Conference Coverage

An increasing number of comorbidities in patients with rheumatoid arthritis correlates with a lower likelihood of reaching treatment targets, according to an analysis conducted with a series of large real-world datasets and presented in a symposium sponsored by the Rheumatology Research Foundation.

When compared to those with the lowest burden of comorbidity in one of these analyses, those with the highest had a nearly 50% lower likelihood (odds ratio, 0.54; 95% confidence interval [CI], 0.34-0.85) of achieving low disease activity or remission, according to Bryant England, MD, PhD, assistant professor in the division of rheumatology at the University of Nebraska, Omaha.

“Patients with more comorbidities struggle to reach treatment targets,” Dr. England said. In the treatment of RA, “we typically focus only on the joints, but these data suggest we need to begin to think more holistically about managing these patients.”

Both the American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR) endorse a treat-to-target management approach in RA guidelines, but only a proportion of patients reach their targets, according to Dr. England. In his series of analyses, Dr. England has been exploring the role of comorbidities as one of the contributing factors.

Looking for real-world data, Dr. England evaluated comorbidities in the Veterans Affairs Rheumatoid Arthritis Registry, which has a male predominant population, the National Databank for Rheumatic Diseases, which is female predominant, the Truven Health Analytics MarketScan Database, and the Rheumatology Informatics System for Effectiveness Registry (RISE).
 

Comorbidities accrue more quickly in RA patients

All of these real-world data support the premise that comorbidities are higher in patients with RA than in those without, and show that the burden of comorbidities rises more quickly in patients with RA. For example, the average number of comorbidities in the MarketScan database of recently diagnosed RA patients was 2.6. Five years later, the average doubled to more than 5. For those without RA, the average at the baseline evaluation was 1.6 and remained below 3 at 5 years.

For the burden of comorbidities in RA, Dr. England prefers the term “multimorbidity” because he believes it captures the interconnections of these chronic diseases, many of which trigger or exacerbate others. When he looked at health history 2 years before the RA diagnosis, multimorbidities were already somewhat higher, but he found that burden “takes off” in the peri-diagnostic period and climbs steeply thereafter.

“The data tell us that multimorbidity becomes more problematic throughout the RA disease course,” said Dr. England, who published some of these data only a few weeks prior to his presentation.

In one effort to evaluate how multimorbidity affects treatment choices and outcome, he selected patients with persistently active disease from the RISE registry, a group expected to be candidates for a treatment change or escalation. The data suggested patients with multimorbidity were less likely than were those without to receive a change of therapy in response to their active disease, but it also demonstrated that patients with multimorbidity were less likely to achieve remission or low disease activity even if the medications were changed.

Each comorbidity lowers odds of remission

When relative burden of comorbidities was assessed by RxRisk score, a validated medication-based measure of chronic disease that recognizes 46 categories of chronic conditions, there was about a 5% lower odds ratio for each RxRisk unit of increase in comorbidity. The relationship was consistent across various cohorts of patients evaluated, according to Dr. England.

When looking for patterns of comorbidities in these large datasets using machine learning, Dr. England reported that there were “striking” relationships between organ systems. This included a pattern of cardiometabolic multimorbidity, cardiopulmonary multimorbidity, and mental health and chronic pain multimorbidity. Surprisingly, the same patterns could be identified in those with or without RA, but the prevalence differed.

“RA was closely associated with all of these different multimorbidity patterns, but the odds of having these patterns were one- to threefold greater,” Dr. England reported.

“The multimorbidity pattern most closely associated with RA was mental health and chronic pain,” he added, noting that the same results were observed across the datasets evaluated.

The implication of this work is that multimorbidity exerts an adverse effect on the course of RA and might be an appropriate target of therapies to improve RA outcomes. Although Dr. England called for better tools to measure multimorbidity and consider how it can be addressed systematically in RA patients with the intention of improving RA control, he believes this is an important direction of research.

“What our data show is that we need to begin to think more holistically about these other diseases in RA patients,” he said.
 

Others support targeting of comorbidities

Vanessa L. Kronzer, MD, a rheumatology fellow at Mayo Clinic, Rochester, Minn., agreed. An author of a study that identified 11 comorbidities significantly associated with RA, either as conditions that predispose to RA or that commonly develop in patients with RA, Dr. Kronzer has drawn the same conclusion in regard to targeting comorbidities in the RA patient.

“Based on mounting evidence that multimorbidity is associated with RA and RA disease activity, taking a broader view of the patient as a whole and his or her comorbidities may help us to not only predict RA but also achieve over disease-specific goals,” Dr. Kronzer said in an interview.

“I suspect that certain comorbidities, perhaps depression as an example, may play a particularly strong role in perpetuating high RA disease activity,” she added. She considers this a ripe area of study for improving clinical strategies in RA.

“Finding out which ones [perpetuate RA] and targeting them could be a reasonable approach to moving forward,” Dr. Kronzer said.

Dr. England and Dr. Kronzer reported having no potential conflicts of interest.

An increasing number of comorbidities in patients with rheumatoid arthritis correlates with a lower likelihood of reaching treatment targets, according to an analysis conducted with a series of large real-world datasets and presented in a symposium sponsored by the Rheumatology Research Foundation.

When compared to those with the lowest burden of comorbidity in one of these analyses, those with the highest had a nearly 50% lower likelihood (odds ratio, 0.54; 95% confidence interval [CI], 0.34-0.85) of achieving low disease activity or remission, according to Bryant England, MD, PhD, assistant professor in the division of rheumatology at the University of Nebraska, Omaha.

“Patients with more comorbidities struggle to reach treatment targets,” Dr. England said. In the treatment of RA, “we typically focus only on the joints, but these data suggest we need to begin to think more holistically about managing these patients.”

Both the American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR) endorse a treat-to-target management approach in RA guidelines, but only a proportion of patients reach their targets, according to Dr. England. In his series of analyses, Dr. England has been exploring the role of comorbidities as one of the contributing factors.

Looking for real-world data, Dr. England evaluated comorbidities in the Veterans Affairs Rheumatoid Arthritis Registry, which has a male predominant population, the National Databank for Rheumatic Diseases, which is female predominant, the Truven Health Analytics MarketScan Database, and the Rheumatology Informatics System for Effectiveness Registry (RISE).
 

Comorbidities accrue more quickly in RA patients

All of these real-world data support the premise that comorbidities are higher in patients with RA than in those without, and show that the burden of comorbidities rises more quickly in patients with RA. For example, the average number of comorbidities in the MarketScan database of recently diagnosed RA patients was 2.6. Five years later, the average doubled to more than 5. For those without RA, the average at the baseline evaluation was 1.6 and remained below 3 at 5 years.

For the burden of comorbidities in RA, Dr. England prefers the term “multimorbidity” because he believes it captures the interconnections of these chronic diseases, many of which trigger or exacerbate others. When he looked at health history 2 years before the RA diagnosis, multimorbidities were already somewhat higher, but he found that burden “takes off” in the peri-diagnostic period and climbs steeply thereafter.

“The data tell us that multimorbidity becomes more problematic throughout the RA disease course,” said Dr. England, who published some of these data only a few weeks prior to his presentation.

In one effort to evaluate how multimorbidity affects treatment choices and outcome, he selected patients with persistently active disease from the RISE registry, a group expected to be candidates for a treatment change or escalation. The data suggested patients with multimorbidity were less likely than were those without to receive a change of therapy in response to their active disease, but it also demonstrated that patients with multimorbidity were less likely to achieve remission or low disease activity even if the medications were changed.

Each comorbidity lowers odds of remission

When relative burden of comorbidities was assessed by RxRisk score, a validated medication-based measure of chronic disease that recognizes 46 categories of chronic conditions, there was about a 5% lower odds ratio for each RxRisk unit of increase in comorbidity. The relationship was consistent across various cohorts of patients evaluated, according to Dr. England.

When looking for patterns of comorbidities in these large datasets using machine learning, Dr. England reported that there were “striking” relationships between organ systems. This included a pattern of cardiometabolic multimorbidity, cardiopulmonary multimorbidity, and mental health and chronic pain multimorbidity. Surprisingly, the same patterns could be identified in those with or without RA, but the prevalence differed.

“RA was closely associated with all of these different multimorbidity patterns, but the odds of having these patterns were one- to threefold greater,” Dr. England reported.

“The multimorbidity pattern most closely associated with RA was mental health and chronic pain,” he added, noting that the same results were observed across the datasets evaluated.

The implication of this work is that multimorbidity exerts an adverse effect on the course of RA and might be an appropriate target of therapies to improve RA outcomes. Although Dr. England called for better tools to measure multimorbidity and consider how it can be addressed systematically in RA patients with the intention of improving RA control, he believes this is an important direction of research.

“What our data show is that we need to begin to think more holistically about these other diseases in RA patients,” he said.
 

Others support targeting of comorbidities

Vanessa L. Kronzer, MD, a rheumatology fellow at Mayo Clinic, Rochester, Minn., agreed. An author of a study that identified 11 comorbidities significantly associated with RA, either as conditions that predispose to RA or that commonly develop in patients with RA, Dr. Kronzer has drawn the same conclusion in regard to targeting comorbidities in the RA patient.

“Based on mounting evidence that multimorbidity is associated with RA and RA disease activity, taking a broader view of the patient as a whole and his or her comorbidities may help us to not only predict RA but also achieve over disease-specific goals,” Dr. Kronzer said in an interview.

“I suspect that certain comorbidities, perhaps depression as an example, may play a particularly strong role in perpetuating high RA disease activity,” she added. She considers this a ripe area of study for improving clinical strategies in RA.

“Finding out which ones [perpetuate RA] and targeting them could be a reasonable approach to moving forward,” Dr. Kronzer said.

Dr. England and Dr. Kronzer reported having no potential conflicts of interest.

An increasing number of comorbidities in patients with rheumatoid arthritis correlates with a lower likelihood of reaching treatment targets, according to an analysis conducted with a series of large real-world datasets and presented in a symposium sponsored by the Rheumatology Research Foundation.

When compared to those with the lowest burden of comorbidity in one of these analyses, those with the highest had a nearly 50% lower likelihood (odds ratio, 0.54; 95% confidence interval [CI], 0.34-0.85) of achieving low disease activity or remission, according to Bryant England, MD, PhD, assistant professor in the division of rheumatology at the University of Nebraska, Omaha.

“Patients with more comorbidities struggle to reach treatment targets,” Dr. England said. In the treatment of RA, “we typically focus only on the joints, but these data suggest we need to begin to think more holistically about managing these patients.”

Both the American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR) endorse a treat-to-target management approach in RA guidelines, but only a proportion of patients reach their targets, according to Dr. England. In his series of analyses, Dr. England has been exploring the role of comorbidities as one of the contributing factors.

Looking for real-world data, Dr. England evaluated comorbidities in the Veterans Affairs Rheumatoid Arthritis Registry, which has a male predominant population, the National Databank for Rheumatic Diseases, which is female predominant, the Truven Health Analytics MarketScan Database, and the Rheumatology Informatics System for Effectiveness Registry (RISE).
 

Comorbidities accrue more quickly in RA patients

All of these real-world data support the premise that comorbidities are higher in patients with RA than in those without, and show that the burden of comorbidities rises more quickly in patients with RA. For example, the average number of comorbidities in the MarketScan database of recently diagnosed RA patients was 2.6. Five years later, the average doubled to more than 5. For those without RA, the average at the baseline evaluation was 1.6 and remained below 3 at 5 years.

For the burden of comorbidities in RA, Dr. England prefers the term “multimorbidity” because he believes it captures the interconnections of these chronic diseases, many of which trigger or exacerbate others. When he looked at health history 2 years before the RA diagnosis, multimorbidities were already somewhat higher, but he found that burden “takes off” in the peri-diagnostic period and climbs steeply thereafter.

“The data tell us that multimorbidity becomes more problematic throughout the RA disease course,” said Dr. England, who published some of these data only a few weeks prior to his presentation.

In one effort to evaluate how multimorbidity affects treatment choices and outcome, he selected patients with persistently active disease from the RISE registry, a group expected to be candidates for a treatment change or escalation. The data suggested patients with multimorbidity were less likely than were those without to receive a change of therapy in response to their active disease, but it also demonstrated that patients with multimorbidity were less likely to achieve remission or low disease activity even if the medications were changed.

Each comorbidity lowers odds of remission

When relative burden of comorbidities was assessed by RxRisk score, a validated medication-based measure of chronic disease that recognizes 46 categories of chronic conditions, there was about a 5% lower odds ratio for each RxRisk unit of increase in comorbidity. The relationship was consistent across various cohorts of patients evaluated, according to Dr. England.

When looking for patterns of comorbidities in these large datasets using machine learning, Dr. England reported that there were “striking” relationships between organ systems. This included a pattern of cardiometabolic multimorbidity, cardiopulmonary multimorbidity, and mental health and chronic pain multimorbidity. Surprisingly, the same patterns could be identified in those with or without RA, but the prevalence differed.

“RA was closely associated with all of these different multimorbidity patterns, but the odds of having these patterns were one- to threefold greater,” Dr. England reported.

“The multimorbidity pattern most closely associated with RA was mental health and chronic pain,” he added, noting that the same results were observed across the datasets evaluated.

The implication of this work is that multimorbidity exerts an adverse effect on the course of RA and might be an appropriate target of therapies to improve RA outcomes. Although Dr. England called for better tools to measure multimorbidity and consider how it can be addressed systematically in RA patients with the intention of improving RA control, he believes this is an important direction of research.

“What our data show is that we need to begin to think more holistically about these other diseases in RA patients,” he said.
 

Others support targeting of comorbidities

Vanessa L. Kronzer, MD, a rheumatology fellow at Mayo Clinic, Rochester, Minn., agreed. An author of a study that identified 11 comorbidities significantly associated with RA, either as conditions that predispose to RA or that commonly develop in patients with RA, Dr. Kronzer has drawn the same conclusion in regard to targeting comorbidities in the RA patient.

“Based on mounting evidence that multimorbidity is associated with RA and RA disease activity, taking a broader view of the patient as a whole and his or her comorbidities may help us to not only predict RA but also achieve over disease-specific goals,” Dr. Kronzer said in an interview.

“I suspect that certain comorbidities, perhaps depression as an example, may play a particularly strong role in perpetuating high RA disease activity,” she added. She considers this a ripe area of study for improving clinical strategies in RA.

“Finding out which ones [perpetuate RA] and targeting them could be a reasonable approach to moving forward,” Dr. Kronzer said.

Dr. England and Dr. Kronzer reported having no potential conflicts of interest.

With the approval by the Food and Drug Administration of the calcineurin inhibitor voclosporin (Lupkynis) in January and belimumab (Benlysta) a month before that, clinicians now have new options for treating lupus nephritis in combination with a background immunosuppressive agent, such as mycophenolate mofetil.

But which combination should clinicians choose?

Brad Rovin, MD, a nephrologist with the Ohio State University Wexner Medical Center, Columbus, who worked on the phase 3 voclosprin trial, pointed to that drug’s fast reduction in proteinuria in a session of the Pan American League of Associations for Rheumatology (PANLAR) 2021 Annual Meeting. That effect on proteinuria is likely due to its effect on podocytes, special epithelial cells that cover the outside of capillaries in the kidney, he said.

These crucial cells have an elaborate cytoskeleton that is stabilized by the protein synaptopodin, which can be subject to harm from calcineurin. But because voclosporin blocks calcineurin, synaptopodin is protected, which consequently protects podocytes and the kidney, Dr. Rovin said.

“There’s a lot of data in the nephrology literature that suggests as you lose podocytes, you actually can develop glomerular sclerosis and loss of renal function,” he said. “In fact, if you lose a critical number of podocytes, then no matter what you do, the kidney is likely to progress to end-stage kidney disease.

“The way I think about it now is, what else do these drugs add? And this idea of preserving the histology of the kidney is really important, and this can be done with voclosporin,” Dr. Rovin said.

Belimumab is also hailed as an effective tool, particularly for the prevention of flares. In the trial leading to its approval), just under 16% of patients experienced a renal-related event or death over 2 years, compared with 28% of the group that received placebo. Those receiving belimumab had a 50% greater chance of reaching the primary efficacy renal response, which was defined as a ratio of urinary protein to creatinine of 0.7 or less, an estimated glomerular filtration rate that was no worse than 20% below the pre-flare value or at least 60 mL/min per 1.73 m², and no use of rescue therapy for treatment failure.

The endpoints in the belimumab lupus nephritis trial were “quite rigorous,” Richard A. Furie, MD, said in the same session at the meeting. Patients with class V lupus nephritis were included in the trial, although disease of this severity is known to be particularly difficult to treat, he noted.

“There’s little question that our patients with lupus nephritis will benefit from such a therapeutic approach” with belimumab and mycophenolate, said Dr. Furie, professor of medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, in Hempstead, N.Y. “But regardless of which combination clinicians use, we are making advances, and that means better outcomes for our patients with lupus and lupus nephritis.”

Graciela Alarcon, MD, MPH, professor emeritus of medicine at the University of Alabama at Birmingham, who moderated the discussion, said there is no sure answer regarding the best choice for clinicians.

“As long as there’s no head-to-head comparison between the two new compounds, I don’t think that the question can be answered,” she said.

Indeed, the answer for many clinicians might be that for certain patients, dual therapy isn’t necessary, Dr. Furie said.

“The fundamental question, before we choose the second drug, is whether a second drug should be chosen,” he said. “There’s a lot of people in the community who are just sticking to the old-fashioned algorithm and that is just choosing one drug, like mycophenolate. ... Others might pick a second drug, but not until they see that mycophenolate is not doing an effective job.”

All agreed that the response rates are still not optimal for patients with lupus nephritis, even with these new combinations – they are still only in the 30%-40% range.

“We haven’t really boosted the response rate to where we want it to be, at least as measured by our current measurements and composite renal response,” Dr. Rovin said.

With voclosporin’s protective effects and belimumab’s flare prevention, the two could potentially be used together at some point, he suggested.

“I think these two drugs show us the possibility that we might use them together and get rid of the older drugs, and really minimize the older drugs and then use them on a longer-term basis to preserve kidney function, as well as keep the lupus in check,” he said.

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

With the approval by the Food and Drug Administration of the calcineurin inhibitor voclosporin (Lupkynis) in January and belimumab (Benlysta) a month before that, clinicians now have new options for treating lupus nephritis in combination with a background immunosuppressive agent, such as mycophenolate mofetil.

But which combination should clinicians choose?

Brad Rovin, MD, a nephrologist with the Ohio State University Wexner Medical Center, Columbus, who worked on the phase 3 voclosprin trial, pointed to that drug’s fast reduction in proteinuria in a session of the Pan American League of Associations for Rheumatology (PANLAR) 2021 Annual Meeting. That effect on proteinuria is likely due to its effect on podocytes, special epithelial cells that cover the outside of capillaries in the kidney, he said.

These crucial cells have an elaborate cytoskeleton that is stabilized by the protein synaptopodin, which can be subject to harm from calcineurin. But because voclosporin blocks calcineurin, synaptopodin is protected, which consequently protects podocytes and the kidney, Dr. Rovin said.

“There’s a lot of data in the nephrology literature that suggests as you lose podocytes, you actually can develop glomerular sclerosis and loss of renal function,” he said. “In fact, if you lose a critical number of podocytes, then no matter what you do, the kidney is likely to progress to end-stage kidney disease.

“The way I think about it now is, what else do these drugs add? And this idea of preserving the histology of the kidney is really important, and this can be done with voclosporin,” Dr. Rovin said.

Belimumab is also hailed as an effective tool, particularly for the prevention of flares. In the trial leading to its approval), just under 16% of patients experienced a renal-related event or death over 2 years, compared with 28% of the group that received placebo. Those receiving belimumab had a 50% greater chance of reaching the primary efficacy renal response, which was defined as a ratio of urinary protein to creatinine of 0.7 or less, an estimated glomerular filtration rate that was no worse than 20% below the pre-flare value or at least 60 mL/min per 1.73 m², and no use of rescue therapy for treatment failure.

The endpoints in the belimumab lupus nephritis trial were “quite rigorous,” Richard A. Furie, MD, said in the same session at the meeting. Patients with class V lupus nephritis were included in the trial, although disease of this severity is known to be particularly difficult to treat, he noted.

“There’s little question that our patients with lupus nephritis will benefit from such a therapeutic approach” with belimumab and mycophenolate, said Dr. Furie, professor of medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, in Hempstead, N.Y. “But regardless of which combination clinicians use, we are making advances, and that means better outcomes for our patients with lupus and lupus nephritis.”

Graciela Alarcon, MD, MPH, professor emeritus of medicine at the University of Alabama at Birmingham, who moderated the discussion, said there is no sure answer regarding the best choice for clinicians.

“As long as there’s no head-to-head comparison between the two new compounds, I don’t think that the question can be answered,” she said.

Indeed, the answer for many clinicians might be that for certain patients, dual therapy isn’t necessary, Dr. Furie said.

“The fundamental question, before we choose the second drug, is whether a second drug should be chosen,” he said. “There’s a lot of people in the community who are just sticking to the old-fashioned algorithm and that is just choosing one drug, like mycophenolate. ... Others might pick a second drug, but not until they see that mycophenolate is not doing an effective job.”

All agreed that the response rates are still not optimal for patients with lupus nephritis, even with these new combinations – they are still only in the 30%-40% range.

“We haven’t really boosted the response rate to where we want it to be, at least as measured by our current measurements and composite renal response,” Dr. Rovin said.

With voclosporin’s protective effects and belimumab’s flare prevention, the two could potentially be used together at some point, he suggested.

“I think these two drugs show us the possibility that we might use them together and get rid of the older drugs, and really minimize the older drugs and then use them on a longer-term basis to preserve kidney function, as well as keep the lupus in check,” he said.

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

With the approval by the Food and Drug Administration of the calcineurin inhibitor voclosporin (Lupkynis) in January and belimumab (Benlysta) a month before that, clinicians now have new options for treating lupus nephritis in combination with a background immunosuppressive agent, such as mycophenolate mofetil.

But which combination should clinicians choose?

Brad Rovin, MD, a nephrologist with the Ohio State University Wexner Medical Center, Columbus, who worked on the phase 3 voclosprin trial, pointed to that drug’s fast reduction in proteinuria in a session of the Pan American League of Associations for Rheumatology (PANLAR) 2021 Annual Meeting. That effect on proteinuria is likely due to its effect on podocytes, special epithelial cells that cover the outside of capillaries in the kidney, he said.

These crucial cells have an elaborate cytoskeleton that is stabilized by the protein synaptopodin, which can be subject to harm from calcineurin. But because voclosporin blocks calcineurin, synaptopodin is protected, which consequently protects podocytes and the kidney, Dr. Rovin said.

“There’s a lot of data in the nephrology literature that suggests as you lose podocytes, you actually can develop glomerular sclerosis and loss of renal function,” he said. “In fact, if you lose a critical number of podocytes, then no matter what you do, the kidney is likely to progress to end-stage kidney disease.

“The way I think about it now is, what else do these drugs add? And this idea of preserving the histology of the kidney is really important, and this can be done with voclosporin,” Dr. Rovin said.

Belimumab is also hailed as an effective tool, particularly for the prevention of flares. In the trial leading to its approval), just under 16% of patients experienced a renal-related event or death over 2 years, compared with 28% of the group that received placebo. Those receiving belimumab had a 50% greater chance of reaching the primary efficacy renal response, which was defined as a ratio of urinary protein to creatinine of 0.7 or less, an estimated glomerular filtration rate that was no worse than 20% below the pre-flare value or at least 60 mL/min per 1.73 m², and no use of rescue therapy for treatment failure.

The endpoints in the belimumab lupus nephritis trial were “quite rigorous,” Richard A. Furie, MD, said in the same session at the meeting. Patients with class V lupus nephritis were included in the trial, although disease of this severity is known to be particularly difficult to treat, he noted.

“There’s little question that our patients with lupus nephritis will benefit from such a therapeutic approach” with belimumab and mycophenolate, said Dr. Furie, professor of medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, in Hempstead, N.Y. “But regardless of which combination clinicians use, we are making advances, and that means better outcomes for our patients with lupus and lupus nephritis.”

Graciela Alarcon, MD, MPH, professor emeritus of medicine at the University of Alabama at Birmingham, who moderated the discussion, said there is no sure answer regarding the best choice for clinicians.

“As long as there’s no head-to-head comparison between the two new compounds, I don’t think that the question can be answered,” she said.

Indeed, the answer for many clinicians might be that for certain patients, dual therapy isn’t necessary, Dr. Furie said.

“The fundamental question, before we choose the second drug, is whether a second drug should be chosen,” he said. “There’s a lot of people in the community who are just sticking to the old-fashioned algorithm and that is just choosing one drug, like mycophenolate. ... Others might pick a second drug, but not until they see that mycophenolate is not doing an effective job.”

All agreed that the response rates are still not optimal for patients with lupus nephritis, even with these new combinations – they are still only in the 30%-40% range.

“We haven’t really boosted the response rate to where we want it to be, at least as measured by our current measurements and composite renal response,” Dr. Rovin said.

With voclosporin’s protective effects and belimumab’s flare prevention, the two could potentially be used together at some point, he suggested.

“I think these two drugs show us the possibility that we might use them together and get rid of the older drugs, and really minimize the older drugs and then use them on a longer-term basis to preserve kidney function, as well as keep the lupus in check,” he said.

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

Sleep problems are prevalent in older adults, and overmedication is a common cause. Insomnia is a concern, and it might not look the same in older adults as it does in younger populations, especially when neurodegenerative disorders may be present. “There’s often not only the inability to get to sleep and stay asleep in older adults but also changes in their biological rhythms, which is why treatments really need to be focused on both,” Ruth M. Benca, MD, PhD, said in an interview.

Dr. Benca spoke on the topic of insomnia in the elderly at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists. She is chair of psychiatry at Wake Forest Baptist Health, Winston-Salem, N.C.

Sleep issues strongly affect quality of life and health outcomes in the elderly, and there isn’t a lot of clear guidance for physicians to manage these issues. “We hear a lot about what we shouldn’t be giving to older adults, but not a lot about what should we be doing,” said Dr. Benca, who spoke at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

Behavioral approaches are important, because quality of sleep is often affected by daytime activities, such as exercise and light exposure, according to Dr. Benca, who said that those factors can and should be addressed by behavioral interventions. Medications should be used as an adjunct to those treatments. “When we do need to use medications, we need to use ones that have been tested and found to be more helpful than harmful in older adults,” Dr. Benca said.

Many Food and Drug Administration–approved drugs should be used with caution or avoided in the elderly. The Beers criteria provide a useful list of potentially problematic drugs, and removing those drugs from consideration leaves just a few options, including the melatonin receptor agonist ramelteon, low doses of the tricyclic antidepressant doxepin, and dual orexin receptor antagonists, which are being tested in older adults, including some with dementia, Dr. Benca said.

Other drugs like benzodiazepines and related “Z” drugs can cause problems like amnesia, confusion, and psychomotor issues. “They’re advised against because there are some concerns about those side effects,” Dr. Benca said.

Sleep disturbance itself can be the result of polypharmacy. Even something as simple as a diuretic can interrupt slumber because of nocturnal bathroom visits. Antihypertensives and drugs that affect the central nervous system, including antidepressants, can affect sleep. “I’ve had patients get horrible dreams and nightmares from antihypertensive drugs. So there’s a very long laundry list of drugs that can affect sleep in a negative way,” said Dr. Benca.

Physicians have a tendency to prescribe more drugs to a patient without eliminating any, which can result in complex situations. “We see this sort of chasing the tail: You give a drug, it may have a positive effect on the primary thing you want to treat, but it has a side effect. When you give another drug to treat that side effect, it in turn has its own side effect. We keep piling on drugs,” Dr. Benca said.

“So if [a patient is] on medications for an indication, and particularly for sleep or other things, and the patient isn’t getting better, what we might want to do is slowly to withdraw things. Even for older adults who are on sleeping medications and maybe are doing better, sometimes we can decrease the dose [of the other drugs], or get them off those drugs or put them on something that might be less likely to have side effects,” Dr. Benca said.

To do that, she suggests taking a history to determine when the sleep problem began, and whether it coincided with adding or changing a medication. Another approach is to look at the list of current medications, and look for drugs that are prescribed for a problem and where the problem still persists. “You might want to take that away first, before you start adding something else,” said Dr. Benca.

Another challenge is that physicians are often unwilling to investigate sleep disorders, which are more common in older adults. Physicians can be reluctant to prescribe sleep medications, and may also be unfamiliar with behavioral interventions. “For a lot of providers, getting into sleep issues is like opening a Pandora’s Box. I think mostly physicians are taught: Don’t do this, and don’t do that. They’re not as well versed in the things that they can and should do,” said Dr. Benca.

If attempts to treat insomnia don’t succeed, or if the physician suspects a movement disorder or primary sleep disorder like sleep apnea, then the patients should be referred to a sleep specialist, according to Dr. Benca.

During the question-and-answer period following her talk, a questioner brought up the increasingly common use of cannabis to improve sleep. That can be tricky because it can be difficult to stop cannabis use, because of the rebound insomnia that may persist. She noted that there are ongoing studies on the potential impact of cannabidiol oil.

Dr. Benca was also asked about patients who take sedatives chronically and seem to be doing well. She emphasized the need for finding the lowest effective dose of a short-acting medication. “Patients should be monitored frequently, at least every 6 months. Just monitor your patient carefully.”

Dr. Benca is a consultant for Eisai, Genomind, Idorsia, Jazz, Merck, Sage, and Sunovion.

Sleep problems are prevalent in older adults, and overmedication is a common cause. Insomnia is a concern, and it might not look the same in older adults as it does in younger populations, especially when neurodegenerative disorders may be present. “There’s often not only the inability to get to sleep and stay asleep in older adults but also changes in their biological rhythms, which is why treatments really need to be focused on both,” Ruth M. Benca, MD, PhD, said in an interview.

Dr. Benca spoke on the topic of insomnia in the elderly at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists. She is chair of psychiatry at Wake Forest Baptist Health, Winston-Salem, N.C.

Sleep issues strongly affect quality of life and health outcomes in the elderly, and there isn’t a lot of clear guidance for physicians to manage these issues. “We hear a lot about what we shouldn’t be giving to older adults, but not a lot about what should we be doing,” said Dr. Benca, who spoke at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

Behavioral approaches are important, because quality of sleep is often affected by daytime activities, such as exercise and light exposure, according to Dr. Benca, who said that those factors can and should be addressed by behavioral interventions. Medications should be used as an adjunct to those treatments. “When we do need to use medications, we need to use ones that have been tested and found to be more helpful than harmful in older adults,” Dr. Benca said.

Many Food and Drug Administration–approved drugs should be used with caution or avoided in the elderly. The Beers criteria provide a useful list of potentially problematic drugs, and removing those drugs from consideration leaves just a few options, including the melatonin receptor agonist ramelteon, low doses of the tricyclic antidepressant doxepin, and dual orexin receptor antagonists, which are being tested in older adults, including some with dementia, Dr. Benca said.

Other drugs like benzodiazepines and related “Z” drugs can cause problems like amnesia, confusion, and psychomotor issues. “They’re advised against because there are some concerns about those side effects,” Dr. Benca said.

Sleep disturbance itself can be the result of polypharmacy. Even something as simple as a diuretic can interrupt slumber because of nocturnal bathroom visits. Antihypertensives and drugs that affect the central nervous system, including antidepressants, can affect sleep. “I’ve had patients get horrible dreams and nightmares from antihypertensive drugs. So there’s a very long laundry list of drugs that can affect sleep in a negative way,” said Dr. Benca.

Physicians have a tendency to prescribe more drugs to a patient without eliminating any, which can result in complex situations. “We see this sort of chasing the tail: You give a drug, it may have a positive effect on the primary thing you want to treat, but it has a side effect. When you give another drug to treat that side effect, it in turn has its own side effect. We keep piling on drugs,” Dr. Benca said.

“So if [a patient is] on medications for an indication, and particularly for sleep or other things, and the patient isn’t getting better, what we might want to do is slowly to withdraw things. Even for older adults who are on sleeping medications and maybe are doing better, sometimes we can decrease the dose [of the other drugs], or get them off those drugs or put them on something that might be less likely to have side effects,” Dr. Benca said.

To do that, she suggests taking a history to determine when the sleep problem began, and whether it coincided with adding or changing a medication. Another approach is to look at the list of current medications, and look for drugs that are prescribed for a problem and where the problem still persists. “You might want to take that away first, before you start adding something else,” said Dr. Benca.

Another challenge is that physicians are often unwilling to investigate sleep disorders, which are more common in older adults. Physicians can be reluctant to prescribe sleep medications, and may also be unfamiliar with behavioral interventions. “For a lot of providers, getting into sleep issues is like opening a Pandora’s Box. I think mostly physicians are taught: Don’t do this, and don’t do that. They’re not as well versed in the things that they can and should do,” said Dr. Benca.

If attempts to treat insomnia don’t succeed, or if the physician suspects a movement disorder or primary sleep disorder like sleep apnea, then the patients should be referred to a sleep specialist, according to Dr. Benca.

During the question-and-answer period following her talk, a questioner brought up the increasingly common use of cannabis to improve sleep. That can be tricky because it can be difficult to stop cannabis use, because of the rebound insomnia that may persist. She noted that there are ongoing studies on the potential impact of cannabidiol oil.

Dr. Benca was also asked about patients who take sedatives chronically and seem to be doing well. She emphasized the need for finding the lowest effective dose of a short-acting medication. “Patients should be monitored frequently, at least every 6 months. Just monitor your patient carefully.”

Dr. Benca is a consultant for Eisai, Genomind, Idorsia, Jazz, Merck, Sage, and Sunovion.

Sleep problems are prevalent in older adults, and overmedication is a common cause. Insomnia is a concern, and it might not look the same in older adults as it does in younger populations, especially when neurodegenerative disorders may be present. “There’s often not only the inability to get to sleep and stay asleep in older adults but also changes in their biological rhythms, which is why treatments really need to be focused on both,” Ruth M. Benca, MD, PhD, said in an interview.

Dr. Benca spoke on the topic of insomnia in the elderly at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists. She is chair of psychiatry at Wake Forest Baptist Health, Winston-Salem, N.C.

Sleep issues strongly affect quality of life and health outcomes in the elderly, and there isn’t a lot of clear guidance for physicians to manage these issues. “We hear a lot about what we shouldn’t be giving to older adults, but not a lot about what should we be doing,” said Dr. Benca, who spoke at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

Behavioral approaches are important, because quality of sleep is often affected by daytime activities, such as exercise and light exposure, according to Dr. Benca, who said that those factors can and should be addressed by behavioral interventions. Medications should be used as an adjunct to those treatments. “When we do need to use medications, we need to use ones that have been tested and found to be more helpful than harmful in older adults,” Dr. Benca said.

Many Food and Drug Administration–approved drugs should be used with caution or avoided in the elderly. The Beers criteria provide a useful list of potentially problematic drugs, and removing those drugs from consideration leaves just a few options, including the melatonin receptor agonist ramelteon, low doses of the tricyclic antidepressant doxepin, and dual orexin receptor antagonists, which are being tested in older adults, including some with dementia, Dr. Benca said.

Other drugs like benzodiazepines and related “Z” drugs can cause problems like amnesia, confusion, and psychomotor issues. “They’re advised against because there are some concerns about those side effects,” Dr. Benca said.

Sleep disturbance itself can be the result of polypharmacy. Even something as simple as a diuretic can interrupt slumber because of nocturnal bathroom visits. Antihypertensives and drugs that affect the central nervous system, including antidepressants, can affect sleep. “I’ve had patients get horrible dreams and nightmares from antihypertensive drugs. So there’s a very long laundry list of drugs that can affect sleep in a negative way,” said Dr. Benca.

Physicians have a tendency to prescribe more drugs to a patient without eliminating any, which can result in complex situations. “We see this sort of chasing the tail: You give a drug, it may have a positive effect on the primary thing you want to treat, but it has a side effect. When you give another drug to treat that side effect, it in turn has its own side effect. We keep piling on drugs,” Dr. Benca said.

“So if [a patient is] on medications for an indication, and particularly for sleep or other things, and the patient isn’t getting better, what we might want to do is slowly to withdraw things. Even for older adults who are on sleeping medications and maybe are doing better, sometimes we can decrease the dose [of the other drugs], or get them off those drugs or put them on something that might be less likely to have side effects,” Dr. Benca said.

To do that, she suggests taking a history to determine when the sleep problem began, and whether it coincided with adding or changing a medication. Another approach is to look at the list of current medications, and look for drugs that are prescribed for a problem and where the problem still persists. “You might want to take that away first, before you start adding something else,” said Dr. Benca.

Another challenge is that physicians are often unwilling to investigate sleep disorders, which are more common in older adults. Physicians can be reluctant to prescribe sleep medications, and may also be unfamiliar with behavioral interventions. “For a lot of providers, getting into sleep issues is like opening a Pandora’s Box. I think mostly physicians are taught: Don’t do this, and don’t do that. They’re not as well versed in the things that they can and should do,” said Dr. Benca.

If attempts to treat insomnia don’t succeed, or if the physician suspects a movement disorder or primary sleep disorder like sleep apnea, then the patients should be referred to a sleep specialist, according to Dr. Benca.

During the question-and-answer period following her talk, a questioner brought up the increasingly common use of cannabis to improve sleep. That can be tricky because it can be difficult to stop cannabis use, because of the rebound insomnia that may persist. She noted that there are ongoing studies on the potential impact of cannabidiol oil.

Dr. Benca was also asked about patients who take sedatives chronically and seem to be doing well. She emphasized the need for finding the lowest effective dose of a short-acting medication. “Patients should be monitored frequently, at least every 6 months. Just monitor your patient carefully.”

Dr. Benca is a consultant for Eisai, Genomind, Idorsia, Jazz, Merck, Sage, and Sunovion.

New efforts – including the development of drugs that target mitochondrial pathways and others that target androgen receptors selectively – are underway for treating sarcopenia in rheumatic diseases, but so far the results have been mixed, an expert said at the Pan American League of Associations for Rheumatology (PANLAR) 2021 Annual Meeting, held recently as a virtual event.

Addressing the problem of reduced muscle mass – experienced by many patients with rheumatic diseases, owing in part to the processes of inflammation and to pain interfering with exercise – is bound to help with outcomes, inasmuch as lean mass and fat mass are linked with disability and early mortality, said Joshua Baker, MD, associate professor of medicine at the University of Pennsylvania, Philadelphia.

Elamipretide, which works by stabilizing mitochondrial pathways that are disrupted in people with sarcopenia, in particular those with mitochondrial disorders, might be the most promising of the therapies being developed. In a study published last year, patients with mitochondrial myopathy experienced significant improvement in gait speed, fatigue, and physical function after 4 weeks, Dr. Baker said.

It’s “an interesting and exciting approach that we need to see more studies about in the future,” he said.

Studies of selective androgen receptor modulators (SARMs), which are similar to anabolic steroids but only target certain androgen receptors so as to prevent side effects, have been a letdown, Dr. Baker said. The idea with SARMs is to enhance growth of certain tissue, such as muscle, without causing side effects in other tissues. Previous trials found that although this approach increased muscle mass, it didn’t produce improvements in measures of physical function.

A myostatin/activin type II receptor blocker, bimagrumab, was recently found to boost lean mass but without improvement in physical function or gait speed.

Still, the focus on improving sarcopenia is an encouraging development, Dr. Baker said.

“New therapies are in the pipeline, and let’s be optimistic and hope that in the future we’ll have lots of options for these patients,” he said.

For now, resistance training remains the best way to tackle the problem. However, the need to have access to trainers, equipment, and gyms, as well as the presence of comorbidities, can make exercise difficult, he said. In addition, routine nutritional supplements, such as with vitamin D, have not been found to improve outcomes, he noted.

The sheer number of people with sarcopenia should make the search for better inventions a priority, suggested Maria Lorena Brance, MD, PhD, professor of medicine at the National University of Rosario, Argentina.

“Prevalence of sarcopenia is very high in autoimmune disease, with representation between 20% and 30%, depending on the pathology,” she said. “So it’s very important to study the presence of sarcopenia.”

Identifying the problem – by first noticing symptoms and then confirming with tests of muscle strength, such as grip tests – would be a big step, the panelists said. Dr. Baker said that among patients with obesity, sarcopenia is more likely to be overlooked, because such patients might not be weak in an absolute sense but might be weak relative to their size.

Dr. Brance said that it’s important to differentiate the value of vitamin D for someone with normal levels in comparison with someone who has a deficiency. Although evidence does not support the use of vitamin D supplements across the board, supplements have been shown to be helpful for patients with low vitamin D levels, she said.

Xavier Ricardo, MD, PhD, professor at Federal University of Rio Grande, Brazil, suggested that sarcopenia may differ from what meets the eye. At his hospital, researchers are studying sarcopenia in patients with systemic sclerosis and have found that in about 20% to 25% of patients, it is present in levels similar to those that occur in patients with rheumatoid arthritis. Researchers are now examining tissue from biopsies to see whether there are differences between the two conditions in the processes of muscle wasting.

“So far, we’re a little bit surprised,” he said. “We expected to have more sarcopenia in these patients, because they do look more frail, more cachexic sometimes.”

Dr. Baker has received consulting fees from Bristol-Myers Squibb, Burns-White, and Gilead. Dr. Ricardo has received consulting fees, speaker fees, or both from AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer, Roche, and UCB. Dr. Brance has disclosed no relevant financial relationships.

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

New efforts – including the development of drugs that target mitochondrial pathways and others that target androgen receptors selectively – are underway for treating sarcopenia in rheumatic diseases, but so far the results have been mixed, an expert said at the Pan American League of Associations for Rheumatology (PANLAR) 2021 Annual Meeting, held recently as a virtual event.

Addressing the problem of reduced muscle mass – experienced by many patients with rheumatic diseases, owing in part to the processes of inflammation and to pain interfering with exercise – is bound to help with outcomes, inasmuch as lean mass and fat mass are linked with disability and early mortality, said Joshua Baker, MD, associate professor of medicine at the University of Pennsylvania, Philadelphia.

Elamipretide, which works by stabilizing mitochondrial pathways that are disrupted in people with sarcopenia, in particular those with mitochondrial disorders, might be the most promising of the therapies being developed. In a study published last year, patients with mitochondrial myopathy experienced significant improvement in gait speed, fatigue, and physical function after 4 weeks, Dr. Baker said.

It’s “an interesting and exciting approach that we need to see more studies about in the future,” he said.

Studies of selective androgen receptor modulators (SARMs), which are similar to anabolic steroids but only target certain androgen receptors so as to prevent side effects, have been a letdown, Dr. Baker said. The idea with SARMs is to enhance growth of certain tissue, such as muscle, without causing side effects in other tissues. Previous trials found that although this approach increased muscle mass, it didn’t produce improvements in measures of physical function.

A myostatin/activin type II receptor blocker, bimagrumab, was recently found to boost lean mass but without improvement in physical function or gait speed.

Still, the focus on improving sarcopenia is an encouraging development, Dr. Baker said.

“New therapies are in the pipeline, and let’s be optimistic and hope that in the future we’ll have lots of options for these patients,” he said.

For now, resistance training remains the best way to tackle the problem. However, the need to have access to trainers, equipment, and gyms, as well as the presence of comorbidities, can make exercise difficult, he said. In addition, routine nutritional supplements, such as with vitamin D, have not been found to improve outcomes, he noted.

The sheer number of people with sarcopenia should make the search for better inventions a priority, suggested Maria Lorena Brance, MD, PhD, professor of medicine at the National University of Rosario, Argentina.

“Prevalence of sarcopenia is very high in autoimmune disease, with representation between 20% and 30%, depending on the pathology,” she said. “So it’s very important to study the presence of sarcopenia.”

Identifying the problem – by first noticing symptoms and then confirming with tests of muscle strength, such as grip tests – would be a big step, the panelists said. Dr. Baker said that among patients with obesity, sarcopenia is more likely to be overlooked, because such patients might not be weak in an absolute sense but might be weak relative to their size.

Dr. Brance said that it’s important to differentiate the value of vitamin D for someone with normal levels in comparison with someone who has a deficiency. Although evidence does not support the use of vitamin D supplements across the board, supplements have been shown to be helpful for patients with low vitamin D levels, she said.

Xavier Ricardo, MD, PhD, professor at Federal University of Rio Grande, Brazil, suggested that sarcopenia may differ from what meets the eye. At his hospital, researchers are studying sarcopenia in patients with systemic sclerosis and have found that in about 20% to 25% of patients, it is present in levels similar to those that occur in patients with rheumatoid arthritis. Researchers are now examining tissue from biopsies to see whether there are differences between the two conditions in the processes of muscle wasting.

“So far, we’re a little bit surprised,” he said. “We expected to have more sarcopenia in these patients, because they do look more frail, more cachexic sometimes.”

Dr. Baker has received consulting fees from Bristol-Myers Squibb, Burns-White, and Gilead. Dr. Ricardo has received consulting fees, speaker fees, or both from AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer, Roche, and UCB. Dr. Brance has disclosed no relevant financial relationships.

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

New efforts – including the development of drugs that target mitochondrial pathways and others that target androgen receptors selectively – are underway for treating sarcopenia in rheumatic diseases, but so far the results have been mixed, an expert said at the Pan American League of Associations for Rheumatology (PANLAR) 2021 Annual Meeting, held recently as a virtual event.

Addressing the problem of reduced muscle mass – experienced by many patients with rheumatic diseases, owing in part to the processes of inflammation and to pain interfering with exercise – is bound to help with outcomes, inasmuch as lean mass and fat mass are linked with disability and early mortality, said Joshua Baker, MD, associate professor of medicine at the University of Pennsylvania, Philadelphia.

Elamipretide, which works by stabilizing mitochondrial pathways that are disrupted in people with sarcopenia, in particular those with mitochondrial disorders, might be the most promising of the therapies being developed. In a study published last year, patients with mitochondrial myopathy experienced significant improvement in gait speed, fatigue, and physical function after 4 weeks, Dr. Baker said.

It’s “an interesting and exciting approach that we need to see more studies about in the future,” he said.

Studies of selective androgen receptor modulators (SARMs), which are similar to anabolic steroids but only target certain androgen receptors so as to prevent side effects, have been a letdown, Dr. Baker said. The idea with SARMs is to enhance growth of certain tissue, such as muscle, without causing side effects in other tissues. Previous trials found that although this approach increased muscle mass, it didn’t produce improvements in measures of physical function.

A myostatin/activin type II receptor blocker, bimagrumab, was recently found to boost lean mass but without improvement in physical function or gait speed.

Still, the focus on improving sarcopenia is an encouraging development, Dr. Baker said.

“New therapies are in the pipeline, and let’s be optimistic and hope that in the future we’ll have lots of options for these patients,” he said.

For now, resistance training remains the best way to tackle the problem. However, the need to have access to trainers, equipment, and gyms, as well as the presence of comorbidities, can make exercise difficult, he said. In addition, routine nutritional supplements, such as with vitamin D, have not been found to improve outcomes, he noted.

The sheer number of people with sarcopenia should make the search for better inventions a priority, suggested Maria Lorena Brance, MD, PhD, professor of medicine at the National University of Rosario, Argentina.

“Prevalence of sarcopenia is very high in autoimmune disease, with representation between 20% and 30%, depending on the pathology,” she said. “So it’s very important to study the presence of sarcopenia.”

Identifying the problem – by first noticing symptoms and then confirming with tests of muscle strength, such as grip tests – would be a big step, the panelists said. Dr. Baker said that among patients with obesity, sarcopenia is more likely to be overlooked, because such patients might not be weak in an absolute sense but might be weak relative to their size.

Dr. Brance said that it’s important to differentiate the value of vitamin D for someone with normal levels in comparison with someone who has a deficiency. Although evidence does not support the use of vitamin D supplements across the board, supplements have been shown to be helpful for patients with low vitamin D levels, she said.

Xavier Ricardo, MD, PhD, professor at Federal University of Rio Grande, Brazil, suggested that sarcopenia may differ from what meets the eye. At his hospital, researchers are studying sarcopenia in patients with systemic sclerosis and have found that in about 20% to 25% of patients, it is present in levels similar to those that occur in patients with rheumatoid arthritis. Researchers are now examining tissue from biopsies to see whether there are differences between the two conditions in the processes of muscle wasting.

“So far, we’re a little bit surprised,” he said. “We expected to have more sarcopenia in these patients, because they do look more frail, more cachexic sometimes.”

Dr. Baker has received consulting fees from Bristol-Myers Squibb, Burns-White, and Gilead. Dr. Ricardo has received consulting fees, speaker fees, or both from AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer, Roche, and UCB. Dr. Brance has disclosed no relevant financial relationships.

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

Patients with alopecia areata (AA) appear to have a gut dysbiosis not seen in healthy individuals, according to research presented at the annual meeting of the Society for Investigative Dermatology.

There have been reports of gut microbiome dysbiosis associated with autoimmune diseases such as rheumatoid arthritis, diabetes, and celiac disease. “It is now clear that these events not just shape the immune response in the gut, but also distant sites and immune-privileged organs,” Tanya Sezin, a doctor of natural science from the University of Lübeck (Germany) and Columbia University, New York, said in her presentation.

Whether the gut microbiome may also play a role as an environmental factor in alopecia areata, another T-cell–mediated autoimmune disease for which there are few available treatment options, is being evaluated at the Christiano Laboratory at Columbia University, Dr. Sezin noted. “Much of the difficulty underlying the lack of an effective treatment has been the incomplete understanding of the pathogenesis of AA.”

She also referred to several case reports describing hair growth in patients who received fecal microbiota transplantation (FMT), including a 20-year-old with alopecia universalis, who experienced hair growth after receiving FMT for Crohn’s disease.

Dr. Sezin and colleagues at the lab first performed a study in mice to test whether the gut microbiome was involved in the pathogenesis of AA. Mice given an antibiotic cocktail of ampicillin, neomycin, and vancomycin prior to or at the time of a skin graft taken from a mouse model of AA to induce AA were protected from hair loss, while mice given the antibiotic cocktail after skin grafting were not protected from hair loss.

“16S rRNA sequencing analysis of the gut microbiota revealed a significant shift in gut microbiome composition in animals treated with antibiotics and protected from hair loss, as reflected by significant changes in alpha and beta diversity,” Dr. Sezin explained. “In AA mice, we also observed differential abundance of families from the Bacteroidetes and Firmicutes phyla.” Specifically, Lactobacillus murinus and Muribaculum intestinale were overrepresented in mice with AA.

The investigators then performed 16S rRNA sequencing on 26 patients with AA, who stopped treatment for 30 days beforehand, and 9 participants who did not have AA as controls. “Though we did not observe difference in alpha and beta diversity, we see changes in the relative abundance of several families belonging to the Firmicutes phyla,” in patients with AA, Dr. Sezin said.

In another cohort of 30 patients with AA and 20 participants without AA, who stopped treatment before the study, Dr. Sezin and colleagues found “differences in the relative abundance of members of the Firmicutes and Bacteroides phyla,” including Bacteroides caccae, Prevotella copri, Syntrophomonas wolfei, Blautia wexlerae, and Eubacterium eligens, she said. “Consistent with our findings, there are previous reports in the literature showing gut dysbiosis in several other autoimmune diseases associated with differential regulation of some of the top species we have identified.”

Dr. Sezin said her group is recruiting patients for a clinical trial evaluating FMT in patients with AA. “We plan to study the association between changes in the gut microbiome and immune cell composition in AA patients undergoing FMT,” she said. “Additionally, functional studies in mice are also currently [being conducted] to further pinpoint the contribution of gut microbiome to the pathogenesis of AA.”

When asked during the discussion session if there was any relationship between the skin microbiome and AA, Dr. Sezin said there was no connection found in mice studies, which she and her colleagues are investigating further. “In the human samples, we are currently recruiting more patients and healthy controls to try to get a better understanding of whether we see differences in the skin microbiome,” she added.

Dr. Sezin explained that how the gut microbiota “is really remediated in alopecia areata” is not well understood. “We think that it is possible that we see intestinal permeability in the gut due to the gut dysbiosis that we see in alopecia areata patients, and this might lead to systemic distribution of bacteria, which might cross-react or present cross reactivity with the antigens” identified in AA, which is also being investigated, she said.

FMT not a ‘simple fix’ for AA

Leslie Castelo-Soccio, MD, PhD, a dermatologist at the Children’s Hospital of Philadelphia, who was not involved with the research, said in an interview that the findings presented by Dr. Sezin show how AA shares similarities with other autoimmune diseases. “It does highlight how important the gut microbiome is to human disease, and that differences in relative abundance of bacteria play one part as a trigger in a genetically susceptible person.”

However, while some autoimmune diseases have a big difference in alpha and beta diversity, for example, “this has not been seen in people with alopecia areata,” Dr. Castelo-Soccio pointed out. “The differences are more subtle in terms of amounts of certain bacteria,” she said, noting that, in this study, the biggest differences were seen in the studies of mice.

Dr. Castelo-Soccio also said there may be also be differences in the gut microbiome in children and adults. “The gut microbiome shifts in very early childhood from a very diverse microbiome to a more ‘adult microbiome’ around age 4, which is the age we see the first peak of many autoimmune diseases, including alopecia areata. I think microbiome work in humans needs to focus on this transition point.”

As for the clinical trial at Columbia that is evaluating FMT in patients with AA, Dr. Castelo-Soccio said she is excited. “There is much to learn about fecal transplant for all diseases and about the role of the gut microbiome and environment. Most of what we know for fecal transplant centers on its use for Clostridium difficile infections.”

Patients and their families have been asking about the potential for FMT in alopecia area, Dr. Castelo-Soccio said, but some believe it is a “simple fix” when the reality is much more complex.

“When I speak to patients and families about this, I explain that currently the ‘active ingredient’ in fecal transplants is not definitively established. In any one donor, the community of bacteria is highly variable and can be from batch to batch. While the short-term risks are relatively low – cramping, diarrhea, discomfort, mode of delivery – there are reports of transmission of infectious bacteria from donors like [Escherichia] coli, which have led to severe infections.”

Long-term safety and durability of effects are also unclear, “so we do not know if a patient receiving one [FMT] will need many in the future. We do not know how changing the microbiome could affect the transplant recipient in terms of noninfectious diseases/disorders. We are learning about the role of microbiome in obesity, insulin resistance, mood disorders. We could be ‘fixing’ one trigger of alopecia but setting up [the] patient for other noninfectious conditions,” Dr. Castelo-Soccio said.

Dr. Sezin and Dr. Castelo-Soccio reported no relevant financial disclosures.

Patients with alopecia areata (AA) appear to have a gut dysbiosis not seen in healthy individuals, according to research presented at the annual meeting of the Society for Investigative Dermatology.

There have been reports of gut microbiome dysbiosis associated with autoimmune diseases such as rheumatoid arthritis, diabetes, and celiac disease. “It is now clear that these events not just shape the immune response in the gut, but also distant sites and immune-privileged organs,” Tanya Sezin, a doctor of natural science from the University of Lübeck (Germany) and Columbia University, New York, said in her presentation.

Whether the gut microbiome may also play a role as an environmental factor in alopecia areata, another T-cell–mediated autoimmune disease for which there are few available treatment options, is being evaluated at the Christiano Laboratory at Columbia University, Dr. Sezin noted. “Much of the difficulty underlying the lack of an effective treatment has been the incomplete understanding of the pathogenesis of AA.”

She also referred to several case reports describing hair growth in patients who received fecal microbiota transplantation (FMT), including a 20-year-old with alopecia universalis, who experienced hair growth after receiving FMT for Crohn’s disease.

Dr. Sezin and colleagues at the lab first performed a study in mice to test whether the gut microbiome was involved in the pathogenesis of AA. Mice given an antibiotic cocktail of ampicillin, neomycin, and vancomycin prior to or at the time of a skin graft taken from a mouse model of AA to induce AA were protected from hair loss, while mice given the antibiotic cocktail after skin grafting were not protected from hair loss.

“16S rRNA sequencing analysis of the gut microbiota revealed a significant shift in gut microbiome composition in animals treated with antibiotics and protected from hair loss, as reflected by significant changes in alpha and beta diversity,” Dr. Sezin explained. “In AA mice, we also observed differential abundance of families from the Bacteroidetes and Firmicutes phyla.” Specifically, Lactobacillus murinus and Muribaculum intestinale were overrepresented in mice with AA.

The investigators then performed 16S rRNA sequencing on 26 patients with AA, who stopped treatment for 30 days beforehand, and 9 participants who did not have AA as controls. “Though we did not observe difference in alpha and beta diversity, we see changes in the relative abundance of several families belonging to the Firmicutes phyla,” in patients with AA, Dr. Sezin said.

In another cohort of 30 patients with AA and 20 participants without AA, who stopped treatment before the study, Dr. Sezin and colleagues found “differences in the relative abundance of members of the Firmicutes and Bacteroides phyla,” including Bacteroides caccae, Prevotella copri, Syntrophomonas wolfei, Blautia wexlerae, and Eubacterium eligens, she said. “Consistent with our findings, there are previous reports in the literature showing gut dysbiosis in several other autoimmune diseases associated with differential regulation of some of the top species we have identified.”

Dr. Sezin said her group is recruiting patients for a clinical trial evaluating FMT in patients with AA. “We plan to study the association between changes in the gut microbiome and immune cell composition in AA patients undergoing FMT,” she said. “Additionally, functional studies in mice are also currently [being conducted] to further pinpoint the contribution of gut microbiome to the pathogenesis of AA.”

When asked during the discussion session if there was any relationship between the skin microbiome and AA, Dr. Sezin said there was no connection found in mice studies, which she and her colleagues are investigating further. “In the human samples, we are currently recruiting more patients and healthy controls to try to get a better understanding of whether we see differences in the skin microbiome,” she added.

Dr. Sezin explained that how the gut microbiota “is really remediated in alopecia areata” is not well understood. “We think that it is possible that we see intestinal permeability in the gut due to the gut dysbiosis that we see in alopecia areata patients, and this might lead to systemic distribution of bacteria, which might cross-react or present cross reactivity with the antigens” identified in AA, which is also being investigated, she said.

FMT not a ‘simple fix’ for AA

Leslie Castelo-Soccio, MD, PhD, a dermatologist at the Children’s Hospital of Philadelphia, who was not involved with the research, said in an interview that the findings presented by Dr. Sezin show how AA shares similarities with other autoimmune diseases. “It does highlight how important the gut microbiome is to human disease, and that differences in relative abundance of bacteria play one part as a trigger in a genetically susceptible person.”

However, while some autoimmune diseases have a big difference in alpha and beta diversity, for example, “this has not been seen in people with alopecia areata,” Dr. Castelo-Soccio pointed out. “The differences are more subtle in terms of amounts of certain bacteria,” she said, noting that, in this study, the biggest differences were seen in the studies of mice.

Dr. Castelo-Soccio also said there may be also be differences in the gut microbiome in children and adults. “The gut microbiome shifts in very early childhood from a very diverse microbiome to a more ‘adult microbiome’ around age 4, which is the age we see the first peak of many autoimmune diseases, including alopecia areata. I think microbiome work in humans needs to focus on this transition point.”

As for the clinical trial at Columbia that is evaluating FMT in patients with AA, Dr. Castelo-Soccio said she is excited. “There is much to learn about fecal transplant for all diseases and about the role of the gut microbiome and environment. Most of what we know for fecal transplant centers on its use for Clostridium difficile infections.”

Patients and their families have been asking about the potential for FMT in alopecia area, Dr. Castelo-Soccio said, but some believe it is a “simple fix” when the reality is much more complex.

“When I speak to patients and families about this, I explain that currently the ‘active ingredient’ in fecal transplants is not definitively established. In any one donor, the community of bacteria is highly variable and can be from batch to batch. While the short-term risks are relatively low – cramping, diarrhea, discomfort, mode of delivery – there are reports of transmission of infectious bacteria from donors like [Escherichia] coli, which have led to severe infections.”

Long-term safety and durability of effects are also unclear, “so we do not know if a patient receiving one [FMT] will need many in the future. We do not know how changing the microbiome could affect the transplant recipient in terms of noninfectious diseases/disorders. We are learning about the role of microbiome in obesity, insulin resistance, mood disorders. We could be ‘fixing’ one trigger of alopecia but setting up [the] patient for other noninfectious conditions,” Dr. Castelo-Soccio said.

Dr. Sezin and Dr. Castelo-Soccio reported no relevant financial disclosures.

Patients with alopecia areata (AA) appear to have a gut dysbiosis not seen in healthy individuals, according to research presented at the annual meeting of the Society for Investigative Dermatology.

There have been reports of gut microbiome dysbiosis associated with autoimmune diseases such as rheumatoid arthritis, diabetes, and celiac disease. “It is now clear that these events not just shape the immune response in the gut, but also distant sites and immune-privileged organs,” Tanya Sezin, a doctor of natural science from the University of Lübeck (Germany) and Columbia University, New York, said in her presentation.

Whether the gut microbiome may also play a role as an environmental factor in alopecia areata, another T-cell–mediated autoimmune disease for which there are few available treatment options, is being evaluated at the Christiano Laboratory at Columbia University, Dr. Sezin noted. “Much of the difficulty underlying the lack of an effective treatment has been the incomplete understanding of the pathogenesis of AA.”

She also referred to several case reports describing hair growth in patients who received fecal microbiota transplantation (FMT), including a 20-year-old with alopecia universalis, who experienced hair growth after receiving FMT for Crohn’s disease.

Dr. Sezin and colleagues at the lab first performed a study in mice to test whether the gut microbiome was involved in the pathogenesis of AA. Mice given an antibiotic cocktail of ampicillin, neomycin, and vancomycin prior to or at the time of a skin graft taken from a mouse model of AA to induce AA were protected from hair loss, while mice given the antibiotic cocktail after skin grafting were not protected from hair loss.

“16S rRNA sequencing analysis of the gut microbiota revealed a significant shift in gut microbiome composition in animals treated with antibiotics and protected from hair loss, as reflected by significant changes in alpha and beta diversity,” Dr. Sezin explained. “In AA mice, we also observed differential abundance of families from the Bacteroidetes and Firmicutes phyla.” Specifically, Lactobacillus murinus and Muribaculum intestinale were overrepresented in mice with AA.

The investigators then performed 16S rRNA sequencing on 26 patients with AA, who stopped treatment for 30 days beforehand, and 9 participants who did not have AA as controls. “Though we did not observe difference in alpha and beta diversity, we see changes in the relative abundance of several families belonging to the Firmicutes phyla,” in patients with AA, Dr. Sezin said.

In another cohort of 30 patients with AA and 20 participants without AA, who stopped treatment before the study, Dr. Sezin and colleagues found “differences in the relative abundance of members of the Firmicutes and Bacteroides phyla,” including Bacteroides caccae, Prevotella copri, Syntrophomonas wolfei, Blautia wexlerae, and Eubacterium eligens, she said. “Consistent with our findings, there are previous reports in the literature showing gut dysbiosis in several other autoimmune diseases associated with differential regulation of some of the top species we have identified.”

Dr. Sezin said her group is recruiting patients for a clinical trial evaluating FMT in patients with AA. “We plan to study the association between changes in the gut microbiome and immune cell composition in AA patients undergoing FMT,” she said. “Additionally, functional studies in mice are also currently [being conducted] to further pinpoint the contribution of gut microbiome to the pathogenesis of AA.”

When asked during the discussion session if there was any relationship between the skin microbiome and AA, Dr. Sezin said there was no connection found in mice studies, which she and her colleagues are investigating further. “In the human samples, we are currently recruiting more patients and healthy controls to try to get a better understanding of whether we see differences in the skin microbiome,” she added.

Dr. Sezin explained that how the gut microbiota “is really remediated in alopecia areata” is not well understood. “We think that it is possible that we see intestinal permeability in the gut due to the gut dysbiosis that we see in alopecia areata patients, and this might lead to systemic distribution of bacteria, which might cross-react or present cross reactivity with the antigens” identified in AA, which is also being investigated, she said.

FMT not a ‘simple fix’ for AA

Leslie Castelo-Soccio, MD, PhD, a dermatologist at the Children’s Hospital of Philadelphia, who was not involved with the research, said in an interview that the findings presented by Dr. Sezin show how AA shares similarities with other autoimmune diseases. “It does highlight how important the gut microbiome is to human disease, and that differences in relative abundance of bacteria play one part as a trigger in a genetically susceptible person.”

However, while some autoimmune diseases have a big difference in alpha and beta diversity, for example, “this has not been seen in people with alopecia areata,” Dr. Castelo-Soccio pointed out. “The differences are more subtle in terms of amounts of certain bacteria,” she said, noting that, in this study, the biggest differences were seen in the studies of mice.

Dr. Castelo-Soccio also said there may be also be differences in the gut microbiome in children and adults. “The gut microbiome shifts in very early childhood from a very diverse microbiome to a more ‘adult microbiome’ around age 4, which is the age we see the first peak of many autoimmune diseases, including alopecia areata. I think microbiome work in humans needs to focus on this transition point.”

As for the clinical trial at Columbia that is evaluating FMT in patients with AA, Dr. Castelo-Soccio said she is excited. “There is much to learn about fecal transplant for all diseases and about the role of the gut microbiome and environment. Most of what we know for fecal transplant centers on its use for Clostridium difficile infections.”

Patients and their families have been asking about the potential for FMT in alopecia area, Dr. Castelo-Soccio said, but some believe it is a “simple fix” when the reality is much more complex.

“When I speak to patients and families about this, I explain that currently the ‘active ingredient’ in fecal transplants is not definitively established. In any one donor, the community of bacteria is highly variable and can be from batch to batch. While the short-term risks are relatively low – cramping, diarrhea, discomfort, mode of delivery – there are reports of transmission of infectious bacteria from donors like [Escherichia] coli, which have led to severe infections.”

Long-term safety and durability of effects are also unclear, “so we do not know if a patient receiving one [FMT] will need many in the future. We do not know how changing the microbiome could affect the transplant recipient in terms of noninfectious diseases/disorders. We are learning about the role of microbiome in obesity, insulin resistance, mood disorders. We could be ‘fixing’ one trigger of alopecia but setting up [the] patient for other noninfectious conditions,” Dr. Castelo-Soccio said.

Dr. Sezin and Dr. Castelo-Soccio reported no relevant financial disclosures.

Wisdom increases with age, and although this personality trait is regarded as nebulous by many, there is evidence that it has biological and neuropsychiatric underpinnings. It could even hold the key to reducing loneliness and burnout among older people.

Courtesy Dr. Tanya T. Nguyen

Those were some of the key messages delivered by Tanya T. Nguyen, PhD, of the department of psychiatry at the University of California, San Diego, who spoke at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

“To many people, wisdom remains a fuzzy concept that’s difficult to operationalize and measure. It’s analogous to the concepts of consciousness, emotions, and cognitions, which at one point were considered nonscientific, but today we accept them as biological and scientific entities,” Dr. Nguyen said during her talk at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

Interest in quantifying and studying wisdom has picked up in recent years, and Dr. Nguyen gave a definition with six elements that includes prosocial behaviors such as empathy and compassion, as well as emotional regulation, self-reflection, decisiveness, and social decision-making. She also included a spirituality component, though she conceded that this is controversial.

She noted that there are cultural variations in the definition of wisdom, but it has changed little over time, suggesting that it may be biological rather than cultural in nature, and therefore may have a neuropsychiatric underpinning.

Loss of some or all characteristics of wisdom occurs in some behaviors and disorders, including most markedly in the neurodegenerative disorder frontotemporal dementia (FTD), which is characterized by damage only in the prefrontal cortex and anterior temporal lobes. It usually occurs before age 60, and patients exhibit poor social awareness, impulsivity, antisocial behavior, and a lack of insight and empathy.

This and other lines of evidence have led to the suggestion that wisdom may be governed by processes in the prefrontal cortex and the limbic striatum. The prefrontal cortex controls executive functions such as planning, predicting, and anticipating events, as well as managing emotional reactions and impulses. “Thus, wisdom involves parts of the brain that balance cold, hard analytical reasoning with primitive desires and drives, which ultimately leads to self-regulation, social insight, theory of mind, and empathy,” said Dr. Nguyen.

Wisdom has long been associated with age, but age is also linked to cognitive decline. A recent discovery that the brain does not stop evolving at older age may help explain this contradiction. Brains develop in a back to front order, so that the prefrontal cortex is the last to mature. As we age, neural activity shifts from the occipital lobes to the prefrontal cortex and its executive decision-making power.

“The brain may recruit higher-order networks to the prefrontal cortex that are associated with wisdom development,” said Dr. Nguyen. She also pointed out that asymmetry between the left and right hemisphere is reduced with age, as tasks that relied on circuits from one hemisphere or another more often call upon both. “In order to make up for lost synapses and neurons with aging, active older adults use more neuronal networks from both hemispheres to perform the same mental activity,” Dr. Nguyen said.

Some interventions can improve scores in traits associated with wisdom in older adults, and could be an important contributor to improvements in health and longevity, said Dr. Nguyen. Randomized, controlled trials have demonstrated that psychosocial or behavioral interventions can improve elements of wisdom such as prosocial behaviors and emotional regulation, both in people with mental illness and in the general population, with moderate to large effect sizes. But such studies don’t prove an effect on overall wisdom.

Dr. Nguyen’s group tested a manualized intervention called Raise Your Resilience, which attempts to improve wisdom, resilience, and perceived stress through engagement in value-based activities. The intervention achieved positive results in 89 participants in senior housing communities, though the effect sizes were small, possibly because of high baseline resilience. A subanalysis suggested that reduction in loneliness was mediated by an increase in compassion.

“One of the most striking findings from our research on wisdom is this consistent and very strongly negative correlation between wisdom and loneliness,” Dr. Nguyen said. She highlighted other U.S. nationwide and cross-cultural studies that showed inverse relationships between loneliness and wisdom.

Loneliness is an important topic because it can contribute to burnout and suicide rates.

“Loneliness has a profound effect on how we show up in the workplace, in school, and in our communities. And that leads to anxiety, depression, depersonalization, and emotional fatigue. All are key features of burnout. And together loneliness and burnout have contributed to increased rates of suicide by 30%, and opioid-related deaths almost sixfold since the late 1990s,” Dr. Nguyen said.

Loneliness also is associated with worse physical health, and it may be linked to wisdom. “Loneliness can be conceptualized as being caused and maintained by objective circumstances, such as physical or social distancing, and by thoughts, behaviors, and feelings surrounding those experiences, including biased perceptions of social relations, and a negative assessment of one’s social skills, which then results in a discrepancy between one’s desired and perceived social relationships, which then can contribute to social withdrawal,” Dr. Nguyen said.

Dr. Nguyen highlighted the AARP Foundation’s Experience Corps program, which recruits older adults to act as mentors and tutors for children in kindergarten through third grade. It involves 15 hours per week over an entire school year, with a focus on child literacy, development, and behavioral management skills. A study revealed a significant impact. “It showed improvements in children’s grades and happiness, as well as seniors’ mental and physical health,” Dr. Nguyen said.

Dr. Nguyen concluded that wisdom “may be a vaccine against compassion fatigue and burnout that drive today’s behavioral epidemics of loneliness, opioid abuse, and suicide. It’s a tool for our times. It’s nuanced, flexible, pragmatic, compassionate, and it presents a reasonable framework for getting along in the often messy world that we all share.”
 

Implications for psychiatrists

Henry A. Nasrallah, MD, who organized the conference, suggested that the benefits of wisdom may not be limited to patients. He pointed out that surgeons often retire at age 60 or 65 because of declining physical skills, while psychiatrists continue to practice.

“We develop more wisdom and better skills, and we can practice into our 60s and 70s. I know psychiatrists who practice sometimes into their 80s. It’s really a wonderful thing to know that what you do in life develops or enhances the neuroplasticity of certain brain regions. In our case, in psychiatry, it is the brain regions involved in wisdom,” commented Dr. Nasrallah, who is a professor of psychiatry, neurology, and neuroscience at the University of Cincinnati.

Dr. Nguyen has no financial disclosures. Dr. Nasrallah has received grants from Abbott, AstraZeneca, Forest, Janssen, Lilly, Pfizer, and Shire, and advises Abbott, AstraZeneca, and Shire.

Wisdom increases with age, and although this personality trait is regarded as nebulous by many, there is evidence that it has biological and neuropsychiatric underpinnings. It could even hold the key to reducing loneliness and burnout among older people.

Courtesy Dr. Tanya T. Nguyen

Those were some of the key messages delivered by Tanya T. Nguyen, PhD, of the department of psychiatry at the University of California, San Diego, who spoke at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

“To many people, wisdom remains a fuzzy concept that’s difficult to operationalize and measure. It’s analogous to the concepts of consciousness, emotions, and cognitions, which at one point were considered nonscientific, but today we accept them as biological and scientific entities,” Dr. Nguyen said during her talk at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

Interest in quantifying and studying wisdom has picked up in recent years, and Dr. Nguyen gave a definition with six elements that includes prosocial behaviors such as empathy and compassion, as well as emotional regulation, self-reflection, decisiveness, and social decision-making. She also included a spirituality component, though she conceded that this is controversial.

She noted that there are cultural variations in the definition of wisdom, but it has changed little over time, suggesting that it may be biological rather than cultural in nature, and therefore may have a neuropsychiatric underpinning.

Loss of some or all characteristics of wisdom occurs in some behaviors and disorders, including most markedly in the neurodegenerative disorder frontotemporal dementia (FTD), which is characterized by damage only in the prefrontal cortex and anterior temporal lobes. It usually occurs before age 60, and patients exhibit poor social awareness, impulsivity, antisocial behavior, and a lack of insight and empathy.

This and other lines of evidence have led to the suggestion that wisdom may be governed by processes in the prefrontal cortex and the limbic striatum. The prefrontal cortex controls executive functions such as planning, predicting, and anticipating events, as well as managing emotional reactions and impulses. “Thus, wisdom involves parts of the brain that balance cold, hard analytical reasoning with primitive desires and drives, which ultimately leads to self-regulation, social insight, theory of mind, and empathy,” said Dr. Nguyen.

Wisdom has long been associated with age, but age is also linked to cognitive decline. A recent discovery that the brain does not stop evolving at older age may help explain this contradiction. Brains develop in a back to front order, so that the prefrontal cortex is the last to mature. As we age, neural activity shifts from the occipital lobes to the prefrontal cortex and its executive decision-making power.

“The brain may recruit higher-order networks to the prefrontal cortex that are associated with wisdom development,” said Dr. Nguyen. She also pointed out that asymmetry between the left and right hemisphere is reduced with age, as tasks that relied on circuits from one hemisphere or another more often call upon both. “In order to make up for lost synapses and neurons with aging, active older adults use more neuronal networks from both hemispheres to perform the same mental activity,” Dr. Nguyen said.

Some interventions can improve scores in traits associated with wisdom in older adults, and could be an important contributor to improvements in health and longevity, said Dr. Nguyen. Randomized, controlled trials have demonstrated that psychosocial or behavioral interventions can improve elements of wisdom such as prosocial behaviors and emotional regulation, both in people with mental illness and in the general population, with moderate to large effect sizes. But such studies don’t prove an effect on overall wisdom.

Dr. Nguyen’s group tested a manualized intervention called Raise Your Resilience, which attempts to improve wisdom, resilience, and perceived stress through engagement in value-based activities. The intervention achieved positive results in 89 participants in senior housing communities, though the effect sizes were small, possibly because of high baseline resilience. A subanalysis suggested that reduction in loneliness was mediated by an increase in compassion.

“One of the most striking findings from our research on wisdom is this consistent and very strongly negative correlation between wisdom and loneliness,” Dr. Nguyen said. She highlighted other U.S. nationwide and cross-cultural studies that showed inverse relationships between loneliness and wisdom.

Loneliness is an important topic because it can contribute to burnout and suicide rates.

“Loneliness has a profound effect on how we show up in the workplace, in school, and in our communities. And that leads to anxiety, depression, depersonalization, and emotional fatigue. All are key features of burnout. And together loneliness and burnout have contributed to increased rates of suicide by 30%, and opioid-related deaths almost sixfold since the late 1990s,” Dr. Nguyen said.

Loneliness also is associated with worse physical health, and it may be linked to wisdom. “Loneliness can be conceptualized as being caused and maintained by objective circumstances, such as physical or social distancing, and by thoughts, behaviors, and feelings surrounding those experiences, including biased perceptions of social relations, and a negative assessment of one’s social skills, which then results in a discrepancy between one’s desired and perceived social relationships, which then can contribute to social withdrawal,” Dr. Nguyen said.

Dr. Nguyen highlighted the AARP Foundation’s Experience Corps program, which recruits older adults to act as mentors and tutors for children in kindergarten through third grade. It involves 15 hours per week over an entire school year, with a focus on child literacy, development, and behavioral management skills. A study revealed a significant impact. “It showed improvements in children’s grades and happiness, as well as seniors’ mental and physical health,” Dr. Nguyen said.

Dr. Nguyen concluded that wisdom “may be a vaccine against compassion fatigue and burnout that drive today’s behavioral epidemics of loneliness, opioid abuse, and suicide. It’s a tool for our times. It’s nuanced, flexible, pragmatic, compassionate, and it presents a reasonable framework for getting along in the often messy world that we all share.”
 

Implications for psychiatrists

Henry A. Nasrallah, MD, who organized the conference, suggested that the benefits of wisdom may not be limited to patients. He pointed out that surgeons often retire at age 60 or 65 because of declining physical skills, while psychiatrists continue to practice.

“We develop more wisdom and better skills, and we can practice into our 60s and 70s. I know psychiatrists who practice sometimes into their 80s. It’s really a wonderful thing to know that what you do in life develops or enhances the neuroplasticity of certain brain regions. In our case, in psychiatry, it is the brain regions involved in wisdom,” commented Dr. Nasrallah, who is a professor of psychiatry, neurology, and neuroscience at the University of Cincinnati.

Dr. Nguyen has no financial disclosures. Dr. Nasrallah has received grants from Abbott, AstraZeneca, Forest, Janssen, Lilly, Pfizer, and Shire, and advises Abbott, AstraZeneca, and Shire.

Wisdom increases with age, and although this personality trait is regarded as nebulous by many, there is evidence that it has biological and neuropsychiatric underpinnings. It could even hold the key to reducing loneliness and burnout among older people.

Courtesy Dr. Tanya T. Nguyen

Those were some of the key messages delivered by Tanya T. Nguyen, PhD, of the department of psychiatry at the University of California, San Diego, who spoke at a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

“To many people, wisdom remains a fuzzy concept that’s difficult to operationalize and measure. It’s analogous to the concepts of consciousness, emotions, and cognitions, which at one point were considered nonscientific, but today we accept them as biological and scientific entities,” Dr. Nguyen said during her talk at the meeting presented by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.

Interest in quantifying and studying wisdom has picked up in recent years, and Dr. Nguyen gave a definition with six elements that includes prosocial behaviors such as empathy and compassion, as well as emotional regulation, self-reflection, decisiveness, and social decision-making. She also included a spirituality component, though she conceded that this is controversial.

She noted that there are cultural variations in the definition of wisdom, but it has changed little over time, suggesting that it may be biological rather than cultural in nature, and therefore may have a neuropsychiatric underpinning.

Loss of some or all characteristics of wisdom occurs in some behaviors and disorders, including most markedly in the neurodegenerative disorder frontotemporal dementia (FTD), which is characterized by damage only in the prefrontal cortex and anterior temporal lobes. It usually occurs before age 60, and patients exhibit poor social awareness, impulsivity, antisocial behavior, and a lack of insight and empathy.

This and other lines of evidence have led to the suggestion that wisdom may be governed by processes in the prefrontal cortex and the limbic striatum. The prefrontal cortex controls executive functions such as planning, predicting, and anticipating events, as well as managing emotional reactions and impulses. “Thus, wisdom involves parts of the brain that balance cold, hard analytical reasoning with primitive desires and drives, which ultimately leads to self-regulation, social insight, theory of mind, and empathy,” said Dr. Nguyen.

Wisdom has long been associated with age, but age is also linked to cognitive decline. A recent discovery that the brain does not stop evolving at older age may help explain this contradiction. Brains develop in a back to front order, so that the prefrontal cortex is the last to mature. As we age, neural activity shifts from the occipital lobes to the prefrontal cortex and its executive decision-making power.

“The brain may recruit higher-order networks to the prefrontal cortex that are associated with wisdom development,” said Dr. Nguyen. She also pointed out that asymmetry between the left and right hemisphere is reduced with age, as tasks that relied on circuits from one hemisphere or another more often call upon both. “In order to make up for lost synapses and neurons with aging, active older adults use more neuronal networks from both hemispheres to perform the same mental activity,” Dr. Nguyen said.

Some interventions can improve scores in traits associated with wisdom in older adults, and could be an important contributor to improvements in health and longevity, said Dr. Nguyen. Randomized, controlled trials have demonstrated that psychosocial or behavioral interventions can improve elements of wisdom such as prosocial behaviors and emotional regulation, both in people with mental illness and in the general population, with moderate to large effect sizes. But such studies don’t prove an effect on overall wisdom.

Dr. Nguyen’s group tested a manualized intervention called Raise Your Resilience, which attempts to improve wisdom, resilience, and perceived stress through engagement in value-based activities. The intervention achieved positive results in 89 participants in senior housing communities, though the effect sizes were small, possibly because of high baseline resilience. A subanalysis suggested that reduction in loneliness was mediated by an increase in compassion.

“One of the most striking findings from our research on wisdom is this consistent and very strongly negative correlation between wisdom and loneliness,” Dr. Nguyen said. She highlighted other U.S. nationwide and cross-cultural studies that showed inverse relationships between loneliness and wisdom.

Loneliness is an important topic because it can contribute to burnout and suicide rates.

“Loneliness has a profound effect on how we show up in the workplace, in school, and in our communities. And that leads to anxiety, depression, depersonalization, and emotional fatigue. All are key features of burnout. And together loneliness and burnout have contributed to increased rates of suicide by 30%, and opioid-related deaths almost sixfold since the late 1990s,” Dr. Nguyen said.

Loneliness also is associated with worse physical health, and it may be linked to wisdom. “Loneliness can be conceptualized as being caused and maintained by objective circumstances, such as physical or social distancing, and by thoughts, behaviors, and feelings surrounding those experiences, including biased perceptions of social relations, and a negative assessment of one’s social skills, which then results in a discrepancy between one’s desired and perceived social relationships, which then can contribute to social withdrawal,” Dr. Nguyen said.

Dr. Nguyen highlighted the AARP Foundation’s Experience Corps program, which recruits older adults to act as mentors and tutors for children in kindergarten through third grade. It involves 15 hours per week over an entire school year, with a focus on child literacy, development, and behavioral management skills. A study revealed a significant impact. “It showed improvements in children’s grades and happiness, as well as seniors’ mental and physical health,” Dr. Nguyen said.

Dr. Nguyen concluded that wisdom “may be a vaccine against compassion fatigue and burnout that drive today’s behavioral epidemics of loneliness, opioid abuse, and suicide. It’s a tool for our times. It’s nuanced, flexible, pragmatic, compassionate, and it presents a reasonable framework for getting along in the often messy world that we all share.”
 

Implications for psychiatrists

Henry A. Nasrallah, MD, who organized the conference, suggested that the benefits of wisdom may not be limited to patients. He pointed out that surgeons often retire at age 60 or 65 because of declining physical skills, while psychiatrists continue to practice.

“We develop more wisdom and better skills, and we can practice into our 60s and 70s. I know psychiatrists who practice sometimes into their 80s. It’s really a wonderful thing to know that what you do in life develops or enhances the neuroplasticity of certain brain regions. In our case, in psychiatry, it is the brain regions involved in wisdom,” commented Dr. Nasrallah, who is a professor of psychiatry, neurology, and neuroscience at the University of Cincinnati.

Dr. Nguyen has no financial disclosures. Dr. Nasrallah has received grants from Abbott, AstraZeneca, Forest, Janssen, Lilly, Pfizer, and Shire, and advises Abbott, AstraZeneca, and Shire.

Structural racism and implicit bias are connected, and both must be addressed to move from awareness of racism to action, said Nathan Chomilo, MD, of HealthPartners/Park Nicollet, Brooklyn Center, Minn., in a presentation at the virtual Pediatric Hospital Medicine annual conference.

“We need pediatricians with the courage to address racism head on,” he said.

One step in moving from awareness to action against structural and institutional racism in medicine is examining policies, Dr. Chomilo said. He cited the creation of Medicare and Medicaid in 1965 as examples of how policy changes can make a difference, illustrated by data from 1955-1975 that showed a significant decrease in infant deaths among Black infants in Mississippi after 1965.

Medicaid expansion has helped to narrow, but not eliminate, racial disparities in health care, Dr. Chomilo said. The impact of Medicare and Medicaid is evident in the current COVID-19 pandemic, as county level data show that areas where more than 25% of the population are uninsured have higher rates of COVID-19 infections, said Dr. Chomilo. Policies that impact access to care also impact their incidence of chronic diseases and risk for severe disease, he noted.

“If you don’t have ready access to a health care provider, you don’t have access to the vaccine, and you don’t have information that would inform your getting the vaccine,” he added.
 

Prioritizing the power of voting

“Voting is one of many ways we can impact structural racism in health care policy,” Dr. Chomilo emphasized.

However, voting inequity remains a challenge, Dr. Chomilo noted. Community level disparities lead to inequity in voting access and subsequent disparities in voter participation, he said. “Leaders are less responsive to nonvoting constituents,” which can result in policies that impact health inequitably, and loop back to community level health disparities, he explained.

Historically, physicians have had an 8%-9% lower voter turnout than the general public, although this may have changed in recent elections, Dr. Chomilo said. He encouraged all clinicians to set an example and vote, and to empower their patients to vote. Evidence shows that enfranchisement of Black voters is associated with reductions in education gaps for Blacks and Whites, and that enfranchisement of women is associated with increased spending on children and lower child mortality, he said. Dr. Chomilo encouraged pediatricians and all clinicians to take advantage of the resources on voting available from the American Academy of Pediatrics (aap.org/votekids).

“When we see more people in a community vote, leaders are more responsive to their needs,” he said.
 

Informing racial identity

“Racial identity is informed by racial socialization,” Dr. Chomilo said. “All of us are socialized along the lines of race; it happens in conversations with parents, family, peers, community.” Another point in moving from awareness to action in eliminating structural racism is recognizing that children are not too young to talk about race, Dr. Chomilo emphasized.

Children start to navigate racial identity and to take note of other differences at an early age. For example, a 3-year-old might ask, “why does that person talk funny, why is that person being pushed in a chair?” Dr. Chomilo said, and it is important for parents and as pediatricians to be prepared for these questions, which are part of normal development. As children get older, they start to reflect on what differences mean for them, which is not rooted in anything negative, he noted.

Children first develop racial identity at home, but children solidify their identities in child care and school settings, Dr. Chomilo said. The American Academy of Pediatrics has acknowledged the potential for racial bias in education and child care, and said in a statement that, “it is critical for pediatricians to recognize the institutional personally mediated, and internalized levels of racism that occur in the educational setting, because education is a critical social determinant of health for children.” In fact, data from children in preschool show that they use racial categories to identify themselves and others, to include or exclude children from activities, and to negotiate power in their social and play networks.

Early intervention matters in educating children about racism, Dr. Chomilo said. “If we were not taught to talk about race, it is on us to learn about it ourselves as well,” he said.

Ultimately, the goal is to create active antiracism among adults and children, said Dr. Chomilo. He encouraged pediatricians and parents not to shut down or discourage children when they raise questions of race, but to take the opportunity to teach. “There may be hurt feelings around what a child said, even if they didn’t mean to offend someone,” he noted. Take the topic seriously, and make racism conversations ongoing; teach children to safely oppose negative messages and behaviors in others, and replace them with something positive, he emphasized.
 

Addressing bias in clinical settings

Dr. Chomilo also encouraged hospitalists to consider internalized racism in clinical settings and take action to build confidence and cultural pride in all patients by ensuring that a pediatric hospital unit is welcoming and representative of the diversity in a given community, with appropriate options for books, movies, and toys. He also encouraged pediatric hospitalists to assess children for experiences of racism as part of a social assessment. Be aware of signs of posttraumatic stress, anxiety, depression, or grief that might have a racial component, he said.

Dr. Chomilo had no financial conflicts to disclose.

Structural racism and implicit bias are connected, and both must be addressed to move from awareness of racism to action, said Nathan Chomilo, MD, of HealthPartners/Park Nicollet, Brooklyn Center, Minn., in a presentation at the virtual Pediatric Hospital Medicine annual conference.

“We need pediatricians with the courage to address racism head on,” he said.

One step in moving from awareness to action against structural and institutional racism in medicine is examining policies, Dr. Chomilo said. He cited the creation of Medicare and Medicaid in 1965 as examples of how policy changes can make a difference, illustrated by data from 1955-1975 that showed a significant decrease in infant deaths among Black infants in Mississippi after 1965.

Medicaid expansion has helped to narrow, but not eliminate, racial disparities in health care, Dr. Chomilo said. The impact of Medicare and Medicaid is evident in the current COVID-19 pandemic, as county level data show that areas where more than 25% of the population are uninsured have higher rates of COVID-19 infections, said Dr. Chomilo. Policies that impact access to care also impact their incidence of chronic diseases and risk for severe disease, he noted.

“If you don’t have ready access to a health care provider, you don’t have access to the vaccine, and you don’t have information that would inform your getting the vaccine,” he added.
 

Prioritizing the power of voting

“Voting is one of many ways we can impact structural racism in health care policy,” Dr. Chomilo emphasized.

However, voting inequity remains a challenge, Dr. Chomilo noted. Community level disparities lead to inequity in voting access and subsequent disparities in voter participation, he said. “Leaders are less responsive to nonvoting constituents,” which can result in policies that impact health inequitably, and loop back to community level health disparities, he explained.

Historically, physicians have had an 8%-9% lower voter turnout than the general public, although this may have changed in recent elections, Dr. Chomilo said. He encouraged all clinicians to set an example and vote, and to empower their patients to vote. Evidence shows that enfranchisement of Black voters is associated with reductions in education gaps for Blacks and Whites, and that enfranchisement of women is associated with increased spending on children and lower child mortality, he said. Dr. Chomilo encouraged pediatricians and all clinicians to take advantage of the resources on voting available from the American Academy of Pediatrics (aap.org/votekids).

“When we see more people in a community vote, leaders are more responsive to their needs,” he said.
 

Informing racial identity

“Racial identity is informed by racial socialization,” Dr. Chomilo said. “All of us are socialized along the lines of race; it happens in conversations with parents, family, peers, community.” Another point in moving from awareness to action in eliminating structural racism is recognizing that children are not too young to talk about race, Dr. Chomilo emphasized.

Children start to navigate racial identity and to take note of other differences at an early age. For example, a 3-year-old might ask, “why does that person talk funny, why is that person being pushed in a chair?” Dr. Chomilo said, and it is important for parents and as pediatricians to be prepared for these questions, which are part of normal development. As children get older, they start to reflect on what differences mean for them, which is not rooted in anything negative, he noted.

Children first develop racial identity at home, but children solidify their identities in child care and school settings, Dr. Chomilo said. The American Academy of Pediatrics has acknowledged the potential for racial bias in education and child care, and said in a statement that, “it is critical for pediatricians to recognize the institutional personally mediated, and internalized levels of racism that occur in the educational setting, because education is a critical social determinant of health for children.” In fact, data from children in preschool show that they use racial categories to identify themselves and others, to include or exclude children from activities, and to negotiate power in their social and play networks.

Early intervention matters in educating children about racism, Dr. Chomilo said. “If we were not taught to talk about race, it is on us to learn about it ourselves as well,” he said.

Ultimately, the goal is to create active antiracism among adults and children, said Dr. Chomilo. He encouraged pediatricians and parents not to shut down or discourage children when they raise questions of race, but to take the opportunity to teach. “There may be hurt feelings around what a child said, even if they didn’t mean to offend someone,” he noted. Take the topic seriously, and make racism conversations ongoing; teach children to safely oppose negative messages and behaviors in others, and replace them with something positive, he emphasized.
 

Addressing bias in clinical settings

Dr. Chomilo also encouraged hospitalists to consider internalized racism in clinical settings and take action to build confidence and cultural pride in all patients by ensuring that a pediatric hospital unit is welcoming and representative of the diversity in a given community, with appropriate options for books, movies, and toys. He also encouraged pediatric hospitalists to assess children for experiences of racism as part of a social assessment. Be aware of signs of posttraumatic stress, anxiety, depression, or grief that might have a racial component, he said.

Dr. Chomilo had no financial conflicts to disclose.

Structural racism and implicit bias are connected, and both must be addressed to move from awareness of racism to action, said Nathan Chomilo, MD, of HealthPartners/Park Nicollet, Brooklyn Center, Minn., in a presentation at the virtual Pediatric Hospital Medicine annual conference.

“We need pediatricians with the courage to address racism head on,” he said.

One step in moving from awareness to action against structural and institutional racism in medicine is examining policies, Dr. Chomilo said. He cited the creation of Medicare and Medicaid in 1965 as examples of how policy changes can make a difference, illustrated by data from 1955-1975 that showed a significant decrease in infant deaths among Black infants in Mississippi after 1965.

Medicaid expansion has helped to narrow, but not eliminate, racial disparities in health care, Dr. Chomilo said. The impact of Medicare and Medicaid is evident in the current COVID-19 pandemic, as county level data show that areas where more than 25% of the population are uninsured have higher rates of COVID-19 infections, said Dr. Chomilo. Policies that impact access to care also impact their incidence of chronic diseases and risk for severe disease, he noted.

“If you don’t have ready access to a health care provider, you don’t have access to the vaccine, and you don’t have information that would inform your getting the vaccine,” he added.
 

Prioritizing the power of voting

“Voting is one of many ways we can impact structural racism in health care policy,” Dr. Chomilo emphasized.

However, voting inequity remains a challenge, Dr. Chomilo noted. Community level disparities lead to inequity in voting access and subsequent disparities in voter participation, he said. “Leaders are less responsive to nonvoting constituents,” which can result in policies that impact health inequitably, and loop back to community level health disparities, he explained.

Historically, physicians have had an 8%-9% lower voter turnout than the general public, although this may have changed in recent elections, Dr. Chomilo said. He encouraged all clinicians to set an example and vote, and to empower their patients to vote. Evidence shows that enfranchisement of Black voters is associated with reductions in education gaps for Blacks and Whites, and that enfranchisement of women is associated with increased spending on children and lower child mortality, he said. Dr. Chomilo encouraged pediatricians and all clinicians to take advantage of the resources on voting available from the American Academy of Pediatrics (aap.org/votekids).

“When we see more people in a community vote, leaders are more responsive to their needs,” he said.
 

Informing racial identity

“Racial identity is informed by racial socialization,” Dr. Chomilo said. “All of us are socialized along the lines of race; it happens in conversations with parents, family, peers, community.” Another point in moving from awareness to action in eliminating structural racism is recognizing that children are not too young to talk about race, Dr. Chomilo emphasized.

Children start to navigate racial identity and to take note of other differences at an early age. For example, a 3-year-old might ask, “why does that person talk funny, why is that person being pushed in a chair?” Dr. Chomilo said, and it is important for parents and as pediatricians to be prepared for these questions, which are part of normal development. As children get older, they start to reflect on what differences mean for them, which is not rooted in anything negative, he noted.

Children first develop racial identity at home, but children solidify their identities in child care and school settings, Dr. Chomilo said. The American Academy of Pediatrics has acknowledged the potential for racial bias in education and child care, and said in a statement that, “it is critical for pediatricians to recognize the institutional personally mediated, and internalized levels of racism that occur in the educational setting, because education is a critical social determinant of health for children.” In fact, data from children in preschool show that they use racial categories to identify themselves and others, to include or exclude children from activities, and to negotiate power in their social and play networks.

Early intervention matters in educating children about racism, Dr. Chomilo said. “If we were not taught to talk about race, it is on us to learn about it ourselves as well,” he said.

Ultimately, the goal is to create active antiracism among adults and children, said Dr. Chomilo. He encouraged pediatricians and parents not to shut down or discourage children when they raise questions of race, but to take the opportunity to teach. “There may be hurt feelings around what a child said, even if they didn’t mean to offend someone,” he noted. Take the topic seriously, and make racism conversations ongoing; teach children to safely oppose negative messages and behaviors in others, and replace them with something positive, he emphasized.
 

Addressing bias in clinical settings

Dr. Chomilo also encouraged hospitalists to consider internalized racism in clinical settings and take action to build confidence and cultural pride in all patients by ensuring that a pediatric hospital unit is welcoming and representative of the diversity in a given community, with appropriate options for books, movies, and toys. He also encouraged pediatric hospitalists to assess children for experiences of racism as part of a social assessment. Be aware of signs of posttraumatic stress, anxiety, depression, or grief that might have a racial component, he said.

Dr. Chomilo had no financial conflicts to disclose.

Most pediatric patients diagnosed with an inflammatory or autoimmune disorder lacked evidence of an immune response to the hepatitis B vaccine, results from a single-center retrospective study showed.

“Hepatitis B is a common viral infection with 2 billion people worldwide having evidence of prior or current infection, and it can present as an acute or chronic infection,” or with chronic sequelae, including cirrhosis and hepatocellular carcinoma, Alexandra Ritter said during the annual meeting of the Society for Pediatric Dermatology. A three-dose vaccination series is recommended beginning at birth, and in 2016, the Centers for Disease Control and Prevention reported that 90.5% of U.S. children aged 19-35 months had completed the series.

While the vaccine series provides protection in healthy individuals more than 95% of the time, a decreased response has been noted in specific pediatric populations, including those with inflammatory and autoimmune diseases. “This is important to note and investigate further because a decreased vaccine response increases the risk for this high-risk population, and the use of boosters is currently debated,” said Ms. Ritter, who is a fourth-year student at the Medical University of South Carolina, Charleston.

To determine the percent of pediatric patients with inflammatory or autoimmune disease who lack evidence of immunity following the hepatitis B vaccine series, Ms. Ritter and colleagues Abigail Truitt and pediatric dermatologist Lara Wine Lee, MD, PhD, of MUSC, retrospectively reviewed the charts of 160 patients between the ages of 6 months and 21 years, who were diagnosed with an autoimmune or autoinflammatory disease, or inflammatory bowel disease (IBD), and had documented evidence of vaccination and serologic testing prior to the start of immunosuppressive therapy.

Of the 160 patients, 100 (63%) had IBD, 34 (21%) had an autoimmune disease, 26 (16%) had an autoinflammatory disease, 89 (56%) were female, and their mean age was 15 years.

The researchers observed variation in the testing ordered between the three patient groups. Specifically, 88.2% of autoimmune patients had hepatitis B surface antigen (HBsAg) testing, compared with 96.15% of patients with an autoinflammatory disease and 67% of patients with IBD, while 76.47% of patients with an autoimmune disease had hepatitis B core antibody (anti-HBc) testing, compared with 88.46% of patients with an autoinflammatory disease and 31% of patients with IBD.

In addition, 82.35% of patients with an autoimmune disease had HBsAg testing, compared with 100% of patients with an autoinflammatory disease and 94% of patients with IBD.

Of the 148 patients who had HBsAg testing ordered and completed prior to starting an immunosuppressive drug, there was no statistically significant difference in the percent of patients showing evidence of an immune response to the hepatitis B vaccine (32.14% among patients with an autoimmune disease, 34.62% among patients with an autoinflammatory disease, and 31.91% among patients with IBD). Combined, 67.57% of tested negative for the hepatitis B surface antibody.

“Our study showed that the majority of these patients did not show serologic evidence of immunity despite being fully vaccinated,” Ms. Ritter said. “There was also variation in the testing ordered and a more standardized approach is needed in this high-risk population.” She acknowledged certain limitations of the study, including its retrospective design and lack of a control group.

“This brings us to our next question of whether this indicates a failure of the vaccine, or the way immunity is tested,” she continued. “The CDC and the European Consensus Group on Hepatitis B Immunity recommend a cutoff of greater than 10 mIU/mL. Those that achieve immunity are protected for up to 20 years due to immune memory, even if their antibody levels later drop. There have been rare cases of immunocompetent individuals having evidence of transient asymptomatic infections when antibody levels drop. The chronic disease has only been documented in infants born to positive mothers. In hemodialysis patients, however, clinically significant infections have been documented when antibody levels drop.”

The CDC only recommends postvaccination testing to infants born to positive mothers, health care workers at high risk, hemodialysis patients, people with HIV and other immunocompromised people, and needle-sharing partners of chronically infected people. This is completed 1-2 months following the third vaccine dose, and those with antibody levels less than 10 mIU/mL should be revaccinated. “As some groups do not respond to the vaccine series, alternative dosing and the intradermal vaccine have been studied and shown to be effective in certain groups,” she said.

When it comes to monitoring immunocompromised individuals and giving booster shots, however, there are conflicting recommendations. The CDC recommends yearly testing and booster shots when levels drop below 10 mIU/mL only in hemodialysis patients, while the European Consensus Group recommends testing every 6-12 months for immunocompromised individuals and boosters when their levels drop below 10 mIU/mL.

“The CDC has not yet determined if other immunocompromised individuals should receive a booster, with more research required, but studies have shown it to be effective,” Ms. Ritter said. In a similar study looking at evidence of immunity in children with connective tissue disease who were on immunosuppressive treatment, 50% had no evidence of protective antibodies, compared with 96% in the control group. “In that study, a booster shot was given, and protective antibody concentrations were found at follow-up,” she said.

The researchers reported having no financial disclosures.

dbrunk@mdedge.com

Most pediatric patients diagnosed with an inflammatory or autoimmune disorder lacked evidence of an immune response to the hepatitis B vaccine, results from a single-center retrospective study showed.

“Hepatitis B is a common viral infection with 2 billion people worldwide having evidence of prior or current infection, and it can present as an acute or chronic infection,” or with chronic sequelae, including cirrhosis and hepatocellular carcinoma, Alexandra Ritter said during the annual meeting of the Society for Pediatric Dermatology. A three-dose vaccination series is recommended beginning at birth, and in 2016, the Centers for Disease Control and Prevention reported that 90.5% of U.S. children aged 19-35 months had completed the series.

While the vaccine series provides protection in healthy individuals more than 95% of the time, a decreased response has been noted in specific pediatric populations, including those with inflammatory and autoimmune diseases. “This is important to note and investigate further because a decreased vaccine response increases the risk for this high-risk population, and the use of boosters is currently debated,” said Ms. Ritter, who is a fourth-year student at the Medical University of South Carolina, Charleston.

To determine the percent of pediatric patients with inflammatory or autoimmune disease who lack evidence of immunity following the hepatitis B vaccine series, Ms. Ritter and colleagues Abigail Truitt and pediatric dermatologist Lara Wine Lee, MD, PhD, of MUSC, retrospectively reviewed the charts of 160 patients between the ages of 6 months and 21 years, who were diagnosed with an autoimmune or autoinflammatory disease, or inflammatory bowel disease (IBD), and had documented evidence of vaccination and serologic testing prior to the start of immunosuppressive therapy.

Of the 160 patients, 100 (63%) had IBD, 34 (21%) had an autoimmune disease, 26 (16%) had an autoinflammatory disease, 89 (56%) were female, and their mean age was 15 years.

The researchers observed variation in the testing ordered between the three patient groups. Specifically, 88.2% of autoimmune patients had hepatitis B surface antigen (HBsAg) testing, compared with 96.15% of patients with an autoinflammatory disease and 67% of patients with IBD, while 76.47% of patients with an autoimmune disease had hepatitis B core antibody (anti-HBc) testing, compared with 88.46% of patients with an autoinflammatory disease and 31% of patients with IBD.

In addition, 82.35% of patients with an autoimmune disease had HBsAg testing, compared with 100% of patients with an autoinflammatory disease and 94% of patients with IBD.

Of the 148 patients who had HBsAg testing ordered and completed prior to starting an immunosuppressive drug, there was no statistically significant difference in the percent of patients showing evidence of an immune response to the hepatitis B vaccine (32.14% among patients with an autoimmune disease, 34.62% among patients with an autoinflammatory disease, and 31.91% among patients with IBD). Combined, 67.57% of tested negative for the hepatitis B surface antibody.

“Our study showed that the majority of these patients did not show serologic evidence of immunity despite being fully vaccinated,” Ms. Ritter said. “There was also variation in the testing ordered and a more standardized approach is needed in this high-risk population.” She acknowledged certain limitations of the study, including its retrospective design and lack of a control group.

“This brings us to our next question of whether this indicates a failure of the vaccine, or the way immunity is tested,” she continued. “The CDC and the European Consensus Group on Hepatitis B Immunity recommend a cutoff of greater than 10 mIU/mL. Those that achieve immunity are protected for up to 20 years due to immune memory, even if their antibody levels later drop. There have been rare cases of immunocompetent individuals having evidence of transient asymptomatic infections when antibody levels drop. The chronic disease has only been documented in infants born to positive mothers. In hemodialysis patients, however, clinically significant infections have been documented when antibody levels drop.”

The CDC only recommends postvaccination testing to infants born to positive mothers, health care workers at high risk, hemodialysis patients, people with HIV and other immunocompromised people, and needle-sharing partners of chronically infected people. This is completed 1-2 months following the third vaccine dose, and those with antibody levels less than 10 mIU/mL should be revaccinated. “As some groups do not respond to the vaccine series, alternative dosing and the intradermal vaccine have been studied and shown to be effective in certain groups,” she said.

When it comes to monitoring immunocompromised individuals and giving booster shots, however, there are conflicting recommendations. The CDC recommends yearly testing and booster shots when levels drop below 10 mIU/mL only in hemodialysis patients, while the European Consensus Group recommends testing every 6-12 months for immunocompromised individuals and boosters when their levels drop below 10 mIU/mL.

“The CDC has not yet determined if other immunocompromised individuals should receive a booster, with more research required, but studies have shown it to be effective,” Ms. Ritter said. In a similar study looking at evidence of immunity in children with connective tissue disease who were on immunosuppressive treatment, 50% had no evidence of protective antibodies, compared with 96% in the control group. “In that study, a booster shot was given, and protective antibody concentrations were found at follow-up,” she said.

The researchers reported having no financial disclosures.

dbrunk@mdedge.com

Most pediatric patients diagnosed with an inflammatory or autoimmune disorder lacked evidence of an immune response to the hepatitis B vaccine, results from a single-center retrospective study showed.

“Hepatitis B is a common viral infection with 2 billion people worldwide having evidence of prior or current infection, and it can present as an acute or chronic infection,” or with chronic sequelae, including cirrhosis and hepatocellular carcinoma, Alexandra Ritter said during the annual meeting of the Society for Pediatric Dermatology. A three-dose vaccination series is recommended beginning at birth, and in 2016, the Centers for Disease Control and Prevention reported that 90.5% of U.S. children aged 19-35 months had completed the series.

While the vaccine series provides protection in healthy individuals more than 95% of the time, a decreased response has been noted in specific pediatric populations, including those with inflammatory and autoimmune diseases. “This is important to note and investigate further because a decreased vaccine response increases the risk for this high-risk population, and the use of boosters is currently debated,” said Ms. Ritter, who is a fourth-year student at the Medical University of South Carolina, Charleston.

To determine the percent of pediatric patients with inflammatory or autoimmune disease who lack evidence of immunity following the hepatitis B vaccine series, Ms. Ritter and colleagues Abigail Truitt and pediatric dermatologist Lara Wine Lee, MD, PhD, of MUSC, retrospectively reviewed the charts of 160 patients between the ages of 6 months and 21 years, who were diagnosed with an autoimmune or autoinflammatory disease, or inflammatory bowel disease (IBD), and had documented evidence of vaccination and serologic testing prior to the start of immunosuppressive therapy.

Of the 160 patients, 100 (63%) had IBD, 34 (21%) had an autoimmune disease, 26 (16%) had an autoinflammatory disease, 89 (56%) were female, and their mean age was 15 years.

The researchers observed variation in the testing ordered between the three patient groups. Specifically, 88.2% of autoimmune patients had hepatitis B surface antigen (HBsAg) testing, compared with 96.15% of patients with an autoinflammatory disease and 67% of patients with IBD, while 76.47% of patients with an autoimmune disease had hepatitis B core antibody (anti-HBc) testing, compared with 88.46% of patients with an autoinflammatory disease and 31% of patients with IBD.

In addition, 82.35% of patients with an autoimmune disease had HBsAg testing, compared with 100% of patients with an autoinflammatory disease and 94% of patients with IBD.

Of the 148 patients who had HBsAg testing ordered and completed prior to starting an immunosuppressive drug, there was no statistically significant difference in the percent of patients showing evidence of an immune response to the hepatitis B vaccine (32.14% among patients with an autoimmune disease, 34.62% among patients with an autoinflammatory disease, and 31.91% among patients with IBD). Combined, 67.57% of tested negative for the hepatitis B surface antibody.

“Our study showed that the majority of these patients did not show serologic evidence of immunity despite being fully vaccinated,” Ms. Ritter said. “There was also variation in the testing ordered and a more standardized approach is needed in this high-risk population.” She acknowledged certain limitations of the study, including its retrospective design and lack of a control group.

“This brings us to our next question of whether this indicates a failure of the vaccine, or the way immunity is tested,” she continued. “The CDC and the European Consensus Group on Hepatitis B Immunity recommend a cutoff of greater than 10 mIU/mL. Those that achieve immunity are protected for up to 20 years due to immune memory, even if their antibody levels later drop. There have been rare cases of immunocompetent individuals having evidence of transient asymptomatic infections when antibody levels drop. The chronic disease has only been documented in infants born to positive mothers. In hemodialysis patients, however, clinically significant infections have been documented when antibody levels drop.”

The CDC only recommends postvaccination testing to infants born to positive mothers, health care workers at high risk, hemodialysis patients, people with HIV and other immunocompromised people, and needle-sharing partners of chronically infected people. This is completed 1-2 months following the third vaccine dose, and those with antibody levels less than 10 mIU/mL should be revaccinated. “As some groups do not respond to the vaccine series, alternative dosing and the intradermal vaccine have been studied and shown to be effective in certain groups,” she said.

When it comes to monitoring immunocompromised individuals and giving booster shots, however, there are conflicting recommendations. The CDC recommends yearly testing and booster shots when levels drop below 10 mIU/mL only in hemodialysis patients, while the European Consensus Group recommends testing every 6-12 months for immunocompromised individuals and boosters when their levels drop below 10 mIU/mL.

“The CDC has not yet determined if other immunocompromised individuals should receive a booster, with more research required, but studies have shown it to be effective,” Ms. Ritter said. In a similar study looking at evidence of immunity in children with connective tissue disease who were on immunosuppressive treatment, 50% had no evidence of protective antibodies, compared with 96% in the control group. “In that study, a booster shot was given, and protective antibody concentrations were found at follow-up,” she said.

The researchers reported having no financial disclosures.

dbrunk@mdedge.com

The long-anticipated American Academy of Pediatrics guidelines for the treatment of well-appearing febrile infants have arrived, and key points include updated guidance for cerebrospinal fluid testing and urine cultures, according to Robert Pantell, MD, and Kenneth Roberts, MD, who presented the guidelines at the virtual Pediatric Hospital Medicine annual conference.

The AAP guideline was published in the August 2021 issue of Pediatrics. The guideline includes 21 key action statements and 40 total recommendations, and describes separate management algorithms for three age groups: infants aged 8-21 days, 22-28 days, and 29-60 days.

Dr. Roberts, of the University of North Carolina at Chapel Hill, and Dr. Pantell, of the University of California, San Francisco, emphasized that all pediatricians should read the full guideline, but they offered an overview of some of the notable points.

Some changes that drove the development of evidence-based guideline included changes in technology, such as the increased use of procalcitonin, the development of large research networks for studies of sufficient size, and a need to reduce the costs of unnecessary care and unnecessary trauma for infants, Dr. Roberts said. Use of data from large networks such as the Pediatric Emergency Care Applied Research Network provided enough evidence to support dividing the aged 8- to 60-day population into three groups.

The guideline applies to well-appearing term infants aged 8-60 days and at least 37 weeks’ gestation, with fever of 38° C (100.4° F) or higher in the past 24 hours in the home or clinical setting. The decision to exclude infants in the first week of life from the guideline was because at this age, infants “are sufficiently different in rates and types of illness, including early-onset bacterial infection,” according to the authors.

Dr. Roberts emphasized that the guidelines apply to “well-appearing infants,” which is not always obvious. “If a clinician is not confident an infant is well appearing, the clinical practice guideline should not be applied,” he said.

The guideline also includes a visual algorithm for each age group.

Dr. Pantell summarized the key action statements for the three age groups, and encouraged pediatricians to review the visual algorithms and footnotes available in the full text of the guideline.

The guideline includes seven key action statements for each of the three age groups. Four of these address evaluations, using urine, blood culture, inflammatory markers (IM), and cerebrospinal fluid (CSF). One action statement focuses on initial treatment, and two on management: hospital admission versus monitoring at home, and treatment cessation.
 

Infants aged 8-21 days

The key action statements for well-appearing infants aged 8-21 days are similar to what clinicians likely would do for ill-appearing infants, the authors noted, based in part on the challenge of assessing an infant this age as “well appearing,” because they don’t yet have the ability to interact with the clinician.

For the 8- to 21-day group, the first two key actions are to obtain a urine specimen and blood culture, Dr. Pantell said. Also, clinicians “should” obtain a CSF for analysis and culture. “We recognize that the ability to get CSF quickly is a challenge,” he added. However, for the 8- to 21-day age group, a new feature is that these infants may be discharged if the CSF is negative. Evaluation in this youngest group states that clinicians “may assess inflammatory markers” including height of fever, absolute neutrophil count, C-reactive protein, and procalcitonin.

Treatment of infants in the 8- to 21-day group “should” include parenteral antimicrobial therapy, according to the guideline, and these infants “should” be actively monitored in the hospital by nurses and staff experienced in neonatal care, Dr. Pantell said. The guideline also includes a key action statement to stop antimicrobials at 24-36 hours if cultures are negative, but to treat identified organisms.
 

Infants aged 22-28 days

In both the 22- to 28-day-old and 29- to 60-day-old groups, the guideline offers opportunities for less testing and treatment, such as avoiding a lumbar puncture, and fewer hospitalizations. The development of a separate guideline for the 22- to 28-day group is something new, said Dr. Pantell. The guideline states that clinicians should obtain urine specimens and blood culture, and should assess IM in this group. Further key action statements note that clinicians “should obtain a CSF if any IM is positive,” but “may” obtain CSF if the infant is hospitalized, if blood and urine cultures have been obtained, and if none of the IMs are abnormal.

As with younger patients, those with a negative CSF can go home, he said. As for treatment, clinicians “should” administer parenteral antimicrobial therapy to infants managed at home even if they have a negative CSF and urinalysis (UA), and no abnormal inflammatory markers Other points for management of infants in this age group at home include verbal teaching and written instructions for caregivers, plans for a re-evaluation at home in 24 hours, and a plan for communication and access to emergency care in case of a change in clinical status, Dr. Pantell explained. The guideline states that infants “should” be hospitalized if CSF is either not obtained or not interpretable, which leaves room for clinical judgment and individual circumstances. Antimicrobials “should” be discontinued in this group once all cultures are negative after 24-36 hours and no other infection requires treatment.
 

Infants aged 29-60 days

For the 29- to 60-day group, there are some differences, the main one is the recommendation of blood cultures in this group, said Dr. Pantell. “We are seeing a lot of UTIs [urinary tract infections], and we would like those treated.” However, clinicians need not obtain a CSF if other IMs are normal, but may do so if any IM is abnormal. Antimicrobial therapy may include ceftriaxone or cephalexin for UTIs, or vancomycin for bacteremia.

Although antimicrobial therapy is an option for UTIs and bacterial meningitis, clinicians “need not” use antimicrobials if CSF is normal, if UA is negative, and if no IMs are abnormal, Dr. Pantell added. Overall, further management of infants in this oldest age group should focus on discharge to home in the absence of abnormal findings, but hospitalization in the presence of abnormal CSF, IMs, or other concerns.

During a question-and-answer session, Dr. Roberts said that, while rectal temperature is preferable, any method is acceptable as a starting point for applying the guideline. Importantly, the guideline still leaves room for clinical judgment. “We hope this will change some thinking as far as whether one model fits all,” he noted. The authors tried to temper the word “should” with the word “may” when possible, so clinicians can say: “I’m going to individualize my decision to the infant in front of me.”

Ultimately, the guideline is meant as a guide, and not an absolute standard of care, the authors said. The language of the key action statements includes the words “should, may, need not” in place of “must, must not.” The guideline recommends factoring family values and preferences into any treatment decisions. “Variations, taking into account individual circumstances, may be appropriate.”

The guideline received no outside funding. The authors had no financial conflicts to disclose.

The long-anticipated American Academy of Pediatrics guidelines for the treatment of well-appearing febrile infants have arrived, and key points include updated guidance for cerebrospinal fluid testing and urine cultures, according to Robert Pantell, MD, and Kenneth Roberts, MD, who presented the guidelines at the virtual Pediatric Hospital Medicine annual conference.

The AAP guideline was published in the August 2021 issue of Pediatrics. The guideline includes 21 key action statements and 40 total recommendations, and describes separate management algorithms for three age groups: infants aged 8-21 days, 22-28 days, and 29-60 days.

Dr. Roberts, of the University of North Carolina at Chapel Hill, and Dr. Pantell, of the University of California, San Francisco, emphasized that all pediatricians should read the full guideline, but they offered an overview of some of the notable points.

Some changes that drove the development of evidence-based guideline included changes in technology, such as the increased use of procalcitonin, the development of large research networks for studies of sufficient size, and a need to reduce the costs of unnecessary care and unnecessary trauma for infants, Dr. Roberts said. Use of data from large networks such as the Pediatric Emergency Care Applied Research Network provided enough evidence to support dividing the aged 8- to 60-day population into three groups.

The guideline applies to well-appearing term infants aged 8-60 days and at least 37 weeks’ gestation, with fever of 38° C (100.4° F) or higher in the past 24 hours in the home or clinical setting. The decision to exclude infants in the first week of life from the guideline was because at this age, infants “are sufficiently different in rates and types of illness, including early-onset bacterial infection,” according to the authors.

Dr. Roberts emphasized that the guidelines apply to “well-appearing infants,” which is not always obvious. “If a clinician is not confident an infant is well appearing, the clinical practice guideline should not be applied,” he said.

The guideline also includes a visual algorithm for each age group.

Dr. Pantell summarized the key action statements for the three age groups, and encouraged pediatricians to review the visual algorithms and footnotes available in the full text of the guideline.

The guideline includes seven key action statements for each of the three age groups. Four of these address evaluations, using urine, blood culture, inflammatory markers (IM), and cerebrospinal fluid (CSF). One action statement focuses on initial treatment, and two on management: hospital admission versus monitoring at home, and treatment cessation.
 

Infants aged 8-21 days

The key action statements for well-appearing infants aged 8-21 days are similar to what clinicians likely would do for ill-appearing infants, the authors noted, based in part on the challenge of assessing an infant this age as “well appearing,” because they don’t yet have the ability to interact with the clinician.

For the 8- to 21-day group, the first two key actions are to obtain a urine specimen and blood culture, Dr. Pantell said. Also, clinicians “should” obtain a CSF for analysis and culture. “We recognize that the ability to get CSF quickly is a challenge,” he added. However, for the 8- to 21-day age group, a new feature is that these infants may be discharged if the CSF is negative. Evaluation in this youngest group states that clinicians “may assess inflammatory markers” including height of fever, absolute neutrophil count, C-reactive protein, and procalcitonin.

Treatment of infants in the 8- to 21-day group “should” include parenteral antimicrobial therapy, according to the guideline, and these infants “should” be actively monitored in the hospital by nurses and staff experienced in neonatal care, Dr. Pantell said. The guideline also includes a key action statement to stop antimicrobials at 24-36 hours if cultures are negative, but to treat identified organisms.
 

Infants aged 22-28 days

In both the 22- to 28-day-old and 29- to 60-day-old groups, the guideline offers opportunities for less testing and treatment, such as avoiding a lumbar puncture, and fewer hospitalizations. The development of a separate guideline for the 22- to 28-day group is something new, said Dr. Pantell. The guideline states that clinicians should obtain urine specimens and blood culture, and should assess IM in this group. Further key action statements note that clinicians “should obtain a CSF if any IM is positive,” but “may” obtain CSF if the infant is hospitalized, if blood and urine cultures have been obtained, and if none of the IMs are abnormal.

As with younger patients, those with a negative CSF can go home, he said. As for treatment, clinicians “should” administer parenteral antimicrobial therapy to infants managed at home even if they have a negative CSF and urinalysis (UA), and no abnormal inflammatory markers Other points for management of infants in this age group at home include verbal teaching and written instructions for caregivers, plans for a re-evaluation at home in 24 hours, and a plan for communication and access to emergency care in case of a change in clinical status, Dr. Pantell explained. The guideline states that infants “should” be hospitalized if CSF is either not obtained or not interpretable, which leaves room for clinical judgment and individual circumstances. Antimicrobials “should” be discontinued in this group once all cultures are negative after 24-36 hours and no other infection requires treatment.
 

Infants aged 29-60 days

For the 29- to 60-day group, there are some differences, the main one is the recommendation of blood cultures in this group, said Dr. Pantell. “We are seeing a lot of UTIs [urinary tract infections], and we would like those treated.” However, clinicians need not obtain a CSF if other IMs are normal, but may do so if any IM is abnormal. Antimicrobial therapy may include ceftriaxone or cephalexin for UTIs, or vancomycin for bacteremia.

Although antimicrobial therapy is an option for UTIs and bacterial meningitis, clinicians “need not” use antimicrobials if CSF is normal, if UA is negative, and if no IMs are abnormal, Dr. Pantell added. Overall, further management of infants in this oldest age group should focus on discharge to home in the absence of abnormal findings, but hospitalization in the presence of abnormal CSF, IMs, or other concerns.

During a question-and-answer session, Dr. Roberts said that, while rectal temperature is preferable, any method is acceptable as a starting point for applying the guideline. Importantly, the guideline still leaves room for clinical judgment. “We hope this will change some thinking as far as whether one model fits all,” he noted. The authors tried to temper the word “should” with the word “may” when possible, so clinicians can say: “I’m going to individualize my decision to the infant in front of me.”

Ultimately, the guideline is meant as a guide, and not an absolute standard of care, the authors said. The language of the key action statements includes the words “should, may, need not” in place of “must, must not.” The guideline recommends factoring family values and preferences into any treatment decisions. “Variations, taking into account individual circumstances, may be appropriate.”

The guideline received no outside funding. The authors had no financial conflicts to disclose.

The long-anticipated American Academy of Pediatrics guidelines for the treatment of well-appearing febrile infants have arrived, and key points include updated guidance for cerebrospinal fluid testing and urine cultures, according to Robert Pantell, MD, and Kenneth Roberts, MD, who presented the guidelines at the virtual Pediatric Hospital Medicine annual conference.

The AAP guideline was published in the August 2021 issue of Pediatrics. The guideline includes 21 key action statements and 40 total recommendations, and describes separate management algorithms for three age groups: infants aged 8-21 days, 22-28 days, and 29-60 days.

Dr. Roberts, of the University of North Carolina at Chapel Hill, and Dr. Pantell, of the University of California, San Francisco, emphasized that all pediatricians should read the full guideline, but they offered an overview of some of the notable points.

Some changes that drove the development of evidence-based guideline included changes in technology, such as the increased use of procalcitonin, the development of large research networks for studies of sufficient size, and a need to reduce the costs of unnecessary care and unnecessary trauma for infants, Dr. Roberts said. Use of data from large networks such as the Pediatric Emergency Care Applied Research Network provided enough evidence to support dividing the aged 8- to 60-day population into three groups.

The guideline applies to well-appearing term infants aged 8-60 days and at least 37 weeks’ gestation, with fever of 38° C (100.4° F) or higher in the past 24 hours in the home or clinical setting. The decision to exclude infants in the first week of life from the guideline was because at this age, infants “are sufficiently different in rates and types of illness, including early-onset bacterial infection,” according to the authors.

Dr. Roberts emphasized that the guidelines apply to “well-appearing infants,” which is not always obvious. “If a clinician is not confident an infant is well appearing, the clinical practice guideline should not be applied,” he said.

The guideline also includes a visual algorithm for each age group.

Dr. Pantell summarized the key action statements for the three age groups, and encouraged pediatricians to review the visual algorithms and footnotes available in the full text of the guideline.

The guideline includes seven key action statements for each of the three age groups. Four of these address evaluations, using urine, blood culture, inflammatory markers (IM), and cerebrospinal fluid (CSF). One action statement focuses on initial treatment, and two on management: hospital admission versus monitoring at home, and treatment cessation.
 

Infants aged 8-21 days

The key action statements for well-appearing infants aged 8-21 days are similar to what clinicians likely would do for ill-appearing infants, the authors noted, based in part on the challenge of assessing an infant this age as “well appearing,” because they don’t yet have the ability to interact with the clinician.

For the 8- to 21-day group, the first two key actions are to obtain a urine specimen and blood culture, Dr. Pantell said. Also, clinicians “should” obtain a CSF for analysis and culture. “We recognize that the ability to get CSF quickly is a challenge,” he added. However, for the 8- to 21-day age group, a new feature is that these infants may be discharged if the CSF is negative. Evaluation in this youngest group states that clinicians “may assess inflammatory markers” including height of fever, absolute neutrophil count, C-reactive protein, and procalcitonin.

Treatment of infants in the 8- to 21-day group “should” include parenteral antimicrobial therapy, according to the guideline, and these infants “should” be actively monitored in the hospital by nurses and staff experienced in neonatal care, Dr. Pantell said. The guideline also includes a key action statement to stop antimicrobials at 24-36 hours if cultures are negative, but to treat identified organisms.
 

Infants aged 22-28 days

In both the 22- to 28-day-old and 29- to 60-day-old groups, the guideline offers opportunities for less testing and treatment, such as avoiding a lumbar puncture, and fewer hospitalizations. The development of a separate guideline for the 22- to 28-day group is something new, said Dr. Pantell. The guideline states that clinicians should obtain urine specimens and blood culture, and should assess IM in this group. Further key action statements note that clinicians “should obtain a CSF if any IM is positive,” but “may” obtain CSF if the infant is hospitalized, if blood and urine cultures have been obtained, and if none of the IMs are abnormal.

As with younger patients, those with a negative CSF can go home, he said. As for treatment, clinicians “should” administer parenteral antimicrobial therapy to infants managed at home even if they have a negative CSF and urinalysis (UA), and no abnormal inflammatory markers Other points for management of infants in this age group at home include verbal teaching and written instructions for caregivers, plans for a re-evaluation at home in 24 hours, and a plan for communication and access to emergency care in case of a change in clinical status, Dr. Pantell explained. The guideline states that infants “should” be hospitalized if CSF is either not obtained or not interpretable, which leaves room for clinical judgment and individual circumstances. Antimicrobials “should” be discontinued in this group once all cultures are negative after 24-36 hours and no other infection requires treatment.
 

Infants aged 29-60 days

For the 29- to 60-day group, there are some differences, the main one is the recommendation of blood cultures in this group, said Dr. Pantell. “We are seeing a lot of UTIs [urinary tract infections], and we would like those treated.” However, clinicians need not obtain a CSF if other IMs are normal, but may do so if any IM is abnormal. Antimicrobial therapy may include ceftriaxone or cephalexin for UTIs, or vancomycin for bacteremia.

Although antimicrobial therapy is an option for UTIs and bacterial meningitis, clinicians “need not” use antimicrobials if CSF is normal, if UA is negative, and if no IMs are abnormal, Dr. Pantell added. Overall, further management of infants in this oldest age group should focus on discharge to home in the absence of abnormal findings, but hospitalization in the presence of abnormal CSF, IMs, or other concerns.

During a question-and-answer session, Dr. Roberts said that, while rectal temperature is preferable, any method is acceptable as a starting point for applying the guideline. Importantly, the guideline still leaves room for clinical judgment. “We hope this will change some thinking as far as whether one model fits all,” he noted. The authors tried to temper the word “should” with the word “may” when possible, so clinicians can say: “I’m going to individualize my decision to the infant in front of me.”

Ultimately, the guideline is meant as a guide, and not an absolute standard of care, the authors said. The language of the key action statements includes the words “should, may, need not” in place of “must, must not.” The guideline recommends factoring family values and preferences into any treatment decisions. “Variations, taking into account individual circumstances, may be appropriate.”

The guideline received no outside funding. The authors had no financial conflicts to disclose.

MS CONFERENCE NEWS

Contents

• Common MS treatment wears off more quickly in Black patients
• A less expensive, more convenient treatment option for MS?
• Investigational drug reduces brain lesions in highly active MS
• Evobrutinib may lower nerve damage biomarker levels
• Disease progression and therapy response vary in MS by ethnicity
• Some MS treatments may heighten COVID risk
• Natalizumab postinfusion reactions

MS CONFERENCE NEWS

Contents

• Common MS treatment wears off more quickly in Black patients
• A less expensive, more convenient treatment option for MS?
• Investigational drug reduces brain lesions in highly active MS
• Evobrutinib may lower nerve damage biomarker levels
• Disease progression and therapy response vary in MS by ethnicity
• Some MS treatments may heighten COVID risk
• Natalizumab postinfusion reactions

MS CONFERENCE NEWS

Contents

• Common MS treatment wears off more quickly in Black patients
• A less expensive, more convenient treatment option for MS?
• Investigational drug reduces brain lesions in highly active MS
• Evobrutinib may lower nerve damage biomarker levels
• Disease progression and therapy response vary in MS by ethnicity
• Some MS treatments may heighten COVID risk
• Natalizumab postinfusion reactions