study, as well as trends for improved patient-reported outcomes.

“This is the first study to demonstrate the therapeutic potential of rezpegaldesleukin,” said presenter Jonathan Silverberg, MD, PhD, MPH, professor of dermatology and director of clinical research at George Washington University, Washington. He added, “These may be some of the most compelling data to date for the field, proving that, at a high level, if you causally increase regulator T cells, you will take down inflammation and improve a disease state.

“For me, this is proof of concept for so many things, and it gets me very excited.”

Dr. Silverberg noted that with the response maintained out to 48 weeks, despite stopping therapy at week 12, the “hope” with the approach of inducing regulator T cells “is that we could induce tolerance and that we could have some potential for disease modification.”

He continued, “Maybe I daren’t use the word ‘cure,’ but can we at least get to something that is truly remitted, where they can stop the drug and maintain that response?”

Dr. Silverberg said rezpegaldesleukin is now being evaluated in a phase 2b study for moderate to severe atopic dermatitis, and a phase 2b trial for alopecia areata is in development.

Tiago dos Reis Matos, MD, PhD, MSc, Amsterdam University Medical Centers, who was not involved in the study, told this news organization that “recombinant human interleukin-2 is an original therapy.”

Instead of blocking or inhibiting inflammation, it stimulates the patient’s immune system to “restore a healthy balance.”

He explained that it “stimulates regulatory T cells, which can be seen as the Peace Corps of the immune system, responsible for maintaining the equilibrium and avoiding uncontrolled inflammation.”

At the meeting, Dr. Silverberg told the audience that although they are the “beneficiaries of riches of new advances” in atopic dermatitis, “still, many observational studies have shown that the majority of patients do not achieve adequate control by the end of their induction periods and clinical trials, in the real world,” with currently available treatments.

Moreover, “there are challenges that come up with any of the different therapies,” he said, with adverse effects an important issue. For example, biologic therapies are associated with conjunctivitis, facial erythema, and arthralgia, and there are boxed warnings for Janus kinase inhibitors.

Dr. Silverberg continued, “Even patients with a favorable response can experience a loss of disease control when they come off therapy.” Consequently, “new strategies are certainly welcome that could potentially induce both deep and potentially therapy-free remission.”

To those ends, he explained that regulatory T cells play a central role in immune homeostasis but have not been “therapeutically relevant until very recently,” when it was posited that increasing their function can “induce that homeostasis, to normalize the inflammatory cascades” seen in a range of conditions, including atopic dermatitis.

Rezpegaldesleukin has high selectivity for regulatory T cells, without causing activation of effector T cells, and has been shown to increase cell numbers in a dose-dependent manner that is sustained for up to 30 days.

The current study involved patients aged 18-70 years with moderate to severe atopic dermatitis and a history of inadequate responses or intolerance to topical medications, and an EASI score ≥ 16.

Participants were randomly assigned to receive subcutaneous rezpegaldesleukin 12 mcg/kg or 24 mcg/kg or placebo every 2 weeks for 12 weeks. They then discontinued treatment and were followed up until week 19, when responders, defined as having a reduction in EASI score ≥ 50%, continued follow-up out to week 48.

Seventeen patients were randomized to higher-dose rezpegaldesleukin, whereas 16 received the lower dose and 10 were assigned to placebo. Dr. Silverberg said that the three groups were “fairly well balanced,” with “fairly good representation” across age, race, and ethnicity groups.

The mean baseline EASI score was between 21.9 and 23.7, and the Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) suggested that there was an even split between moderate and severe atopic dermatitis, although the higher-dose rezpegaldesleukin group had more patients with moderate disease.

By week 12, rezpegaldesleukin was associated with significantly greater improvements in EASI scores vs. placebo. Patients on the higher dose had a mean 83% improvement over baseline vs. 65% with the lower dose and 47% with placebo (P = .002 for the higher dose vs. placebo).

Crucially, these differences were maintained up to week 48 in patients, particularly in the higher-dose group.

There was also a nonsignificant increase in the proportion of patients who achieved a reduction in EASI scores ≥ 75% over baseline with the active drug: 41% at week 12 with higher-dose rezpegaldesleukin, 25% with the lower dose, and 20% with placebo. Again, the benefit was maintained up to week 48.

The mean improvement in BSA score from baseline with rezpegaldesleukin was significantly greater than that seen with placebo, at 72% with the higher dose, 55% with the lower dose, and 36% with placebo (P = .0158 for the higher dose vs. placebo).

Although improvements in vIGA-AD scores over baseline with rezpegaldesleukin were not substantial at week 12, by week 48 there was a marked difference between higher-dose rezpegaldesleukin and placebo, with 40.0% of patients responding to the drug vs. 0% in the latter group.

A similar pattern was seen for the Itch Numeric Rating Scale, in which 55.6% of patients treated with higher-dose rezpegaldesleukin responding by week 48, compared with 0% of those who received placebo.

Greater improvements in the Dermatology Life Quality Index (DLQI) and Patient Oriented Eczema Measure (POEM) over baseline with higher-dose rezpegaldesleukin vs. plain placebo were also noted, despite a strong response in the latter group.

Dr. Silverberg reported that all treatment-emergent adverse effects in the two rezpegaldesleukin treatment arms were mild to moderate, with no severe or serious events observed.

The most common adverse events were mild to moderate injection-site reactions, seen in 75.0% of the lower-dose rezpegaldesleukin group and 58.8% the of higher-dose group. There were no cases of conjunctivitis.

The study was sponsored by Eli Lilly and Company in collaboration with Nektar Therapeutics.

Dr. Silverberg declares relationships with AbbVie, Alamar, Aldena, Amgen, AOBiome, Arcutis, Arena, Asana, ASLAN, BioMX, Biosion, Bodewell, Boehringer-Ingelheim, Bristol-Myers Squibb, Cara, Castle Biosciences, Celgene, Connect Biopharma, CorEvitas, Dermavant, DermTech, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, LEO Pharma, Nektar, Novartis, Optum, Pfizer, RAPT, Recludix, Regeneron, Sanofi-Genzyme, Shaperon, Target RWE, Union, and UpToDate.

A version of this article appeared on Medscape.com.

BERLIN – A novel regulatory T cell–stimulating therapy appears to significantly improve atopic dermatitis in patients with moderate to severe disease and may even benefit quality of life, suggest results from a phase 1b trial.

The research was presented at the annual congress of the European Academy of Dermatology and Venereology.

More than 40 patients were randomly assigned to receive one of two dosages of a highly selective recombinant interleukin (IL)-2 conjugate, rezpegaldesleukin, or placebo for 12 weeks, after which responders were observed out to 48 weeks. The higher dosage was associated with significant improvements in Eczema Area and Severity Index (EASI) and Body Surface Area (BSA) scores, which were maintained over the course of the study, as well as trends for improved patient-reported outcomes.

“This is the first study to demonstrate the therapeutic potential of rezpegaldesleukin,” said presenter Jonathan Silverberg, MD, PhD, MPH, professor of dermatology and director of clinical research at George Washington University, Washington. He added, “These may be some of the most compelling data to date for the field, proving that, at a high level, if you causally increase regulator T cells, you will take down inflammation and improve a disease state.

“For me, this is proof of concept for so many things, and it gets me very excited.”

Dr. Silverberg noted that with the response maintained out to 48 weeks, despite stopping therapy at week 12, the “hope” with the approach of inducing regulator T cells “is that we could induce tolerance and that we could have some potential for disease modification.”

He continued, “Maybe I daren’t use the word ‘cure,’ but can we at least get to something that is truly remitted, where they can stop the drug and maintain that response?”

Dr. Silverberg said rezpegaldesleukin is now being evaluated in a phase 2b study for moderate to severe atopic dermatitis, and a phase 2b trial for alopecia areata is in development.

Tiago dos Reis Matos, MD, PhD, MSc, Amsterdam University Medical Centers, who was not involved in the study, told this news organization that “recombinant human interleukin-2 is an original therapy.”

Instead of blocking or inhibiting inflammation, it stimulates the patient’s immune system to “restore a healthy balance.”

He explained that it “stimulates regulatory T cells, which can be seen as the Peace Corps of the immune system, responsible for maintaining the equilibrium and avoiding uncontrolled inflammation.”

At the meeting, Dr. Silverberg told the audience that although they are the “beneficiaries of riches of new advances” in atopic dermatitis, “still, many observational studies have shown that the majority of patients do not achieve adequate control by the end of their induction periods and clinical trials, in the real world,” with currently available treatments.

Moreover, “there are challenges that come up with any of the different therapies,” he said, with adverse effects an important issue. For example, biologic therapies are associated with conjunctivitis, facial erythema, and arthralgia, and there are boxed warnings for Janus kinase inhibitors.

Dr. Silverberg continued, “Even patients with a favorable response can experience a loss of disease control when they come off therapy.” Consequently, “new strategies are certainly welcome that could potentially induce both deep and potentially therapy-free remission.”

To those ends, he explained that regulatory T cells play a central role in immune homeostasis but have not been “therapeutically relevant until very recently,” when it was posited that increasing their function can “induce that homeostasis, to normalize the inflammatory cascades” seen in a range of conditions, including atopic dermatitis.

Rezpegaldesleukin has high selectivity for regulatory T cells, without causing activation of effector T cells, and has been shown to increase cell numbers in a dose-dependent manner that is sustained for up to 30 days.

The current study involved patients aged 18-70 years with moderate to severe atopic dermatitis and a history of inadequate responses or intolerance to topical medications, and an EASI score ≥ 16.

Participants were randomly assigned to receive subcutaneous rezpegaldesleukin 12 mcg/kg or 24 mcg/kg or placebo every 2 weeks for 12 weeks. They then discontinued treatment and were followed up until week 19, when responders, defined as having a reduction in EASI score ≥ 50%, continued follow-up out to week 48.

Seventeen patients were randomized to higher-dose rezpegaldesleukin, whereas 16 received the lower dose and 10 were assigned to placebo. Dr. Silverberg said that the three groups were “fairly well balanced,” with “fairly good representation” across age, race, and ethnicity groups.

The mean baseline EASI score was between 21.9 and 23.7, and the Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) suggested that there was an even split between moderate and severe atopic dermatitis, although the higher-dose rezpegaldesleukin group had more patients with moderate disease.

By week 12, rezpegaldesleukin was associated with significantly greater improvements in EASI scores vs. placebo. Patients on the higher dose had a mean 83% improvement over baseline vs. 65% with the lower dose and 47% with placebo (P = .002 for the higher dose vs. placebo).

Crucially, these differences were maintained up to week 48 in patients, particularly in the higher-dose group.

There was also a nonsignificant increase in the proportion of patients who achieved a reduction in EASI scores ≥ 75% over baseline with the active drug: 41% at week 12 with higher-dose rezpegaldesleukin, 25% with the lower dose, and 20% with placebo. Again, the benefit was maintained up to week 48.

The mean improvement in BSA score from baseline with rezpegaldesleukin was significantly greater than that seen with placebo, at 72% with the higher dose, 55% with the lower dose, and 36% with placebo (P = .0158 for the higher dose vs. placebo).

Although improvements in vIGA-AD scores over baseline with rezpegaldesleukin were not substantial at week 12, by week 48 there was a marked difference between higher-dose rezpegaldesleukin and placebo, with 40.0% of patients responding to the drug vs. 0% in the latter group.

A similar pattern was seen for the Itch Numeric Rating Scale, in which 55.6% of patients treated with higher-dose rezpegaldesleukin responding by week 48, compared with 0% of those who received placebo.

Greater improvements in the Dermatology Life Quality Index (DLQI) and Patient Oriented Eczema Measure (POEM) over baseline with higher-dose rezpegaldesleukin vs. plain placebo were also noted, despite a strong response in the latter group.

Dr. Silverberg reported that all treatment-emergent adverse effects in the two rezpegaldesleukin treatment arms were mild to moderate, with no severe or serious events observed.

The most common adverse events were mild to moderate injection-site reactions, seen in 75.0% of the lower-dose rezpegaldesleukin group and 58.8% the of higher-dose group. There were no cases of conjunctivitis.

The study was sponsored by Eli Lilly and Company in collaboration with Nektar Therapeutics.

Dr. Silverberg declares relationships with AbbVie, Alamar, Aldena, Amgen, AOBiome, Arcutis, Arena, Asana, ASLAN, BioMX, Biosion, Bodewell, Boehringer-Ingelheim, Bristol-Myers Squibb, Cara, Castle Biosciences, Celgene, Connect Biopharma, CorEvitas, Dermavant, DermTech, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, LEO Pharma, Nektar, Novartis, Optum, Pfizer, RAPT, Recludix, Regeneron, Sanofi-Genzyme, Shaperon, Target RWE, Union, and UpToDate.

A version of this article appeared on Medscape.com.