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XEN-D0501, a transient receptor potential vanilloid 1 (TRPV1) antagonist, is gaining attention for its potential as an oral tablet to treat type 2 diabetes, obesity, and cardiovascular diseases. Dorte X. Gram, PhD, founder of Pila Pharma, a Swedish pharmaceutical company investigating XEN-D0501, first noticed the connection more than 20 years ago as a researcher at Novo Nordisk. 

“In my very first experiments, I noticed that mice who would normally become diabetic didn’t get diabetes at all,” she said in an interview.

These surprising observations prompted Gram to investigate further the potential role of the TRPV1 receptor in regulating metabolism, leading her to file a patent and pursue the development of TRPV1 antagonists for obesity and related conditions. 

The company has received enough attention from investors that it witnessed a triple-digit percentage gain on the Nasdaq First North stock exchange in 2024.

While XEN-D0501 shows promise, researchers urge caution, as the drug is still in early development. “There is simply no quality human data to say anything about the possibilities for this pathway,” said John B. Dixon, PhD, professor at Iverson Health Innovation Research Institute, Swinburne University of Technology, Melbourne, Australia.

 

What Is TRPV1 and How Do TRPV1 Modulators Work? 

TRPV1 is a homotetrameric receptor with six transmembrane domains expressed primarily in sensory nerve fibers. It is responsible for detecting noxious signals, including heat and chemical irritants — particularly capsaicin, the active component of chili peppers.

TRPV1 mediates the sensation of burning pain, often associated with inflammation and heat exposure. It also helps detect and regulate body temperature and influences the release of inflammatory mediators. In the central nervous system, it affects synaptic function and plasticity.

Given TRPV1’s broad physiologic role, its modulation has potential for treating several conditions, including pain disorders, inflammation, and cardiovascular diseases. 

Studies have shown that activating TRPV1 can help counter diet-induced obesity by increasing thermogenesis in brown adipose tissue and improving metabolic activity. TRPV1 agonists such as capsaicin have been shown to reduce weight gain in high-fat-diet‒induced obese mice, with clinical trials further supporting its potential for decreasing body weight in people with overweight. 

For instance, a clinical trial showed that participants with obesity taking capsinoid supplementation for 12 weeks experienced a reduction in body weight compared with those who took a placebo. 

While TRPV1 agonists have been more commonly studied for obesity management, most studies involving antagonists have focused on pain relief, inflammation, and conditions like erythromelalgia rather than weight loss. 

However, some evidence suggests that TRPV1 antagonism may influence metabolism. For example, in one study, mice lacking TRPV1 were resistant to obesity, “but that is not sufficient [to come to any conclusion],” said Vincenzo Di Marzo, PhD, director of the Joint International Research Unit for the Chemical and Biomolecular Study of the Microbiome in Metabolic Health and Nutrition between the Consiglio Nazionale delle Ricerche, Italy, and Université Laval, Quebec City, Canada. He was not involved in the study.

Gram admits that the picture around the mechanism of action of TRPV1 modulators is unclear. “There is not a consensus in the literature about the effect of this receptor. Should it be agonized or should it be antagonized?” she said. 

 

What Is XEN-D0501?

XEN-D0501 is a novel selective TRPV1 antagonist, which Pila Pharma is developing for treating erythromelalgia, a rare condition that causes burning pain, redness, and hotness in the skin, especially the feet. It has received orphan-drug status for this indication in the United States. 

Initially, the company explored XEN-D0501 for treating overactive bladder, but the development of the drug for this condition has been discontinued. Now, attention has moved to investigating XEN-D0501 for its potential in treating type 2 diabetes, obesity, and cardiovascular disease.

Although phase 2a clinical trials showed that XEN-D0501 is generally well tolerated in healthy participants, it has been associated with several side effects, including hyperthermia and oral discomfort, thought to be due to TRPV1 antagonism at sensory nerve endings in the mouth, in addition to transient urinary retention and postvoiding residual volumes, indicating potential issues with bladder function.

Another phase 2a trial (PP-CT03) is planned to assess the maximum tolerable dose of XEN-D0501 in people with obesity and type 2 diabetes, focusing on safety and potential effects on body weight. Gram said that early data show these populations experience less hyperthermia than healthy participants. However, the mechanism behind it is still not understood. These studies also showed some positive effects on insulin sensitivity and a biomarker for heart failure.

“The company data provided so far for XEN-D0501 are promising but still too preliminary,” said Di Marzo.

The company is now planning a further 3-month-long dose-escalation study in people with obesity and diabetes. “If these studies show that the molecule is as efficacious and safe as we think it is, then it would make life a lot better for a lot of people because it is a tablet, not an injectable,” Gram said.

Also being explored by the company is the potential of the molecule for treating cardiovascular diseases, particularly abdominal aortic aneurysms, and as a potential nonopioid painkiller. 

Dixon and Di Marzo disclosed no relevant financial relationships. Gram is founder and CSO at Pila Pharma.

A version of this article appeared on Medscape.com.

XEN-D0501, a transient receptor potential vanilloid 1 (TRPV1) antagonist, is gaining attention for its potential as an oral tablet to treat type 2 diabetes, obesity, and cardiovascular diseases. Dorte X. Gram, PhD, founder of Pila Pharma, a Swedish pharmaceutical company investigating XEN-D0501, first noticed the connection more than 20 years ago as a researcher at Novo Nordisk. 

“In my very first experiments, I noticed that mice who would normally become diabetic didn’t get diabetes at all,” she said in an interview.

These surprising observations prompted Gram to investigate further the potential role of the TRPV1 receptor in regulating metabolism, leading her to file a patent and pursue the development of TRPV1 antagonists for obesity and related conditions. 

The company has received enough attention from investors that it witnessed a triple-digit percentage gain on the Nasdaq First North stock exchange in 2024.

While XEN-D0501 shows promise, researchers urge caution, as the drug is still in early development. “There is simply no quality human data to say anything about the possibilities for this pathway,” said John B. Dixon, PhD, professor at Iverson Health Innovation Research Institute, Swinburne University of Technology, Melbourne, Australia.

 

What Is TRPV1 and How Do TRPV1 Modulators Work? 

TRPV1 is a homotetrameric receptor with six transmembrane domains expressed primarily in sensory nerve fibers. It is responsible for detecting noxious signals, including heat and chemical irritants — particularly capsaicin, the active component of chili peppers.

TRPV1 mediates the sensation of burning pain, often associated with inflammation and heat exposure. It also helps detect and regulate body temperature and influences the release of inflammatory mediators. In the central nervous system, it affects synaptic function and plasticity.

Given TRPV1’s broad physiologic role, its modulation has potential for treating several conditions, including pain disorders, inflammation, and cardiovascular diseases. 

Studies have shown that activating TRPV1 can help counter diet-induced obesity by increasing thermogenesis in brown adipose tissue and improving metabolic activity. TRPV1 agonists such as capsaicin have been shown to reduce weight gain in high-fat-diet‒induced obese mice, with clinical trials further supporting its potential for decreasing body weight in people with overweight. 

For instance, a clinical trial showed that participants with obesity taking capsinoid supplementation for 12 weeks experienced a reduction in body weight compared with those who took a placebo. 

While TRPV1 agonists have been more commonly studied for obesity management, most studies involving antagonists have focused on pain relief, inflammation, and conditions like erythromelalgia rather than weight loss. 

However, some evidence suggests that TRPV1 antagonism may influence metabolism. For example, in one study, mice lacking TRPV1 were resistant to obesity, “but that is not sufficient [to come to any conclusion],” said Vincenzo Di Marzo, PhD, director of the Joint International Research Unit for the Chemical and Biomolecular Study of the Microbiome in Metabolic Health and Nutrition between the Consiglio Nazionale delle Ricerche, Italy, and Université Laval, Quebec City, Canada. He was not involved in the study.

Gram admits that the picture around the mechanism of action of TRPV1 modulators is unclear. “There is not a consensus in the literature about the effect of this receptor. Should it be agonized or should it be antagonized?” she said. 

 

What Is XEN-D0501?

XEN-D0501 is a novel selective TRPV1 antagonist, which Pila Pharma is developing for treating erythromelalgia, a rare condition that causes burning pain, redness, and hotness in the skin, especially the feet. It has received orphan-drug status for this indication in the United States. 

Initially, the company explored XEN-D0501 for treating overactive bladder, but the development of the drug for this condition has been discontinued. Now, attention has moved to investigating XEN-D0501 for its potential in treating type 2 diabetes, obesity, and cardiovascular disease.

Although phase 2a clinical trials showed that XEN-D0501 is generally well tolerated in healthy participants, it has been associated with several side effects, including hyperthermia and oral discomfort, thought to be due to TRPV1 antagonism at sensory nerve endings in the mouth, in addition to transient urinary retention and postvoiding residual volumes, indicating potential issues with bladder function.

Another phase 2a trial (PP-CT03) is planned to assess the maximum tolerable dose of XEN-D0501 in people with obesity and type 2 diabetes, focusing on safety and potential effects on body weight. Gram said that early data show these populations experience less hyperthermia than healthy participants. However, the mechanism behind it is still not understood. These studies also showed some positive effects on insulin sensitivity and a biomarker for heart failure.

“The company data provided so far for XEN-D0501 are promising but still too preliminary,” said Di Marzo.

The company is now planning a further 3-month-long dose-escalation study in people with obesity and diabetes. “If these studies show that the molecule is as efficacious and safe as we think it is, then it would make life a lot better for a lot of people because it is a tablet, not an injectable,” Gram said.

Also being explored by the company is the potential of the molecule for treating cardiovascular diseases, particularly abdominal aortic aneurysms, and as a potential nonopioid painkiller. 

Dixon and Di Marzo disclosed no relevant financial relationships. Gram is founder and CSO at Pila Pharma.

A version of this article appeared on Medscape.com.

XEN-D0501, a transient receptor potential vanilloid 1 (TRPV1) antagonist, is gaining attention for its potential as an oral tablet to treat type 2 diabetes, obesity, and cardiovascular diseases. Dorte X. Gram, PhD, founder of Pila Pharma, a Swedish pharmaceutical company investigating XEN-D0501, first noticed the connection more than 20 years ago as a researcher at Novo Nordisk. 

“In my very first experiments, I noticed that mice who would normally become diabetic didn’t get diabetes at all,” she said in an interview.

These surprising observations prompted Gram to investigate further the potential role of the TRPV1 receptor in regulating metabolism, leading her to file a patent and pursue the development of TRPV1 antagonists for obesity and related conditions. 

The company has received enough attention from investors that it witnessed a triple-digit percentage gain on the Nasdaq First North stock exchange in 2024.

While XEN-D0501 shows promise, researchers urge caution, as the drug is still in early development. “There is simply no quality human data to say anything about the possibilities for this pathway,” said John B. Dixon, PhD, professor at Iverson Health Innovation Research Institute, Swinburne University of Technology, Melbourne, Australia.

 

What Is TRPV1 and How Do TRPV1 Modulators Work? 

TRPV1 is a homotetrameric receptor with six transmembrane domains expressed primarily in sensory nerve fibers. It is responsible for detecting noxious signals, including heat and chemical irritants — particularly capsaicin, the active component of chili peppers.

TRPV1 mediates the sensation of burning pain, often associated with inflammation and heat exposure. It also helps detect and regulate body temperature and influences the release of inflammatory mediators. In the central nervous system, it affects synaptic function and plasticity.

Given TRPV1’s broad physiologic role, its modulation has potential for treating several conditions, including pain disorders, inflammation, and cardiovascular diseases. 

Studies have shown that activating TRPV1 can help counter diet-induced obesity by increasing thermogenesis in brown adipose tissue and improving metabolic activity. TRPV1 agonists such as capsaicin have been shown to reduce weight gain in high-fat-diet‒induced obese mice, with clinical trials further supporting its potential for decreasing body weight in people with overweight. 

For instance, a clinical trial showed that participants with obesity taking capsinoid supplementation for 12 weeks experienced a reduction in body weight compared with those who took a placebo. 

While TRPV1 agonists have been more commonly studied for obesity management, most studies involving antagonists have focused on pain relief, inflammation, and conditions like erythromelalgia rather than weight loss. 

However, some evidence suggests that TRPV1 antagonism may influence metabolism. For example, in one study, mice lacking TRPV1 were resistant to obesity, “but that is not sufficient [to come to any conclusion],” said Vincenzo Di Marzo, PhD, director of the Joint International Research Unit for the Chemical and Biomolecular Study of the Microbiome in Metabolic Health and Nutrition between the Consiglio Nazionale delle Ricerche, Italy, and Université Laval, Quebec City, Canada. He was not involved in the study.

Gram admits that the picture around the mechanism of action of TRPV1 modulators is unclear. “There is not a consensus in the literature about the effect of this receptor. Should it be agonized or should it be antagonized?” she said. 

 

What Is XEN-D0501?

XEN-D0501 is a novel selective TRPV1 antagonist, which Pila Pharma is developing for treating erythromelalgia, a rare condition that causes burning pain, redness, and hotness in the skin, especially the feet. It has received orphan-drug status for this indication in the United States. 

Initially, the company explored XEN-D0501 for treating overactive bladder, but the development of the drug for this condition has been discontinued. Now, attention has moved to investigating XEN-D0501 for its potential in treating type 2 diabetes, obesity, and cardiovascular disease.

Although phase 2a clinical trials showed that XEN-D0501 is generally well tolerated in healthy participants, it has been associated with several side effects, including hyperthermia and oral discomfort, thought to be due to TRPV1 antagonism at sensory nerve endings in the mouth, in addition to transient urinary retention and postvoiding residual volumes, indicating potential issues with bladder function.

Another phase 2a trial (PP-CT03) is planned to assess the maximum tolerable dose of XEN-D0501 in people with obesity and type 2 diabetes, focusing on safety and potential effects on body weight. Gram said that early data show these populations experience less hyperthermia than healthy participants. However, the mechanism behind it is still not understood. These studies also showed some positive effects on insulin sensitivity and a biomarker for heart failure.

“The company data provided so far for XEN-D0501 are promising but still too preliminary,” said Di Marzo.

The company is now planning a further 3-month-long dose-escalation study in people with obesity and diabetes. “If these studies show that the molecule is as efficacious and safe as we think it is, then it would make life a lot better for a lot of people because it is a tablet, not an injectable,” Gram said.

Also being explored by the company is the potential of the molecule for treating cardiovascular diseases, particularly abdominal aortic aneurysms, and as a potential nonopioid painkiller. 

Dixon and Di Marzo disclosed no relevant financial relationships. Gram is founder and CSO at Pila Pharma.

A version of this article appeared on Medscape.com.

TOPLINE:

Achieving serum urate to below 6 mg/dL with urate-lowering therapy (ULT) in patients with gout and chronic kidney disease (CKD) stage III is not linked to an increased risk for severe or end-stage kidney disease.

METHODOLOGY:

• Researchers emulated analyses of a hypothetical target trial using a cloning, censoring, and weighting approach to evaluate the association between achieving target serum urate level with ULT and the progression of CKD in patients with gout and CKD stage III.
• They included 14,972 patients (mean age, 73.1 years; 37.7% women) from a general practice database who had a mean baseline serum urate level of 8.9 mg/dL and initiated ULTs such as allopurinol or febuxostat.
• Participants were divided into two groups: Those who achieved a target serum urate level < 6 mg/dL and those who did not within 1 year after the initiation of ULT; the mean follow-up duration was a little more than 3 years in both groups.
• The primary outcome was the occurrence of severe or end-stage kidney disease over 5 years of initiating ULT, defined by an estimated glomerular filtration rate below 30 mL/min per 1.73 m² on two occasions more than 90 days apart within 1 year, or at least one Read code for CKD stages IV or V, dialysis, or kidney transplant.
• A prespecified noninferiority margin for the hazard ratio was set at 1.2 to compare the outcomes between those who achieved the target serum urate level < 6 mg/dL and those who did not.

TAKEAWAY:

• Among the patients who initiated ULT, 31.8% achieved a target serum urate level < 6 mg/dL within 1 year.
• The 5-year risk for severe or end-stage kidney disease was lower (10.32%) in participants with gout and stage III CKD who achieved the target serum urate level than in those who did not (12.73%).
• The adjusted 5-year risk difference for severe to end-stage kidney disease was not inferior in patients who achieved the target serum urate level vs those who did not (adjusted hazard ratio [aHR], 0.89; 95% CI, 0.80-0.98; P for noninferiority < .001); results were consistent for end-stage kidney disease alone (aHR, 0.67; P for noninferiority = .001).
• Similarly, in participants with gout and CKD stages II-III, the 5-year risks for severe or end-stage kidney disease (aHR, 0.91) and end-stage kidney disease alone (aHR, 0.73) were noninferior in the group that did vs that did not achieve target serum urate levels, with P for noninferiority being < .001 and .003, respectively.

IN PRACTICE:

“Our findings suggest that lowering serum urate levels to < 6 mg/dL is generally well tolerated and may even slow CKD progression in these individuals. Initiatives to optimize the use and adherence to ULT could benefit clinicians and patients,” the authors wrote.

SOURCE:

This study was led by Yilun Wang, MD, PhD, Xiangya Hospital, Central South University, Changsha, China. It was published online in JAMA Internal Medicine.

LIMITATIONS:

Residual confounding may still have been present despite rigorous methods to control it, as is common in observational studies. Participants who achieved target serum urate levels may have received better healthcare, adhered to other treatments more consistently, and used ULT for a longer duration. The findings may have limited generalizability, as participants who did not achieve target serum urate levels prior to initiation were excluded.

DISCLOSURES:

This study was supported by the China National Key Research and Development Plan, the National Natural Science Foundation of China, the Project Program of the National Clinical Research Center for Geriatric Disorders, and other sources. Two authors reported receiving personal fees and/or grants from multiple pharmaceutical companies.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Achieving serum urate to below 6 mg/dL with urate-lowering therapy (ULT) in patients with gout and chronic kidney disease (CKD) stage III is not linked to an increased risk for severe or end-stage kidney disease.

METHODOLOGY:

• Researchers emulated analyses of a hypothetical target trial using a cloning, censoring, and weighting approach to evaluate the association between achieving target serum urate level with ULT and the progression of CKD in patients with gout and CKD stage III.
• They included 14,972 patients (mean age, 73.1 years; 37.7% women) from a general practice database who had a mean baseline serum urate level of 8.9 mg/dL and initiated ULTs such as allopurinol or febuxostat.
• Participants were divided into two groups: Those who achieved a target serum urate level < 6 mg/dL and those who did not within 1 year after the initiation of ULT; the mean follow-up duration was a little more than 3 years in both groups.
• The primary outcome was the occurrence of severe or end-stage kidney disease over 5 years of initiating ULT, defined by an estimated glomerular filtration rate below 30 mL/min per 1.73 m² on two occasions more than 90 days apart within 1 year, or at least one Read code for CKD stages IV or V, dialysis, or kidney transplant.
• A prespecified noninferiority margin for the hazard ratio was set at 1.2 to compare the outcomes between those who achieved the target serum urate level < 6 mg/dL and those who did not.

TAKEAWAY:

• Among the patients who initiated ULT, 31.8% achieved a target serum urate level < 6 mg/dL within 1 year.
• The 5-year risk for severe or end-stage kidney disease was lower (10.32%) in participants with gout and stage III CKD who achieved the target serum urate level than in those who did not (12.73%).
• The adjusted 5-year risk difference for severe to end-stage kidney disease was not inferior in patients who achieved the target serum urate level vs those who did not (adjusted hazard ratio [aHR], 0.89; 95% CI, 0.80-0.98; P for noninferiority < .001); results were consistent for end-stage kidney disease alone (aHR, 0.67; P for noninferiority = .001).
• Similarly, in participants with gout and CKD stages II-III, the 5-year risks for severe or end-stage kidney disease (aHR, 0.91) and end-stage kidney disease alone (aHR, 0.73) were noninferior in the group that did vs that did not achieve target serum urate levels, with P for noninferiority being < .001 and .003, respectively.

IN PRACTICE:

“Our findings suggest that lowering serum urate levels to < 6 mg/dL is generally well tolerated and may even slow CKD progression in these individuals. Initiatives to optimize the use and adherence to ULT could benefit clinicians and patients,” the authors wrote.

SOURCE:

This study was led by Yilun Wang, MD, PhD, Xiangya Hospital, Central South University, Changsha, China. It was published online in JAMA Internal Medicine.

LIMITATIONS:

Residual confounding may still have been present despite rigorous methods to control it, as is common in observational studies. Participants who achieved target serum urate levels may have received better healthcare, adhered to other treatments more consistently, and used ULT for a longer duration. The findings may have limited generalizability, as participants who did not achieve target serum urate levels prior to initiation were excluded.

DISCLOSURES:

This study was supported by the China National Key Research and Development Plan, the National Natural Science Foundation of China, the Project Program of the National Clinical Research Center for Geriatric Disorders, and other sources. Two authors reported receiving personal fees and/or grants from multiple pharmaceutical companies.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Achieving serum urate to below 6 mg/dL with urate-lowering therapy (ULT) in patients with gout and chronic kidney disease (CKD) stage III is not linked to an increased risk for severe or end-stage kidney disease.

METHODOLOGY:

• Researchers emulated analyses of a hypothetical target trial using a cloning, censoring, and weighting approach to evaluate the association between achieving target serum urate level with ULT and the progression of CKD in patients with gout and CKD stage III.
• They included 14,972 patients (mean age, 73.1 years; 37.7% women) from a general practice database who had a mean baseline serum urate level of 8.9 mg/dL and initiated ULTs such as allopurinol or febuxostat.
• Participants were divided into two groups: Those who achieved a target serum urate level < 6 mg/dL and those who did not within 1 year after the initiation of ULT; the mean follow-up duration was a little more than 3 years in both groups.
• The primary outcome was the occurrence of severe or end-stage kidney disease over 5 years of initiating ULT, defined by an estimated glomerular filtration rate below 30 mL/min per 1.73 m² on two occasions more than 90 days apart within 1 year, or at least one Read code for CKD stages IV or V, dialysis, or kidney transplant.
• A prespecified noninferiority margin for the hazard ratio was set at 1.2 to compare the outcomes between those who achieved the target serum urate level < 6 mg/dL and those who did not.

TAKEAWAY:

• Among the patients who initiated ULT, 31.8% achieved a target serum urate level < 6 mg/dL within 1 year.
• The 5-year risk for severe or end-stage kidney disease was lower (10.32%) in participants with gout and stage III CKD who achieved the target serum urate level than in those who did not (12.73%).
• The adjusted 5-year risk difference for severe to end-stage kidney disease was not inferior in patients who achieved the target serum urate level vs those who did not (adjusted hazard ratio [aHR], 0.89; 95% CI, 0.80-0.98; P for noninferiority < .001); results were consistent for end-stage kidney disease alone (aHR, 0.67; P for noninferiority = .001).
• Similarly, in participants with gout and CKD stages II-III, the 5-year risks for severe or end-stage kidney disease (aHR, 0.91) and end-stage kidney disease alone (aHR, 0.73) were noninferior in the group that did vs that did not achieve target serum urate levels, with P for noninferiority being < .001 and .003, respectively.

IN PRACTICE:

“Our findings suggest that lowering serum urate levels to < 6 mg/dL is generally well tolerated and may even slow CKD progression in these individuals. Initiatives to optimize the use and adherence to ULT could benefit clinicians and patients,” the authors wrote.

SOURCE:

This study was led by Yilun Wang, MD, PhD, Xiangya Hospital, Central South University, Changsha, China. It was published online in JAMA Internal Medicine.

LIMITATIONS:

Residual confounding may still have been present despite rigorous methods to control it, as is common in observational studies. Participants who achieved target serum urate levels may have received better healthcare, adhered to other treatments more consistently, and used ULT for a longer duration. The findings may have limited generalizability, as participants who did not achieve target serum urate levels prior to initiation were excluded.

DISCLOSURES:

This study was supported by the China National Key Research and Development Plan, the National Natural Science Foundation of China, the Project Program of the National Clinical Research Center for Geriatric Disorders, and other sources. Two authors reported receiving personal fees and/or grants from multiple pharmaceutical companies.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Genetic markers, specifically tumor necrosis factor alpha receptor 2 (TNFR2) gene polymorphisms, may predict response to TNF inhibitor therapy in patients with rheumatoid arthritis (RA). This approach could optimize treatment and improve patient outcomes.

METHODOLOGY:

• The study aimed to determine if TNFR2 gene polymorphisms could serve as biomarkers for treatment responsiveness to TNF inhibitors.
• It included 52 adult patients with RA (average age, 57.4 years; mean body mass index, 31.4; 65% women; 80% White) who had a mean disease duration of 8.9 years and started treatment with a single TNF inhibitor (infliximab, adalimumab, etanercept, golimumab, or certolizumab pegol).
• TNFR2-M (methionine) and TNFR2-R(arginine) gene polymorphisms were identified using genomic DNA isolated from patients’ blood samples to determine M/M, M/R, or R/R genotypes.
• The primary outcome was nonresponse to TNF inhibitors, defined as discontinuation of medication in < 3 months.
• The relationship between TNF inhibitor responsiveness and TNFR2 gene polymorphisms was analyzed using univariable logistic regression.

TAKEAWAY:

• Genomic DNA analysis revealed that 28 patients were homozygous for methionine, 22 were heterozygous, and two were homozygous for arginine.
• Of these, 96.4% of patients with the M/M genotype were responders to TNF inhibitors, whereas 75% of those with the M/R genotype and 50% with the R/R genotype were responders.
• Patients with the M/M genotype had approximately 10 times higher odds of responding to TNF inhibitors than those with the M/R and R/R genotypes (odds ratio, 10.12; P = .04).

IN PRACTICE:

“Identifying predictors for nonresponsiveness to TNF antagonists based on TNFR2 gene polymorphisms may become a valuable tool for personalized medicine, allowing for a more specific TNF [inhibitor] therapy in RA patients,” the authors wrote. “Given that TNF [inhibitor] therapy is used for many autoimmune conditions beyond RA, this genotyping could potentially serve as a useful framework for personalized treatment strategies in other autoimmune diseases to delay or reduce disease progression overall.”

SOURCE:

This study was led by Elaine Husni, MD, MPH, Lerner Research Institute, Cleveland Clinic in Ohio. It was published online on November 7, 2024, in Seminars in Arthritis and Rheumatism and presented as a poster at the American College of Rheumatology (ACR) 2024 Annual Meeting.

LIMITATIONS:

This study’s sample size was relatively small.

DISCLOSURES:

This study was supported by the Arthritis Foundation and in part by the National Institutes of Health. No relevant conflicts of interest were disclosed by the authors.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Genetic markers, specifically tumor necrosis factor alpha receptor 2 (TNFR2) gene polymorphisms, may predict response to TNF inhibitor therapy in patients with rheumatoid arthritis (RA). This approach could optimize treatment and improve patient outcomes.

METHODOLOGY:

• The study aimed to determine if TNFR2 gene polymorphisms could serve as biomarkers for treatment responsiveness to TNF inhibitors.
• It included 52 adult patients with RA (average age, 57.4 years; mean body mass index, 31.4; 65% women; 80% White) who had a mean disease duration of 8.9 years and started treatment with a single TNF inhibitor (infliximab, adalimumab, etanercept, golimumab, or certolizumab pegol).
• TNFR2-M (methionine) and TNFR2-R(arginine) gene polymorphisms were identified using genomic DNA isolated from patients’ blood samples to determine M/M, M/R, or R/R genotypes.
• The primary outcome was nonresponse to TNF inhibitors, defined as discontinuation of medication in < 3 months.
• The relationship between TNF inhibitor responsiveness and TNFR2 gene polymorphisms was analyzed using univariable logistic regression.

TAKEAWAY:

• Genomic DNA analysis revealed that 28 patients were homozygous for methionine, 22 were heterozygous, and two were homozygous for arginine.
• Of these, 96.4% of patients with the M/M genotype were responders to TNF inhibitors, whereas 75% of those with the M/R genotype and 50% with the R/R genotype were responders.
• Patients with the M/M genotype had approximately 10 times higher odds of responding to TNF inhibitors than those with the M/R and R/R genotypes (odds ratio, 10.12; P = .04).

IN PRACTICE:

“Identifying predictors for nonresponsiveness to TNF antagonists based on TNFR2 gene polymorphisms may become a valuable tool for personalized medicine, allowing for a more specific TNF [inhibitor] therapy in RA patients,” the authors wrote. “Given that TNF [inhibitor] therapy is used for many autoimmune conditions beyond RA, this genotyping could potentially serve as a useful framework for personalized treatment strategies in other autoimmune diseases to delay or reduce disease progression overall.”

SOURCE:

This study was led by Elaine Husni, MD, MPH, Lerner Research Institute, Cleveland Clinic in Ohio. It was published online on November 7, 2024, in Seminars in Arthritis and Rheumatism and presented as a poster at the American College of Rheumatology (ACR) 2024 Annual Meeting.

LIMITATIONS:

This study’s sample size was relatively small.

DISCLOSURES:

This study was supported by the Arthritis Foundation and in part by the National Institutes of Health. No relevant conflicts of interest were disclosed by the authors.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Genetic markers, specifically tumor necrosis factor alpha receptor 2 (TNFR2) gene polymorphisms, may predict response to TNF inhibitor therapy in patients with rheumatoid arthritis (RA). This approach could optimize treatment and improve patient outcomes.

METHODOLOGY:

• The study aimed to determine if TNFR2 gene polymorphisms could serve as biomarkers for treatment responsiveness to TNF inhibitors.
• It included 52 adult patients with RA (average age, 57.4 years; mean body mass index, 31.4; 65% women; 80% White) who had a mean disease duration of 8.9 years and started treatment with a single TNF inhibitor (infliximab, adalimumab, etanercept, golimumab, or certolizumab pegol).
• TNFR2-M (methionine) and TNFR2-R(arginine) gene polymorphisms were identified using genomic DNA isolated from patients’ blood samples to determine M/M, M/R, or R/R genotypes.
• The primary outcome was nonresponse to TNF inhibitors, defined as discontinuation of medication in < 3 months.
• The relationship between TNF inhibitor responsiveness and TNFR2 gene polymorphisms was analyzed using univariable logistic regression.

TAKEAWAY:

• Genomic DNA analysis revealed that 28 patients were homozygous for methionine, 22 were heterozygous, and two were homozygous for arginine.
• Of these, 96.4% of patients with the M/M genotype were responders to TNF inhibitors, whereas 75% of those with the M/R genotype and 50% with the R/R genotype were responders.
• Patients with the M/M genotype had approximately 10 times higher odds of responding to TNF inhibitors than those with the M/R and R/R genotypes (odds ratio, 10.12; P = .04).

IN PRACTICE:

“Identifying predictors for nonresponsiveness to TNF antagonists based on TNFR2 gene polymorphisms may become a valuable tool for personalized medicine, allowing for a more specific TNF [inhibitor] therapy in RA patients,” the authors wrote. “Given that TNF [inhibitor] therapy is used for many autoimmune conditions beyond RA, this genotyping could potentially serve as a useful framework for personalized treatment strategies in other autoimmune diseases to delay or reduce disease progression overall.”

SOURCE:

This study was led by Elaine Husni, MD, MPH, Lerner Research Institute, Cleveland Clinic in Ohio. It was published online on November 7, 2024, in Seminars in Arthritis and Rheumatism and presented as a poster at the American College of Rheumatology (ACR) 2024 Annual Meeting.

LIMITATIONS:

This study’s sample size was relatively small.

DISCLOSURES:

This study was supported by the Arthritis Foundation and in part by the National Institutes of Health. No relevant conflicts of interest were disclosed by the authors.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

More Americans than ever are hurting with enduring, life-restricting pain. Like obesity, this condition is on the rise, according to figures in a new National Center for Health Statistics (NCHS) Data Brief from the Centers for Disease Control and Prevention (CDC).

In 2023, 24.3% of US adults had chronic pain, and 8.5% had high-impact chronic pain (HICP) that frequently limited daily activities in the past 3 months. Both types increased with age and with decreasing urbanization level. Women were more likely than men to have HICP (23.2% vs 7.3%). 

Like obesity, chronic pain is multifactorial and is best managed with multidisciplinary intervention, said Jianguo Cheng, MD, PhD, a professor of anesthesiology and medical director of the Cleveland Clinic Consortium for Pain in Ohio. “It’s a complex mix of genetic, biological, and psychosocial dimensions that can cause ongoing pain out of proportion to the original limited injury that triggered it.”

While today’s longer lifespans are the primary driver of the increase, noted Martin Cheatle, PhD, an associate professor of psychiatry, anesthesiology, and critical care and director of behavioral medicine at the Penn Pain Medicine Center at the University of Pennsylvania’s Perelman School of Medicine, Philadelphia, another important factor is the more than 100 million Americans who suffer from obesity. “Obesity is a major risk factor for chronic pain conditions including advancing joint disease, low back pain, and diabetic neuropathies,” he said.

Age is an amplifier, agreed Beth Darnall, PhD, a professor of anesthesiology and perioperative and pain medicine and director of the Pain Relief Innovations Lab at Stanford University in Palo Alto, California, but the increases in chronic pain and HICP cut across age strata. 

“Across the board we see striking increases in chronic pain, such as a 5% increase for those 65 and older, and a nearly 2% increase in HICP in that same age group,” Darnall said, referencing the changes from 2019 data in the new NCHS Data Brief. “And an almost 4% increase was observed for the youngest adult age category,18 to 29. Some of our research is now focusing on how to best treat chronic pain in young adults.”

The rise in chronic pain is broadly linked to the overall decline in the health of the US population, as indicated by the CDC 2024’s Chronic Disease Prevalence in the US: Sociodemographic and Geographic Variations by Zip Code Tabulation Area.

 

The Opioid Crisis and COVID

Beginning in 2016, in response to the opioid crisis and CDC guidelines, opioid prescribing for chronic pain rapidly dropped, both in terms of new prescriptions and tapering of doses of long-term users. “Reduced opioid prescribing yielded benefits for some patients but created new problems and harms for other patients,” said Darnall. Cheng added that the CDC’s recommendations on opioid prescribing were widely misinterpreted and were applied to patients with painful conditions such as cancer and sickle cell disease who were not intended to be affected by the guidelines. “In addition, although medical opioid prescribing dropped by 50%, overdose deaths from non-medical opioid sources increased by more 50%.”

Currently, most opioid overdoses are related to heroin, fentanyl, and newer drugs of abuse such as xylazine. “Most pain clinicians would agree that opioids are not first-line therapy for chronic non-cancer pain, but in a select number of well-vetted patients, opioids can be very effective in improving functionality and quality of life as part of a multimodal approach to pain care,” Cheatle said. 

The impact of the opioid crisis is complex, said Cheatle, noting that only 8%-10% of pain patients on long-term opioid therapy develop a use disorder. “However, opioids were overly prescribed due to clinicians’ lack of training in core competencies of pain management and the insurance companies’ refusal to adequately cover non-opioid therapies such as acupuncture, cognitive behavioral therapy, extended physical therapy, and medical massage,” he said. 

He pointed out that in the late 1990s there were more than 1000 multidisciplinary pain centers, whereas currently there are many fewer owing to lack of insurance reimbursement. “This results in more possibly avoidable invasive surgeries, which can further contribute to the increase in chronic pain.” 

The COVID pandemic further exacerbated the pain problem and delayed access to timely medical interventions for many people. Some adopted a more sedentary lifestyle, already entrenched in today’s technology-driven society, leading in turn to weight gain and more chronic pain. “The isolation and lack of normal human connections during the pandemic could exacerbate pain and loss of autonomy,” Cheatle said. And some individuals developed painful neurologic conditions related to long-haul COVID, for which there is no effective treatment. 

 

Best Approach

“Historically, pain has been treated as a purely biomedical issue. Bringing a biopsychosocial perspective to pain care can support pain relief,” said Darnall. Multiple national clinical guidance documents have called for a comprehensive approach that considers the whole person: their circumstances, their needs, their stressors, and their environment. “And we must provide patients meaningful access to the lowest-risk, non-pharmacologic treatments first – and ideally early on,” she said.

Even effective medications rarely make a person pain free, so other approaches are needed in tandem, Darnall said. Support for stronger patient competency in self-management of chronic pain is mounting.

“It’s vitally important that we help people know how to help themselves have less pain – how to steer their mind and body toward relief by using pain relief skills,” she said. “By so doing they can cultivate a critical level of control over their pain and are less at its mercy, which supports good mood and is shown to help people be more active as the impacts of pain diminish.”

Darnall outlined a recent development in the primary care setting that involves offering patients a brief program in pain-relief skills training. Within Veterans Affairs primary care, for example, patients receive several 30-minute sessions in pain reduction techniques. Outside of the VA, primary care clinics are incorporating an evidence-based, one-session 2-hour pain relief skills class called Empowered Relief, as standard care. 

The class teaches participants three pain management skills and creates a personalized plan for each that includes a free app for ongoing daily use.

Since pain causes agitation in the central nervous system, manifested as fast heart rate, rapid breathing, muscle tension, and distress, people learn various ways to calm the central nervous system – with, for example, a sound technology known as binaural audio to deepen the relaxation response. “They also learn to identify and target worry about pain and develop self-soothing actions to interrupt unhelpful patterns,” Darnall said. 

Data from randomized chronic pain studies, including one by her group using a virtual reality training program for lower back pain, show that 3 months after the training program people report clinically meaningful reductions in pain intensity, pain interference with daily activities, and sleep disturbance, as well as pain-related distress, anxiety, and fatigue

While psychological and complementary approaches have been effective in improving function and mood, there are barriers to accessing them, said Cheatle, such as lack of insurance coverage and the stigma associated with nontraditional, especially psychological, care.

 

Prevention

Good lifestyle behaviors promote better health as people age. “Maintaining a healthy weight, staying active, prioritizing good sleep, and avoiding smoking and alcohol use can support better health and buffer against chronic diseases and pain,” Darnall said.

Cheatle noted the importance of maintaining a safe work environment and avoiding injury risks by, for example, wearing a seatbelt or a cycling helmet. 

 

The Future 

“We need to ensure all individuals have access to effective, low-burden pain treatments, including evidence-based treatments they can receive from home so as to minimize treatment disparities.” Darnall said. Also needed is better comprehensive treatment for acute and chronic pain alike. “If we treat acute pain better, we will have fewer people transitioning to the chronic pain state.”

To that end, added Cheng, healthcare professionals in every specialty from doctors and nurses to psychologists and chiropractors need to develop co-competencies in pain management. 

For Cheatle, the near future looks bleak. “There are some pioneering bioengineering approaches to reduce chronic pain and novel pharmacologic agents such as calcitonin gene-related peptide inhibitors for intractable migraines, but just changing insurance reimbursement for a comprehensive approach to chronic pain care and bolstering healthcare provider education on core pain competencies will benefit the over 50 million adults who suffer from chronic pain.” 

Cheng, however, is more sanguine. “I don’t expect miracles in 10 years’ time, but we’re making rapid progress in understanding the genetics of chronic pain and the mechanisms of disease and therapy. We’re developing biomarkers to help in prognosis and monitor disease progress.” In the meantime, he pointed to an expanding array of non-pharmaceutical options, including neuromodulatory approaches such as nerve blocks and spinal cord stimulation.

Cheng, Cheatle, and Darnall disclosed no relevant competing interests.

A version of this article appeared on Medscape.com.

More Americans than ever are hurting with enduring, life-restricting pain. Like obesity, this condition is on the rise, according to figures in a new National Center for Health Statistics (NCHS) Data Brief from the Centers for Disease Control and Prevention (CDC).

In 2023, 24.3% of US adults had chronic pain, and 8.5% had high-impact chronic pain (HICP) that frequently limited daily activities in the past 3 months. Both types increased with age and with decreasing urbanization level. Women were more likely than men to have HICP (23.2% vs 7.3%). 

Like obesity, chronic pain is multifactorial and is best managed with multidisciplinary intervention, said Jianguo Cheng, MD, PhD, a professor of anesthesiology and medical director of the Cleveland Clinic Consortium for Pain in Ohio. “It’s a complex mix of genetic, biological, and psychosocial dimensions that can cause ongoing pain out of proportion to the original limited injury that triggered it.”

While today’s longer lifespans are the primary driver of the increase, noted Martin Cheatle, PhD, an associate professor of psychiatry, anesthesiology, and critical care and director of behavioral medicine at the Penn Pain Medicine Center at the University of Pennsylvania’s Perelman School of Medicine, Philadelphia, another important factor is the more than 100 million Americans who suffer from obesity. “Obesity is a major risk factor for chronic pain conditions including advancing joint disease, low back pain, and diabetic neuropathies,” he said.

Age is an amplifier, agreed Beth Darnall, PhD, a professor of anesthesiology and perioperative and pain medicine and director of the Pain Relief Innovations Lab at Stanford University in Palo Alto, California, but the increases in chronic pain and HICP cut across age strata. 

“Across the board we see striking increases in chronic pain, such as a 5% increase for those 65 and older, and a nearly 2% increase in HICP in that same age group,” Darnall said, referencing the changes from 2019 data in the new NCHS Data Brief. “And an almost 4% increase was observed for the youngest adult age category,18 to 29. Some of our research is now focusing on how to best treat chronic pain in young adults.”

The rise in chronic pain is broadly linked to the overall decline in the health of the US population, as indicated by the CDC 2024’s Chronic Disease Prevalence in the US: Sociodemographic and Geographic Variations by Zip Code Tabulation Area.

 

The Opioid Crisis and COVID

Beginning in 2016, in response to the opioid crisis and CDC guidelines, opioid prescribing for chronic pain rapidly dropped, both in terms of new prescriptions and tapering of doses of long-term users. “Reduced opioid prescribing yielded benefits for some patients but created new problems and harms for other patients,” said Darnall. Cheng added that the CDC’s recommendations on opioid prescribing were widely misinterpreted and were applied to patients with painful conditions such as cancer and sickle cell disease who were not intended to be affected by the guidelines. “In addition, although medical opioid prescribing dropped by 50%, overdose deaths from non-medical opioid sources increased by more 50%.”

Currently, most opioid overdoses are related to heroin, fentanyl, and newer drugs of abuse such as xylazine. “Most pain clinicians would agree that opioids are not first-line therapy for chronic non-cancer pain, but in a select number of well-vetted patients, opioids can be very effective in improving functionality and quality of life as part of a multimodal approach to pain care,” Cheatle said. 

The impact of the opioid crisis is complex, said Cheatle, noting that only 8%-10% of pain patients on long-term opioid therapy develop a use disorder. “However, opioids were overly prescribed due to clinicians’ lack of training in core competencies of pain management and the insurance companies’ refusal to adequately cover non-opioid therapies such as acupuncture, cognitive behavioral therapy, extended physical therapy, and medical massage,” he said. 

He pointed out that in the late 1990s there were more than 1000 multidisciplinary pain centers, whereas currently there are many fewer owing to lack of insurance reimbursement. “This results in more possibly avoidable invasive surgeries, which can further contribute to the increase in chronic pain.” 

The COVID pandemic further exacerbated the pain problem and delayed access to timely medical interventions for many people. Some adopted a more sedentary lifestyle, already entrenched in today’s technology-driven society, leading in turn to weight gain and more chronic pain. “The isolation and lack of normal human connections during the pandemic could exacerbate pain and loss of autonomy,” Cheatle said. And some individuals developed painful neurologic conditions related to long-haul COVID, for which there is no effective treatment. 

 

Best Approach

“Historically, pain has been treated as a purely biomedical issue. Bringing a biopsychosocial perspective to pain care can support pain relief,” said Darnall. Multiple national clinical guidance documents have called for a comprehensive approach that considers the whole person: their circumstances, their needs, their stressors, and their environment. “And we must provide patients meaningful access to the lowest-risk, non-pharmacologic treatments first – and ideally early on,” she said.

Even effective medications rarely make a person pain free, so other approaches are needed in tandem, Darnall said. Support for stronger patient competency in self-management of chronic pain is mounting.

“It’s vitally important that we help people know how to help themselves have less pain – how to steer their mind and body toward relief by using pain relief skills,” she said. “By so doing they can cultivate a critical level of control over their pain and are less at its mercy, which supports good mood and is shown to help people be more active as the impacts of pain diminish.”

Darnall outlined a recent development in the primary care setting that involves offering patients a brief program in pain-relief skills training. Within Veterans Affairs primary care, for example, patients receive several 30-minute sessions in pain reduction techniques. Outside of the VA, primary care clinics are incorporating an evidence-based, one-session 2-hour pain relief skills class called Empowered Relief, as standard care. 

The class teaches participants three pain management skills and creates a personalized plan for each that includes a free app for ongoing daily use.

Since pain causes agitation in the central nervous system, manifested as fast heart rate, rapid breathing, muscle tension, and distress, people learn various ways to calm the central nervous system – with, for example, a sound technology known as binaural audio to deepen the relaxation response. “They also learn to identify and target worry about pain and develop self-soothing actions to interrupt unhelpful patterns,” Darnall said. 

Data from randomized chronic pain studies, including one by her group using a virtual reality training program for lower back pain, show that 3 months after the training program people report clinically meaningful reductions in pain intensity, pain interference with daily activities, and sleep disturbance, as well as pain-related distress, anxiety, and fatigue

While psychological and complementary approaches have been effective in improving function and mood, there are barriers to accessing them, said Cheatle, such as lack of insurance coverage and the stigma associated with nontraditional, especially psychological, care.

 

Prevention

Good lifestyle behaviors promote better health as people age. “Maintaining a healthy weight, staying active, prioritizing good sleep, and avoiding smoking and alcohol use can support better health and buffer against chronic diseases and pain,” Darnall said.

Cheatle noted the importance of maintaining a safe work environment and avoiding injury risks by, for example, wearing a seatbelt or a cycling helmet. 

 

The Future 

“We need to ensure all individuals have access to effective, low-burden pain treatments, including evidence-based treatments they can receive from home so as to minimize treatment disparities.” Darnall said. Also needed is better comprehensive treatment for acute and chronic pain alike. “If we treat acute pain better, we will have fewer people transitioning to the chronic pain state.”

To that end, added Cheng, healthcare professionals in every specialty from doctors and nurses to psychologists and chiropractors need to develop co-competencies in pain management. 

For Cheatle, the near future looks bleak. “There are some pioneering bioengineering approaches to reduce chronic pain and novel pharmacologic agents such as calcitonin gene-related peptide inhibitors for intractable migraines, but just changing insurance reimbursement for a comprehensive approach to chronic pain care and bolstering healthcare provider education on core pain competencies will benefit the over 50 million adults who suffer from chronic pain.” 

Cheng, however, is more sanguine. “I don’t expect miracles in 10 years’ time, but we’re making rapid progress in understanding the genetics of chronic pain and the mechanisms of disease and therapy. We’re developing biomarkers to help in prognosis and monitor disease progress.” In the meantime, he pointed to an expanding array of non-pharmaceutical options, including neuromodulatory approaches such as nerve blocks and spinal cord stimulation.

Cheng, Cheatle, and Darnall disclosed no relevant competing interests.

A version of this article appeared on Medscape.com.

More Americans than ever are hurting with enduring, life-restricting pain. Like obesity, this condition is on the rise, according to figures in a new National Center for Health Statistics (NCHS) Data Brief from the Centers for Disease Control and Prevention (CDC).

In 2023, 24.3% of US adults had chronic pain, and 8.5% had high-impact chronic pain (HICP) that frequently limited daily activities in the past 3 months. Both types increased with age and with decreasing urbanization level. Women were more likely than men to have HICP (23.2% vs 7.3%). 

Like obesity, chronic pain is multifactorial and is best managed with multidisciplinary intervention, said Jianguo Cheng, MD, PhD, a professor of anesthesiology and medical director of the Cleveland Clinic Consortium for Pain in Ohio. “It’s a complex mix of genetic, biological, and psychosocial dimensions that can cause ongoing pain out of proportion to the original limited injury that triggered it.”

While today’s longer lifespans are the primary driver of the increase, noted Martin Cheatle, PhD, an associate professor of psychiatry, anesthesiology, and critical care and director of behavioral medicine at the Penn Pain Medicine Center at the University of Pennsylvania’s Perelman School of Medicine, Philadelphia, another important factor is the more than 100 million Americans who suffer from obesity. “Obesity is a major risk factor for chronic pain conditions including advancing joint disease, low back pain, and diabetic neuropathies,” he said.

Age is an amplifier, agreed Beth Darnall, PhD, a professor of anesthesiology and perioperative and pain medicine and director of the Pain Relief Innovations Lab at Stanford University in Palo Alto, California, but the increases in chronic pain and HICP cut across age strata. 

“Across the board we see striking increases in chronic pain, such as a 5% increase for those 65 and older, and a nearly 2% increase in HICP in that same age group,” Darnall said, referencing the changes from 2019 data in the new NCHS Data Brief. “And an almost 4% increase was observed for the youngest adult age category,18 to 29. Some of our research is now focusing on how to best treat chronic pain in young adults.”

The rise in chronic pain is broadly linked to the overall decline in the health of the US population, as indicated by the CDC 2024’s Chronic Disease Prevalence in the US: Sociodemographic and Geographic Variations by Zip Code Tabulation Area.

 

The Opioid Crisis and COVID

Beginning in 2016, in response to the opioid crisis and CDC guidelines, opioid prescribing for chronic pain rapidly dropped, both in terms of new prescriptions and tapering of doses of long-term users. “Reduced opioid prescribing yielded benefits for some patients but created new problems and harms for other patients,” said Darnall. Cheng added that the CDC’s recommendations on opioid prescribing were widely misinterpreted and were applied to patients with painful conditions such as cancer and sickle cell disease who were not intended to be affected by the guidelines. “In addition, although medical opioid prescribing dropped by 50%, overdose deaths from non-medical opioid sources increased by more 50%.”

Currently, most opioid overdoses are related to heroin, fentanyl, and newer drugs of abuse such as xylazine. “Most pain clinicians would agree that opioids are not first-line therapy for chronic non-cancer pain, but in a select number of well-vetted patients, opioids can be very effective in improving functionality and quality of life as part of a multimodal approach to pain care,” Cheatle said. 

The impact of the opioid crisis is complex, said Cheatle, noting that only 8%-10% of pain patients on long-term opioid therapy develop a use disorder. “However, opioids were overly prescribed due to clinicians’ lack of training in core competencies of pain management and the insurance companies’ refusal to adequately cover non-opioid therapies such as acupuncture, cognitive behavioral therapy, extended physical therapy, and medical massage,” he said. 

He pointed out that in the late 1990s there were more than 1000 multidisciplinary pain centers, whereas currently there are many fewer owing to lack of insurance reimbursement. “This results in more possibly avoidable invasive surgeries, which can further contribute to the increase in chronic pain.” 

The COVID pandemic further exacerbated the pain problem and delayed access to timely medical interventions for many people. Some adopted a more sedentary lifestyle, already entrenched in today’s technology-driven society, leading in turn to weight gain and more chronic pain. “The isolation and lack of normal human connections during the pandemic could exacerbate pain and loss of autonomy,” Cheatle said. And some individuals developed painful neurologic conditions related to long-haul COVID, for which there is no effective treatment. 

 

Best Approach

“Historically, pain has been treated as a purely biomedical issue. Bringing a biopsychosocial perspective to pain care can support pain relief,” said Darnall. Multiple national clinical guidance documents have called for a comprehensive approach that considers the whole person: their circumstances, their needs, their stressors, and their environment. “And we must provide patients meaningful access to the lowest-risk, non-pharmacologic treatments first – and ideally early on,” she said.

Even effective medications rarely make a person pain free, so other approaches are needed in tandem, Darnall said. Support for stronger patient competency in self-management of chronic pain is mounting.

“It’s vitally important that we help people know how to help themselves have less pain – how to steer their mind and body toward relief by using pain relief skills,” she said. “By so doing they can cultivate a critical level of control over their pain and are less at its mercy, which supports good mood and is shown to help people be more active as the impacts of pain diminish.”

Darnall outlined a recent development in the primary care setting that involves offering patients a brief program in pain-relief skills training. Within Veterans Affairs primary care, for example, patients receive several 30-minute sessions in pain reduction techniques. Outside of the VA, primary care clinics are incorporating an evidence-based, one-session 2-hour pain relief skills class called Empowered Relief, as standard care. 

The class teaches participants three pain management skills and creates a personalized plan for each that includes a free app for ongoing daily use.

Since pain causes agitation in the central nervous system, manifested as fast heart rate, rapid breathing, muscle tension, and distress, people learn various ways to calm the central nervous system – with, for example, a sound technology known as binaural audio to deepen the relaxation response. “They also learn to identify and target worry about pain and develop self-soothing actions to interrupt unhelpful patterns,” Darnall said. 

Data from randomized chronic pain studies, including one by her group using a virtual reality training program for lower back pain, show that 3 months after the training program people report clinically meaningful reductions in pain intensity, pain interference with daily activities, and sleep disturbance, as well as pain-related distress, anxiety, and fatigue

While psychological and complementary approaches have been effective in improving function and mood, there are barriers to accessing them, said Cheatle, such as lack of insurance coverage and the stigma associated with nontraditional, especially psychological, care.

 

Prevention

Good lifestyle behaviors promote better health as people age. “Maintaining a healthy weight, staying active, prioritizing good sleep, and avoiding smoking and alcohol use can support better health and buffer against chronic diseases and pain,” Darnall said.

Cheatle noted the importance of maintaining a safe work environment and avoiding injury risks by, for example, wearing a seatbelt or a cycling helmet. 

 

The Future 

“We need to ensure all individuals have access to effective, low-burden pain treatments, including evidence-based treatments they can receive from home so as to minimize treatment disparities.” Darnall said. Also needed is better comprehensive treatment for acute and chronic pain alike. “If we treat acute pain better, we will have fewer people transitioning to the chronic pain state.”

To that end, added Cheng, healthcare professionals in every specialty from doctors and nurses to psychologists and chiropractors need to develop co-competencies in pain management. 

For Cheatle, the near future looks bleak. “There are some pioneering bioengineering approaches to reduce chronic pain and novel pharmacologic agents such as calcitonin gene-related peptide inhibitors for intractable migraines, but just changing insurance reimbursement for a comprehensive approach to chronic pain care and bolstering healthcare provider education on core pain competencies will benefit the over 50 million adults who suffer from chronic pain.” 

Cheng, however, is more sanguine. “I don’t expect miracles in 10 years’ time, but we’re making rapid progress in understanding the genetics of chronic pain and the mechanisms of disease and therapy. We’re developing biomarkers to help in prognosis and monitor disease progress.” In the meantime, he pointed to an expanding array of non-pharmaceutical options, including neuromodulatory approaches such as nerve blocks and spinal cord stimulation.

Cheng, Cheatle, and Darnall disclosed no relevant competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

Perfluorohexanoic acid (PFHxA) is found in fluoroelastomer watch bands at concentrations of up to 16,662 ng/g, highlighting the need for further research on dermal absorption and exposure risks.

METHODOLOGY:

• Fluoroelastomers are a subclass of polymeric per- and polyfluoroalkyl substances (PFAS), which are used to help wearable device materials maintain their appearance and structure after contact with the skin, sweat, and personal care products (eg, sunscreen).
• Researchers investigated the presence of PFAS in 22 new and used US fitness and smart watch bands from a range of brands and price points, of which 13 were advertised as containing fluoroelastomers.
• Total fluorine concentrations were measured using particle-induced gamma-ray emission spectroscopy with cut pieces of the watch bands.
• Solvent extraction was performed, and targeted analysis for 20 PFAS compounds was conducted using liquid chromatography-tandem mass spectrometry.
• A subset of six watch bands, with the highest and lowest detectable PFAS concentrations (three each), was subjected to a direct total oxidative precursor assay to determine the presence of PFAS precursors.

TAKEAWAY:

• Watch bands advertised as containing fluoroelastomers had total fluorine concentrations ranging from 28.5% to 90.7%; only two of the nine bands not advertised to contain fluoroelastomers had concentrations of this PFAS, which ranged from 28.1% to 49.7%.
• Expensive watch bands showed high fluorine levels, with concentrations ranging from 49.7% to 90.7%, whereas inexpensive bands contained less than 1% fluorine on their surface.
• PFHxA was the most common PFAS, detected in 41% of the watch bands.
• PFXxA had a median concentration of 773 ng/g, much higher than the concentrations found in other consumer products, with one sample showing a concentration of 16,662 ng/g.
• Bands containing high PFHxA concentrations had total PFAS levels between 253 and 2016 ng/g, whereas those with low or no PFHxA concentrations had total PFAS levels between 3 and 24 ng/g.

IN PRACTICE:

“The thousands of ng/g of PFHxA available, paired with watch band users often wearing these items for more than 12 h per day, poses an opportunity for significant transfer to the dermis and subsequent human exposure,” the authors wrote.

“If the consumer wishes to purchase a higher-priced band, we suggest that they read the product descriptions and avoid any that are listed as containing fluoroelastomers,” said the study’s lead author in a press release.
 

SOURCE:

The study was led by Alyssa Wicks, University of Notre Dame in Indiana, and published online in Environmental Science & Technology Letters.

LIMITATIONS: 

No limitations were reported in the study. 

DISCLOSURES:

The study received funding from the University of Notre Dame. The authors declared no competing financial interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Perfluorohexanoic acid (PFHxA) is found in fluoroelastomer watch bands at concentrations of up to 16,662 ng/g, highlighting the need for further research on dermal absorption and exposure risks.

METHODOLOGY:

• Fluoroelastomers are a subclass of polymeric per- and polyfluoroalkyl substances (PFAS), which are used to help wearable device materials maintain their appearance and structure after contact with the skin, sweat, and personal care products (eg, sunscreen).
• Researchers investigated the presence of PFAS in 22 new and used US fitness and smart watch bands from a range of brands and price points, of which 13 were advertised as containing fluoroelastomers.
• Total fluorine concentrations were measured using particle-induced gamma-ray emission spectroscopy with cut pieces of the watch bands.
• Solvent extraction was performed, and targeted analysis for 20 PFAS compounds was conducted using liquid chromatography-tandem mass spectrometry.
• A subset of six watch bands, with the highest and lowest detectable PFAS concentrations (three each), was subjected to a direct total oxidative precursor assay to determine the presence of PFAS precursors.

TAKEAWAY:

• Watch bands advertised as containing fluoroelastomers had total fluorine concentrations ranging from 28.5% to 90.7%; only two of the nine bands not advertised to contain fluoroelastomers had concentrations of this PFAS, which ranged from 28.1% to 49.7%.
• Expensive watch bands showed high fluorine levels, with concentrations ranging from 49.7% to 90.7%, whereas inexpensive bands contained less than 1% fluorine on their surface.
• PFHxA was the most common PFAS, detected in 41% of the watch bands.
• PFXxA had a median concentration of 773 ng/g, much higher than the concentrations found in other consumer products, with one sample showing a concentration of 16,662 ng/g.
• Bands containing high PFHxA concentrations had total PFAS levels between 253 and 2016 ng/g, whereas those with low or no PFHxA concentrations had total PFAS levels between 3 and 24 ng/g.

IN PRACTICE:

“The thousands of ng/g of PFHxA available, paired with watch band users often wearing these items for more than 12 h per day, poses an opportunity for significant transfer to the dermis and subsequent human exposure,” the authors wrote.

“If the consumer wishes to purchase a higher-priced band, we suggest that they read the product descriptions and avoid any that are listed as containing fluoroelastomers,” said the study’s lead author in a press release.
 

SOURCE:

The study was led by Alyssa Wicks, University of Notre Dame in Indiana, and published online in Environmental Science & Technology Letters.

LIMITATIONS: 

No limitations were reported in the study. 

DISCLOSURES:

The study received funding from the University of Notre Dame. The authors declared no competing financial interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Perfluorohexanoic acid (PFHxA) is found in fluoroelastomer watch bands at concentrations of up to 16,662 ng/g, highlighting the need for further research on dermal absorption and exposure risks.

METHODOLOGY:

• Fluoroelastomers are a subclass of polymeric per- and polyfluoroalkyl substances (PFAS), which are used to help wearable device materials maintain their appearance and structure after contact with the skin, sweat, and personal care products (eg, sunscreen).
• Researchers investigated the presence of PFAS in 22 new and used US fitness and smart watch bands from a range of brands and price points, of which 13 were advertised as containing fluoroelastomers.
• Total fluorine concentrations were measured using particle-induced gamma-ray emission spectroscopy with cut pieces of the watch bands.
• Solvent extraction was performed, and targeted analysis for 20 PFAS compounds was conducted using liquid chromatography-tandem mass spectrometry.
• A subset of six watch bands, with the highest and lowest detectable PFAS concentrations (three each), was subjected to a direct total oxidative precursor assay to determine the presence of PFAS precursors.

TAKEAWAY:

• Watch bands advertised as containing fluoroelastomers had total fluorine concentrations ranging from 28.5% to 90.7%; only two of the nine bands not advertised to contain fluoroelastomers had concentrations of this PFAS, which ranged from 28.1% to 49.7%.
• Expensive watch bands showed high fluorine levels, with concentrations ranging from 49.7% to 90.7%, whereas inexpensive bands contained less than 1% fluorine on their surface.
• PFHxA was the most common PFAS, detected in 41% of the watch bands.
• PFXxA had a median concentration of 773 ng/g, much higher than the concentrations found in other consumer products, with one sample showing a concentration of 16,662 ng/g.
• Bands containing high PFHxA concentrations had total PFAS levels between 253 and 2016 ng/g, whereas those with low or no PFHxA concentrations had total PFAS levels between 3 and 24 ng/g.

IN PRACTICE:

“The thousands of ng/g of PFHxA available, paired with watch band users often wearing these items for more than 12 h per day, poses an opportunity for significant transfer to the dermis and subsequent human exposure,” the authors wrote.

“If the consumer wishes to purchase a higher-priced band, we suggest that they read the product descriptions and avoid any that are listed as containing fluoroelastomers,” said the study’s lead author in a press release.
 

SOURCE:

The study was led by Alyssa Wicks, University of Notre Dame in Indiana, and published online in Environmental Science & Technology Letters.

LIMITATIONS: 

No limitations were reported in the study. 

DISCLOSURES:

The study received funding from the University of Notre Dame. The authors declared no competing financial interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

On a recent Sunday morning in Los Angeles, 10 members of Gamblers Anonymous gathered in a park for their regular meeting. After, they shared advice for how physicians can best help patients with problem gambling.

“If a patient talks about financial distress, spouse issues, physical issues, or has blood pressure issues, suspect gambling,” one woman said. Another said, if a physician asks about gambling and the patient says, “Just a little,” chances are that person is an active gambler.

The bottom line: None of the people — who spoke for themselves and not on behalf of Gamblers Anonymous — said they had been asked by their doctors about gambling issues. All said they would welcome such questions.

Gambling is on the rise, and gambling disorder is now recognized in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). The condition is viewed as similar to substance-related disorders in its clinical expression, brain origin, comorbidity, physiology, and treatment.

Primary care physicians (PCPs), more than any of their colleagues, are likely to encounter a patient with an undetected gambling disorder, according to experts, as it often intertwines with physical and mental health concerns. Those conditions bring the patient to their clinicians, although the patients may not link those issues with their gambling. The physicians may not either.

Few PCPs broach the topic. “I would say the majority of physicians do not screen for it,” said Brian K. Unwin, MD, FAAFP, AGSF, a family medicine physician and geriatrician at the Carilion Center for Healthy Aging and professor at the Virginia Tech Carilion School of Medicine, Roanoke.

The clinician who does take steps to screen for the problem is “exceptionally rare,” said Timothy W. Fong, MD, clinical professor of psychiatry at the University of California, Los Angeles (UCLA) and co-director of the UCLA Gambling Studies Program. Launched in 2005, the program conducts research, provides prevention and treatment services, and offers training to healthcare providers and the community.

A Las Vegas physician said colleagues in her area are likewise largely unaware, despite the strong connection with the city and gaming. “I do not think most primary care physicians are routinely asking about gambling,” said Maureen Strohm, MD, president of the Nevada Society of Addiction Medicine. Strohm also directs the addiction medicine fellowship at HCA Sunrise Health GME Consortium at Southern Hills Hospital & Medical Center in Las Vegas and cares for patients with substance abuse issues.

But physicians should look for gambling issues, she said, especially in those with known substance abuse disorders. “We encourage incorporation of gambling as another question in comprehensive assessment of patients, since it’s rarely an isolated issue in our treatment settings,” Strohm said.

 

Gritty Reputation Goes Glam, With No Shortage of Opportunities

Why a rise in gambling? Its reputation, for one thing. “It used to be, if you enjoyed gambling, you were viewed as, what — a person of vice, a person of sin,” Fong said. “That’s completely changed. Engaging in gambling is more accepted — and not just accepted but normalized and even glamorized. In some circles, if you don’t gamble, it’s like, ‘What is wrong with you?’ ”

Opportunities to gamble have increased, including a boom in mobile sports betting. Sports betting online, in person, or both now is legal in 39 states and the District of Columbia. The rate of gambling problems among sports bettors is at least twice as high as that for other gamblers, the National Council on Problem Gambling found. As Fong puts it: “The casino comes to you.”

With the rise in opportunities to bet has come an increase in gambling-related disorders. Statistics vary greatly, but Unwin cites a meta-analysis published in 2023 that found moderate-risk or at-risk gambling affects 2.4% of the adult population and pathologic or problem gambling affects 1.29%. He first noticed problem gambling in young soldiers when he was a military doctor and published on it in 2000.

However, the percentage of people with gambling issues seeking care in PCPs’ offices is much higher, probably from 5% to 16%, research has found. “When you survey people who go to the primary care physicians, the number [with a gambling issue] could be as high as 10%-15% of those going for any medical reason,” Fong said. “Many times, their stories are hidden.”

In November, The Lancet Public Health Commission said it views problem gambling as an expanding public health threat.

 

Seeing the Red Flags

“In a perfect world, it would be great to ask all patients” about gambling issues, Unwin said. A more realistic approach, given clinical workloads, is to be alert to the possibility, especially in patients with depression or substance abuse, which often accompany gambling issues.

Learn to look at patterns, Unwin said. “If a patient has had impulsivity issues, is a young male, has had depression and alcohol issues, let’s look and see what else is going on.” 

Other red flags include anyone with an active mental health problem or with a family history of known gambling problems, Fong said.

Some personality traits are linked with a higher likelihood of gambling issues, including highly impulsive behavior and risk-taking behavior. Many problem gamblers are “not very good with loss aversion. They lose a bunch and shrug it off and go back the next day,” Fong noted.

Often, however, the clues are not obvious. Unwin remembers caring for an older couple, and the wife set up an appointment with him — not to talk about her health but to discuss his gambling. “My husband has spent us into debt,” she said. Unwin recalled being completely surprised.

The situation illustrates the flaw in the stereotypical profile of a problem. “In our mind’s eye, it’s often an older White male who talks loudly, is perhaps counterculture,” Fong said. But he often sees young and older people from all cultures and all economic levels struggling with gambling: “Like other forms of addiction, it cuts across all demographics.”

 

Inside a Gambler’s Brain

Many physicians struggle to understand the attraction of gambling, Fong said. They ask: “How can you be addicted to a behavior? Why can’t you just stop?” He tells them: “If people could do that, they would not have a biological psychiatric disorder,” which is what gambling disorder is.

The urge to gamble can be so strong, “You can’t think of anything else,” Fong said. “It screws up your day.” Gamblers say they’re after the “action,” the euphoric state similar to the highs produced from some drugs. Compared with recreational gamblers, problem gamblers rely more on long-term learning than short-term reward?, and so are less able to learn from their losses in the immediate past, research by Fong and others found.

 

Seeking Treatment

One in five problem gamblers seeks help, and 1 in 25 with a moderate-risk habit do so, Unwin said, citing a 2022 study.

To identify concerning behaviors, physicians can turn to two brief screeners that take just minutes:

• The Brief Biosocial Gambling Screen includes just three questions; a yes to any one suggests a gambling problem.
• The Lie-Bet two-question screener can help determine if a person needs a referral for a gambling problem.

“People tend to be pretty honest with their doctor when asked about gambling,” Fong said. “Even the act of asking is enough to get people to start thinking.”

To meet the DSM-5 criteria for gambling disorder, patients must exhibit at least four or more concerning behaviors in the previous 12 months.

For available treatments, “our toolbox is growing,” Fong said. “Psychotherapy probably works best,” including cognitive-behavioral therapy and relapse prevention approaches. “Twelve-step programs work very well,” Fong added.

Medications used for alcohol use disorder, such as naltrexone, an opioid antagonist, are prescribed for gambling disorder, with some success, he said. Often, developing a positive therapeutic relationship with a person who does not judge them is enough to change behavior, Fong said.

To provide treatment and other services, the UCLA program collaborates with the state Office of Problem Gambling. “We know that at least 70% of our patients who stay in treatment and participate in treatment make really meaningful gains and improvement in some part of their lives,” Fong said. “They do gamble less; they do gamble with less money.

 

Goal: Cold Turkey or Harm Reduction?

Fong tells gamblers seeking help: “My goal is to reduce the harm related to your gambling.” In working with patients, he identifies forms that are most problematic and those less likely to cause problems. For some, sports betting may be an issue, but going to Las Vegas a few times a year to play the slots may not generate harm for them. Many patients still gamble, he said, but have a better quality of life if they focus on health and wellness.

“Abstinence is just one domain,” Fong said. The others — home, health, self-care, a sense of purpose, community — are important, too. He helps patients to focus on those.”

Of all the addictions, gambling is one physicians are largely unaware of, Fong said. “And the patients have something that can be treated.”

Unwin, Strohm, and Fong reported no relevant financial disclosures. Physicians can attend open meetings of Gamblers Anonymous to find out more. Members of the group are available to speak to clinicians.

A version of this article appeared on Medscape.com.

On a recent Sunday morning in Los Angeles, 10 members of Gamblers Anonymous gathered in a park for their regular meeting. After, they shared advice for how physicians can best help patients with problem gambling.

“If a patient talks about financial distress, spouse issues, physical issues, or has blood pressure issues, suspect gambling,” one woman said. Another said, if a physician asks about gambling and the patient says, “Just a little,” chances are that person is an active gambler.

The bottom line: None of the people — who spoke for themselves and not on behalf of Gamblers Anonymous — said they had been asked by their doctors about gambling issues. All said they would welcome such questions.

Gambling is on the rise, and gambling disorder is now recognized in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). The condition is viewed as similar to substance-related disorders in its clinical expression, brain origin, comorbidity, physiology, and treatment.

Primary care physicians (PCPs), more than any of their colleagues, are likely to encounter a patient with an undetected gambling disorder, according to experts, as it often intertwines with physical and mental health concerns. Those conditions bring the patient to their clinicians, although the patients may not link those issues with their gambling. The physicians may not either.

Few PCPs broach the topic. “I would say the majority of physicians do not screen for it,” said Brian K. Unwin, MD, FAAFP, AGSF, a family medicine physician and geriatrician at the Carilion Center for Healthy Aging and professor at the Virginia Tech Carilion School of Medicine, Roanoke.

The clinician who does take steps to screen for the problem is “exceptionally rare,” said Timothy W. Fong, MD, clinical professor of psychiatry at the University of California, Los Angeles (UCLA) and co-director of the UCLA Gambling Studies Program. Launched in 2005, the program conducts research, provides prevention and treatment services, and offers training to healthcare providers and the community.

A Las Vegas physician said colleagues in her area are likewise largely unaware, despite the strong connection with the city and gaming. “I do not think most primary care physicians are routinely asking about gambling,” said Maureen Strohm, MD, president of the Nevada Society of Addiction Medicine. Strohm also directs the addiction medicine fellowship at HCA Sunrise Health GME Consortium at Southern Hills Hospital & Medical Center in Las Vegas and cares for patients with substance abuse issues.

But physicians should look for gambling issues, she said, especially in those with known substance abuse disorders. “We encourage incorporation of gambling as another question in comprehensive assessment of patients, since it’s rarely an isolated issue in our treatment settings,” Strohm said.

 

Gritty Reputation Goes Glam, With No Shortage of Opportunities

Why a rise in gambling? Its reputation, for one thing. “It used to be, if you enjoyed gambling, you were viewed as, what — a person of vice, a person of sin,” Fong said. “That’s completely changed. Engaging in gambling is more accepted — and not just accepted but normalized and even glamorized. In some circles, if you don’t gamble, it’s like, ‘What is wrong with you?’ ”

Opportunities to gamble have increased, including a boom in mobile sports betting. Sports betting online, in person, or both now is legal in 39 states and the District of Columbia. The rate of gambling problems among sports bettors is at least twice as high as that for other gamblers, the National Council on Problem Gambling found. As Fong puts it: “The casino comes to you.”

With the rise in opportunities to bet has come an increase in gambling-related disorders. Statistics vary greatly, but Unwin cites a meta-analysis published in 2023 that found moderate-risk or at-risk gambling affects 2.4% of the adult population and pathologic or problem gambling affects 1.29%. He first noticed problem gambling in young soldiers when he was a military doctor and published on it in 2000.

However, the percentage of people with gambling issues seeking care in PCPs’ offices is much higher, probably from 5% to 16%, research has found. “When you survey people who go to the primary care physicians, the number [with a gambling issue] could be as high as 10%-15% of those going for any medical reason,” Fong said. “Many times, their stories are hidden.”

In November, The Lancet Public Health Commission said it views problem gambling as an expanding public health threat.

 

Seeing the Red Flags

“In a perfect world, it would be great to ask all patients” about gambling issues, Unwin said. A more realistic approach, given clinical workloads, is to be alert to the possibility, especially in patients with depression or substance abuse, which often accompany gambling issues.

Learn to look at patterns, Unwin said. “If a patient has had impulsivity issues, is a young male, has had depression and alcohol issues, let’s look and see what else is going on.” 

Other red flags include anyone with an active mental health problem or with a family history of known gambling problems, Fong said.

Some personality traits are linked with a higher likelihood of gambling issues, including highly impulsive behavior and risk-taking behavior. Many problem gamblers are “not very good with loss aversion. They lose a bunch and shrug it off and go back the next day,” Fong noted.

Often, however, the clues are not obvious. Unwin remembers caring for an older couple, and the wife set up an appointment with him — not to talk about her health but to discuss his gambling. “My husband has spent us into debt,” she said. Unwin recalled being completely surprised.

The situation illustrates the flaw in the stereotypical profile of a problem. “In our mind’s eye, it’s often an older White male who talks loudly, is perhaps counterculture,” Fong said. But he often sees young and older people from all cultures and all economic levels struggling with gambling: “Like other forms of addiction, it cuts across all demographics.”

 

Inside a Gambler’s Brain

Many physicians struggle to understand the attraction of gambling, Fong said. They ask: “How can you be addicted to a behavior? Why can’t you just stop?” He tells them: “If people could do that, they would not have a biological psychiatric disorder,” which is what gambling disorder is.

The urge to gamble can be so strong, “You can’t think of anything else,” Fong said. “It screws up your day.” Gamblers say they’re after the “action,” the euphoric state similar to the highs produced from some drugs. Compared with recreational gamblers, problem gamblers rely more on long-term learning than short-term reward?, and so are less able to learn from their losses in the immediate past, research by Fong and others found.

 

Seeking Treatment

One in five problem gamblers seeks help, and 1 in 25 with a moderate-risk habit do so, Unwin said, citing a 2022 study.

To identify concerning behaviors, physicians can turn to two brief screeners that take just minutes:

• The Brief Biosocial Gambling Screen includes just three questions; a yes to any one suggests a gambling problem.
• The Lie-Bet two-question screener can help determine if a person needs a referral for a gambling problem.

“People tend to be pretty honest with their doctor when asked about gambling,” Fong said. “Even the act of asking is enough to get people to start thinking.”

To meet the DSM-5 criteria for gambling disorder, patients must exhibit at least four or more concerning behaviors in the previous 12 months.

For available treatments, “our toolbox is growing,” Fong said. “Psychotherapy probably works best,” including cognitive-behavioral therapy and relapse prevention approaches. “Twelve-step programs work very well,” Fong added.

Medications used for alcohol use disorder, such as naltrexone, an opioid antagonist, are prescribed for gambling disorder, with some success, he said. Often, developing a positive therapeutic relationship with a person who does not judge them is enough to change behavior, Fong said.

To provide treatment and other services, the UCLA program collaborates with the state Office of Problem Gambling. “We know that at least 70% of our patients who stay in treatment and participate in treatment make really meaningful gains and improvement in some part of their lives,” Fong said. “They do gamble less; they do gamble with less money.

 

Goal: Cold Turkey or Harm Reduction?

Fong tells gamblers seeking help: “My goal is to reduce the harm related to your gambling.” In working with patients, he identifies forms that are most problematic and those less likely to cause problems. For some, sports betting may be an issue, but going to Las Vegas a few times a year to play the slots may not generate harm for them. Many patients still gamble, he said, but have a better quality of life if they focus on health and wellness.

“Abstinence is just one domain,” Fong said. The others — home, health, self-care, a sense of purpose, community — are important, too. He helps patients to focus on those.”

Of all the addictions, gambling is one physicians are largely unaware of, Fong said. “And the patients have something that can be treated.”

Unwin, Strohm, and Fong reported no relevant financial disclosures. Physicians can attend open meetings of Gamblers Anonymous to find out more. Members of the group are available to speak to clinicians.

A version of this article appeared on Medscape.com.

On a recent Sunday morning in Los Angeles, 10 members of Gamblers Anonymous gathered in a park for their regular meeting. After, they shared advice for how physicians can best help patients with problem gambling.

“If a patient talks about financial distress, spouse issues, physical issues, or has blood pressure issues, suspect gambling,” one woman said. Another said, if a physician asks about gambling and the patient says, “Just a little,” chances are that person is an active gambler.

The bottom line: None of the people — who spoke for themselves and not on behalf of Gamblers Anonymous — said they had been asked by their doctors about gambling issues. All said they would welcome such questions.

Gambling is on the rise, and gambling disorder is now recognized in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). The condition is viewed as similar to substance-related disorders in its clinical expression, brain origin, comorbidity, physiology, and treatment.

Primary care physicians (PCPs), more than any of their colleagues, are likely to encounter a patient with an undetected gambling disorder, according to experts, as it often intertwines with physical and mental health concerns. Those conditions bring the patient to their clinicians, although the patients may not link those issues with their gambling. The physicians may not either.

Few PCPs broach the topic. “I would say the majority of physicians do not screen for it,” said Brian K. Unwin, MD, FAAFP, AGSF, a family medicine physician and geriatrician at the Carilion Center for Healthy Aging and professor at the Virginia Tech Carilion School of Medicine, Roanoke.

The clinician who does take steps to screen for the problem is “exceptionally rare,” said Timothy W. Fong, MD, clinical professor of psychiatry at the University of California, Los Angeles (UCLA) and co-director of the UCLA Gambling Studies Program. Launched in 2005, the program conducts research, provides prevention and treatment services, and offers training to healthcare providers and the community.

A Las Vegas physician said colleagues in her area are likewise largely unaware, despite the strong connection with the city and gaming. “I do not think most primary care physicians are routinely asking about gambling,” said Maureen Strohm, MD, president of the Nevada Society of Addiction Medicine. Strohm also directs the addiction medicine fellowship at HCA Sunrise Health GME Consortium at Southern Hills Hospital & Medical Center in Las Vegas and cares for patients with substance abuse issues.

But physicians should look for gambling issues, she said, especially in those with known substance abuse disorders. “We encourage incorporation of gambling as another question in comprehensive assessment of patients, since it’s rarely an isolated issue in our treatment settings,” Strohm said.

 

Gritty Reputation Goes Glam, With No Shortage of Opportunities

Why a rise in gambling? Its reputation, for one thing. “It used to be, if you enjoyed gambling, you were viewed as, what — a person of vice, a person of sin,” Fong said. “That’s completely changed. Engaging in gambling is more accepted — and not just accepted but normalized and even glamorized. In some circles, if you don’t gamble, it’s like, ‘What is wrong with you?’ ”

Opportunities to gamble have increased, including a boom in mobile sports betting. Sports betting online, in person, or both now is legal in 39 states and the District of Columbia. The rate of gambling problems among sports bettors is at least twice as high as that for other gamblers, the National Council on Problem Gambling found. As Fong puts it: “The casino comes to you.”

With the rise in opportunities to bet has come an increase in gambling-related disorders. Statistics vary greatly, but Unwin cites a meta-analysis published in 2023 that found moderate-risk or at-risk gambling affects 2.4% of the adult population and pathologic or problem gambling affects 1.29%. He first noticed problem gambling in young soldiers when he was a military doctor and published on it in 2000.

However, the percentage of people with gambling issues seeking care in PCPs’ offices is much higher, probably from 5% to 16%, research has found. “When you survey people who go to the primary care physicians, the number [with a gambling issue] could be as high as 10%-15% of those going for any medical reason,” Fong said. “Many times, their stories are hidden.”

In November, The Lancet Public Health Commission said it views problem gambling as an expanding public health threat.

 

Seeing the Red Flags

“In a perfect world, it would be great to ask all patients” about gambling issues, Unwin said. A more realistic approach, given clinical workloads, is to be alert to the possibility, especially in patients with depression or substance abuse, which often accompany gambling issues.

Learn to look at patterns, Unwin said. “If a patient has had impulsivity issues, is a young male, has had depression and alcohol issues, let’s look and see what else is going on.” 

Other red flags include anyone with an active mental health problem or with a family history of known gambling problems, Fong said.

Some personality traits are linked with a higher likelihood of gambling issues, including highly impulsive behavior and risk-taking behavior. Many problem gamblers are “not very good with loss aversion. They lose a bunch and shrug it off and go back the next day,” Fong noted.

Often, however, the clues are not obvious. Unwin remembers caring for an older couple, and the wife set up an appointment with him — not to talk about her health but to discuss his gambling. “My husband has spent us into debt,” she said. Unwin recalled being completely surprised.

The situation illustrates the flaw in the stereotypical profile of a problem. “In our mind’s eye, it’s often an older White male who talks loudly, is perhaps counterculture,” Fong said. But he often sees young and older people from all cultures and all economic levels struggling with gambling: “Like other forms of addiction, it cuts across all demographics.”

 

Inside a Gambler’s Brain

Many physicians struggle to understand the attraction of gambling, Fong said. They ask: “How can you be addicted to a behavior? Why can’t you just stop?” He tells them: “If people could do that, they would not have a biological psychiatric disorder,” which is what gambling disorder is.

The urge to gamble can be so strong, “You can’t think of anything else,” Fong said. “It screws up your day.” Gamblers say they’re after the “action,” the euphoric state similar to the highs produced from some drugs. Compared with recreational gamblers, problem gamblers rely more on long-term learning than short-term reward?, and so are less able to learn from their losses in the immediate past, research by Fong and others found.

 

Seeking Treatment

One in five problem gamblers seeks help, and 1 in 25 with a moderate-risk habit do so, Unwin said, citing a 2022 study.

To identify concerning behaviors, physicians can turn to two brief screeners that take just minutes:

• The Brief Biosocial Gambling Screen includes just three questions; a yes to any one suggests a gambling problem.
• The Lie-Bet two-question screener can help determine if a person needs a referral for a gambling problem.

“People tend to be pretty honest with their doctor when asked about gambling,” Fong said. “Even the act of asking is enough to get people to start thinking.”

To meet the DSM-5 criteria for gambling disorder, patients must exhibit at least four or more concerning behaviors in the previous 12 months.

For available treatments, “our toolbox is growing,” Fong said. “Psychotherapy probably works best,” including cognitive-behavioral therapy and relapse prevention approaches. “Twelve-step programs work very well,” Fong added.

Medications used for alcohol use disorder, such as naltrexone, an opioid antagonist, are prescribed for gambling disorder, with some success, he said. Often, developing a positive therapeutic relationship with a person who does not judge them is enough to change behavior, Fong said.

To provide treatment and other services, the UCLA program collaborates with the state Office of Problem Gambling. “We know that at least 70% of our patients who stay in treatment and participate in treatment make really meaningful gains and improvement in some part of their lives,” Fong said. “They do gamble less; they do gamble with less money.

 

Goal: Cold Turkey or Harm Reduction?

Fong tells gamblers seeking help: “My goal is to reduce the harm related to your gambling.” In working with patients, he identifies forms that are most problematic and those less likely to cause problems. For some, sports betting may be an issue, but going to Las Vegas a few times a year to play the slots may not generate harm for them. Many patients still gamble, he said, but have a better quality of life if they focus on health and wellness.

“Abstinence is just one domain,” Fong said. The others — home, health, self-care, a sense of purpose, community — are important, too. He helps patients to focus on those.”

Of all the addictions, gambling is one physicians are largely unaware of, Fong said. “And the patients have something that can be treated.”

Unwin, Strohm, and Fong reported no relevant financial disclosures. Physicians can attend open meetings of Gamblers Anonymous to find out more. Members of the group are available to speak to clinicians.

A version of this article appeared on Medscape.com.

TOPLINE: 

Among children with traumatic injury, those of Black ethnicity are more likely than those of White ethnicity to be suspected of experiencing child abuse. Young patients and those from low socioeconomic backgrounds also face an increased likelihood of suspicion for child abuse (SCA).

METHODOLOGY:

• Researchers analyzed data on pediatric patients admitted to hospitals after sustaining a traumatic injury between 2006 and 2016 using the Kids’ Inpatient Database (KID) to investigate racial and ethnic disparities in cases in which SCA codes from the 9th and 10th editions of the International Classification of Diseases were used.
• The analysis included a weighted total of 634,309 pediatric patients with complete data, comprising 13,579 patients in the SCA subgroup and 620,730 in the non-SCA subgroup.
• Patient demographics, injury severity, and hospitalization characteristics were classified by race and ethnicity.
• The primary outcome was differences in racial and ethnic composition between the SCA and non-SCA groups, as well as compared with the overall US population using 2010 US Census data.

TAKEAWAY:

• Black patients had 75% higher odds of having a SCA code, compared with White patients; the latter ethnicity was relatively underrepresented in the SCA subgroup, compared with the distribution reported by the US Census.
• Black patients had 10% higher odds of having a SCA code (odds ratio, 1.10; P =.004) than White patients, after socioeconomic factors such as insurance type, household income based on zip code, and injury severity were controlled for.
• Black patients in the SCA subgroup experienced a 26.5% (P < .001) longer hospital stay for mild to moderate injuries and a 40.1% (P < .001) longer stay for serious injuries compared with White patients.
• Patients in the SCA subgroup were significantly younger (mean, 1.70 years vs 9.70 years), were more likely to have Medicaid insurance (76.6% vs 42.0%), and had higher mortality rates (5.6% vs 1.0%) than those in the non-SCA subgroup; they were also more likely to come from lower socioeconomic backgrounds and present with more severe injuries.

IN PRACTICE:

“However, we can identify and appropriately respond to patients with potential child abuse in an equitable way by using clinical decision support tools, seeking clinical consultation of child abuse pediatricians, practicing cultural humility, and enhancing the education and training for health care professionals on child abuse recognition, response, and prevention,” Allison M. Jackson, MD, MPH, of the Child and Adolescent Protection Center at Children’s National Hospital, Washington, DC, wrote in an accompanying editorial.

SOURCE:

The study was led by Fereshteh Salimi-Jazi, MD, of Stanford University School of Medicine in California. It was published online on December 18, 2024, in JAMA Network Open.

LIMITATIONS: 

The study relied on data from KID, which has limitations such as potential coding errors and the inability to follow patients over time. The database combines race and ethnicity in a single field as well. The study only included hospitalized patients, which may not represent all clinician suspicions of SCA cases.

DISCLOSURES:

This study was supported by a grant from the National Center for Advancing Translational Sciences of the National Institutes of Health. The authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE: 

Among children with traumatic injury, those of Black ethnicity are more likely than those of White ethnicity to be suspected of experiencing child abuse. Young patients and those from low socioeconomic backgrounds also face an increased likelihood of suspicion for child abuse (SCA).

METHODOLOGY:

• Researchers analyzed data on pediatric patients admitted to hospitals after sustaining a traumatic injury between 2006 and 2016 using the Kids’ Inpatient Database (KID) to investigate racial and ethnic disparities in cases in which SCA codes from the 9th and 10th editions of the International Classification of Diseases were used.
• The analysis included a weighted total of 634,309 pediatric patients with complete data, comprising 13,579 patients in the SCA subgroup and 620,730 in the non-SCA subgroup.
• Patient demographics, injury severity, and hospitalization characteristics were classified by race and ethnicity.
• The primary outcome was differences in racial and ethnic composition between the SCA and non-SCA groups, as well as compared with the overall US population using 2010 US Census data.

TAKEAWAY:

• Black patients had 75% higher odds of having a SCA code, compared with White patients; the latter ethnicity was relatively underrepresented in the SCA subgroup, compared with the distribution reported by the US Census.
• Black patients had 10% higher odds of having a SCA code (odds ratio, 1.10; P =.004) than White patients, after socioeconomic factors such as insurance type, household income based on zip code, and injury severity were controlled for.
• Black patients in the SCA subgroup experienced a 26.5% (P < .001) longer hospital stay for mild to moderate injuries and a 40.1% (P < .001) longer stay for serious injuries compared with White patients.
• Patients in the SCA subgroup were significantly younger (mean, 1.70 years vs 9.70 years), were more likely to have Medicaid insurance (76.6% vs 42.0%), and had higher mortality rates (5.6% vs 1.0%) than those in the non-SCA subgroup; they were also more likely to come from lower socioeconomic backgrounds and present with more severe injuries.

IN PRACTICE:

“However, we can identify and appropriately respond to patients with potential child abuse in an equitable way by using clinical decision support tools, seeking clinical consultation of child abuse pediatricians, practicing cultural humility, and enhancing the education and training for health care professionals on child abuse recognition, response, and prevention,” Allison M. Jackson, MD, MPH, of the Child and Adolescent Protection Center at Children’s National Hospital, Washington, DC, wrote in an accompanying editorial.

SOURCE:

The study was led by Fereshteh Salimi-Jazi, MD, of Stanford University School of Medicine in California. It was published online on December 18, 2024, in JAMA Network Open.

LIMITATIONS: 

The study relied on data from KID, which has limitations such as potential coding errors and the inability to follow patients over time. The database combines race and ethnicity in a single field as well. The study only included hospitalized patients, which may not represent all clinician suspicions of SCA cases.

DISCLOSURES:

This study was supported by a grant from the National Center for Advancing Translational Sciences of the National Institutes of Health. The authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE: 

Among children with traumatic injury, those of Black ethnicity are more likely than those of White ethnicity to be suspected of experiencing child abuse. Young patients and those from low socioeconomic backgrounds also face an increased likelihood of suspicion for child abuse (SCA).

METHODOLOGY:

• Researchers analyzed data on pediatric patients admitted to hospitals after sustaining a traumatic injury between 2006 and 2016 using the Kids’ Inpatient Database (KID) to investigate racial and ethnic disparities in cases in which SCA codes from the 9th and 10th editions of the International Classification of Diseases were used.
• The analysis included a weighted total of 634,309 pediatric patients with complete data, comprising 13,579 patients in the SCA subgroup and 620,730 in the non-SCA subgroup.
• Patient demographics, injury severity, and hospitalization characteristics were classified by race and ethnicity.
• The primary outcome was differences in racial and ethnic composition between the SCA and non-SCA groups, as well as compared with the overall US population using 2010 US Census data.

TAKEAWAY:

• Black patients had 75% higher odds of having a SCA code, compared with White patients; the latter ethnicity was relatively underrepresented in the SCA subgroup, compared with the distribution reported by the US Census.
• Black patients had 10% higher odds of having a SCA code (odds ratio, 1.10; P =.004) than White patients, after socioeconomic factors such as insurance type, household income based on zip code, and injury severity were controlled for.
• Black patients in the SCA subgroup experienced a 26.5% (P < .001) longer hospital stay for mild to moderate injuries and a 40.1% (P < .001) longer stay for serious injuries compared with White patients.
• Patients in the SCA subgroup were significantly younger (mean, 1.70 years vs 9.70 years), were more likely to have Medicaid insurance (76.6% vs 42.0%), and had higher mortality rates (5.6% vs 1.0%) than those in the non-SCA subgroup; they were also more likely to come from lower socioeconomic backgrounds and present with more severe injuries.

IN PRACTICE:

“However, we can identify and appropriately respond to patients with potential child abuse in an equitable way by using clinical decision support tools, seeking clinical consultation of child abuse pediatricians, practicing cultural humility, and enhancing the education and training for health care professionals on child abuse recognition, response, and prevention,” Allison M. Jackson, MD, MPH, of the Child and Adolescent Protection Center at Children’s National Hospital, Washington, DC, wrote in an accompanying editorial.

SOURCE:

The study was led by Fereshteh Salimi-Jazi, MD, of Stanford University School of Medicine in California. It was published online on December 18, 2024, in JAMA Network Open.

LIMITATIONS: 

The study relied on data from KID, which has limitations such as potential coding errors and the inability to follow patients over time. The database combines race and ethnicity in a single field as well. The study only included hospitalized patients, which may not represent all clinician suspicions of SCA cases.

DISCLOSURES:

This study was supported by a grant from the National Center for Advancing Translational Sciences of the National Institutes of Health. The authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Total intravenous anesthesia (TIVA) enables earlier intraoperative monitoring of facial nerve activity than sevoflurane anesthesia during ear surgery, with reduced patient-ventilator dyssynchrony and fewer requirements for postoperative antiemetics.

METHODOLOGY:

• Researchers evaluated the difference in the timeliness of intraoperative monitoring of facial nerve activity during ear surgery with TIVA vs sevoflurane anesthesia.
• They included 98 patients aged 18-74 years undergoing ear surgery between November 2021 and November 2022; patients were randomly assigned to receive either TIVA or sevoflurane during the procedure. Of these, 92 were included in the final analysis.
• Neuromuscular function was monitored quantitatively throughout anesthesia with train-of-four counts and train-of-four ratios.
• The time from the administration of rocuronium to the start of facial nerve monitoring was recorded.
• The primary outcome measure focused on the recovery index, defined as the time interval between a train-of-four ratio of 0.25 and 0.75; the key secondary outcome was the time to reach a train-of-four ratio of 0.25 from rocuronium administration.

TAKEAWAY:

•  
• The time to reach a train-of-four ratio of 0.25 was achieved earlier with TIVA than with sevoflurane (34 minutes vs 51 minutes; P < .001).
• Patient-ventilator dyssynchrony occurred less frequently in the TIVA group than in the sevoflurane group (15% vs 39%; P = .01).
• Postoperative requests for antiemetics were less frequent in the TIVA group than in the sevoflurane group (2% vs 17%; P = .03).

IN PRACTICE:

“We suggest that TIVA may be a better choice than sevoflurane anesthesia to meet an earlier request” for intraoperative facial nerve monitoring by surgeons, the study authors wrote.

SOURCE:

The study was led by Yu Jeong Bang, MD, of the Department of Anesthesiology and Pain Medicine at Sungkyunkwan University School of Medicine, in Seoul, Republic of Korea. It was published online on November 27, 2024, in The Canadian Journal of Anesthesia.

LIMITATIONS:

A careful interpretation of results may be necessary when clinicians use balanced anesthesia, such as sevoflurane with adjuvants like opioids or nonopioids. The feasibility of intraoperative facial nerve monitoring was decided by the surgeon during surgery, and the lowest stimulation intensity threshold for electromyography amplitude was not detected, as it was not the focus of this study. Although patients requiring intraoperative facial nerve monitoring during ear surgery were enrolled, some did not undergo the procedure based on the surgeon’s judgment.

DISCLOSURES:

This study did not receive any funding. The authors disclosed no relevant conflicts of interest.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Total intravenous anesthesia (TIVA) enables earlier intraoperative monitoring of facial nerve activity than sevoflurane anesthesia during ear surgery, with reduced patient-ventilator dyssynchrony and fewer requirements for postoperative antiemetics.

METHODOLOGY:

• Researchers evaluated the difference in the timeliness of intraoperative monitoring of facial nerve activity during ear surgery with TIVA vs sevoflurane anesthesia.
• They included 98 patients aged 18-74 years undergoing ear surgery between November 2021 and November 2022; patients were randomly assigned to receive either TIVA or sevoflurane during the procedure. Of these, 92 were included in the final analysis.
• Neuromuscular function was monitored quantitatively throughout anesthesia with train-of-four counts and train-of-four ratios.
• The time from the administration of rocuronium to the start of facial nerve monitoring was recorded.
• The primary outcome measure focused on the recovery index, defined as the time interval between a train-of-four ratio of 0.25 and 0.75; the key secondary outcome was the time to reach a train-of-four ratio of 0.25 from rocuronium administration.

TAKEAWAY:

•  
• The time to reach a train-of-four ratio of 0.25 was achieved earlier with TIVA than with sevoflurane (34 minutes vs 51 minutes; P < .001).
• Patient-ventilator dyssynchrony occurred less frequently in the TIVA group than in the sevoflurane group (15% vs 39%; P = .01).
• Postoperative requests for antiemetics were less frequent in the TIVA group than in the sevoflurane group (2% vs 17%; P = .03).

IN PRACTICE:

“We suggest that TIVA may be a better choice than sevoflurane anesthesia to meet an earlier request” for intraoperative facial nerve monitoring by surgeons, the study authors wrote.

SOURCE:

The study was led by Yu Jeong Bang, MD, of the Department of Anesthesiology and Pain Medicine at Sungkyunkwan University School of Medicine, in Seoul, Republic of Korea. It was published online on November 27, 2024, in The Canadian Journal of Anesthesia.

LIMITATIONS:

A careful interpretation of results may be necessary when clinicians use balanced anesthesia, such as sevoflurane with adjuvants like opioids or nonopioids. The feasibility of intraoperative facial nerve monitoring was decided by the surgeon during surgery, and the lowest stimulation intensity threshold for electromyography amplitude was not detected, as it was not the focus of this study. Although patients requiring intraoperative facial nerve monitoring during ear surgery were enrolled, some did not undergo the procedure based on the surgeon’s judgment.

DISCLOSURES:

This study did not receive any funding. The authors disclosed no relevant conflicts of interest.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Total intravenous anesthesia (TIVA) enables earlier intraoperative monitoring of facial nerve activity than sevoflurane anesthesia during ear surgery, with reduced patient-ventilator dyssynchrony and fewer requirements for postoperative antiemetics.

METHODOLOGY:

• Researchers evaluated the difference in the timeliness of intraoperative monitoring of facial nerve activity during ear surgery with TIVA vs sevoflurane anesthesia.
• They included 98 patients aged 18-74 years undergoing ear surgery between November 2021 and November 2022; patients were randomly assigned to receive either TIVA or sevoflurane during the procedure. Of these, 92 were included in the final analysis.
• Neuromuscular function was monitored quantitatively throughout anesthesia with train-of-four counts and train-of-four ratios.
• The time from the administration of rocuronium to the start of facial nerve monitoring was recorded.
• The primary outcome measure focused on the recovery index, defined as the time interval between a train-of-four ratio of 0.25 and 0.75; the key secondary outcome was the time to reach a train-of-four ratio of 0.25 from rocuronium administration.

TAKEAWAY:

•  
• The time to reach a train-of-four ratio of 0.25 was achieved earlier with TIVA than with sevoflurane (34 minutes vs 51 minutes; P < .001).
• Patient-ventilator dyssynchrony occurred less frequently in the TIVA group than in the sevoflurane group (15% vs 39%; P = .01).
• Postoperative requests for antiemetics were less frequent in the TIVA group than in the sevoflurane group (2% vs 17%; P = .03).

IN PRACTICE:

“We suggest that TIVA may be a better choice than sevoflurane anesthesia to meet an earlier request” for intraoperative facial nerve monitoring by surgeons, the study authors wrote.

SOURCE:

The study was led by Yu Jeong Bang, MD, of the Department of Anesthesiology and Pain Medicine at Sungkyunkwan University School of Medicine, in Seoul, Republic of Korea. It was published online on November 27, 2024, in The Canadian Journal of Anesthesia.

LIMITATIONS:

A careful interpretation of results may be necessary when clinicians use balanced anesthesia, such as sevoflurane with adjuvants like opioids or nonopioids. The feasibility of intraoperative facial nerve monitoring was decided by the surgeon during surgery, and the lowest stimulation intensity threshold for electromyography amplitude was not detected, as it was not the focus of this study. Although patients requiring intraoperative facial nerve monitoring during ear surgery were enrolled, some did not undergo the procedure based on the surgeon’s judgment.

DISCLOSURES:

This study did not receive any funding. The authors disclosed no relevant conflicts of interest.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Clinicians frequently reach out to Catherine Varney, DO, asking if it’s safe to prescribe glucagon-like peptide 1 receptor agonists (GLP-1 RAs) to patients with thyroid disorders, such as hypothyroidism, goiter, hyperthyroidism, and nodules.

The concerns often stem from prior animal studies that revealed a link between the medications and abnormal alterations in thyroid C cells.

“What physicians need to understand is that the increased risk of thyroid cancers is specifically in those with a personal or family history of multiple endocrine neoplasia 2 (MEN2) syndrome or medullary thyroid carcinoma [MTC],” said Varney, an assistant professor of family medicine at the University of Virginia (UVA) and obesity medicine director for UVA Health, both in Charlottesville.

MTC is a common manifestation of the MEN2 syndrome, a genetic disorder that affects the endocrine glands and can cause tumors in the thyroid gland. However, MTC is very rare, making up only 3%-5% of all thyroid cancers, Varney said.

More common types of thyroid cancers, such as papillary thyroid cancer, are not contraindications to GLP-1 RAs, said Laura Davisson, MD, MPH, a professor of medicine and director of Medical Weight Management at West Virginia University, Morgantown. Papillary thyroid cancer makes up about 80% of all thyroid cancers.

If physicians are thinking about prescribing GLP-1 RAs, it’s important to learn the specific types of thyroid disorders in a patient or in their family history, Davisson said. A history of thyroid conditions, such as Graves disease, Hashimoto thyroiditis, or disorders requiring a patient to take thyroid medicine, such as levothyroxine, does not preclude a person from taking GLP-1 RAs.

If a patient does not know their family history, then a discussion about whether GLP-1 RAs are right for them should take place, Davisson said.

“They should take into consideration the risks and benefits of the medicine, and the fact that medullary thyroid cancer and MEN2 syndrome are rare, making the chances of them running in their family low,” she said. “If the patient understands the risks, they may decide the potential benefits may outweigh the risks.”

Keep in mind that the elevated risk for medullary thyroid carcinoma has not been clearly demonstrated in humans during clinical trials, only in rodents, Varney added. Rodents are more likely to develop thyroid cancer after exposure to a GLP-1 RA because rodents have higher numbers of GLP-1 receptors in their thyroid cells.

The risk for thyroid cancer is also dose dependent, and the amount of GLP-1 RA that induced thyroid tumors in the rodents was 8-60 times higher than that given to humans, Varney said.

“Nonetheless, there have been case reports of MTC in humans after taking GLP-1 RA,” she said.

 

What About GLP-1 RAs and Pancreatitis?

Pancreatitis is another condition that requires consideration when it comes to prescribing GLP-1 RAs.

While some studies show that GLP-1 RA analogs can increase the risk for pancreatitis, it’s important to know the reason behind pancreatitis before making a prescription decision, said Anila Chadha, MD, a family physician and obesity medicine physician at Dignity Health in Bakersfield, California.

If the pancreatitis is caused by alcohol or is medication induced, GLP-1 RAs are not recommended, Chadha said. If gallbladder stones are behind the pancreatitis, that’s different.

“If a patient has a well-documented history of gallstone-induced pancreatitis and the patient has had a cholecystectomy, it would be OK to prescribe GLP-1 [medications] after shared decision-making with the patient,” she said.

Some patients worry about taking GLP-1 RAs if they have other types of pancreatic disease beyond pancreatitis, said Davisson, but guidelines do not identify conditions such as pancreatic cysts or a family history of pancreatic cancer as contraindications to GLP-1 RAs.

However, be mindful that GLP-1 RA medications can increase gallbladder disease, Chadha said. A 2022 analysis in JAMA Internal Medicine, for example, found that the use of GLP-1 RAs was associated with an increased risk for gallbladder or biliary diseases, especially when used at higher doses, for longer durations, and for weight loss.

If a history of gallstones is present, physicians should tell patients that GLP-1 RA analogs can increase biliary colic, chances of cholecystitis, or even cholecystitis, Chadha said.

Gallbladder disease itself is not a contraindication, she said, but these patients can experience more disease complications when taking GLP-1 RAs.

Varney recently treated a middle-aged female patient who experienced biliary colic after taking a GLP-1 RA medication. The patient had a starting body mass index (BMI) of about 45 and lost 24% of her starting weight over 12 months using a combination of strengthening and cardiovascular training; a reduced-calorie, high-protein diet; and semaglutide for weight loss, Varney said.

The patient began developing upper gastrointestinal symptoms, including mild biliary colic, without concerning lab findings. An ultrasound revealed that she had new gallstones, compared with an ultrasound a few years prior. Varney started the patient on ursodeoxycholic acid, and over the course of 6 weeks, the patient’s symptoms gradually improved and eventually resolved.

“In a situation like this, many physicians might have discontinued the obesity medication, potentially deciding not to restart it due to the symptoms she was experiencing,” Varney said. “However, I believe it’s important to recognize that these medications offer far more than just weight loss benefits. The positive effects extend to cardiovascular, metabolic, and mental health, which are often overlooked when the focus is solely on the number on the scale or BMI.”

Other medical conditions that GLP-1 RAs may exacerbate include gastroparesis and diabetic retinopathy, Chadha noted. GLP-1 RA drugs can worsen these conditions and are not recommended for patients with such a history.

Nor are GLP-1 RA medications a good idea for patients struggling with severe constipation.

“It is very difficult to tolerate these medications because it can make constipation worse,” Chadha said. “In addition, if a patient struggles with severe heartburn, it can make the tolerability of these medications difficult.”

 

What Patients Should Know Before Using GLP-1 RAs

Not every overweight patient is a good candidate for GLP-1 RAs, and it’s important that doctors explain why the medications may not be right for them, Davisson said.

“If a patient only has a few pounds to lose (15-20 lb) and does not accept that these medications are intended to be a long-term treatment for the chronic diseases of diabetes or obesity, then they might not be a good candidate for the medication,” Davisson said.

Also essential is making sure patients are willing to follow appropriate healthy eating guidelines when on the medications, including getting enough protein and produce to maintain lean body mass and the necessary fiber to keep bowel habits regular.

Varney often hears concerns from physicians about the long-term effects of GLP-1 RAs. She said this class of medications has been used for nearly 20 years to treat type 2 diabetes, and the data over the past two decades have shown that the benefits of GLP-1 RAs far outweigh the risks for most patients.

Recent studies have also highlighted significant long-term benefits, including a marked reduction in cardiovascular events, heart failure, and kidney disease, she said.

“These outcomes underscore the effectiveness and safety of GLP-1 RAs not just for obesity treatment but for improving overall health, particularly in high-risk populations,” she said. “As physicians, it’s crucial to consider this extensive body of evidence when evaluating the use of these medications for patients, especially when the potential health benefits extend well beyond weight loss alone.”

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

Clinicians frequently reach out to Catherine Varney, DO, asking if it’s safe to prescribe glucagon-like peptide 1 receptor agonists (GLP-1 RAs) to patients with thyroid disorders, such as hypothyroidism, goiter, hyperthyroidism, and nodules.

The concerns often stem from prior animal studies that revealed a link between the medications and abnormal alterations in thyroid C cells.

“What physicians need to understand is that the increased risk of thyroid cancers is specifically in those with a personal or family history of multiple endocrine neoplasia 2 (MEN2) syndrome or medullary thyroid carcinoma [MTC],” said Varney, an assistant professor of family medicine at the University of Virginia (UVA) and obesity medicine director for UVA Health, both in Charlottesville.

MTC is a common manifestation of the MEN2 syndrome, a genetic disorder that affects the endocrine glands and can cause tumors in the thyroid gland. However, MTC is very rare, making up only 3%-5% of all thyroid cancers, Varney said.

More common types of thyroid cancers, such as papillary thyroid cancer, are not contraindications to GLP-1 RAs, said Laura Davisson, MD, MPH, a professor of medicine and director of Medical Weight Management at West Virginia University, Morgantown. Papillary thyroid cancer makes up about 80% of all thyroid cancers.

If physicians are thinking about prescribing GLP-1 RAs, it’s important to learn the specific types of thyroid disorders in a patient or in their family history, Davisson said. A history of thyroid conditions, such as Graves disease, Hashimoto thyroiditis, or disorders requiring a patient to take thyroid medicine, such as levothyroxine, does not preclude a person from taking GLP-1 RAs.

If a patient does not know their family history, then a discussion about whether GLP-1 RAs are right for them should take place, Davisson said.

“They should take into consideration the risks and benefits of the medicine, and the fact that medullary thyroid cancer and MEN2 syndrome are rare, making the chances of them running in their family low,” she said. “If the patient understands the risks, they may decide the potential benefits may outweigh the risks.”

Keep in mind that the elevated risk for medullary thyroid carcinoma has not been clearly demonstrated in humans during clinical trials, only in rodents, Varney added. Rodents are more likely to develop thyroid cancer after exposure to a GLP-1 RA because rodents have higher numbers of GLP-1 receptors in their thyroid cells.

The risk for thyroid cancer is also dose dependent, and the amount of GLP-1 RA that induced thyroid tumors in the rodents was 8-60 times higher than that given to humans, Varney said.

“Nonetheless, there have been case reports of MTC in humans after taking GLP-1 RA,” she said.

 

What About GLP-1 RAs and Pancreatitis?

Pancreatitis is another condition that requires consideration when it comes to prescribing GLP-1 RAs.

While some studies show that GLP-1 RA analogs can increase the risk for pancreatitis, it’s important to know the reason behind pancreatitis before making a prescription decision, said Anila Chadha, MD, a family physician and obesity medicine physician at Dignity Health in Bakersfield, California.

If the pancreatitis is caused by alcohol or is medication induced, GLP-1 RAs are not recommended, Chadha said. If gallbladder stones are behind the pancreatitis, that’s different.

“If a patient has a well-documented history of gallstone-induced pancreatitis and the patient has had a cholecystectomy, it would be OK to prescribe GLP-1 [medications] after shared decision-making with the patient,” she said.

Some patients worry about taking GLP-1 RAs if they have other types of pancreatic disease beyond pancreatitis, said Davisson, but guidelines do not identify conditions such as pancreatic cysts or a family history of pancreatic cancer as contraindications to GLP-1 RAs.

However, be mindful that GLP-1 RA medications can increase gallbladder disease, Chadha said. A 2022 analysis in JAMA Internal Medicine, for example, found that the use of GLP-1 RAs was associated with an increased risk for gallbladder or biliary diseases, especially when used at higher doses, for longer durations, and for weight loss.

If a history of gallstones is present, physicians should tell patients that GLP-1 RA analogs can increase biliary colic, chances of cholecystitis, or even cholecystitis, Chadha said.

Gallbladder disease itself is not a contraindication, she said, but these patients can experience more disease complications when taking GLP-1 RAs.

Varney recently treated a middle-aged female patient who experienced biliary colic after taking a GLP-1 RA medication. The patient had a starting body mass index (BMI) of about 45 and lost 24% of her starting weight over 12 months using a combination of strengthening and cardiovascular training; a reduced-calorie, high-protein diet; and semaglutide for weight loss, Varney said.

The patient began developing upper gastrointestinal symptoms, including mild biliary colic, without concerning lab findings. An ultrasound revealed that she had new gallstones, compared with an ultrasound a few years prior. Varney started the patient on ursodeoxycholic acid, and over the course of 6 weeks, the patient’s symptoms gradually improved and eventually resolved.

“In a situation like this, many physicians might have discontinued the obesity medication, potentially deciding not to restart it due to the symptoms she was experiencing,” Varney said. “However, I believe it’s important to recognize that these medications offer far more than just weight loss benefits. The positive effects extend to cardiovascular, metabolic, and mental health, which are often overlooked when the focus is solely on the number on the scale or BMI.”

Other medical conditions that GLP-1 RAs may exacerbate include gastroparesis and diabetic retinopathy, Chadha noted. GLP-1 RA drugs can worsen these conditions and are not recommended for patients with such a history.

Nor are GLP-1 RA medications a good idea for patients struggling with severe constipation.

“It is very difficult to tolerate these medications because it can make constipation worse,” Chadha said. “In addition, if a patient struggles with severe heartburn, it can make the tolerability of these medications difficult.”

 

What Patients Should Know Before Using GLP-1 RAs

Not every overweight patient is a good candidate for GLP-1 RAs, and it’s important that doctors explain why the medications may not be right for them, Davisson said.

“If a patient only has a few pounds to lose (15-20 lb) and does not accept that these medications are intended to be a long-term treatment for the chronic diseases of diabetes or obesity, then they might not be a good candidate for the medication,” Davisson said.

Also essential is making sure patients are willing to follow appropriate healthy eating guidelines when on the medications, including getting enough protein and produce to maintain lean body mass and the necessary fiber to keep bowel habits regular.

Varney often hears concerns from physicians about the long-term effects of GLP-1 RAs. She said this class of medications has been used for nearly 20 years to treat type 2 diabetes, and the data over the past two decades have shown that the benefits of GLP-1 RAs far outweigh the risks for most patients.

Recent studies have also highlighted significant long-term benefits, including a marked reduction in cardiovascular events, heart failure, and kidney disease, she said.

“These outcomes underscore the effectiveness and safety of GLP-1 RAs not just for obesity treatment but for improving overall health, particularly in high-risk populations,” she said. “As physicians, it’s crucial to consider this extensive body of evidence when evaluating the use of these medications for patients, especially when the potential health benefits extend well beyond weight loss alone.”

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

Clinicians frequently reach out to Catherine Varney, DO, asking if it’s safe to prescribe glucagon-like peptide 1 receptor agonists (GLP-1 RAs) to patients with thyroid disorders, such as hypothyroidism, goiter, hyperthyroidism, and nodules.

The concerns often stem from prior animal studies that revealed a link between the medications and abnormal alterations in thyroid C cells.

“What physicians need to understand is that the increased risk of thyroid cancers is specifically in those with a personal or family history of multiple endocrine neoplasia 2 (MEN2) syndrome or medullary thyroid carcinoma [MTC],” said Varney, an assistant professor of family medicine at the University of Virginia (UVA) and obesity medicine director for UVA Health, both in Charlottesville.

MTC is a common manifestation of the MEN2 syndrome, a genetic disorder that affects the endocrine glands and can cause tumors in the thyroid gland. However, MTC is very rare, making up only 3%-5% of all thyroid cancers, Varney said.

More common types of thyroid cancers, such as papillary thyroid cancer, are not contraindications to GLP-1 RAs, said Laura Davisson, MD, MPH, a professor of medicine and director of Medical Weight Management at West Virginia University, Morgantown. Papillary thyroid cancer makes up about 80% of all thyroid cancers.

If physicians are thinking about prescribing GLP-1 RAs, it’s important to learn the specific types of thyroid disorders in a patient or in their family history, Davisson said. A history of thyroid conditions, such as Graves disease, Hashimoto thyroiditis, or disorders requiring a patient to take thyroid medicine, such as levothyroxine, does not preclude a person from taking GLP-1 RAs.

If a patient does not know their family history, then a discussion about whether GLP-1 RAs are right for them should take place, Davisson said.

“They should take into consideration the risks and benefits of the medicine, and the fact that medullary thyroid cancer and MEN2 syndrome are rare, making the chances of them running in their family low,” she said. “If the patient understands the risks, they may decide the potential benefits may outweigh the risks.”

Keep in mind that the elevated risk for medullary thyroid carcinoma has not been clearly demonstrated in humans during clinical trials, only in rodents, Varney added. Rodents are more likely to develop thyroid cancer after exposure to a GLP-1 RA because rodents have higher numbers of GLP-1 receptors in their thyroid cells.

The risk for thyroid cancer is also dose dependent, and the amount of GLP-1 RA that induced thyroid tumors in the rodents was 8-60 times higher than that given to humans, Varney said.

“Nonetheless, there have been case reports of MTC in humans after taking GLP-1 RA,” she said.

 

What About GLP-1 RAs and Pancreatitis?

Pancreatitis is another condition that requires consideration when it comes to prescribing GLP-1 RAs.

While some studies show that GLP-1 RA analogs can increase the risk for pancreatitis, it’s important to know the reason behind pancreatitis before making a prescription decision, said Anila Chadha, MD, a family physician and obesity medicine physician at Dignity Health in Bakersfield, California.

If the pancreatitis is caused by alcohol or is medication induced, GLP-1 RAs are not recommended, Chadha said. If gallbladder stones are behind the pancreatitis, that’s different.

“If a patient has a well-documented history of gallstone-induced pancreatitis and the patient has had a cholecystectomy, it would be OK to prescribe GLP-1 [medications] after shared decision-making with the patient,” she said.

Some patients worry about taking GLP-1 RAs if they have other types of pancreatic disease beyond pancreatitis, said Davisson, but guidelines do not identify conditions such as pancreatic cysts or a family history of pancreatic cancer as contraindications to GLP-1 RAs.

However, be mindful that GLP-1 RA medications can increase gallbladder disease, Chadha said. A 2022 analysis in JAMA Internal Medicine, for example, found that the use of GLP-1 RAs was associated with an increased risk for gallbladder or biliary diseases, especially when used at higher doses, for longer durations, and for weight loss.

If a history of gallstones is present, physicians should tell patients that GLP-1 RA analogs can increase biliary colic, chances of cholecystitis, or even cholecystitis, Chadha said.

Gallbladder disease itself is not a contraindication, she said, but these patients can experience more disease complications when taking GLP-1 RAs.

Varney recently treated a middle-aged female patient who experienced biliary colic after taking a GLP-1 RA medication. The patient had a starting body mass index (BMI) of about 45 and lost 24% of her starting weight over 12 months using a combination of strengthening and cardiovascular training; a reduced-calorie, high-protein diet; and semaglutide for weight loss, Varney said.

The patient began developing upper gastrointestinal symptoms, including mild biliary colic, without concerning lab findings. An ultrasound revealed that she had new gallstones, compared with an ultrasound a few years prior. Varney started the patient on ursodeoxycholic acid, and over the course of 6 weeks, the patient’s symptoms gradually improved and eventually resolved.

“In a situation like this, many physicians might have discontinued the obesity medication, potentially deciding not to restart it due to the symptoms she was experiencing,” Varney said. “However, I believe it’s important to recognize that these medications offer far more than just weight loss benefits. The positive effects extend to cardiovascular, metabolic, and mental health, which are often overlooked when the focus is solely on the number on the scale or BMI.”

Other medical conditions that GLP-1 RAs may exacerbate include gastroparesis and diabetic retinopathy, Chadha noted. GLP-1 RA drugs can worsen these conditions and are not recommended for patients with such a history.

Nor are GLP-1 RA medications a good idea for patients struggling with severe constipation.

“It is very difficult to tolerate these medications because it can make constipation worse,” Chadha said. “In addition, if a patient struggles with severe heartburn, it can make the tolerability of these medications difficult.”

 

What Patients Should Know Before Using GLP-1 RAs

Not every overweight patient is a good candidate for GLP-1 RAs, and it’s important that doctors explain why the medications may not be right for them, Davisson said.

“If a patient only has a few pounds to lose (15-20 lb) and does not accept that these medications are intended to be a long-term treatment for the chronic diseases of diabetes or obesity, then they might not be a good candidate for the medication,” Davisson said.

Also essential is making sure patients are willing to follow appropriate healthy eating guidelines when on the medications, including getting enough protein and produce to maintain lean body mass and the necessary fiber to keep bowel habits regular.

Varney often hears concerns from physicians about the long-term effects of GLP-1 RAs. She said this class of medications has been used for nearly 20 years to treat type 2 diabetes, and the data over the past two decades have shown that the benefits of GLP-1 RAs far outweigh the risks for most patients.

Recent studies have also highlighted significant long-term benefits, including a marked reduction in cardiovascular events, heart failure, and kidney disease, she said.

“These outcomes underscore the effectiveness and safety of GLP-1 RAs not just for obesity treatment but for improving overall health, particularly in high-risk populations,” she said. “As physicians, it’s crucial to consider this extensive body of evidence when evaluating the use of these medications for patients, especially when the potential health benefits extend well beyond weight loss alone.”

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

TOPLINE:

Among older veterans with type 2 diabetes (T2D), the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors as an add-on therapy is associated with a higher risk for peripheral artery disease (PAD)-related surgical events than the use of dipeptidyl peptidase 4 (DPP-4) inhibitors.

METHODOLOGY:

• Some placebo-controlled randomized trials have reported an increased risk for amputation with the use of SGLT2 inhibitors in patients with underlying cardiovascular diseases; however, the evidence remains unconfirmed by other subsequent trials.
• Researchers conducted a retrospective study of US veterans with T2D initiating SGLT2 inhibitors or DPP-4 inhibitors (a reference drug) as an add-on to metformin, sulfonylurea, or insulin treatment alone or in combination.
• The primary outcome was the time to the first surgical event for PAD (amputation, peripheral revascularization and bypass, or peripheral vascular stent).
• A Cox proportional hazards model was used to compare PAD event risk between the SGLT2 inhibitor and DPP-4 inhibitor groups, allowing events up to 90 days or 360 days after stopping SGLT2 inhibitors.

TAKEAWAY:

• After propensity score weighting, 76,072 episodes of SGLT2 inhibitor use (94% empagliflozin, 4% canagliflozin, and 2% dapagliflozin) and 75,833 episodes of DPP-4 inhibitor use (45% saxagliptin, 34% alogliptin, 15% sitagliptin, and 6% linagliptin) were included.
• Participants had a median age of 69 years and a median duration of diabetes of 10.1 years.
• SGLT2 inhibitor users had higher PAD-related surgical events than DPP-4 inhibitor users (874 vs 780), with event rates of 11.2 vs 10.0 per 1000 person-years (adjusted hazard ratio [aHR], 1.18).
• The cumulative probability of PAD-related surgical events at 4 years was higher for SGLT2 inhibitor users than for DPP-4 inhibitor users (4.0% vs 2.8%, respectively).
• The results remained consistent after 90 and 360 days of stopping SGLT2 inhibitors.
• SGLT2 inhibitor use was also associated with a higher risk for amputation (aHR, 1.15) and revascularization (aHR, 1.25) events than DPP-4 inhibitor use.

IN PRACTICE:

“These results underscore the need to determine the safety of [SGLT2 inhibitor] use among patients with diabetes who remain at very high risk for PAD,” the authors wrote.

SOURCE:

This study was led by Katherine E. Griffin, Geriatric Research Education and Clinical Center, Tennessee Valley Healthcare System, Nashville, and published online in Diabetes Care.

LIMITATIONS:

The study excluded patients whose initial diabetes treatment was not metformin, insulin, or sulfonylurea, which might have influenced the interpretation of the results. The median follow-up period of approximately 0.7 years for both groups may have affected the number of amputations and revascularization events observed. The study population primarily comprised White men, limiting generalizability to women and other demographic groups.

DISCLOSURES:

The study received funding through an investigator-initiated grant from the Veterans Affairs Clinical Science Research and Development. Two authors received partial research support through a grant from the Center for Diabetes Translation Research. All authors received partial support from the VETWISE-LHS Center of Innovation. No potential conflicts of interest relevant to the article were reported.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Among older veterans with type 2 diabetes (T2D), the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors as an add-on therapy is associated with a higher risk for peripheral artery disease (PAD)-related surgical events than the use of dipeptidyl peptidase 4 (DPP-4) inhibitors.

METHODOLOGY:

• Some placebo-controlled randomized trials have reported an increased risk for amputation with the use of SGLT2 inhibitors in patients with underlying cardiovascular diseases; however, the evidence remains unconfirmed by other subsequent trials.
• Researchers conducted a retrospective study of US veterans with T2D initiating SGLT2 inhibitors or DPP-4 inhibitors (a reference drug) as an add-on to metformin, sulfonylurea, or insulin treatment alone or in combination.
• The primary outcome was the time to the first surgical event for PAD (amputation, peripheral revascularization and bypass, or peripheral vascular stent).
• A Cox proportional hazards model was used to compare PAD event risk between the SGLT2 inhibitor and DPP-4 inhibitor groups, allowing events up to 90 days or 360 days after stopping SGLT2 inhibitors.

TAKEAWAY:

• After propensity score weighting, 76,072 episodes of SGLT2 inhibitor use (94% empagliflozin, 4% canagliflozin, and 2% dapagliflozin) and 75,833 episodes of DPP-4 inhibitor use (45% saxagliptin, 34% alogliptin, 15% sitagliptin, and 6% linagliptin) were included.
• Participants had a median age of 69 years and a median duration of diabetes of 10.1 years.
• SGLT2 inhibitor users had higher PAD-related surgical events than DPP-4 inhibitor users (874 vs 780), with event rates of 11.2 vs 10.0 per 1000 person-years (adjusted hazard ratio [aHR], 1.18).
• The cumulative probability of PAD-related surgical events at 4 years was higher for SGLT2 inhibitor users than for DPP-4 inhibitor users (4.0% vs 2.8%, respectively).
• The results remained consistent after 90 and 360 days of stopping SGLT2 inhibitors.
• SGLT2 inhibitor use was also associated with a higher risk for amputation (aHR, 1.15) and revascularization (aHR, 1.25) events than DPP-4 inhibitor use.

IN PRACTICE:

“These results underscore the need to determine the safety of [SGLT2 inhibitor] use among patients with diabetes who remain at very high risk for PAD,” the authors wrote.

SOURCE:

This study was led by Katherine E. Griffin, Geriatric Research Education and Clinical Center, Tennessee Valley Healthcare System, Nashville, and published online in Diabetes Care.

LIMITATIONS:

The study excluded patients whose initial diabetes treatment was not metformin, insulin, or sulfonylurea, which might have influenced the interpretation of the results. The median follow-up period of approximately 0.7 years for both groups may have affected the number of amputations and revascularization events observed. The study population primarily comprised White men, limiting generalizability to women and other demographic groups.

DISCLOSURES:

The study received funding through an investigator-initiated grant from the Veterans Affairs Clinical Science Research and Development. Two authors received partial research support through a grant from the Center for Diabetes Translation Research. All authors received partial support from the VETWISE-LHS Center of Innovation. No potential conflicts of interest relevant to the article were reported.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Among older veterans with type 2 diabetes (T2D), the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors as an add-on therapy is associated with a higher risk for peripheral artery disease (PAD)-related surgical events than the use of dipeptidyl peptidase 4 (DPP-4) inhibitors.

METHODOLOGY:

• Some placebo-controlled randomized trials have reported an increased risk for amputation with the use of SGLT2 inhibitors in patients with underlying cardiovascular diseases; however, the evidence remains unconfirmed by other subsequent trials.
• Researchers conducted a retrospective study of US veterans with T2D initiating SGLT2 inhibitors or DPP-4 inhibitors (a reference drug) as an add-on to metformin, sulfonylurea, or insulin treatment alone or in combination.
• The primary outcome was the time to the first surgical event for PAD (amputation, peripheral revascularization and bypass, or peripheral vascular stent).
• A Cox proportional hazards model was used to compare PAD event risk between the SGLT2 inhibitor and DPP-4 inhibitor groups, allowing events up to 90 days or 360 days after stopping SGLT2 inhibitors.

TAKEAWAY:

• After propensity score weighting, 76,072 episodes of SGLT2 inhibitor use (94% empagliflozin, 4% canagliflozin, and 2% dapagliflozin) and 75,833 episodes of DPP-4 inhibitor use (45% saxagliptin, 34% alogliptin, 15% sitagliptin, and 6% linagliptin) were included.
• Participants had a median age of 69 years and a median duration of diabetes of 10.1 years.
• SGLT2 inhibitor users had higher PAD-related surgical events than DPP-4 inhibitor users (874 vs 780), with event rates of 11.2 vs 10.0 per 1000 person-years (adjusted hazard ratio [aHR], 1.18).
• The cumulative probability of PAD-related surgical events at 4 years was higher for SGLT2 inhibitor users than for DPP-4 inhibitor users (4.0% vs 2.8%, respectively).
• The results remained consistent after 90 and 360 days of stopping SGLT2 inhibitors.
• SGLT2 inhibitor use was also associated with a higher risk for amputation (aHR, 1.15) and revascularization (aHR, 1.25) events than DPP-4 inhibitor use.

IN PRACTICE:

“These results underscore the need to determine the safety of [SGLT2 inhibitor] use among patients with diabetes who remain at very high risk for PAD,” the authors wrote.

SOURCE:

This study was led by Katherine E. Griffin, Geriatric Research Education and Clinical Center, Tennessee Valley Healthcare System, Nashville, and published online in Diabetes Care.

LIMITATIONS:

The study excluded patients whose initial diabetes treatment was not metformin, insulin, or sulfonylurea, which might have influenced the interpretation of the results. The median follow-up period of approximately 0.7 years for both groups may have affected the number of amputations and revascularization events observed. The study population primarily comprised White men, limiting generalizability to women and other demographic groups.

DISCLOSURES:

The study received funding through an investigator-initiated grant from the Veterans Affairs Clinical Science Research and Development. Two authors received partial research support through a grant from the Center for Diabetes Translation Research. All authors received partial support from the VETWISE-LHS Center of Innovation. No potential conflicts of interest relevant to the article were reported.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.