MDedge Rheumatology

Key clinical point: Adults with pre-existing psoriatic arthritis (PsA) who underwent surgery for lumbar degenerative disease (LDD) faced increased odds of unfavorable discharge and venous thromboembolism (VTE) events compared with those without PsA.

Major finding: A diagnosis of PsA in patients who underwent LDD surgery increased the odds of unfavorable discharge by 26% (adjusted odds ratio [aOR] 1.26; 95% CI 1.03-1.55) and nearly doubled the risk for VTE (aOR 1.99; 95% CI 1.05-3.75).

Study details: This population-based retrospective study included 467,814 patients (age ≥ 20 years) who underwent surgery for LDD, of whom 883 patients had pre-existing PsA and were matched to 8830 patients without PsA.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Chen MY et al. Psoriatic arthritis increases the risk of venous thromboembolism following degenerative lumbar spine surgery: An analysis of U.S. Nationwide Inpatient Sample 2005–2018. Heliyon. 2023;10(1):E23613 (Dec 12). doi: 10.1016/j.heliyon.2023.e23613

Key clinical point: Adults with pre-existing psoriatic arthritis (PsA) who underwent surgery for lumbar degenerative disease (LDD) faced increased odds of unfavorable discharge and venous thromboembolism (VTE) events compared with those without PsA.

Major finding: A diagnosis of PsA in patients who underwent LDD surgery increased the odds of unfavorable discharge by 26% (adjusted odds ratio [aOR] 1.26; 95% CI 1.03-1.55) and nearly doubled the risk for VTE (aOR 1.99; 95% CI 1.05-3.75).

Study details: This population-based retrospective study included 467,814 patients (age ≥ 20 years) who underwent surgery for LDD, of whom 883 patients had pre-existing PsA and were matched to 8830 patients without PsA.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Chen MY et al. Psoriatic arthritis increases the risk of venous thromboembolism following degenerative lumbar spine surgery: An analysis of U.S. Nationwide Inpatient Sample 2005–2018. Heliyon. 2023;10(1):E23613 (Dec 12). doi: 10.1016/j.heliyon.2023.e23613

Key clinical point: Adults with pre-existing psoriatic arthritis (PsA) who underwent surgery for lumbar degenerative disease (LDD) faced increased odds of unfavorable discharge and venous thromboembolism (VTE) events compared with those without PsA.

Major finding: A diagnosis of PsA in patients who underwent LDD surgery increased the odds of unfavorable discharge by 26% (adjusted odds ratio [aOR] 1.26; 95% CI 1.03-1.55) and nearly doubled the risk for VTE (aOR 1.99; 95% CI 1.05-3.75).

Study details: This population-based retrospective study included 467,814 patients (age ≥ 20 years) who underwent surgery for LDD, of whom 883 patients had pre-existing PsA and were matched to 8830 patients without PsA.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Chen MY et al. Psoriatic arthritis increases the risk of venous thromboembolism following degenerative lumbar spine surgery: An analysis of U.S. Nationwide Inpatient Sample 2005–2018. Heliyon. 2023;10(1):E23613 (Dec 12). doi: 10.1016/j.heliyon.2023.e23613

Key clinical point: Female patients with psoriatic arthritis (PsA) who received tumor necrosis factor inhibitors (TNFi) and interleukin-17 inhibitors (IL-17i) showed lower treatment persistence than male patients with PsA who received the same therapeutic class of drugs.

Major finding: Women demonstrated 20%-40% lower treatment persistence rates than men for TNFi (adjusted hazard ratio [aHR] 1.4; 99% CI 1.3-1.5) and IL-17i (aHR 1.2; 99% CI 1.1-1.3) therapies; however, the treatment persistence between both sexes was comparable for IL12/23i (aHR 1.1; 99% CI 0.9-1.3), IL23i (aHR 1.1; 99% CI 0.7-1.5), and Janus kinase inhibitor (aHR 1.2; 99% CI 0.9-1.6) therapies.

Study details: This nationwide cohort study included 14,778 patients with PsA who were new users of targeted therapies, of whom 57% were women and 43% were men.

Disclosures: This study did not receive any specific grant. Two authors declared receiving subsidy or consulting fees from or being an investigator for various pharmaceutical companies. Other authors declared no conflicts of interest.

Source: Pina Vegas L et al. Influence of sex on the persistence of different classes of targeted therapies for psoriatic arthritis: A cohort study of 14 778 patients from the French health insurance database (SNDS). RMD Open. 2023;9:e003570 (Dec 19). doi: 10.1136/rmdopen-2023-003570

Key clinical point: Female patients with psoriatic arthritis (PsA) who received tumor necrosis factor inhibitors (TNFi) and interleukin-17 inhibitors (IL-17i) showed lower treatment persistence than male patients with PsA who received the same therapeutic class of drugs.

Major finding: Women demonstrated 20%-40% lower treatment persistence rates than men for TNFi (adjusted hazard ratio [aHR] 1.4; 99% CI 1.3-1.5) and IL-17i (aHR 1.2; 99% CI 1.1-1.3) therapies; however, the treatment persistence between both sexes was comparable for IL12/23i (aHR 1.1; 99% CI 0.9-1.3), IL23i (aHR 1.1; 99% CI 0.7-1.5), and Janus kinase inhibitor (aHR 1.2; 99% CI 0.9-1.6) therapies.

Study details: This nationwide cohort study included 14,778 patients with PsA who were new users of targeted therapies, of whom 57% were women and 43% were men.

Disclosures: This study did not receive any specific grant. Two authors declared receiving subsidy or consulting fees from or being an investigator for various pharmaceutical companies. Other authors declared no conflicts of interest.

Source: Pina Vegas L et al. Influence of sex on the persistence of different classes of targeted therapies for psoriatic arthritis: A cohort study of 14 778 patients from the French health insurance database (SNDS). RMD Open. 2023;9:e003570 (Dec 19). doi: 10.1136/rmdopen-2023-003570

Key clinical point: Female patients with psoriatic arthritis (PsA) who received tumor necrosis factor inhibitors (TNFi) and interleukin-17 inhibitors (IL-17i) showed lower treatment persistence than male patients with PsA who received the same therapeutic class of drugs.

Major finding: Women demonstrated 20%-40% lower treatment persistence rates than men for TNFi (adjusted hazard ratio [aHR] 1.4; 99% CI 1.3-1.5) and IL-17i (aHR 1.2; 99% CI 1.1-1.3) therapies; however, the treatment persistence between both sexes was comparable for IL12/23i (aHR 1.1; 99% CI 0.9-1.3), IL23i (aHR 1.1; 99% CI 0.7-1.5), and Janus kinase inhibitor (aHR 1.2; 99% CI 0.9-1.6) therapies.

Study details: This nationwide cohort study included 14,778 patients with PsA who were new users of targeted therapies, of whom 57% were women and 43% were men.

Disclosures: This study did not receive any specific grant. Two authors declared receiving subsidy or consulting fees from or being an investigator for various pharmaceutical companies. Other authors declared no conflicts of interest.

Source: Pina Vegas L et al. Influence of sex on the persistence of different classes of targeted therapies for psoriatic arthritis: A cohort study of 14 778 patients from the French health insurance database (SNDS). RMD Open. 2023;9:e003570 (Dec 19). doi: 10.1136/rmdopen-2023-003570

Key clinical point: Although Psoriatic Arthritis Impact of Disease questionnaire-12 items (PsAID-12) scores were higher in patients with psoriatic arthritis (PsA) who did vs did not have a treatment escalation, physicians relied more on their assessment of disease activity while making treatment-related decisions.

Major finding: Higher mean PsAID-12 score correlated with higher odds of treatment escalation in patients with PsA (odds ratio [OR] 1.58; P < .0001), whereas physician’s assessment of disease activity had the most significant impact on likelihood of treatment escalation (OR 2.68; P < .0001). Longer disease duration, treatment with nonbiologics, and a higher swollen joint count also increased the odds for treatment escalation.

Study details: Findings are from a cross-sectional analysis (the ASSIST study) that included 503 patients with PsA (age ≥ 18 years), of whom 160 patients underwent treatment escalation.

Disclosures: This study was funded by Amgen, and the National Institute for Health Research Oxford Biomedical Research Centre. Several authors declared receiving grants, honoraria, consultancy fees, or travel support from or having ties with various sources, including Amgen.

Source: Coyle C et al. How do patient reported outcome measures affect treatment intensification and patient satisfaction in the management of psoriatic arthritis? A cross sectional study of 503 patients. Rheumatology (Oxford). 2024 (Jan 8). doi: 10.1093/rheumatology/kead679

Key clinical point: Although Psoriatic Arthritis Impact of Disease questionnaire-12 items (PsAID-12) scores were higher in patients with psoriatic arthritis (PsA) who did vs did not have a treatment escalation, physicians relied more on their assessment of disease activity while making treatment-related decisions.

Major finding: Higher mean PsAID-12 score correlated with higher odds of treatment escalation in patients with PsA (odds ratio [OR] 1.58; P < .0001), whereas physician’s assessment of disease activity had the most significant impact on likelihood of treatment escalation (OR 2.68; P < .0001). Longer disease duration, treatment with nonbiologics, and a higher swollen joint count also increased the odds for treatment escalation.

Study details: Findings are from a cross-sectional analysis (the ASSIST study) that included 503 patients with PsA (age ≥ 18 years), of whom 160 patients underwent treatment escalation.

Disclosures: This study was funded by Amgen, and the National Institute for Health Research Oxford Biomedical Research Centre. Several authors declared receiving grants, honoraria, consultancy fees, or travel support from or having ties with various sources, including Amgen.

Source: Coyle C et al. How do patient reported outcome measures affect treatment intensification and patient satisfaction in the management of psoriatic arthritis? A cross sectional study of 503 patients. Rheumatology (Oxford). 2024 (Jan 8). doi: 10.1093/rheumatology/kead679

Key clinical point: Although Psoriatic Arthritis Impact of Disease questionnaire-12 items (PsAID-12) scores were higher in patients with psoriatic arthritis (PsA) who did vs did not have a treatment escalation, physicians relied more on their assessment of disease activity while making treatment-related decisions.

Major finding: Higher mean PsAID-12 score correlated with higher odds of treatment escalation in patients with PsA (odds ratio [OR] 1.58; P < .0001), whereas physician’s assessment of disease activity had the most significant impact on likelihood of treatment escalation (OR 2.68; P < .0001). Longer disease duration, treatment with nonbiologics, and a higher swollen joint count also increased the odds for treatment escalation.

Study details: Findings are from a cross-sectional analysis (the ASSIST study) that included 503 patients with PsA (age ≥ 18 years), of whom 160 patients underwent treatment escalation.

Disclosures: This study was funded by Amgen, and the National Institute for Health Research Oxford Biomedical Research Centre. Several authors declared receiving grants, honoraria, consultancy fees, or travel support from or having ties with various sources, including Amgen.

Source: Coyle C et al. How do patient reported outcome measures affect treatment intensification and patient satisfaction in the management of psoriatic arthritis? A cross sectional study of 503 patients. Rheumatology (Oxford). 2024 (Jan 8). doi: 10.1093/rheumatology/kead679

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) have overlapping neurologic symptoms — particularly profound fatigue. The similarity between these two conditions has led to the question of whether they are indeed distinct central nervous system (CNS) entities, or whether they exist along a spectrum and are actually two different manifestations of the same disease process.

A new study utilized a novel methodology — unbiased quantitative mass spectrometry-based proteomics — to investigate this question by analyzing cerebrospinal fluid (CSF) in a group of patients with ME/CFS and another group of patients diagnosed with both ME/CFS and FM.

Close to 2,100 proteins were identified, of which nearly 1,800 were common to both conditions.

“ME/CFS and fibromyalgia do not appear to be distinct entities, with respect to their cerebrospinal fluid proteins,” lead author Steven Schutzer, MD, professor of medicine, Rutgers New Jersey School of Medicine, told this news organization.

“Work is underway to solve the multiple mysteries of ME/CFS, fibromyalgia, and other neurologic-associated diseases,” he continued. “We have further affirmed that we have a precise objective discovery tool in our hands. Collectively studying multiple diseases brings clarity to each individual disease.”

The study was published in the December 2023 issue of Annals of Medicine.
 

Cutting-Edge Technology

“ME/CFS is characterized by disabling fatigue, and FM is an illness characterized by body-wide pain,” Dr. Schutzer said. These “medically unexplained” illnesses often coexist by current definitions, and the overlap between them has suggested that they may be part of the “same illness spectrum.”

But co-investigator Benjamin Natelson, MD, professor of neurology and director of the Pain and Fatigue Study Center, Mount Sinai, New York, and others found in previous research that there are distinct differences between the conditions, raising the possibility that there may be different pathophysiological processes.

“The physicians and scientists on our team have had longstanding interest in studying neurologic diseases with cutting-edge tools such as mass spectrometry applied to CSF,” Dr. Schutzer said. “We have had success using this message to distinguish diseases such as ME/CFS from post-treatment Lyme disease, multiple sclerosis, and healthy normal people.”

Dr. Schutzer explained that Dr. Natelson had acquired CSF samples from “well-characterized [ME/CFS] patients and controls.”

Since the cause of ME/CFS is “unknown,” it seemed “ripe to investigate it further with the discovery tool of mass spectrometry” by harnessing the “most advanced equipment in the country at the pacific Northwest National Laboratory, which is part of the US Department of Energy.”

Dr. Schutzer noted that it was the “merger of different clinical and laboratory expertise” that enabled them to address whether ME/CFS and FM are two distinct disease processes.

The choice of analyzing CSF is that it’s the fluid closest to the brain, he added. “A lot of people have studied ME/CFS peripherally because they don’t have access to spinal fluid or it’s easier to look peripherally in the blood, but that doesn’t mean that the blood is where the real ‘action’ is occurring.”

The researchers compared the CSF of 15 patients with ME/CFS only to 15 patients with ME/CFS+FM using mass spectrometry-based proteomics, which they had employed in previous research to see whether ME/CFS was distinct from persistent neurologic Lyme disease syndrome.

This technology has become the “method of choice and discovery tool to rapidly uncover protein biomarkers that can distinguish one disease from another,” the authors stated.

In particular, in unbiased quantitative mass spectrometry-based proteomics, the researchers do not have to know in advance what’s in a sample before studying it, Dr. Schutzer explained.
 

Shared Pathophysiology?

Both groups of patients were of similar age (41.3 ± 9.4 years and 40.1 ± 11.0 years, respectively), with no differences in gender or rates of current comorbid psychiatric diagnoses between the groups.

The researchers quantified a total of 2,083 proteins, including 1,789 that were specifically quantified in all of the CSF samples, regardless of the presence or absence of FM.

Several analyses (including an ANOVA analysis with adjusted P values, a Random Forest machine learning approach that looked at relative protein abundance changes between those with ME/CFS and ME/CFS+FM, and unsupervised hierarchical clustering analyses) did not find distinguishing differences between the groups.

“The sum of these results does not support the hypothesis that ME/CFS and ME/CFS+FM are distinct entities, as currently defined,” the authors stated.

They noted that both conditions are “medically unexplained,” with core symptoms of pain, fatigue, sleep problems, and cognitive difficulty. The fact that these two syndromes coexist so often has led to the assumption that the “similarities between them outweigh the differences,” they wrote.

They pointed to some differences between the conditions, including an increase in substance P in the CSF of FM patients, but not in ME/CFS patients reported by others. There are also some immunological, physiological and genetic differences.

But if the conclusion that the two illnesses may share a similar pathophysiological basis is supported by other research that includes FM-only patients as comparators to those with ME/CFS, “this would support the notion that the two illnesses fall along a common illness spectrum and may be approached as a single entity — with implications for both diagnosis and the development of new treatment approaches,” they concluded.
 

‘Noncontributory’ Findings

Commenting on the research, Robert G. Lahita, MD, PhD, director of the Institute for Autoimmune and Rheumatic Diseases, St. Joseph Health, Wayne, New Jersey, stated that he does not regard these diseases as neurologic but rather as rheumatologic.

“Most neurologists don’t see these diseases, but as a rheumatologist, I see them every day,” said Dr. Lahita, professor of medicine at Hackensack (New Jersey) Meridian School of Medicine and a clinical professor of medicine at Rutgers New Jersey Medical School, New Brunswick. “ME/CFS isn’t as common in my practice, but we do deal with many post-COVID patients who are afflicted mostly with ME/CFS.”

He noted that an important reason for fatigue in FM is that patients generally don’t sleep, or their sleep is disrupted. This is different from the cause of fatigue in ME/CFS.

In addition, the small sample size and the lack of difference between males and females were both limitations of the current study, said Dr. Lahita, who was not involved in this research. “We know that FM disproportionately affects women — in my practice, for example, over 95% of the patients with FM are female — while ME/CFS affects both genders similarly.”

Using proteomics as a biomarker was also problematic, according to Dr. Lahita. “It would have been more valuable to investigate differences in cytokines, for example,” he suggested.

Ultimately, Dr. Lahita thinks that the study is “non-contributory to the field and, as complex as the analysis was, it does nothing to shed differentiate the two conditions or explain the syndromes themselves.”

He added that it would have been more valuable to compare ME/CFS not only to ME/CFS plus FM but also with FM without ME/CFS and to healthy controls, and perhaps to a group with an autoimmune condition, such as lupus or Hashimoto’s thyroiditis.

Dr. Schutzer acknowledged that a limitation of the current study is that his team was unable analyze the CSF of patients with only FM. He and his colleagues “combed the world’s labs” for existing CSF samples of patients with FM alone but were unable to obtain any. “We see this study as a ‘stepping stone’ and hope that future studies will include patients with FM who are willing to donate CSF samples that we can use for comparison,” he said.

The authors received support from the National Institutes of Health, National Institute of Allergy and Infectious Diseases, and National Institute of Neurological Disorders and Stroke. Dr. Schutzer, coauthors, and Dr. Lahita reported no relevant financial relationships.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) have overlapping neurologic symptoms — particularly profound fatigue. The similarity between these two conditions has led to the question of whether they are indeed distinct central nervous system (CNS) entities, or whether they exist along a spectrum and are actually two different manifestations of the same disease process.

A new study utilized a novel methodology — unbiased quantitative mass spectrometry-based proteomics — to investigate this question by analyzing cerebrospinal fluid (CSF) in a group of patients with ME/CFS and another group of patients diagnosed with both ME/CFS and FM.

Close to 2,100 proteins were identified, of which nearly 1,800 were common to both conditions.

“ME/CFS and fibromyalgia do not appear to be distinct entities, with respect to their cerebrospinal fluid proteins,” lead author Steven Schutzer, MD, professor of medicine, Rutgers New Jersey School of Medicine, told this news organization.

“Work is underway to solve the multiple mysteries of ME/CFS, fibromyalgia, and other neurologic-associated diseases,” he continued. “We have further affirmed that we have a precise objective discovery tool in our hands. Collectively studying multiple diseases brings clarity to each individual disease.”

The study was published in the December 2023 issue of Annals of Medicine.
 

Cutting-Edge Technology

“ME/CFS is characterized by disabling fatigue, and FM is an illness characterized by body-wide pain,” Dr. Schutzer said. These “medically unexplained” illnesses often coexist by current definitions, and the overlap between them has suggested that they may be part of the “same illness spectrum.”

But co-investigator Benjamin Natelson, MD, professor of neurology and director of the Pain and Fatigue Study Center, Mount Sinai, New York, and others found in previous research that there are distinct differences between the conditions, raising the possibility that there may be different pathophysiological processes.

“The physicians and scientists on our team have had longstanding interest in studying neurologic diseases with cutting-edge tools such as mass spectrometry applied to CSF,” Dr. Schutzer said. “We have had success using this message to distinguish diseases such as ME/CFS from post-treatment Lyme disease, multiple sclerosis, and healthy normal people.”

Dr. Schutzer explained that Dr. Natelson had acquired CSF samples from “well-characterized [ME/CFS] patients and controls.”

Since the cause of ME/CFS is “unknown,” it seemed “ripe to investigate it further with the discovery tool of mass spectrometry” by harnessing the “most advanced equipment in the country at the pacific Northwest National Laboratory, which is part of the US Department of Energy.”

Dr. Schutzer noted that it was the “merger of different clinical and laboratory expertise” that enabled them to address whether ME/CFS and FM are two distinct disease processes.

The choice of analyzing CSF is that it’s the fluid closest to the brain, he added. “A lot of people have studied ME/CFS peripherally because they don’t have access to spinal fluid or it’s easier to look peripherally in the blood, but that doesn’t mean that the blood is where the real ‘action’ is occurring.”

The researchers compared the CSF of 15 patients with ME/CFS only to 15 patients with ME/CFS+FM using mass spectrometry-based proteomics, which they had employed in previous research to see whether ME/CFS was distinct from persistent neurologic Lyme disease syndrome.

This technology has become the “method of choice and discovery tool to rapidly uncover protein biomarkers that can distinguish one disease from another,” the authors stated.

In particular, in unbiased quantitative mass spectrometry-based proteomics, the researchers do not have to know in advance what’s in a sample before studying it, Dr. Schutzer explained.
 

Shared Pathophysiology?

Both groups of patients were of similar age (41.3 ± 9.4 years and 40.1 ± 11.0 years, respectively), with no differences in gender or rates of current comorbid psychiatric diagnoses between the groups.

The researchers quantified a total of 2,083 proteins, including 1,789 that were specifically quantified in all of the CSF samples, regardless of the presence or absence of FM.

Several analyses (including an ANOVA analysis with adjusted P values, a Random Forest machine learning approach that looked at relative protein abundance changes between those with ME/CFS and ME/CFS+FM, and unsupervised hierarchical clustering analyses) did not find distinguishing differences between the groups.

“The sum of these results does not support the hypothesis that ME/CFS and ME/CFS+FM are distinct entities, as currently defined,” the authors stated.

They noted that both conditions are “medically unexplained,” with core symptoms of pain, fatigue, sleep problems, and cognitive difficulty. The fact that these two syndromes coexist so often has led to the assumption that the “similarities between them outweigh the differences,” they wrote.

They pointed to some differences between the conditions, including an increase in substance P in the CSF of FM patients, but not in ME/CFS patients reported by others. There are also some immunological, physiological and genetic differences.

But if the conclusion that the two illnesses may share a similar pathophysiological basis is supported by other research that includes FM-only patients as comparators to those with ME/CFS, “this would support the notion that the two illnesses fall along a common illness spectrum and may be approached as a single entity — with implications for both diagnosis and the development of new treatment approaches,” they concluded.
 

‘Noncontributory’ Findings

Commenting on the research, Robert G. Lahita, MD, PhD, director of the Institute for Autoimmune and Rheumatic Diseases, St. Joseph Health, Wayne, New Jersey, stated that he does not regard these diseases as neurologic but rather as rheumatologic.

“Most neurologists don’t see these diseases, but as a rheumatologist, I see them every day,” said Dr. Lahita, professor of medicine at Hackensack (New Jersey) Meridian School of Medicine and a clinical professor of medicine at Rutgers New Jersey Medical School, New Brunswick. “ME/CFS isn’t as common in my practice, but we do deal with many post-COVID patients who are afflicted mostly with ME/CFS.”

He noted that an important reason for fatigue in FM is that patients generally don’t sleep, or their sleep is disrupted. This is different from the cause of fatigue in ME/CFS.

In addition, the small sample size and the lack of difference between males and females were both limitations of the current study, said Dr. Lahita, who was not involved in this research. “We know that FM disproportionately affects women — in my practice, for example, over 95% of the patients with FM are female — while ME/CFS affects both genders similarly.”

Using proteomics as a biomarker was also problematic, according to Dr. Lahita. “It would have been more valuable to investigate differences in cytokines, for example,” he suggested.

Ultimately, Dr. Lahita thinks that the study is “non-contributory to the field and, as complex as the analysis was, it does nothing to shed differentiate the two conditions or explain the syndromes themselves.”

He added that it would have been more valuable to compare ME/CFS not only to ME/CFS plus FM but also with FM without ME/CFS and to healthy controls, and perhaps to a group with an autoimmune condition, such as lupus or Hashimoto’s thyroiditis.

Dr. Schutzer acknowledged that a limitation of the current study is that his team was unable analyze the CSF of patients with only FM. He and his colleagues “combed the world’s labs” for existing CSF samples of patients with FM alone but were unable to obtain any. “We see this study as a ‘stepping stone’ and hope that future studies will include patients with FM who are willing to donate CSF samples that we can use for comparison,” he said.

The authors received support from the National Institutes of Health, National Institute of Allergy and Infectious Diseases, and National Institute of Neurological Disorders and Stroke. Dr. Schutzer, coauthors, and Dr. Lahita reported no relevant financial relationships.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) have overlapping neurologic symptoms — particularly profound fatigue. The similarity between these two conditions has led to the question of whether they are indeed distinct central nervous system (CNS) entities, or whether they exist along a spectrum and are actually two different manifestations of the same disease process.

A new study utilized a novel methodology — unbiased quantitative mass spectrometry-based proteomics — to investigate this question by analyzing cerebrospinal fluid (CSF) in a group of patients with ME/CFS and another group of patients diagnosed with both ME/CFS and FM.

Close to 2,100 proteins were identified, of which nearly 1,800 were common to both conditions.

“ME/CFS and fibromyalgia do not appear to be distinct entities, with respect to their cerebrospinal fluid proteins,” lead author Steven Schutzer, MD, professor of medicine, Rutgers New Jersey School of Medicine, told this news organization.

“Work is underway to solve the multiple mysteries of ME/CFS, fibromyalgia, and other neurologic-associated diseases,” he continued. “We have further affirmed that we have a precise objective discovery tool in our hands. Collectively studying multiple diseases brings clarity to each individual disease.”

The study was published in the December 2023 issue of Annals of Medicine.
 

Cutting-Edge Technology

“ME/CFS is characterized by disabling fatigue, and FM is an illness characterized by body-wide pain,” Dr. Schutzer said. These “medically unexplained” illnesses often coexist by current definitions, and the overlap between them has suggested that they may be part of the “same illness spectrum.”

But co-investigator Benjamin Natelson, MD, professor of neurology and director of the Pain and Fatigue Study Center, Mount Sinai, New York, and others found in previous research that there are distinct differences between the conditions, raising the possibility that there may be different pathophysiological processes.

“The physicians and scientists on our team have had longstanding interest in studying neurologic diseases with cutting-edge tools such as mass spectrometry applied to CSF,” Dr. Schutzer said. “We have had success using this message to distinguish diseases such as ME/CFS from post-treatment Lyme disease, multiple sclerosis, and healthy normal people.”

Dr. Schutzer explained that Dr. Natelson had acquired CSF samples from “well-characterized [ME/CFS] patients and controls.”

Since the cause of ME/CFS is “unknown,” it seemed “ripe to investigate it further with the discovery tool of mass spectrometry” by harnessing the “most advanced equipment in the country at the pacific Northwest National Laboratory, which is part of the US Department of Energy.”

Dr. Schutzer noted that it was the “merger of different clinical and laboratory expertise” that enabled them to address whether ME/CFS and FM are two distinct disease processes.

The choice of analyzing CSF is that it’s the fluid closest to the brain, he added. “A lot of people have studied ME/CFS peripherally because they don’t have access to spinal fluid or it’s easier to look peripherally in the blood, but that doesn’t mean that the blood is where the real ‘action’ is occurring.”

The researchers compared the CSF of 15 patients with ME/CFS only to 15 patients with ME/CFS+FM using mass spectrometry-based proteomics, which they had employed in previous research to see whether ME/CFS was distinct from persistent neurologic Lyme disease syndrome.

This technology has become the “method of choice and discovery tool to rapidly uncover protein biomarkers that can distinguish one disease from another,” the authors stated.

In particular, in unbiased quantitative mass spectrometry-based proteomics, the researchers do not have to know in advance what’s in a sample before studying it, Dr. Schutzer explained.
 

Shared Pathophysiology?

Both groups of patients were of similar age (41.3 ± 9.4 years and 40.1 ± 11.0 years, respectively), with no differences in gender or rates of current comorbid psychiatric diagnoses between the groups.

The researchers quantified a total of 2,083 proteins, including 1,789 that were specifically quantified in all of the CSF samples, regardless of the presence or absence of FM.

Several analyses (including an ANOVA analysis with adjusted P values, a Random Forest machine learning approach that looked at relative protein abundance changes between those with ME/CFS and ME/CFS+FM, and unsupervised hierarchical clustering analyses) did not find distinguishing differences between the groups.

“The sum of these results does not support the hypothesis that ME/CFS and ME/CFS+FM are distinct entities, as currently defined,” the authors stated.

They noted that both conditions are “medically unexplained,” with core symptoms of pain, fatigue, sleep problems, and cognitive difficulty. The fact that these two syndromes coexist so often has led to the assumption that the “similarities between them outweigh the differences,” they wrote.

They pointed to some differences between the conditions, including an increase in substance P in the CSF of FM patients, but not in ME/CFS patients reported by others. There are also some immunological, physiological and genetic differences.

But if the conclusion that the two illnesses may share a similar pathophysiological basis is supported by other research that includes FM-only patients as comparators to those with ME/CFS, “this would support the notion that the two illnesses fall along a common illness spectrum and may be approached as a single entity — with implications for both diagnosis and the development of new treatment approaches,” they concluded.
 

‘Noncontributory’ Findings

Commenting on the research, Robert G. Lahita, MD, PhD, director of the Institute for Autoimmune and Rheumatic Diseases, St. Joseph Health, Wayne, New Jersey, stated that he does not regard these diseases as neurologic but rather as rheumatologic.

“Most neurologists don’t see these diseases, but as a rheumatologist, I see them every day,” said Dr. Lahita, professor of medicine at Hackensack (New Jersey) Meridian School of Medicine and a clinical professor of medicine at Rutgers New Jersey Medical School, New Brunswick. “ME/CFS isn’t as common in my practice, but we do deal with many post-COVID patients who are afflicted mostly with ME/CFS.”

He noted that an important reason for fatigue in FM is that patients generally don’t sleep, or their sleep is disrupted. This is different from the cause of fatigue in ME/CFS.

In addition, the small sample size and the lack of difference between males and females were both limitations of the current study, said Dr. Lahita, who was not involved in this research. “We know that FM disproportionately affects women — in my practice, for example, over 95% of the patients with FM are female — while ME/CFS affects both genders similarly.”

Using proteomics as a biomarker was also problematic, according to Dr. Lahita. “It would have been more valuable to investigate differences in cytokines, for example,” he suggested.

Ultimately, Dr. Lahita thinks that the study is “non-contributory to the field and, as complex as the analysis was, it does nothing to shed differentiate the two conditions or explain the syndromes themselves.”

He added that it would have been more valuable to compare ME/CFS not only to ME/CFS plus FM but also with FM without ME/CFS and to healthy controls, and perhaps to a group with an autoimmune condition, such as lupus or Hashimoto’s thyroiditis.

Dr. Schutzer acknowledged that a limitation of the current study is that his team was unable analyze the CSF of patients with only FM. He and his colleagues “combed the world’s labs” for existing CSF samples of patients with FM alone but were unable to obtain any. “We see this study as a ‘stepping stone’ and hope that future studies will include patients with FM who are willing to donate CSF samples that we can use for comparison,” he said.

The authors received support from the National Institutes of Health, National Institute of Allergy and Infectious Diseases, and National Institute of Neurological Disorders and Stroke. Dr. Schutzer, coauthors, and Dr. Lahita reported no relevant financial relationships.

TOPLINE:

Exercise with weight machines or elastic resistance bands yielded similar improvements in strength and function in adults with psoriatic arthritis (PsA) after 12 weeks.

METHODOLOGY:

• Researchers recruited 41 adults aged 18-65 years with PsA who were then randomized to a functional training group (FT) or a resistance exercise group (RE) for 12 weeks of twice-weekly, 55-minute sessions under the supervision of a physical trainer.
• Functional training involved the use of elastic bands to work upper body, lower body, and trunk muscles including the biceps, triceps, back quadriceps, glutes, and hips; the RE used weight machines instead of bands.
• Participants were evaluated at baseline and after 6 and 12 weeks of training sessions; the primary outcome was functional status based on the Health Assessment Questionnaire for the Spondyloarthropathies (HAQ-S).
• Secondary outcomes included the Bath Ankylosing Spondylitis Functional Index (BASFI) to assess functional capacity, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Disease Activity Score in 28 joints (DAS28) to assess disease activity, and the Short Form 36 (SF-36) to measure quality of life.

TAKEAWAY:

• Participants in both groups showed significant improvement from baseline on the primary outcome measure, with no significant differences between the groups on the primary outcome of function or secondary measures of function and disease activity after 12 weeks.
• Significant intragroup changes occurred between times for both groups on the HAQ-S, BASFI, BASDAI, and DAS28 (P = .001, .007, .001, and .001, respectively).
• Improvement in quality of life was significant from baseline and similar between the FT and RE, with the exception of the “social aspects” domain, for which only the FT showed significant improvement.
• No intervention-related adverse events were reported in either group.

IN PRACTICE:

Despite the absence of consensus guidelines on the use and effectiveness of FT and RE, “we can conclude that both FT and RE have similar effectiveness in improving functional capacity, functional status, disease activity, general quality of life, and muscle strength in patients with psoriatic arthritis,” the researchers wrote.

SOURCE:

The study was led by Diego Roger Silva, MD, of the Universidade Federal de São Paulo, Brazil, and published online in Advances in Rheumatology.

LIMITATIONS:

The study population was recruited from outpatient clinics, and the mean age of 52 years was higher than in previous studies; the study also lacked long-term follow-up data.

DISCLOSURES:

The study received no outside funding. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Exercise with weight machines or elastic resistance bands yielded similar improvements in strength and function in adults with psoriatic arthritis (PsA) after 12 weeks.

METHODOLOGY:

• Researchers recruited 41 adults aged 18-65 years with PsA who were then randomized to a functional training group (FT) or a resistance exercise group (RE) for 12 weeks of twice-weekly, 55-minute sessions under the supervision of a physical trainer.
• Functional training involved the use of elastic bands to work upper body, lower body, and trunk muscles including the biceps, triceps, back quadriceps, glutes, and hips; the RE used weight machines instead of bands.
• Participants were evaluated at baseline and after 6 and 12 weeks of training sessions; the primary outcome was functional status based on the Health Assessment Questionnaire for the Spondyloarthropathies (HAQ-S).
• Secondary outcomes included the Bath Ankylosing Spondylitis Functional Index (BASFI) to assess functional capacity, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Disease Activity Score in 28 joints (DAS28) to assess disease activity, and the Short Form 36 (SF-36) to measure quality of life.

TAKEAWAY:

• Participants in both groups showed significant improvement from baseline on the primary outcome measure, with no significant differences between the groups on the primary outcome of function or secondary measures of function and disease activity after 12 weeks.
• Significant intragroup changes occurred between times for both groups on the HAQ-S, BASFI, BASDAI, and DAS28 (P = .001, .007, .001, and .001, respectively).
• Improvement in quality of life was significant from baseline and similar between the FT and RE, with the exception of the “social aspects” domain, for which only the FT showed significant improvement.
• No intervention-related adverse events were reported in either group.

IN PRACTICE:

Despite the absence of consensus guidelines on the use and effectiveness of FT and RE, “we can conclude that both FT and RE have similar effectiveness in improving functional capacity, functional status, disease activity, general quality of life, and muscle strength in patients with psoriatic arthritis,” the researchers wrote.

SOURCE:

The study was led by Diego Roger Silva, MD, of the Universidade Federal de São Paulo, Brazil, and published online in Advances in Rheumatology.

LIMITATIONS:

The study population was recruited from outpatient clinics, and the mean age of 52 years was higher than in previous studies; the study also lacked long-term follow-up data.

DISCLOSURES:

The study received no outside funding. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Exercise with weight machines or elastic resistance bands yielded similar improvements in strength and function in adults with psoriatic arthritis (PsA) after 12 weeks.

METHODOLOGY:

• Researchers recruited 41 adults aged 18-65 years with PsA who were then randomized to a functional training group (FT) or a resistance exercise group (RE) for 12 weeks of twice-weekly, 55-minute sessions under the supervision of a physical trainer.
• Functional training involved the use of elastic bands to work upper body, lower body, and trunk muscles including the biceps, triceps, back quadriceps, glutes, and hips; the RE used weight machines instead of bands.
• Participants were evaluated at baseline and after 6 and 12 weeks of training sessions; the primary outcome was functional status based on the Health Assessment Questionnaire for the Spondyloarthropathies (HAQ-S).
• Secondary outcomes included the Bath Ankylosing Spondylitis Functional Index (BASFI) to assess functional capacity, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Disease Activity Score in 28 joints (DAS28) to assess disease activity, and the Short Form 36 (SF-36) to measure quality of life.

TAKEAWAY:

• Participants in both groups showed significant improvement from baseline on the primary outcome measure, with no significant differences between the groups on the primary outcome of function or secondary measures of function and disease activity after 12 weeks.
• Significant intragroup changes occurred between times for both groups on the HAQ-S, BASFI, BASDAI, and DAS28 (P = .001, .007, .001, and .001, respectively).
• Improvement in quality of life was significant from baseline and similar between the FT and RE, with the exception of the “social aspects” domain, for which only the FT showed significant improvement.
• No intervention-related adverse events were reported in either group.

IN PRACTICE:

Despite the absence of consensus guidelines on the use and effectiveness of FT and RE, “we can conclude that both FT and RE have similar effectiveness in improving functional capacity, functional status, disease activity, general quality of life, and muscle strength in patients with psoriatic arthritis,” the researchers wrote.

SOURCE:

The study was led by Diego Roger Silva, MD, of the Universidade Federal de São Paulo, Brazil, and published online in Advances in Rheumatology.

LIMITATIONS:

The study population was recruited from outpatient clinics, and the mean age of 52 years was higher than in previous studies; the study also lacked long-term follow-up data.

DISCLOSURES:

The study received no outside funding. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Adults whose rheumatoid arthritis caused them severe functional limitations showed significant improvement in measures of function and quality of life following at least 1 year of a personalized, supervised exercise program than those who received usual care.

METHODOLOGY:

• Researchers randomized 217 adults with rheumatoid arthritis and severe functional limitations to an active exercise intervention delivered by a physical therapist (PT) or usual care; the mean age of the participants was approximately 59 years, and approximately 90% were female.
• The intervention consisted of individualized goal setting, active exercises adapted to functional limitations, and education about self-management of physical activity in two sessions per week for the first 12 weeks, followed by once weekly sessions with the option for additional sessions if needed. The primary care PTs in the Netherlands who treated the patients were primarily recruited through a national network of PTs with specific expertise regarding rheumatic diseases.
• In considering each participant’s three most limited activities, the study’s primary outcome at 52 weeks measured the change from the one ranked highest at baseline on the Patient-Specific Complaints Numeric Rating Scale (PSC1 NRS); secondary outcomes included changes in the NRS for participants’ second and third most difficult activities, as well as the Patient Reported Outcome Measurement Information System Physical Function-10, the Health Assessment Questionnaire-Disability Index, the Rheumatoid Arthritis Quality of Life Questionnaire, the 36-Item Short-Form Health Survey (SF-36) Physical and Mental Component Summary Scales (PCS and MCS), and the 6-minute walk test.

TAKEAWAY:

• At 52 weeks, the change in PSC1 NRS was significantly greater in the intervention group than in the usual care group, with a mean difference of −1.7 and a between-group effect size from baseline of 0.7.
• Improvements in secondary outcome measures at 52 weeks also were significantly greater in the intervention group than in the usual care group, with the exception of the SF-36 MCS, which showed no difference between the groups.
• A total of 89 participants in the intervention group and 45 participants in the usual care group responded to questions about muscle soreness and fatigue; 70% and 60%, and 71% and 64%, of each group reported these conditions, respectively.

IN PRACTICE:

“The completion of the trial substantiates the feasibility of recruiting and training primary care [physical therapists] to deliver a complex intervention,” although more research is needed to explore long-term outcomes and cost-effectiveness, the researchers wrote.

SOURCE:

The lead author on the study was Max M.H. Teuwen, MSc, a PhD candidate at Leiden University Medical Center, Leiden, the Netherlands. The study was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

The participants were not blinded to their group, and blinded assessors became aware of the allocations, which might have impacted measurements; other limitations included lack of data on medication changes and the exclusion of physical activity amount as an outcome measure.

DISCLOSURES:

The study was supported by the Netherlands Organization for Health Research and Development; the Ministry of Health, Welfare and Sport; the Royal Dutch Society for Physical Therapy; and the Dutch Arthritis Society. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Adults whose rheumatoid arthritis caused them severe functional limitations showed significant improvement in measures of function and quality of life following at least 1 year of a personalized, supervised exercise program than those who received usual care.

METHODOLOGY:

• Researchers randomized 217 adults with rheumatoid arthritis and severe functional limitations to an active exercise intervention delivered by a physical therapist (PT) or usual care; the mean age of the participants was approximately 59 years, and approximately 90% were female.
• The intervention consisted of individualized goal setting, active exercises adapted to functional limitations, and education about self-management of physical activity in two sessions per week for the first 12 weeks, followed by once weekly sessions with the option for additional sessions if needed. The primary care PTs in the Netherlands who treated the patients were primarily recruited through a national network of PTs with specific expertise regarding rheumatic diseases.
• In considering each participant’s three most limited activities, the study’s primary outcome at 52 weeks measured the change from the one ranked highest at baseline on the Patient-Specific Complaints Numeric Rating Scale (PSC1 NRS); secondary outcomes included changes in the NRS for participants’ second and third most difficult activities, as well as the Patient Reported Outcome Measurement Information System Physical Function-10, the Health Assessment Questionnaire-Disability Index, the Rheumatoid Arthritis Quality of Life Questionnaire, the 36-Item Short-Form Health Survey (SF-36) Physical and Mental Component Summary Scales (PCS and MCS), and the 6-minute walk test.

TAKEAWAY:

• At 52 weeks, the change in PSC1 NRS was significantly greater in the intervention group than in the usual care group, with a mean difference of −1.7 and a between-group effect size from baseline of 0.7.
• Improvements in secondary outcome measures at 52 weeks also were significantly greater in the intervention group than in the usual care group, with the exception of the SF-36 MCS, which showed no difference between the groups.
• A total of 89 participants in the intervention group and 45 participants in the usual care group responded to questions about muscle soreness and fatigue; 70% and 60%, and 71% and 64%, of each group reported these conditions, respectively.

IN PRACTICE:

“The completion of the trial substantiates the feasibility of recruiting and training primary care [physical therapists] to deliver a complex intervention,” although more research is needed to explore long-term outcomes and cost-effectiveness, the researchers wrote.

SOURCE:

The lead author on the study was Max M.H. Teuwen, MSc, a PhD candidate at Leiden University Medical Center, Leiden, the Netherlands. The study was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

The participants were not blinded to their group, and blinded assessors became aware of the allocations, which might have impacted measurements; other limitations included lack of data on medication changes and the exclusion of physical activity amount as an outcome measure.

DISCLOSURES:

The study was supported by the Netherlands Organization for Health Research and Development; the Ministry of Health, Welfare and Sport; the Royal Dutch Society for Physical Therapy; and the Dutch Arthritis Society. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Adults whose rheumatoid arthritis caused them severe functional limitations showed significant improvement in measures of function and quality of life following at least 1 year of a personalized, supervised exercise program than those who received usual care.

METHODOLOGY:

• Researchers randomized 217 adults with rheumatoid arthritis and severe functional limitations to an active exercise intervention delivered by a physical therapist (PT) or usual care; the mean age of the participants was approximately 59 years, and approximately 90% were female.
• The intervention consisted of individualized goal setting, active exercises adapted to functional limitations, and education about self-management of physical activity in two sessions per week for the first 12 weeks, followed by once weekly sessions with the option for additional sessions if needed. The primary care PTs in the Netherlands who treated the patients were primarily recruited through a national network of PTs with specific expertise regarding rheumatic diseases.
• In considering each participant’s three most limited activities, the study’s primary outcome at 52 weeks measured the change from the one ranked highest at baseline on the Patient-Specific Complaints Numeric Rating Scale (PSC1 NRS); secondary outcomes included changes in the NRS for participants’ second and third most difficult activities, as well as the Patient Reported Outcome Measurement Information System Physical Function-10, the Health Assessment Questionnaire-Disability Index, the Rheumatoid Arthritis Quality of Life Questionnaire, the 36-Item Short-Form Health Survey (SF-36) Physical and Mental Component Summary Scales (PCS and MCS), and the 6-minute walk test.

TAKEAWAY:

• At 52 weeks, the change in PSC1 NRS was significantly greater in the intervention group than in the usual care group, with a mean difference of −1.7 and a between-group effect size from baseline of 0.7.
• Improvements in secondary outcome measures at 52 weeks also were significantly greater in the intervention group than in the usual care group, with the exception of the SF-36 MCS, which showed no difference between the groups.
• A total of 89 participants in the intervention group and 45 participants in the usual care group responded to questions about muscle soreness and fatigue; 70% and 60%, and 71% and 64%, of each group reported these conditions, respectively.

IN PRACTICE:

“The completion of the trial substantiates the feasibility of recruiting and training primary care [physical therapists] to deliver a complex intervention,” although more research is needed to explore long-term outcomes and cost-effectiveness, the researchers wrote.

SOURCE:

The lead author on the study was Max M.H. Teuwen, MSc, a PhD candidate at Leiden University Medical Center, Leiden, the Netherlands. The study was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

The participants were not blinded to their group, and blinded assessors became aware of the allocations, which might have impacted measurements; other limitations included lack of data on medication changes and the exclusion of physical activity amount as an outcome measure.

DISCLOSURES:

The study was supported by the Netherlands Organization for Health Research and Development; the Ministry of Health, Welfare and Sport; the Royal Dutch Society for Physical Therapy; and the Dutch Arthritis Society. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

A new diagnostic tool can effectively discriminate different rheumatologic conditions and could potentially aid in the diagnosis of early inflammatory arthritis.

The algorithm — called Genetic Probability tool (G-PROB) — uses genetic information to calculate the probability of certain diseases.

University of Manchester

“At such an early stage of disease, it’s not always easy to determine what the final outcome will be with respect to final diagnosis,” said John Bowes, PhD, a senior lecturer in the division of musculoskeletal & dermatological sciences at the University of Manchester in the United Kingdom. He was a senior author of the newest study of G-PROB. “What we are hoping for here is that genetics can help [clinicians] with the decision-making process and hopefully accelerate the correct diagnosis and get individuals onto the correct treatment as early as possible.”
 

Creating the Algorithm

G-PROB was first developed by an international group of scientists with the goal of using genetic risk scores to predict the probabilities of common diagnoses for patients with early signs of arthritis, such as synovitis and joint swelling. According to the study authors, about 80% of these types of patients are eventually diagnosed with the following conditions: Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and gout.

The algorithm combines existing knowledge about single-nucleotide polymorphisms from prior genomic studies to create genetic risk scores — also called polygenic risk score (PRS) — for multiple diseases. Using these scores, the program then calculates the probabilities of certain diagnoses for a patient, based on the assumption that at least one disease was present.

In this first study, researchers trained the tool on simulated data and then tested it in three patient cohorts totaling about 1700 individuals from the Electronic Medical Records and Genomics database and Mass General Brigham Biobank. In the initial study, G-PROB identified a likely diagnosis in 45% of patients, with a positive predictive value (PPV) of 64%. Adding these genetic scores to clinical data improved diagnostic accuracy from 39% to 51%.
 

Validating G-PROB

But data from these biobanks may not necessarily be representative of early arthritis in patients appearing in outpatient clinics, noted Dr. Bowes. In this new study, researchers sought to independently validate the original study’s findings using data from the Norfolk Arthritis Register, a community-based, long-term observational study on inflammatory polyarthritis. The team applied G-PROB in this cohort and then compared the tool’s probabilities for common rheumatic conditions to the final clinician diagnosis.

The study ultimately included 1047 individuals with early inflammatory arthritis with genotype data. In the cohort, more than 70% (756 individuals) were diagnosed with RA. Of the remaining patients, 104 had PsA, 18 had SLE, 16 had AS, and 12 had gout. The research team also added an “other diseases” category to the algorithm. A total of 141 patients fell into this category and were diagnosed with diseases including chronic pain syndrome (52 individuals), polymyalgia rheumatica (29 individuals), and Sjögren’s syndrome (9 individuals).

G-PROB was best at excluding diagnoses: Probabilities under 5% for a single disease corresponded to a negative predictive value (NPV) of 96%. If probabilities for two diseases were both < 5%, the NPV was 94%.

For patients with a single probability above 50%, the tool had a PPV of 70.3%. In 55.7% of all patients, the disease with the highest probability ended up being the final diagnosis.

Generally, PRSs, as well as tests using biomarkers, were better at excluding diagnoses than affirming them, noted Matthew Brown, MBBS, MD, a professor of medicine at King’s College London, who was not involved with the research. If disease prevalence is low, then a test aimed at diagnosis of that disease would be better at excluding a diagnosis than affirming it, he explained.

Queensland University of Technology

Can G-PROB Improve Diagnosis?

The new study’s key contribution was that it independently validated findings from a previous study, noted Katherine Liao, MD, a rheumatologist at Brigham and Women’s Hospital in Boston, Massachusetts. She coauthored an accompanying editorial to the newest study and coauthored the original G-PROB paper.

Dr. Liao

This new study also brought up an important question about G-PROB that has yet to be tested: Will this tool help clinicians make more efficient and accurate diagnoses in practice?

A prospective trial would be necessary to begin answering this question, both Dr. Bowes and Dr. Liao agreed. For example, one clinician group would have access to G-PROB data, while another would not, and “see if that helps [the first group] make the diagnosis faster or more accurately,” Dr. Liao said.

Dr. Bowes was also interested in exploring if combining G-PROB with other clinical data would improve diagnostic performance.

“Genetics isn’t the full story,” he said. Dr. Bowes saw genetics as one additional, complementary tool in a clinician’s toolbox.

Future studies were needed to understand the clinical utility of genetic information in conjunction with current diagnostic practices, such as imaging, physical exams, and lab results, Dr. Liao and her editorial coauthors argued. 

“For example, in cardiovascular disease, the clinical utility of polygenic risk scores has been defined by their ability to improve risk stratification beyond what is already achieved with more common risk factors and measures such as cholesterol levels, smoking status, and coronary calcium scores,” Dr. Liao and her coauthors wrote. “Similarly, a polygenic risk score for breast cancer would not be clinically implemented alone for risk prediction but rather as one risk factor among others, such as hormonal and reproductive factors and prior mammographic data.”
 

Future of Genetics in Rheumatology

An additional hurdle for using tools like G-PROB was that a patient must have undergone DNA sequencing, and these data must be available to clinicians. Even a decade ago, this type of testing may have seemed unrealistic to incorporate in daily practice, Dr. Liao noted, but technological advancements continue to make genetic sequencing more accessible to the public.

There are already efforts in the United Kingdom to incorporate genetics into healthcare, including trials for PRSs and heart disease, noted Dr. Bowes, as well as large-scale studies such as Our Future Health.

“As these population-based studies expand more, a high proportion of individuals should hopefully have access to this kind of data,” he said.

Brown added that genetic testing is already used to make rheumatology diagnoses.

“[HLA] B-27 testing, for example, is an extremely commonly used test to assist in the diagnosis of ankylosing spondylitis. Is it that different to change to a PRS as opposed to a straight HLA testing? I don’t think it is,” he said.

While there would need to be systematic training for clinicians to understand how to calculate and use PRSs in daily practice, Dr. Brown did not think this adjustment would be too difficult.

“There is a lot of exceptionalism about genetics, which is actually inappropriate,” he said. “This is actually just a quantitative score that should be easy for people to interpret.”

Dr. Bowes and Dr. Brown reported no relevant financial relationships. Dr. Liao worked as a consultant for UCB.

A version of this article appeared on Medscape.com.

A new diagnostic tool can effectively discriminate different rheumatologic conditions and could potentially aid in the diagnosis of early inflammatory arthritis.

The algorithm — called Genetic Probability tool (G-PROB) — uses genetic information to calculate the probability of certain diseases.

University of Manchester

“At such an early stage of disease, it’s not always easy to determine what the final outcome will be with respect to final diagnosis,” said John Bowes, PhD, a senior lecturer in the division of musculoskeletal & dermatological sciences at the University of Manchester in the United Kingdom. He was a senior author of the newest study of G-PROB. “What we are hoping for here is that genetics can help [clinicians] with the decision-making process and hopefully accelerate the correct diagnosis and get individuals onto the correct treatment as early as possible.”
 

Creating the Algorithm

G-PROB was first developed by an international group of scientists with the goal of using genetic risk scores to predict the probabilities of common diagnoses for patients with early signs of arthritis, such as synovitis and joint swelling. According to the study authors, about 80% of these types of patients are eventually diagnosed with the following conditions: Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and gout.

The algorithm combines existing knowledge about single-nucleotide polymorphisms from prior genomic studies to create genetic risk scores — also called polygenic risk score (PRS) — for multiple diseases. Using these scores, the program then calculates the probabilities of certain diagnoses for a patient, based on the assumption that at least one disease was present.

In this first study, researchers trained the tool on simulated data and then tested it in three patient cohorts totaling about 1700 individuals from the Electronic Medical Records and Genomics database and Mass General Brigham Biobank. In the initial study, G-PROB identified a likely diagnosis in 45% of patients, with a positive predictive value (PPV) of 64%. Adding these genetic scores to clinical data improved diagnostic accuracy from 39% to 51%.
 

Validating G-PROB

But data from these biobanks may not necessarily be representative of early arthritis in patients appearing in outpatient clinics, noted Dr. Bowes. In this new study, researchers sought to independently validate the original study’s findings using data from the Norfolk Arthritis Register, a community-based, long-term observational study on inflammatory polyarthritis. The team applied G-PROB in this cohort and then compared the tool’s probabilities for common rheumatic conditions to the final clinician diagnosis.

The study ultimately included 1047 individuals with early inflammatory arthritis with genotype data. In the cohort, more than 70% (756 individuals) were diagnosed with RA. Of the remaining patients, 104 had PsA, 18 had SLE, 16 had AS, and 12 had gout. The research team also added an “other diseases” category to the algorithm. A total of 141 patients fell into this category and were diagnosed with diseases including chronic pain syndrome (52 individuals), polymyalgia rheumatica (29 individuals), and Sjögren’s syndrome (9 individuals).

G-PROB was best at excluding diagnoses: Probabilities under 5% for a single disease corresponded to a negative predictive value (NPV) of 96%. If probabilities for two diseases were both < 5%, the NPV was 94%.

For patients with a single probability above 50%, the tool had a PPV of 70.3%. In 55.7% of all patients, the disease with the highest probability ended up being the final diagnosis.

Generally, PRSs, as well as tests using biomarkers, were better at excluding diagnoses than affirming them, noted Matthew Brown, MBBS, MD, a professor of medicine at King’s College London, who was not involved with the research. If disease prevalence is low, then a test aimed at diagnosis of that disease would be better at excluding a diagnosis than affirming it, he explained.

Queensland University of Technology

Can G-PROB Improve Diagnosis?

The new study’s key contribution was that it independently validated findings from a previous study, noted Katherine Liao, MD, a rheumatologist at Brigham and Women’s Hospital in Boston, Massachusetts. She coauthored an accompanying editorial to the newest study and coauthored the original G-PROB paper.

Dr. Liao

This new study also brought up an important question about G-PROB that has yet to be tested: Will this tool help clinicians make more efficient and accurate diagnoses in practice?

A prospective trial would be necessary to begin answering this question, both Dr. Bowes and Dr. Liao agreed. For example, one clinician group would have access to G-PROB data, while another would not, and “see if that helps [the first group] make the diagnosis faster or more accurately,” Dr. Liao said.

Dr. Bowes was also interested in exploring if combining G-PROB with other clinical data would improve diagnostic performance.

“Genetics isn’t the full story,” he said. Dr. Bowes saw genetics as one additional, complementary tool in a clinician’s toolbox.

Future studies were needed to understand the clinical utility of genetic information in conjunction with current diagnostic practices, such as imaging, physical exams, and lab results, Dr. Liao and her editorial coauthors argued. 

“For example, in cardiovascular disease, the clinical utility of polygenic risk scores has been defined by their ability to improve risk stratification beyond what is already achieved with more common risk factors and measures such as cholesterol levels, smoking status, and coronary calcium scores,” Dr. Liao and her coauthors wrote. “Similarly, a polygenic risk score for breast cancer would not be clinically implemented alone for risk prediction but rather as one risk factor among others, such as hormonal and reproductive factors and prior mammographic data.”
 

Future of Genetics in Rheumatology

An additional hurdle for using tools like G-PROB was that a patient must have undergone DNA sequencing, and these data must be available to clinicians. Even a decade ago, this type of testing may have seemed unrealistic to incorporate in daily practice, Dr. Liao noted, but technological advancements continue to make genetic sequencing more accessible to the public.

There are already efforts in the United Kingdom to incorporate genetics into healthcare, including trials for PRSs and heart disease, noted Dr. Bowes, as well as large-scale studies such as Our Future Health.

“As these population-based studies expand more, a high proportion of individuals should hopefully have access to this kind of data,” he said.

Brown added that genetic testing is already used to make rheumatology diagnoses.

“[HLA] B-27 testing, for example, is an extremely commonly used test to assist in the diagnosis of ankylosing spondylitis. Is it that different to change to a PRS as opposed to a straight HLA testing? I don’t think it is,” he said.

While there would need to be systematic training for clinicians to understand how to calculate and use PRSs in daily practice, Dr. Brown did not think this adjustment would be too difficult.

“There is a lot of exceptionalism about genetics, which is actually inappropriate,” he said. “This is actually just a quantitative score that should be easy for people to interpret.”

Dr. Bowes and Dr. Brown reported no relevant financial relationships. Dr. Liao worked as a consultant for UCB.

A version of this article appeared on Medscape.com.

A new diagnostic tool can effectively discriminate different rheumatologic conditions and could potentially aid in the diagnosis of early inflammatory arthritis.

The algorithm — called Genetic Probability tool (G-PROB) — uses genetic information to calculate the probability of certain diseases.

University of Manchester

“At such an early stage of disease, it’s not always easy to determine what the final outcome will be with respect to final diagnosis,” said John Bowes, PhD, a senior lecturer in the division of musculoskeletal & dermatological sciences at the University of Manchester in the United Kingdom. He was a senior author of the newest study of G-PROB. “What we are hoping for here is that genetics can help [clinicians] with the decision-making process and hopefully accelerate the correct diagnosis and get individuals onto the correct treatment as early as possible.”
 

Creating the Algorithm

G-PROB was first developed by an international group of scientists with the goal of using genetic risk scores to predict the probabilities of common diagnoses for patients with early signs of arthritis, such as synovitis and joint swelling. According to the study authors, about 80% of these types of patients are eventually diagnosed with the following conditions: Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and gout.

The algorithm combines existing knowledge about single-nucleotide polymorphisms from prior genomic studies to create genetic risk scores — also called polygenic risk score (PRS) — for multiple diseases. Using these scores, the program then calculates the probabilities of certain diagnoses for a patient, based on the assumption that at least one disease was present.

In this first study, researchers trained the tool on simulated data and then tested it in three patient cohorts totaling about 1700 individuals from the Electronic Medical Records and Genomics database and Mass General Brigham Biobank. In the initial study, G-PROB identified a likely diagnosis in 45% of patients, with a positive predictive value (PPV) of 64%. Adding these genetic scores to clinical data improved diagnostic accuracy from 39% to 51%.
 

Validating G-PROB

But data from these biobanks may not necessarily be representative of early arthritis in patients appearing in outpatient clinics, noted Dr. Bowes. In this new study, researchers sought to independently validate the original study’s findings using data from the Norfolk Arthritis Register, a community-based, long-term observational study on inflammatory polyarthritis. The team applied G-PROB in this cohort and then compared the tool’s probabilities for common rheumatic conditions to the final clinician diagnosis.

The study ultimately included 1047 individuals with early inflammatory arthritis with genotype data. In the cohort, more than 70% (756 individuals) were diagnosed with RA. Of the remaining patients, 104 had PsA, 18 had SLE, 16 had AS, and 12 had gout. The research team also added an “other diseases” category to the algorithm. A total of 141 patients fell into this category and were diagnosed with diseases including chronic pain syndrome (52 individuals), polymyalgia rheumatica (29 individuals), and Sjögren’s syndrome (9 individuals).

G-PROB was best at excluding diagnoses: Probabilities under 5% for a single disease corresponded to a negative predictive value (NPV) of 96%. If probabilities for two diseases were both < 5%, the NPV was 94%.

For patients with a single probability above 50%, the tool had a PPV of 70.3%. In 55.7% of all patients, the disease with the highest probability ended up being the final diagnosis.

Generally, PRSs, as well as tests using biomarkers, were better at excluding diagnoses than affirming them, noted Matthew Brown, MBBS, MD, a professor of medicine at King’s College London, who was not involved with the research. If disease prevalence is low, then a test aimed at diagnosis of that disease would be better at excluding a diagnosis than affirming it, he explained.

Queensland University of Technology

Can G-PROB Improve Diagnosis?

The new study’s key contribution was that it independently validated findings from a previous study, noted Katherine Liao, MD, a rheumatologist at Brigham and Women’s Hospital in Boston, Massachusetts. She coauthored an accompanying editorial to the newest study and coauthored the original G-PROB paper.

Dr. Liao

This new study also brought up an important question about G-PROB that has yet to be tested: Will this tool help clinicians make more efficient and accurate diagnoses in practice?

A prospective trial would be necessary to begin answering this question, both Dr. Bowes and Dr. Liao agreed. For example, one clinician group would have access to G-PROB data, while another would not, and “see if that helps [the first group] make the diagnosis faster or more accurately,” Dr. Liao said.

Dr. Bowes was also interested in exploring if combining G-PROB with other clinical data would improve diagnostic performance.

“Genetics isn’t the full story,” he said. Dr. Bowes saw genetics as one additional, complementary tool in a clinician’s toolbox.

Future studies were needed to understand the clinical utility of genetic information in conjunction with current diagnostic practices, such as imaging, physical exams, and lab results, Dr. Liao and her editorial coauthors argued. 

“For example, in cardiovascular disease, the clinical utility of polygenic risk scores has been defined by their ability to improve risk stratification beyond what is already achieved with more common risk factors and measures such as cholesterol levels, smoking status, and coronary calcium scores,” Dr. Liao and her coauthors wrote. “Similarly, a polygenic risk score for breast cancer would not be clinically implemented alone for risk prediction but rather as one risk factor among others, such as hormonal and reproductive factors and prior mammographic data.”
 

Future of Genetics in Rheumatology

An additional hurdle for using tools like G-PROB was that a patient must have undergone DNA sequencing, and these data must be available to clinicians. Even a decade ago, this type of testing may have seemed unrealistic to incorporate in daily practice, Dr. Liao noted, but technological advancements continue to make genetic sequencing more accessible to the public.

There are already efforts in the United Kingdom to incorporate genetics into healthcare, including trials for PRSs and heart disease, noted Dr. Bowes, as well as large-scale studies such as Our Future Health.

“As these population-based studies expand more, a high proportion of individuals should hopefully have access to this kind of data,” he said.

Brown added that genetic testing is already used to make rheumatology diagnoses.

“[HLA] B-27 testing, for example, is an extremely commonly used test to assist in the diagnosis of ankylosing spondylitis. Is it that different to change to a PRS as opposed to a straight HLA testing? I don’t think it is,” he said.

While there would need to be systematic training for clinicians to understand how to calculate and use PRSs in daily practice, Dr. Brown did not think this adjustment would be too difficult.

“There is a lot of exceptionalism about genetics, which is actually inappropriate,” he said. “This is actually just a quantitative score that should be easy for people to interpret.”

Dr. Bowes and Dr. Brown reported no relevant financial relationships. Dr. Liao worked as a consultant for UCB.

A version of this article appeared on Medscape.com.

It’s an appealing concept: Stop addictive behaviors for a while — think social media, video games, gambling, porn, junk food, drugs, alcohol (dry January, anyone?) — to reset your brain’s reward circuitry, so you can feel great minus the bad habits.

People call it dopamine fasting, abstinence sampling, or dopamine detox. But is shutting off the rush of that feel-good neurotransmitter really the key to kicking addictions?

TikTok influencers and Silicon Valley execs seem to think so. But so do some physicians.

Prominent among the proponents is Anna Lembke, MD, professor of psychiatry at Stanford University School of Medicine and chief of the Stanford Addiction Medicine Dual Diagnosis Clinic. There, the dopamine fast is an early intervention framework for many of her patients.

“What we have seen in those patients is that not only does craving begin to subside in about 4 weeks, but that mood and anxiety and sleep and all these other parameters and markers of good mental health also improve,” Dr. Lembke said.

Any clinician, regardless of background, can adopt this framework, the Dopamine Nation author said during her talk at the American College of Lifestyle Medicine (ACLM) conference last fall. “There is this idea in medicine that we have to leave addiction to the Betty Ford Clinic or to an addiction psychiatrist,” she told the gathering. “But there’s so much that we can do, no matter what our training and no matter our treatment setting.”  

But is dopamine fasting right for your patients? Some experts said it’s an oversimplified or even dangerous approach. Here’s what to know.

Dopamine and the Brain

From the prefrontal cortex — your brain’s control center — to the nucleus accumbens and ventral tegmental area located deep in your limbic system, dopamine bridges gaps between neurons to deliver critical messages about pleasure, reward, and motivation. 

We all have a baseline level of dopamine. Substances and behaviors we like — everything from chocolate and sex to cocaine and amphetamines — increase dopamine firing. 

“When we seek healthy rewards, like a good meal out in a restaurant or having a nice chat with friends, dopaminergic neurons fire, and dopamine is released,” said Birgitta Dresp, PhD, a cognitive psychologist and research director with the Centre National de la Recherche Scientifique in Paris. “That gives us a good feeling.”

But over time, with chronic exposure to hyperpleasurable stimuli, your brain adapts. Dopamine receptors downregulate and shrink, and your “hedonic setpoint,” or baseline happiness level, drops. You now need more of your favorite stimuli to feel as good as you did before.

This primitive brain wiring served evolutionary purposes, helping our ancestors relentlessly pursue scarce resources like food. But in our modern world full of easily accessible, novel, potent, and stimulating activities, our brains are constantly trying to compensate. Paradoxically, this constant “self-titillation” may be contributing to our national and global mental health crisis, Dr. Lembke suggested.

“Human activity has changed the world we live in,” said Dr. Lembke, “and now this ancient mechanistic structure has become a liability of sorts.”

The Dopamine Fast in Action

To reset this wiring, Dr. Lembke recommended a 4-week fast from a person’s “drug of choice.” But this isn’t the trendy tech-bro quick cure-all where you abstain from everything that brings you joy. It’s a targeted intervention usually aimed at one behavior or substance at a time. The fast allows a person to understand “the nature of the hijacked brain,” and breaking free motivates them to change habits long term, said Dr. Lembke.

Although the first 2 weeks are difficult, she found that many patients feel better and more motivated after 4 weeks.

How do you identify patients who might benefit from a dopamine fast? Start with “how much” and proceed to “why.” Instead of asking how much of a substance or behavior they indulge in per week, which can be inaccurate, Dr. Lembke uses a “timeline follow-back” technique — how much yesterday, the day before that, and so on. This can lead to an “aha” moment when they see the week’s true total, she told the ACLM conference.  

She also explored why they do it. Often patients say they are self-medicating or that the substance helps with their anxiety or depression. When people are compulsively continuing to use despite negative consequences, she might recommend a 4-week reset.

Important exceptions: Dr. Lembke did not recommend dopamine fasting to anyone who has repeatedly and unsuccessfully tried to quit a drug on their own nor anyone for whom withdrawal is life-threatening.

For people who can safely try the dopamine fast, she recommended “self-binding” strategies to help them stay the course. Consider the people, places, and things that encourage you to use, and try to avoid them. For example, delete your social media apps if you’re trying to detox from social media. Put physical distance between you and your phone. For foods and substances, keep them out of the house. 

Dr. Lembke also recommended “hormesis,” painful but productive activities like exercise. Your brain’s system for pleasure and pain are closely related, so these activities affect reward circuitry.

“You’re intentionally doing things that are hard, which doesn’t initially release dopamine, in contrast to intoxicants, but you get a gradual increase that remains elevated even after that activity is stopped, which is a nice way to get dopamine indirectly,” she said.

If patients plan to resume their “drug of choice” after the dopamine fast, Dr. Lembke helps them plan how much they will consume and when. For some, this works. Others, unfortunately, go back to using as much or more than they did before. But in many cases, she said, patients feel better and find that their “drug of choice” wasn’t serving them as well as they thought. 

Critiques of Dopamine Fasting

Dopamine fasting isn’t for everyone, and experts debate its safety and effectiveness. Here are some common concerns: 

It’s too simplistic. Peter Grinspoon, MD, a primary care physician at Massachusetts General Hospital and instructor at Harvard Medical School, said dopamine fasting isn’t really fasting — you don’t have a finite store of dopamine to conserve or deplete in a fixed amount of time. Even if you abstain from certain pleasures, your brain will still produce some dopamine.

What makes more sense, he said, is gradual “dopamine retargeting,” seeking rewards from healthy pleasurable activities.

“Addiction is a disease of isolation, and learning to take pleasure in the healthy things in life, like a nice home-cooked meal or a walk in the woods or a hug or a swim in the ocean, is exactly what addiction recovery is about,” he said. “Because once you learn to do that and to be happy, there’s no longer any room for the drug and you’re not nearly as susceptible to relapse.”

A related concern is that the dopamine system isn’t the only part of your brain that matters in addiction. “There are other bits of the brain which are much more important for controlling temptation,” said Trevor W. Robbins, PhD, professor of cognitive neuroscience and director of research at the Behavioural and Clinical Neuroscience Institute at the University of Cambridge. Dopamine plays an important role in addiction and recovery, “but to call this a dopamine fast, it’s just a trendy saying to make it sound exciting,” he said.

Empirical evidence is lacking. Without clinical trials to back it up, dopamine fasting lacks evidence on safety and effectiveness, said David Tzall, PsyD, a psychologist practicing in Brooklyn. “It sounds kind of fun, right? To think like, oh, I’ll just stop doing this for a while, and my body will correct itself,” said Dr. Tzall. “I think that’s a very dangerous thing because we don’t have enough evidence on it to think of how it can be effective or how it can be dangerous.”

Dr. Lembke “would like to see more evidence, too,” beyond clinical observation and expert consensus. Future research could also reveal who is most likely to benefit and how long the fast should last for maximum benefit.

It’s too much a one-size-fits-all approach. “Stopping a drug of choice is going to look different for a lot of people,” said Dr. Tzall. Some people can quit smoking cold turkey; others need to phase it out. Some need nicotine patches; some don’t. Some can do it alone; others need help. 

The individual’s why behind addiction is also crucial. Without their drug or habit, can they “cope with the stressors of life?” Dr. Tzall asked. They may need new strategies. And if they quit before they are ready and fail, they could end up feeling even worse than they did before.

Experts do agree on one thing: We can do more to help people who are struggling. “It’s very good that people are having discussions around tempering consumption because we clearly have a serious drug and alcohol addiction, obesity, and digital media problem,” said Dr. Lembke.

A version of this article appeared on Medscape.com.

It’s an appealing concept: Stop addictive behaviors for a while — think social media, video games, gambling, porn, junk food, drugs, alcohol (dry January, anyone?) — to reset your brain’s reward circuitry, so you can feel great minus the bad habits.

People call it dopamine fasting, abstinence sampling, or dopamine detox. But is shutting off the rush of that feel-good neurotransmitter really the key to kicking addictions?

TikTok influencers and Silicon Valley execs seem to think so. But so do some physicians.

Prominent among the proponents is Anna Lembke, MD, professor of psychiatry at Stanford University School of Medicine and chief of the Stanford Addiction Medicine Dual Diagnosis Clinic. There, the dopamine fast is an early intervention framework for many of her patients.

“What we have seen in those patients is that not only does craving begin to subside in about 4 weeks, but that mood and anxiety and sleep and all these other parameters and markers of good mental health also improve,” Dr. Lembke said.

Any clinician, regardless of background, can adopt this framework, the Dopamine Nation author said during her talk at the American College of Lifestyle Medicine (ACLM) conference last fall. “There is this idea in medicine that we have to leave addiction to the Betty Ford Clinic or to an addiction psychiatrist,” she told the gathering. “But there’s so much that we can do, no matter what our training and no matter our treatment setting.”  

But is dopamine fasting right for your patients? Some experts said it’s an oversimplified or even dangerous approach. Here’s what to know.

Dopamine and the Brain

From the prefrontal cortex — your brain’s control center — to the nucleus accumbens and ventral tegmental area located deep in your limbic system, dopamine bridges gaps between neurons to deliver critical messages about pleasure, reward, and motivation. 

We all have a baseline level of dopamine. Substances and behaviors we like — everything from chocolate and sex to cocaine and amphetamines — increase dopamine firing. 

“When we seek healthy rewards, like a good meal out in a restaurant or having a nice chat with friends, dopaminergic neurons fire, and dopamine is released,” said Birgitta Dresp, PhD, a cognitive psychologist and research director with the Centre National de la Recherche Scientifique in Paris. “That gives us a good feeling.”

But over time, with chronic exposure to hyperpleasurable stimuli, your brain adapts. Dopamine receptors downregulate and shrink, and your “hedonic setpoint,” or baseline happiness level, drops. You now need more of your favorite stimuli to feel as good as you did before.

This primitive brain wiring served evolutionary purposes, helping our ancestors relentlessly pursue scarce resources like food. But in our modern world full of easily accessible, novel, potent, and stimulating activities, our brains are constantly trying to compensate. Paradoxically, this constant “self-titillation” may be contributing to our national and global mental health crisis, Dr. Lembke suggested.

“Human activity has changed the world we live in,” said Dr. Lembke, “and now this ancient mechanistic structure has become a liability of sorts.”

The Dopamine Fast in Action

To reset this wiring, Dr. Lembke recommended a 4-week fast from a person’s “drug of choice.” But this isn’t the trendy tech-bro quick cure-all where you abstain from everything that brings you joy. It’s a targeted intervention usually aimed at one behavior or substance at a time. The fast allows a person to understand “the nature of the hijacked brain,” and breaking free motivates them to change habits long term, said Dr. Lembke.

Although the first 2 weeks are difficult, she found that many patients feel better and more motivated after 4 weeks.

How do you identify patients who might benefit from a dopamine fast? Start with “how much” and proceed to “why.” Instead of asking how much of a substance or behavior they indulge in per week, which can be inaccurate, Dr. Lembke uses a “timeline follow-back” technique — how much yesterday, the day before that, and so on. This can lead to an “aha” moment when they see the week’s true total, she told the ACLM conference.  

She also explored why they do it. Often patients say they are self-medicating or that the substance helps with their anxiety or depression. When people are compulsively continuing to use despite negative consequences, she might recommend a 4-week reset.

Important exceptions: Dr. Lembke did not recommend dopamine fasting to anyone who has repeatedly and unsuccessfully tried to quit a drug on their own nor anyone for whom withdrawal is life-threatening.

For people who can safely try the dopamine fast, she recommended “self-binding” strategies to help them stay the course. Consider the people, places, and things that encourage you to use, and try to avoid them. For example, delete your social media apps if you’re trying to detox from social media. Put physical distance between you and your phone. For foods and substances, keep them out of the house. 

Dr. Lembke also recommended “hormesis,” painful but productive activities like exercise. Your brain’s system for pleasure and pain are closely related, so these activities affect reward circuitry.

“You’re intentionally doing things that are hard, which doesn’t initially release dopamine, in contrast to intoxicants, but you get a gradual increase that remains elevated even after that activity is stopped, which is a nice way to get dopamine indirectly,” she said.

If patients plan to resume their “drug of choice” after the dopamine fast, Dr. Lembke helps them plan how much they will consume and when. For some, this works. Others, unfortunately, go back to using as much or more than they did before. But in many cases, she said, patients feel better and find that their “drug of choice” wasn’t serving them as well as they thought. 

Critiques of Dopamine Fasting

Dopamine fasting isn’t for everyone, and experts debate its safety and effectiveness. Here are some common concerns: 

It’s too simplistic. Peter Grinspoon, MD, a primary care physician at Massachusetts General Hospital and instructor at Harvard Medical School, said dopamine fasting isn’t really fasting — you don’t have a finite store of dopamine to conserve or deplete in a fixed amount of time. Even if you abstain from certain pleasures, your brain will still produce some dopamine.

What makes more sense, he said, is gradual “dopamine retargeting,” seeking rewards from healthy pleasurable activities.

“Addiction is a disease of isolation, and learning to take pleasure in the healthy things in life, like a nice home-cooked meal or a walk in the woods or a hug or a swim in the ocean, is exactly what addiction recovery is about,” he said. “Because once you learn to do that and to be happy, there’s no longer any room for the drug and you’re not nearly as susceptible to relapse.”

A related concern is that the dopamine system isn’t the only part of your brain that matters in addiction. “There are other bits of the brain which are much more important for controlling temptation,” said Trevor W. Robbins, PhD, professor of cognitive neuroscience and director of research at the Behavioural and Clinical Neuroscience Institute at the University of Cambridge. Dopamine plays an important role in addiction and recovery, “but to call this a dopamine fast, it’s just a trendy saying to make it sound exciting,” he said.

Empirical evidence is lacking. Without clinical trials to back it up, dopamine fasting lacks evidence on safety and effectiveness, said David Tzall, PsyD, a psychologist practicing in Brooklyn. “It sounds kind of fun, right? To think like, oh, I’ll just stop doing this for a while, and my body will correct itself,” said Dr. Tzall. “I think that’s a very dangerous thing because we don’t have enough evidence on it to think of how it can be effective or how it can be dangerous.”

Dr. Lembke “would like to see more evidence, too,” beyond clinical observation and expert consensus. Future research could also reveal who is most likely to benefit and how long the fast should last for maximum benefit.

It’s too much a one-size-fits-all approach. “Stopping a drug of choice is going to look different for a lot of people,” said Dr. Tzall. Some people can quit smoking cold turkey; others need to phase it out. Some need nicotine patches; some don’t. Some can do it alone; others need help. 

The individual’s why behind addiction is also crucial. Without their drug or habit, can they “cope with the stressors of life?” Dr. Tzall asked. They may need new strategies. And if they quit before they are ready and fail, they could end up feeling even worse than they did before.

Experts do agree on one thing: We can do more to help people who are struggling. “It’s very good that people are having discussions around tempering consumption because we clearly have a serious drug and alcohol addiction, obesity, and digital media problem,” said Dr. Lembke.

A version of this article appeared on Medscape.com.

It’s an appealing concept: Stop addictive behaviors for a while — think social media, video games, gambling, porn, junk food, drugs, alcohol (dry January, anyone?) — to reset your brain’s reward circuitry, so you can feel great minus the bad habits.

People call it dopamine fasting, abstinence sampling, or dopamine detox. But is shutting off the rush of that feel-good neurotransmitter really the key to kicking addictions?

TikTok influencers and Silicon Valley execs seem to think so. But so do some physicians.

Prominent among the proponents is Anna Lembke, MD, professor of psychiatry at Stanford University School of Medicine and chief of the Stanford Addiction Medicine Dual Diagnosis Clinic. There, the dopamine fast is an early intervention framework for many of her patients.

“What we have seen in those patients is that not only does craving begin to subside in about 4 weeks, but that mood and anxiety and sleep and all these other parameters and markers of good mental health also improve,” Dr. Lembke said.

Any clinician, regardless of background, can adopt this framework, the Dopamine Nation author said during her talk at the American College of Lifestyle Medicine (ACLM) conference last fall. “There is this idea in medicine that we have to leave addiction to the Betty Ford Clinic or to an addiction psychiatrist,” she told the gathering. “But there’s so much that we can do, no matter what our training and no matter our treatment setting.”  

But is dopamine fasting right for your patients? Some experts said it’s an oversimplified or even dangerous approach. Here’s what to know.

Dopamine and the Brain

From the prefrontal cortex — your brain’s control center — to the nucleus accumbens and ventral tegmental area located deep in your limbic system, dopamine bridges gaps between neurons to deliver critical messages about pleasure, reward, and motivation. 

We all have a baseline level of dopamine. Substances and behaviors we like — everything from chocolate and sex to cocaine and amphetamines — increase dopamine firing. 

“When we seek healthy rewards, like a good meal out in a restaurant or having a nice chat with friends, dopaminergic neurons fire, and dopamine is released,” said Birgitta Dresp, PhD, a cognitive psychologist and research director with the Centre National de la Recherche Scientifique in Paris. “That gives us a good feeling.”

But over time, with chronic exposure to hyperpleasurable stimuli, your brain adapts. Dopamine receptors downregulate and shrink, and your “hedonic setpoint,” or baseline happiness level, drops. You now need more of your favorite stimuli to feel as good as you did before.

This primitive brain wiring served evolutionary purposes, helping our ancestors relentlessly pursue scarce resources like food. But in our modern world full of easily accessible, novel, potent, and stimulating activities, our brains are constantly trying to compensate. Paradoxically, this constant “self-titillation” may be contributing to our national and global mental health crisis, Dr. Lembke suggested.

“Human activity has changed the world we live in,” said Dr. Lembke, “and now this ancient mechanistic structure has become a liability of sorts.”

The Dopamine Fast in Action

To reset this wiring, Dr. Lembke recommended a 4-week fast from a person’s “drug of choice.” But this isn’t the trendy tech-bro quick cure-all where you abstain from everything that brings you joy. It’s a targeted intervention usually aimed at one behavior or substance at a time. The fast allows a person to understand “the nature of the hijacked brain,” and breaking free motivates them to change habits long term, said Dr. Lembke.

Although the first 2 weeks are difficult, she found that many patients feel better and more motivated after 4 weeks.

How do you identify patients who might benefit from a dopamine fast? Start with “how much” and proceed to “why.” Instead of asking how much of a substance or behavior they indulge in per week, which can be inaccurate, Dr. Lembke uses a “timeline follow-back” technique — how much yesterday, the day before that, and so on. This can lead to an “aha” moment when they see the week’s true total, she told the ACLM conference.  

She also explored why they do it. Often patients say they are self-medicating or that the substance helps with their anxiety or depression. When people are compulsively continuing to use despite negative consequences, she might recommend a 4-week reset.

Important exceptions: Dr. Lembke did not recommend dopamine fasting to anyone who has repeatedly and unsuccessfully tried to quit a drug on their own nor anyone for whom withdrawal is life-threatening.

For people who can safely try the dopamine fast, she recommended “self-binding” strategies to help them stay the course. Consider the people, places, and things that encourage you to use, and try to avoid them. For example, delete your social media apps if you’re trying to detox from social media. Put physical distance between you and your phone. For foods and substances, keep them out of the house. 

Dr. Lembke also recommended “hormesis,” painful but productive activities like exercise. Your brain’s system for pleasure and pain are closely related, so these activities affect reward circuitry.

“You’re intentionally doing things that are hard, which doesn’t initially release dopamine, in contrast to intoxicants, but you get a gradual increase that remains elevated even after that activity is stopped, which is a nice way to get dopamine indirectly,” she said.

If patients plan to resume their “drug of choice” after the dopamine fast, Dr. Lembke helps them plan how much they will consume and when. For some, this works. Others, unfortunately, go back to using as much or more than they did before. But in many cases, she said, patients feel better and find that their “drug of choice” wasn’t serving them as well as they thought. 

Critiques of Dopamine Fasting

Dopamine fasting isn’t for everyone, and experts debate its safety and effectiveness. Here are some common concerns: 

It’s too simplistic. Peter Grinspoon, MD, a primary care physician at Massachusetts General Hospital and instructor at Harvard Medical School, said dopamine fasting isn’t really fasting — you don’t have a finite store of dopamine to conserve or deplete in a fixed amount of time. Even if you abstain from certain pleasures, your brain will still produce some dopamine.

What makes more sense, he said, is gradual “dopamine retargeting,” seeking rewards from healthy pleasurable activities.

“Addiction is a disease of isolation, and learning to take pleasure in the healthy things in life, like a nice home-cooked meal or a walk in the woods or a hug or a swim in the ocean, is exactly what addiction recovery is about,” he said. “Because once you learn to do that and to be happy, there’s no longer any room for the drug and you’re not nearly as susceptible to relapse.”

A related concern is that the dopamine system isn’t the only part of your brain that matters in addiction. “There are other bits of the brain which are much more important for controlling temptation,” said Trevor W. Robbins, PhD, professor of cognitive neuroscience and director of research at the Behavioural and Clinical Neuroscience Institute at the University of Cambridge. Dopamine plays an important role in addiction and recovery, “but to call this a dopamine fast, it’s just a trendy saying to make it sound exciting,” he said.

Empirical evidence is lacking. Without clinical trials to back it up, dopamine fasting lacks evidence on safety and effectiveness, said David Tzall, PsyD, a psychologist practicing in Brooklyn. “It sounds kind of fun, right? To think like, oh, I’ll just stop doing this for a while, and my body will correct itself,” said Dr. Tzall. “I think that’s a very dangerous thing because we don’t have enough evidence on it to think of how it can be effective or how it can be dangerous.”

Dr. Lembke “would like to see more evidence, too,” beyond clinical observation and expert consensus. Future research could also reveal who is most likely to benefit and how long the fast should last for maximum benefit.

It’s too much a one-size-fits-all approach. “Stopping a drug of choice is going to look different for a lot of people,” said Dr. Tzall. Some people can quit smoking cold turkey; others need to phase it out. Some need nicotine patches; some don’t. Some can do it alone; others need help. 

The individual’s why behind addiction is also crucial. Without their drug or habit, can they “cope with the stressors of life?” Dr. Tzall asked. They may need new strategies. And if they quit before they are ready and fail, they could end up feeling even worse than they did before.

Experts do agree on one thing: We can do more to help people who are struggling. “It’s very good that people are having discussions around tempering consumption because we clearly have a serious drug and alcohol addiction, obesity, and digital media problem,” said Dr. Lembke.

A version of this article appeared on Medscape.com.

TOPLINE:

A combination of remote, supervised aerobic training, resistance training, and a hypocaloric diet significantly improved cardiovascular risk factors in adults with rheumatoid arthritis (RA) and overweight or obesity.

METHODOLOGY:

• The researchers recruited 24 adults aged 60-80 years with RA who met criteria for overweight or obesity; participants were randomized to a Supervised Weight Loss and Exercise Training (SWET) or Counseling Health as Treatment (CHAT) program for 16 weeks.
• The SWET intervention included remote supervision of aerobic training of 150 minutes/week moderate-to-vigorous intensity, 2 days per week of resistance training, and a hypocaloric diet based on a weight loss goal of 7% of body weight. The CHAT patients served as controls and completed two lifestyle counseling sessions followed by monthly check-ins.
• The primary outcome was change in a composite measure of cardiovascular risk based on metabolic syndrome z-score (MSSc), a continuous weighted score of five metabolic syndrome components: Waist circumference, mean arterial blood pressure, fasting glucose, triglycerides, and high-density lipoprotein cholesterol.

TAKEAWAY:

• Both groups showed improvement in the primary outcome of MSSc, with absolute changes from baseline of −1.67 for the SWET group and −1.34 for the CHAT group (P < .01 for both).
• Participants in the SWET group showed significantly more improvement in secondary outcome measures of body weight, fat mass, and disease activity score in 28 joints based on C-reactive protein (DAS28-CRP), as well as greater improvement in patient-reported physical and mental health, physical function, and fatigue, than those in the CHAT group, but the CHAT group improved significantly compared with their baseline.
• The strongest specific effects for the different components of the intervention were those of aerobic training on physical function and fatigue, resistance training on DAS28-CRP, and weight loss on MSSc.
• Neither group experienced significant changes in lean mass, absolute peak V02, unilateral isometric knee extension, or bilateral grip strength.

IN PRACTICE:

“Findings from our study indicate, at a minimum, integrating even 2 hours of healthy lifestyle counseling may improve RA management, let alone demonstrate the substantial impact that can be provided by a comprehensive, remotely supervised lifestyle intervention,” the researchers wrote.

SOURCE:

The lead author on the study was Brian J. Andonian, MD, of Duke University, Durham, North Carolina. The study was published online in ACR Open Rheumatology.

LIMITATIONS:

The small sample size was a limitation of the study findings, as was the lack of blinding and high level of motivation in the CHAT group, who had greater improvements than expected in weight loss and increased physical activity; the study also was conducted during the COVID-19 pandemic, with potential physical and mental effects on participants who tested positive during the study period.

DISCLOSURES:

The study was supported by the US National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Claude D. Pepper Older Americans Independence Center of the US National Institute on Aging.

A version of this article appeared on Medscape.com.

TOPLINE:

A combination of remote, supervised aerobic training, resistance training, and a hypocaloric diet significantly improved cardiovascular risk factors in adults with rheumatoid arthritis (RA) and overweight or obesity.

METHODOLOGY:

• The researchers recruited 24 adults aged 60-80 years with RA who met criteria for overweight or obesity; participants were randomized to a Supervised Weight Loss and Exercise Training (SWET) or Counseling Health as Treatment (CHAT) program for 16 weeks.
• The SWET intervention included remote supervision of aerobic training of 150 minutes/week moderate-to-vigorous intensity, 2 days per week of resistance training, and a hypocaloric diet based on a weight loss goal of 7% of body weight. The CHAT patients served as controls and completed two lifestyle counseling sessions followed by monthly check-ins.
• The primary outcome was change in a composite measure of cardiovascular risk based on metabolic syndrome z-score (MSSc), a continuous weighted score of five metabolic syndrome components: Waist circumference, mean arterial blood pressure, fasting glucose, triglycerides, and high-density lipoprotein cholesterol.

TAKEAWAY:

• Both groups showed improvement in the primary outcome of MSSc, with absolute changes from baseline of −1.67 for the SWET group and −1.34 for the CHAT group (P < .01 for both).
• Participants in the SWET group showed significantly more improvement in secondary outcome measures of body weight, fat mass, and disease activity score in 28 joints based on C-reactive protein (DAS28-CRP), as well as greater improvement in patient-reported physical and mental health, physical function, and fatigue, than those in the CHAT group, but the CHAT group improved significantly compared with their baseline.
• The strongest specific effects for the different components of the intervention were those of aerobic training on physical function and fatigue, resistance training on DAS28-CRP, and weight loss on MSSc.
• Neither group experienced significant changes in lean mass, absolute peak V02, unilateral isometric knee extension, or bilateral grip strength.

IN PRACTICE:

“Findings from our study indicate, at a minimum, integrating even 2 hours of healthy lifestyle counseling may improve RA management, let alone demonstrate the substantial impact that can be provided by a comprehensive, remotely supervised lifestyle intervention,” the researchers wrote.

SOURCE:

The lead author on the study was Brian J. Andonian, MD, of Duke University, Durham, North Carolina. The study was published online in ACR Open Rheumatology.

LIMITATIONS:

The small sample size was a limitation of the study findings, as was the lack of blinding and high level of motivation in the CHAT group, who had greater improvements than expected in weight loss and increased physical activity; the study also was conducted during the COVID-19 pandemic, with potential physical and mental effects on participants who tested positive during the study period.

DISCLOSURES:

The study was supported by the US National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Claude D. Pepper Older Americans Independence Center of the US National Institute on Aging.

A version of this article appeared on Medscape.com.

TOPLINE:

A combination of remote, supervised aerobic training, resistance training, and a hypocaloric diet significantly improved cardiovascular risk factors in adults with rheumatoid arthritis (RA) and overweight or obesity.

METHODOLOGY:

• The researchers recruited 24 adults aged 60-80 years with RA who met criteria for overweight or obesity; participants were randomized to a Supervised Weight Loss and Exercise Training (SWET) or Counseling Health as Treatment (CHAT) program for 16 weeks.
• The SWET intervention included remote supervision of aerobic training of 150 minutes/week moderate-to-vigorous intensity, 2 days per week of resistance training, and a hypocaloric diet based on a weight loss goal of 7% of body weight. The CHAT patients served as controls and completed two lifestyle counseling sessions followed by monthly check-ins.
• The primary outcome was change in a composite measure of cardiovascular risk based on metabolic syndrome z-score (MSSc), a continuous weighted score of five metabolic syndrome components: Waist circumference, mean arterial blood pressure, fasting glucose, triglycerides, and high-density lipoprotein cholesterol.

TAKEAWAY:

• Both groups showed improvement in the primary outcome of MSSc, with absolute changes from baseline of −1.67 for the SWET group and −1.34 for the CHAT group (P < .01 for both).
• Participants in the SWET group showed significantly more improvement in secondary outcome measures of body weight, fat mass, and disease activity score in 28 joints based on C-reactive protein (DAS28-CRP), as well as greater improvement in patient-reported physical and mental health, physical function, and fatigue, than those in the CHAT group, but the CHAT group improved significantly compared with their baseline.
• The strongest specific effects for the different components of the intervention were those of aerobic training on physical function and fatigue, resistance training on DAS28-CRP, and weight loss on MSSc.
• Neither group experienced significant changes in lean mass, absolute peak V02, unilateral isometric knee extension, or bilateral grip strength.

IN PRACTICE:

“Findings from our study indicate, at a minimum, integrating even 2 hours of healthy lifestyle counseling may improve RA management, let alone demonstrate the substantial impact that can be provided by a comprehensive, remotely supervised lifestyle intervention,” the researchers wrote.

SOURCE:

The lead author on the study was Brian J. Andonian, MD, of Duke University, Durham, North Carolina. The study was published online in ACR Open Rheumatology.

LIMITATIONS:

The small sample size was a limitation of the study findings, as was the lack of blinding and high level of motivation in the CHAT group, who had greater improvements than expected in weight loss and increased physical activity; the study also was conducted during the COVID-19 pandemic, with potential physical and mental effects on participants who tested positive during the study period.

DISCLOSURES:

The study was supported by the US National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Claude D. Pepper Older Americans Independence Center of the US National Institute on Aging.

A version of this article appeared on Medscape.com.

About 20% of US physicians took less than 1 week of vacation in the previous year, a new study found. When doctors did go on vacation, 70% reported working on their days off to handle patient-related tasks.

Burnout was more likely among doctors who worked more during vacations and lacked coverage in responding to electronic health messages from patients, according to the cross-sectional study, which was published on January 12, 2024, in JAMA Network Open.“It’s important to provide physicians with adequate time to disconnect from work and recharge,” said study coauthor Tait Shanafelt, MD, chief wellness officer at Stanford Medicine, in an interview.

The study’s conclusion that most US physicians work on their days off “is a marker of inadequate staffing, suboptimal teamwork, and poorly designed coverage systems,” he added. “Simply allocating people a number of vacation days is not enough.”

According to Dr. Shanafelt, there’s been little research into vacation’s impact on physician well-being. However, it is clear that work overload and exhaustion are major problems among American physicians. “Inadequate time off may magnify these challenges.”

Research suggests that physicians suffer more burnout than other US workers even after adjusting for confounders, he said. Extensive evidence shows that burnout in physicians contributes to medical errors and erodes quality of care and patient satisfaction, he added.

For the new study, researchers mailed surveys to 3671 members of the American Medical Association from 2020 to 2021, and 1162 (31.7%) responded. Another 6348 (7.1%) responded to an email survey sent to 90,000 physicians. An analysis suggested the respondents were representative of all US practicing physicians. 

Among 3024 respondents who responded to a subsurvey about vacations, about 40% took more than 15 days of vacation over the past year, about 40% took 6-15 days, and about 20% took 5 or fewer days. 

Fewer than half of physicians said their electronic health record (EHR) inboxes were fully covered by others while they were away. About 70% said they worked while on vacation, with nearly 15% working an hour or more each day.

Emergency physicians were the least likely and anesthesiologists were the most likely to take at least 15 days of vacation per year, according to the study. 

Women were more likely than men to work 30 or more minutes a day on vacation. Physicians aged 65 years and older were more likely to take 15 or more days of vacation per year than those under 35 years.

An adjusted analysis linked complete EHR inbox coverage to lower odds of taking time during vacation to work (odds ratio [OR], 0.68; 95% CI, 0.57-0.80).

“For many, difficulty finding clinical coverage, lack of EHR inbox coverage, and returning to an overwhelming backlog of EHR inbox work at were identified as barriers to taking vacation,” Dr. Shanafelt said.

Researchers linked lower rates of burnout to taking more than 3 weeks of vacation per year (OR, 0.59-0.66, depending on time spent; 95% CI, 0.40-0.98) vs none. They also linked less burnout to full EHR inbox coverage while on vacation (OR, 0.74; 95% CI, 0.63-0.88) and more burnout to spending 30 minutes or more on work while on a typical vacation day (OR, 1.58-1.97, depending on time spent; 95% CI, 1.22-2.77). 

Study limitations include the low participation rate and lack of insight into causation. It’s not clear how burnout and less vacation time are related and whether one causes the other, Shanafelt said. “It is possible there are a number of interacting factors rather than a simple, linear relationship.”

In an interview, Lazar J. Greenfield, Jr., MD, PhD, professor and chairman of neurology at UConn Health, Farmington, Connecticut, said his department encourages clinicians to plan vacations well ahead of time, and “we make a real strong effort to make sure that people are fully covered and someone has their Epic inbox.”

Dr. Greenfield, who wasn’t involved in the new study, recommended that physicians plan active vacations, so they have less downtime to catch up on work matters. But he acknowledged that stepping away from emails can be difficult, especially when physicians fear pileups of work upon their return or don’t want to annoy patients with tardy responses.

“They have a hard time disengaging from their moral obligations to patients,” he said. “Another issue, particularly in my field of neurology, is that there’s a lot of subspecialties. Finding somebody with the exact subspecialty and expertise to cover a very specific patient population they treat can be really hard.”

The Stanford WellMD Center, Mayo Clinic Department of Medicine Program on Physician Well-being, and American Medical Association funded the study.

Dr. Shanafelt discloses coinventing the Well-Being Index and its derivatives with another study author; Mayo Clinic licensed the Well-Being Index and pays them royalties outside the submitted work. Dr. Shanafelt also reported support for grand rounds, lectures, and advising for healthcare organizations outside the submitted work. Other authors reported personal fees from Marvin Behavioral Health and grants from the National Institute of Nursing Research, National Science Foundation, and Med Ed Solutions. 

Dr. Greenfield had no disclosures.

A version of this article appeared on Medscape.com. 

About 20% of US physicians took less than 1 week of vacation in the previous year, a new study found. When doctors did go on vacation, 70% reported working on their days off to handle patient-related tasks.

Burnout was more likely among doctors who worked more during vacations and lacked coverage in responding to electronic health messages from patients, according to the cross-sectional study, which was published on January 12, 2024, in JAMA Network Open.“It’s important to provide physicians with adequate time to disconnect from work and recharge,” said study coauthor Tait Shanafelt, MD, chief wellness officer at Stanford Medicine, in an interview.

The study’s conclusion that most US physicians work on their days off “is a marker of inadequate staffing, suboptimal teamwork, and poorly designed coverage systems,” he added. “Simply allocating people a number of vacation days is not enough.”

According to Dr. Shanafelt, there’s been little research into vacation’s impact on physician well-being. However, it is clear that work overload and exhaustion are major problems among American physicians. “Inadequate time off may magnify these challenges.”

Research suggests that physicians suffer more burnout than other US workers even after adjusting for confounders, he said. Extensive evidence shows that burnout in physicians contributes to medical errors and erodes quality of care and patient satisfaction, he added.

For the new study, researchers mailed surveys to 3671 members of the American Medical Association from 2020 to 2021, and 1162 (31.7%) responded. Another 6348 (7.1%) responded to an email survey sent to 90,000 physicians. An analysis suggested the respondents were representative of all US practicing physicians. 

Among 3024 respondents who responded to a subsurvey about vacations, about 40% took more than 15 days of vacation over the past year, about 40% took 6-15 days, and about 20% took 5 or fewer days. 

Fewer than half of physicians said their electronic health record (EHR) inboxes were fully covered by others while they were away. About 70% said they worked while on vacation, with nearly 15% working an hour or more each day.

Emergency physicians were the least likely and anesthesiologists were the most likely to take at least 15 days of vacation per year, according to the study. 

Women were more likely than men to work 30 or more minutes a day on vacation. Physicians aged 65 years and older were more likely to take 15 or more days of vacation per year than those under 35 years.

An adjusted analysis linked complete EHR inbox coverage to lower odds of taking time during vacation to work (odds ratio [OR], 0.68; 95% CI, 0.57-0.80).

“For many, difficulty finding clinical coverage, lack of EHR inbox coverage, and returning to an overwhelming backlog of EHR inbox work at were identified as barriers to taking vacation,” Dr. Shanafelt said.

Researchers linked lower rates of burnout to taking more than 3 weeks of vacation per year (OR, 0.59-0.66, depending on time spent; 95% CI, 0.40-0.98) vs none. They also linked less burnout to full EHR inbox coverage while on vacation (OR, 0.74; 95% CI, 0.63-0.88) and more burnout to spending 30 minutes or more on work while on a typical vacation day (OR, 1.58-1.97, depending on time spent; 95% CI, 1.22-2.77). 

Study limitations include the low participation rate and lack of insight into causation. It’s not clear how burnout and less vacation time are related and whether one causes the other, Shanafelt said. “It is possible there are a number of interacting factors rather than a simple, linear relationship.”

In an interview, Lazar J. Greenfield, Jr., MD, PhD, professor and chairman of neurology at UConn Health, Farmington, Connecticut, said his department encourages clinicians to plan vacations well ahead of time, and “we make a real strong effort to make sure that people are fully covered and someone has their Epic inbox.”

Dr. Greenfield, who wasn’t involved in the new study, recommended that physicians plan active vacations, so they have less downtime to catch up on work matters. But he acknowledged that stepping away from emails can be difficult, especially when physicians fear pileups of work upon their return or don’t want to annoy patients with tardy responses.

“They have a hard time disengaging from their moral obligations to patients,” he said. “Another issue, particularly in my field of neurology, is that there’s a lot of subspecialties. Finding somebody with the exact subspecialty and expertise to cover a very specific patient population they treat can be really hard.”

The Stanford WellMD Center, Mayo Clinic Department of Medicine Program on Physician Well-being, and American Medical Association funded the study.

Dr. Shanafelt discloses coinventing the Well-Being Index and its derivatives with another study author; Mayo Clinic licensed the Well-Being Index and pays them royalties outside the submitted work. Dr. Shanafelt also reported support for grand rounds, lectures, and advising for healthcare organizations outside the submitted work. Other authors reported personal fees from Marvin Behavioral Health and grants from the National Institute of Nursing Research, National Science Foundation, and Med Ed Solutions. 

Dr. Greenfield had no disclosures.

A version of this article appeared on Medscape.com. 

About 20% of US physicians took less than 1 week of vacation in the previous year, a new study found. When doctors did go on vacation, 70% reported working on their days off to handle patient-related tasks.

Burnout was more likely among doctors who worked more during vacations and lacked coverage in responding to electronic health messages from patients, according to the cross-sectional study, which was published on January 12, 2024, in JAMA Network Open.“It’s important to provide physicians with adequate time to disconnect from work and recharge,” said study coauthor Tait Shanafelt, MD, chief wellness officer at Stanford Medicine, in an interview.

The study’s conclusion that most US physicians work on their days off “is a marker of inadequate staffing, suboptimal teamwork, and poorly designed coverage systems,” he added. “Simply allocating people a number of vacation days is not enough.”

According to Dr. Shanafelt, there’s been little research into vacation’s impact on physician well-being. However, it is clear that work overload and exhaustion are major problems among American physicians. “Inadequate time off may magnify these challenges.”

Research suggests that physicians suffer more burnout than other US workers even after adjusting for confounders, he said. Extensive evidence shows that burnout in physicians contributes to medical errors and erodes quality of care and patient satisfaction, he added.

For the new study, researchers mailed surveys to 3671 members of the American Medical Association from 2020 to 2021, and 1162 (31.7%) responded. Another 6348 (7.1%) responded to an email survey sent to 90,000 physicians. An analysis suggested the respondents were representative of all US practicing physicians. 

Among 3024 respondents who responded to a subsurvey about vacations, about 40% took more than 15 days of vacation over the past year, about 40% took 6-15 days, and about 20% took 5 or fewer days. 

Fewer than half of physicians said their electronic health record (EHR) inboxes were fully covered by others while they were away. About 70% said they worked while on vacation, with nearly 15% working an hour or more each day.

Emergency physicians were the least likely and anesthesiologists were the most likely to take at least 15 days of vacation per year, according to the study. 

Women were more likely than men to work 30 or more minutes a day on vacation. Physicians aged 65 years and older were more likely to take 15 or more days of vacation per year than those under 35 years.

An adjusted analysis linked complete EHR inbox coverage to lower odds of taking time during vacation to work (odds ratio [OR], 0.68; 95% CI, 0.57-0.80).

“For many, difficulty finding clinical coverage, lack of EHR inbox coverage, and returning to an overwhelming backlog of EHR inbox work at were identified as barriers to taking vacation,” Dr. Shanafelt said.

Researchers linked lower rates of burnout to taking more than 3 weeks of vacation per year (OR, 0.59-0.66, depending on time spent; 95% CI, 0.40-0.98) vs none. They also linked less burnout to full EHR inbox coverage while on vacation (OR, 0.74; 95% CI, 0.63-0.88) and more burnout to spending 30 minutes or more on work while on a typical vacation day (OR, 1.58-1.97, depending on time spent; 95% CI, 1.22-2.77). 

Study limitations include the low participation rate and lack of insight into causation. It’s not clear how burnout and less vacation time are related and whether one causes the other, Shanafelt said. “It is possible there are a number of interacting factors rather than a simple, linear relationship.”

In an interview, Lazar J. Greenfield, Jr., MD, PhD, professor and chairman of neurology at UConn Health, Farmington, Connecticut, said his department encourages clinicians to plan vacations well ahead of time, and “we make a real strong effort to make sure that people are fully covered and someone has their Epic inbox.”

Dr. Greenfield, who wasn’t involved in the new study, recommended that physicians plan active vacations, so they have less downtime to catch up on work matters. But he acknowledged that stepping away from emails can be difficult, especially when physicians fear pileups of work upon their return or don’t want to annoy patients with tardy responses.

“They have a hard time disengaging from their moral obligations to patients,” he said. “Another issue, particularly in my field of neurology, is that there’s a lot of subspecialties. Finding somebody with the exact subspecialty and expertise to cover a very specific patient population they treat can be really hard.”

The Stanford WellMD Center, Mayo Clinic Department of Medicine Program on Physician Well-being, and American Medical Association funded the study.

Dr. Shanafelt discloses coinventing the Well-Being Index and its derivatives with another study author; Mayo Clinic licensed the Well-Being Index and pays them royalties outside the submitted work. Dr. Shanafelt also reported support for grand rounds, lectures, and advising for healthcare organizations outside the submitted work. Other authors reported personal fees from Marvin Behavioral Health and grants from the National Institute of Nursing Research, National Science Foundation, and Med Ed Solutions. 

Dr. Greenfield had no disclosures.

A version of this article appeared on Medscape.com.