Clinician Reviews

A new statement from the Endocrine Society on hormones and aging highlights the differences between normal aging and disease, and when treatment is and isn’t appropriate.

The idea of the statement “is to be complete, but also to clarify some misunderstandings. ...We tried to be very clear in the language about what we know, where we can go, where we shouldn’t go, and what we still need to learn,” statement coauthor Cynthia A. Stuenkel, MD, of the University of California, San Diego, said in an interview.

The document is divided into nine parts or axes: growth hormone, adrenal, ovarian, testicular, thyroid, osteoporosis, vitamin D deficiency, type 2 diabetes, and water metabolism. Each section covers natural history and observational data in older individuals, available therapies, clinical trial data on efficacy and safety in older individuals, bulleted “key points,” and research gaps.

“Hormones and Aging: An Endocrine Society Scientific Statement” was presented at the annual meeting of the Endocrine Society and published online in the Journal of Clinical Endocrinology & Metabolism.

During a press briefing, writing group chair Anne R. Cappola, MD, of the University of Pennsylvania, Philadelphia, said the goal is to “provide a really concise summary across each of these areas. ... There are multiple hormonal changes that occur with age, so we really couldn’t limit ourselves to just one gland or the few that we commonly think about. We wanted to cover all the axes.”

The statement tackles several controversial areas, including hormone therapy for menopausal symptoms in women and hypogonadal symptoms in men, diabetes treatment goals in older adults, distinguishing between age-associated changes in thyroid function and early hypothyroidism, and vitamin D supplementation in older adults.

“Hormones have these almost mythical qualities to some people. ... ‘If I just had my hormones back the way they were, it would all work out.’ What we want to do is make sure that patients are being treated appropriately and that their symptoms are being heard and managed and ascribed to the appropriate problems and not necessarily to hormonal problems when they are not. ... Part of what we need to do is [provide] the evidence that we have, which includes evidence of when not to prescribe as well as [when] to prescribe,” Dr. Cappola said.
 

Not designed to be read all at once

In the menopause section, for example, one “key point” is that menopausal symptoms are common, vary in degree and bother, and can be effectively treated with a variety of therapies proven effective in randomized clinical trials. Another key point is that menopausal hormone therapy is safest for women who are younger than 60 years and less than 10 years since starting menopause.

“It’s almost 20 years since the original Women’s Health Initiative, and that led to an incredible falloff of prescribing hormone therapy and a falloff in teaching of our students, residents, fellows, and practitioners about [menopausal] hormone therapy. ... Hopefully, by issuing this kind of aging statement it gets people to read, think, and learn more. And, hopefully, we can improve the education of physicians. ... Menopause is a universal experience. Clinicians should know about it,” noted Dr. Stuenkel, who chaired the menopause section writing panel.

In the type 2 diabetes section, in the bullet points it is noted that oral glucose tolerance testing may reveal abnormal glucose status in older adults that are not picked up with hemoglobin A1c or fasting glucose levels and that glycemic targets should be individualized.

Asked to comment on the statement, Michele Bellantoni, MD, said: “This was a huge undertaking because there are so many areas of expertise here. I thought they did a very good job of reviewing the literature and showing each of the different hormonal axes. ... It’s a good go-to review.”  

“I thought it was a very good attempt to catalog and provide opportunities for policy, and particularly at [the National Institutes of Health], as they look at funding to show where are these gaps and to support appropriate research. I think the most important aspect to come of this is identifying research gaps for funding opportunities. I very much support that,” noted Dr. Bellantoni, who is clinical director of the division of geriatric medicine at Johns Hopkins University, Baltimore.

However, she also said that the 40-page document might be a bit much for busy clinicians, despite the bullet points at the end of each section.

“I would love to see an editorial that puts into perspective the take-home messages or a subsequent article that distills this into every day practice of care of older adults, both preventative and treatment care. ... I think that would be so useful.”

During the briefing, Dr. Cappola noted that the document need not be read all at once.

“It ended up being a large document, but you should not be intimidated by it because each section is only about 2,000 words. So, it’s really a kind of one-stop shop to be able to look across all these axes at once. We also wanted people to think about the common themes that occur across all these axes when considering what’s going on right now and for future research,” she said.

Dr. Stuenkel, Dr. Cappola, and Dr. Bellantoni reported no relevant financial relationships.

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

A new statement from the Endocrine Society on hormones and aging highlights the differences between normal aging and disease, and when treatment is and isn’t appropriate.

The idea of the statement “is to be complete, but also to clarify some misunderstandings. ...We tried to be very clear in the language about what we know, where we can go, where we shouldn’t go, and what we still need to learn,” statement coauthor Cynthia A. Stuenkel, MD, of the University of California, San Diego, said in an interview.

The document is divided into nine parts or axes: growth hormone, adrenal, ovarian, testicular, thyroid, osteoporosis, vitamin D deficiency, type 2 diabetes, and water metabolism. Each section covers natural history and observational data in older individuals, available therapies, clinical trial data on efficacy and safety in older individuals, bulleted “key points,” and research gaps.

“Hormones and Aging: An Endocrine Society Scientific Statement” was presented at the annual meeting of the Endocrine Society and published online in the Journal of Clinical Endocrinology & Metabolism.

During a press briefing, writing group chair Anne R. Cappola, MD, of the University of Pennsylvania, Philadelphia, said the goal is to “provide a really concise summary across each of these areas. ... There are multiple hormonal changes that occur with age, so we really couldn’t limit ourselves to just one gland or the few that we commonly think about. We wanted to cover all the axes.”

The statement tackles several controversial areas, including hormone therapy for menopausal symptoms in women and hypogonadal symptoms in men, diabetes treatment goals in older adults, distinguishing between age-associated changes in thyroid function and early hypothyroidism, and vitamin D supplementation in older adults.

“Hormones have these almost mythical qualities to some people. ... ‘If I just had my hormones back the way they were, it would all work out.’ What we want to do is make sure that patients are being treated appropriately and that their symptoms are being heard and managed and ascribed to the appropriate problems and not necessarily to hormonal problems when they are not. ... Part of what we need to do is [provide] the evidence that we have, which includes evidence of when not to prescribe as well as [when] to prescribe,” Dr. Cappola said.
 

Not designed to be read all at once

In the menopause section, for example, one “key point” is that menopausal symptoms are common, vary in degree and bother, and can be effectively treated with a variety of therapies proven effective in randomized clinical trials. Another key point is that menopausal hormone therapy is safest for women who are younger than 60 years and less than 10 years since starting menopause.

“It’s almost 20 years since the original Women’s Health Initiative, and that led to an incredible falloff of prescribing hormone therapy and a falloff in teaching of our students, residents, fellows, and practitioners about [menopausal] hormone therapy. ... Hopefully, by issuing this kind of aging statement it gets people to read, think, and learn more. And, hopefully, we can improve the education of physicians. ... Menopause is a universal experience. Clinicians should know about it,” noted Dr. Stuenkel, who chaired the menopause section writing panel.

In the type 2 diabetes section, in the bullet points it is noted that oral glucose tolerance testing may reveal abnormal glucose status in older adults that are not picked up with hemoglobin A1c or fasting glucose levels and that glycemic targets should be individualized.

Asked to comment on the statement, Michele Bellantoni, MD, said: “This was a huge undertaking because there are so many areas of expertise here. I thought they did a very good job of reviewing the literature and showing each of the different hormonal axes. ... It’s a good go-to review.”  

“I thought it was a very good attempt to catalog and provide opportunities for policy, and particularly at [the National Institutes of Health], as they look at funding to show where are these gaps and to support appropriate research. I think the most important aspect to come of this is identifying research gaps for funding opportunities. I very much support that,” noted Dr. Bellantoni, who is clinical director of the division of geriatric medicine at Johns Hopkins University, Baltimore.

However, she also said that the 40-page document might be a bit much for busy clinicians, despite the bullet points at the end of each section.

“I would love to see an editorial that puts into perspective the take-home messages or a subsequent article that distills this into every day practice of care of older adults, both preventative and treatment care. ... I think that would be so useful.”

During the briefing, Dr. Cappola noted that the document need not be read all at once.

“It ended up being a large document, but you should not be intimidated by it because each section is only about 2,000 words. So, it’s really a kind of one-stop shop to be able to look across all these axes at once. We also wanted people to think about the common themes that occur across all these axes when considering what’s going on right now and for future research,” she said.

Dr. Stuenkel, Dr. Cappola, and Dr. Bellantoni reported no relevant financial relationships.

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

A new statement from the Endocrine Society on hormones and aging highlights the differences between normal aging and disease, and when treatment is and isn’t appropriate.

The idea of the statement “is to be complete, but also to clarify some misunderstandings. ...We tried to be very clear in the language about what we know, where we can go, where we shouldn’t go, and what we still need to learn,” statement coauthor Cynthia A. Stuenkel, MD, of the University of California, San Diego, said in an interview.

The document is divided into nine parts or axes: growth hormone, adrenal, ovarian, testicular, thyroid, osteoporosis, vitamin D deficiency, type 2 diabetes, and water metabolism. Each section covers natural history and observational data in older individuals, available therapies, clinical trial data on efficacy and safety in older individuals, bulleted “key points,” and research gaps.

“Hormones and Aging: An Endocrine Society Scientific Statement” was presented at the annual meeting of the Endocrine Society and published online in the Journal of Clinical Endocrinology & Metabolism.

During a press briefing, writing group chair Anne R. Cappola, MD, of the University of Pennsylvania, Philadelphia, said the goal is to “provide a really concise summary across each of these areas. ... There are multiple hormonal changes that occur with age, so we really couldn’t limit ourselves to just one gland or the few that we commonly think about. We wanted to cover all the axes.”

The statement tackles several controversial areas, including hormone therapy for menopausal symptoms in women and hypogonadal symptoms in men, diabetes treatment goals in older adults, distinguishing between age-associated changes in thyroid function and early hypothyroidism, and vitamin D supplementation in older adults.

“Hormones have these almost mythical qualities to some people. ... ‘If I just had my hormones back the way they were, it would all work out.’ What we want to do is make sure that patients are being treated appropriately and that their symptoms are being heard and managed and ascribed to the appropriate problems and not necessarily to hormonal problems when they are not. ... Part of what we need to do is [provide] the evidence that we have, which includes evidence of when not to prescribe as well as [when] to prescribe,” Dr. Cappola said.
 

Not designed to be read all at once

In the menopause section, for example, one “key point” is that menopausal symptoms are common, vary in degree and bother, and can be effectively treated with a variety of therapies proven effective in randomized clinical trials. Another key point is that menopausal hormone therapy is safest for women who are younger than 60 years and less than 10 years since starting menopause.

“It’s almost 20 years since the original Women’s Health Initiative, and that led to an incredible falloff of prescribing hormone therapy and a falloff in teaching of our students, residents, fellows, and practitioners about [menopausal] hormone therapy. ... Hopefully, by issuing this kind of aging statement it gets people to read, think, and learn more. And, hopefully, we can improve the education of physicians. ... Menopause is a universal experience. Clinicians should know about it,” noted Dr. Stuenkel, who chaired the menopause section writing panel.

In the type 2 diabetes section, in the bullet points it is noted that oral glucose tolerance testing may reveal abnormal glucose status in older adults that are not picked up with hemoglobin A1c or fasting glucose levels and that glycemic targets should be individualized.

Asked to comment on the statement, Michele Bellantoni, MD, said: “This was a huge undertaking because there are so many areas of expertise here. I thought they did a very good job of reviewing the literature and showing each of the different hormonal axes. ... It’s a good go-to review.”  

“I thought it was a very good attempt to catalog and provide opportunities for policy, and particularly at [the National Institutes of Health], as they look at funding to show where are these gaps and to support appropriate research. I think the most important aspect to come of this is identifying research gaps for funding opportunities. I very much support that,” noted Dr. Bellantoni, who is clinical director of the division of geriatric medicine at Johns Hopkins University, Baltimore.

However, she also said that the 40-page document might be a bit much for busy clinicians, despite the bullet points at the end of each section.

“I would love to see an editorial that puts into perspective the take-home messages or a subsequent article that distills this into every day practice of care of older adults, both preventative and treatment care. ... I think that would be so useful.”

During the briefing, Dr. Cappola noted that the document need not be read all at once.

“It ended up being a large document, but you should not be intimidated by it because each section is only about 2,000 words. So, it’s really a kind of one-stop shop to be able to look across all these axes at once. We also wanted people to think about the common themes that occur across all these axes when considering what’s going on right now and for future research,” she said.

Dr. Stuenkel, Dr. Cappola, and Dr. Bellantoni reported no relevant financial relationships.

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

Given current driving restrictions after syncope, visits to the emergency department for syncope are not significantly associated with increased risk for a subsequent car crash, data suggest.

In a case-crossover study that examined health and driving data for about 3,000 drivers in British Columbia, researchers found similar rates of ED visits for syncope before the dates of car crashes (1.6%) and before control dates (1.2%).

“An emergency visit for syncope did not appear to increase the risk of subsequent traffic crash,” lead author John A. Staples, MD, MPH, clinical associate professor of general internal medicine at the University of British Columbia, Vancouver, said in an interview.

The findings were published online in the Canadian Journal of Cardiology.
 

Case-crossover study

Syncope prompts more than 1 million visits to EDs in the United States each year. About 9% of patients with syncope have recurrence within 1 year.

Some jurisdictions legally require clinicians to advise patients at higher risk for syncope recurrence to stop driving temporarily. But guidelines about when and whom to restrict are not standardized, said Dr. Staples.

“I came to this topic because I work as a physician in a hospital and, a few years ago, I advised a young woman who suffered a serious injury after she passed out while driving and crashed her car,” he added. “She wanted to know if she could drive again and when. I found out that there wasn’t much evidence that could guide my advice to her. That is what planted the seed that eventually grew into this study.”

The researchers examined driving data from the Insurance Corporation of British Columbia and detailed ED visit data from regional health authorities. They included licensed drivers who were diagnosed with syncope and collapse at an ED between 2010 and 2015 in their study. The researchers focused on eligible participants who were involved in a motor vehicle collision between August 2011 and December 2015.

For each patient, the date of the crash was used to establish three control dates without crashes. The control dates were 26 weeks, 52 weeks, and 78 weeks before the crash. The investigators compared the rate of emergency visit for syncope in the 28 days before the crash with the rate of emergency visit for syncope in the 28 days before each control date.

An emergency visit for syncope occurred in 47 of 3,026 precrash intervals and 112 of 9,078 control intervals. This result indicated that syncope was not significantly associated with subsequent crash (adjusted odds ratio, 1.27; P = .18).

In addition, there was no significant association between syncope and crash in subgroups considered to be at higher risk for adverse outcomes after syncope, such as patients older than 65 years and patients with cardiovascular disease or cardiac syncope.
 

Gaps in data

“It’s a complicated study design but one that’s helpful to understand the temporal relationship between syncope and crash,” said Dr. Staples. “If we had found that the syncope visit was more likely to occur in the 4 weeks before the crash than in earlier matched 4-week control periods, we would have concluded that syncope transiently increases crash risk.”

Dr. Staples emphasized that this was a real-world study and that some patients with syncope at higher risk for a car crash likely stopped driving. “This study doesn’t say there’s no relationship between syncope and subsequent crash, just that our current practices, including current driving restrictions, seem to do an acceptable job of preventing some crashes.”

Limitations of the study influence the interpretation of the results. For example, the data sources did not indicate how patients modified their driving, said Dr. Staples.

Also lacking is information about how physicians identified which patients were at heightened risk for another syncope episode and advised those patients not to drive. “Now would be a good time to start to think about what other studies are needed to better tailor driving restrictions for the right patient,” said Dr. Staples.
 

‘A messy situation’

In a comment, Deepak L. Bhatt, MD, MPH, professor of cardiovascular medicine at Icahn School of Medicine at Mount Sinai, New York, called the conclusions “well thought out.” He said the study addressed a common, often perplexing problem in a practical way. Dr. Bhatt was not involved in the research.

“This study is trying to address the issue of what to do with people who have had syncope or fainting and have had a car crash. In general, we don’t really know what to do with those people, but there’s a lot of concern for many reasons, for both the patient and the public. There are potential legal liabilities, and the whole thing, generally speaking, tends to be a messy situation. Usually, the default position physicians take is to be very cautious and conservative, and restrict driving,” said Dr. Bhatt.

The study is reassuring, he added. “The authors have contextualized this risk very nicely. Physicians worry a lot about patients who have had an episode of syncope while driving and restrict their patients’ driving, at least temporarily. But as a society, we are much more permissive about people who drive drunk or under the influence, or who drive without seat belts, or who speed, or text while driving. So, within that larger context, we are extremely worried about this one source of risk that is probably less than these other sources of risk.”

Most of the time, the cause of the syncope is benign, said Dr. Bhatt. “We rule out the bad things, like a heart attack or cardiac arrest, seizure, and arrhythmia. Afterwards, the risk from driving is relatively small.” The study results support current practices and suggest “that we probably don’t need to be excessive with our restrictions.

“There is going to be a wide variation in practice, with some physicians wanting to be more restrictive, but there is a lot of subjectivity in how these recommendations are acted on in real life. That’s why I think this study really should reassure physicians that it’s okay to use common sense and good medical judgment when giving advice on driving to their patients,” Dr. Bhatt concluded.

The study was supported by the Canadian Institutes of Health Research and the Heart and Stroke Foundation Canada. Dr. Staples and Dr. Bhatt reported no relevant financial relationships.

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

Given current driving restrictions after syncope, visits to the emergency department for syncope are not significantly associated with increased risk for a subsequent car crash, data suggest.

In a case-crossover study that examined health and driving data for about 3,000 drivers in British Columbia, researchers found similar rates of ED visits for syncope before the dates of car crashes (1.6%) and before control dates (1.2%).

“An emergency visit for syncope did not appear to increase the risk of subsequent traffic crash,” lead author John A. Staples, MD, MPH, clinical associate professor of general internal medicine at the University of British Columbia, Vancouver, said in an interview.

The findings were published online in the Canadian Journal of Cardiology.
 

Case-crossover study

Syncope prompts more than 1 million visits to EDs in the United States each year. About 9% of patients with syncope have recurrence within 1 year.

Some jurisdictions legally require clinicians to advise patients at higher risk for syncope recurrence to stop driving temporarily. But guidelines about when and whom to restrict are not standardized, said Dr. Staples.

“I came to this topic because I work as a physician in a hospital and, a few years ago, I advised a young woman who suffered a serious injury after she passed out while driving and crashed her car,” he added. “She wanted to know if she could drive again and when. I found out that there wasn’t much evidence that could guide my advice to her. That is what planted the seed that eventually grew into this study.”

The researchers examined driving data from the Insurance Corporation of British Columbia and detailed ED visit data from regional health authorities. They included licensed drivers who were diagnosed with syncope and collapse at an ED between 2010 and 2015 in their study. The researchers focused on eligible participants who were involved in a motor vehicle collision between August 2011 and December 2015.

For each patient, the date of the crash was used to establish three control dates without crashes. The control dates were 26 weeks, 52 weeks, and 78 weeks before the crash. The investigators compared the rate of emergency visit for syncope in the 28 days before the crash with the rate of emergency visit for syncope in the 28 days before each control date.

An emergency visit for syncope occurred in 47 of 3,026 precrash intervals and 112 of 9,078 control intervals. This result indicated that syncope was not significantly associated with subsequent crash (adjusted odds ratio, 1.27; P = .18).

In addition, there was no significant association between syncope and crash in subgroups considered to be at higher risk for adverse outcomes after syncope, such as patients older than 65 years and patients with cardiovascular disease or cardiac syncope.
 

Gaps in data

“It’s a complicated study design but one that’s helpful to understand the temporal relationship between syncope and crash,” said Dr. Staples. “If we had found that the syncope visit was more likely to occur in the 4 weeks before the crash than in earlier matched 4-week control periods, we would have concluded that syncope transiently increases crash risk.”

Dr. Staples emphasized that this was a real-world study and that some patients with syncope at higher risk for a car crash likely stopped driving. “This study doesn’t say there’s no relationship between syncope and subsequent crash, just that our current practices, including current driving restrictions, seem to do an acceptable job of preventing some crashes.”

Limitations of the study influence the interpretation of the results. For example, the data sources did not indicate how patients modified their driving, said Dr. Staples.

Also lacking is information about how physicians identified which patients were at heightened risk for another syncope episode and advised those patients not to drive. “Now would be a good time to start to think about what other studies are needed to better tailor driving restrictions for the right patient,” said Dr. Staples.
 

‘A messy situation’

In a comment, Deepak L. Bhatt, MD, MPH, professor of cardiovascular medicine at Icahn School of Medicine at Mount Sinai, New York, called the conclusions “well thought out.” He said the study addressed a common, often perplexing problem in a practical way. Dr. Bhatt was not involved in the research.

“This study is trying to address the issue of what to do with people who have had syncope or fainting and have had a car crash. In general, we don’t really know what to do with those people, but there’s a lot of concern for many reasons, for both the patient and the public. There are potential legal liabilities, and the whole thing, generally speaking, tends to be a messy situation. Usually, the default position physicians take is to be very cautious and conservative, and restrict driving,” said Dr. Bhatt.

The study is reassuring, he added. “The authors have contextualized this risk very nicely. Physicians worry a lot about patients who have had an episode of syncope while driving and restrict their patients’ driving, at least temporarily. But as a society, we are much more permissive about people who drive drunk or under the influence, or who drive without seat belts, or who speed, or text while driving. So, within that larger context, we are extremely worried about this one source of risk that is probably less than these other sources of risk.”

Most of the time, the cause of the syncope is benign, said Dr. Bhatt. “We rule out the bad things, like a heart attack or cardiac arrest, seizure, and arrhythmia. Afterwards, the risk from driving is relatively small.” The study results support current practices and suggest “that we probably don’t need to be excessive with our restrictions.

“There is going to be a wide variation in practice, with some physicians wanting to be more restrictive, but there is a lot of subjectivity in how these recommendations are acted on in real life. That’s why I think this study really should reassure physicians that it’s okay to use common sense and good medical judgment when giving advice on driving to their patients,” Dr. Bhatt concluded.

The study was supported by the Canadian Institutes of Health Research and the Heart and Stroke Foundation Canada. Dr. Staples and Dr. Bhatt reported no relevant financial relationships.

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

Given current driving restrictions after syncope, visits to the emergency department for syncope are not significantly associated with increased risk for a subsequent car crash, data suggest.

In a case-crossover study that examined health and driving data for about 3,000 drivers in British Columbia, researchers found similar rates of ED visits for syncope before the dates of car crashes (1.6%) and before control dates (1.2%).

“An emergency visit for syncope did not appear to increase the risk of subsequent traffic crash,” lead author John A. Staples, MD, MPH, clinical associate professor of general internal medicine at the University of British Columbia, Vancouver, said in an interview.

The findings were published online in the Canadian Journal of Cardiology.
 

Case-crossover study

Syncope prompts more than 1 million visits to EDs in the United States each year. About 9% of patients with syncope have recurrence within 1 year.

Some jurisdictions legally require clinicians to advise patients at higher risk for syncope recurrence to stop driving temporarily. But guidelines about when and whom to restrict are not standardized, said Dr. Staples.

“I came to this topic because I work as a physician in a hospital and, a few years ago, I advised a young woman who suffered a serious injury after she passed out while driving and crashed her car,” he added. “She wanted to know if she could drive again and when. I found out that there wasn’t much evidence that could guide my advice to her. That is what planted the seed that eventually grew into this study.”

The researchers examined driving data from the Insurance Corporation of British Columbia and detailed ED visit data from regional health authorities. They included licensed drivers who were diagnosed with syncope and collapse at an ED between 2010 and 2015 in their study. The researchers focused on eligible participants who were involved in a motor vehicle collision between August 2011 and December 2015.

For each patient, the date of the crash was used to establish three control dates without crashes. The control dates were 26 weeks, 52 weeks, and 78 weeks before the crash. The investigators compared the rate of emergency visit for syncope in the 28 days before the crash with the rate of emergency visit for syncope in the 28 days before each control date.

An emergency visit for syncope occurred in 47 of 3,026 precrash intervals and 112 of 9,078 control intervals. This result indicated that syncope was not significantly associated with subsequent crash (adjusted odds ratio, 1.27; P = .18).

In addition, there was no significant association between syncope and crash in subgroups considered to be at higher risk for adverse outcomes after syncope, such as patients older than 65 years and patients with cardiovascular disease or cardiac syncope.
 

Gaps in data

“It’s a complicated study design but one that’s helpful to understand the temporal relationship between syncope and crash,” said Dr. Staples. “If we had found that the syncope visit was more likely to occur in the 4 weeks before the crash than in earlier matched 4-week control periods, we would have concluded that syncope transiently increases crash risk.”

Dr. Staples emphasized that this was a real-world study and that some patients with syncope at higher risk for a car crash likely stopped driving. “This study doesn’t say there’s no relationship between syncope and subsequent crash, just that our current practices, including current driving restrictions, seem to do an acceptable job of preventing some crashes.”

Limitations of the study influence the interpretation of the results. For example, the data sources did not indicate how patients modified their driving, said Dr. Staples.

Also lacking is information about how physicians identified which patients were at heightened risk for another syncope episode and advised those patients not to drive. “Now would be a good time to start to think about what other studies are needed to better tailor driving restrictions for the right patient,” said Dr. Staples.
 

‘A messy situation’

In a comment, Deepak L. Bhatt, MD, MPH, professor of cardiovascular medicine at Icahn School of Medicine at Mount Sinai, New York, called the conclusions “well thought out.” He said the study addressed a common, often perplexing problem in a practical way. Dr. Bhatt was not involved in the research.

“This study is trying to address the issue of what to do with people who have had syncope or fainting and have had a car crash. In general, we don’t really know what to do with those people, but there’s a lot of concern for many reasons, for both the patient and the public. There are potential legal liabilities, and the whole thing, generally speaking, tends to be a messy situation. Usually, the default position physicians take is to be very cautious and conservative, and restrict driving,” said Dr. Bhatt.

The study is reassuring, he added. “The authors have contextualized this risk very nicely. Physicians worry a lot about patients who have had an episode of syncope while driving and restrict their patients’ driving, at least temporarily. But as a society, we are much more permissive about people who drive drunk or under the influence, or who drive without seat belts, or who speed, or text while driving. So, within that larger context, we are extremely worried about this one source of risk that is probably less than these other sources of risk.”

Most of the time, the cause of the syncope is benign, said Dr. Bhatt. “We rule out the bad things, like a heart attack or cardiac arrest, seizure, and arrhythmia. Afterwards, the risk from driving is relatively small.” The study results support current practices and suggest “that we probably don’t need to be excessive with our restrictions.

“There is going to be a wide variation in practice, with some physicians wanting to be more restrictive, but there is a lot of subjectivity in how these recommendations are acted on in real life. That’s why I think this study really should reassure physicians that it’s okay to use common sense and good medical judgment when giving advice on driving to their patients,” Dr. Bhatt concluded.

The study was supported by the Canadian Institutes of Health Research and the Heart and Stroke Foundation Canada. Dr. Staples and Dr. Bhatt reported no relevant financial relationships.

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

CHICAGO – Twice as many U.S. adults have obesity based on assessment of their fat volume by dual-energy X-ray absorptiometry (DEXA) scan compared with measurement of body mass index (BMI), a finding that highlights the shortcomings of BMI and adds to the growing case that BMI alone should not be the default gauge for obesity.

“BMI vastly underestimates true obesity,” Aayush Visaria, MD, said at the annual meeting of the Endocrine Society.

His findings highlight that “BMI should be supplemented with other measures of obesity” for the management of individual patients, with assessments that could include a bioelectrical impedance scale or waist circumference, said Dr. Visaria, a researcher at Rutgers Robert Wood Johnson Medical School in New Brunswick, N.J.

Dr. Visaria cited a new policy issued by the American Medical Association a couple of days before his presentation, which advises that BMI “be used in conjunction with other valid measures of risk such as, but not limited to, measurements of visceral fat, body adiposity index, body composition, relative fat mass, waist circumference, and genetic/metabolic factors.”

“We’re at the start of the end of BMI,” Dr. Visaria declared during a press briefing at the meeting.

He said DEXA is not practical or cost-effective for obesity screening in routine practice. Therefore, he predicts that waist circumference, often expressed as waist-to-height ratio, will be measured more often, although he acknowledged that waist measurement can be difficult. However, better physician training on the measure should help it become the norm.

Another useful tool for obesity measurement he foresees quickly becoming widespread is bathroom scales that record both weight and body fat percentage using a small electric current to make a bioelectrical impedance measure of adiposity.

Bioimpedance scales will provide more standardized measurements than waist circumference and “revolutionize how we measure obesity,” Dr. Visaria predicted. They are “very accessible and cheap,” he noted, with many models sold for less than $100.
 

Obesity prevalence of 74%

The study by Dr. Visaria and colleagues used data from 9,784 U.S. adults aged 20-59 years (average age, 39 years) collected in several National Health and Nutrition Examination Surveys during 2011-2018. All these participants underwent DEXA assessment of their total body fat as well as a BMI calculation.

Using standard obesity cutoffs for both BMI and total body fat, Dr. Visaria found that DEXA rated 74% of participants as having obesity based on body fat compared with 36% based on BMI.

Among the 64% of the study group who were not obese by BMI, DEXA scans showed 53% of this subgroup did have obesity based on body fat content. Among those with a normal BMI, 43% had obesity by DEXA result.

Further analysis showed that when Dr. Visaria added waist circumference to BMI to enlarge the diagnostic net for obesity it cut the percentage of adults missed as having obesity by BMI alone nearly in half.

Additional analyses showed that the rate of missed diagnoses of obesity by BMI was most common only among people of Hispanic or Asian ethnicity, with both groups showing a 49% rate of obesity by DEXA among those with normal-range BMIs.

The rate of missed obesity diagnoses was highest among all women, with a 59% prevalence of obesity by DEXA among women with a normal-range BMI.

The study received no commercial funding. Dr. Visaria has reported no relevant financial relationships.

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

CHICAGO – Twice as many U.S. adults have obesity based on assessment of their fat volume by dual-energy X-ray absorptiometry (DEXA) scan compared with measurement of body mass index (BMI), a finding that highlights the shortcomings of BMI and adds to the growing case that BMI alone should not be the default gauge for obesity.

“BMI vastly underestimates true obesity,” Aayush Visaria, MD, said at the annual meeting of the Endocrine Society.

His findings highlight that “BMI should be supplemented with other measures of obesity” for the management of individual patients, with assessments that could include a bioelectrical impedance scale or waist circumference, said Dr. Visaria, a researcher at Rutgers Robert Wood Johnson Medical School in New Brunswick, N.J.

Dr. Visaria cited a new policy issued by the American Medical Association a couple of days before his presentation, which advises that BMI “be used in conjunction with other valid measures of risk such as, but not limited to, measurements of visceral fat, body adiposity index, body composition, relative fat mass, waist circumference, and genetic/metabolic factors.”

“We’re at the start of the end of BMI,” Dr. Visaria declared during a press briefing at the meeting.

He said DEXA is not practical or cost-effective for obesity screening in routine practice. Therefore, he predicts that waist circumference, often expressed as waist-to-height ratio, will be measured more often, although he acknowledged that waist measurement can be difficult. However, better physician training on the measure should help it become the norm.

Another useful tool for obesity measurement he foresees quickly becoming widespread is bathroom scales that record both weight and body fat percentage using a small electric current to make a bioelectrical impedance measure of adiposity.

Bioimpedance scales will provide more standardized measurements than waist circumference and “revolutionize how we measure obesity,” Dr. Visaria predicted. They are “very accessible and cheap,” he noted, with many models sold for less than $100.
 

Obesity prevalence of 74%

The study by Dr. Visaria and colleagues used data from 9,784 U.S. adults aged 20-59 years (average age, 39 years) collected in several National Health and Nutrition Examination Surveys during 2011-2018. All these participants underwent DEXA assessment of their total body fat as well as a BMI calculation.

Using standard obesity cutoffs for both BMI and total body fat, Dr. Visaria found that DEXA rated 74% of participants as having obesity based on body fat compared with 36% based on BMI.

Among the 64% of the study group who were not obese by BMI, DEXA scans showed 53% of this subgroup did have obesity based on body fat content. Among those with a normal BMI, 43% had obesity by DEXA result.

Further analysis showed that when Dr. Visaria added waist circumference to BMI to enlarge the diagnostic net for obesity it cut the percentage of adults missed as having obesity by BMI alone nearly in half.

Additional analyses showed that the rate of missed diagnoses of obesity by BMI was most common only among people of Hispanic or Asian ethnicity, with both groups showing a 49% rate of obesity by DEXA among those with normal-range BMIs.

The rate of missed obesity diagnoses was highest among all women, with a 59% prevalence of obesity by DEXA among women with a normal-range BMI.

The study received no commercial funding. Dr. Visaria has reported no relevant financial relationships.

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

CHICAGO – Twice as many U.S. adults have obesity based on assessment of their fat volume by dual-energy X-ray absorptiometry (DEXA) scan compared with measurement of body mass index (BMI), a finding that highlights the shortcomings of BMI and adds to the growing case that BMI alone should not be the default gauge for obesity.

“BMI vastly underestimates true obesity,” Aayush Visaria, MD, said at the annual meeting of the Endocrine Society.

His findings highlight that “BMI should be supplemented with other measures of obesity” for the management of individual patients, with assessments that could include a bioelectrical impedance scale or waist circumference, said Dr. Visaria, a researcher at Rutgers Robert Wood Johnson Medical School in New Brunswick, N.J.

Dr. Visaria cited a new policy issued by the American Medical Association a couple of days before his presentation, which advises that BMI “be used in conjunction with other valid measures of risk such as, but not limited to, measurements of visceral fat, body adiposity index, body composition, relative fat mass, waist circumference, and genetic/metabolic factors.”

“We’re at the start of the end of BMI,” Dr. Visaria declared during a press briefing at the meeting.

He said DEXA is not practical or cost-effective for obesity screening in routine practice. Therefore, he predicts that waist circumference, often expressed as waist-to-height ratio, will be measured more often, although he acknowledged that waist measurement can be difficult. However, better physician training on the measure should help it become the norm.

Another useful tool for obesity measurement he foresees quickly becoming widespread is bathroom scales that record both weight and body fat percentage using a small electric current to make a bioelectrical impedance measure of adiposity.

Bioimpedance scales will provide more standardized measurements than waist circumference and “revolutionize how we measure obesity,” Dr. Visaria predicted. They are “very accessible and cheap,” he noted, with many models sold for less than $100.
 

Obesity prevalence of 74%

The study by Dr. Visaria and colleagues used data from 9,784 U.S. adults aged 20-59 years (average age, 39 years) collected in several National Health and Nutrition Examination Surveys during 2011-2018. All these participants underwent DEXA assessment of their total body fat as well as a BMI calculation.

Using standard obesity cutoffs for both BMI and total body fat, Dr. Visaria found that DEXA rated 74% of participants as having obesity based on body fat compared with 36% based on BMI.

Among the 64% of the study group who were not obese by BMI, DEXA scans showed 53% of this subgroup did have obesity based on body fat content. Among those with a normal BMI, 43% had obesity by DEXA result.

Further analysis showed that when Dr. Visaria added waist circumference to BMI to enlarge the diagnostic net for obesity it cut the percentage of adults missed as having obesity by BMI alone nearly in half.

Additional analyses showed that the rate of missed diagnoses of obesity by BMI was most common only among people of Hispanic or Asian ethnicity, with both groups showing a 49% rate of obesity by DEXA among those with normal-range BMIs.

The rate of missed obesity diagnoses was highest among all women, with a 59% prevalence of obesity by DEXA among women with a normal-range BMI.

The study received no commercial funding. Dr. Visaria has reported no relevant financial relationships.

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

Men who illicitly used anabolic-androgenic steroids to bulk up and then turned to illegal, web-based regimens for treating their steroid withdrawal complications have provided important clues for new approaches to treating a growing worldwide population of men who abuse steroids.

A retrospective, observational study at one steroid addiction center in Glasgow examined 641 men who had stopped using steroids within the prior 3 years in 2015-2022 and who had self-administered certain agents, collectively known as post-cycle therapy (PCT) – within 3 months of stopping steroids.

They had a significant 3.8-fold increased rate of normalization of their levels of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), compared with men who either never used PCT or began it more than 3 months after stopping steroids, Channa N. Jayasena, PhD, MRCP, FRCPath, reported at the annual meeting of the Endocrine Society.

These testosterone, LH, and FSH levels served as a “surrogate marker of biochemical recovery from hypogonadism,” he explained. Normalization also occurred “slightly sooner” in men who began using PCT early after steroid cessation, added Dr. Jayasena, a reproductive endocrinologist at Imperial College, London.

When men recovered their endogenous testosterone-producing capacity, it occurred after an average of about 13 weeks on PCT and after an average of about 19 weeks without PCT, a significant difference.

“There is a vacuum of medical advice on what to do” when men stop taking steroids, said Dr. Jayasena during a press briefing at the meeting. “We can’t recommend anything yet because [our studies] have not proven causality” between the post-cycle therapy that many men start after stopping steroids and any symptom improvement they experience.”

The next step is to test the PCT agents in a prospective, controlled study, an investigation Dr. Jayasena and colleagues are eager to launch. The goal is to determine whether PCT is truly effective, the optimal doses, and whether the treatments are safe.
 

‘Incredibly sophisticated’ online community

The agents that constitute PCT include human chorionic gonadotropin (hCG, the “pregnancy hormone”), selective estrogen receptor modulators (SERMs), and aromatase inhibitors (AIs). SERMs and AIs are licensed only for use in women, the former for osteoporosis and breast cancer and the latter for breast cancer.

All of these agents, as well as others, are advertised by various illegal websites as treatments that can restore endogenous testosterone production in men whose native testosterone shut down during their steroid self-medication.

Restored testosterone resolves many of the adverse effects of steroid withdrawal such as diminished libido and erections, and depressed mood and energy.

Men buy PCT agents illegally from various websites. “There is an enormous, incredibly sophisticated community online that influences” PCT, and an “incredibly refined worldwide distribution network,” Dr. Jayasena explained.

His study included 410 men who turned to PCT after steroid cessation and 170 who did not.
 

Largest study of hormone recovery when men stop taking steroids

In a further multivariate analysis of the observational data, men who had used four or more different steroid treatments fared worse – with a significant 75% reduced rate of testosterone normalization with PCT – compared with men who had used a single steroid agent.

And men who had been on a steroid regimen for more than 6 months also fared badly – with a significant 66% reduced rate of testosterone normalization with PCT, compared with men on a steroid regimen for 3 months or less.

“This is the largest study of hormone recovery when men stop taking steroids,” Dr. Jayasena noted.

And the data “require corroboration within an interventional study to determine causality.”

“We need further studies to help doctors and other health care professionals advise men about the risks of anabolic steroid use and support those who are motivated to stop,” Dr. Jayasena said.

He cautioned that the study has several limitations: biases were potentially introduced based on recruitment and on recall by participants; clinicians drew blood specimens used to measure hormone levels at random times; and participants may have engaged in concealed drug use and used steroid and PCT agents that did not contain the substances advertised.

Nevertheless, “Our data provide primary evidence that self-administered PCT drugs may be associated with improved biochemical recovery” from steroid-induced hypogonadism, and they “may have important therapeutic implications for the future treatment of men who are motivated to stop” steroids.

The study received no commercial funding. Dr. Jayasena has received research funding from Logixx Pharma.

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

Men who illicitly used anabolic-androgenic steroids to bulk up and then turned to illegal, web-based regimens for treating their steroid withdrawal complications have provided important clues for new approaches to treating a growing worldwide population of men who abuse steroids.

A retrospective, observational study at one steroid addiction center in Glasgow examined 641 men who had stopped using steroids within the prior 3 years in 2015-2022 and who had self-administered certain agents, collectively known as post-cycle therapy (PCT) – within 3 months of stopping steroids.

They had a significant 3.8-fold increased rate of normalization of their levels of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), compared with men who either never used PCT or began it more than 3 months after stopping steroids, Channa N. Jayasena, PhD, MRCP, FRCPath, reported at the annual meeting of the Endocrine Society.

These testosterone, LH, and FSH levels served as a “surrogate marker of biochemical recovery from hypogonadism,” he explained. Normalization also occurred “slightly sooner” in men who began using PCT early after steroid cessation, added Dr. Jayasena, a reproductive endocrinologist at Imperial College, London.

When men recovered their endogenous testosterone-producing capacity, it occurred after an average of about 13 weeks on PCT and after an average of about 19 weeks without PCT, a significant difference.

“There is a vacuum of medical advice on what to do” when men stop taking steroids, said Dr. Jayasena during a press briefing at the meeting. “We can’t recommend anything yet because [our studies] have not proven causality” between the post-cycle therapy that many men start after stopping steroids and any symptom improvement they experience.”

The next step is to test the PCT agents in a prospective, controlled study, an investigation Dr. Jayasena and colleagues are eager to launch. The goal is to determine whether PCT is truly effective, the optimal doses, and whether the treatments are safe.
 

‘Incredibly sophisticated’ online community

The agents that constitute PCT include human chorionic gonadotropin (hCG, the “pregnancy hormone”), selective estrogen receptor modulators (SERMs), and aromatase inhibitors (AIs). SERMs and AIs are licensed only for use in women, the former for osteoporosis and breast cancer and the latter for breast cancer.

All of these agents, as well as others, are advertised by various illegal websites as treatments that can restore endogenous testosterone production in men whose native testosterone shut down during their steroid self-medication.

Restored testosterone resolves many of the adverse effects of steroid withdrawal such as diminished libido and erections, and depressed mood and energy.

Men buy PCT agents illegally from various websites. “There is an enormous, incredibly sophisticated community online that influences” PCT, and an “incredibly refined worldwide distribution network,” Dr. Jayasena explained.

His study included 410 men who turned to PCT after steroid cessation and 170 who did not.
 

Largest study of hormone recovery when men stop taking steroids

In a further multivariate analysis of the observational data, men who had used four or more different steroid treatments fared worse – with a significant 75% reduced rate of testosterone normalization with PCT – compared with men who had used a single steroid agent.

And men who had been on a steroid regimen for more than 6 months also fared badly – with a significant 66% reduced rate of testosterone normalization with PCT, compared with men on a steroid regimen for 3 months or less.

“This is the largest study of hormone recovery when men stop taking steroids,” Dr. Jayasena noted.

And the data “require corroboration within an interventional study to determine causality.”

“We need further studies to help doctors and other health care professionals advise men about the risks of anabolic steroid use and support those who are motivated to stop,” Dr. Jayasena said.

He cautioned that the study has several limitations: biases were potentially introduced based on recruitment and on recall by participants; clinicians drew blood specimens used to measure hormone levels at random times; and participants may have engaged in concealed drug use and used steroid and PCT agents that did not contain the substances advertised.

Nevertheless, “Our data provide primary evidence that self-administered PCT drugs may be associated with improved biochemical recovery” from steroid-induced hypogonadism, and they “may have important therapeutic implications for the future treatment of men who are motivated to stop” steroids.

The study received no commercial funding. Dr. Jayasena has received research funding from Logixx Pharma.

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

Men who illicitly used anabolic-androgenic steroids to bulk up and then turned to illegal, web-based regimens for treating their steroid withdrawal complications have provided important clues for new approaches to treating a growing worldwide population of men who abuse steroids.

A retrospective, observational study at one steroid addiction center in Glasgow examined 641 men who had stopped using steroids within the prior 3 years in 2015-2022 and who had self-administered certain agents, collectively known as post-cycle therapy (PCT) – within 3 months of stopping steroids.

They had a significant 3.8-fold increased rate of normalization of their levels of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), compared with men who either never used PCT or began it more than 3 months after stopping steroids, Channa N. Jayasena, PhD, MRCP, FRCPath, reported at the annual meeting of the Endocrine Society.

These testosterone, LH, and FSH levels served as a “surrogate marker of biochemical recovery from hypogonadism,” he explained. Normalization also occurred “slightly sooner” in men who began using PCT early after steroid cessation, added Dr. Jayasena, a reproductive endocrinologist at Imperial College, London.

When men recovered their endogenous testosterone-producing capacity, it occurred after an average of about 13 weeks on PCT and after an average of about 19 weeks without PCT, a significant difference.

“There is a vacuum of medical advice on what to do” when men stop taking steroids, said Dr. Jayasena during a press briefing at the meeting. “We can’t recommend anything yet because [our studies] have not proven causality” between the post-cycle therapy that many men start after stopping steroids and any symptom improvement they experience.”

The next step is to test the PCT agents in a prospective, controlled study, an investigation Dr. Jayasena and colleagues are eager to launch. The goal is to determine whether PCT is truly effective, the optimal doses, and whether the treatments are safe.
 

‘Incredibly sophisticated’ online community

The agents that constitute PCT include human chorionic gonadotropin (hCG, the “pregnancy hormone”), selective estrogen receptor modulators (SERMs), and aromatase inhibitors (AIs). SERMs and AIs are licensed only for use in women, the former for osteoporosis and breast cancer and the latter for breast cancer.

All of these agents, as well as others, are advertised by various illegal websites as treatments that can restore endogenous testosterone production in men whose native testosterone shut down during their steroid self-medication.

Restored testosterone resolves many of the adverse effects of steroid withdrawal such as diminished libido and erections, and depressed mood and energy.

Men buy PCT agents illegally from various websites. “There is an enormous, incredibly sophisticated community online that influences” PCT, and an “incredibly refined worldwide distribution network,” Dr. Jayasena explained.

His study included 410 men who turned to PCT after steroid cessation and 170 who did not.
 

Largest study of hormone recovery when men stop taking steroids

In a further multivariate analysis of the observational data, men who had used four or more different steroid treatments fared worse – with a significant 75% reduced rate of testosterone normalization with PCT – compared with men who had used a single steroid agent.

And men who had been on a steroid regimen for more than 6 months also fared badly – with a significant 66% reduced rate of testosterone normalization with PCT, compared with men on a steroid regimen for 3 months or less.

“This is the largest study of hormone recovery when men stop taking steroids,” Dr. Jayasena noted.

And the data “require corroboration within an interventional study to determine causality.”

“We need further studies to help doctors and other health care professionals advise men about the risks of anabolic steroid use and support those who are motivated to stop,” Dr. Jayasena said.

He cautioned that the study has several limitations: biases were potentially introduced based on recruitment and on recall by participants; clinicians drew blood specimens used to measure hormone levels at random times; and participants may have engaged in concealed drug use and used steroid and PCT agents that did not contain the substances advertised.

Nevertheless, “Our data provide primary evidence that self-administered PCT drugs may be associated with improved biochemical recovery” from steroid-induced hypogonadism, and they “may have important therapeutic implications for the future treatment of men who are motivated to stop” steroids.

The study received no commercial funding. Dr. Jayasena has received research funding from Logixx Pharma.

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

The Food and Drug Administration draft guidance released recently on possible contamination of tattoo ink was not concerning Whitney Donohue, 34, owner of Forget Me Not Tattoo in Billings, Mont. 

“I get our ink directly through the manufacturer – not at a store or through Amazon or eBay,” she said. “You never know if it’s going to be repackaged.”

Tattoo artists themselves, she said, regulate the quality of ink they use. 

Still, the threat is real, said Bruce Brod, MD, a clinical professor of dermatology at the University of Pennsylvania Health System. “I’ve seen several different infections from tattooing, and they are from organisms that tend to contaminate things in damp, liquid-type environments.”

The FDA released the new draft guidance aiming to reduce the use of pathogen-contaminated tattoo ink, which can cause stubborn infections that are especially hard to treat, dermatologists said.

“Tattooing involves puncturing the epidermis about 100 times per second with needles and depositing ink 1.5 to 2 millimeters below the surface of the skin, deep into the dermis,” the guidance states. “Contaminated tattoo ink can cause infections and serious injuries. Because these inks are injected, pathogens or other harmful substances in these inks can travel from the injection site through the blood and lymphatic systems to other parts of the body.”

The guidance comes as body art continues to get more popular. According to a 2019 poll, 30% of Americans had at least one tattoo – up from 21% in 2012. Forty percent of people 18-34 and 36% of those ages 35-54 had at least one tattoo. And though they are commonplace, tattoos come with medical risks that should be known beforehand, doctors said. 

Commonly reported symptoms of tattoo ink–associated infections include rashes, blisters, painful nodules, and severe abscesses. One of the most common bacteria found in contaminated tattoo ink is nontuberculous mycobacteria, which is related to the bacteria that causes tuberculosis and can be found in soil and water.

The guidance lists several unsanitary manufacturing conditions that may lead to ink contamination, including: 

• Preparing or packing of tattoo inks in facilities that are hard to sanitize, such as carpeted areas
• Ink or ink components left uncovered, especially near open air ducts
• Unsanitary mixing of tattoo inks, including with unclean utensils or containers
• Lack of appropriate attire by staff, failure to use hairnets, lab coats, aprons, gowns, masks, or gloves

“Infections will often spread along the drainage channels in the skin and create squiggly, uneven lines of big red, lumpy nodules,” Dr. Brod said. 

Between 2003 and 2023, there were 18 recalls of tattoo inks that were contaminated with various microorganisms, according to the FDA. In May 2019, the FDA issued a safety alert advising consumers, tattoo artists, and retailers to avoid using or selling certain tattoo inks contaminated with microorganisms.

Reputable ink manufacturers use a process called gamma radiation, which refers to electromagnetic radiation of high frequencies to kill microorganisms in the ink and its packaging.

Most of the trustworthy, high-quality ink manufacturers are well-known among tattoo artists, Ms. Donohue said. 

While she has seen customers with sensitive skin have allergic reactions, she has not seen someone come back with an infection in her 9 years working in the tattoo industry.

Because tattoo ink is considered a cosmetic product, there is not much regulatory oversight involved, which means the sterility and quality of ingredients vary, said Teo Soleymani, MD, an assistant clinical professor of dermatology and dermatological surgery at the UCLA David Geffen School of Medicine.

“Cosmeceuticals aren’t regulated by the FDA like prescription medication,” he said. “What we’ve seen many times is inadvertent contamination during the application process or contamination while the inks are being made.”

In years past, unclean needles spreading hepatitis and HIV were more of a concern, but those rates have dropped significantly, Dr. Soleymani said. 

The infections that have increased are from rare bacteria that exist in stagnant water. And they are injected into a part of the body that allows them to evade the immune system, he said: shallow enough that there aren’t many associated blood vessels, but not still below the layer of skin that gets sloughed off every 28 days. 

Sometimes, antibiotics alone won’t cut it, and the tattoo will require surgical removal. 

“The aesthetic you were going for has to be not only removed, but you’re left with a surgical scar,” Dr. Soleymani said. “Tattoos can be beautiful, but they can come with unwanted visitors that can cause months of misery.”

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

The Food and Drug Administration draft guidance released recently on possible contamination of tattoo ink was not concerning Whitney Donohue, 34, owner of Forget Me Not Tattoo in Billings, Mont. 

“I get our ink directly through the manufacturer – not at a store or through Amazon or eBay,” she said. “You never know if it’s going to be repackaged.”

Tattoo artists themselves, she said, regulate the quality of ink they use. 

Still, the threat is real, said Bruce Brod, MD, a clinical professor of dermatology at the University of Pennsylvania Health System. “I’ve seen several different infections from tattooing, and they are from organisms that tend to contaminate things in damp, liquid-type environments.”

The FDA released the new draft guidance aiming to reduce the use of pathogen-contaminated tattoo ink, which can cause stubborn infections that are especially hard to treat, dermatologists said.

“Tattooing involves puncturing the epidermis about 100 times per second with needles and depositing ink 1.5 to 2 millimeters below the surface of the skin, deep into the dermis,” the guidance states. “Contaminated tattoo ink can cause infections and serious injuries. Because these inks are injected, pathogens or other harmful substances in these inks can travel from the injection site through the blood and lymphatic systems to other parts of the body.”

The guidance comes as body art continues to get more popular. According to a 2019 poll, 30% of Americans had at least one tattoo – up from 21% in 2012. Forty percent of people 18-34 and 36% of those ages 35-54 had at least one tattoo. And though they are commonplace, tattoos come with medical risks that should be known beforehand, doctors said. 

Commonly reported symptoms of tattoo ink–associated infections include rashes, blisters, painful nodules, and severe abscesses. One of the most common bacteria found in contaminated tattoo ink is nontuberculous mycobacteria, which is related to the bacteria that causes tuberculosis and can be found in soil and water.

The guidance lists several unsanitary manufacturing conditions that may lead to ink contamination, including: 

• Preparing or packing of tattoo inks in facilities that are hard to sanitize, such as carpeted areas
• Ink or ink components left uncovered, especially near open air ducts
• Unsanitary mixing of tattoo inks, including with unclean utensils or containers
• Lack of appropriate attire by staff, failure to use hairnets, lab coats, aprons, gowns, masks, or gloves

“Infections will often spread along the drainage channels in the skin and create squiggly, uneven lines of big red, lumpy nodules,” Dr. Brod said. 

Between 2003 and 2023, there were 18 recalls of tattoo inks that were contaminated with various microorganisms, according to the FDA. In May 2019, the FDA issued a safety alert advising consumers, tattoo artists, and retailers to avoid using or selling certain tattoo inks contaminated with microorganisms.

Reputable ink manufacturers use a process called gamma radiation, which refers to electromagnetic radiation of high frequencies to kill microorganisms in the ink and its packaging.

Most of the trustworthy, high-quality ink manufacturers are well-known among tattoo artists, Ms. Donohue said. 

While she has seen customers with sensitive skin have allergic reactions, she has not seen someone come back with an infection in her 9 years working in the tattoo industry.

Because tattoo ink is considered a cosmetic product, there is not much regulatory oversight involved, which means the sterility and quality of ingredients vary, said Teo Soleymani, MD, an assistant clinical professor of dermatology and dermatological surgery at the UCLA David Geffen School of Medicine.

“Cosmeceuticals aren’t regulated by the FDA like prescription medication,” he said. “What we’ve seen many times is inadvertent contamination during the application process or contamination while the inks are being made.”

In years past, unclean needles spreading hepatitis and HIV were more of a concern, but those rates have dropped significantly, Dr. Soleymani said. 

The infections that have increased are from rare bacteria that exist in stagnant water. And they are injected into a part of the body that allows them to evade the immune system, he said: shallow enough that there aren’t many associated blood vessels, but not still below the layer of skin that gets sloughed off every 28 days. 

Sometimes, antibiotics alone won’t cut it, and the tattoo will require surgical removal. 

“The aesthetic you were going for has to be not only removed, but you’re left with a surgical scar,” Dr. Soleymani said. “Tattoos can be beautiful, but they can come with unwanted visitors that can cause months of misery.”

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

The Food and Drug Administration draft guidance released recently on possible contamination of tattoo ink was not concerning Whitney Donohue, 34, owner of Forget Me Not Tattoo in Billings, Mont. 

“I get our ink directly through the manufacturer – not at a store or through Amazon or eBay,” she said. “You never know if it’s going to be repackaged.”

Tattoo artists themselves, she said, regulate the quality of ink they use. 

Still, the threat is real, said Bruce Brod, MD, a clinical professor of dermatology at the University of Pennsylvania Health System. “I’ve seen several different infections from tattooing, and they are from organisms that tend to contaminate things in damp, liquid-type environments.”

The FDA released the new draft guidance aiming to reduce the use of pathogen-contaminated tattoo ink, which can cause stubborn infections that are especially hard to treat, dermatologists said.

“Tattooing involves puncturing the epidermis about 100 times per second with needles and depositing ink 1.5 to 2 millimeters below the surface of the skin, deep into the dermis,” the guidance states. “Contaminated tattoo ink can cause infections and serious injuries. Because these inks are injected, pathogens or other harmful substances in these inks can travel from the injection site through the blood and lymphatic systems to other parts of the body.”

The guidance comes as body art continues to get more popular. According to a 2019 poll, 30% of Americans had at least one tattoo – up from 21% in 2012. Forty percent of people 18-34 and 36% of those ages 35-54 had at least one tattoo. And though they are commonplace, tattoos come with medical risks that should be known beforehand, doctors said. 

Commonly reported symptoms of tattoo ink–associated infections include rashes, blisters, painful nodules, and severe abscesses. One of the most common bacteria found in contaminated tattoo ink is nontuberculous mycobacteria, which is related to the bacteria that causes tuberculosis and can be found in soil and water.

The guidance lists several unsanitary manufacturing conditions that may lead to ink contamination, including: 

• Preparing or packing of tattoo inks in facilities that are hard to sanitize, such as carpeted areas
• Ink or ink components left uncovered, especially near open air ducts
• Unsanitary mixing of tattoo inks, including with unclean utensils or containers
• Lack of appropriate attire by staff, failure to use hairnets, lab coats, aprons, gowns, masks, or gloves

“Infections will often spread along the drainage channels in the skin and create squiggly, uneven lines of big red, lumpy nodules,” Dr. Brod said. 

Between 2003 and 2023, there were 18 recalls of tattoo inks that were contaminated with various microorganisms, according to the FDA. In May 2019, the FDA issued a safety alert advising consumers, tattoo artists, and retailers to avoid using or selling certain tattoo inks contaminated with microorganisms.

Reputable ink manufacturers use a process called gamma radiation, which refers to electromagnetic radiation of high frequencies to kill microorganisms in the ink and its packaging.

Most of the trustworthy, high-quality ink manufacturers are well-known among tattoo artists, Ms. Donohue said. 

While she has seen customers with sensitive skin have allergic reactions, she has not seen someone come back with an infection in her 9 years working in the tattoo industry.

Because tattoo ink is considered a cosmetic product, there is not much regulatory oversight involved, which means the sterility and quality of ingredients vary, said Teo Soleymani, MD, an assistant clinical professor of dermatology and dermatological surgery at the UCLA David Geffen School of Medicine.

“Cosmeceuticals aren’t regulated by the FDA like prescription medication,” he said. “What we’ve seen many times is inadvertent contamination during the application process or contamination while the inks are being made.”

In years past, unclean needles spreading hepatitis and HIV were more of a concern, but those rates have dropped significantly, Dr. Soleymani said. 

The infections that have increased are from rare bacteria that exist in stagnant water. And they are injected into a part of the body that allows them to evade the immune system, he said: shallow enough that there aren’t many associated blood vessels, but not still below the layer of skin that gets sloughed off every 28 days. 

Sometimes, antibiotics alone won’t cut it, and the tattoo will require surgical removal. 

“The aesthetic you were going for has to be not only removed, but you’re left with a surgical scar,” Dr. Soleymani said. “Tattoos can be beautiful, but they can come with unwanted visitors that can cause months of misery.”

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

CHICAGO – Polycystic ovary syndrome (PCOS) appears to shorten a woman’s lifespan, new data suggest.

In the study, involving nearly 10,000 women with PCOS and matched controls from Finland, women with PCOS died on average a year earlier than their age-matched counterparts, primarily from diseases of the circulatory system, cancer, and diabetes.

PCOS is the most common endocrine disorder of reproductive-age women, of whom about 50%-70% also have obesity.

“I think we need to acknowledge that this is a health burden and not just a reproductive problem. In many cases we deal with the reproductive problem, and then these women are left alone. … So I think the message is we need to look beyond the reproductive outcomes, which are … really good. We can manage that,” said Terhi T. Piltonen, MD, PhD, during a press briefing held June 15 at the annual meeting of the Endocrine Society.

“I think the difficult part is [managing] the lifelong health for these women and supporting them to achieve the best health they can get. We need a multidisciplinary effort and to put more resources into the research,” added Dr. Piltonen, professor in the departments of ob.gyn. and reproductive endocrinology at the University of Oulu, Finland.

Indeed, Punith Kempegowda, MD, PhD, of the University of Birmingham (England) observed: “In our medical schools in the U.K., over 5 years, students get 45 minutes [of education] on PCOS, and they’re expected to learn about it.”

And over the last 20 years, funding for research into the condition has totaled less than a half percent of overall medical funding. “And we’re talking about 10% of all women. …We need to acknowledge it and educate people more. We need more published studies to understand more about it,” he noted.

Asked to comment, Greg Dodell, MD, owner and president of Central Park Endocrinology, New York, said: “PCOS is about a lot more than fertility, and that may not be the goal or on the mind of a woman at the time they start having symptoms of PCOS or get the diagnosis.”

“PCOS is largely a metabolic condition rooted in insulin resistance, and therefore, the potential clinical outcomes, including mortality, are important to recognize.”

Dr. Dodell, who has a special interest in PCOS, advised that, for women with the condition, “focus on reducing insulin resistance with health-promoting behaviors and medications as needed. Data demonstrate that improving fitness, irrespective of a change in weight, can improve metabolic markers.” And, he advised that these women be routinely screened for mental health issues.

He also noted, “PCOS occurs across the size spectrum, but those patients in larger bodies may face weight stigma which has negative health consequences. These patients may avoid going to doctors for routine health screenings, so it is an important issue to continue to address.”

Women with PCOS lose a year of life

The new data come from 9,839 women with PCOS and 70,705 age- and region-matched controls from the Finnish Care Register for Health Care. The group with PCOS had been diagnosed at a mean age of 27 years.

The mean follow-up time was 13.1 years in both groups, during which 1,003 controls and 177 women with PCOS died. The mean age at death was 51.4 years for the PCOS group versus 52.6 years for the control women, a significant difference (P < .001).

Causes of death that were significantly higher among the women with PCOS versus controls after adjustments were cancer (hazard ratio, 1.39), and diseases of the circulatory system (1.68).

In more specific subcategories, after adjustment for education, the women with PCOS had increased mortality from nonischemic diseases, such as hypertensive heart disease, pulmonary embolism, etc. (HR, 2.06), and diabetes (HR, 2.85).

One study limitation was the inability to adjust for body mass index, Dr. Piltonen noted.

Dr. Piltonen, Dr. Kempegowda, and Dr. Dodell have no disclosures.

CHICAGO – Polycystic ovary syndrome (PCOS) appears to shorten a woman’s lifespan, new data suggest.

In the study, involving nearly 10,000 women with PCOS and matched controls from Finland, women with PCOS died on average a year earlier than their age-matched counterparts, primarily from diseases of the circulatory system, cancer, and diabetes.

PCOS is the most common endocrine disorder of reproductive-age women, of whom about 50%-70% also have obesity.

“I think we need to acknowledge that this is a health burden and not just a reproductive problem. In many cases we deal with the reproductive problem, and then these women are left alone. … So I think the message is we need to look beyond the reproductive outcomes, which are … really good. We can manage that,” said Terhi T. Piltonen, MD, PhD, during a press briefing held June 15 at the annual meeting of the Endocrine Society.

“I think the difficult part is [managing] the lifelong health for these women and supporting them to achieve the best health they can get. We need a multidisciplinary effort and to put more resources into the research,” added Dr. Piltonen, professor in the departments of ob.gyn. and reproductive endocrinology at the University of Oulu, Finland.

Indeed, Punith Kempegowda, MD, PhD, of the University of Birmingham (England) observed: “In our medical schools in the U.K., over 5 years, students get 45 minutes [of education] on PCOS, and they’re expected to learn about it.”

And over the last 20 years, funding for research into the condition has totaled less than a half percent of overall medical funding. “And we’re talking about 10% of all women. …We need to acknowledge it and educate people more. We need more published studies to understand more about it,” he noted.

Asked to comment, Greg Dodell, MD, owner and president of Central Park Endocrinology, New York, said: “PCOS is about a lot more than fertility, and that may not be the goal or on the mind of a woman at the time they start having symptoms of PCOS or get the diagnosis.”

“PCOS is largely a metabolic condition rooted in insulin resistance, and therefore, the potential clinical outcomes, including mortality, are important to recognize.”

Dr. Dodell, who has a special interest in PCOS, advised that, for women with the condition, “focus on reducing insulin resistance with health-promoting behaviors and medications as needed. Data demonstrate that improving fitness, irrespective of a change in weight, can improve metabolic markers.” And, he advised that these women be routinely screened for mental health issues.

He also noted, “PCOS occurs across the size spectrum, but those patients in larger bodies may face weight stigma which has negative health consequences. These patients may avoid going to doctors for routine health screenings, so it is an important issue to continue to address.”

Women with PCOS lose a year of life

The new data come from 9,839 women with PCOS and 70,705 age- and region-matched controls from the Finnish Care Register for Health Care. The group with PCOS had been diagnosed at a mean age of 27 years.

The mean follow-up time was 13.1 years in both groups, during which 1,003 controls and 177 women with PCOS died. The mean age at death was 51.4 years for the PCOS group versus 52.6 years for the control women, a significant difference (P < .001).

Causes of death that were significantly higher among the women with PCOS versus controls after adjustments were cancer (hazard ratio, 1.39), and diseases of the circulatory system (1.68).

In more specific subcategories, after adjustment for education, the women with PCOS had increased mortality from nonischemic diseases, such as hypertensive heart disease, pulmonary embolism, etc. (HR, 2.06), and diabetes (HR, 2.85).

One study limitation was the inability to adjust for body mass index, Dr. Piltonen noted.

Dr. Piltonen, Dr. Kempegowda, and Dr. Dodell have no disclosures.

CHICAGO – Polycystic ovary syndrome (PCOS) appears to shorten a woman’s lifespan, new data suggest.

In the study, involving nearly 10,000 women with PCOS and matched controls from Finland, women with PCOS died on average a year earlier than their age-matched counterparts, primarily from diseases of the circulatory system, cancer, and diabetes.

PCOS is the most common endocrine disorder of reproductive-age women, of whom about 50%-70% also have obesity.

“I think we need to acknowledge that this is a health burden and not just a reproductive problem. In many cases we deal with the reproductive problem, and then these women are left alone. … So I think the message is we need to look beyond the reproductive outcomes, which are … really good. We can manage that,” said Terhi T. Piltonen, MD, PhD, during a press briefing held June 15 at the annual meeting of the Endocrine Society.

“I think the difficult part is [managing] the lifelong health for these women and supporting them to achieve the best health they can get. We need a multidisciplinary effort and to put more resources into the research,” added Dr. Piltonen, professor in the departments of ob.gyn. and reproductive endocrinology at the University of Oulu, Finland.

Indeed, Punith Kempegowda, MD, PhD, of the University of Birmingham (England) observed: “In our medical schools in the U.K., over 5 years, students get 45 minutes [of education] on PCOS, and they’re expected to learn about it.”

And over the last 20 years, funding for research into the condition has totaled less than a half percent of overall medical funding. “And we’re talking about 10% of all women. …We need to acknowledge it and educate people more. We need more published studies to understand more about it,” he noted.

Asked to comment, Greg Dodell, MD, owner and president of Central Park Endocrinology, New York, said: “PCOS is about a lot more than fertility, and that may not be the goal or on the mind of a woman at the time they start having symptoms of PCOS or get the diagnosis.”

“PCOS is largely a metabolic condition rooted in insulin resistance, and therefore, the potential clinical outcomes, including mortality, are important to recognize.”

Dr. Dodell, who has a special interest in PCOS, advised that, for women with the condition, “focus on reducing insulin resistance with health-promoting behaviors and medications as needed. Data demonstrate that improving fitness, irrespective of a change in weight, can improve metabolic markers.” And, he advised that these women be routinely screened for mental health issues.

He also noted, “PCOS occurs across the size spectrum, but those patients in larger bodies may face weight stigma which has negative health consequences. These patients may avoid going to doctors for routine health screenings, so it is an important issue to continue to address.”

Women with PCOS lose a year of life

The new data come from 9,839 women with PCOS and 70,705 age- and region-matched controls from the Finnish Care Register for Health Care. The group with PCOS had been diagnosed at a mean age of 27 years.

The mean follow-up time was 13.1 years in both groups, during which 1,003 controls and 177 women with PCOS died. The mean age at death was 51.4 years for the PCOS group versus 52.6 years for the control women, a significant difference (P < .001).

Causes of death that were significantly higher among the women with PCOS versus controls after adjustments were cancer (hazard ratio, 1.39), and diseases of the circulatory system (1.68).

In more specific subcategories, after adjustment for education, the women with PCOS had increased mortality from nonischemic diseases, such as hypertensive heart disease, pulmonary embolism, etc. (HR, 2.06), and diabetes (HR, 2.85).

One study limitation was the inability to adjust for body mass index, Dr. Piltonen noted.

Dr. Piltonen, Dr. Kempegowda, and Dr. Dodell have no disclosures.

Human Rights Watch, the nonprofit that for decades has called attention to the victims of war, famine, and political repression around the world, is taking aim at U.S. hospitals for pushing millions of American patients into debt.

In a new report, the group calls for stronger government action to protect Americans from aggressive billing and debt collection by nonprofit hospitals, which Human Rights Watch said are systematically undermining patients’ human rights.

“Given the high prevalence of hospital-related medical debt in the U.S., this system is clearly not working,” concludes the report, which draws extensively on an ongoing investigation of medical debt by KFF Health News and NPR.

The report continues: “The U.S. model of subsidizing privately operated hospitals with tax exemptions in the hope that they will increase the accessibility of hospital care for un- and underinsured patients allows for abusive medical billing and debt collection practices and undermines human rights, including the right to health.”

Nationwide, about 100 million people – or 41% of adults – have some form of health care debt, a KFF survey conducted for the KFF Health News–NPR project found. And while patient debt is being driven by a range of medical and dental bills, polls and studies suggest hospitals are a major contributor.

About a third of U.S. adults with health care debt owed money for hospitalization, KFF’s polling found. Close to half of those owed at least $5,000. About a quarter owed $10,000 or more.

The scale of this crisis – which is unparalleled among wealthy nations – compelled Human Rights Watch to release the new report, said researcher Matt McConnell, its author. “Historically, Human Rights Watch has been an organization that has focused on international human rights issues,” he said. “But on medical debt, the U.S. is a real outlier. What you see is a system that privileges a few but creates large barriers to people accessing basic health rights.”

Hospital industry officials defend their work, citing hospitals’ broader work to help the communities they serve. “As a field, hospitals provide more benefit to their communities than any other sector in health care,” Melinda Hatton, general counsel at the American Hospital Association, wrote in a response to the Human Right Watch report.

Federal law requires private, tax-exempt hospitals – which make up more than half the nation’s medical centers – to provide care at no cost or at a discount to low-income patients. But reporting by KFF Health News and others has found that many hospitals make this aid difficult for patients to get.

At the same time, thousands of medical centers – including many tax-exempt ones – engage in aggressive debt collection tactics to pursue patients, including garnishing patients’ wages, placing liens on their homes, or selling their debt to third-party debt collectors.

Overall, KFF Health News found that most of the nation’s approximately 5,100 hospitals serving the general public have policies to use legal action or other aggressive tactics against patients. And one in five will deny nonemergency care to people with outstanding debt.

“Medical debt is drowning many low-income and working families while hospitals continue to benefit from nonprofit tax status as they pursue families for medical debt,” said Marceline White, executive director of Economic Action Maryland. The advocacy group has helped enact tighter rules to ensure Maryland hospitals make financial assistance more easily accessible and to restrict hospitals from some aggressive debt collection tactics, such as placing liens on patients’ homes.

Similar efforts are underway in other states, including Colorado, New Mexico, New York, Oregon, and Washington. But many patient and consumer advocates say stronger federal action is needed to expand patient protections.

The Human Rights Watch report – titled “In Sheep’s Clothing: United States’ Poorly Regulated Nonprofit Hospitals Undermine Health Care Access” – lists more than a dozen recommendations. These include:

• Congress should pass legislation to ensure that hospitals provide at least the same amount of charity care as they receive in public subsidies.
• The IRS should set uniform national standards on patients’ eligibility for financial assistance at nonprofit hospitals. Currently, hospitals are free to set their own standards, resulting in widespread variation, which can confuse patients.
• The Consumer Financial Protection Bureau, a federal watchdog agency, should crack down on debt collectors that do not ensure that patients have been screened for financial assistance before being pursued.
• The federal Centers for Medicare & Medicaid Services, which administers the two mammoth public insurance programs, should penalize hospitals that do not provide adequate financial assistance to patients.

“Nonprofit hospitals are contributing to medical debt and engaging in abusive billing and debt collection practices,” Mr. McConnell said. “The reason this keeps happening is the absence of clear guidelines and the federal government’s inadequate enforcement of existing regulations.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.

Human Rights Watch, the nonprofit that for decades has called attention to the victims of war, famine, and political repression around the world, is taking aim at U.S. hospitals for pushing millions of American patients into debt.

In a new report, the group calls for stronger government action to protect Americans from aggressive billing and debt collection by nonprofit hospitals, which Human Rights Watch said are systematically undermining patients’ human rights.

“Given the high prevalence of hospital-related medical debt in the U.S., this system is clearly not working,” concludes the report, which draws extensively on an ongoing investigation of medical debt by KFF Health News and NPR.

The report continues: “The U.S. model of subsidizing privately operated hospitals with tax exemptions in the hope that they will increase the accessibility of hospital care for un- and underinsured patients allows for abusive medical billing and debt collection practices and undermines human rights, including the right to health.”

Nationwide, about 100 million people – or 41% of adults – have some form of health care debt, a KFF survey conducted for the KFF Health News–NPR project found. And while patient debt is being driven by a range of medical and dental bills, polls and studies suggest hospitals are a major contributor.

About a third of U.S. adults with health care debt owed money for hospitalization, KFF’s polling found. Close to half of those owed at least $5,000. About a quarter owed $10,000 or more.

The scale of this crisis – which is unparalleled among wealthy nations – compelled Human Rights Watch to release the new report, said researcher Matt McConnell, its author. “Historically, Human Rights Watch has been an organization that has focused on international human rights issues,” he said. “But on medical debt, the U.S. is a real outlier. What you see is a system that privileges a few but creates large barriers to people accessing basic health rights.”

Hospital industry officials defend their work, citing hospitals’ broader work to help the communities they serve. “As a field, hospitals provide more benefit to their communities than any other sector in health care,” Melinda Hatton, general counsel at the American Hospital Association, wrote in a response to the Human Right Watch report.

Federal law requires private, tax-exempt hospitals – which make up more than half the nation’s medical centers – to provide care at no cost or at a discount to low-income patients. But reporting by KFF Health News and others has found that many hospitals make this aid difficult for patients to get.

At the same time, thousands of medical centers – including many tax-exempt ones – engage in aggressive debt collection tactics to pursue patients, including garnishing patients’ wages, placing liens on their homes, or selling their debt to third-party debt collectors.

Overall, KFF Health News found that most of the nation’s approximately 5,100 hospitals serving the general public have policies to use legal action or other aggressive tactics against patients. And one in five will deny nonemergency care to people with outstanding debt.

“Medical debt is drowning many low-income and working families while hospitals continue to benefit from nonprofit tax status as they pursue families for medical debt,” said Marceline White, executive director of Economic Action Maryland. The advocacy group has helped enact tighter rules to ensure Maryland hospitals make financial assistance more easily accessible and to restrict hospitals from some aggressive debt collection tactics, such as placing liens on patients’ homes.

Similar efforts are underway in other states, including Colorado, New Mexico, New York, Oregon, and Washington. But many patient and consumer advocates say stronger federal action is needed to expand patient protections.

The Human Rights Watch report – titled “In Sheep’s Clothing: United States’ Poorly Regulated Nonprofit Hospitals Undermine Health Care Access” – lists more than a dozen recommendations. These include:

• Congress should pass legislation to ensure that hospitals provide at least the same amount of charity care as they receive in public subsidies.
• The IRS should set uniform national standards on patients’ eligibility for financial assistance at nonprofit hospitals. Currently, hospitals are free to set their own standards, resulting in widespread variation, which can confuse patients.
• The Consumer Financial Protection Bureau, a federal watchdog agency, should crack down on debt collectors that do not ensure that patients have been screened for financial assistance before being pursued.
• The federal Centers for Medicare & Medicaid Services, which administers the two mammoth public insurance programs, should penalize hospitals that do not provide adequate financial assistance to patients.

“Nonprofit hospitals are contributing to medical debt and engaging in abusive billing and debt collection practices,” Mr. McConnell said. “The reason this keeps happening is the absence of clear guidelines and the federal government’s inadequate enforcement of existing regulations.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.

Human Rights Watch, the nonprofit that for decades has called attention to the victims of war, famine, and political repression around the world, is taking aim at U.S. hospitals for pushing millions of American patients into debt.

In a new report, the group calls for stronger government action to protect Americans from aggressive billing and debt collection by nonprofit hospitals, which Human Rights Watch said are systematically undermining patients’ human rights.

“Given the high prevalence of hospital-related medical debt in the U.S., this system is clearly not working,” concludes the report, which draws extensively on an ongoing investigation of medical debt by KFF Health News and NPR.

The report continues: “The U.S. model of subsidizing privately operated hospitals with tax exemptions in the hope that they will increase the accessibility of hospital care for un- and underinsured patients allows for abusive medical billing and debt collection practices and undermines human rights, including the right to health.”

Nationwide, about 100 million people – or 41% of adults – have some form of health care debt, a KFF survey conducted for the KFF Health News–NPR project found. And while patient debt is being driven by a range of medical and dental bills, polls and studies suggest hospitals are a major contributor.

About a third of U.S. adults with health care debt owed money for hospitalization, KFF’s polling found. Close to half of those owed at least $5,000. About a quarter owed $10,000 or more.

The scale of this crisis – which is unparalleled among wealthy nations – compelled Human Rights Watch to release the new report, said researcher Matt McConnell, its author. “Historically, Human Rights Watch has been an organization that has focused on international human rights issues,” he said. “But on medical debt, the U.S. is a real outlier. What you see is a system that privileges a few but creates large barriers to people accessing basic health rights.”

Hospital industry officials defend their work, citing hospitals’ broader work to help the communities they serve. “As a field, hospitals provide more benefit to their communities than any other sector in health care,” Melinda Hatton, general counsel at the American Hospital Association, wrote in a response to the Human Right Watch report.

Federal law requires private, tax-exempt hospitals – which make up more than half the nation’s medical centers – to provide care at no cost or at a discount to low-income patients. But reporting by KFF Health News and others has found that many hospitals make this aid difficult for patients to get.

At the same time, thousands of medical centers – including many tax-exempt ones – engage in aggressive debt collection tactics to pursue patients, including garnishing patients’ wages, placing liens on their homes, or selling their debt to third-party debt collectors.

Overall, KFF Health News found that most of the nation’s approximately 5,100 hospitals serving the general public have policies to use legal action or other aggressive tactics against patients. And one in five will deny nonemergency care to people with outstanding debt.

“Medical debt is drowning many low-income and working families while hospitals continue to benefit from nonprofit tax status as they pursue families for medical debt,” said Marceline White, executive director of Economic Action Maryland. The advocacy group has helped enact tighter rules to ensure Maryland hospitals make financial assistance more easily accessible and to restrict hospitals from some aggressive debt collection tactics, such as placing liens on patients’ homes.

Similar efforts are underway in other states, including Colorado, New Mexico, New York, Oregon, and Washington. But many patient and consumer advocates say stronger federal action is needed to expand patient protections.

The Human Rights Watch report – titled “In Sheep’s Clothing: United States’ Poorly Regulated Nonprofit Hospitals Undermine Health Care Access” – lists more than a dozen recommendations. These include:

• Congress should pass legislation to ensure that hospitals provide at least the same amount of charity care as they receive in public subsidies.
• The IRS should set uniform national standards on patients’ eligibility for financial assistance at nonprofit hospitals. Currently, hospitals are free to set their own standards, resulting in widespread variation, which can confuse patients.
• The Consumer Financial Protection Bureau, a federal watchdog agency, should crack down on debt collectors that do not ensure that patients have been screened for financial assistance before being pursued.
• The federal Centers for Medicare & Medicaid Services, which administers the two mammoth public insurance programs, should penalize hospitals that do not provide adequate financial assistance to patients.

“Nonprofit hospitals are contributing to medical debt and engaging in abusive billing and debt collection practices,” Mr. McConnell said. “The reason this keeps happening is the absence of clear guidelines and the federal government’s inadequate enforcement of existing regulations.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.

In patients with persistent dyspnea following a pulmonary embolism, rehabilitation should be considered as a treatment option, according to findings from a randomized, controlled trial comparing usual care to a twice-weekly, 8-week physical exercise program.

The prevalence of persistent dyspnea, functional limitations, and reduced quality of life (QoL) after pulmonary embolism (PE) ranges from 30% to 50% in published studies. While the underlying mechanisms remain unclear and are likely multifactorial, Øyvind Jervan, MD, and colleagues reported, research suggests that deconditioning and psychological factors contribute substantially to post-PE impairment. Optimal management remains unknown. Symptom improvement following rehabilitation programs in chronic obstructive pulmonary disease and in cardiac diseases is well documented, however, but evidence in the post–pulmonary embolism setting is limited.

The investigators randomized adult patients 1:1 from two hospitals (Osfold Hospital and Akershus University Hospital) with PE identified via computed tomography pulmonary angiography 6-72 months prior to study inclusion to either a supervised outpatient exercise program or usual care. The once- or twice-weekly home-based program was tailored to each participant and included a 90-minute educational session on the cardiopulmonary system, diagnosis and treatment of PE and its possible long-term effects, the benefits of exercise and physical activity, and the management of breathlessness. Also during the intervention period, participants were given a simple home-based exercise program to be performed once or twice weekly. Differences between groups in the Incremental Shuttle Walk Test (ISWT), a standardized walking test that assesses exercise capacity, was the primary endpoint. Secondary endpoints included an endurance walk test (ESWT) and measures of symptoms and QoL.

Among 211 participants (median age 57 years; 56% men), the median time from diagnosis to inclusion was 10.3 months. Median baseline walking distance on the ISWT was 695 m with 21% achieving the 1,020-m maximum distance. At follow-up, a between-group difference of 53.0 m favored the rehabilitation group (89 evaluable subjects; 87 in usual care) (P = .0035). While subgroup analysis revealed a greater difference for those with shorter time from diagnosis (6-12 months vs. 12.1-72 months), the between-group differences were nonsignificant. Also, no ISWT differences between the intervention and control group were found for those with higher pulmonary embolism severity and dyspnea scores. The walk endurance test revealed no between-group differences.

Scores at follow-up on the Pulmonary Embolism-QoL questionnaire favored the rehabilitation group (mean difference –4%; P = .041), but there were no differences in generic QoL, dyspnea scores, or the ESWT.

“The present study adds to the growing evidence of the benefits of rehabilitation after PE,” the researchers stated. Although several recent studies have shown rehabilitation after PE results that were promising, the authors pointed out that most of these studies have been small or have lacked a control group, with great variations between them with respect to time, mode, and duration of intervention. In addition, the current study is the largest one addressing the effect of rehabilitation after PE to demonstrate in subjects with persistent dyspnea a positive effect on exercise capacity and QoL.

The researchers also commented that the small detected mean difference of 53 m in walking distance was lower than has been considered a worthwhile improvement by some, and its clinical relevance can be debated. Other studies, however, have used mean group differences of 40-62 m as clinically meaningful. The authors underscored also that the ISWT data were subject to a considerable ceiling effect which may underestimate the effect size.

Addressing study limitations, the researchers added that: “The rehabilitation program in the present study consisted mainly of exercise training. It is unknown whether the addition of occupational therapy, psychology, or dietary therapy would provide additional benefits for the participants. Most participants had mild symptoms, which may have limited the potential benefits of our rehabilitation program.”

The project was funded by Østfold Hospital Trust. Dr. Jervan reported no relevant conflicts of interest.

In patients with persistent dyspnea following a pulmonary embolism, rehabilitation should be considered as a treatment option, according to findings from a randomized, controlled trial comparing usual care to a twice-weekly, 8-week physical exercise program.

The prevalence of persistent dyspnea, functional limitations, and reduced quality of life (QoL) after pulmonary embolism (PE) ranges from 30% to 50% in published studies. While the underlying mechanisms remain unclear and are likely multifactorial, Øyvind Jervan, MD, and colleagues reported, research suggests that deconditioning and psychological factors contribute substantially to post-PE impairment. Optimal management remains unknown. Symptom improvement following rehabilitation programs in chronic obstructive pulmonary disease and in cardiac diseases is well documented, however, but evidence in the post–pulmonary embolism setting is limited.

The investigators randomized adult patients 1:1 from two hospitals (Osfold Hospital and Akershus University Hospital) with PE identified via computed tomography pulmonary angiography 6-72 months prior to study inclusion to either a supervised outpatient exercise program or usual care. The once- or twice-weekly home-based program was tailored to each participant and included a 90-minute educational session on the cardiopulmonary system, diagnosis and treatment of PE and its possible long-term effects, the benefits of exercise and physical activity, and the management of breathlessness. Also during the intervention period, participants were given a simple home-based exercise program to be performed once or twice weekly. Differences between groups in the Incremental Shuttle Walk Test (ISWT), a standardized walking test that assesses exercise capacity, was the primary endpoint. Secondary endpoints included an endurance walk test (ESWT) and measures of symptoms and QoL.

Among 211 participants (median age 57 years; 56% men), the median time from diagnosis to inclusion was 10.3 months. Median baseline walking distance on the ISWT was 695 m with 21% achieving the 1,020-m maximum distance. At follow-up, a between-group difference of 53.0 m favored the rehabilitation group (89 evaluable subjects; 87 in usual care) (P = .0035). While subgroup analysis revealed a greater difference for those with shorter time from diagnosis (6-12 months vs. 12.1-72 months), the between-group differences were nonsignificant. Also, no ISWT differences between the intervention and control group were found for those with higher pulmonary embolism severity and dyspnea scores. The walk endurance test revealed no between-group differences.

Scores at follow-up on the Pulmonary Embolism-QoL questionnaire favored the rehabilitation group (mean difference –4%; P = .041), but there were no differences in generic QoL, dyspnea scores, or the ESWT.

“The present study adds to the growing evidence of the benefits of rehabilitation after PE,” the researchers stated. Although several recent studies have shown rehabilitation after PE results that were promising, the authors pointed out that most of these studies have been small or have lacked a control group, with great variations between them with respect to time, mode, and duration of intervention. In addition, the current study is the largest one addressing the effect of rehabilitation after PE to demonstrate in subjects with persistent dyspnea a positive effect on exercise capacity and QoL.

The researchers also commented that the small detected mean difference of 53 m in walking distance was lower than has been considered a worthwhile improvement by some, and its clinical relevance can be debated. Other studies, however, have used mean group differences of 40-62 m as clinically meaningful. The authors underscored also that the ISWT data were subject to a considerable ceiling effect which may underestimate the effect size.

Addressing study limitations, the researchers added that: “The rehabilitation program in the present study consisted mainly of exercise training. It is unknown whether the addition of occupational therapy, psychology, or dietary therapy would provide additional benefits for the participants. Most participants had mild symptoms, which may have limited the potential benefits of our rehabilitation program.”

The project was funded by Østfold Hospital Trust. Dr. Jervan reported no relevant conflicts of interest.

In patients with persistent dyspnea following a pulmonary embolism, rehabilitation should be considered as a treatment option, according to findings from a randomized, controlled trial comparing usual care to a twice-weekly, 8-week physical exercise program.

The prevalence of persistent dyspnea, functional limitations, and reduced quality of life (QoL) after pulmonary embolism (PE) ranges from 30% to 50% in published studies. While the underlying mechanisms remain unclear and are likely multifactorial, Øyvind Jervan, MD, and colleagues reported, research suggests that deconditioning and psychological factors contribute substantially to post-PE impairment. Optimal management remains unknown. Symptom improvement following rehabilitation programs in chronic obstructive pulmonary disease and in cardiac diseases is well documented, however, but evidence in the post–pulmonary embolism setting is limited.

The investigators randomized adult patients 1:1 from two hospitals (Osfold Hospital and Akershus University Hospital) with PE identified via computed tomography pulmonary angiography 6-72 months prior to study inclusion to either a supervised outpatient exercise program or usual care. The once- or twice-weekly home-based program was tailored to each participant and included a 90-minute educational session on the cardiopulmonary system, diagnosis and treatment of PE and its possible long-term effects, the benefits of exercise and physical activity, and the management of breathlessness. Also during the intervention period, participants were given a simple home-based exercise program to be performed once or twice weekly. Differences between groups in the Incremental Shuttle Walk Test (ISWT), a standardized walking test that assesses exercise capacity, was the primary endpoint. Secondary endpoints included an endurance walk test (ESWT) and measures of symptoms and QoL.

Among 211 participants (median age 57 years; 56% men), the median time from diagnosis to inclusion was 10.3 months. Median baseline walking distance on the ISWT was 695 m with 21% achieving the 1,020-m maximum distance. At follow-up, a between-group difference of 53.0 m favored the rehabilitation group (89 evaluable subjects; 87 in usual care) (P = .0035). While subgroup analysis revealed a greater difference for those with shorter time from diagnosis (6-12 months vs. 12.1-72 months), the between-group differences were nonsignificant. Also, no ISWT differences between the intervention and control group were found for those with higher pulmonary embolism severity and dyspnea scores. The walk endurance test revealed no between-group differences.

Scores at follow-up on the Pulmonary Embolism-QoL questionnaire favored the rehabilitation group (mean difference –4%; P = .041), but there were no differences in generic QoL, dyspnea scores, or the ESWT.

“The present study adds to the growing evidence of the benefits of rehabilitation after PE,” the researchers stated. Although several recent studies have shown rehabilitation after PE results that were promising, the authors pointed out that most of these studies have been small or have lacked a control group, with great variations between them with respect to time, mode, and duration of intervention. In addition, the current study is the largest one addressing the effect of rehabilitation after PE to demonstrate in subjects with persistent dyspnea a positive effect on exercise capacity and QoL.

The researchers also commented that the small detected mean difference of 53 m in walking distance was lower than has been considered a worthwhile improvement by some, and its clinical relevance can be debated. Other studies, however, have used mean group differences of 40-62 m as clinically meaningful. The authors underscored also that the ISWT data were subject to a considerable ceiling effect which may underestimate the effect size.

Addressing study limitations, the researchers added that: “The rehabilitation program in the present study consisted mainly of exercise training. It is unknown whether the addition of occupational therapy, psychology, or dietary therapy would provide additional benefits for the participants. Most participants had mild symptoms, which may have limited the potential benefits of our rehabilitation program.”

The project was funded by Østfold Hospital Trust. Dr. Jervan reported no relevant conflicts of interest.

Patients with persistent depressive or cognitive symptoms after mild to moderate COVID-19 (COVID-DC) may have gliosis and inflammation, data suggest.

In a case-control study of 40 patients who were treated at a tertiary care psychiatric hospital in Canada, the level of translocator protein total distribution volume (TSPO VT), a marker of gliosis, was 9.23 mL/cm³ among patients with COVID-DC and 7.72 mL/cm³ among control persons. Differences were particularly notable in the ventral striatum and dorsal putamen.

“Most theories assume there is inflammation in the brain [with] long COVID,” but that assumption had not been studied, author Jeffrey H. Meyer, MD, PhD, Canada Research Chair in Neurochemistry of Major Depressive Disorder at the University of Toronto, said in an interview. “Such information is pivotal to developing treatments.”

The study was published online in JAMA Psychiatry.
 

Quantifiable marker

The investigators sought to determine whether levels of TSPO VT, which are quantifiable with PET, are elevated in the dorsal putamen, ventral striatum, prefrontal cortex, anterior cingulate cortex, and hippocampus of patients with COVID-DC, compared with patients without this syndrome. These brain regions were chosen, according to the authors, “because injury in these regions, which can cause gliosis, also induces symptoms of COVID-DC.”

The study was conducted from April 2021 through June 30, 2022. The investigators compared levels of TSPO VT in the selected brain regions of 20 participants with COVID-DC (mean age, 32.7 years; 60% women) with that of 20 control persons (mean age, 33.3 years; 55% women). TSPO VT was measured with fluorine F18–labeled N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide PET.

The difference in TSPO VT was most noticeable in the ventral striatum (mean difference, 1.97 mL/cm³) and dorsal putamen (mean difference, 1.70 mL/cm³). The study authors suggest that gliosis in these areas may explain some of the persistent symptoms reported in structured clinical interviews and assessed on neuropsychological and psychological testing.

For patients with COVID-DC, motor speed on the finger-tapping test was negatively associated with dorsal putamen TSPO VT (r, −0.53). The 10 participants with COVID-DC whose speed was lowest had higher mean dorsal putamen TSPO VT levels than those of control persons by 2.3 mL/cm³.

The investigators could not assess a possible association between the ventral striatum TSPO VT and anhedonia because all participants had these symptoms. No significant correlations were found between depression and TSPO VT in the prefrontal cortex or anterior cingulate cortex.

The authors acknowledged that the study was cross-sectional, and so the duration of persistently elevated TSPO VT is not yet known. In addition, elevation in TSPO VT is not completely specific to glial cells, and although correlations with finger-tapping test performance reflect associations between brain changes and symptoms, they do not prove cause and effect.

“Presently, clinicians can use treatments for symptoms in other illnesses that are [also] common with long COVID. We need better than this,” said Dr. Meyer. “Clients with long COVID should be able to state their symptoms, and the practitioner should have an evidence-based matching treatment to recommend.”

Research is ongoing. “We are acquiring more information regarding different types of inflammation in the brain, whether there is ongoing injury, and whether treatments that influence inflammation are helpful,” said Dr. Meyer.
 

Jigsaw puzzle

“While this is an important piece in the jigsaw puzzle of neuroinflammation in chronic neurological disease, it is important to keep in mind that we still lack understanding of the complex picture for several reasons,” Alexander Gerhard, MD, honorary senior lecturer in neuroscience at the University of Manchester, England, wrote in an accompanying editorial.

Among these reasons is that the PET technique used in the study is noisy and not restricted to glial cells, he wrote. TSPO expression is only one part of the brain’s neuroinflammatory response, but PET techniques “do not currently allow us to distinguish between different states of microglial activation.” In addition, “a much more detailed understanding of microglial activation at different time points” is needed before neuroinflammatory changes can be targeted therapeutically, Dr. Gerhard wrote.

In a comment, Vilma Gabbay, MD, professor of psychiatry and neuroscience and director of biomarkers and dimensional psychiatry in the Psychiatry Research Institute at Montefiore Einstein, Albert Einstein College of Medicine, New York, said that “this is an important initial step to better understand the neuropsychiatric consequences of COVID even in only a mild and moderate viral illness.” TSPO imaging through PET scanning has been used as an index for neuroinflammation and gliosis. Researchers have used it to study neurodegenerative diseases, but as the authors noted, the ligand is not specific for gliosis.

“Follow-up large cohort studies including other measures of neuroimaging modalities assessing circuitry and neurochemistry are needed,” she said. “Similarly, studying the blood-brain barrier will also allow us to better understand how the immune reaction in the blood transitions to the brain.”

This field of research is evolving, and clinical trials are ongoing, Dr. Gabbay added. Meanwhile, clinicians should monitor for, assess, and treat neuropsychiatric symptoms and “follow the literature for new research and management recommendations.”

The study was primarily funded by a Canadian Institutes of Health Research Project grant to the authors, with some funding from the Canadian Institute for Military and Veteran Health Research. Dr. Meyer received support from their Canada Research Chair awards and received grants and support from several pharmaceutical companies outside of the submitted work. Dr. Gerhard and Dr. Gabbay disclosed no relevant financial relationships.

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

Patients with persistent depressive or cognitive symptoms after mild to moderate COVID-19 (COVID-DC) may have gliosis and inflammation, data suggest.

In a case-control study of 40 patients who were treated at a tertiary care psychiatric hospital in Canada, the level of translocator protein total distribution volume (TSPO VT), a marker of gliosis, was 9.23 mL/cm³ among patients with COVID-DC and 7.72 mL/cm³ among control persons. Differences were particularly notable in the ventral striatum and dorsal putamen.

“Most theories assume there is inflammation in the brain [with] long COVID,” but that assumption had not been studied, author Jeffrey H. Meyer, MD, PhD, Canada Research Chair in Neurochemistry of Major Depressive Disorder at the University of Toronto, said in an interview. “Such information is pivotal to developing treatments.”

The study was published online in JAMA Psychiatry.
 

Quantifiable marker

The investigators sought to determine whether levels of TSPO VT, which are quantifiable with PET, are elevated in the dorsal putamen, ventral striatum, prefrontal cortex, anterior cingulate cortex, and hippocampus of patients with COVID-DC, compared with patients without this syndrome. These brain regions were chosen, according to the authors, “because injury in these regions, which can cause gliosis, also induces symptoms of COVID-DC.”

The study was conducted from April 2021 through June 30, 2022. The investigators compared levels of TSPO VT in the selected brain regions of 20 participants with COVID-DC (mean age, 32.7 years; 60% women) with that of 20 control persons (mean age, 33.3 years; 55% women). TSPO VT was measured with fluorine F18–labeled N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide PET.

The difference in TSPO VT was most noticeable in the ventral striatum (mean difference, 1.97 mL/cm³) and dorsal putamen (mean difference, 1.70 mL/cm³). The study authors suggest that gliosis in these areas may explain some of the persistent symptoms reported in structured clinical interviews and assessed on neuropsychological and psychological testing.

For patients with COVID-DC, motor speed on the finger-tapping test was negatively associated with dorsal putamen TSPO VT (r, −0.53). The 10 participants with COVID-DC whose speed was lowest had higher mean dorsal putamen TSPO VT levels than those of control persons by 2.3 mL/cm³.

The investigators could not assess a possible association between the ventral striatum TSPO VT and anhedonia because all participants had these symptoms. No significant correlations were found between depression and TSPO VT in the prefrontal cortex or anterior cingulate cortex.

The authors acknowledged that the study was cross-sectional, and so the duration of persistently elevated TSPO VT is not yet known. In addition, elevation in TSPO VT is not completely specific to glial cells, and although correlations with finger-tapping test performance reflect associations between brain changes and symptoms, they do not prove cause and effect.

“Presently, clinicians can use treatments for symptoms in other illnesses that are [also] common with long COVID. We need better than this,” said Dr. Meyer. “Clients with long COVID should be able to state their symptoms, and the practitioner should have an evidence-based matching treatment to recommend.”

Research is ongoing. “We are acquiring more information regarding different types of inflammation in the brain, whether there is ongoing injury, and whether treatments that influence inflammation are helpful,” said Dr. Meyer.
 

Jigsaw puzzle

“While this is an important piece in the jigsaw puzzle of neuroinflammation in chronic neurological disease, it is important to keep in mind that we still lack understanding of the complex picture for several reasons,” Alexander Gerhard, MD, honorary senior lecturer in neuroscience at the University of Manchester, England, wrote in an accompanying editorial.

Among these reasons is that the PET technique used in the study is noisy and not restricted to glial cells, he wrote. TSPO expression is only one part of the brain’s neuroinflammatory response, but PET techniques “do not currently allow us to distinguish between different states of microglial activation.” In addition, “a much more detailed understanding of microglial activation at different time points” is needed before neuroinflammatory changes can be targeted therapeutically, Dr. Gerhard wrote.

In a comment, Vilma Gabbay, MD, professor of psychiatry and neuroscience and director of biomarkers and dimensional psychiatry in the Psychiatry Research Institute at Montefiore Einstein, Albert Einstein College of Medicine, New York, said that “this is an important initial step to better understand the neuropsychiatric consequences of COVID even in only a mild and moderate viral illness.” TSPO imaging through PET scanning has been used as an index for neuroinflammation and gliosis. Researchers have used it to study neurodegenerative diseases, but as the authors noted, the ligand is not specific for gliosis.

“Follow-up large cohort studies including other measures of neuroimaging modalities assessing circuitry and neurochemistry are needed,” she said. “Similarly, studying the blood-brain barrier will also allow us to better understand how the immune reaction in the blood transitions to the brain.”

This field of research is evolving, and clinical trials are ongoing, Dr. Gabbay added. Meanwhile, clinicians should monitor for, assess, and treat neuropsychiatric symptoms and “follow the literature for new research and management recommendations.”

The study was primarily funded by a Canadian Institutes of Health Research Project grant to the authors, with some funding from the Canadian Institute for Military and Veteran Health Research. Dr. Meyer received support from their Canada Research Chair awards and received grants and support from several pharmaceutical companies outside of the submitted work. Dr. Gerhard and Dr. Gabbay disclosed no relevant financial relationships.

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

Patients with persistent depressive or cognitive symptoms after mild to moderate COVID-19 (COVID-DC) may have gliosis and inflammation, data suggest.

In a case-control study of 40 patients who were treated at a tertiary care psychiatric hospital in Canada, the level of translocator protein total distribution volume (TSPO VT), a marker of gliosis, was 9.23 mL/cm³ among patients with COVID-DC and 7.72 mL/cm³ among control persons. Differences were particularly notable in the ventral striatum and dorsal putamen.

“Most theories assume there is inflammation in the brain [with] long COVID,” but that assumption had not been studied, author Jeffrey H. Meyer, MD, PhD, Canada Research Chair in Neurochemistry of Major Depressive Disorder at the University of Toronto, said in an interview. “Such information is pivotal to developing treatments.”

The study was published online in JAMA Psychiatry.
 

Quantifiable marker

The investigators sought to determine whether levels of TSPO VT, which are quantifiable with PET, are elevated in the dorsal putamen, ventral striatum, prefrontal cortex, anterior cingulate cortex, and hippocampus of patients with COVID-DC, compared with patients without this syndrome. These brain regions were chosen, according to the authors, “because injury in these regions, which can cause gliosis, also induces symptoms of COVID-DC.”

The study was conducted from April 2021 through June 30, 2022. The investigators compared levels of TSPO VT in the selected brain regions of 20 participants with COVID-DC (mean age, 32.7 years; 60% women) with that of 20 control persons (mean age, 33.3 years; 55% women). TSPO VT was measured with fluorine F18–labeled N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide PET.

The difference in TSPO VT was most noticeable in the ventral striatum (mean difference, 1.97 mL/cm³) and dorsal putamen (mean difference, 1.70 mL/cm³). The study authors suggest that gliosis in these areas may explain some of the persistent symptoms reported in structured clinical interviews and assessed on neuropsychological and psychological testing.

For patients with COVID-DC, motor speed on the finger-tapping test was negatively associated with dorsal putamen TSPO VT (r, −0.53). The 10 participants with COVID-DC whose speed was lowest had higher mean dorsal putamen TSPO VT levels than those of control persons by 2.3 mL/cm³.

The investigators could not assess a possible association between the ventral striatum TSPO VT and anhedonia because all participants had these symptoms. No significant correlations were found between depression and TSPO VT in the prefrontal cortex or anterior cingulate cortex.

The authors acknowledged that the study was cross-sectional, and so the duration of persistently elevated TSPO VT is not yet known. In addition, elevation in TSPO VT is not completely specific to glial cells, and although correlations with finger-tapping test performance reflect associations between brain changes and symptoms, they do not prove cause and effect.

“Presently, clinicians can use treatments for symptoms in other illnesses that are [also] common with long COVID. We need better than this,” said Dr. Meyer. “Clients with long COVID should be able to state their symptoms, and the practitioner should have an evidence-based matching treatment to recommend.”

Research is ongoing. “We are acquiring more information regarding different types of inflammation in the brain, whether there is ongoing injury, and whether treatments that influence inflammation are helpful,” said Dr. Meyer.
 

Jigsaw puzzle

“While this is an important piece in the jigsaw puzzle of neuroinflammation in chronic neurological disease, it is important to keep in mind that we still lack understanding of the complex picture for several reasons,” Alexander Gerhard, MD, honorary senior lecturer in neuroscience at the University of Manchester, England, wrote in an accompanying editorial.

Among these reasons is that the PET technique used in the study is noisy and not restricted to glial cells, he wrote. TSPO expression is only one part of the brain’s neuroinflammatory response, but PET techniques “do not currently allow us to distinguish between different states of microglial activation.” In addition, “a much more detailed understanding of microglial activation at different time points” is needed before neuroinflammatory changes can be targeted therapeutically, Dr. Gerhard wrote.

In a comment, Vilma Gabbay, MD, professor of psychiatry and neuroscience and director of biomarkers and dimensional psychiatry in the Psychiatry Research Institute at Montefiore Einstein, Albert Einstein College of Medicine, New York, said that “this is an important initial step to better understand the neuropsychiatric consequences of COVID even in only a mild and moderate viral illness.” TSPO imaging through PET scanning has been used as an index for neuroinflammation and gliosis. Researchers have used it to study neurodegenerative diseases, but as the authors noted, the ligand is not specific for gliosis.

“Follow-up large cohort studies including other measures of neuroimaging modalities assessing circuitry and neurochemistry are needed,” she said. “Similarly, studying the blood-brain barrier will also allow us to better understand how the immune reaction in the blood transitions to the brain.”

This field of research is evolving, and clinical trials are ongoing, Dr. Gabbay added. Meanwhile, clinicians should monitor for, assess, and treat neuropsychiatric symptoms and “follow the literature for new research and management recommendations.”

The study was primarily funded by a Canadian Institutes of Health Research Project grant to the authors, with some funding from the Canadian Institute for Military and Veteran Health Research. Dr. Meyer received support from their Canada Research Chair awards and received grants and support from several pharmaceutical companies outside of the submitted work. Dr. Gerhard and Dr. Gabbay disclosed no relevant financial relationships.

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

MILAN – The impact of the COVID-19 pandemic on patients with rheumatic and nonrheumatic autoimmune diseases is ongoing and not yet fully comprehended. New data presented at the annual European Congress of Rheumatology, primarily derived from the global COVID-19 in Autoimmune Diseases (COVAD) survey but not limited to it, provide reassurance regarding the protection and safety of COVID-19 vaccines for older and younger adults, as well as for pregnant and breastfeeding women. These data also explore the influence of underlying diseases and medications on breakthrough SARS-CoV-2 infections and infection outcomes.

Safety of vaccines in patients with autoimmune or immune-mediated diseases

Following vaccination, even with low levels of antibodies, the risk of severe COVID-19 remains relatively low for patients who receive immunosuppressive therapy for various immune-mediated inflammatory diseases (IMIDs). This encouraging finding comes from the Nor-vaC study, presented by Hilde Ørbo, MD, of the Center for Treatment of Rheumatic and Musculoskeletal Diseases, Diakonhjemmet Hospital, Oslo.

During the presentation, Dr. Ørbo stated: “We did not find any specific diagnosis or medication associated with a significantly higher risk of hospitalization.” Receiving booster doses of the vaccine, having high levels of anti-spike antibodies after vaccination, and achieving hybrid immunity are correlated with further reductions in the risk of breakthrough SARS-CoV-2 infections.

Dr. Hilde Ørbo

Between Feb. 15, 2021, and Feb. 15, 2023, COVID-19 affected a similar proportion among the 729 patients and 350 healthy control persons (67% and 68%, respectively). Among the patients, 22 reported severe COVID-19, whereas none of the healthy control persons did. However, there were no fatalities among the patients. The study cohort consisted of patients with various IMIDs; 70% had an inflammatory joint disease. The use of immunosuppressive medications also varied, with 63% of patients using tumor necrosis factor inhibitors, either as monotherapy or in combination with other treatments, and other patients taking medications such as methotrexate, interleukin inhibitors, Janus kinase inhibitors, vedolizumab (Entyvio), and others.

While being older than 70 years and the presence of comorbidities were identified as risk factors for severe COVID-19, there was a significant reduction in risk with each additional vaccine dose. These results support the protective role of repeated COVID-19 vaccination for patients with IMIDs who are receiving immunosuppressive therapies; they yield a favorable prognosis even with the Omicron variant.

The study further compared the risk of severe COVID-19 between a group with hybrid immunity (having received three vaccine doses and experiencing breakthrough infection with the Omicron variant) and a group that received a fourth vaccine dose within the same time frame. The difference was striking: Hybrid immunity was associated with a 5.8-fold decrease in risk, compared with four-dose vaccination (P < .0001).

The level of antibodies, measured 2-4 weeks after the last vaccination, was predictive of the risk of breakthrough COVID-19. An antibody level above 6000 binding antibody units/mL after vaccination was significantly associated with a reduction in risk. “We can conclude that patients who receive multiple vaccine doses have a lower risk of COVID-19,” Dr. Ørbo said. “In patients who recently experienced breakthrough infections, the administration of a booster vaccine dose might be delayed.”

EULAR

“The virus has undergone changes throughout the pandemic, while the vaccines have remained relatively stable. Are we anticipating more infections over time?” asked Hendrik Schulze-Koops, MD, PhD, of Ludwig Maximilians University of Munich (Germany), the session moderator. In response, Dr. Ørbo stated that 85% of the recorded infections in the study occurred after the emergence of the Omicron variant, and time was considered a covariable in the analysis.

These data shed light on a topic discussed by Pedro Machado, MD, PhD, professor and consultant in rheumatology and neuromuscular diseases at University College London, during his scientific session talk entitled, “Unsolved Issues of COVID Vaccination and Re-vaccination.” Dr. Machado referred to the VROOM study published in 2022, which examined the interruption of methotrexate for 2 weeks following booster administration. Both groups demonstrated a significant antibody response, but the group that stopped taking methotrexate showed double the antibody titers.

However, he emphasized, “what remains unknown is the clinical relevance of these differences in terms of severe infection, hospitalization, or even death. The potential benefit of increased immunogenicity by interrupting conventional synthetic disease-modifying antirheumatic drugs [csDMARDs] such as methotrexate before or after vaccination needs to be balanced against the potential risk of disease flare. Ultimately, decision-making should be individualized based on factors such as comorbidities, disease activity, and other considerations.” The results presented by Dr. Ørbo suggest that, while there may be a clinical difference in terms of severe infection, the overall prognosis for vaccinated patients is reasonably good.

Regarding other DMARDs, such as biologics, the approach may differ. Dr. Machado suggested: “In patients using rituximab or other B cell–depleting therapies, SARS-CoV-2 vaccination should be scheduled in a way that optimizes vaccine immunogenicity. A minimum of 10 B cells/mcL of blood is likely a relevant threshold above which a sufficient cellular and immune response is established.”
 

COVID vaccines are safe for pregnant and breastfeeding women

According to data from the COVAD study, which comprised two global cross-sectional surveys conducted in 2021 and 2022, the COVID-19 vaccine appeared safe for pregnant and breastfeeding women with autoimmune diseases (AID).

Presenter Laura Andreoli, MD, PhD, of the University of Brescia (Italy), said that, although pregnant patients with AID reported more adverse events related to vaccination, these rates were not significantly higher than those among pregnant, healthy control persons who were without AID. No difference in adverse events was observed between breastfeeding women and healthy control persons, and the incidence of disease flares did not significantly differ among all groups.

“In summary, this study provides initial insights into the safety of COVID-19 vaccination during the gestational and postpartum periods in women with autoimmune diseases. These reassuring observations will hopefully improve clinician-patient communication and address hesitancy towards COVID-19 vaccination, as the benefits for the mother and fetus through passive immunization appear to outweigh potential risks,” Dr. Andreoli said in an interview.

“The large number of participants and the global geographical spread of the COVAD survey were very beneficial in gaining access to this important subset of patients,” added Dr. Andreoli. However, she acknowledged that patients with low socioeconomic status and/or high disability were likely underrepresented. While no data on pregnancy outcomes have been collected thus far, Dr. Andreoli expressed the desire to include them in the study’s follow-up.

The COVAD survey data also indicate that, in general, vaccine hesitancy among patients with AID is decreasing; from 2021 to 2022, it declined from 16.5% to 5.1%, as Dr. Machado indicated in his presentation.
 

Multiple factors contribute to breakthrough infections

The risk of breakthrough SARS-CoV-2 infections after vaccination varies among patients with rheumatoid arthritis and rheumatic or nonrheumatic autoimmune diseases, primarily depending on the underlying condition rather than the immunosuppressive medication. Environmental factors also appear to play a role. This complex landscape emerges from a further analysis of the COVAD survey dataset.

Alessia Alunno, MD, PhD, of the University of L’Aquila (Italy), presented a detailed and occasionally counterintuitive picture of similarities and differences among young adult patients (aged 18-35 years), mostly women, with various rheumatic and nonrheumatic diseases in relation to COVID-19. Most notably, the type of disease seemed to have more significance than the immunosuppression resulting from the treatment regimen. This held true for vaccine safety as well as for the risk of breakthrough COVID-19 and symptom profiles.

Patients with rheumatic disease (RMD) and nonrheumatic autoimmune disease (nr-AD) had significantly different therapeutic profiles on average. Before vaccination, 45% of patients with RMD used glucocorticoids (GC), and 91% used immunosuppressants (IS). In contrast, only 9.5% of nr-AD patients used GC, and 21% were taking IS.

Interestingly, the overall prevalence of reported SARS-CoV-2 infections was not influenced by medication and was practically identical (25% to 28%) across all groups. However, there were intriguing differences in the occurrence of infections before and after vaccination between disease groups. Prevaccine infections were less frequent among patients with RMD compared with healthy control persons (adjusted odds ratio, 0.6), while the rates were similar among patients with nr-AD and healthy control persons. On the other hand, breakthrough infections were more frequent in patients with RMD (aOR, 2.7), whereas the rate was similar between healthy control persons and patients with nr-AD.

Despite a much lower rate of GC/IS use, patients with nr-AD experienced repeated infections more frequently. In contrast, patients with RMD were less prone to multiple infections, even compared with healthy control persons (aOR, 0.5).

Regarding the disease profile, fewer than 5% of all infected patients required advanced therapies for SARS-CoV-2 infection. Notably, all SARS-CoV-2 infections in patients with nr-AD were symptomatic, whereas among patients with RMD and healthy control persons, the incidence of asymptomatic infections was 3%. The rate of hospital admissions was 4% for patients with RMD, compared with 2% for patients with nr-AD and 1% for control persons. The RMD group exhibited some differences between prevaccine infections and breakthrough infections, including a significantly lower frequency of loss of smell and taste during breakthrough infections. Overall, patients with RMD and COVID-19 experienced cough, runny nose, throat pain, nausea, and vomiting more frequently. In contrast, patients with nr-AD had a much higher risk of skin rashes during breakthrough infections (aOR, 8.7).

Vaccine adverse events (AEs) were also influenced by the underlying disease. Patients with RMD and those with nr-AD were more likely to experience mild AEs after the first or second dose, compared with healthy control persons (adjusted OR, 2.4 and 2.0, respectively). The most common early, mild AEs across all groups were injection-site pain, headache, and fatigue, but they occurred more frequently in the nr-AD group than in the RMD or healthy control group. Additionally, fever and chills occurred more frequently among the nr-AD group. Late, mild AEs and severe AEs were rare and affected all groups equally.

“The overall incidence of AEs was very low. Our results certainly do not undermine the safety of vaccines,” Dr. Alunno said.

Disease flares were more common after vaccination (10% with RMD and 7% with nr-AD) than after infection (5% with RMD and 1.5% with nr-AD). Furthermore, in many cases, after vaccination, flares required a change of medications, particularly for patients with RMD.

Dr. Naveen Ravichandran

Additional results from the COVAD survey from January to July 2022, presented by Naveen Ravichandran, MD, DM, of Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India, revealed a higher prevalence (OR, 1.2; P = .001) of breakthrough infections among patients with RA. A total of 22.6% of patients with RA experienced breakthrough infections, compared with 20.6% for patients with other autoimmune rheumatic diseases and 18.4% of healthy control persons. Hospitalizations and the need for advanced treatment were also more common among patients with RA (30.9%) than among healthy control persons (13.9%). Patients with RA who had breakthrough infections tended to be older (closer to 50 years of age on average) and female, and they were more likely to have comorbidities and mental disorders. The human development index of the patient’s country of residence also played a role. Further research is necessary to understand how breakthrough infection outcomes are affected by a patient’s socioeconomic situation.

According to Dr. Ravichandran, medication was not a significant factor, except for the use of steroids and rituximab, which were associated with a higher risk of severe COVID-19 and hospitalization. Patients using rituximab, in particular, faced significantly increased odds for hospitalization (OR, 3.4) and severe breakthrough COVID-19 (OR, 3.0).

Session moderator Kim Lauper, MD, of the University of Geneva, cautioned: “The roles of disease and medication are challenging to separate. Some diseases require a more aggressive immunosuppressive regimen. It’s possible that different diseases affect the immune system differently, but it is not easy to demonstrate.”

The complications observed in the data warrant further study, as mentioned by Dr. Schulze-Koops: “We have a problem tied to the time line of the pandemic, where we had different viruses, different population behaviors, different treatments, and different standards of care over time. We also have differences between ethnic communities and regions of the world. But most importantly, we have different viruses: From the original strain to Delta to Omicron, we know they have very different clinical outcomes. I believe we need more scientific research to unravel these factors.”

Dr. Ørbo, Dr. Ravichandran, Dr. Andreoli, and Dr. Alunno reported no relevant financial relationships. Dr. Machado has received grants and/or honoraria from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Janssen, Merck Sharp & Dohme, Novartis, Orphazyme, Pfizer, Roche, and UCB.

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

MILAN – The impact of the COVID-19 pandemic on patients with rheumatic and nonrheumatic autoimmune diseases is ongoing and not yet fully comprehended. New data presented at the annual European Congress of Rheumatology, primarily derived from the global COVID-19 in Autoimmune Diseases (COVAD) survey but not limited to it, provide reassurance regarding the protection and safety of COVID-19 vaccines for older and younger adults, as well as for pregnant and breastfeeding women. These data also explore the influence of underlying diseases and medications on breakthrough SARS-CoV-2 infections and infection outcomes.

Safety of vaccines in patients with autoimmune or immune-mediated diseases

Following vaccination, even with low levels of antibodies, the risk of severe COVID-19 remains relatively low for patients who receive immunosuppressive therapy for various immune-mediated inflammatory diseases (IMIDs). This encouraging finding comes from the Nor-vaC study, presented by Hilde Ørbo, MD, of the Center for Treatment of Rheumatic and Musculoskeletal Diseases, Diakonhjemmet Hospital, Oslo.

During the presentation, Dr. Ørbo stated: “We did not find any specific diagnosis or medication associated with a significantly higher risk of hospitalization.” Receiving booster doses of the vaccine, having high levels of anti-spike antibodies after vaccination, and achieving hybrid immunity are correlated with further reductions in the risk of breakthrough SARS-CoV-2 infections.

Dr. Hilde Ørbo

Between Feb. 15, 2021, and Feb. 15, 2023, COVID-19 affected a similar proportion among the 729 patients and 350 healthy control persons (67% and 68%, respectively). Among the patients, 22 reported severe COVID-19, whereas none of the healthy control persons did. However, there were no fatalities among the patients. The study cohort consisted of patients with various IMIDs; 70% had an inflammatory joint disease. The use of immunosuppressive medications also varied, with 63% of patients using tumor necrosis factor inhibitors, either as monotherapy or in combination with other treatments, and other patients taking medications such as methotrexate, interleukin inhibitors, Janus kinase inhibitors, vedolizumab (Entyvio), and others.

While being older than 70 years and the presence of comorbidities were identified as risk factors for severe COVID-19, there was a significant reduction in risk with each additional vaccine dose. These results support the protective role of repeated COVID-19 vaccination for patients with IMIDs who are receiving immunosuppressive therapies; they yield a favorable prognosis even with the Omicron variant.

The study further compared the risk of severe COVID-19 between a group with hybrid immunity (having received three vaccine doses and experiencing breakthrough infection with the Omicron variant) and a group that received a fourth vaccine dose within the same time frame. The difference was striking: Hybrid immunity was associated with a 5.8-fold decrease in risk, compared with four-dose vaccination (P < .0001).

The level of antibodies, measured 2-4 weeks after the last vaccination, was predictive of the risk of breakthrough COVID-19. An antibody level above 6000 binding antibody units/mL after vaccination was significantly associated with a reduction in risk. “We can conclude that patients who receive multiple vaccine doses have a lower risk of COVID-19,” Dr. Ørbo said. “In patients who recently experienced breakthrough infections, the administration of a booster vaccine dose might be delayed.”

EULAR

“The virus has undergone changes throughout the pandemic, while the vaccines have remained relatively stable. Are we anticipating more infections over time?” asked Hendrik Schulze-Koops, MD, PhD, of Ludwig Maximilians University of Munich (Germany), the session moderator. In response, Dr. Ørbo stated that 85% of the recorded infections in the study occurred after the emergence of the Omicron variant, and time was considered a covariable in the analysis.

These data shed light on a topic discussed by Pedro Machado, MD, PhD, professor and consultant in rheumatology and neuromuscular diseases at University College London, during his scientific session talk entitled, “Unsolved Issues of COVID Vaccination and Re-vaccination.” Dr. Machado referred to the VROOM study published in 2022, which examined the interruption of methotrexate for 2 weeks following booster administration. Both groups demonstrated a significant antibody response, but the group that stopped taking methotrexate showed double the antibody titers.

However, he emphasized, “what remains unknown is the clinical relevance of these differences in terms of severe infection, hospitalization, or even death. The potential benefit of increased immunogenicity by interrupting conventional synthetic disease-modifying antirheumatic drugs [csDMARDs] such as methotrexate before or after vaccination needs to be balanced against the potential risk of disease flare. Ultimately, decision-making should be individualized based on factors such as comorbidities, disease activity, and other considerations.” The results presented by Dr. Ørbo suggest that, while there may be a clinical difference in terms of severe infection, the overall prognosis for vaccinated patients is reasonably good.

Regarding other DMARDs, such as biologics, the approach may differ. Dr. Machado suggested: “In patients using rituximab or other B cell–depleting therapies, SARS-CoV-2 vaccination should be scheduled in a way that optimizes vaccine immunogenicity. A minimum of 10 B cells/mcL of blood is likely a relevant threshold above which a sufficient cellular and immune response is established.”
 

COVID vaccines are safe for pregnant and breastfeeding women

According to data from the COVAD study, which comprised two global cross-sectional surveys conducted in 2021 and 2022, the COVID-19 vaccine appeared safe for pregnant and breastfeeding women with autoimmune diseases (AID).

Presenter Laura Andreoli, MD, PhD, of the University of Brescia (Italy), said that, although pregnant patients with AID reported more adverse events related to vaccination, these rates were not significantly higher than those among pregnant, healthy control persons who were without AID. No difference in adverse events was observed between breastfeeding women and healthy control persons, and the incidence of disease flares did not significantly differ among all groups.

“In summary, this study provides initial insights into the safety of COVID-19 vaccination during the gestational and postpartum periods in women with autoimmune diseases. These reassuring observations will hopefully improve clinician-patient communication and address hesitancy towards COVID-19 vaccination, as the benefits for the mother and fetus through passive immunization appear to outweigh potential risks,” Dr. Andreoli said in an interview.

“The large number of participants and the global geographical spread of the COVAD survey were very beneficial in gaining access to this important subset of patients,” added Dr. Andreoli. However, she acknowledged that patients with low socioeconomic status and/or high disability were likely underrepresented. While no data on pregnancy outcomes have been collected thus far, Dr. Andreoli expressed the desire to include them in the study’s follow-up.

The COVAD survey data also indicate that, in general, vaccine hesitancy among patients with AID is decreasing; from 2021 to 2022, it declined from 16.5% to 5.1%, as Dr. Machado indicated in his presentation.
 

Multiple factors contribute to breakthrough infections

The risk of breakthrough SARS-CoV-2 infections after vaccination varies among patients with rheumatoid arthritis and rheumatic or nonrheumatic autoimmune diseases, primarily depending on the underlying condition rather than the immunosuppressive medication. Environmental factors also appear to play a role. This complex landscape emerges from a further analysis of the COVAD survey dataset.

Alessia Alunno, MD, PhD, of the University of L’Aquila (Italy), presented a detailed and occasionally counterintuitive picture of similarities and differences among young adult patients (aged 18-35 years), mostly women, with various rheumatic and nonrheumatic diseases in relation to COVID-19. Most notably, the type of disease seemed to have more significance than the immunosuppression resulting from the treatment regimen. This held true for vaccine safety as well as for the risk of breakthrough COVID-19 and symptom profiles.

Patients with rheumatic disease (RMD) and nonrheumatic autoimmune disease (nr-AD) had significantly different therapeutic profiles on average. Before vaccination, 45% of patients with RMD used glucocorticoids (GC), and 91% used immunosuppressants (IS). In contrast, only 9.5% of nr-AD patients used GC, and 21% were taking IS.

Interestingly, the overall prevalence of reported SARS-CoV-2 infections was not influenced by medication and was practically identical (25% to 28%) across all groups. However, there were intriguing differences in the occurrence of infections before and after vaccination between disease groups. Prevaccine infections were less frequent among patients with RMD compared with healthy control persons (adjusted odds ratio, 0.6), while the rates were similar among patients with nr-AD and healthy control persons. On the other hand, breakthrough infections were more frequent in patients with RMD (aOR, 2.7), whereas the rate was similar between healthy control persons and patients with nr-AD.

Despite a much lower rate of GC/IS use, patients with nr-AD experienced repeated infections more frequently. In contrast, patients with RMD were less prone to multiple infections, even compared with healthy control persons (aOR, 0.5).

Regarding the disease profile, fewer than 5% of all infected patients required advanced therapies for SARS-CoV-2 infection. Notably, all SARS-CoV-2 infections in patients with nr-AD were symptomatic, whereas among patients with RMD and healthy control persons, the incidence of asymptomatic infections was 3%. The rate of hospital admissions was 4% for patients with RMD, compared with 2% for patients with nr-AD and 1% for control persons. The RMD group exhibited some differences between prevaccine infections and breakthrough infections, including a significantly lower frequency of loss of smell and taste during breakthrough infections. Overall, patients with RMD and COVID-19 experienced cough, runny nose, throat pain, nausea, and vomiting more frequently. In contrast, patients with nr-AD had a much higher risk of skin rashes during breakthrough infections (aOR, 8.7).

Vaccine adverse events (AEs) were also influenced by the underlying disease. Patients with RMD and those with nr-AD were more likely to experience mild AEs after the first or second dose, compared with healthy control persons (adjusted OR, 2.4 and 2.0, respectively). The most common early, mild AEs across all groups were injection-site pain, headache, and fatigue, but they occurred more frequently in the nr-AD group than in the RMD or healthy control group. Additionally, fever and chills occurred more frequently among the nr-AD group. Late, mild AEs and severe AEs were rare and affected all groups equally.

“The overall incidence of AEs was very low. Our results certainly do not undermine the safety of vaccines,” Dr. Alunno said.

Disease flares were more common after vaccination (10% with RMD and 7% with nr-AD) than after infection (5% with RMD and 1.5% with nr-AD). Furthermore, in many cases, after vaccination, flares required a change of medications, particularly for patients with RMD.

Dr. Naveen Ravichandran

Additional results from the COVAD survey from January to July 2022, presented by Naveen Ravichandran, MD, DM, of Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India, revealed a higher prevalence (OR, 1.2; P = .001) of breakthrough infections among patients with RA. A total of 22.6% of patients with RA experienced breakthrough infections, compared with 20.6% for patients with other autoimmune rheumatic diseases and 18.4% of healthy control persons. Hospitalizations and the need for advanced treatment were also more common among patients with RA (30.9%) than among healthy control persons (13.9%). Patients with RA who had breakthrough infections tended to be older (closer to 50 years of age on average) and female, and they were more likely to have comorbidities and mental disorders. The human development index of the patient’s country of residence also played a role. Further research is necessary to understand how breakthrough infection outcomes are affected by a patient’s socioeconomic situation.

According to Dr. Ravichandran, medication was not a significant factor, except for the use of steroids and rituximab, which were associated with a higher risk of severe COVID-19 and hospitalization. Patients using rituximab, in particular, faced significantly increased odds for hospitalization (OR, 3.4) and severe breakthrough COVID-19 (OR, 3.0).

Session moderator Kim Lauper, MD, of the University of Geneva, cautioned: “The roles of disease and medication are challenging to separate. Some diseases require a more aggressive immunosuppressive regimen. It’s possible that different diseases affect the immune system differently, but it is not easy to demonstrate.”

The complications observed in the data warrant further study, as mentioned by Dr. Schulze-Koops: “We have a problem tied to the time line of the pandemic, where we had different viruses, different population behaviors, different treatments, and different standards of care over time. We also have differences between ethnic communities and regions of the world. But most importantly, we have different viruses: From the original strain to Delta to Omicron, we know they have very different clinical outcomes. I believe we need more scientific research to unravel these factors.”

Dr. Ørbo, Dr. Ravichandran, Dr. Andreoli, and Dr. Alunno reported no relevant financial relationships. Dr. Machado has received grants and/or honoraria from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Janssen, Merck Sharp & Dohme, Novartis, Orphazyme, Pfizer, Roche, and UCB.

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

MILAN – The impact of the COVID-19 pandemic on patients with rheumatic and nonrheumatic autoimmune diseases is ongoing and not yet fully comprehended. New data presented at the annual European Congress of Rheumatology, primarily derived from the global COVID-19 in Autoimmune Diseases (COVAD) survey but not limited to it, provide reassurance regarding the protection and safety of COVID-19 vaccines for older and younger adults, as well as for pregnant and breastfeeding women. These data also explore the influence of underlying diseases and medications on breakthrough SARS-CoV-2 infections and infection outcomes.

Safety of vaccines in patients with autoimmune or immune-mediated diseases

Following vaccination, even with low levels of antibodies, the risk of severe COVID-19 remains relatively low for patients who receive immunosuppressive therapy for various immune-mediated inflammatory diseases (IMIDs). This encouraging finding comes from the Nor-vaC study, presented by Hilde Ørbo, MD, of the Center for Treatment of Rheumatic and Musculoskeletal Diseases, Diakonhjemmet Hospital, Oslo.

During the presentation, Dr. Ørbo stated: “We did not find any specific diagnosis or medication associated with a significantly higher risk of hospitalization.” Receiving booster doses of the vaccine, having high levels of anti-spike antibodies after vaccination, and achieving hybrid immunity are correlated with further reductions in the risk of breakthrough SARS-CoV-2 infections.

Dr. Hilde Ørbo

Between Feb. 15, 2021, and Feb. 15, 2023, COVID-19 affected a similar proportion among the 729 patients and 350 healthy control persons (67% and 68%, respectively). Among the patients, 22 reported severe COVID-19, whereas none of the healthy control persons did. However, there were no fatalities among the patients. The study cohort consisted of patients with various IMIDs; 70% had an inflammatory joint disease. The use of immunosuppressive medications also varied, with 63% of patients using tumor necrosis factor inhibitors, either as monotherapy or in combination with other treatments, and other patients taking medications such as methotrexate, interleukin inhibitors, Janus kinase inhibitors, vedolizumab (Entyvio), and others.

While being older than 70 years and the presence of comorbidities were identified as risk factors for severe COVID-19, there was a significant reduction in risk with each additional vaccine dose. These results support the protective role of repeated COVID-19 vaccination for patients with IMIDs who are receiving immunosuppressive therapies; they yield a favorable prognosis even with the Omicron variant.

The study further compared the risk of severe COVID-19 between a group with hybrid immunity (having received three vaccine doses and experiencing breakthrough infection with the Omicron variant) and a group that received a fourth vaccine dose within the same time frame. The difference was striking: Hybrid immunity was associated with a 5.8-fold decrease in risk, compared with four-dose vaccination (P < .0001).

The level of antibodies, measured 2-4 weeks after the last vaccination, was predictive of the risk of breakthrough COVID-19. An antibody level above 6000 binding antibody units/mL after vaccination was significantly associated with a reduction in risk. “We can conclude that patients who receive multiple vaccine doses have a lower risk of COVID-19,” Dr. Ørbo said. “In patients who recently experienced breakthrough infections, the administration of a booster vaccine dose might be delayed.”

EULAR

“The virus has undergone changes throughout the pandemic, while the vaccines have remained relatively stable. Are we anticipating more infections over time?” asked Hendrik Schulze-Koops, MD, PhD, of Ludwig Maximilians University of Munich (Germany), the session moderator. In response, Dr. Ørbo stated that 85% of the recorded infections in the study occurred after the emergence of the Omicron variant, and time was considered a covariable in the analysis.

These data shed light on a topic discussed by Pedro Machado, MD, PhD, professor and consultant in rheumatology and neuromuscular diseases at University College London, during his scientific session talk entitled, “Unsolved Issues of COVID Vaccination and Re-vaccination.” Dr. Machado referred to the VROOM study published in 2022, which examined the interruption of methotrexate for 2 weeks following booster administration. Both groups demonstrated a significant antibody response, but the group that stopped taking methotrexate showed double the antibody titers.

However, he emphasized, “what remains unknown is the clinical relevance of these differences in terms of severe infection, hospitalization, or even death. The potential benefit of increased immunogenicity by interrupting conventional synthetic disease-modifying antirheumatic drugs [csDMARDs] such as methotrexate before or after vaccination needs to be balanced against the potential risk of disease flare. Ultimately, decision-making should be individualized based on factors such as comorbidities, disease activity, and other considerations.” The results presented by Dr. Ørbo suggest that, while there may be a clinical difference in terms of severe infection, the overall prognosis for vaccinated patients is reasonably good.

Regarding other DMARDs, such as biologics, the approach may differ. Dr. Machado suggested: “In patients using rituximab or other B cell–depleting therapies, SARS-CoV-2 vaccination should be scheduled in a way that optimizes vaccine immunogenicity. A minimum of 10 B cells/mcL of blood is likely a relevant threshold above which a sufficient cellular and immune response is established.”
 

COVID vaccines are safe for pregnant and breastfeeding women

According to data from the COVAD study, which comprised two global cross-sectional surveys conducted in 2021 and 2022, the COVID-19 vaccine appeared safe for pregnant and breastfeeding women with autoimmune diseases (AID).

Presenter Laura Andreoli, MD, PhD, of the University of Brescia (Italy), said that, although pregnant patients with AID reported more adverse events related to vaccination, these rates were not significantly higher than those among pregnant, healthy control persons who were without AID. No difference in adverse events was observed between breastfeeding women and healthy control persons, and the incidence of disease flares did not significantly differ among all groups.

“In summary, this study provides initial insights into the safety of COVID-19 vaccination during the gestational and postpartum periods in women with autoimmune diseases. These reassuring observations will hopefully improve clinician-patient communication and address hesitancy towards COVID-19 vaccination, as the benefits for the mother and fetus through passive immunization appear to outweigh potential risks,” Dr. Andreoli said in an interview.

“The large number of participants and the global geographical spread of the COVAD survey were very beneficial in gaining access to this important subset of patients,” added Dr. Andreoli. However, she acknowledged that patients with low socioeconomic status and/or high disability were likely underrepresented. While no data on pregnancy outcomes have been collected thus far, Dr. Andreoli expressed the desire to include them in the study’s follow-up.

The COVAD survey data also indicate that, in general, vaccine hesitancy among patients with AID is decreasing; from 2021 to 2022, it declined from 16.5% to 5.1%, as Dr. Machado indicated in his presentation.
 

Multiple factors contribute to breakthrough infections

The risk of breakthrough SARS-CoV-2 infections after vaccination varies among patients with rheumatoid arthritis and rheumatic or nonrheumatic autoimmune diseases, primarily depending on the underlying condition rather than the immunosuppressive medication. Environmental factors also appear to play a role. This complex landscape emerges from a further analysis of the COVAD survey dataset.

Alessia Alunno, MD, PhD, of the University of L’Aquila (Italy), presented a detailed and occasionally counterintuitive picture of similarities and differences among young adult patients (aged 18-35 years), mostly women, with various rheumatic and nonrheumatic diseases in relation to COVID-19. Most notably, the type of disease seemed to have more significance than the immunosuppression resulting from the treatment regimen. This held true for vaccine safety as well as for the risk of breakthrough COVID-19 and symptom profiles.

Patients with rheumatic disease (RMD) and nonrheumatic autoimmune disease (nr-AD) had significantly different therapeutic profiles on average. Before vaccination, 45% of patients with RMD used glucocorticoids (GC), and 91% used immunosuppressants (IS). In contrast, only 9.5% of nr-AD patients used GC, and 21% were taking IS.

Interestingly, the overall prevalence of reported SARS-CoV-2 infections was not influenced by medication and was practically identical (25% to 28%) across all groups. However, there were intriguing differences in the occurrence of infections before and after vaccination between disease groups. Prevaccine infections were less frequent among patients with RMD compared with healthy control persons (adjusted odds ratio, 0.6), while the rates were similar among patients with nr-AD and healthy control persons. On the other hand, breakthrough infections were more frequent in patients with RMD (aOR, 2.7), whereas the rate was similar between healthy control persons and patients with nr-AD.

Despite a much lower rate of GC/IS use, patients with nr-AD experienced repeated infections more frequently. In contrast, patients with RMD were less prone to multiple infections, even compared with healthy control persons (aOR, 0.5).

Regarding the disease profile, fewer than 5% of all infected patients required advanced therapies for SARS-CoV-2 infection. Notably, all SARS-CoV-2 infections in patients with nr-AD were symptomatic, whereas among patients with RMD and healthy control persons, the incidence of asymptomatic infections was 3%. The rate of hospital admissions was 4% for patients with RMD, compared with 2% for patients with nr-AD and 1% for control persons. The RMD group exhibited some differences between prevaccine infections and breakthrough infections, including a significantly lower frequency of loss of smell and taste during breakthrough infections. Overall, patients with RMD and COVID-19 experienced cough, runny nose, throat pain, nausea, and vomiting more frequently. In contrast, patients with nr-AD had a much higher risk of skin rashes during breakthrough infections (aOR, 8.7).

Vaccine adverse events (AEs) were also influenced by the underlying disease. Patients with RMD and those with nr-AD were more likely to experience mild AEs after the first or second dose, compared with healthy control persons (adjusted OR, 2.4 and 2.0, respectively). The most common early, mild AEs across all groups were injection-site pain, headache, and fatigue, but they occurred more frequently in the nr-AD group than in the RMD or healthy control group. Additionally, fever and chills occurred more frequently among the nr-AD group. Late, mild AEs and severe AEs were rare and affected all groups equally.

“The overall incidence of AEs was very low. Our results certainly do not undermine the safety of vaccines,” Dr. Alunno said.

Disease flares were more common after vaccination (10% with RMD and 7% with nr-AD) than after infection (5% with RMD and 1.5% with nr-AD). Furthermore, in many cases, after vaccination, flares required a change of medications, particularly for patients with RMD.

Dr. Naveen Ravichandran

Additional results from the COVAD survey from January to July 2022, presented by Naveen Ravichandran, MD, DM, of Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India, revealed a higher prevalence (OR, 1.2; P = .001) of breakthrough infections among patients with RA. A total of 22.6% of patients with RA experienced breakthrough infections, compared with 20.6% for patients with other autoimmune rheumatic diseases and 18.4% of healthy control persons. Hospitalizations and the need for advanced treatment were also more common among patients with RA (30.9%) than among healthy control persons (13.9%). Patients with RA who had breakthrough infections tended to be older (closer to 50 years of age on average) and female, and they were more likely to have comorbidities and mental disorders. The human development index of the patient’s country of residence also played a role. Further research is necessary to understand how breakthrough infection outcomes are affected by a patient’s socioeconomic situation.

According to Dr. Ravichandran, medication was not a significant factor, except for the use of steroids and rituximab, which were associated with a higher risk of severe COVID-19 and hospitalization. Patients using rituximab, in particular, faced significantly increased odds for hospitalization (OR, 3.4) and severe breakthrough COVID-19 (OR, 3.0).

Session moderator Kim Lauper, MD, of the University of Geneva, cautioned: “The roles of disease and medication are challenging to separate. Some diseases require a more aggressive immunosuppressive regimen. It’s possible that different diseases affect the immune system differently, but it is not easy to demonstrate.”

The complications observed in the data warrant further study, as mentioned by Dr. Schulze-Koops: “We have a problem tied to the time line of the pandemic, where we had different viruses, different population behaviors, different treatments, and different standards of care over time. We also have differences between ethnic communities and regions of the world. But most importantly, we have different viruses: From the original strain to Delta to Omicron, we know they have very different clinical outcomes. I believe we need more scientific research to unravel these factors.”

Dr. Ørbo, Dr. Ravichandran, Dr. Andreoli, and Dr. Alunno reported no relevant financial relationships. Dr. Machado has received grants and/or honoraria from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Janssen, Merck Sharp & Dohme, Novartis, Orphazyme, Pfizer, Roche, and UCB.

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