Skin reactions at insulin pump infusion sites are common among people with type 1 diabetes who use the devices and can lead to delivery failure, new research suggests.
 

Insulin pump use is increasingly common, but many patients experience infusion-site failure that in some cases leads to discontinuation. In a novel investigation, researchers at the University of Washington, Seattle, used biopsies and noninvasive imaging to compare insulin pump sites with control sites in 30 patients. Several differences were found at pump sites in comparison with control sites, including fibrosis, inflammation, eosinophils, and increased vessel density.

“These findings support allergic sensitization as a potentially common reaction at [insulin pump] sites. The leading candidates causing this include insulin preservatives, plastic materials, and adhesive glue used in device manufacturing,” wrote Andrea Kalus, MD, of the university’s dermatology division, and colleagues. The findings were published recently in Diabetes Care.

The inflammatory response, they wrote, “may result in tissue changes responsible for the infusion-site failures seen frequently in clinical practice.”

Such infusion site problems represent an “Achilles heel” of these otherwise highly beneficial devices, lead author Irl Hirsch, MD, professor of medicine in the division of metabolism, endocrinology, and nutrition, said in a statement. “It doesn’t really matter how good the technology is. We still don’t understand what is happening with the infusion sites, much less to [be able to] fix it.”
 

Significant differences between pump and nonpump sites

In the cross-sectional study, Dr. Kalus and colleagues used noninvasive optical coherence tomography (OCT) immediately prior to performing punch biopsies at three sites: the site currently in active use, the “recovery site” used 3-5 days prior to the procedures, and control sites never used for pump infusion. Punch biopsies were also performed at those sites.

The mean age of the patients was 48.3 years, the mean diabetes duration was 30.4 years, and the mean duration of pump use was 15.8 years. Nearly all patients (93.3%) reported itchiness at the site, and 76.7% reported skin redness.

Of the 25 patients for whom OCT imaging was successful, statistical analysis showed significant differences in vascular area density and the optical attenuation coefficient, a surrogate for skin inflammation, between the pump and control sites and between recovery sites and current pump sites. The greater vessel density is likely a result of injury and repair related to catheter insertion, the authors said.

In the biopsy samples, both current and recovery sites showed increased fibrosis, fibrin, inflammation, fat necrosis, vascularity, and eosinophils, compared with the control sites, but no significant differences were found between current and recovery sites.

Eosinophils: ‘The most surprising histologic finding’

Eosinophils were found in 73% of skin biopsy specimens from current sites and in 75% of specimens from recovery sites, compared with none from the control sites (for both, P < .01). In all study participants, eosinophils were found in at least one current and/or recovery infusion site deep in the dermis near the interface with fat. The number of eosinophils ranged from 0 to 31 per high-power field, with a median of 4.

The number of eosinophils didn’t vary by type of insulin or brand of pump, but higher counts were seen in those who had used pumps for less than 10 years, compared with more than 20 years (P = .02).

The prevalence and degree of eosinophils were “the most surprising histologic finding,” the authors wrote, adding that “eosinophils are not typically present as a component of resident inflammatory cells in the skin.”

While eosinophils may be present in normal wound healing, “the absolute number and density of eosinophil in these samples support a delayed-type hypersensitivity response, which is typically observed between 2 and 7 days after exposure to an allergen. ... Eosinophils are often correlated with symptoms of itchiness and likely explain the high percentage of participants who reported itchiness in this study,” Dr. Kalus and colleagues wrote.
 

Correlation found between inflammation and glycemic control

All participants used the Dexcom G6 continuous glucose monitor as part of their usual care. Inflammation scores were positively correlated with insulin dose (P = .009) and were negatively correlated with time in range (P = .01).

No other OCT or biopsy findings differed by duration of pump use, previous use of animal insulin, or type of insulin.

The reason for these findings is unclear, Dr. Hirsch said. “How much was the catheter or the insulin causing the irritation around the sites? How much was it from the preservatives, or is this because of the insulin pump itself? All these questions need to be answered in future studies. ... The real goal of all of this is to minimize skin damage and improve the experience for our patients.”

The study was funded by the Leona M. and Harry B. Helmsley Charitable Trust. Dr. Hirsch reported grants and contracts from Insulet, Medtronic, and Dexcom outside the submitted work; consulting fees from Abbott Diabetes Care, Lifescan, and Hagar outside the submitted work; and honoraria for lectures, presentations, participation on speaker’s bureaus, manuscript writing, or educational events as section editor for UpToDate outside the submitted work. Dr. Kalus has no disclosures.

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

Skin reactions at insulin pump infusion sites are common among people with type 1 diabetes who use the devices and can lead to delivery failure, new research suggests.
 

Insulin pump use is increasingly common, but many patients experience infusion-site failure that in some cases leads to discontinuation. In a novel investigation, researchers at the University of Washington, Seattle, used biopsies and noninvasive imaging to compare insulin pump sites with control sites in 30 patients. Several differences were found at pump sites in comparison with control sites, including fibrosis, inflammation, eosinophils, and increased vessel density.

“These findings support allergic sensitization as a potentially common reaction at [insulin pump] sites. The leading candidates causing this include insulin preservatives, plastic materials, and adhesive glue used in device manufacturing,” wrote Andrea Kalus, MD, of the university’s dermatology division, and colleagues. The findings were published recently in Diabetes Care.

The inflammatory response, they wrote, “may result in tissue changes responsible for the infusion-site failures seen frequently in clinical practice.”

Such infusion site problems represent an “Achilles heel” of these otherwise highly beneficial devices, lead author Irl Hirsch, MD, professor of medicine in the division of metabolism, endocrinology, and nutrition, said in a statement. “It doesn’t really matter how good the technology is. We still don’t understand what is happening with the infusion sites, much less to [be able to] fix it.”
 

Significant differences between pump and nonpump sites

In the cross-sectional study, Dr. Kalus and colleagues used noninvasive optical coherence tomography (OCT) immediately prior to performing punch biopsies at three sites: the site currently in active use, the “recovery site” used 3-5 days prior to the procedures, and control sites never used for pump infusion. Punch biopsies were also performed at those sites.

The mean age of the patients was 48.3 years, the mean diabetes duration was 30.4 years, and the mean duration of pump use was 15.8 years. Nearly all patients (93.3%) reported itchiness at the site, and 76.7% reported skin redness.

Of the 25 patients for whom OCT imaging was successful, statistical analysis showed significant differences in vascular area density and the optical attenuation coefficient, a surrogate for skin inflammation, between the pump and control sites and between recovery sites and current pump sites. The greater vessel density is likely a result of injury and repair related to catheter insertion, the authors said.

In the biopsy samples, both current and recovery sites showed increased fibrosis, fibrin, inflammation, fat necrosis, vascularity, and eosinophils, compared with the control sites, but no significant differences were found between current and recovery sites.

Eosinophils: ‘The most surprising histologic finding’

Eosinophils were found in 73% of skin biopsy specimens from current sites and in 75% of specimens from recovery sites, compared with none from the control sites (for both, P < .01). In all study participants, eosinophils were found in at least one current and/or recovery infusion site deep in the dermis near the interface with fat. The number of eosinophils ranged from 0 to 31 per high-power field, with a median of 4.

The number of eosinophils didn’t vary by type of insulin or brand of pump, but higher counts were seen in those who had used pumps for less than 10 years, compared with more than 20 years (P = .02).

The prevalence and degree of eosinophils were “the most surprising histologic finding,” the authors wrote, adding that “eosinophils are not typically present as a component of resident inflammatory cells in the skin.”

While eosinophils may be present in normal wound healing, “the absolute number and density of eosinophil in these samples support a delayed-type hypersensitivity response, which is typically observed between 2 and 7 days after exposure to an allergen. ... Eosinophils are often correlated with symptoms of itchiness and likely explain the high percentage of participants who reported itchiness in this study,” Dr. Kalus and colleagues wrote.
 

Correlation found between inflammation and glycemic control

All participants used the Dexcom G6 continuous glucose monitor as part of their usual care. Inflammation scores were positively correlated with insulin dose (P = .009) and were negatively correlated with time in range (P = .01).

No other OCT or biopsy findings differed by duration of pump use, previous use of animal insulin, or type of insulin.

The reason for these findings is unclear, Dr. Hirsch said. “How much was the catheter or the insulin causing the irritation around the sites? How much was it from the preservatives, or is this because of the insulin pump itself? All these questions need to be answered in future studies. ... The real goal of all of this is to minimize skin damage and improve the experience for our patients.”

The study was funded by the Leona M. and Harry B. Helmsley Charitable Trust. Dr. Hirsch reported grants and contracts from Insulet, Medtronic, and Dexcom outside the submitted work; consulting fees from Abbott Diabetes Care, Lifescan, and Hagar outside the submitted work; and honoraria for lectures, presentations, participation on speaker’s bureaus, manuscript writing, or educational events as section editor for UpToDate outside the submitted work. Dr. Kalus has no disclosures.

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

Skin reactions at insulin pump infusion sites are common among people with type 1 diabetes who use the devices and can lead to delivery failure, new research suggests.
 

Insulin pump use is increasingly common, but many patients experience infusion-site failure that in some cases leads to discontinuation. In a novel investigation, researchers at the University of Washington, Seattle, used biopsies and noninvasive imaging to compare insulin pump sites with control sites in 30 patients. Several differences were found at pump sites in comparison with control sites, including fibrosis, inflammation, eosinophils, and increased vessel density.

“These findings support allergic sensitization as a potentially common reaction at [insulin pump] sites. The leading candidates causing this include insulin preservatives, plastic materials, and adhesive glue used in device manufacturing,” wrote Andrea Kalus, MD, of the university’s dermatology division, and colleagues. The findings were published recently in Diabetes Care.

The inflammatory response, they wrote, “may result in tissue changes responsible for the infusion-site failures seen frequently in clinical practice.”

Such infusion site problems represent an “Achilles heel” of these otherwise highly beneficial devices, lead author Irl Hirsch, MD, professor of medicine in the division of metabolism, endocrinology, and nutrition, said in a statement. “It doesn’t really matter how good the technology is. We still don’t understand what is happening with the infusion sites, much less to [be able to] fix it.”
 

Significant differences between pump and nonpump sites

In the cross-sectional study, Dr. Kalus and colleagues used noninvasive optical coherence tomography (OCT) immediately prior to performing punch biopsies at three sites: the site currently in active use, the “recovery site” used 3-5 days prior to the procedures, and control sites never used for pump infusion. Punch biopsies were also performed at those sites.

The mean age of the patients was 48.3 years, the mean diabetes duration was 30.4 years, and the mean duration of pump use was 15.8 years. Nearly all patients (93.3%) reported itchiness at the site, and 76.7% reported skin redness.

Of the 25 patients for whom OCT imaging was successful, statistical analysis showed significant differences in vascular area density and the optical attenuation coefficient, a surrogate for skin inflammation, between the pump and control sites and between recovery sites and current pump sites. The greater vessel density is likely a result of injury and repair related to catheter insertion, the authors said.

In the biopsy samples, both current and recovery sites showed increased fibrosis, fibrin, inflammation, fat necrosis, vascularity, and eosinophils, compared with the control sites, but no significant differences were found between current and recovery sites.

Eosinophils: ‘The most surprising histologic finding’

Eosinophils were found in 73% of skin biopsy specimens from current sites and in 75% of specimens from recovery sites, compared with none from the control sites (for both, P < .01). In all study participants, eosinophils were found in at least one current and/or recovery infusion site deep in the dermis near the interface with fat. The number of eosinophils ranged from 0 to 31 per high-power field, with a median of 4.

The number of eosinophils didn’t vary by type of insulin or brand of pump, but higher counts were seen in those who had used pumps for less than 10 years, compared with more than 20 years (P = .02).

The prevalence and degree of eosinophils were “the most surprising histologic finding,” the authors wrote, adding that “eosinophils are not typically present as a component of resident inflammatory cells in the skin.”

While eosinophils may be present in normal wound healing, “the absolute number and density of eosinophil in these samples support a delayed-type hypersensitivity response, which is typically observed between 2 and 7 days after exposure to an allergen. ... Eosinophils are often correlated with symptoms of itchiness and likely explain the high percentage of participants who reported itchiness in this study,” Dr. Kalus and colleagues wrote.
 

Correlation found between inflammation and glycemic control

All participants used the Dexcom G6 continuous glucose monitor as part of their usual care. Inflammation scores were positively correlated with insulin dose (P = .009) and were negatively correlated with time in range (P = .01).

No other OCT or biopsy findings differed by duration of pump use, previous use of animal insulin, or type of insulin.

The reason for these findings is unclear, Dr. Hirsch said. “How much was the catheter or the insulin causing the irritation around the sites? How much was it from the preservatives, or is this because of the insulin pump itself? All these questions need to be answered in future studies. ... The real goal of all of this is to minimize skin damage and improve the experience for our patients.”

The study was funded by the Leona M. and Harry B. Helmsley Charitable Trust. Dr. Hirsch reported grants and contracts from Insulet, Medtronic, and Dexcom outside the submitted work; consulting fees from Abbott Diabetes Care, Lifescan, and Hagar outside the submitted work; and honoraria for lectures, presentations, participation on speaker’s bureaus, manuscript writing, or educational events as section editor for UpToDate outside the submitted work. Dr. Kalus has no disclosures.

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

Two scores, one simple and one comprehensive, may predict inflammatory arthritis (IA) in people who are already at elevated risk for these immune-related conditions, according to new research from England.

If validated in further studies, a new simple score using common biomarkers may help identify individuals who can be managed in primary care as well as higher-risk patients who should be referred to a rheumatologist.

The researchers designed a second comprehensive score adding genetics and ultrasound as a tool to identify patients at highest risk for IA for intervention studies and to guide clinical monitoring and care by specialists.

Richard Mark Kirkner/MDedge News

Though there are blood markers and early symptoms in patients that may signal a higher risk for IA, “we don’t know what to do with those people yet,” said Kevin D. Deane, MD, PhD, associate professor of medicine and chair in rheumatology research at the University of Colorado at Denver, Aurora.

“Understanding how to assess these people and predict who’s going to go on to get full blown IA that we should actually treat is very beneficial to the field,” Dr. Deane said. He was not involved with the research but had reviewed an early draft of the paper.
 

Study seeks to stratify at-risk population

For the study, researchers recruited 455 participants from June 2008 to November 2021, primarily through the UK Primary Care Clinical Research Network. All individuals had new musculoskeletal symptoms, a positive test for anticitrullinated protein antibodies (anti-CCP), and no clinical synovitis.

The researchers selected for anti-CCP positivity because these antibodies are associated with a more aggressive arthritis phenotype. Interventional trials have also found that these anti-CCP–positive individuals are the most responsive to disease-modifying antirheumatic therapy prior to IA development. Patients were followed for at least 48 weeks or until an IA diagnosis.

Using data from this cohort, the team ran statistical analyses guided by potential clinical impact. For the simple score, they aimed to ensure that most people who would go on to develop IA would be identified earlier in clinical practice. For the comprehensive score, they wanted to balance the potential harm of giving preventive treatment to someone who would not develop IA with failing to provide preventive treatment to someone who would develop IA, the authors write.

They developed two scores: a simple score to identify people at lower risk for IA and a comprehensive score to stratify high-risk individuals. The simple score used anti-CCP level, rheumatoid factor value, early morning stiffness, and erythrocyte sedimentation rate to calculate risk.

In addition to these factors, the comprehensive score added smoking history, ultrasound abnormalities, genetic markers for the rheumatoid arthritis shared epitope, as well as patient-reported outcomes from the Health Assessment Questionnaire and the visual analogue scale for global pain.

The study was published in the Annals of Internal Medicine.


 

Simple score rates more than half as low risk

The simple score identified 249 low-risk individuals, defined as having a less than 10% chance of developing IA within 1 year, with a 5% false-negative rate. This score can help determine which individuals do not need to be referred to a specialist even though they have some known risk factors, said Paul Emery, MD, director of the Leeds Biomedical Research Centre and clinical professor at the University of Leeds in England. He is a co–senior author of the research.

“If you had unlimited resources, you’d refer everyone. But in the real world, we would be overloaded in secondary care, and it just wouldn’t work,” he said. “This is a way of making sure the right people are referred into secondary care.”

The comprehensive score identified 119 high-risk individuals, defined as having a 50% chance or greater of developing IA in 5 years, with a false-positive rate of 29%. Of this high-risk group, 40% developed IA within 1 year, and 71% developed IA in 5 years.

Beyond identifying those who should be referred to specialist care, Dr. Emery noted, this score could be used in research studies to find patients for experimental clinical trials aimed at delaying or preventing the onset of IA.

Both Dr. Emery and Dr. Deane agreed that further research is needed to validate these findings in different patient populations as well as to understand how the scores could be integrated into clinical practice.
 

What is the role of anti-CCP tests in primary care?

The study also brings up additional questions about the use of anti-CCP tests in primary care, Dr. Deane said. Though previously considered a “specialty test” 10-15 years ago, “now, we really want primary care to do this test along with the rheumatoid factor test,” he noted.

Because the study only included individuals with anti-CCP antibodies, it did not touch on which patients should be getting tested in the first place. Would all patients coming into primary care with joint pain benefit from these blood-marker tests, Deane asked, or would only certain patients qualify? “I think that’s uncertain, and we need to learn more,” he said.

An additional caveat is that the researchers used abnormal ultrasound findings as a predictor of future IA in the comprehensive model, but many clinicians already use ultrasound to identify arthritis, Dr. Deane said.

“If a rheumatologist sees power Doppler signal or erosions, even if the physical examination of a joint didn’t find swelling or inflammation, then they are likely to say that this person has IA now,” and will start treatment, he said. “Because of that, it could be challenging to use ultrasound as a ‘predictive’ marker in clinical practice,” he added, but additional research could help elucidate when to wait on treatment even with abnormal ultrasound findings.

This study was funded by the UK National Institute for Health and Care Research Leeds Biomedical Research Centre. Dr. Emery disclosed financial relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, Novartis, and Samsung Bioepis. Dr. Deane reports receiving consulting fees from Werfen.

A version of this article appeared on Medscape.com.

Two scores, one simple and one comprehensive, may predict inflammatory arthritis (IA) in people who are already at elevated risk for these immune-related conditions, according to new research from England.

If validated in further studies, a new simple score using common biomarkers may help identify individuals who can be managed in primary care as well as higher-risk patients who should be referred to a rheumatologist.

The researchers designed a second comprehensive score adding genetics and ultrasound as a tool to identify patients at highest risk for IA for intervention studies and to guide clinical monitoring and care by specialists.

Richard Mark Kirkner/MDedge News

Though there are blood markers and early symptoms in patients that may signal a higher risk for IA, “we don’t know what to do with those people yet,” said Kevin D. Deane, MD, PhD, associate professor of medicine and chair in rheumatology research at the University of Colorado at Denver, Aurora.

“Understanding how to assess these people and predict who’s going to go on to get full blown IA that we should actually treat is very beneficial to the field,” Dr. Deane said. He was not involved with the research but had reviewed an early draft of the paper.
 

Study seeks to stratify at-risk population

For the study, researchers recruited 455 participants from June 2008 to November 2021, primarily through the UK Primary Care Clinical Research Network. All individuals had new musculoskeletal symptoms, a positive test for anticitrullinated protein antibodies (anti-CCP), and no clinical synovitis.

The researchers selected for anti-CCP positivity because these antibodies are associated with a more aggressive arthritis phenotype. Interventional trials have also found that these anti-CCP–positive individuals are the most responsive to disease-modifying antirheumatic therapy prior to IA development. Patients were followed for at least 48 weeks or until an IA diagnosis.

Using data from this cohort, the team ran statistical analyses guided by potential clinical impact. For the simple score, they aimed to ensure that most people who would go on to develop IA would be identified earlier in clinical practice. For the comprehensive score, they wanted to balance the potential harm of giving preventive treatment to someone who would not develop IA with failing to provide preventive treatment to someone who would develop IA, the authors write.

They developed two scores: a simple score to identify people at lower risk for IA and a comprehensive score to stratify high-risk individuals. The simple score used anti-CCP level, rheumatoid factor value, early morning stiffness, and erythrocyte sedimentation rate to calculate risk.

In addition to these factors, the comprehensive score added smoking history, ultrasound abnormalities, genetic markers for the rheumatoid arthritis shared epitope, as well as patient-reported outcomes from the Health Assessment Questionnaire and the visual analogue scale for global pain.

The study was published in the Annals of Internal Medicine.


 

Simple score rates more than half as low risk

The simple score identified 249 low-risk individuals, defined as having a less than 10% chance of developing IA within 1 year, with a 5% false-negative rate. This score can help determine which individuals do not need to be referred to a specialist even though they have some known risk factors, said Paul Emery, MD, director of the Leeds Biomedical Research Centre and clinical professor at the University of Leeds in England. He is a co–senior author of the research.

“If you had unlimited resources, you’d refer everyone. But in the real world, we would be overloaded in secondary care, and it just wouldn’t work,” he said. “This is a way of making sure the right people are referred into secondary care.”

The comprehensive score identified 119 high-risk individuals, defined as having a 50% chance or greater of developing IA in 5 years, with a false-positive rate of 29%. Of this high-risk group, 40% developed IA within 1 year, and 71% developed IA in 5 years.

Beyond identifying those who should be referred to specialist care, Dr. Emery noted, this score could be used in research studies to find patients for experimental clinical trials aimed at delaying or preventing the onset of IA.

Both Dr. Emery and Dr. Deane agreed that further research is needed to validate these findings in different patient populations as well as to understand how the scores could be integrated into clinical practice.
 

What is the role of anti-CCP tests in primary care?

The study also brings up additional questions about the use of anti-CCP tests in primary care, Dr. Deane said. Though previously considered a “specialty test” 10-15 years ago, “now, we really want primary care to do this test along with the rheumatoid factor test,” he noted.

Because the study only included individuals with anti-CCP antibodies, it did not touch on which patients should be getting tested in the first place. Would all patients coming into primary care with joint pain benefit from these blood-marker tests, Deane asked, or would only certain patients qualify? “I think that’s uncertain, and we need to learn more,” he said.

An additional caveat is that the researchers used abnormal ultrasound findings as a predictor of future IA in the comprehensive model, but many clinicians already use ultrasound to identify arthritis, Dr. Deane said.

“If a rheumatologist sees power Doppler signal or erosions, even if the physical examination of a joint didn’t find swelling or inflammation, then they are likely to say that this person has IA now,” and will start treatment, he said. “Because of that, it could be challenging to use ultrasound as a ‘predictive’ marker in clinical practice,” he added, but additional research could help elucidate when to wait on treatment even with abnormal ultrasound findings.

This study was funded by the UK National Institute for Health and Care Research Leeds Biomedical Research Centre. Dr. Emery disclosed financial relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, Novartis, and Samsung Bioepis. Dr. Deane reports receiving consulting fees from Werfen.

A version of this article appeared on Medscape.com.

Two scores, one simple and one comprehensive, may predict inflammatory arthritis (IA) in people who are already at elevated risk for these immune-related conditions, according to new research from England.

If validated in further studies, a new simple score using common biomarkers may help identify individuals who can be managed in primary care as well as higher-risk patients who should be referred to a rheumatologist.

The researchers designed a second comprehensive score adding genetics and ultrasound as a tool to identify patients at highest risk for IA for intervention studies and to guide clinical monitoring and care by specialists.

Richard Mark Kirkner/MDedge News

Though there are blood markers and early symptoms in patients that may signal a higher risk for IA, “we don’t know what to do with those people yet,” said Kevin D. Deane, MD, PhD, associate professor of medicine and chair in rheumatology research at the University of Colorado at Denver, Aurora.

“Understanding how to assess these people and predict who’s going to go on to get full blown IA that we should actually treat is very beneficial to the field,” Dr. Deane said. He was not involved with the research but had reviewed an early draft of the paper.
 

Study seeks to stratify at-risk population

For the study, researchers recruited 455 participants from June 2008 to November 2021, primarily through the UK Primary Care Clinical Research Network. All individuals had new musculoskeletal symptoms, a positive test for anticitrullinated protein antibodies (anti-CCP), and no clinical synovitis.

The researchers selected for anti-CCP positivity because these antibodies are associated with a more aggressive arthritis phenotype. Interventional trials have also found that these anti-CCP–positive individuals are the most responsive to disease-modifying antirheumatic therapy prior to IA development. Patients were followed for at least 48 weeks or until an IA diagnosis.

Using data from this cohort, the team ran statistical analyses guided by potential clinical impact. For the simple score, they aimed to ensure that most people who would go on to develop IA would be identified earlier in clinical practice. For the comprehensive score, they wanted to balance the potential harm of giving preventive treatment to someone who would not develop IA with failing to provide preventive treatment to someone who would develop IA, the authors write.

They developed two scores: a simple score to identify people at lower risk for IA and a comprehensive score to stratify high-risk individuals. The simple score used anti-CCP level, rheumatoid factor value, early morning stiffness, and erythrocyte sedimentation rate to calculate risk.

In addition to these factors, the comprehensive score added smoking history, ultrasound abnormalities, genetic markers for the rheumatoid arthritis shared epitope, as well as patient-reported outcomes from the Health Assessment Questionnaire and the visual analogue scale for global pain.

The study was published in the Annals of Internal Medicine.


 

Simple score rates more than half as low risk

The simple score identified 249 low-risk individuals, defined as having a less than 10% chance of developing IA within 1 year, with a 5% false-negative rate. This score can help determine which individuals do not need to be referred to a specialist even though they have some known risk factors, said Paul Emery, MD, director of the Leeds Biomedical Research Centre and clinical professor at the University of Leeds in England. He is a co–senior author of the research.

“If you had unlimited resources, you’d refer everyone. But in the real world, we would be overloaded in secondary care, and it just wouldn’t work,” he said. “This is a way of making sure the right people are referred into secondary care.”

The comprehensive score identified 119 high-risk individuals, defined as having a 50% chance or greater of developing IA in 5 years, with a false-positive rate of 29%. Of this high-risk group, 40% developed IA within 1 year, and 71% developed IA in 5 years.

Beyond identifying those who should be referred to specialist care, Dr. Emery noted, this score could be used in research studies to find patients for experimental clinical trials aimed at delaying or preventing the onset of IA.

Both Dr. Emery and Dr. Deane agreed that further research is needed to validate these findings in different patient populations as well as to understand how the scores could be integrated into clinical practice.
 

What is the role of anti-CCP tests in primary care?

The study also brings up additional questions about the use of anti-CCP tests in primary care, Dr. Deane said. Though previously considered a “specialty test” 10-15 years ago, “now, we really want primary care to do this test along with the rheumatoid factor test,” he noted.

Because the study only included individuals with anti-CCP antibodies, it did not touch on which patients should be getting tested in the first place. Would all patients coming into primary care with joint pain benefit from these blood-marker tests, Deane asked, or would only certain patients qualify? “I think that’s uncertain, and we need to learn more,” he said.

An additional caveat is that the researchers used abnormal ultrasound findings as a predictor of future IA in the comprehensive model, but many clinicians already use ultrasound to identify arthritis, Dr. Deane said.

“If a rheumatologist sees power Doppler signal or erosions, even if the physical examination of a joint didn’t find swelling or inflammation, then they are likely to say that this person has IA now,” and will start treatment, he said. “Because of that, it could be challenging to use ultrasound as a ‘predictive’ marker in clinical practice,” he added, but additional research could help elucidate when to wait on treatment even with abnormal ultrasound findings.

This study was funded by the UK National Institute for Health and Care Research Leeds Biomedical Research Centre. Dr. Emery disclosed financial relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, Novartis, and Samsung Bioepis. Dr. Deane reports receiving consulting fees from Werfen.

A version of this article appeared on Medscape.com.

The treatment landscape of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) has been transformed over the past decade with the advent of targeted therapies, including Bruton tyrosine kinase (BTK) inhibitors. Covalent BTK inhibitors, which are available in both the frontline and relapsed/refractory settings, include ibrutinib, acalabrutinib, and zanubrutinib.^1-3

BTK inhibitors have also demonstrated activity in higher-risk subgroups, including patients harboring TP53 aberrations. Clinical trials have shown encouraging outcomes of BTK inhibitors in these patients, and real-world studies have demonstrated similar findings.^4-6 Recently, a real-world Italian registry study similarly showed favorable outcomes in 747 patients with CLL carrying 17p- or TP53 or both mutations treated with first-line ibrutinib. in what appears to be the largest real-world analysis of this patient population (Rigolin et al). At 24 months, the median overall survival was not reached; the estimated treatment persistence and survival rates were 63.4% (95% CI 60.0%-67.0%) and 82.6% (95% CI 79.9%-85.4%), respectively. The median time to treatment discontinuation was 37.4 months (95% CI 34.8-42.2 months). Disease progression or death was the reason for discontinuation in 45.8% of patients. Although ibrutinib is not generally the favored BTK inhibitor given an improved safety profile with next-generation options, these data provide real-world estimates for outcomes with BTK inhibitors in this large dataset of high-risk patients.

Although outcomes have improved for patients with CLL or SLL, it is common for resistance to targeted therapy to eventually occur. Noncovalent BTK inhibitors, such as pirtobrutinib, offer a promising approach for this population. The BRUIN trial was a phase 1/2 trial of pirtobrutinib in patients with relapsed/refractory CLL or SLL (Mato et al). A total of 317 patients were treated, including 247 who had previously received a BTK inhibitor. Patients had been treated with a median of three prior lines of therapy and over 40% had been treated with a BCL-2 inhibitor. The overall response rate was 73.3% (95% CI 67.3%-78.7%) and increased to 82.2% (95% CI 76.8%-86.7%) when partial response with lymphocytosis was included. At a 19.4-month median follow-up, the median progression-free survival was 19.6 (95% CI 16.9-22.1) months. The drug was also well-tolerated, with 2.8% of patients discontinuing therapy owing to treatment-related adverse events. Adverse events that can be seen with BTK inhibition, including hypertension, atrial fibrillation or flutter, and bleeding, were rare. This trial demonstrates that CLL/SLL cells can maintain dependency on the B-cell receptor pathway following treatment with a covalent inhibitor and that ongoing BTK inhibition using a novel mechanism is a feasible strategy. The optimal sequencing of pirtobrutinib with other available therapies, including BCL-2 inhibitors, remains unknown.

BTK inhibitors are also active in mantle cell lymphoma (MCL). They are approved for relapsed/refractory disease and are being studied in earlier lines of therapy. Whereas early progression of disease (POD) has been shown to be an important prognostic marker in MCL, the impact of early relapse on outcome specifically after BTK inhibitor initiation is less clear.⁷ A recent multicente retrospective observational study aimed to determine the impact on time-to-POD between rituximab-containing front-line therapy and second-line BTK inhibitor and overall outcomes (Villa et al). This study included 360 adult patients with relapsed or refractory MCL treated with second-line BTK inhibitor. Not surprisingly, the authors found that patients with POD within 24 months of first-line therapy had significantly shorter median progression-free survival (0.45 year vs 2.3 years; P < .001) and overall survival (0.9 year vs 5.5 years P < .001) compared with patients with relapse beyond 24 months. Furthermore, they found that Ki-67 ≥ 30% and Mantle Cell Lymphoma International Prognostic Index (MIPI) were also associated with progression‐free survival and overall survival from the start of a second-line BTK inhibitor, though to a lesser extent than time-to-POD. These variables were subsequently used to determine a second-line BTK MIPI, which can help inform which patients are most likely to benefit from a BTK inhibitor compared with other available options, such as chimeric antigen receptor (CAR) T-cell therapy or a clinical trial strategy.

BTK inhibitors are an important drug class for the treatment of lymphoid cancers and have changed the treatment paradigms in CLL/SLL and MCL. Additional studies evaluating combination strategies, sequencing approaches, time-limited options, and predictors of response are likely to further refine optimization of use in these diseases.

Additional References

1.         Barr PM, Owen C, Robak T, et al. Up to 8-year follow-up from RESONATE-2: first-line ibrutinib treatment for patients with chronic lymphocytic leukemia. Blood Adv. 2022;6:3440-3450. doi:10.1182/bloodadvances.2021006434

2.         Sharman JP, Egyed M, Jurczak W, et al. Efficacy and safety in a 4-year follow-up of the ELEVATE-TN study comparing acalabrutinib with or without obinutuzumab versus obinutuzumab plus chlorambucil in treatment-naive chronic lymphocytic leukemia. Leukemia. 2022;36:1171-1175. doi:10.1038/s41375-021-01485-x

3.         Tam CS, Brown JR, Kahl BS, et al. Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial. Lancet Oncol. 2022;23:1031-1043. doi:10.1016/S1470-2045(22)00293-5

4.         Ahn IE, Tian X, Wiestner A. Ibrutinib for chronic lymphocytic leukemia with TP53 alterations. N Engl J Med. 2020;383:498-500. doi:10.1056/NEJMc2005943

5.         Allan JN, Shanafelt T, Wiestner A, et al. Long-term efficacy of first-line ibrutinib treatment for chronic lymphocytic leukaemia in patients with TP53 aberrations: a pooled analysis from four clinical trials. Br J Haematol. 2022;196:947-953. doi:10.1111/bjh.17984

6.         Mato AR, Tang B, Azmi S, et al. A clinical practice comparison of patients with chronic lymphocytic leukemia with and without deletion 17p receiving first-line treatment with ibrutinib. Haematologica. 2022;107:2630-2640. doi:10.3324/haematol.2021.280376

7.         Bond DA, Switchenko JM, Villa D, et al. Early relapse identifies MCL patients with inferior survival after intensive or less intensive frontline therapy. Blood Adv. 2021;5:5179-5189. doi:10.1182/bloodadvances.2021004765

The treatment landscape of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) has been transformed over the past decade with the advent of targeted therapies, including Bruton tyrosine kinase (BTK) inhibitors. Covalent BTK inhibitors, which are available in both the frontline and relapsed/refractory settings, include ibrutinib, acalabrutinib, and zanubrutinib.^1-3

BTK inhibitors have also demonstrated activity in higher-risk subgroups, including patients harboring TP53 aberrations. Clinical trials have shown encouraging outcomes of BTK inhibitors in these patients, and real-world studies have demonstrated similar findings.^4-6 Recently, a real-world Italian registry study similarly showed favorable outcomes in 747 patients with CLL carrying 17p- or TP53 or both mutations treated with first-line ibrutinib. in what appears to be the largest real-world analysis of this patient population (Rigolin et al). At 24 months, the median overall survival was not reached; the estimated treatment persistence and survival rates were 63.4% (95% CI 60.0%-67.0%) and 82.6% (95% CI 79.9%-85.4%), respectively. The median time to treatment discontinuation was 37.4 months (95% CI 34.8-42.2 months). Disease progression or death was the reason for discontinuation in 45.8% of patients. Although ibrutinib is not generally the favored BTK inhibitor given an improved safety profile with next-generation options, these data provide real-world estimates for outcomes with BTK inhibitors in this large dataset of high-risk patients.

Although outcomes have improved for patients with CLL or SLL, it is common for resistance to targeted therapy to eventually occur. Noncovalent BTK inhibitors, such as pirtobrutinib, offer a promising approach for this population. The BRUIN trial was a phase 1/2 trial of pirtobrutinib in patients with relapsed/refractory CLL or SLL (Mato et al). A total of 317 patients were treated, including 247 who had previously received a BTK inhibitor. Patients had been treated with a median of three prior lines of therapy and over 40% had been treated with a BCL-2 inhibitor. The overall response rate was 73.3% (95% CI 67.3%-78.7%) and increased to 82.2% (95% CI 76.8%-86.7%) when partial response with lymphocytosis was included. At a 19.4-month median follow-up, the median progression-free survival was 19.6 (95% CI 16.9-22.1) months. The drug was also well-tolerated, with 2.8% of patients discontinuing therapy owing to treatment-related adverse events. Adverse events that can be seen with BTK inhibition, including hypertension, atrial fibrillation or flutter, and bleeding, were rare. This trial demonstrates that CLL/SLL cells can maintain dependency on the B-cell receptor pathway following treatment with a covalent inhibitor and that ongoing BTK inhibition using a novel mechanism is a feasible strategy. The optimal sequencing of pirtobrutinib with other available therapies, including BCL-2 inhibitors, remains unknown.

BTK inhibitors are also active in mantle cell lymphoma (MCL). They are approved for relapsed/refractory disease and are being studied in earlier lines of therapy. Whereas early progression of disease (POD) has been shown to be an important prognostic marker in MCL, the impact of early relapse on outcome specifically after BTK inhibitor initiation is less clear.⁷ A recent multicente retrospective observational study aimed to determine the impact on time-to-POD between rituximab-containing front-line therapy and second-line BTK inhibitor and overall outcomes (Villa et al). This study included 360 adult patients with relapsed or refractory MCL treated with second-line BTK inhibitor. Not surprisingly, the authors found that patients with POD within 24 months of first-line therapy had significantly shorter median progression-free survival (0.45 year vs 2.3 years; P < .001) and overall survival (0.9 year vs 5.5 years P < .001) compared with patients with relapse beyond 24 months. Furthermore, they found that Ki-67 ≥ 30% and Mantle Cell Lymphoma International Prognostic Index (MIPI) were also associated with progression‐free survival and overall survival from the start of a second-line BTK inhibitor, though to a lesser extent than time-to-POD. These variables were subsequently used to determine a second-line BTK MIPI, which can help inform which patients are most likely to benefit from a BTK inhibitor compared with other available options, such as chimeric antigen receptor (CAR) T-cell therapy or a clinical trial strategy.

BTK inhibitors are an important drug class for the treatment of lymphoid cancers and have changed the treatment paradigms in CLL/SLL and MCL. Additional studies evaluating combination strategies, sequencing approaches, time-limited options, and predictors of response are likely to further refine optimization of use in these diseases.

Additional References

1.         Barr PM, Owen C, Robak T, et al. Up to 8-year follow-up from RESONATE-2: first-line ibrutinib treatment for patients with chronic lymphocytic leukemia. Blood Adv. 2022;6:3440-3450. doi:10.1182/bloodadvances.2021006434

2.         Sharman JP, Egyed M, Jurczak W, et al. Efficacy and safety in a 4-year follow-up of the ELEVATE-TN study comparing acalabrutinib with or without obinutuzumab versus obinutuzumab plus chlorambucil in treatment-naive chronic lymphocytic leukemia. Leukemia. 2022;36:1171-1175. doi:10.1038/s41375-021-01485-x

3.         Tam CS, Brown JR, Kahl BS, et al. Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial. Lancet Oncol. 2022;23:1031-1043. doi:10.1016/S1470-2045(22)00293-5

4.         Ahn IE, Tian X, Wiestner A. Ibrutinib for chronic lymphocytic leukemia with TP53 alterations. N Engl J Med. 2020;383:498-500. doi:10.1056/NEJMc2005943

5.         Allan JN, Shanafelt T, Wiestner A, et al. Long-term efficacy of first-line ibrutinib treatment for chronic lymphocytic leukaemia in patients with TP53 aberrations: a pooled analysis from four clinical trials. Br J Haematol. 2022;196:947-953. doi:10.1111/bjh.17984

6.         Mato AR, Tang B, Azmi S, et al. A clinical practice comparison of patients with chronic lymphocytic leukemia with and without deletion 17p receiving first-line treatment with ibrutinib. Haematologica. 2022;107:2630-2640. doi:10.3324/haematol.2021.280376

7.         Bond DA, Switchenko JM, Villa D, et al. Early relapse identifies MCL patients with inferior survival after intensive or less intensive frontline therapy. Blood Adv. 2021;5:5179-5189. doi:10.1182/bloodadvances.2021004765

The treatment landscape of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) has been transformed over the past decade with the advent of targeted therapies, including Bruton tyrosine kinase (BTK) inhibitors. Covalent BTK inhibitors, which are available in both the frontline and relapsed/refractory settings, include ibrutinib, acalabrutinib, and zanubrutinib.^1-3

BTK inhibitors have also demonstrated activity in higher-risk subgroups, including patients harboring TP53 aberrations. Clinical trials have shown encouraging outcomes of BTK inhibitors in these patients, and real-world studies have demonstrated similar findings.^4-6 Recently, a real-world Italian registry study similarly showed favorable outcomes in 747 patients with CLL carrying 17p- or TP53 or both mutations treated with first-line ibrutinib. in what appears to be the largest real-world analysis of this patient population (Rigolin et al). At 24 months, the median overall survival was not reached; the estimated treatment persistence and survival rates were 63.4% (95% CI 60.0%-67.0%) and 82.6% (95% CI 79.9%-85.4%), respectively. The median time to treatment discontinuation was 37.4 months (95% CI 34.8-42.2 months). Disease progression or death was the reason for discontinuation in 45.8% of patients. Although ibrutinib is not generally the favored BTK inhibitor given an improved safety profile with next-generation options, these data provide real-world estimates for outcomes with BTK inhibitors in this large dataset of high-risk patients.

Although outcomes have improved for patients with CLL or SLL, it is common for resistance to targeted therapy to eventually occur. Noncovalent BTK inhibitors, such as pirtobrutinib, offer a promising approach for this population. The BRUIN trial was a phase 1/2 trial of pirtobrutinib in patients with relapsed/refractory CLL or SLL (Mato et al). A total of 317 patients were treated, including 247 who had previously received a BTK inhibitor. Patients had been treated with a median of three prior lines of therapy and over 40% had been treated with a BCL-2 inhibitor. The overall response rate was 73.3% (95% CI 67.3%-78.7%) and increased to 82.2% (95% CI 76.8%-86.7%) when partial response with lymphocytosis was included. At a 19.4-month median follow-up, the median progression-free survival was 19.6 (95% CI 16.9-22.1) months. The drug was also well-tolerated, with 2.8% of patients discontinuing therapy owing to treatment-related adverse events. Adverse events that can be seen with BTK inhibition, including hypertension, atrial fibrillation or flutter, and bleeding, were rare. This trial demonstrates that CLL/SLL cells can maintain dependency on the B-cell receptor pathway following treatment with a covalent inhibitor and that ongoing BTK inhibition using a novel mechanism is a feasible strategy. The optimal sequencing of pirtobrutinib with other available therapies, including BCL-2 inhibitors, remains unknown.

BTK inhibitors are also active in mantle cell lymphoma (MCL). They are approved for relapsed/refractory disease and are being studied in earlier lines of therapy. Whereas early progression of disease (POD) has been shown to be an important prognostic marker in MCL, the impact of early relapse on outcome specifically after BTK inhibitor initiation is less clear.⁷ A recent multicente retrospective observational study aimed to determine the impact on time-to-POD between rituximab-containing front-line therapy and second-line BTK inhibitor and overall outcomes (Villa et al). This study included 360 adult patients with relapsed or refractory MCL treated with second-line BTK inhibitor. Not surprisingly, the authors found that patients with POD within 24 months of first-line therapy had significantly shorter median progression-free survival (0.45 year vs 2.3 years; P < .001) and overall survival (0.9 year vs 5.5 years P < .001) compared with patients with relapse beyond 24 months. Furthermore, they found that Ki-67 ≥ 30% and Mantle Cell Lymphoma International Prognostic Index (MIPI) were also associated with progression‐free survival and overall survival from the start of a second-line BTK inhibitor, though to a lesser extent than time-to-POD. These variables were subsequently used to determine a second-line BTK MIPI, which can help inform which patients are most likely to benefit from a BTK inhibitor compared with other available options, such as chimeric antigen receptor (CAR) T-cell therapy or a clinical trial strategy.

BTK inhibitors are an important drug class for the treatment of lymphoid cancers and have changed the treatment paradigms in CLL/SLL and MCL. Additional studies evaluating combination strategies, sequencing approaches, time-limited options, and predictors of response are likely to further refine optimization of use in these diseases.

Additional References

1.         Barr PM, Owen C, Robak T, et al. Up to 8-year follow-up from RESONATE-2: first-line ibrutinib treatment for patients with chronic lymphocytic leukemia. Blood Adv. 2022;6:3440-3450. doi:10.1182/bloodadvances.2021006434

2.         Sharman JP, Egyed M, Jurczak W, et al. Efficacy and safety in a 4-year follow-up of the ELEVATE-TN study comparing acalabrutinib with or without obinutuzumab versus obinutuzumab plus chlorambucil in treatment-naive chronic lymphocytic leukemia. Leukemia. 2022;36:1171-1175. doi:10.1038/s41375-021-01485-x

3.         Tam CS, Brown JR, Kahl BS, et al. Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial. Lancet Oncol. 2022;23:1031-1043. doi:10.1016/S1470-2045(22)00293-5

4.         Ahn IE, Tian X, Wiestner A. Ibrutinib for chronic lymphocytic leukemia with TP53 alterations. N Engl J Med. 2020;383:498-500. doi:10.1056/NEJMc2005943

5.         Allan JN, Shanafelt T, Wiestner A, et al. Long-term efficacy of first-line ibrutinib treatment for chronic lymphocytic leukaemia in patients with TP53 aberrations: a pooled analysis from four clinical trials. Br J Haematol. 2022;196:947-953. doi:10.1111/bjh.17984

6.         Mato AR, Tang B, Azmi S, et al. A clinical practice comparison of patients with chronic lymphocytic leukemia with and without deletion 17p receiving first-line treatment with ibrutinib. Haematologica. 2022;107:2630-2640. doi:10.3324/haematol.2021.280376

7.         Bond DA, Switchenko JM, Villa D, et al. Early relapse identifies MCL patients with inferior survival after intensive or less intensive frontline therapy. Blood Adv. 2021;5:5179-5189. doi:10.1182/bloodadvances.2021004765

For the sixth year in a row, Johns Hopkins Hospital in Baltimore has been named the top hospital for rheumatology by U.S. News & World Report.

The No. 2 slot went to the Hospital for Special Surgery (HSS), New York. The Cleveland Clinic took third place. The magazine announced the 2023-2024 rankings on Aug. 1.

Most specialty rankings are determined through data on patient outcomes and hospital performance, but rheumatology rankings, as well as those for ophthalmology and psychiatry, were determined through expert opinion. For these three specialties, most care is delivered in outpatient settings, according to U.S. News & World Report, and “the number of outpatients who die in these specialties is so low that risk-adjusted mortality rates ... are not significantly tied to the quality of care.” Thus, the rankings are based on specialist responses to U.S. News surveys from the past 3 years.

The rankings for 11 rheumatology hospitals are as follows:

• 1. Johns Hopkins Hospital
• 2. HSS, New York–Presbyterian University Hospital of Columbia and Cornell
• 3. Cleveland Clinic
• 4. Mayo Clinic, Rochester, Minn.
• 5. Brigham and Women’s Hospital, Boston
• 6. Massachusetts General Hospital, Boston
• 7. UCSF Health-UCSF Medical Center, San Francisco
• 8. NYU Langone Hospitals, New York
• 9. UCLA Medical Center, Los Angeles
• 10. University of Alabama at Birmingham Hospital
• 11. University of Michigan Health–Ann Arbor

Nearly all hospitals on this list also made the Best Hospitals Honor Roll for 2023-2024. These Honor Roll hospitals excelled in care across multiple specialties. The University of Alabama at Birmingham Hospital was not on the honor roll but was ranked among the nation’s top 50 hospitals in cardiology, diabetes & endocrinology, gastroenterology, geriatrics, and obstetrics & gynecology.

A version of this article appeared on Medscape.com.

For the sixth year in a row, Johns Hopkins Hospital in Baltimore has been named the top hospital for rheumatology by U.S. News & World Report.

The No. 2 slot went to the Hospital for Special Surgery (HSS), New York. The Cleveland Clinic took third place. The magazine announced the 2023-2024 rankings on Aug. 1.

Most specialty rankings are determined through data on patient outcomes and hospital performance, but rheumatology rankings, as well as those for ophthalmology and psychiatry, were determined through expert opinion. For these three specialties, most care is delivered in outpatient settings, according to U.S. News & World Report, and “the number of outpatients who die in these specialties is so low that risk-adjusted mortality rates ... are not significantly tied to the quality of care.” Thus, the rankings are based on specialist responses to U.S. News surveys from the past 3 years.

The rankings for 11 rheumatology hospitals are as follows:

• 1. Johns Hopkins Hospital
• 2. HSS, New York–Presbyterian University Hospital of Columbia and Cornell
• 3. Cleveland Clinic
• 4. Mayo Clinic, Rochester, Minn.
• 5. Brigham and Women’s Hospital, Boston
• 6. Massachusetts General Hospital, Boston
• 7. UCSF Health-UCSF Medical Center, San Francisco
• 8. NYU Langone Hospitals, New York
• 9. UCLA Medical Center, Los Angeles
• 10. University of Alabama at Birmingham Hospital
• 11. University of Michigan Health–Ann Arbor

Nearly all hospitals on this list also made the Best Hospitals Honor Roll for 2023-2024. These Honor Roll hospitals excelled in care across multiple specialties. The University of Alabama at Birmingham Hospital was not on the honor roll but was ranked among the nation’s top 50 hospitals in cardiology, diabetes & endocrinology, gastroenterology, geriatrics, and obstetrics & gynecology.

A version of this article appeared on Medscape.com.

For the sixth year in a row, Johns Hopkins Hospital in Baltimore has been named the top hospital for rheumatology by U.S. News & World Report.

The No. 2 slot went to the Hospital for Special Surgery (HSS), New York. The Cleveland Clinic took third place. The magazine announced the 2023-2024 rankings on Aug. 1.

Most specialty rankings are determined through data on patient outcomes and hospital performance, but rheumatology rankings, as well as those for ophthalmology and psychiatry, were determined through expert opinion. For these three specialties, most care is delivered in outpatient settings, according to U.S. News & World Report, and “the number of outpatients who die in these specialties is so low that risk-adjusted mortality rates ... are not significantly tied to the quality of care.” Thus, the rankings are based on specialist responses to U.S. News surveys from the past 3 years.

The rankings for 11 rheumatology hospitals are as follows:

• 1. Johns Hopkins Hospital
• 2. HSS, New York–Presbyterian University Hospital of Columbia and Cornell
• 3. Cleveland Clinic
• 4. Mayo Clinic, Rochester, Minn.
• 5. Brigham and Women’s Hospital, Boston
• 6. Massachusetts General Hospital, Boston
• 7. UCSF Health-UCSF Medical Center, San Francisco
• 8. NYU Langone Hospitals, New York
• 9. UCLA Medical Center, Los Angeles
• 10. University of Alabama at Birmingham Hospital
• 11. University of Michigan Health–Ann Arbor

Nearly all hospitals on this list also made the Best Hospitals Honor Roll for 2023-2024. These Honor Roll hospitals excelled in care across multiple specialties. The University of Alabama at Birmingham Hospital was not on the honor roll but was ranked among the nation’s top 50 hospitals in cardiology, diabetes & endocrinology, gastroenterology, geriatrics, and obstetrics & gynecology.

A version of this article appeared on Medscape.com.

In patients aged 2-11 years, roflumilast cream was well tolerated and improved signs and symptoms of psoriasis over 4 weeks, according to results from a pair of phase two studies.

“Limited topical treatments are approved for children younger than 12 years old with psoriasis,” researchers led by Adelaide A. Hebert, MD, wrote in their abstract. The results were presented during a poster session at the annual meeting of the Society for Pediatric Dermatology.

Roflumilast cream 0.3% (Zoryve) is a once-daily, topical nonsteroidal treatment from Arcutis Biotherapeutics. A phosphodiesterase-4 inhibitor, it was approved by the Food and Drug Administration in 2022 for mild, moderate and severe psoriasis in individuals aged 12 and older, including intertriginous psoriasis.

For the analysis, Dr. Hebert, chief of pediatric dermatology at the University of Texas, Houston, and colleagues conducted two 4-week, phase 2, open-label safety studies of roflumilast cream 0.3%.

One, study 216, enrolled 10 children aged 2-5, and all but one were Black. The other, study 215, enrolled 20 children aged 6-11, and half were Black and nearly half were White. At baseline, patients had 2% or greater body surface area (BSA) involvement and an Investigator Global Assessment (IGA) score of at least mild.

Caregivers applied roflumilast cream to all affected areas once daily for 28 days. The researchers collected pharmacokinetic samples at week 2 and week 4. The primary endpoints were pharmacokinetic, safety, and tolerability.

Efficacy was evaluated as exploratory endpoints: An IGA of clear or almost clear plus a 2-grade or more improvement from baseline, a 50% or greater improvement and a 75% or greater improvement on the Psoriasis Area and Severity Index (PASI-50 and PASI-75), a 4-point or greater reduction in the Worst Itch–Numeric Rating Scale (WI-NRS) in patients with a baseline score of 4 or greater, a mean change from baseline in BSA, and improvement in the Children’s Dermatology Life Quality Index (CDLQI).

At baseline, the mean BSA was similar for patients enrolled in studies 216 and 215 (9.6% and 8.8%, respectively), and 80% of all patients had baseline IGA of moderate. By week 2, the mean roflumilast and N-oxide predose plasma concentrations among patients in the younger group were 2.15 and 22.4 ng/mL, compared with 3.15 and 28.9 ng/mL among those in the older group. At week 4, the mean roflumilast and N-oxide predose concentrations were 2.04 and 15.8 ng/mL in the younger group (study 216), compared with 1.68 and 15.7 ng/mL in the older group (study 215).

As for efficacy, 90% and 40% of patients in studies 216 and 215 achieved IGA success at week 4, respectively, while 90% and 50% achieved PASI-75, 90% and 40% achieved WI-NRS success, and the mean BSA reductions at week 4 were 79.1% and 44.4%. Meanwhile, one younger patient in study 216 reported a treatment-emergent adverse event (TEAE) of headache, which was considered mild, while four older patients in study 215 reported 8 TEAEs, which were considered mild and ranged from back pain to nasal congestion.

“The rapid onset of action was surprising but exceedingly rewarding for the subjects enrolled in the study,” Dr. Hebert told this news organization after the meeting. “The PASI scores and itch scores were markedly improved at the end of the 4-week clinical trial. Patient and parents alike were pleased to use a steroid-free option with once-daily application and rapid onset of action to help control plaque psoriasis.”

In the poster abstract, she and her coauthors concluded that “under maximal use conditions in children aged 2-11 years, roflumilast cream 0.3% was well tolerated and improved signs and symptoms of psoriasis with measured improvements in IGA score, PASI score, BSA involvement, CDLQI, and WI-NRS. Overall, pharmacokinetics, safety, tolerability, and efficacy in patients aged 2-11 years were consistent with prior results in adults and adolescents.”

The study was funded by Arcutis Biotherapeutics. Dr. Hebert reported that she is an investigator for Arcutis. About half the coauthors are employees of Arcutis, and the other half disclosed grants, research funding and/or honoraria from the company. Research grants from the company for this study were paid to the McGovern Medical School at the University of Texas.

In patients aged 2-11 years, roflumilast cream was well tolerated and improved signs and symptoms of psoriasis over 4 weeks, according to results from a pair of phase two studies.

“Limited topical treatments are approved for children younger than 12 years old with psoriasis,” researchers led by Adelaide A. Hebert, MD, wrote in their abstract. The results were presented during a poster session at the annual meeting of the Society for Pediatric Dermatology.

Roflumilast cream 0.3% (Zoryve) is a once-daily, topical nonsteroidal treatment from Arcutis Biotherapeutics. A phosphodiesterase-4 inhibitor, it was approved by the Food and Drug Administration in 2022 for mild, moderate and severe psoriasis in individuals aged 12 and older, including intertriginous psoriasis.

For the analysis, Dr. Hebert, chief of pediatric dermatology at the University of Texas, Houston, and colleagues conducted two 4-week, phase 2, open-label safety studies of roflumilast cream 0.3%.

One, study 216, enrolled 10 children aged 2-5, and all but one were Black. The other, study 215, enrolled 20 children aged 6-11, and half were Black and nearly half were White. At baseline, patients had 2% or greater body surface area (BSA) involvement and an Investigator Global Assessment (IGA) score of at least mild.

Caregivers applied roflumilast cream to all affected areas once daily for 28 days. The researchers collected pharmacokinetic samples at week 2 and week 4. The primary endpoints were pharmacokinetic, safety, and tolerability.

Efficacy was evaluated as exploratory endpoints: An IGA of clear or almost clear plus a 2-grade or more improvement from baseline, a 50% or greater improvement and a 75% or greater improvement on the Psoriasis Area and Severity Index (PASI-50 and PASI-75), a 4-point or greater reduction in the Worst Itch–Numeric Rating Scale (WI-NRS) in patients with a baseline score of 4 or greater, a mean change from baseline in BSA, and improvement in the Children’s Dermatology Life Quality Index (CDLQI).

At baseline, the mean BSA was similar for patients enrolled in studies 216 and 215 (9.6% and 8.8%, respectively), and 80% of all patients had baseline IGA of moderate. By week 2, the mean roflumilast and N-oxide predose plasma concentrations among patients in the younger group were 2.15 and 22.4 ng/mL, compared with 3.15 and 28.9 ng/mL among those in the older group. At week 4, the mean roflumilast and N-oxide predose concentrations were 2.04 and 15.8 ng/mL in the younger group (study 216), compared with 1.68 and 15.7 ng/mL in the older group (study 215).

As for efficacy, 90% and 40% of patients in studies 216 and 215 achieved IGA success at week 4, respectively, while 90% and 50% achieved PASI-75, 90% and 40% achieved WI-NRS success, and the mean BSA reductions at week 4 were 79.1% and 44.4%. Meanwhile, one younger patient in study 216 reported a treatment-emergent adverse event (TEAE) of headache, which was considered mild, while four older patients in study 215 reported 8 TEAEs, which were considered mild and ranged from back pain to nasal congestion.

“The rapid onset of action was surprising but exceedingly rewarding for the subjects enrolled in the study,” Dr. Hebert told this news organization after the meeting. “The PASI scores and itch scores were markedly improved at the end of the 4-week clinical trial. Patient and parents alike were pleased to use a steroid-free option with once-daily application and rapid onset of action to help control plaque psoriasis.”

In the poster abstract, she and her coauthors concluded that “under maximal use conditions in children aged 2-11 years, roflumilast cream 0.3% was well tolerated and improved signs and symptoms of psoriasis with measured improvements in IGA score, PASI score, BSA involvement, CDLQI, and WI-NRS. Overall, pharmacokinetics, safety, tolerability, and efficacy in patients aged 2-11 years were consistent with prior results in adults and adolescents.”

The study was funded by Arcutis Biotherapeutics. Dr. Hebert reported that she is an investigator for Arcutis. About half the coauthors are employees of Arcutis, and the other half disclosed grants, research funding and/or honoraria from the company. Research grants from the company for this study were paid to the McGovern Medical School at the University of Texas.

In patients aged 2-11 years, roflumilast cream was well tolerated and improved signs and symptoms of psoriasis over 4 weeks, according to results from a pair of phase two studies.

“Limited topical treatments are approved for children younger than 12 years old with psoriasis,” researchers led by Adelaide A. Hebert, MD, wrote in their abstract. The results were presented during a poster session at the annual meeting of the Society for Pediatric Dermatology.

Roflumilast cream 0.3% (Zoryve) is a once-daily, topical nonsteroidal treatment from Arcutis Biotherapeutics. A phosphodiesterase-4 inhibitor, it was approved by the Food and Drug Administration in 2022 for mild, moderate and severe psoriasis in individuals aged 12 and older, including intertriginous psoriasis.

For the analysis, Dr. Hebert, chief of pediatric dermatology at the University of Texas, Houston, and colleagues conducted two 4-week, phase 2, open-label safety studies of roflumilast cream 0.3%.

One, study 216, enrolled 10 children aged 2-5, and all but one were Black. The other, study 215, enrolled 20 children aged 6-11, and half were Black and nearly half were White. At baseline, patients had 2% or greater body surface area (BSA) involvement and an Investigator Global Assessment (IGA) score of at least mild.

Caregivers applied roflumilast cream to all affected areas once daily for 28 days. The researchers collected pharmacokinetic samples at week 2 and week 4. The primary endpoints were pharmacokinetic, safety, and tolerability.

Efficacy was evaluated as exploratory endpoints: An IGA of clear or almost clear plus a 2-grade or more improvement from baseline, a 50% or greater improvement and a 75% or greater improvement on the Psoriasis Area and Severity Index (PASI-50 and PASI-75), a 4-point or greater reduction in the Worst Itch–Numeric Rating Scale (WI-NRS) in patients with a baseline score of 4 or greater, a mean change from baseline in BSA, and improvement in the Children’s Dermatology Life Quality Index (CDLQI).

At baseline, the mean BSA was similar for patients enrolled in studies 216 and 215 (9.6% and 8.8%, respectively), and 80% of all patients had baseline IGA of moderate. By week 2, the mean roflumilast and N-oxide predose plasma concentrations among patients in the younger group were 2.15 and 22.4 ng/mL, compared with 3.15 and 28.9 ng/mL among those in the older group. At week 4, the mean roflumilast and N-oxide predose concentrations were 2.04 and 15.8 ng/mL in the younger group (study 216), compared with 1.68 and 15.7 ng/mL in the older group (study 215).

As for efficacy, 90% and 40% of patients in studies 216 and 215 achieved IGA success at week 4, respectively, while 90% and 50% achieved PASI-75, 90% and 40% achieved WI-NRS success, and the mean BSA reductions at week 4 were 79.1% and 44.4%. Meanwhile, one younger patient in study 216 reported a treatment-emergent adverse event (TEAE) of headache, which was considered mild, while four older patients in study 215 reported 8 TEAEs, which were considered mild and ranged from back pain to nasal congestion.

“The rapid onset of action was surprising but exceedingly rewarding for the subjects enrolled in the study,” Dr. Hebert told this news organization after the meeting. “The PASI scores and itch scores were markedly improved at the end of the 4-week clinical trial. Patient and parents alike were pleased to use a steroid-free option with once-daily application and rapid onset of action to help control plaque psoriasis.”

In the poster abstract, she and her coauthors concluded that “under maximal use conditions in children aged 2-11 years, roflumilast cream 0.3% was well tolerated and improved signs and symptoms of psoriasis with measured improvements in IGA score, PASI score, BSA involvement, CDLQI, and WI-NRS. Overall, pharmacokinetics, safety, tolerability, and efficacy in patients aged 2-11 years were consistent with prior results in adults and adolescents.”

The study was funded by Arcutis Biotherapeutics. Dr. Hebert reported that she is an investigator for Arcutis. About half the coauthors are employees of Arcutis, and the other half disclosed grants, research funding and/or honoraria from the company. Research grants from the company for this study were paid to the McGovern Medical School at the University of Texas.

Under a new Medicare pilot program that will begin in 2024, the federal government will pay clinicians to coordinate at-home dementia support services, including respite care for family members.

A Department of Health & Human Services initiative, part of the aim of the Guiding an Improved Dementia Experience (GUIDE) program is to help Medicare beneficiaries with dementia stay in the community for as long as possible. It is estimated that there are 6.7 million Americans living with Alzheimer’s disease or some other form of dementia, said HHS.

The program is voluntary and will be open to Medicare-enrolled clinicians and other providers who can assemble an interdisciplinary care team and meet the program’s participation criteria.

“Our new GUIDE Model has the potential to improve the quality of life for people with dementia and alleviate the significant strain on our families,” said HHS Secretary Xavier Becerra, in a statement.

“Not only is dementia care management a proven way to improve the quality of care and quality of life for those living with Alzheimer’s and other dementia, but now we know that it would also save the federal government billions of dollars,” Robert Egge, Alzheimer’s Association chief public policy officer and Alzheimer’s Impact Movement (AIM) executive director, said in a statement.

Mr. Egge cited a recent analysis commissioned by AIM that found that dementia care management would save the federal government nearly $21 billion over 10 years.

“People living with dementia and their caregivers too often struggle to manage their health care and connect with key supports that can allow them to remain in their homes and communities,” said Centers for Medicare & Medicaid Services Administrator Chiquita Brooks-LaSure, in the HHS statement.

“Fragmented care contributes to the mental and physical health strain of caring for someone with dementia, as well as the substantial financial burden,” she said, adding that Black, Hispanic, Asian American, Native Hawaiian, and Pacific Islander populations have been especially disadvantaged.

The GUIDE Model will provide new resources and greater access to specialty care to those communities, said Ms. Brooks-LaSure.

Care teams that seek to participate in the GUIDE model must have a care navigator who has received required training in dementia, assessment, and care planning.

The teams also must have a clinician with dementia proficiency as recognized by experience caring for adults with cognitive impairment; experience caring for patients aged 65 years old or older; or specialty designation in neurology, psychiatry, geriatrics, geriatric psychiatry, behavioral neurology, or geriatric neurology.

Medicare beneficiaries will be eligible if they are not residing in a nursing home; are not enrolled in hospice; and have a confirmed dementia diagnosis.

Beneficiaries who receive care from GUIDE participants will be placed in one of five “tiers,” based on a combination of disease stage and caregiver status. Beneficiary needs, and care intensity and payment, increase by tier.

GUIDE teams will receive a monthly, per-beneficiary amount for providing care management and coordination and caregiver education and support services. They can also bill for respite services – up to an annual cap – for Medicare beneficiaries who have an unpaid caregiver.

Clinicians seeking to participate in GUIDE can apply beginning in the fall. The program will run for 8 years beginning July 1, 2024.

Alzheimer’s Association President and CEO Joanne Pike, DrPH, said in a statement that the organization had “advocated for this approach for years, believing it [to be] the key to addressing systemic challenges faced by those with dementia, their families and those who provide them with care and support.”

The John A. Hartford Foundation noted that it also had long pushed for a comprehensive dementia care program. “Comprehensive dementia care supports both the medical and nonmedical needs of patients and their family caregivers,” said Foundation President Terry Fulmer, PhD, RN, FAAN, in a statement.

“Notably and necessarily, the model will help improve equity in access to care for underserved communities by addressing unpaid caregiver needs, including respite services and screening for health-related social needs,” added Dr. Fulmer.

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

Under a new Medicare pilot program that will begin in 2024, the federal government will pay clinicians to coordinate at-home dementia support services, including respite care for family members.

A Department of Health & Human Services initiative, part of the aim of the Guiding an Improved Dementia Experience (GUIDE) program is to help Medicare beneficiaries with dementia stay in the community for as long as possible. It is estimated that there are 6.7 million Americans living with Alzheimer’s disease or some other form of dementia, said HHS.

The program is voluntary and will be open to Medicare-enrolled clinicians and other providers who can assemble an interdisciplinary care team and meet the program’s participation criteria.

“Our new GUIDE Model has the potential to improve the quality of life for people with dementia and alleviate the significant strain on our families,” said HHS Secretary Xavier Becerra, in a statement.

“Not only is dementia care management a proven way to improve the quality of care and quality of life for those living with Alzheimer’s and other dementia, but now we know that it would also save the federal government billions of dollars,” Robert Egge, Alzheimer’s Association chief public policy officer and Alzheimer’s Impact Movement (AIM) executive director, said in a statement.

Mr. Egge cited a recent analysis commissioned by AIM that found that dementia care management would save the federal government nearly $21 billion over 10 years.

“People living with dementia and their caregivers too often struggle to manage their health care and connect with key supports that can allow them to remain in their homes and communities,” said Centers for Medicare & Medicaid Services Administrator Chiquita Brooks-LaSure, in the HHS statement.

“Fragmented care contributes to the mental and physical health strain of caring for someone with dementia, as well as the substantial financial burden,” she said, adding that Black, Hispanic, Asian American, Native Hawaiian, and Pacific Islander populations have been especially disadvantaged.

The GUIDE Model will provide new resources and greater access to specialty care to those communities, said Ms. Brooks-LaSure.

Care teams that seek to participate in the GUIDE model must have a care navigator who has received required training in dementia, assessment, and care planning.

The teams also must have a clinician with dementia proficiency as recognized by experience caring for adults with cognitive impairment; experience caring for patients aged 65 years old or older; or specialty designation in neurology, psychiatry, geriatrics, geriatric psychiatry, behavioral neurology, or geriatric neurology.

Medicare beneficiaries will be eligible if they are not residing in a nursing home; are not enrolled in hospice; and have a confirmed dementia diagnosis.

Beneficiaries who receive care from GUIDE participants will be placed in one of five “tiers,” based on a combination of disease stage and caregiver status. Beneficiary needs, and care intensity and payment, increase by tier.

GUIDE teams will receive a monthly, per-beneficiary amount for providing care management and coordination and caregiver education and support services. They can also bill for respite services – up to an annual cap – for Medicare beneficiaries who have an unpaid caregiver.

Clinicians seeking to participate in GUIDE can apply beginning in the fall. The program will run for 8 years beginning July 1, 2024.

Alzheimer’s Association President and CEO Joanne Pike, DrPH, said in a statement that the organization had “advocated for this approach for years, believing it [to be] the key to addressing systemic challenges faced by those with dementia, their families and those who provide them with care and support.”

The John A. Hartford Foundation noted that it also had long pushed for a comprehensive dementia care program. “Comprehensive dementia care supports both the medical and nonmedical needs of patients and their family caregivers,” said Foundation President Terry Fulmer, PhD, RN, FAAN, in a statement.

“Notably and necessarily, the model will help improve equity in access to care for underserved communities by addressing unpaid caregiver needs, including respite services and screening for health-related social needs,” added Dr. Fulmer.

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

Under a new Medicare pilot program that will begin in 2024, the federal government will pay clinicians to coordinate at-home dementia support services, including respite care for family members.

A Department of Health & Human Services initiative, part of the aim of the Guiding an Improved Dementia Experience (GUIDE) program is to help Medicare beneficiaries with dementia stay in the community for as long as possible. It is estimated that there are 6.7 million Americans living with Alzheimer’s disease or some other form of dementia, said HHS.

The program is voluntary and will be open to Medicare-enrolled clinicians and other providers who can assemble an interdisciplinary care team and meet the program’s participation criteria.

“Our new GUIDE Model has the potential to improve the quality of life for people with dementia and alleviate the significant strain on our families,” said HHS Secretary Xavier Becerra, in a statement.

“Not only is dementia care management a proven way to improve the quality of care and quality of life for those living with Alzheimer’s and other dementia, but now we know that it would also save the federal government billions of dollars,” Robert Egge, Alzheimer’s Association chief public policy officer and Alzheimer’s Impact Movement (AIM) executive director, said in a statement.

Mr. Egge cited a recent analysis commissioned by AIM that found that dementia care management would save the federal government nearly $21 billion over 10 years.

“People living with dementia and their caregivers too often struggle to manage their health care and connect with key supports that can allow them to remain in their homes and communities,” said Centers for Medicare & Medicaid Services Administrator Chiquita Brooks-LaSure, in the HHS statement.

“Fragmented care contributes to the mental and physical health strain of caring for someone with dementia, as well as the substantial financial burden,” she said, adding that Black, Hispanic, Asian American, Native Hawaiian, and Pacific Islander populations have been especially disadvantaged.

The GUIDE Model will provide new resources and greater access to specialty care to those communities, said Ms. Brooks-LaSure.

Care teams that seek to participate in the GUIDE model must have a care navigator who has received required training in dementia, assessment, and care planning.

The teams also must have a clinician with dementia proficiency as recognized by experience caring for adults with cognitive impairment; experience caring for patients aged 65 years old or older; or specialty designation in neurology, psychiatry, geriatrics, geriatric psychiatry, behavioral neurology, or geriatric neurology.

Medicare beneficiaries will be eligible if they are not residing in a nursing home; are not enrolled in hospice; and have a confirmed dementia diagnosis.

Beneficiaries who receive care from GUIDE participants will be placed in one of five “tiers,” based on a combination of disease stage and caregiver status. Beneficiary needs, and care intensity and payment, increase by tier.

GUIDE teams will receive a monthly, per-beneficiary amount for providing care management and coordination and caregiver education and support services. They can also bill for respite services – up to an annual cap – for Medicare beneficiaries who have an unpaid caregiver.

Clinicians seeking to participate in GUIDE can apply beginning in the fall. The program will run for 8 years beginning July 1, 2024.

Alzheimer’s Association President and CEO Joanne Pike, DrPH, said in a statement that the organization had “advocated for this approach for years, believing it [to be] the key to addressing systemic challenges faced by those with dementia, their families and those who provide them with care and support.”

The John A. Hartford Foundation noted that it also had long pushed for a comprehensive dementia care program. “Comprehensive dementia care supports both the medical and nonmedical needs of patients and their family caregivers,” said Foundation President Terry Fulmer, PhD, RN, FAAN, in a statement.

“Notably and necessarily, the model will help improve equity in access to care for underserved communities by addressing unpaid caregiver needs, including respite services and screening for health-related social needs,” added Dr. Fulmer.

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

Nonalcohol substance use disorder (SUD) was 2.5 times more common in people who had gastric bypass surgery, compared with a control group who received usual obesity care, a new prospective study has found.

The findings suggest that the risk for nonalcohol SUD should be carefully explained to patients getting a gastric bypass and that the risk should be considered in care before and after the surgery, said the study authors and editorialists.

Though alcohol use disorder is a well-known side effect for some bariatric procedures, little is known about the link between the procedures and other substance abuse, wrote the study authors, led by Per-Arne Svensson, PhD, with the department of molecular and clinical medicine, Institute of Medicine, at the University of Gothenburg (Sweden).

The study was published online in Obesity.

The researchers analyzed data from the SOS study. It was originally designed to compare bariatric surgery with usual obesity care, with overall mortality as the primary outcome. The protocol also called for reporting negative effects of included treatments.

The study was conducted throughout Sweden at 25 public surgical departments and 480 primary health centers. Participants were between ages 37 and 60 years and had a body mass index of at least 34 kg/m² for men and 38 for women.

After people with previous nonalcoholic SUD were excluded, the study population included 1,990 patients who had undergone bariatric surgery between September 1987 and January 2001, as well as 2,030 matched controls who received usual obesity care. The three types of bariatric surgery were gastric bypass (264 patients), vertical banded gastroplasty (1,353), and gastric banding (373), as chosen by the surgeons.

The follow-up was nearly 24 years.
 

Link found only with gastric bypass

The researchers identified participants who had nonalcoholic SUDs using the ICD from the Swedish National Patient Register covering hospital treatment (hospital stays or hospital-based outpatient care) but not primary care.

Only gastric bypass was associated with an increased incidence of nonalcoholic SUD (adjusted hazard ratio, 2.54; 95% confidence interval, 1.14-5.65), compared with controls during the follow-up period.

Among those who had gastric bypass surgery, three developed opioid-related disorders; three had sedative-, hypnotic-, or anxiolytic-related disorders; and three had other psychoactive substance–related disorders, the study authors wrote.

The researchers found no statistical difference in the incidence of nonalcoholic SUD when the groups who had undergone different surgical procedures were compared with each other.

“It is important to acknowledge that the number of affected patients was relatively low, in the single digits,” Jihad Kudsi, MD, a bariatric surgeon and chairman of surgery at Duly Health and Care, Oak Brook, Ill., said in a press release.

The findings “highlight the critical role of bariatric behavioral health clinicians in the comprehensive evaluation and care of patients both before and after weight loss surgery,” added Dr. Kudsi, who was not associated with the research.
 

Bariatric surgery candidates should be warned, monitored

The data indicate that patients who are candidates for bariatric surgery should be “carefully warned” about risks for nonalcoholic SUD and be monitored after the procedure, wrote James E. Mitchell, MD, a psychiatrist with the department of psychiatry and behavioral science, University of North Dakota, Fargo, and Devika Umashanker, MD, with Obesity Medicine, Hartford (Conn.) Health Care, in an accompanying editorial.

They acknowledged, however, that monitoring can be difficult given the typical low rate of follow-up of these patients.

Though the reasons for the rise in nonalcoholic SUD are not clear, Dr. Mitchell and Dr. Umashanker said biologic and psychosocial issues may be contributors to the increase.

The persistence of medical comorbidities and a lack of noted improvement in quality of life or physical mobility after the surgery has been addressed in a paper on suicide risk after bariatric surgery, the study authors also noted.

Dr. Svensson said in an interview that a mechanism for alcohol abuse after gastric bypass surgery is more evident, as measured by “increased blood alcohol levels after the surgery for a given amount of alcohol.” However, for other addictive substances, the mechanism is not obvious and needs further study.

The editorialists reminded clinicians that measuring phosphatidylethanol can be very useful in identifying and quantifying recent alcohol intake, suggesting that all clinicians, not just those in bariatric surgery clinics, should be aware of the connection between the procedures and subsequent alcohol abuse and monitor those patients carefully.

Both the study authors and the editorialists pointed out that the SOS cohort was recruited when vertical banded gastroplasty and banding were commonly used, and both methods are now rarely, if ever, used. Gastric sleeve procedures are now the most common approach, and those patients were not included in the study.

“However, gastric bypass surgery patients were included, albeit in a minority of the sample,” Dr. Mitchell and Dr. Umashanker wrote. In addition, the sample size of patients with SUD was too small to determine the drugs that were being abused.

Dr. Svensson said in an interview the main limitation is that SUD events were identified in the Swedish National Patient Register, which misses nonhospitalized patients.

“This register is very complete for hospitals, but it does not include SUD events detected in the primary health care setting,” he said. “Hence, the absolute number of events is probably a clear underestimation. However, it is unlikely that this limitation would affect the study groups (control group vs. groups with different surgical procedures) in different ways and hence the conclusions from this study are most likely valid.”

The study authors and the editorialists reported no relevant financial relationships.

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

Nonalcohol substance use disorder (SUD) was 2.5 times more common in people who had gastric bypass surgery, compared with a control group who received usual obesity care, a new prospective study has found.

The findings suggest that the risk for nonalcohol SUD should be carefully explained to patients getting a gastric bypass and that the risk should be considered in care before and after the surgery, said the study authors and editorialists.

Though alcohol use disorder is a well-known side effect for some bariatric procedures, little is known about the link between the procedures and other substance abuse, wrote the study authors, led by Per-Arne Svensson, PhD, with the department of molecular and clinical medicine, Institute of Medicine, at the University of Gothenburg (Sweden).

The study was published online in Obesity.

The researchers analyzed data from the SOS study. It was originally designed to compare bariatric surgery with usual obesity care, with overall mortality as the primary outcome. The protocol also called for reporting negative effects of included treatments.

The study was conducted throughout Sweden at 25 public surgical departments and 480 primary health centers. Participants were between ages 37 and 60 years and had a body mass index of at least 34 kg/m² for men and 38 for women.

After people with previous nonalcoholic SUD were excluded, the study population included 1,990 patients who had undergone bariatric surgery between September 1987 and January 2001, as well as 2,030 matched controls who received usual obesity care. The three types of bariatric surgery were gastric bypass (264 patients), vertical banded gastroplasty (1,353), and gastric banding (373), as chosen by the surgeons.

The follow-up was nearly 24 years.
 

Link found only with gastric bypass

The researchers identified participants who had nonalcoholic SUDs using the ICD from the Swedish National Patient Register covering hospital treatment (hospital stays or hospital-based outpatient care) but not primary care.

Only gastric bypass was associated with an increased incidence of nonalcoholic SUD (adjusted hazard ratio, 2.54; 95% confidence interval, 1.14-5.65), compared with controls during the follow-up period.

Among those who had gastric bypass surgery, three developed opioid-related disorders; three had sedative-, hypnotic-, or anxiolytic-related disorders; and three had other psychoactive substance–related disorders, the study authors wrote.

The researchers found no statistical difference in the incidence of nonalcoholic SUD when the groups who had undergone different surgical procedures were compared with each other.

“It is important to acknowledge that the number of affected patients was relatively low, in the single digits,” Jihad Kudsi, MD, a bariatric surgeon and chairman of surgery at Duly Health and Care, Oak Brook, Ill., said in a press release.

The findings “highlight the critical role of bariatric behavioral health clinicians in the comprehensive evaluation and care of patients both before and after weight loss surgery,” added Dr. Kudsi, who was not associated with the research.
 

Bariatric surgery candidates should be warned, monitored

The data indicate that patients who are candidates for bariatric surgery should be “carefully warned” about risks for nonalcoholic SUD and be monitored after the procedure, wrote James E. Mitchell, MD, a psychiatrist with the department of psychiatry and behavioral science, University of North Dakota, Fargo, and Devika Umashanker, MD, with Obesity Medicine, Hartford (Conn.) Health Care, in an accompanying editorial.

They acknowledged, however, that monitoring can be difficult given the typical low rate of follow-up of these patients.

Though the reasons for the rise in nonalcoholic SUD are not clear, Dr. Mitchell and Dr. Umashanker said biologic and psychosocial issues may be contributors to the increase.

The persistence of medical comorbidities and a lack of noted improvement in quality of life or physical mobility after the surgery has been addressed in a paper on suicide risk after bariatric surgery, the study authors also noted.

Dr. Svensson said in an interview that a mechanism for alcohol abuse after gastric bypass surgery is more evident, as measured by “increased blood alcohol levels after the surgery for a given amount of alcohol.” However, for other addictive substances, the mechanism is not obvious and needs further study.

The editorialists reminded clinicians that measuring phosphatidylethanol can be very useful in identifying and quantifying recent alcohol intake, suggesting that all clinicians, not just those in bariatric surgery clinics, should be aware of the connection between the procedures and subsequent alcohol abuse and monitor those patients carefully.

Both the study authors and the editorialists pointed out that the SOS cohort was recruited when vertical banded gastroplasty and banding were commonly used, and both methods are now rarely, if ever, used. Gastric sleeve procedures are now the most common approach, and those patients were not included in the study.

“However, gastric bypass surgery patients were included, albeit in a minority of the sample,” Dr. Mitchell and Dr. Umashanker wrote. In addition, the sample size of patients with SUD was too small to determine the drugs that were being abused.

Dr. Svensson said in an interview the main limitation is that SUD events were identified in the Swedish National Patient Register, which misses nonhospitalized patients.

“This register is very complete for hospitals, but it does not include SUD events detected in the primary health care setting,” he said. “Hence, the absolute number of events is probably a clear underestimation. However, it is unlikely that this limitation would affect the study groups (control group vs. groups with different surgical procedures) in different ways and hence the conclusions from this study are most likely valid.”

The study authors and the editorialists reported no relevant financial relationships.

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

Nonalcohol substance use disorder (SUD) was 2.5 times more common in people who had gastric bypass surgery, compared with a control group who received usual obesity care, a new prospective study has found.

The findings suggest that the risk for nonalcohol SUD should be carefully explained to patients getting a gastric bypass and that the risk should be considered in care before and after the surgery, said the study authors and editorialists.

Though alcohol use disorder is a well-known side effect for some bariatric procedures, little is known about the link between the procedures and other substance abuse, wrote the study authors, led by Per-Arne Svensson, PhD, with the department of molecular and clinical medicine, Institute of Medicine, at the University of Gothenburg (Sweden).

The study was published online in Obesity.

The researchers analyzed data from the SOS study. It was originally designed to compare bariatric surgery with usual obesity care, with overall mortality as the primary outcome. The protocol also called for reporting negative effects of included treatments.

The study was conducted throughout Sweden at 25 public surgical departments and 480 primary health centers. Participants were between ages 37 and 60 years and had a body mass index of at least 34 kg/m² for men and 38 for women.

After people with previous nonalcoholic SUD were excluded, the study population included 1,990 patients who had undergone bariatric surgery between September 1987 and January 2001, as well as 2,030 matched controls who received usual obesity care. The three types of bariatric surgery were gastric bypass (264 patients), vertical banded gastroplasty (1,353), and gastric banding (373), as chosen by the surgeons.

The follow-up was nearly 24 years.
 

Link found only with gastric bypass

The researchers identified participants who had nonalcoholic SUDs using the ICD from the Swedish National Patient Register covering hospital treatment (hospital stays or hospital-based outpatient care) but not primary care.

Only gastric bypass was associated with an increased incidence of nonalcoholic SUD (adjusted hazard ratio, 2.54; 95% confidence interval, 1.14-5.65), compared with controls during the follow-up period.

Among those who had gastric bypass surgery, three developed opioid-related disorders; three had sedative-, hypnotic-, or anxiolytic-related disorders; and three had other psychoactive substance–related disorders, the study authors wrote.

The researchers found no statistical difference in the incidence of nonalcoholic SUD when the groups who had undergone different surgical procedures were compared with each other.

“It is important to acknowledge that the number of affected patients was relatively low, in the single digits,” Jihad Kudsi, MD, a bariatric surgeon and chairman of surgery at Duly Health and Care, Oak Brook, Ill., said in a press release.

The findings “highlight the critical role of bariatric behavioral health clinicians in the comprehensive evaluation and care of patients both before and after weight loss surgery,” added Dr. Kudsi, who was not associated with the research.
 

Bariatric surgery candidates should be warned, monitored

The data indicate that patients who are candidates for bariatric surgery should be “carefully warned” about risks for nonalcoholic SUD and be monitored after the procedure, wrote James E. Mitchell, MD, a psychiatrist with the department of psychiatry and behavioral science, University of North Dakota, Fargo, and Devika Umashanker, MD, with Obesity Medicine, Hartford (Conn.) Health Care, in an accompanying editorial.

They acknowledged, however, that monitoring can be difficult given the typical low rate of follow-up of these patients.

Though the reasons for the rise in nonalcoholic SUD are not clear, Dr. Mitchell and Dr. Umashanker said biologic and psychosocial issues may be contributors to the increase.

The persistence of medical comorbidities and a lack of noted improvement in quality of life or physical mobility after the surgery has been addressed in a paper on suicide risk after bariatric surgery, the study authors also noted.

Dr. Svensson said in an interview that a mechanism for alcohol abuse after gastric bypass surgery is more evident, as measured by “increased blood alcohol levels after the surgery for a given amount of alcohol.” However, for other addictive substances, the mechanism is not obvious and needs further study.

The editorialists reminded clinicians that measuring phosphatidylethanol can be very useful in identifying and quantifying recent alcohol intake, suggesting that all clinicians, not just those in bariatric surgery clinics, should be aware of the connection between the procedures and subsequent alcohol abuse and monitor those patients carefully.

Both the study authors and the editorialists pointed out that the SOS cohort was recruited when vertical banded gastroplasty and banding were commonly used, and both methods are now rarely, if ever, used. Gastric sleeve procedures are now the most common approach, and those patients were not included in the study.

“However, gastric bypass surgery patients were included, albeit in a minority of the sample,” Dr. Mitchell and Dr. Umashanker wrote. In addition, the sample size of patients with SUD was too small to determine the drugs that were being abused.

Dr. Svensson said in an interview the main limitation is that SUD events were identified in the Swedish National Patient Register, which misses nonhospitalized patients.

“This register is very complete for hospitals, but it does not include SUD events detected in the primary health care setting,” he said. “Hence, the absolute number of events is probably a clear underestimation. However, it is unlikely that this limitation would affect the study groups (control group vs. groups with different surgical procedures) in different ways and hence the conclusions from this study are most likely valid.”

The study authors and the editorialists reported no relevant financial relationships.

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

Taking folic acid supplements before conception and in the first trimester of pregnancy continues to be a major line of defense against neural tube defects.

In a statement published in JAMA, the U.S. Preventive Services Task Force recommended that all people planning on becoming pregnant or who could become pregnant take a daily supplement of 0.4-0.8 mg (400-800 mcg) of folic acid to prevent neural tube defects. 

The task force also found that folic acid is not associated with maternal cancer or autism, which were the concerns of some researchers. The current findings regarding potential harm align with earlier evidence examining possible risks.

The recommendation also aligns with previous recommendations from the USPSTF and is supported by 12 more recent observational studies. Neural tube defects occur in an estimated 3,000 pregnancies per year.

Folic acid deficiency is common due to diet, impaired folate metabolism, and poor nutrient uptake as a result of medications or bariatric surgery. 

“As much as we’ve been trying to get the word out there, we still need to get it out there even more,” Wanda Nicholson, MD, MPH, MBA, vice chair of the USPSTF, told this news organization. “It’s so simple and straightforward and can be so impactful for the health of the baby.”

Neural tube formation occurs 26-28 days after fertilization. Folic acid supplementation is essential for all people who may become pregnant, considering half of the pregnancies in the United States are unplanned, according to the USPSTF.

“In many cases, neural tube formation has already occurred, or not occurred appropriately, before someone realizes that they’re pregnant,” Dr. Nicholson said. “That’s why it’s so important to start taking folic acid one month prior to conception if you’re planning on becoming pregnant, and if you’re capable of being pregnant but not planning pregnancy, yes, we’re advocating that you also proceed with folic acid supplementation.”

Primary care physicians play a key role in patient education and ensuring that all patients receive adequate folic acid, according to Spencer McClelland, MD, an obstetrician-gynecologist at Denver Health, who was not involved in the statement. Dr. McClelland advised that clinicians recommend patients who are or could get pregnant take a multivitamin, because most brands will contain the recommended dosage of folic acid.

“There’s some confusion about folic acid,” he said. “Many patients know that they should be on a prenatal vitamin, but most don’t know that the reason we’re recommending a prenatal vitamin is almost entirely because of the value of folic acid, and everything else in the prenatal vitamin is kind of icing on the cake.”

For patients trying to get pregnant, the risk for neural tube defects “is one of many examples of the importance of preconception counseling,” Dr. McClelland said.

Dr. Nicholson noted that the recommended 0.4-0.8 mg of folic acid per day is for patients without heightened deficiency due to medications or bariatric surgery. At-risk patients should receive counseling from their physician to determine the correct amount to take.

The authors report no conflicts of interest, financial or otherwise.

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

Taking folic acid supplements before conception and in the first trimester of pregnancy continues to be a major line of defense against neural tube defects.

In a statement published in JAMA, the U.S. Preventive Services Task Force recommended that all people planning on becoming pregnant or who could become pregnant take a daily supplement of 0.4-0.8 mg (400-800 mcg) of folic acid to prevent neural tube defects. 

The task force also found that folic acid is not associated with maternal cancer or autism, which were the concerns of some researchers. The current findings regarding potential harm align with earlier evidence examining possible risks.

The recommendation also aligns with previous recommendations from the USPSTF and is supported by 12 more recent observational studies. Neural tube defects occur in an estimated 3,000 pregnancies per year.

Folic acid deficiency is common due to diet, impaired folate metabolism, and poor nutrient uptake as a result of medications or bariatric surgery. 

“As much as we’ve been trying to get the word out there, we still need to get it out there even more,” Wanda Nicholson, MD, MPH, MBA, vice chair of the USPSTF, told this news organization. “It’s so simple and straightforward and can be so impactful for the health of the baby.”

Neural tube formation occurs 26-28 days after fertilization. Folic acid supplementation is essential for all people who may become pregnant, considering half of the pregnancies in the United States are unplanned, according to the USPSTF.

“In many cases, neural tube formation has already occurred, or not occurred appropriately, before someone realizes that they’re pregnant,” Dr. Nicholson said. “That’s why it’s so important to start taking folic acid one month prior to conception if you’re planning on becoming pregnant, and if you’re capable of being pregnant but not planning pregnancy, yes, we’re advocating that you also proceed with folic acid supplementation.”

Primary care physicians play a key role in patient education and ensuring that all patients receive adequate folic acid, according to Spencer McClelland, MD, an obstetrician-gynecologist at Denver Health, who was not involved in the statement. Dr. McClelland advised that clinicians recommend patients who are or could get pregnant take a multivitamin, because most brands will contain the recommended dosage of folic acid.

“There’s some confusion about folic acid,” he said. “Many patients know that they should be on a prenatal vitamin, but most don’t know that the reason we’re recommending a prenatal vitamin is almost entirely because of the value of folic acid, and everything else in the prenatal vitamin is kind of icing on the cake.”

For patients trying to get pregnant, the risk for neural tube defects “is one of many examples of the importance of preconception counseling,” Dr. McClelland said.

Dr. Nicholson noted that the recommended 0.4-0.8 mg of folic acid per day is for patients without heightened deficiency due to medications or bariatric surgery. At-risk patients should receive counseling from their physician to determine the correct amount to take.

The authors report no conflicts of interest, financial or otherwise.

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

Taking folic acid supplements before conception and in the first trimester of pregnancy continues to be a major line of defense against neural tube defects.

In a statement published in JAMA, the U.S. Preventive Services Task Force recommended that all people planning on becoming pregnant or who could become pregnant take a daily supplement of 0.4-0.8 mg (400-800 mcg) of folic acid to prevent neural tube defects. 

The task force also found that folic acid is not associated with maternal cancer or autism, which were the concerns of some researchers. The current findings regarding potential harm align with earlier evidence examining possible risks.

The recommendation also aligns with previous recommendations from the USPSTF and is supported by 12 more recent observational studies. Neural tube defects occur in an estimated 3,000 pregnancies per year.

Folic acid deficiency is common due to diet, impaired folate metabolism, and poor nutrient uptake as a result of medications or bariatric surgery. 

“As much as we’ve been trying to get the word out there, we still need to get it out there even more,” Wanda Nicholson, MD, MPH, MBA, vice chair of the USPSTF, told this news organization. “It’s so simple and straightforward and can be so impactful for the health of the baby.”

Neural tube formation occurs 26-28 days after fertilization. Folic acid supplementation is essential for all people who may become pregnant, considering half of the pregnancies in the United States are unplanned, according to the USPSTF.

“In many cases, neural tube formation has already occurred, or not occurred appropriately, before someone realizes that they’re pregnant,” Dr. Nicholson said. “That’s why it’s so important to start taking folic acid one month prior to conception if you’re planning on becoming pregnant, and if you’re capable of being pregnant but not planning pregnancy, yes, we’re advocating that you also proceed with folic acid supplementation.”

Primary care physicians play a key role in patient education and ensuring that all patients receive adequate folic acid, according to Spencer McClelland, MD, an obstetrician-gynecologist at Denver Health, who was not involved in the statement. Dr. McClelland advised that clinicians recommend patients who are or could get pregnant take a multivitamin, because most brands will contain the recommended dosage of folic acid.

“There’s some confusion about folic acid,” he said. “Many patients know that they should be on a prenatal vitamin, but most don’t know that the reason we’re recommending a prenatal vitamin is almost entirely because of the value of folic acid, and everything else in the prenatal vitamin is kind of icing on the cake.”

For patients trying to get pregnant, the risk for neural tube defects “is one of many examples of the importance of preconception counseling,” Dr. McClelland said.

Dr. Nicholson noted that the recommended 0.4-0.8 mg of folic acid per day is for patients without heightened deficiency due to medications or bariatric surgery. At-risk patients should receive counseling from their physician to determine the correct amount to take.

The authors report no conflicts of interest, financial or otherwise.

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

Chronic pain, and back pain in particular, is among the most frequent concerns for patients in the primary care setting. Roughly 8% of adults in the United States say they suffer from chronic low back pain, and many of them say the pain is significant enough to impair their ability to move, work, and otherwise enjoy life. All this, despite decades of research and countless millions in funding to find the optimal approach to treating chronic pain.

As the United States crawls out of the opioid epidemic, a group of pain specialists is hoping to identify effective, personalized approaches to managing back pain. Daniel Clauw, MD, professor of anesthesiology, internal medicine, and psychiatry at the University of Michigan, Ann Arbor, is helping lead the BEST trial. With projected enrollment of nearly 800 patients, BEST will be the largest federally funded clinical trial of interventions to treat chronic low back pain.

In an interview, Dr. Clauw spoke about the ongoing trial and the state of research into chronic pain generally. The interview has been edited for length and clarity.
 

What are your thoughts on the current state of primary care physicians’ understanding and management of pain?

Primary care physicians need a lot of help in demystifying the diagnosis and treatment of any kind of pain, but back pain is a really good place to start. When it comes to back pain, most primary care physicians are not any more knowledgeable than a layperson.

What has the opioid debacle-cum-tragedy taught you about pain management, particular as regards people with chronic pain?

I don’t feel opioids should ever be used to treat chronic low back pain. The few long-term studies that have been performed using opioids for longer than 3 months suggest that they often make pain worse rather than just failing to make pain better – and we know they are associated with a significantly increased all-cause mortality with increased deaths from myocardial infarction, accidents, and suicides, in addition to overdose.

Given how many patients experience back pain, how did we come to the point at which primary care physicians are so ill equipped?

We’ve had terrible pain curricula in medical schools. To give you an example: I’m one of the leading pain experts in the world and I’m not allowed to teach our medical students their pain curriculum. The students learn about neurophysiology and the anatomy of the nerves, not what’s relevant in pain.

This is notorious in medical school: Curricula are almost impossible to modify and change. So it starts with poor training in medical school. And then, regardless of what education they do or don’t get in medical school, a lot of their education about pain management is through our residencies – mainly in inpatient settings, where you’re really seeing the management of acute pain and not the management of chronic pain.

People get more accustomed to managing acute pain, where opioids are a reasonable option. It’s just that when you start managing subacute or chronic pain, opioids don’t work as well.

The other big problem is that historically, most people trained in medicine think that if you have pain in your elbow, there’s got to be something wrong in your elbow. This third mechanism of pain, central sensitization – or nociplastic pain – the kind of pain that we see in fibromyalgia, headache, and low back pain, where the pain is coming from the brain – that’s confusing to people. People can have pain without any damage or inflammation to that region of the body.

Physicians are trained that if there’s pain, there’s something wrong and we have to do surgery or there’s been some trauma. Most chronic pain is none of that. There’s a big disconnect between how people are trained, and then when they go out and are seeing a tremendous number of people with chronic pain.
 

What are the different types of pain, and how should they inform clinicians’ understanding about what approaches might work for managing their patients in pain?

The way the central nervous system responds to pain is analogous to the loudness of an electric guitar. You can make an electric guitar louder either by strumming the strings harder or by turning up the amplifier. For many people with fibromyalgia, low back pain, and endometriosis, for example, the problem is really more that the amplifier is turned up too high rather than its being that the guitar is strummed too strongly. That kind of pain where the pain is not due to anatomic damage or inflammation is particularly flummoxing for providers.

Can you explain the design of the new study?

It’s a 13-site study looking at four treatments: enhanced self-care, cognitive-behavioral therapy, physical therapy, and duloxetine. It’s a big precision medicine trial, trying to take everything we’ve learned and putting it all into one big study.

We’re using a SMART design, which randomizes people to two of those treatments, unless they are very much improved from the first treatment. To be eligible for the trial, you have to be able to be randomized to three of the four treatments, and people can’t choose which of the four they get.

We give them one of those treatments for 12 weeks, and at the end of 12 weeks we make the call – “Did you respond or not respond?” – and then we go back to the phenotypic data we collected at the beginning of that trial and say, “What information at baseline that we collected predicts that someone is going to respond better to duloxetine or worse to duloxetine?” And then we create the phenotype that responds best to each of those four treatments.

None of our treatments works so well that someone doesn’t end up getting randomized to a second treatment. About 85% of people so far need a second treatment because they still have enough pain that they want more relief. But the nice thing about that is we’ve already done all the functional brain imaging and all these really expensive and time-consuming things.

We’re hoping to have around 700-800 people total in this trial, which means that around 170 people will get randomized to each of the four initial treatments. No one’s ever done a study that has functional brain imaging and all these other things in it with more than 80 or 100 people. The scale of this is totally unprecedented.
 

Given that the individual therapies don’t appear to be all that successful on their own, what is your goal?

The primary aim is to match the phenotypic characteristics of a patient with chronic low back pain with treatment response to each of these four treatments. So at the end, we can give clinicians information on which of the patients is going to respond to physical therapy, for instance.

Right now, about one out of three people respond to most treatments for pain. We think by doing a trial like this, we can take treatments that work in one out of three people and make them work in one out of two or two out of three people just by using them in the right people.
 

How do you differentiate between these types of pain in your study?

We phenotype people by asking them a number of questions. We also do brain imaging, look at their back with MRI, test biomechanics, and then give them four different treatments that we know work in groups of people with low back pain.

We think one of the first parts of the phenotype is, do they have pain just in their back? Or do they have pain in their back plus a lot of other body regions? Because the more body regions that people have pain in, the more likely it is that this is an amplifier problem rather than a guitar problem.

Treatments like physical therapy, surgery, and injections are going to work better for people in whom the pain is a guitar problem rather than an amplifier problem. And drugs like duloxetine, which works in the brain, and cognitive-behavioral therapy are going to work a lot better in the people with pain in multiple sites besides the back.
 

To pick up on your metaphor, do any symptoms help clinicians differentiate between the guitar and the amplifier?

Sleep problems, fatigue, memory problems, and mood problems are common in patients with chronic pain and are more common with amplifier pain. Because again, those are all central nervous system problems. And so we see that the people that have anxiety, depression, and a lot of distress are more likely to have this kind of pain.

Does medical imaging help?

There’s a terrible relationship between what you see on an MRI of the back and whether someone has pain or how severe the pain is going to be. There’s always going to be individuals that have a lot of anatomic damage who don’t have any pain because they happen to be on the other end of the continuum from fibromyalgia; they’re actually pain-insensitive people.

What are your thoughts about ketamine as a possible treatment for chronic pain?

I have a mentee who’s doing a ketamine trial. We’re doing psilocybin trials in patients with fibromyalgia. Ketamine is such a dirty drug; it has so many different mechanisms of action. It does have some psychedelic effects, but it also is an NMDA blocker. It really has so many different effects.

I think it’s being thrown around like water in settings where we don’t yet know it to be efficacious. Even the data in treatment-refractory depression are pretty weak, but we’re so desperate to do something for those patients. If you’re trying to harness the psychedelic properties of ketamine, I think there’s other psychedelics that are a lot more interesting, which is why we’re using psilocybin for a subset of patients. Most of us in the pain field think that the psychedelics will work best for the people with chronic pain who have a lot of comorbid psychiatric illness, especially the ones with a lot of trauma. These drugs will allow us therapeutically to get at a lot of these patients with the side-by-side psychotherapy that’s being done as people are getting care in the medicalized setting.
 

Dr. Clauw reported conflicts of interest with Pfizer, Tonix, Theravance, Zynerba, Samumed, Aptinyx, Daiichi Sankyo, Intec, Regeneron, Teva, Lundbeck, Virios, and Cerephex.

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

Chronic pain, and back pain in particular, is among the most frequent concerns for patients in the primary care setting. Roughly 8% of adults in the United States say they suffer from chronic low back pain, and many of them say the pain is significant enough to impair their ability to move, work, and otherwise enjoy life. All this, despite decades of research and countless millions in funding to find the optimal approach to treating chronic pain.

As the United States crawls out of the opioid epidemic, a group of pain specialists is hoping to identify effective, personalized approaches to managing back pain. Daniel Clauw, MD, professor of anesthesiology, internal medicine, and psychiatry at the University of Michigan, Ann Arbor, is helping lead the BEST trial. With projected enrollment of nearly 800 patients, BEST will be the largest federally funded clinical trial of interventions to treat chronic low back pain.

In an interview, Dr. Clauw spoke about the ongoing trial and the state of research into chronic pain generally. The interview has been edited for length and clarity.
 

What are your thoughts on the current state of primary care physicians’ understanding and management of pain?

Primary care physicians need a lot of help in demystifying the diagnosis and treatment of any kind of pain, but back pain is a really good place to start. When it comes to back pain, most primary care physicians are not any more knowledgeable than a layperson.

What has the opioid debacle-cum-tragedy taught you about pain management, particular as regards people with chronic pain?

I don’t feel opioids should ever be used to treat chronic low back pain. The few long-term studies that have been performed using opioids for longer than 3 months suggest that they often make pain worse rather than just failing to make pain better – and we know they are associated with a significantly increased all-cause mortality with increased deaths from myocardial infarction, accidents, and suicides, in addition to overdose.

Given how many patients experience back pain, how did we come to the point at which primary care physicians are so ill equipped?

We’ve had terrible pain curricula in medical schools. To give you an example: I’m one of the leading pain experts in the world and I’m not allowed to teach our medical students their pain curriculum. The students learn about neurophysiology and the anatomy of the nerves, not what’s relevant in pain.

This is notorious in medical school: Curricula are almost impossible to modify and change. So it starts with poor training in medical school. And then, regardless of what education they do or don’t get in medical school, a lot of their education about pain management is through our residencies – mainly in inpatient settings, where you’re really seeing the management of acute pain and not the management of chronic pain.

People get more accustomed to managing acute pain, where opioids are a reasonable option. It’s just that when you start managing subacute or chronic pain, opioids don’t work as well.

The other big problem is that historically, most people trained in medicine think that if you have pain in your elbow, there’s got to be something wrong in your elbow. This third mechanism of pain, central sensitization – or nociplastic pain – the kind of pain that we see in fibromyalgia, headache, and low back pain, where the pain is coming from the brain – that’s confusing to people. People can have pain without any damage or inflammation to that region of the body.

Physicians are trained that if there’s pain, there’s something wrong and we have to do surgery or there’s been some trauma. Most chronic pain is none of that. There’s a big disconnect between how people are trained, and then when they go out and are seeing a tremendous number of people with chronic pain.
 

What are the different types of pain, and how should they inform clinicians’ understanding about what approaches might work for managing their patients in pain?

The way the central nervous system responds to pain is analogous to the loudness of an electric guitar. You can make an electric guitar louder either by strumming the strings harder or by turning up the amplifier. For many people with fibromyalgia, low back pain, and endometriosis, for example, the problem is really more that the amplifier is turned up too high rather than its being that the guitar is strummed too strongly. That kind of pain where the pain is not due to anatomic damage or inflammation is particularly flummoxing for providers.

Can you explain the design of the new study?

It’s a 13-site study looking at four treatments: enhanced self-care, cognitive-behavioral therapy, physical therapy, and duloxetine. It’s a big precision medicine trial, trying to take everything we’ve learned and putting it all into one big study.

We’re using a SMART design, which randomizes people to two of those treatments, unless they are very much improved from the first treatment. To be eligible for the trial, you have to be able to be randomized to three of the four treatments, and people can’t choose which of the four they get.

We give them one of those treatments for 12 weeks, and at the end of 12 weeks we make the call – “Did you respond or not respond?” – and then we go back to the phenotypic data we collected at the beginning of that trial and say, “What information at baseline that we collected predicts that someone is going to respond better to duloxetine or worse to duloxetine?” And then we create the phenotype that responds best to each of those four treatments.

None of our treatments works so well that someone doesn’t end up getting randomized to a second treatment. About 85% of people so far need a second treatment because they still have enough pain that they want more relief. But the nice thing about that is we’ve already done all the functional brain imaging and all these really expensive and time-consuming things.

We’re hoping to have around 700-800 people total in this trial, which means that around 170 people will get randomized to each of the four initial treatments. No one’s ever done a study that has functional brain imaging and all these other things in it with more than 80 or 100 people. The scale of this is totally unprecedented.
 

Given that the individual therapies don’t appear to be all that successful on their own, what is your goal?

The primary aim is to match the phenotypic characteristics of a patient with chronic low back pain with treatment response to each of these four treatments. So at the end, we can give clinicians information on which of the patients is going to respond to physical therapy, for instance.

Right now, about one out of three people respond to most treatments for pain. We think by doing a trial like this, we can take treatments that work in one out of three people and make them work in one out of two or two out of three people just by using them in the right people.
 

How do you differentiate between these types of pain in your study?

We phenotype people by asking them a number of questions. We also do brain imaging, look at their back with MRI, test biomechanics, and then give them four different treatments that we know work in groups of people with low back pain.

We think one of the first parts of the phenotype is, do they have pain just in their back? Or do they have pain in their back plus a lot of other body regions? Because the more body regions that people have pain in, the more likely it is that this is an amplifier problem rather than a guitar problem.

Treatments like physical therapy, surgery, and injections are going to work better for people in whom the pain is a guitar problem rather than an amplifier problem. And drugs like duloxetine, which works in the brain, and cognitive-behavioral therapy are going to work a lot better in the people with pain in multiple sites besides the back.
 

To pick up on your metaphor, do any symptoms help clinicians differentiate between the guitar and the amplifier?

Sleep problems, fatigue, memory problems, and mood problems are common in patients with chronic pain and are more common with amplifier pain. Because again, those are all central nervous system problems. And so we see that the people that have anxiety, depression, and a lot of distress are more likely to have this kind of pain.

Does medical imaging help?

There’s a terrible relationship between what you see on an MRI of the back and whether someone has pain or how severe the pain is going to be. There’s always going to be individuals that have a lot of anatomic damage who don’t have any pain because they happen to be on the other end of the continuum from fibromyalgia; they’re actually pain-insensitive people.

What are your thoughts about ketamine as a possible treatment for chronic pain?

I have a mentee who’s doing a ketamine trial. We’re doing psilocybin trials in patients with fibromyalgia. Ketamine is such a dirty drug; it has so many different mechanisms of action. It does have some psychedelic effects, but it also is an NMDA blocker. It really has so many different effects.

I think it’s being thrown around like water in settings where we don’t yet know it to be efficacious. Even the data in treatment-refractory depression are pretty weak, but we’re so desperate to do something for those patients. If you’re trying to harness the psychedelic properties of ketamine, I think there’s other psychedelics that are a lot more interesting, which is why we’re using psilocybin for a subset of patients. Most of us in the pain field think that the psychedelics will work best for the people with chronic pain who have a lot of comorbid psychiatric illness, especially the ones with a lot of trauma. These drugs will allow us therapeutically to get at a lot of these patients with the side-by-side psychotherapy that’s being done as people are getting care in the medicalized setting.
 

Dr. Clauw reported conflicts of interest with Pfizer, Tonix, Theravance, Zynerba, Samumed, Aptinyx, Daiichi Sankyo, Intec, Regeneron, Teva, Lundbeck, Virios, and Cerephex.

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

Chronic pain, and back pain in particular, is among the most frequent concerns for patients in the primary care setting. Roughly 8% of adults in the United States say they suffer from chronic low back pain, and many of them say the pain is significant enough to impair their ability to move, work, and otherwise enjoy life. All this, despite decades of research and countless millions in funding to find the optimal approach to treating chronic pain.

As the United States crawls out of the opioid epidemic, a group of pain specialists is hoping to identify effective, personalized approaches to managing back pain. Daniel Clauw, MD, professor of anesthesiology, internal medicine, and psychiatry at the University of Michigan, Ann Arbor, is helping lead the BEST trial. With projected enrollment of nearly 800 patients, BEST will be the largest federally funded clinical trial of interventions to treat chronic low back pain.

In an interview, Dr. Clauw spoke about the ongoing trial and the state of research into chronic pain generally. The interview has been edited for length and clarity.
 

What are your thoughts on the current state of primary care physicians’ understanding and management of pain?

Primary care physicians need a lot of help in demystifying the diagnosis and treatment of any kind of pain, but back pain is a really good place to start. When it comes to back pain, most primary care physicians are not any more knowledgeable than a layperson.

What has the opioid debacle-cum-tragedy taught you about pain management, particular as regards people with chronic pain?

I don’t feel opioids should ever be used to treat chronic low back pain. The few long-term studies that have been performed using opioids for longer than 3 months suggest that they often make pain worse rather than just failing to make pain better – and we know they are associated with a significantly increased all-cause mortality with increased deaths from myocardial infarction, accidents, and suicides, in addition to overdose.

Given how many patients experience back pain, how did we come to the point at which primary care physicians are so ill equipped?

We’ve had terrible pain curricula in medical schools. To give you an example: I’m one of the leading pain experts in the world and I’m not allowed to teach our medical students their pain curriculum. The students learn about neurophysiology and the anatomy of the nerves, not what’s relevant in pain.

This is notorious in medical school: Curricula are almost impossible to modify and change. So it starts with poor training in medical school. And then, regardless of what education they do or don’t get in medical school, a lot of their education about pain management is through our residencies – mainly in inpatient settings, where you’re really seeing the management of acute pain and not the management of chronic pain.

People get more accustomed to managing acute pain, where opioids are a reasonable option. It’s just that when you start managing subacute or chronic pain, opioids don’t work as well.

The other big problem is that historically, most people trained in medicine think that if you have pain in your elbow, there’s got to be something wrong in your elbow. This third mechanism of pain, central sensitization – or nociplastic pain – the kind of pain that we see in fibromyalgia, headache, and low back pain, where the pain is coming from the brain – that’s confusing to people. People can have pain without any damage or inflammation to that region of the body.

Physicians are trained that if there’s pain, there’s something wrong and we have to do surgery or there’s been some trauma. Most chronic pain is none of that. There’s a big disconnect between how people are trained, and then when they go out and are seeing a tremendous number of people with chronic pain.
 

What are the different types of pain, and how should they inform clinicians’ understanding about what approaches might work for managing their patients in pain?

The way the central nervous system responds to pain is analogous to the loudness of an electric guitar. You can make an electric guitar louder either by strumming the strings harder or by turning up the amplifier. For many people with fibromyalgia, low back pain, and endometriosis, for example, the problem is really more that the amplifier is turned up too high rather than its being that the guitar is strummed too strongly. That kind of pain where the pain is not due to anatomic damage or inflammation is particularly flummoxing for providers.

Can you explain the design of the new study?

It’s a 13-site study looking at four treatments: enhanced self-care, cognitive-behavioral therapy, physical therapy, and duloxetine. It’s a big precision medicine trial, trying to take everything we’ve learned and putting it all into one big study.

We’re using a SMART design, which randomizes people to two of those treatments, unless they are very much improved from the first treatment. To be eligible for the trial, you have to be able to be randomized to three of the four treatments, and people can’t choose which of the four they get.

We give them one of those treatments for 12 weeks, and at the end of 12 weeks we make the call – “Did you respond or not respond?” – and then we go back to the phenotypic data we collected at the beginning of that trial and say, “What information at baseline that we collected predicts that someone is going to respond better to duloxetine or worse to duloxetine?” And then we create the phenotype that responds best to each of those four treatments.

None of our treatments works so well that someone doesn’t end up getting randomized to a second treatment. About 85% of people so far need a second treatment because they still have enough pain that they want more relief. But the nice thing about that is we’ve already done all the functional brain imaging and all these really expensive and time-consuming things.

We’re hoping to have around 700-800 people total in this trial, which means that around 170 people will get randomized to each of the four initial treatments. No one’s ever done a study that has functional brain imaging and all these other things in it with more than 80 or 100 people. The scale of this is totally unprecedented.
 

Given that the individual therapies don’t appear to be all that successful on their own, what is your goal?

The primary aim is to match the phenotypic characteristics of a patient with chronic low back pain with treatment response to each of these four treatments. So at the end, we can give clinicians information on which of the patients is going to respond to physical therapy, for instance.

Right now, about one out of three people respond to most treatments for pain. We think by doing a trial like this, we can take treatments that work in one out of three people and make them work in one out of two or two out of three people just by using them in the right people.
 

How do you differentiate between these types of pain in your study?

We phenotype people by asking them a number of questions. We also do brain imaging, look at their back with MRI, test biomechanics, and then give them four different treatments that we know work in groups of people with low back pain.

We think one of the first parts of the phenotype is, do they have pain just in their back? Or do they have pain in their back plus a lot of other body regions? Because the more body regions that people have pain in, the more likely it is that this is an amplifier problem rather than a guitar problem.

Treatments like physical therapy, surgery, and injections are going to work better for people in whom the pain is a guitar problem rather than an amplifier problem. And drugs like duloxetine, which works in the brain, and cognitive-behavioral therapy are going to work a lot better in the people with pain in multiple sites besides the back.
 

To pick up on your metaphor, do any symptoms help clinicians differentiate between the guitar and the amplifier?

Sleep problems, fatigue, memory problems, and mood problems are common in patients with chronic pain and are more common with amplifier pain. Because again, those are all central nervous system problems. And so we see that the people that have anxiety, depression, and a lot of distress are more likely to have this kind of pain.

Does medical imaging help?

There’s a terrible relationship between what you see on an MRI of the back and whether someone has pain or how severe the pain is going to be. There’s always going to be individuals that have a lot of anatomic damage who don’t have any pain because they happen to be on the other end of the continuum from fibromyalgia; they’re actually pain-insensitive people.

What are your thoughts about ketamine as a possible treatment for chronic pain?

I have a mentee who’s doing a ketamine trial. We’re doing psilocybin trials in patients with fibromyalgia. Ketamine is such a dirty drug; it has so many different mechanisms of action. It does have some psychedelic effects, but it also is an NMDA blocker. It really has so many different effects.

I think it’s being thrown around like water in settings where we don’t yet know it to be efficacious. Even the data in treatment-refractory depression are pretty weak, but we’re so desperate to do something for those patients. If you’re trying to harness the psychedelic properties of ketamine, I think there’s other psychedelics that are a lot more interesting, which is why we’re using psilocybin for a subset of patients. Most of us in the pain field think that the psychedelics will work best for the people with chronic pain who have a lot of comorbid psychiatric illness, especially the ones with a lot of trauma. These drugs will allow us therapeutically to get at a lot of these patients with the side-by-side psychotherapy that’s being done as people are getting care in the medicalized setting.
 

Dr. Clauw reported conflicts of interest with Pfizer, Tonix, Theravance, Zynerba, Samumed, Aptinyx, Daiichi Sankyo, Intec, Regeneron, Teva, Lundbeck, Virios, and Cerephex.

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