Federal Practitioner

Since gabapentin was approved by the US Food and Drug Administration (FDA) for treatment of partial-onset seizures and postherpetic neuralgia, it has been used in many different ways, many off-label indications, and with several recent safety warnings.

Early Problems

After FDA approval in 1993 (for partial seizures), gabapentin was promoted by its maker (Park-Davis) for off-label indications, especially for pain. There was no FDA approval for that indication and the studies the company had done were deemed to have been manipulated in a subsequent lawsuit.¹ Gabapentin became the nonopioid go-to medication for treatment of pain despite underwhelming evidence.
 

Studies on Neuropathy

In the largest trial of gabapentin for diabetic peripheral neuropathy, Rauck and colleagues found no significant difference in pain relief between gabapentin and placebo.² A Cochrane review of gabapentin for neuropathic pain concluded that about 30%-40% of patients taking gabapentin for diabetic neuropathy achieved meaningful pain relief with gabapentin use, with a number needed to treat (NNT) of 6.6.³ The review also concluded that for postherpetic neuralgia (an FDA-approved indication) 78% of patients had moderate to substantial benefit with gabapentin (NNT 4.8 for moderate benefit).

Side Effects of Gabapentin

From the Cochrane review, the most common side effects were:  dizziness (19%), somnolence (14%), peripheral edema (7%), and gait disturbance (14%). The number needed to harm for gabapentin was 7.⁵ The two side effects listed here that are often overlooked that I want to highlight are peripheral edema and gait disturbance. I have seen these both fairly frequently over the years. A side effect not found in the Cochrane review was weight gain. Weight gain with gabapentin was reported in a meta-analysis of drugs that can cause weight gain.⁴

New Warnings

In December 2019, the FDA released a warning on the potential for serious respiratory problems with gabapentin and pregabalin in patients with certain risk factors: opioid use or use of other drugs that depress the central nervous system, COPD, and other severe lung diseases.⁵ Rahman and colleagues found that compared with nonuse, gabapentinoid use was associated with increased risk for severe COPD exacerbation (hazard ratio, 1.39; 95% confidence interval, 1.29-1.50).⁶

Off-Label Uses

Primary care professionals frequently use gabapentin for two off-label indications that are incorporated into practice guidelines. Ryan et al. studied gabapentin in patients with refractory, unexplained chronic cough.⁷ In a randomized, placebo-controlled trial, gabapentin improved cough-specific quality of life compared with placebo (P = .004; NNT 3.58). Use of gabapentin for treatment of unexplained, refractory cough has been included in several chronic cough practice guidelines.^8,9

Gabapentin has been studied for the treatment of restless legs syndrome and has been recommended as an option to treat moderate to severe restless legs syndrome in the American Academy of Sleep Medicine Guidelines.¹⁰

Pearl of the Month:

Gabapentin is used widely for many different pain syndromes. The best evidence is for postherpetic neuralgia and diabetic neuropathy. Be aware of the side effects and risks of use in patients with pulmonary disease and who are taking CNS-depressant medications.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Landefeld CS, Steinman MA. The Neurontin legacy: marketing through misinformation and manipulation. N Engl J Med. 2009;360(2):103-6.

2. Rauck R et al. A randomized, controlled trial of gabapentin enacarbil in subjects with neuropathic pain associated with diabetic peripheral neuropathy. Pain Pract. 2013;13(6):485-96.

3. Wiffen PJ et al. Gabapentin for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2017;6(6):CD007938.

4. Domecq JP et al. Clinical review: Drugs commonly associated with weight change: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2015 Feb;100(2):363-70.

5. 12-19-2019 FDA Drug Safety Communication. FDA warns about serious breathing problems with seizure and nerve pain medicines gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica, Lyrica CR).

6. Rahman AA et al. Gabapentinoids and risk for severe exacerbation in chronic obstructive pulmonary disease: A population-based cohort study. Ann Intern Med. 2024 Feb;177(2):144-54.

7. Ryan NM et al. Gabapentin for refractory chronic cough: a randomised, double-blind, placebo-controlled trial. Lancet 2012;380(9853):1583-9.

8. Gibson P et al. Treatment of unexplained chronic cough: CHEST guideline and expert panel report. Chest. 2016 Jan;149(1):27-44.

9. De Vincentis A et al. Chronic cough in adults: recommendations from an Italian intersociety consensus. Aging Clin Exp Res 2022;34:1529.

10. Aurora RN et al. The treatment of restless legs syndrome and periodic limb movement disorder in adults — an update for 2012: Practice parameters with an evidence-based systematic review and meta-analyses: An American Academy of Sleep Medicine Clinical Practice Guideline. Sleep 2012;35:1039.

Since gabapentin was approved by the US Food and Drug Administration (FDA) for treatment of partial-onset seizures and postherpetic neuralgia, it has been used in many different ways, many off-label indications, and with several recent safety warnings.

Early Problems

After FDA approval in 1993 (for partial seizures), gabapentin was promoted by its maker (Park-Davis) for off-label indications, especially for pain. There was no FDA approval for that indication and the studies the company had done were deemed to have been manipulated in a subsequent lawsuit.¹ Gabapentin became the nonopioid go-to medication for treatment of pain despite underwhelming evidence.
 

Studies on Neuropathy

In the largest trial of gabapentin for diabetic peripheral neuropathy, Rauck and colleagues found no significant difference in pain relief between gabapentin and placebo.² A Cochrane review of gabapentin for neuropathic pain concluded that about 30%-40% of patients taking gabapentin for diabetic neuropathy achieved meaningful pain relief with gabapentin use, with a number needed to treat (NNT) of 6.6.³ The review also concluded that for postherpetic neuralgia (an FDA-approved indication) 78% of patients had moderate to substantial benefit with gabapentin (NNT 4.8 for moderate benefit).

Side Effects of Gabapentin

From the Cochrane review, the most common side effects were:  dizziness (19%), somnolence (14%), peripheral edema (7%), and gait disturbance (14%). The number needed to harm for gabapentin was 7.⁵ The two side effects listed here that are often overlooked that I want to highlight are peripheral edema and gait disturbance. I have seen these both fairly frequently over the years. A side effect not found in the Cochrane review was weight gain. Weight gain with gabapentin was reported in a meta-analysis of drugs that can cause weight gain.⁴

New Warnings

In December 2019, the FDA released a warning on the potential for serious respiratory problems with gabapentin and pregabalin in patients with certain risk factors: opioid use or use of other drugs that depress the central nervous system, COPD, and other severe lung diseases.⁵ Rahman and colleagues found that compared with nonuse, gabapentinoid use was associated with increased risk for severe COPD exacerbation (hazard ratio, 1.39; 95% confidence interval, 1.29-1.50).⁶

Off-Label Uses

Primary care professionals frequently use gabapentin for two off-label indications that are incorporated into practice guidelines. Ryan et al. studied gabapentin in patients with refractory, unexplained chronic cough.⁷ In a randomized, placebo-controlled trial, gabapentin improved cough-specific quality of life compared with placebo (P = .004; NNT 3.58). Use of gabapentin for treatment of unexplained, refractory cough has been included in several chronic cough practice guidelines.^8,9

Gabapentin has been studied for the treatment of restless legs syndrome and has been recommended as an option to treat moderate to severe restless legs syndrome in the American Academy of Sleep Medicine Guidelines.¹⁰

Pearl of the Month:

Gabapentin is used widely for many different pain syndromes. The best evidence is for postherpetic neuralgia and diabetic neuropathy. Be aware of the side effects and risks of use in patients with pulmonary disease and who are taking CNS-depressant medications.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Landefeld CS, Steinman MA. The Neurontin legacy: marketing through misinformation and manipulation. N Engl J Med. 2009;360(2):103-6.

2. Rauck R et al. A randomized, controlled trial of gabapentin enacarbil in subjects with neuropathic pain associated with diabetic peripheral neuropathy. Pain Pract. 2013;13(6):485-96.

3. Wiffen PJ et al. Gabapentin for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2017;6(6):CD007938.

4. Domecq JP et al. Clinical review: Drugs commonly associated with weight change: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2015 Feb;100(2):363-70.

5. 12-19-2019 FDA Drug Safety Communication. FDA warns about serious breathing problems with seizure and nerve pain medicines gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica, Lyrica CR).

6. Rahman AA et al. Gabapentinoids and risk for severe exacerbation in chronic obstructive pulmonary disease: A population-based cohort study. Ann Intern Med. 2024 Feb;177(2):144-54.

7. Ryan NM et al. Gabapentin for refractory chronic cough: a randomised, double-blind, placebo-controlled trial. Lancet 2012;380(9853):1583-9.

8. Gibson P et al. Treatment of unexplained chronic cough: CHEST guideline and expert panel report. Chest. 2016 Jan;149(1):27-44.

9. De Vincentis A et al. Chronic cough in adults: recommendations from an Italian intersociety consensus. Aging Clin Exp Res 2022;34:1529.

10. Aurora RN et al. The treatment of restless legs syndrome and periodic limb movement disorder in adults — an update for 2012: Practice parameters with an evidence-based systematic review and meta-analyses: An American Academy of Sleep Medicine Clinical Practice Guideline. Sleep 2012;35:1039.

Since gabapentin was approved by the US Food and Drug Administration (FDA) for treatment of partial-onset seizures and postherpetic neuralgia, it has been used in many different ways, many off-label indications, and with several recent safety warnings.

Early Problems

After FDA approval in 1993 (for partial seizures), gabapentin was promoted by its maker (Park-Davis) for off-label indications, especially for pain. There was no FDA approval for that indication and the studies the company had done were deemed to have been manipulated in a subsequent lawsuit.¹ Gabapentin became the nonopioid go-to medication for treatment of pain despite underwhelming evidence.
 

Studies on Neuropathy

In the largest trial of gabapentin for diabetic peripheral neuropathy, Rauck and colleagues found no significant difference in pain relief between gabapentin and placebo.² A Cochrane review of gabapentin for neuropathic pain concluded that about 30%-40% of patients taking gabapentin for diabetic neuropathy achieved meaningful pain relief with gabapentin use, with a number needed to treat (NNT) of 6.6.³ The review also concluded that for postherpetic neuralgia (an FDA-approved indication) 78% of patients had moderate to substantial benefit with gabapentin (NNT 4.8 for moderate benefit).

Side Effects of Gabapentin

From the Cochrane review, the most common side effects were:  dizziness (19%), somnolence (14%), peripheral edema (7%), and gait disturbance (14%). The number needed to harm for gabapentin was 7.⁵ The two side effects listed here that are often overlooked that I want to highlight are peripheral edema and gait disturbance. I have seen these both fairly frequently over the years. A side effect not found in the Cochrane review was weight gain. Weight gain with gabapentin was reported in a meta-analysis of drugs that can cause weight gain.⁴

New Warnings

In December 2019, the FDA released a warning on the potential for serious respiratory problems with gabapentin and pregabalin in patients with certain risk factors: opioid use or use of other drugs that depress the central nervous system, COPD, and other severe lung diseases.⁵ Rahman and colleagues found that compared with nonuse, gabapentinoid use was associated with increased risk for severe COPD exacerbation (hazard ratio, 1.39; 95% confidence interval, 1.29-1.50).⁶

Off-Label Uses

Primary care professionals frequently use gabapentin for two off-label indications that are incorporated into practice guidelines. Ryan et al. studied gabapentin in patients with refractory, unexplained chronic cough.⁷ In a randomized, placebo-controlled trial, gabapentin improved cough-specific quality of life compared with placebo (P = .004; NNT 3.58). Use of gabapentin for treatment of unexplained, refractory cough has been included in several chronic cough practice guidelines.^8,9

Gabapentin has been studied for the treatment of restless legs syndrome and has been recommended as an option to treat moderate to severe restless legs syndrome in the American Academy of Sleep Medicine Guidelines.¹⁰

Pearl of the Month:

Gabapentin is used widely for many different pain syndromes. The best evidence is for postherpetic neuralgia and diabetic neuropathy. Be aware of the side effects and risks of use in patients with pulmonary disease and who are taking CNS-depressant medications.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Landefeld CS, Steinman MA. The Neurontin legacy: marketing through misinformation and manipulation. N Engl J Med. 2009;360(2):103-6.

2. Rauck R et al. A randomized, controlled trial of gabapentin enacarbil in subjects with neuropathic pain associated with diabetic peripheral neuropathy. Pain Pract. 2013;13(6):485-96.

3. Wiffen PJ et al. Gabapentin for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2017;6(6):CD007938.

4. Domecq JP et al. Clinical review: Drugs commonly associated with weight change: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2015 Feb;100(2):363-70.

5. 12-19-2019 FDA Drug Safety Communication. FDA warns about serious breathing problems with seizure and nerve pain medicines gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica, Lyrica CR).

6. Rahman AA et al. Gabapentinoids and risk for severe exacerbation in chronic obstructive pulmonary disease: A population-based cohort study. Ann Intern Med. 2024 Feb;177(2):144-54.

7. Ryan NM et al. Gabapentin for refractory chronic cough: a randomised, double-blind, placebo-controlled trial. Lancet 2012;380(9853):1583-9.

8. Gibson P et al. Treatment of unexplained chronic cough: CHEST guideline and expert panel report. Chest. 2016 Jan;149(1):27-44.

9. De Vincentis A et al. Chronic cough in adults: recommendations from an Italian intersociety consensus. Aging Clin Exp Res 2022;34:1529.

10. Aurora RN et al. The treatment of restless legs syndrome and periodic limb movement disorder in adults — an update for 2012: Practice parameters with an evidence-based systematic review and meta-analyses: An American Academy of Sleep Medicine Clinical Practice Guideline. Sleep 2012;35:1039.

A new analysis has detected a signal of suicidal ideation associated with the glucagon-like peptide 1 receptor agonist (GLP-1 RA) semaglutide, especially among individuals concurrently using antidepressants or benzodiazepines. 

However, the investigators and outside experts urge caution in drawing any firm conclusions based on the study’s observations. 

“Clinicians should not interpret these results as proof of causal relationship between suicidal ideation and semaglutide, as our pharmacovigilance study showed an association between the use of semaglutide and reports of suicidal ideation,” study investigator Georgios Schoretsanitis, MD, PhD, Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, New York, told this news organization.

Nonetheless, “physicians prescribing semaglutide should inform their patients about the medications’ risks and assess the psychiatric history and evaluate the mental state of patients before starting treatment with semaglutide,” Dr. Schoretsanitis said. 

“For patients with history of mental disorders or suicidal ideation/behaviors/attempts, physicians should be cautious and regularly monitor their mental state while taking semaglutide. If needed, the treating physician should involve different specialists, including a psychiatrist and/or clinical psychologists,” he added. 

The study was published online on August 20 in JAMA Network Open. 
 

Emerging Concerns

GLP-1 RAs are increasingly prescribed not only for type 2 diabetes but also for weight loss. However, concerns have emerged about a potential association with suicidality, which has prompted a closer look by regulators in the United States and Europe. 

Dr. Schoretsanitis and colleagues evaluated potential signals of suicidality related to semaglutide and liraglutide using data from global World Health Organization database of suspected adverse drug reactions (ADRs). 

They conducted sensitivity analyses including patients with co-reported use of antidepressants and benzodiazepines and using dapagliflozin, metformin, and orlistat as comparators. 

Between November 2000 and August 2023, there were 107 cases of suicidal and/or self-injurious ADRs reported with semaglutide (median age, 48 years; 55% women) and 162 reported with liraglutide (median age 47 years; 61% women). 

The researchers noted that a “significant disproportionality” signal emerged for semaglutide-associated suicidal ideation (reporting odds ratio [ROR], 1.45), when compared with comparator drugs. 

This signal remained significant in sensitivity analyses that included patients on concurrent antidepressants (ROR, 4.45) and benzodiazepines (ROR, 4.07), “suggesting that people with anxiety and depressive disorders may be at higher probability of reporting suicidal ideation when medicated with semaglutide,” the authors wrote. 

No significant disproportionality signal was detected for liraglutide regarding suicidal ideation (ROR, 1.04). 

However, the authors noted that pooled data from previous phase 2 and 3 trials on liraglutide vs placebo for weight management identified a potential risk for suicidal ideation, with nine of 3384 participants in the liraglutide group vs two of 1941 in the placebo group reporting suicidal ideation or behavior during the trial (0.27% vs 0.10%). 
 

More Research Needed 

GLP-1 RAs “should be used cautiously until further data are available on this topic,” Dr. Schoretsanitis said. 

“Further real-world studies should investigate the risk of suicidal ideation or behavior in people treated with these drugs in every-day clinical practice. We categorically discourage off-label use of GLP1-RA and without any medical supervision,” he added.

The coauthors of an invited commentary published with the study note that between 2020 and 2023, GLP-1 RA use rose 594% in younger people, particularly in women.

This “timely and well-conducted study” by Dr. Schoretsanitis and colleagues adds “an important piece to the very relevant safety issue” related to GLP-1 RAs, wrote Francesco Salvo, MD, PhD, with Université de Bordeaux, and Jean-Luc Faillie, MD, PhD, with Université de Montpellier, both in France. 

Pending further studies, the position of the US Food and Drug Administration (FDA) recommending caution “continues to be reasonable. Whatever the cause, depression or suicidality are rare but extremely severe events and need to be prevented and managed as much as possible. 

“Waiting for more precise data, GPL-1 receptor agonists, and appetite suppressants in general, should be prescribed with great caution in patients with a history of depression or suicidal attempts, while in patients with new onset of depression without other apparent precipitants, immediate discontinuation of GLP-1 receptor agonists should be considered,” wrote Dr. Salvo and Dr. Faillie. 

Outside experts also weighed in on the study in a statement from the UK nonprofit Science Media Centre. 

The paper presents, “at best, weak evidence of an association between semaglutide and suicidality,” Ian Douglas, PhD, professor of pharmacoepidemiology, London School of Hygiene & Tropical Medicine, United Kingdom, said in the statement. “Signal detection studies in pharmacovigilance databases are good for generating hypotheses but are not suitable for assessing whether there is a causal association between a drug and an outcome.”

Stephen Evans, MSc, emeritus professor of pharmacoepidemiology, London School of Hygiene & Tropical Medicine, cautioned that the study has “major limitations.”

“This paper is based just on spontaneous reports which are sent to regulatory authorities in the country of the person reporting a suspected adverse reaction. These are sent by health professionals and patients to authorities, but are very subject to bias, including effects of media reporting. The evidence is extremely weak for a genuine effect in this instance,” Mr. Evans said. 

The study had no specific funding. Dr. Schoretsanitis reported receiving personal fees from HLS, Dexcel, Saladax, and Thermo Fisher outside the submitted work. Dr. Salvo and Dr. Faillie have no conflicts of interest. Dr. Douglas has received research grants from GSK and AstraZeneca. Mr. Evans has no conflicts of interest. 
 

A version of this article appeared on Medscape.com.

A new analysis has detected a signal of suicidal ideation associated with the glucagon-like peptide 1 receptor agonist (GLP-1 RA) semaglutide, especially among individuals concurrently using antidepressants or benzodiazepines. 

However, the investigators and outside experts urge caution in drawing any firm conclusions based on the study’s observations. 

“Clinicians should not interpret these results as proof of causal relationship between suicidal ideation and semaglutide, as our pharmacovigilance study showed an association between the use of semaglutide and reports of suicidal ideation,” study investigator Georgios Schoretsanitis, MD, PhD, Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, New York, told this news organization.

Nonetheless, “physicians prescribing semaglutide should inform their patients about the medications’ risks and assess the psychiatric history and evaluate the mental state of patients before starting treatment with semaglutide,” Dr. Schoretsanitis said. 

“For patients with history of mental disorders or suicidal ideation/behaviors/attempts, physicians should be cautious and regularly monitor their mental state while taking semaglutide. If needed, the treating physician should involve different specialists, including a psychiatrist and/or clinical psychologists,” he added. 

The study was published online on August 20 in JAMA Network Open. 
 

Emerging Concerns

GLP-1 RAs are increasingly prescribed not only for type 2 diabetes but also for weight loss. However, concerns have emerged about a potential association with suicidality, which has prompted a closer look by regulators in the United States and Europe. 

Dr. Schoretsanitis and colleagues evaluated potential signals of suicidality related to semaglutide and liraglutide using data from global World Health Organization database of suspected adverse drug reactions (ADRs). 

They conducted sensitivity analyses including patients with co-reported use of antidepressants and benzodiazepines and using dapagliflozin, metformin, and orlistat as comparators. 

Between November 2000 and August 2023, there were 107 cases of suicidal and/or self-injurious ADRs reported with semaglutide (median age, 48 years; 55% women) and 162 reported with liraglutide (median age 47 years; 61% women). 

The researchers noted that a “significant disproportionality” signal emerged for semaglutide-associated suicidal ideation (reporting odds ratio [ROR], 1.45), when compared with comparator drugs. 

This signal remained significant in sensitivity analyses that included patients on concurrent antidepressants (ROR, 4.45) and benzodiazepines (ROR, 4.07), “suggesting that people with anxiety and depressive disorders may be at higher probability of reporting suicidal ideation when medicated with semaglutide,” the authors wrote. 

No significant disproportionality signal was detected for liraglutide regarding suicidal ideation (ROR, 1.04). 

However, the authors noted that pooled data from previous phase 2 and 3 trials on liraglutide vs placebo for weight management identified a potential risk for suicidal ideation, with nine of 3384 participants in the liraglutide group vs two of 1941 in the placebo group reporting suicidal ideation or behavior during the trial (0.27% vs 0.10%). 
 

More Research Needed 

GLP-1 RAs “should be used cautiously until further data are available on this topic,” Dr. Schoretsanitis said. 

“Further real-world studies should investigate the risk of suicidal ideation or behavior in people treated with these drugs in every-day clinical practice. We categorically discourage off-label use of GLP1-RA and without any medical supervision,” he added.

The coauthors of an invited commentary published with the study note that between 2020 and 2023, GLP-1 RA use rose 594% in younger people, particularly in women.

This “timely and well-conducted study” by Dr. Schoretsanitis and colleagues adds “an important piece to the very relevant safety issue” related to GLP-1 RAs, wrote Francesco Salvo, MD, PhD, with Université de Bordeaux, and Jean-Luc Faillie, MD, PhD, with Université de Montpellier, both in France. 

Pending further studies, the position of the US Food and Drug Administration (FDA) recommending caution “continues to be reasonable. Whatever the cause, depression or suicidality are rare but extremely severe events and need to be prevented and managed as much as possible. 

“Waiting for more precise data, GPL-1 receptor agonists, and appetite suppressants in general, should be prescribed with great caution in patients with a history of depression or suicidal attempts, while in patients with new onset of depression without other apparent precipitants, immediate discontinuation of GLP-1 receptor agonists should be considered,” wrote Dr. Salvo and Dr. Faillie. 

Outside experts also weighed in on the study in a statement from the UK nonprofit Science Media Centre. 

The paper presents, “at best, weak evidence of an association between semaglutide and suicidality,” Ian Douglas, PhD, professor of pharmacoepidemiology, London School of Hygiene & Tropical Medicine, United Kingdom, said in the statement. “Signal detection studies in pharmacovigilance databases are good for generating hypotheses but are not suitable for assessing whether there is a causal association between a drug and an outcome.”

Stephen Evans, MSc, emeritus professor of pharmacoepidemiology, London School of Hygiene & Tropical Medicine, cautioned that the study has “major limitations.”

“This paper is based just on spontaneous reports which are sent to regulatory authorities in the country of the person reporting a suspected adverse reaction. These are sent by health professionals and patients to authorities, but are very subject to bias, including effects of media reporting. The evidence is extremely weak for a genuine effect in this instance,” Mr. Evans said. 

The study had no specific funding. Dr. Schoretsanitis reported receiving personal fees from HLS, Dexcel, Saladax, and Thermo Fisher outside the submitted work. Dr. Salvo and Dr. Faillie have no conflicts of interest. Dr. Douglas has received research grants from GSK and AstraZeneca. Mr. Evans has no conflicts of interest. 
 

A version of this article appeared on Medscape.com.

A new analysis has detected a signal of suicidal ideation associated with the glucagon-like peptide 1 receptor agonist (GLP-1 RA) semaglutide, especially among individuals concurrently using antidepressants or benzodiazepines. 

However, the investigators and outside experts urge caution in drawing any firm conclusions based on the study’s observations. 

“Clinicians should not interpret these results as proof of causal relationship between suicidal ideation and semaglutide, as our pharmacovigilance study showed an association between the use of semaglutide and reports of suicidal ideation,” study investigator Georgios Schoretsanitis, MD, PhD, Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, New York, told this news organization.

Nonetheless, “physicians prescribing semaglutide should inform their patients about the medications’ risks and assess the psychiatric history and evaluate the mental state of patients before starting treatment with semaglutide,” Dr. Schoretsanitis said. 

“For patients with history of mental disorders or suicidal ideation/behaviors/attempts, physicians should be cautious and regularly monitor their mental state while taking semaglutide. If needed, the treating physician should involve different specialists, including a psychiatrist and/or clinical psychologists,” he added. 

The study was published online on August 20 in JAMA Network Open. 
 

Emerging Concerns

GLP-1 RAs are increasingly prescribed not only for type 2 diabetes but also for weight loss. However, concerns have emerged about a potential association with suicidality, which has prompted a closer look by regulators in the United States and Europe. 

Dr. Schoretsanitis and colleagues evaluated potential signals of suicidality related to semaglutide and liraglutide using data from global World Health Organization database of suspected adverse drug reactions (ADRs). 

They conducted sensitivity analyses including patients with co-reported use of antidepressants and benzodiazepines and using dapagliflozin, metformin, and orlistat as comparators. 

Between November 2000 and August 2023, there were 107 cases of suicidal and/or self-injurious ADRs reported with semaglutide (median age, 48 years; 55% women) and 162 reported with liraglutide (median age 47 years; 61% women). 

The researchers noted that a “significant disproportionality” signal emerged for semaglutide-associated suicidal ideation (reporting odds ratio [ROR], 1.45), when compared with comparator drugs. 

This signal remained significant in sensitivity analyses that included patients on concurrent antidepressants (ROR, 4.45) and benzodiazepines (ROR, 4.07), “suggesting that people with anxiety and depressive disorders may be at higher probability of reporting suicidal ideation when medicated with semaglutide,” the authors wrote. 

No significant disproportionality signal was detected for liraglutide regarding suicidal ideation (ROR, 1.04). 

However, the authors noted that pooled data from previous phase 2 and 3 trials on liraglutide vs placebo for weight management identified a potential risk for suicidal ideation, with nine of 3384 participants in the liraglutide group vs two of 1941 in the placebo group reporting suicidal ideation or behavior during the trial (0.27% vs 0.10%). 
 

More Research Needed 

GLP-1 RAs “should be used cautiously until further data are available on this topic,” Dr. Schoretsanitis said. 

“Further real-world studies should investigate the risk of suicidal ideation or behavior in people treated with these drugs in every-day clinical practice. We categorically discourage off-label use of GLP1-RA and without any medical supervision,” he added.

The coauthors of an invited commentary published with the study note that between 2020 and 2023, GLP-1 RA use rose 594% in younger people, particularly in women.

This “timely and well-conducted study” by Dr. Schoretsanitis and colleagues adds “an important piece to the very relevant safety issue” related to GLP-1 RAs, wrote Francesco Salvo, MD, PhD, with Université de Bordeaux, and Jean-Luc Faillie, MD, PhD, with Université de Montpellier, both in France. 

Pending further studies, the position of the US Food and Drug Administration (FDA) recommending caution “continues to be reasonable. Whatever the cause, depression or suicidality are rare but extremely severe events and need to be prevented and managed as much as possible. 

“Waiting for more precise data, GPL-1 receptor agonists, and appetite suppressants in general, should be prescribed with great caution in patients with a history of depression or suicidal attempts, while in patients with new onset of depression without other apparent precipitants, immediate discontinuation of GLP-1 receptor agonists should be considered,” wrote Dr. Salvo and Dr. Faillie. 

Outside experts also weighed in on the study in a statement from the UK nonprofit Science Media Centre. 

The paper presents, “at best, weak evidence of an association between semaglutide and suicidality,” Ian Douglas, PhD, professor of pharmacoepidemiology, London School of Hygiene & Tropical Medicine, United Kingdom, said in the statement. “Signal detection studies in pharmacovigilance databases are good for generating hypotheses but are not suitable for assessing whether there is a causal association between a drug and an outcome.”

Stephen Evans, MSc, emeritus professor of pharmacoepidemiology, London School of Hygiene & Tropical Medicine, cautioned that the study has “major limitations.”

“This paper is based just on spontaneous reports which are sent to regulatory authorities in the country of the person reporting a suspected adverse reaction. These are sent by health professionals and patients to authorities, but are very subject to bias, including effects of media reporting. The evidence is extremely weak for a genuine effect in this instance,” Mr. Evans said. 

The study had no specific funding. Dr. Schoretsanitis reported receiving personal fees from HLS, Dexcel, Saladax, and Thermo Fisher outside the submitted work. Dr. Salvo and Dr. Faillie have no conflicts of interest. Dr. Douglas has received research grants from GSK and AstraZeneca. Mr. Evans has no conflicts of interest. 
 

A version of this article appeared on Medscape.com.

TOPLINE:

Mindfulness-based interventions (MBIs) via telehealth improves pain-related function and biopsychosocial outcomes in veterans with chronic pain as compared with usual care.

METHODOLOGY:

• Researchers conducted a randomized clinical trial of 811 veterans who had moderate to severe chronic pain and were recruited from three Veterans Affairs facilities in the United States.
• Participants were divided into three groups: Group MBI (270), self-paced MBI (271), and usual care (270), with interventions lasting 8 weeks.
• The primary outcome was pain-related function measured using a scale on interference from pain in areas like mood, walking, work, relationships, and sleep at 10 weeks, 6 months, and 1 year.
• Secondary outcomes included pain intensity, anxiety, fatigue, sleep disturbance, participation in social roles and activities, depression, and posttraumatic stress disorder (PTSD).

TAKEAWAY:

• Pain-related function significantly improved in participants in both the MBI groups versus usual care group, with a mean difference of −0.4 (95% CI, −0.7 to −0.2) for group MBI and −0.7 (95% CI, −1.0 to −0.4) for self-paced MBI (P < .001).
• Compared with the usual care group, both the MBI groups had significantly improved secondary outcomes, including pain intensity, depression, and PTSD.
• The probability of achieving 30% improvement in pain-related function was higher for group MBI at 10 weeks and 6 months and for self-paced MBI at all three timepoints.
• No significant differences were found between the MBI groups for primary and secondary outcomes.

IN PRACTICE:

“The viability and similarity of both these approaches for delivering MBIs increase patient options for meeting their individual needs and could help accelerate and improve the implementation of nonpharmacological pain treatment in health care systems,” the study authors wrote.

SOURCE:

The study was led by Diana J. Burgess, PhD, of the Center for Care Delivery and Outcomes Research, VA Health Systems Research in Minneapolis, Minnesota, and published online in JAMA Internal Medicine. 

LIMITATIONS:

The trial was not designed to compare less resource-intensive MBIs with more intensive mindfulness-based stress reduction programs or in-person MBIs. The study did not address cost-effectiveness or control for time, attention, and other contextual factors. The high nonresponse rate (81%) to initial recruitment may have affected the generalizability of the findings.

DISCLOSURES:

The study was supported by the Pain Management Collaboratory–Pragmatic Clinical Trials Demonstration. Various authors reported grants from the National Center for Complementary and Integrative Health and the National Institute of Nursing Research.

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 first appeared on Medscape.com.

TOPLINE:

Mindfulness-based interventions (MBIs) via telehealth improves pain-related function and biopsychosocial outcomes in veterans with chronic pain as compared with usual care.

METHODOLOGY:

• Researchers conducted a randomized clinical trial of 811 veterans who had moderate to severe chronic pain and were recruited from three Veterans Affairs facilities in the United States.
• Participants were divided into three groups: Group MBI (270), self-paced MBI (271), and usual care (270), with interventions lasting 8 weeks.
• The primary outcome was pain-related function measured using a scale on interference from pain in areas like mood, walking, work, relationships, and sleep at 10 weeks, 6 months, and 1 year.
• Secondary outcomes included pain intensity, anxiety, fatigue, sleep disturbance, participation in social roles and activities, depression, and posttraumatic stress disorder (PTSD).

TAKEAWAY:

• Pain-related function significantly improved in participants in both the MBI groups versus usual care group, with a mean difference of −0.4 (95% CI, −0.7 to −0.2) for group MBI and −0.7 (95% CI, −1.0 to −0.4) for self-paced MBI (P < .001).
• Compared with the usual care group, both the MBI groups had significantly improved secondary outcomes, including pain intensity, depression, and PTSD.
• The probability of achieving 30% improvement in pain-related function was higher for group MBI at 10 weeks and 6 months and for self-paced MBI at all three timepoints.
• No significant differences were found between the MBI groups for primary and secondary outcomes.

IN PRACTICE:

“The viability and similarity of both these approaches for delivering MBIs increase patient options for meeting their individual needs and could help accelerate and improve the implementation of nonpharmacological pain treatment in health care systems,” the study authors wrote.

SOURCE:

The study was led by Diana J. Burgess, PhD, of the Center for Care Delivery and Outcomes Research, VA Health Systems Research in Minneapolis, Minnesota, and published online in JAMA Internal Medicine. 

LIMITATIONS:

The trial was not designed to compare less resource-intensive MBIs with more intensive mindfulness-based stress reduction programs or in-person MBIs. The study did not address cost-effectiveness or control for time, attention, and other contextual factors. The high nonresponse rate (81%) to initial recruitment may have affected the generalizability of the findings.

DISCLOSURES:

The study was supported by the Pain Management Collaboratory–Pragmatic Clinical Trials Demonstration. Various authors reported grants from the National Center for Complementary and Integrative Health and the National Institute of Nursing Research.

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 first appeared on Medscape.com.

TOPLINE:

Mindfulness-based interventions (MBIs) via telehealth improves pain-related function and biopsychosocial outcomes in veterans with chronic pain as compared with usual care.

METHODOLOGY:

• Researchers conducted a randomized clinical trial of 811 veterans who had moderate to severe chronic pain and were recruited from three Veterans Affairs facilities in the United States.
• Participants were divided into three groups: Group MBI (270), self-paced MBI (271), and usual care (270), with interventions lasting 8 weeks.
• The primary outcome was pain-related function measured using a scale on interference from pain in areas like mood, walking, work, relationships, and sleep at 10 weeks, 6 months, and 1 year.
• Secondary outcomes included pain intensity, anxiety, fatigue, sleep disturbance, participation in social roles and activities, depression, and posttraumatic stress disorder (PTSD).

TAKEAWAY:

• Pain-related function significantly improved in participants in both the MBI groups versus usual care group, with a mean difference of −0.4 (95% CI, −0.7 to −0.2) for group MBI and −0.7 (95% CI, −1.0 to −0.4) for self-paced MBI (P < .001).
• Compared with the usual care group, both the MBI groups had significantly improved secondary outcomes, including pain intensity, depression, and PTSD.
• The probability of achieving 30% improvement in pain-related function was higher for group MBI at 10 weeks and 6 months and for self-paced MBI at all three timepoints.
• No significant differences were found between the MBI groups for primary and secondary outcomes.

IN PRACTICE:

“The viability and similarity of both these approaches for delivering MBIs increase patient options for meeting their individual needs and could help accelerate and improve the implementation of nonpharmacological pain treatment in health care systems,” the study authors wrote.

SOURCE:

The study was led by Diana J. Burgess, PhD, of the Center for Care Delivery and Outcomes Research, VA Health Systems Research in Minneapolis, Minnesota, and published online in JAMA Internal Medicine. 

LIMITATIONS:

The trial was not designed to compare less resource-intensive MBIs with more intensive mindfulness-based stress reduction programs or in-person MBIs. The study did not address cost-effectiveness or control for time, attention, and other contextual factors. The high nonresponse rate (81%) to initial recruitment may have affected the generalizability of the findings.

DISCLOSURES:

The study was supported by the Pain Management Collaboratory–Pragmatic Clinical Trials Demonstration. Various authors reported grants from the National Center for Complementary and Integrative Health and the National Institute of Nursing Research.

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 first appeared on Medscape.com.

TOPLINE:

Age-related hearing loss and peripheral neuropathy in older adults reduce longevity both directly and indirectly by affecting balance and gait.

METHODOLOGY:

• Researchers analyzed 793 older adults recruited from primary care practices participating in the OKLAHOMA Studies in 1999.
• Participants completed a questionnaire and underwent a physical examination; timed gait assessments (50 ft); and tests for peripheral nerve function, balance, and hearing.
• Hearing thresholds were tested at 20, 25, and 40 dB, respectively, and at sound frequencies of 500, 1000, 2000, and 4000 Hz.
• Researchers tracked mortality data over 22 years.

TAKEAWAY:

• Overall, 83% participants experienced hearing loss. Regular use of hearing aids was low, reported in 19% and 55% of those with moderate and severe hearing loss, respectively.
• Hearing loss was linked to impaired balance (P = .0014), slower walking (P = .0024), and reduced survival time (P = .0001). Moderate to severe hearing loss was strongly associated with reduced survival time (odds ratio, 1.36; P = .001), independent of the use of hearing aids.
• Peripheral neuropathy was present in 32% participants. The condition also increased the risk for death over the study period (hazard ratio [HR], 1.32; P = .003). Participants with both hearing loss and peripheral neuropathy showed reduced balance and survival time compared with people with either condition alone (HR, 1.55; P < .0001).

IN PRACTICE:

“Like peripheral neuropathy, advanced-age hearing loss is associated with reduced life expectancy, probably mediated in part through an adverse impact on balance,” the authors wrote. “Greater appreciation for the serious impacts of hearing loss and peripheral neuropathy could lead to further efforts to understand their causes and improve prevention and treatment strategies.”

SOURCE:

The study was led by James W. Mold, MD, MPH, of the University of Oklahoma Health Sciences Center, Oklahoma City. It was published online in the Journal of the American Geriatrics Society.

LIMITATIONS:

The dataset was collected in 1999 and may not entirely represent the current cohorts of older primary care patients. The absence of soundproof rooms and the exclusion of some components of the standard audiometric evaluation may have affected low-frequency sound measurements. Furthermore, physical examination was a less accurate measure of peripheral neuropathy. Information on the duration or severity of predictors and causes of death was not available.

DISCLOSURES:

The study was funded by the Presbyterian Health Foundation. The authors did not disclose any competing 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:

Age-related hearing loss and peripheral neuropathy in older adults reduce longevity both directly and indirectly by affecting balance and gait.

METHODOLOGY:

• Researchers analyzed 793 older adults recruited from primary care practices participating in the OKLAHOMA Studies in 1999.
• Participants completed a questionnaire and underwent a physical examination; timed gait assessments (50 ft); and tests for peripheral nerve function, balance, and hearing.
• Hearing thresholds were tested at 20, 25, and 40 dB, respectively, and at sound frequencies of 500, 1000, 2000, and 4000 Hz.
• Researchers tracked mortality data over 22 years.

TAKEAWAY:

• Overall, 83% participants experienced hearing loss. Regular use of hearing aids was low, reported in 19% and 55% of those with moderate and severe hearing loss, respectively.
• Hearing loss was linked to impaired balance (P = .0014), slower walking (P = .0024), and reduced survival time (P = .0001). Moderate to severe hearing loss was strongly associated with reduced survival time (odds ratio, 1.36; P = .001), independent of the use of hearing aids.
• Peripheral neuropathy was present in 32% participants. The condition also increased the risk for death over the study period (hazard ratio [HR], 1.32; P = .003). Participants with both hearing loss and peripheral neuropathy showed reduced balance and survival time compared with people with either condition alone (HR, 1.55; P < .0001).

IN PRACTICE:

“Like peripheral neuropathy, advanced-age hearing loss is associated with reduced life expectancy, probably mediated in part through an adverse impact on balance,” the authors wrote. “Greater appreciation for the serious impacts of hearing loss and peripheral neuropathy could lead to further efforts to understand their causes and improve prevention and treatment strategies.”

SOURCE:

The study was led by James W. Mold, MD, MPH, of the University of Oklahoma Health Sciences Center, Oklahoma City. It was published online in the Journal of the American Geriatrics Society.

LIMITATIONS:

The dataset was collected in 1999 and may not entirely represent the current cohorts of older primary care patients. The absence of soundproof rooms and the exclusion of some components of the standard audiometric evaluation may have affected low-frequency sound measurements. Furthermore, physical examination was a less accurate measure of peripheral neuropathy. Information on the duration or severity of predictors and causes of death was not available.

DISCLOSURES:

The study was funded by the Presbyterian Health Foundation. The authors did not disclose any competing 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:

Age-related hearing loss and peripheral neuropathy in older adults reduce longevity both directly and indirectly by affecting balance and gait.

METHODOLOGY:

• Researchers analyzed 793 older adults recruited from primary care practices participating in the OKLAHOMA Studies in 1999.
• Participants completed a questionnaire and underwent a physical examination; timed gait assessments (50 ft); and tests for peripheral nerve function, balance, and hearing.
• Hearing thresholds were tested at 20, 25, and 40 dB, respectively, and at sound frequencies of 500, 1000, 2000, and 4000 Hz.
• Researchers tracked mortality data over 22 years.

TAKEAWAY:

• Overall, 83% participants experienced hearing loss. Regular use of hearing aids was low, reported in 19% and 55% of those with moderate and severe hearing loss, respectively.
• Hearing loss was linked to impaired balance (P = .0014), slower walking (P = .0024), and reduced survival time (P = .0001). Moderate to severe hearing loss was strongly associated with reduced survival time (odds ratio, 1.36; P = .001), independent of the use of hearing aids.
• Peripheral neuropathy was present in 32% participants. The condition also increased the risk for death over the study period (hazard ratio [HR], 1.32; P = .003). Participants with both hearing loss and peripheral neuropathy showed reduced balance and survival time compared with people with either condition alone (HR, 1.55; P < .0001).

IN PRACTICE:

“Like peripheral neuropathy, advanced-age hearing loss is associated with reduced life expectancy, probably mediated in part through an adverse impact on balance,” the authors wrote. “Greater appreciation for the serious impacts of hearing loss and peripheral neuropathy could lead to further efforts to understand their causes and improve prevention and treatment strategies.”

SOURCE:

The study was led by James W. Mold, MD, MPH, of the University of Oklahoma Health Sciences Center, Oklahoma City. It was published online in the Journal of the American Geriatrics Society.

LIMITATIONS:

The dataset was collected in 1999 and may not entirely represent the current cohorts of older primary care patients. The absence of soundproof rooms and the exclusion of some components of the standard audiometric evaluation may have affected low-frequency sound measurements. Furthermore, physical examination was a less accurate measure of peripheral neuropathy. Information on the duration or severity of predictors and causes of death was not available.

DISCLOSURES:

The study was funded by the Presbyterian Health Foundation. The authors did not disclose any competing 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.

Cold snare endoscopic mucosal resection (EMR) may be a safe therapeutic option for selected large colorectal polyps, thanks to a safety profile superior to that of hot EMR.

In findings from Germany’s randomized controlled CHRONICLE trial, published in Gastroenterology , the cold technique almost eliminated major adverse events (AEs) — but at the cost of higher rates of recurrence and residual adenoma at first follow-up.

“The exact definition of the ideal lesions requires further research,” wrote investigators led by Ingo Steinbrück, MD, of the Department of Medicine and Gastroenterology at the Academic Teaching Hospital of the University of Freiburg, Freiburg im Breisgau, Germany. “Further studies have to confirm to what extent polyp size and histology can determine an individualized approach.”

Evangelisches Diakoniekrankenhaus Freiburg

The Study

From June 2021 to July 2023, the 19-center intention-to-treat analysis enrolled 363 patients (48.2% women) with a total of 396 polyps and randomly assigned those with polyps of ≥ 20 mm to cold (n = 193) or hot EMR (n = 203). The primary outcome was major AEs such as perforation or post-endoscopic bleeding.

Major AEs occurred in 1.0% of the cold group and in 7.9% of the hot group (P = .001, odds ratio [OR], 0.12; 95% CI, 0.03-0.54).

Rates for perforation and post-endoscopic bleeding were significantly lower in the cold group, with 0 vs 8 (0% vs 3.9%, P = .007) perforations in the two groups, respectively, as well as 1.0% vs 4.4% (P = .040) for postprocedural bleeding.

Somewhat surprisingly, intraprocedural bleeding was also less common in the cold EMR group at 14% vs 23%.

Residual adenoma, however, was found more frequently in the cold group at 23.7% vs 13.8% (OR, 1.94; 95% CI,1.12-3.38; P = .020).

Commenting on the study but not involved in it, Seth Crockett, MD, MPH, AGAF, a professor of medicine in the Division of Gastroenterology and Hepatology at Oregon Health & Science University in Portland, Oregon, called the CHRONICLE findings very important.

Oregon Health &amp; Science University

Implications

This study has several implications, Dr. Crockett said. First, more research and innovation are needed to develop techniques to maximize complete resection during cold EMR and minimize residual polyp rates. “Ideally, this would involve other cold techniques so as not to offset the safety benefits of cold EMR,” he noted.

Second, patient selection is important, as cold EMR is likely more suitable for those with serrated lesions and for those in whom follow-up can be assured, he added. “For patients who have the largest polyps, particularly lesions of the laterally spreading tumor, nodular mixed type, and those who do not wish to participate in surveillance, hot EMR may be preferable, at least at this point.”

The authors agreed that new technical development that improves the outcomes and cost-effectiveness of cold snare polypectomy and combines its demonstrated safety with recurrence reduction is necessary, as are studies to identify optimal candidate lesions.

“The next step is to evaluate whether cold snare EMR with additional measures leads to a recurrence rate comparable to hot snare EMR with margin coagulation,” Dr. Steinbrück said. “If this is the case, cold snare resection may be the future treatment of choice for all large nonpedunculated polyps without suspected malignancy in the colorectum.”

This work was supported by the Gastroenterology Foundation, Küsnacht, Switzerland. Dr. Steinbrück reported lecture fees and travel grants from Olympus Medical, a polypectomy device maker, and Falk Pharma. Numerous coauthors disclosed financial relationships with pharmaceutical and medical device companies, including Olympus Medical. Dr. Crockett disclosed no competing interests relevant to his comments.

A version of this article appeared on Medscape.com.

Cold snare endoscopic mucosal resection (EMR) may be a safe therapeutic option for selected large colorectal polyps, thanks to a safety profile superior to that of hot EMR.

In findings from Germany’s randomized controlled CHRONICLE trial, published in Gastroenterology , the cold technique almost eliminated major adverse events (AEs) — but at the cost of higher rates of recurrence and residual adenoma at first follow-up.

“The exact definition of the ideal lesions requires further research,” wrote investigators led by Ingo Steinbrück, MD, of the Department of Medicine and Gastroenterology at the Academic Teaching Hospital of the University of Freiburg, Freiburg im Breisgau, Germany. “Further studies have to confirm to what extent polyp size and histology can determine an individualized approach.”

Evangelisches Diakoniekrankenhaus Freiburg

The Study

From June 2021 to July 2023, the 19-center intention-to-treat analysis enrolled 363 patients (48.2% women) with a total of 396 polyps and randomly assigned those with polyps of ≥ 20 mm to cold (n = 193) or hot EMR (n = 203). The primary outcome was major AEs such as perforation or post-endoscopic bleeding.

Major AEs occurred in 1.0% of the cold group and in 7.9% of the hot group (P = .001, odds ratio [OR], 0.12; 95% CI, 0.03-0.54).

Rates for perforation and post-endoscopic bleeding were significantly lower in the cold group, with 0 vs 8 (0% vs 3.9%, P = .007) perforations in the two groups, respectively, as well as 1.0% vs 4.4% (P = .040) for postprocedural bleeding.

Somewhat surprisingly, intraprocedural bleeding was also less common in the cold EMR group at 14% vs 23%.

Residual adenoma, however, was found more frequently in the cold group at 23.7% vs 13.8% (OR, 1.94; 95% CI,1.12-3.38; P = .020).

Commenting on the study but not involved in it, Seth Crockett, MD, MPH, AGAF, a professor of medicine in the Division of Gastroenterology and Hepatology at Oregon Health & Science University in Portland, Oregon, called the CHRONICLE findings very important.

Oregon Health &amp; Science University

Implications

This study has several implications, Dr. Crockett said. First, more research and innovation are needed to develop techniques to maximize complete resection during cold EMR and minimize residual polyp rates. “Ideally, this would involve other cold techniques so as not to offset the safety benefits of cold EMR,” he noted.

Second, patient selection is important, as cold EMR is likely more suitable for those with serrated lesions and for those in whom follow-up can be assured, he added. “For patients who have the largest polyps, particularly lesions of the laterally spreading tumor, nodular mixed type, and those who do not wish to participate in surveillance, hot EMR may be preferable, at least at this point.”

The authors agreed that new technical development that improves the outcomes and cost-effectiveness of cold snare polypectomy and combines its demonstrated safety with recurrence reduction is necessary, as are studies to identify optimal candidate lesions.

“The next step is to evaluate whether cold snare EMR with additional measures leads to a recurrence rate comparable to hot snare EMR with margin coagulation,” Dr. Steinbrück said. “If this is the case, cold snare resection may be the future treatment of choice for all large nonpedunculated polyps without suspected malignancy in the colorectum.”

This work was supported by the Gastroenterology Foundation, Küsnacht, Switzerland. Dr. Steinbrück reported lecture fees and travel grants from Olympus Medical, a polypectomy device maker, and Falk Pharma. Numerous coauthors disclosed financial relationships with pharmaceutical and medical device companies, including Olympus Medical. Dr. Crockett disclosed no competing interests relevant to his comments.

A version of this article appeared on Medscape.com.

Cold snare endoscopic mucosal resection (EMR) may be a safe therapeutic option for selected large colorectal polyps, thanks to a safety profile superior to that of hot EMR.

In findings from Germany’s randomized controlled CHRONICLE trial, published in Gastroenterology , the cold technique almost eliminated major adverse events (AEs) — but at the cost of higher rates of recurrence and residual adenoma at first follow-up.

“The exact definition of the ideal lesions requires further research,” wrote investigators led by Ingo Steinbrück, MD, of the Department of Medicine and Gastroenterology at the Academic Teaching Hospital of the University of Freiburg, Freiburg im Breisgau, Germany. “Further studies have to confirm to what extent polyp size and histology can determine an individualized approach.”

Evangelisches Diakoniekrankenhaus Freiburg

The Study

From June 2021 to July 2023, the 19-center intention-to-treat analysis enrolled 363 patients (48.2% women) with a total of 396 polyps and randomly assigned those with polyps of ≥ 20 mm to cold (n = 193) or hot EMR (n = 203). The primary outcome was major AEs such as perforation or post-endoscopic bleeding.

Major AEs occurred in 1.0% of the cold group and in 7.9% of the hot group (P = .001, odds ratio [OR], 0.12; 95% CI, 0.03-0.54).

Rates for perforation and post-endoscopic bleeding were significantly lower in the cold group, with 0 vs 8 (0% vs 3.9%, P = .007) perforations in the two groups, respectively, as well as 1.0% vs 4.4% (P = .040) for postprocedural bleeding.

Somewhat surprisingly, intraprocedural bleeding was also less common in the cold EMR group at 14% vs 23%.

Residual adenoma, however, was found more frequently in the cold group at 23.7% vs 13.8% (OR, 1.94; 95% CI,1.12-3.38; P = .020).

Commenting on the study but not involved in it, Seth Crockett, MD, MPH, AGAF, a professor of medicine in the Division of Gastroenterology and Hepatology at Oregon Health & Science University in Portland, Oregon, called the CHRONICLE findings very important.

Oregon Health &amp; Science University

Implications

This study has several implications, Dr. Crockett said. First, more research and innovation are needed to develop techniques to maximize complete resection during cold EMR and minimize residual polyp rates. “Ideally, this would involve other cold techniques so as not to offset the safety benefits of cold EMR,” he noted.

Second, patient selection is important, as cold EMR is likely more suitable for those with serrated lesions and for those in whom follow-up can be assured, he added. “For patients who have the largest polyps, particularly lesions of the laterally spreading tumor, nodular mixed type, and those who do not wish to participate in surveillance, hot EMR may be preferable, at least at this point.”

The authors agreed that new technical development that improves the outcomes and cost-effectiveness of cold snare polypectomy and combines its demonstrated safety with recurrence reduction is necessary, as are studies to identify optimal candidate lesions.

“The next step is to evaluate whether cold snare EMR with additional measures leads to a recurrence rate comparable to hot snare EMR with margin coagulation,” Dr. Steinbrück said. “If this is the case, cold snare resection may be the future treatment of choice for all large nonpedunculated polyps without suspected malignancy in the colorectum.”

This work was supported by the Gastroenterology Foundation, Küsnacht, Switzerland. Dr. Steinbrück reported lecture fees and travel grants from Olympus Medical, a polypectomy device maker, and Falk Pharma. Numerous coauthors disclosed financial relationships with pharmaceutical and medical device companies, including Olympus Medical. Dr. Crockett disclosed no competing interests relevant to his comments.

A version of this article appeared on Medscape.com.

TOPLINE:

A smartphone app that delivers acceptance and commitment therapy (ACT), a type of cognitive behavioral therapy, improves overall well-being and reduces the severity of pain, fatigue, sleep issues, and depression to a greater extent than daily symptom tracking in patients with fibromyalgia.

METHODOLOGY:

• Researchers conducted the phase 3 PROSPER-FM trial at 25 community sites in the United States to assess the efficacy and safety of digital ACT for patients with fibromyalgia.
• A total of 275 adult patients aged 22-75 years with fibromyalgia were randomly assigned to either the digital ACT group (n = 140) or the active control group (n = 135) for 12 weeks.
• Patients in the digital ACT group received a self-guided, smartphone-delivered program in which they learned and practiced the core ACT skills of acceptance, values, mindfulness, defusion, self as context, and willingness and committed action to build psychological flexibility, while the control group underwent daily symptom tracking and received educational materials.
• The primary endpoint was the response rate on the Patient Global Impression of Change (PGIC) at week 12, which is an indicator of patient well-being.
• The secondary endpoints included changes in the Revised Fibromyalgia Impact Questionnaire (FIQ-R) total score and pain intensity, pain interference, and sleep interference scores.

TAKEAWAY:

• At week 12, 71% of the patients in the digital ACT group responded with a minimally improved or better change in the PGIC response, compared with only 22% of the patients in the control group (P < .0001).
• The digital ACT group showed a significant reduction in the impact of fibromyalgia, with a between-group effect size of d = 0.65 (P < .0001) at week 12. The FIQ-R total score significantly improved within 3 weeks of using the self-guided digital ACT app.
• The use of digital ACT also demonstrated positive effects on the levels of weekly pain intensity (P = .001) and depression (P < .0001), compared with the control group.
• No serious adverse effects related to the app were reported, and both groups demonstrated high rates of adherence, with most (72%) participants in the digital ACT group completing at least 42 sessions.

IN PRACTICE:

“The results found in the study are essential for professionals who care for patients with fibromyalgia as they present a new viable treatment alternative,” Guilherme Torres Vilarino, PhD, Santa Catarina State University, Florianópolis, Brazil, wrote in an accompanying editorial.

SOURCE:

This study was led by R. Michael Gendreau, MD, PhD, Gendreau Consulting, Poway, California. It was published online  in The Lancet.

LIMITATIONS:

The study population predominantly consisted of women and White individuals, which may limit the generalizability of the findings to more diverse populations. Additionally, the study was conducted in the United States, and the results may thus not be applicable to other countries with different racial, ethnic, educational, and economic characteristics. The study duration was 12 weeks, and the long-term benefits of digital ACT have not yet been shown.

DISCLOSURES:

This study was funded by Swing Therapeutics. Seven authors declared having stock options and/or receiving salary from Swing Therapeutics. Other authors reported having many ties with several sources, including Swing Therapeutics.

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 first appeared on Medscape.com.

TOPLINE:

A smartphone app that delivers acceptance and commitment therapy (ACT), a type of cognitive behavioral therapy, improves overall well-being and reduces the severity of pain, fatigue, sleep issues, and depression to a greater extent than daily symptom tracking in patients with fibromyalgia.

METHODOLOGY:

• Researchers conducted the phase 3 PROSPER-FM trial at 25 community sites in the United States to assess the efficacy and safety of digital ACT for patients with fibromyalgia.
• A total of 275 adult patients aged 22-75 years with fibromyalgia were randomly assigned to either the digital ACT group (n = 140) or the active control group (n = 135) for 12 weeks.
• Patients in the digital ACT group received a self-guided, smartphone-delivered program in which they learned and practiced the core ACT skills of acceptance, values, mindfulness, defusion, self as context, and willingness and committed action to build psychological flexibility, while the control group underwent daily symptom tracking and received educational materials.
• The primary endpoint was the response rate on the Patient Global Impression of Change (PGIC) at week 12, which is an indicator of patient well-being.
• The secondary endpoints included changes in the Revised Fibromyalgia Impact Questionnaire (FIQ-R) total score and pain intensity, pain interference, and sleep interference scores.

TAKEAWAY:

• At week 12, 71% of the patients in the digital ACT group responded with a minimally improved or better change in the PGIC response, compared with only 22% of the patients in the control group (P < .0001).
• The digital ACT group showed a significant reduction in the impact of fibromyalgia, with a between-group effect size of d = 0.65 (P < .0001) at week 12. The FIQ-R total score significantly improved within 3 weeks of using the self-guided digital ACT app.
• The use of digital ACT also demonstrated positive effects on the levels of weekly pain intensity (P = .001) and depression (P < .0001), compared with the control group.
• No serious adverse effects related to the app were reported, and both groups demonstrated high rates of adherence, with most (72%) participants in the digital ACT group completing at least 42 sessions.

IN PRACTICE:

“The results found in the study are essential for professionals who care for patients with fibromyalgia as they present a new viable treatment alternative,” Guilherme Torres Vilarino, PhD, Santa Catarina State University, Florianópolis, Brazil, wrote in an accompanying editorial.

SOURCE:

This study was led by R. Michael Gendreau, MD, PhD, Gendreau Consulting, Poway, California. It was published online  in The Lancet.

LIMITATIONS:

The study population predominantly consisted of women and White individuals, which may limit the generalizability of the findings to more diverse populations. Additionally, the study was conducted in the United States, and the results may thus not be applicable to other countries with different racial, ethnic, educational, and economic characteristics. The study duration was 12 weeks, and the long-term benefits of digital ACT have not yet been shown.

DISCLOSURES:

This study was funded by Swing Therapeutics. Seven authors declared having stock options and/or receiving salary from Swing Therapeutics. Other authors reported having many ties with several sources, including Swing Therapeutics.

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 first appeared on Medscape.com.

TOPLINE:

A smartphone app that delivers acceptance and commitment therapy (ACT), a type of cognitive behavioral therapy, improves overall well-being and reduces the severity of pain, fatigue, sleep issues, and depression to a greater extent than daily symptom tracking in patients with fibromyalgia.

METHODOLOGY:

• Researchers conducted the phase 3 PROSPER-FM trial at 25 community sites in the United States to assess the efficacy and safety of digital ACT for patients with fibromyalgia.
• A total of 275 adult patients aged 22-75 years with fibromyalgia were randomly assigned to either the digital ACT group (n = 140) or the active control group (n = 135) for 12 weeks.
• Patients in the digital ACT group received a self-guided, smartphone-delivered program in which they learned and practiced the core ACT skills of acceptance, values, mindfulness, defusion, self as context, and willingness and committed action to build psychological flexibility, while the control group underwent daily symptom tracking and received educational materials.
• The primary endpoint was the response rate on the Patient Global Impression of Change (PGIC) at week 12, which is an indicator of patient well-being.
• The secondary endpoints included changes in the Revised Fibromyalgia Impact Questionnaire (FIQ-R) total score and pain intensity, pain interference, and sleep interference scores.

TAKEAWAY:

• At week 12, 71% of the patients in the digital ACT group responded with a minimally improved or better change in the PGIC response, compared with only 22% of the patients in the control group (P < .0001).
• The digital ACT group showed a significant reduction in the impact of fibromyalgia, with a between-group effect size of d = 0.65 (P < .0001) at week 12. The FIQ-R total score significantly improved within 3 weeks of using the self-guided digital ACT app.
• The use of digital ACT also demonstrated positive effects on the levels of weekly pain intensity (P = .001) and depression (P < .0001), compared with the control group.
• No serious adverse effects related to the app were reported, and both groups demonstrated high rates of adherence, with most (72%) participants in the digital ACT group completing at least 42 sessions.

IN PRACTICE:

“The results found in the study are essential for professionals who care for patients with fibromyalgia as they present a new viable treatment alternative,” Guilherme Torres Vilarino, PhD, Santa Catarina State University, Florianópolis, Brazil, wrote in an accompanying editorial.

SOURCE:

This study was led by R. Michael Gendreau, MD, PhD, Gendreau Consulting, Poway, California. It was published online  in The Lancet.

LIMITATIONS:

The study population predominantly consisted of women and White individuals, which may limit the generalizability of the findings to more diverse populations. Additionally, the study was conducted in the United States, and the results may thus not be applicable to other countries with different racial, ethnic, educational, and economic characteristics. The study duration was 12 weeks, and the long-term benefits of digital ACT have not yet been shown.

DISCLOSURES:

This study was funded by Swing Therapeutics. Seven authors declared having stock options and/or receiving salary from Swing Therapeutics. Other authors reported having many ties with several sources, including Swing Therapeutics.

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 first appeared on Medscape.com.

The number of patients treated with anticoagulants has significantly increased over the past decade, largely owing to the introduction of direct oral anticoagulants (DOACs). Currently, more than 6 million people nationwide are taking anticoagulants; these include patients receiving care through the Veterans Health Administration.

However, the growing use of oral anticoagulants has been accompanied by a rise in anticoagulant-related bleeding incidents. Dr Geoffrey Barnes from the University of Michigan discusses strategies to assess and manage bleeding events, and he reviews the most current recommendations on the appropriate selection and use of anticoagulation reversal agents.

Dr Barnes also underscores the importance of monitoring for thromboembolic complications in patients treated for life-threatening bleeding to prevent post-bleed thromboembolic events.

--

Associate Professor, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Pfizer; Bristol-Myers Squibb; Janssen; Bayer; AstraZeneca; Sanofi; Anthos; Abbott Vascular; Boston Scientific

Received research grant from: Boston Scientific

The number of patients treated with anticoagulants has significantly increased over the past decade, largely owing to the introduction of direct oral anticoagulants (DOACs). Currently, more than 6 million people nationwide are taking anticoagulants; these include patients receiving care through the Veterans Health Administration.

However, the growing use of oral anticoagulants has been accompanied by a rise in anticoagulant-related bleeding incidents. Dr Geoffrey Barnes from the University of Michigan discusses strategies to assess and manage bleeding events, and he reviews the most current recommendations on the appropriate selection and use of anticoagulation reversal agents.

Dr Barnes also underscores the importance of monitoring for thromboembolic complications in patients treated for life-threatening bleeding to prevent post-bleed thromboembolic events.

--

Associate Professor, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Pfizer; Bristol-Myers Squibb; Janssen; Bayer; AstraZeneca; Sanofi; Anthos; Abbott Vascular; Boston Scientific

Received research grant from: Boston Scientific

The number of patients treated with anticoagulants has significantly increased over the past decade, largely owing to the introduction of direct oral anticoagulants (DOACs). Currently, more than 6 million people nationwide are taking anticoagulants; these include patients receiving care through the Veterans Health Administration.

However, the growing use of oral anticoagulants has been accompanied by a rise in anticoagulant-related bleeding incidents. Dr Geoffrey Barnes from the University of Michigan discusses strategies to assess and manage bleeding events, and he reviews the most current recommendations on the appropriate selection and use of anticoagulation reversal agents.

Dr Barnes also underscores the importance of monitoring for thromboembolic complications in patients treated for life-threatening bleeding to prevent post-bleed thromboembolic events.

--

Associate Professor, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Pfizer; Bristol-Myers Squibb; Janssen; Bayer; AstraZeneca; Sanofi; Anthos; Abbott Vascular; Boston Scientific

Received research grant from: Boston Scientific

TOPLINE:

Liver transplant improved progression-free survival (PFS) in carefully selected patients with unresectable colorectal liver metastasis; however, the overall survival and recurrence rate benefits did not reach statistical significance.

METHODOLOGY:

• Research has shown promising results for well-selected patients with unresectable colorectal liver metastasis undergoing liver transplant; however, the absence of a suitable comparison group makes it difficult to evaluate the overall effectiveness of this treatment method. 
• Researchers evaluated 33 patients with colorectal cancer and unresectable liver metastasis (mean age, 43.5 years; 52% women) who were eligible for liver transplants, according to validated selection criteria. 
• Of these, 20 patients (61%) underwent a liver transplant, while 13 (39%) declined transplantation and received alternative therapy. 
• Patients who received liver transplants did not undergo regular chemotherapy until recurrence, whereas those in the alternative therapy group continued systemic chemotherapy, with hepatic artery infusion pump placement (n = 5), liver resections (n = 6), and locoregional therapies (n = 6). 
• The main outcomes of the study were overall survival and PFS. 

TAKEAWAY:

• The median follow-up duration was 986 days in the liver transplant group and 657 days in the alternative therapy group. 
• Patients who underwent liver transplant showed higher PFS rates at 1 year (90.0% vs 41.7%), 2 years (72.7% vs 10.4%), and 3 years (36.4% vs 10.4%). The PFS gains were statistically significant (P < .01). 
• Overall survival was also higher in the transplant group — 100% vs 83.9% at 1 year, and 90.0% vs 73.4% at both 2 and 3 years. The differences, however, did not reach significance (P = .12). 
• Liver transplant was associated with a lower recurrence rate (5% vs 23%), which also did not reach significance (P = .28) possibly because of the small patient population. 

IN PRACTICE:

“This study represents the best available data for evaluating alternatives to [liver transplant],” the authors wrote, adding that the patients should be “referred for multidisciplinary evaluation to transplant oncology centers with strict criteria.”

SOURCE:

The study was led by Matthew M. Byrne, MD, Department of Surgery, University of Rochester Medical Center, Rochester, New York, and was published online in JAMA Surgery.

LIMITATIONS:

The patient population was small, making it difficult to interpret statistical significance. The inclusion of patients with financial and social support might limit generalizability. The survival was calculated from the date of transplant or dropout. Additionally, the study did not explore sex-based differences in treatment choice.

DISCLOSURES:

The authors did not disclose any funding information. One author reported holding shares with HistoSonics, not related to the submitted work.

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 first appeared on Medscape.com.

TOPLINE:

Liver transplant improved progression-free survival (PFS) in carefully selected patients with unresectable colorectal liver metastasis; however, the overall survival and recurrence rate benefits did not reach statistical significance.

METHODOLOGY:

• Research has shown promising results for well-selected patients with unresectable colorectal liver metastasis undergoing liver transplant; however, the absence of a suitable comparison group makes it difficult to evaluate the overall effectiveness of this treatment method. 
• Researchers evaluated 33 patients with colorectal cancer and unresectable liver metastasis (mean age, 43.5 years; 52% women) who were eligible for liver transplants, according to validated selection criteria. 
• Of these, 20 patients (61%) underwent a liver transplant, while 13 (39%) declined transplantation and received alternative therapy. 
• Patients who received liver transplants did not undergo regular chemotherapy until recurrence, whereas those in the alternative therapy group continued systemic chemotherapy, with hepatic artery infusion pump placement (n = 5), liver resections (n = 6), and locoregional therapies (n = 6). 
• The main outcomes of the study were overall survival and PFS. 

TAKEAWAY:

• The median follow-up duration was 986 days in the liver transplant group and 657 days in the alternative therapy group. 
• Patients who underwent liver transplant showed higher PFS rates at 1 year (90.0% vs 41.7%), 2 years (72.7% vs 10.4%), and 3 years (36.4% vs 10.4%). The PFS gains were statistically significant (P < .01). 
• Overall survival was also higher in the transplant group — 100% vs 83.9% at 1 year, and 90.0% vs 73.4% at both 2 and 3 years. The differences, however, did not reach significance (P = .12). 
• Liver transplant was associated with a lower recurrence rate (5% vs 23%), which also did not reach significance (P = .28) possibly because of the small patient population. 

IN PRACTICE:

“This study represents the best available data for evaluating alternatives to [liver transplant],” the authors wrote, adding that the patients should be “referred for multidisciplinary evaluation to transplant oncology centers with strict criteria.”

SOURCE:

The study was led by Matthew M. Byrne, MD, Department of Surgery, University of Rochester Medical Center, Rochester, New York, and was published online in JAMA Surgery.

LIMITATIONS:

The patient population was small, making it difficult to interpret statistical significance. The inclusion of patients with financial and social support might limit generalizability. The survival was calculated from the date of transplant or dropout. Additionally, the study did not explore sex-based differences in treatment choice.

DISCLOSURES:

The authors did not disclose any funding information. One author reported holding shares with HistoSonics, not related to the submitted work.

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 first appeared on Medscape.com.

TOPLINE:

Liver transplant improved progression-free survival (PFS) in carefully selected patients with unresectable colorectal liver metastasis; however, the overall survival and recurrence rate benefits did not reach statistical significance.

METHODOLOGY:

• Research has shown promising results for well-selected patients with unresectable colorectal liver metastasis undergoing liver transplant; however, the absence of a suitable comparison group makes it difficult to evaluate the overall effectiveness of this treatment method. 
• Researchers evaluated 33 patients with colorectal cancer and unresectable liver metastasis (mean age, 43.5 years; 52% women) who were eligible for liver transplants, according to validated selection criteria. 
• Of these, 20 patients (61%) underwent a liver transplant, while 13 (39%) declined transplantation and received alternative therapy. 
• Patients who received liver transplants did not undergo regular chemotherapy until recurrence, whereas those in the alternative therapy group continued systemic chemotherapy, with hepatic artery infusion pump placement (n = 5), liver resections (n = 6), and locoregional therapies (n = 6). 
• The main outcomes of the study were overall survival and PFS. 

TAKEAWAY:

• The median follow-up duration was 986 days in the liver transplant group and 657 days in the alternative therapy group. 
• Patients who underwent liver transplant showed higher PFS rates at 1 year (90.0% vs 41.7%), 2 years (72.7% vs 10.4%), and 3 years (36.4% vs 10.4%). The PFS gains were statistically significant (P < .01). 
• Overall survival was also higher in the transplant group — 100% vs 83.9% at 1 year, and 90.0% vs 73.4% at both 2 and 3 years. The differences, however, did not reach significance (P = .12). 
• Liver transplant was associated with a lower recurrence rate (5% vs 23%), which also did not reach significance (P = .28) possibly because of the small patient population. 

IN PRACTICE:

“This study represents the best available data for evaluating alternatives to [liver transplant],” the authors wrote, adding that the patients should be “referred for multidisciplinary evaluation to transplant oncology centers with strict criteria.”

SOURCE:

The study was led by Matthew M. Byrne, MD, Department of Surgery, University of Rochester Medical Center, Rochester, New York, and was published online in JAMA Surgery.

LIMITATIONS:

The patient population was small, making it difficult to interpret statistical significance. The inclusion of patients with financial and social support might limit generalizability. The survival was calculated from the date of transplant or dropout. Additionally, the study did not explore sex-based differences in treatment choice.

DISCLOSURES:

The authors did not disclose any funding information. One author reported holding shares with HistoSonics, not related to the submitted work.

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 first appeared on Medscape.com.

Having an ostomy is a dreaded prospect for many patients with rectal cancer.

To defer, and potentially avoid, this life-altering surgery, the watch-and-wait approach has become increasingly common among patients with locally advanced disease who have a complete response to neoadjuvant chemoradiation.

About 80% of these patients who have a complete clinical response — a perfectly healed scar where the tumor used to be and other favorable features — can forgo total mesorectal excision and preserve their rectum.

The success of watch-and-wait among complete responders has led some centers to offer the approach in patients with near-complete responses to neoadjuvant chemoradiation.

But watch-and-wait for near-complete clinical responders “is very controversial,” Alan P. Venook, MD, a gastrointestinal oncologist at the University of California, San Francisco (UCSF), told this news organization.

“You sure as hell don’t want to miss a chance to cure a patient,” Dr. Venook said.

A near-complete clinical response essentially means there is no sign of the tumor 8 weeks after total neoadjuvant therapy, but the tumor bed hasn’t completely healed.

The goal of watch-and-wait in this scenario is to give near-complete response lesions time to become complete responses.

But there’s no clear way to predict which tumors will evolve into a clinical complete response.

Recent studies evaluating the conversion rate have reported that anywhere from 39% to about 90% of near-complete responders became complete responders. Some of the variation likely comes down to differences in the clinical stage of patients evaluated in each study as well as the limited number of patients who achieve a near-complete response overall.

Other concerns have emerged that waiting for near-complete responses to become complete leaves extra time for some tumors to metastasize and that tumor regrowth is much higher compared with complete responders.

A recent study found that 13% of near-complete responders who preserved their rectum on watch-and-wait developed distant metastases vs about 5% of long-term complete responders. The study also found that just over half of near-complete responders have tumor regrowth compared with about one in five complete responders.

But even with regrowth, “surgery is still curative,” explained Julio Garcia-Aguilar, MD, PhD, a pioneer of watch-and-wait for rectal cancer.

And overall, around 50%-60% of patients with a near-complete response can avoid surgery and preserve their rectum.
 

Selecting Patients for Watch-and-Wait

The key to deciding which patients are right for watch-and-wait is to understand how a near-complete clinical response was defined in the OPRA trial, a landmark randomized trial led by Dr. Garcia-Aguilar that helped establish watch-and-wait as an option in rectal cancer.

OPRA defined a near-complete response as no visible tumor but, in the tumor bed, mild erythema, superficial ulceration, minor mucosal abnormality or small nodules, and an irregular mucosa. The criteria also included no palpable tumor with smooth induration or a minor mucosal abnormality on the digital rectal exam.

The National Comprehensive Cancer Network mirrored the definition when, for the first time, it recommended watch-and-wait as an option for near-complete response in its 2023 rectal cancer guidelines. The group also added a few MRI requirements.

UCSF offers the watch-and-wait option to some patients with near-complete responses, but each decision is made on a case-by-case basis by a tumor board considering numerous measures of tumor aggressiveness.

Even then, “we have, in many cases, struggled to figure out what the right choices are,” Dr. Venook said.

For those chosen for watch-and-wait, Dr. Venook noted that UCSF has top-notch surgeons, radiation oncologists, medical oncologists, and pathologists who have the resources to follow patients closely.

For community practices without the resources of a major cancer center, watch-and-wait for near-complete response to rectal cancer “is really asking a lot,” Dr. Venook said.

Dr. Garcia-Aguilar, a colorectal surgeon at Memorial Sloan Kettering Cancer Center in New York City, explained that after years of studying the issue, he is comfortable with watch-and-wait in near-complete responders as long as it’s done carefully and in patients who will comply with ongoing surveillance.

Dr. Garcia-Aguilar explained that, after diagnosing a near-complete response 8 weeks following total neoadjuvant therapy, the patient needs to come back 6 weeks later. At that point, it’s time to assess whether that near-complete response is evolving into a complete response or not evolving into a complete response.

If it’s evolving into a complete response, surveillance continues about every 8 weeks, but if the tumor has stopped responding, “you take [the patient] to the operating room,” Dr. Garcia-Aguilar said.

As for the bigger safety concern — that near clinical complete response tumors will metastasize — Dr. Garcia-Aguilar’s opinion is that micrometastases are probably already there when the rectal cancer is first diagnosed and will manifest themselves “no matter what happens to the primary tumor.”

Because of that, he noted, “I don’t think the risk is very high” when surgery is delayed a few months to give near-complete response patients a chance to keep their rectum.

The way to answer the metastasis question is to do a randomized trial pitting surgery against watch-and-wait in patients with near-clinical complete response rectal cancer.

However, Dr. Garcia-Aguilar doesn’t think that trial will ever happen. Patients won’t allow themselves to be randomized to surgery once they find out they might be able to avoid a permanent ostomy, he said.

Dr. Venook had no disclosures. Dr. Garcia-Aguilar reported personal fees from Medtronic, Johnson & Johnson, and Intuitive Surgical.
 

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

Having an ostomy is a dreaded prospect for many patients with rectal cancer.

To defer, and potentially avoid, this life-altering surgery, the watch-and-wait approach has become increasingly common among patients with locally advanced disease who have a complete response to neoadjuvant chemoradiation.

About 80% of these patients who have a complete clinical response — a perfectly healed scar where the tumor used to be and other favorable features — can forgo total mesorectal excision and preserve their rectum.

The success of watch-and-wait among complete responders has led some centers to offer the approach in patients with near-complete responses to neoadjuvant chemoradiation.

But watch-and-wait for near-complete clinical responders “is very controversial,” Alan P. Venook, MD, a gastrointestinal oncologist at the University of California, San Francisco (UCSF), told this news organization.

“You sure as hell don’t want to miss a chance to cure a patient,” Dr. Venook said.

A near-complete clinical response essentially means there is no sign of the tumor 8 weeks after total neoadjuvant therapy, but the tumor bed hasn’t completely healed.

The goal of watch-and-wait in this scenario is to give near-complete response lesions time to become complete responses.

But there’s no clear way to predict which tumors will evolve into a clinical complete response.

Recent studies evaluating the conversion rate have reported that anywhere from 39% to about 90% of near-complete responders became complete responders. Some of the variation likely comes down to differences in the clinical stage of patients evaluated in each study as well as the limited number of patients who achieve a near-complete response overall.

Other concerns have emerged that waiting for near-complete responses to become complete leaves extra time for some tumors to metastasize and that tumor regrowth is much higher compared with complete responders.

A recent study found that 13% of near-complete responders who preserved their rectum on watch-and-wait developed distant metastases vs about 5% of long-term complete responders. The study also found that just over half of near-complete responders have tumor regrowth compared with about one in five complete responders.

But even with regrowth, “surgery is still curative,” explained Julio Garcia-Aguilar, MD, PhD, a pioneer of watch-and-wait for rectal cancer.

And overall, around 50%-60% of patients with a near-complete response can avoid surgery and preserve their rectum.
 

Selecting Patients for Watch-and-Wait

The key to deciding which patients are right for watch-and-wait is to understand how a near-complete clinical response was defined in the OPRA trial, a landmark randomized trial led by Dr. Garcia-Aguilar that helped establish watch-and-wait as an option in rectal cancer.

OPRA defined a near-complete response as no visible tumor but, in the tumor bed, mild erythema, superficial ulceration, minor mucosal abnormality or small nodules, and an irregular mucosa. The criteria also included no palpable tumor with smooth induration or a minor mucosal abnormality on the digital rectal exam.

The National Comprehensive Cancer Network mirrored the definition when, for the first time, it recommended watch-and-wait as an option for near-complete response in its 2023 rectal cancer guidelines. The group also added a few MRI requirements.

UCSF offers the watch-and-wait option to some patients with near-complete responses, but each decision is made on a case-by-case basis by a tumor board considering numerous measures of tumor aggressiveness.

Even then, “we have, in many cases, struggled to figure out what the right choices are,” Dr. Venook said.

For those chosen for watch-and-wait, Dr. Venook noted that UCSF has top-notch surgeons, radiation oncologists, medical oncologists, and pathologists who have the resources to follow patients closely.

For community practices without the resources of a major cancer center, watch-and-wait for near-complete response to rectal cancer “is really asking a lot,” Dr. Venook said.

Dr. Garcia-Aguilar, a colorectal surgeon at Memorial Sloan Kettering Cancer Center in New York City, explained that after years of studying the issue, he is comfortable with watch-and-wait in near-complete responders as long as it’s done carefully and in patients who will comply with ongoing surveillance.

Dr. Garcia-Aguilar explained that, after diagnosing a near-complete response 8 weeks following total neoadjuvant therapy, the patient needs to come back 6 weeks later. At that point, it’s time to assess whether that near-complete response is evolving into a complete response or not evolving into a complete response.

If it’s evolving into a complete response, surveillance continues about every 8 weeks, but if the tumor has stopped responding, “you take [the patient] to the operating room,” Dr. Garcia-Aguilar said.

As for the bigger safety concern — that near clinical complete response tumors will metastasize — Dr. Garcia-Aguilar’s opinion is that micrometastases are probably already there when the rectal cancer is first diagnosed and will manifest themselves “no matter what happens to the primary tumor.”

Because of that, he noted, “I don’t think the risk is very high” when surgery is delayed a few months to give near-complete response patients a chance to keep their rectum.

The way to answer the metastasis question is to do a randomized trial pitting surgery against watch-and-wait in patients with near-clinical complete response rectal cancer.

However, Dr. Garcia-Aguilar doesn’t think that trial will ever happen. Patients won’t allow themselves to be randomized to surgery once they find out they might be able to avoid a permanent ostomy, he said.

Dr. Venook had no disclosures. Dr. Garcia-Aguilar reported personal fees from Medtronic, Johnson & Johnson, and Intuitive Surgical.
 

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

Having an ostomy is a dreaded prospect for many patients with rectal cancer.

To defer, and potentially avoid, this life-altering surgery, the watch-and-wait approach has become increasingly common among patients with locally advanced disease who have a complete response to neoadjuvant chemoradiation.

About 80% of these patients who have a complete clinical response — a perfectly healed scar where the tumor used to be and other favorable features — can forgo total mesorectal excision and preserve their rectum.

The success of watch-and-wait among complete responders has led some centers to offer the approach in patients with near-complete responses to neoadjuvant chemoradiation.

But watch-and-wait for near-complete clinical responders “is very controversial,” Alan P. Venook, MD, a gastrointestinal oncologist at the University of California, San Francisco (UCSF), told this news organization.

“You sure as hell don’t want to miss a chance to cure a patient,” Dr. Venook said.

A near-complete clinical response essentially means there is no sign of the tumor 8 weeks after total neoadjuvant therapy, but the tumor bed hasn’t completely healed.

The goal of watch-and-wait in this scenario is to give near-complete response lesions time to become complete responses.

But there’s no clear way to predict which tumors will evolve into a clinical complete response.

Recent studies evaluating the conversion rate have reported that anywhere from 39% to about 90% of near-complete responders became complete responders. Some of the variation likely comes down to differences in the clinical stage of patients evaluated in each study as well as the limited number of patients who achieve a near-complete response overall.

Other concerns have emerged that waiting for near-complete responses to become complete leaves extra time for some tumors to metastasize and that tumor regrowth is much higher compared with complete responders.

A recent study found that 13% of near-complete responders who preserved their rectum on watch-and-wait developed distant metastases vs about 5% of long-term complete responders. The study also found that just over half of near-complete responders have tumor regrowth compared with about one in five complete responders.

But even with regrowth, “surgery is still curative,” explained Julio Garcia-Aguilar, MD, PhD, a pioneer of watch-and-wait for rectal cancer.

And overall, around 50%-60% of patients with a near-complete response can avoid surgery and preserve their rectum.
 

Selecting Patients for Watch-and-Wait

The key to deciding which patients are right for watch-and-wait is to understand how a near-complete clinical response was defined in the OPRA trial, a landmark randomized trial led by Dr. Garcia-Aguilar that helped establish watch-and-wait as an option in rectal cancer.

OPRA defined a near-complete response as no visible tumor but, in the tumor bed, mild erythema, superficial ulceration, minor mucosal abnormality or small nodules, and an irregular mucosa. The criteria also included no palpable tumor with smooth induration or a minor mucosal abnormality on the digital rectal exam.

The National Comprehensive Cancer Network mirrored the definition when, for the first time, it recommended watch-and-wait as an option for near-complete response in its 2023 rectal cancer guidelines. The group also added a few MRI requirements.

UCSF offers the watch-and-wait option to some patients with near-complete responses, but each decision is made on a case-by-case basis by a tumor board considering numerous measures of tumor aggressiveness.

Even then, “we have, in many cases, struggled to figure out what the right choices are,” Dr. Venook said.

For those chosen for watch-and-wait, Dr. Venook noted that UCSF has top-notch surgeons, radiation oncologists, medical oncologists, and pathologists who have the resources to follow patients closely.

For community practices without the resources of a major cancer center, watch-and-wait for near-complete response to rectal cancer “is really asking a lot,” Dr. Venook said.

Dr. Garcia-Aguilar, a colorectal surgeon at Memorial Sloan Kettering Cancer Center in New York City, explained that after years of studying the issue, he is comfortable with watch-and-wait in near-complete responders as long as it’s done carefully and in patients who will comply with ongoing surveillance.

Dr. Garcia-Aguilar explained that, after diagnosing a near-complete response 8 weeks following total neoadjuvant therapy, the patient needs to come back 6 weeks later. At that point, it’s time to assess whether that near-complete response is evolving into a complete response or not evolving into a complete response.

If it’s evolving into a complete response, surveillance continues about every 8 weeks, but if the tumor has stopped responding, “you take [the patient] to the operating room,” Dr. Garcia-Aguilar said.

As for the bigger safety concern — that near clinical complete response tumors will metastasize — Dr. Garcia-Aguilar’s opinion is that micrometastases are probably already there when the rectal cancer is first diagnosed and will manifest themselves “no matter what happens to the primary tumor.”

Because of that, he noted, “I don’t think the risk is very high” when surgery is delayed a few months to give near-complete response patients a chance to keep their rectum.

The way to answer the metastasis question is to do a randomized trial pitting surgery against watch-and-wait in patients with near-clinical complete response rectal cancer.

However, Dr. Garcia-Aguilar doesn’t think that trial will ever happen. Patients won’t allow themselves to be randomized to surgery once they find out they might be able to avoid a permanent ostomy, he said.

Dr. Venook had no disclosures. Dr. Garcia-Aguilar reported personal fees from Medtronic, Johnson & Johnson, and Intuitive Surgical.
 

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

TOPLINE:

Stereotactic body radiotherapy (SBRT) is a safe treatment option for patients with oligometastatic cancer, with only 0.5% of patients experiencing severe acute toxicities within 6 months, according to a large real-world analysis.

METHODOLOGY:

• Advances in cancer imaging have helped identify more patients with oligometastatic disease. Although the standard treatment approach typically involves systemic therapy such as chemotherapy and immunotherapy, SBRT has increasingly become an option for these patients. However, the toxicities associated with SBRT remain less clear.
• OligoCare, a European, prospective, registry-based, single-arm observational study, aims to provide real-world outcomes among patients with oligometastatic cancer who received SBRT. In this analysis, the researchers evaluated early toxicities among 1468 patients with different primary cancers — non–small cell lung cancer (NSCLC; 19.7%), colorectal cancer (20%), breast cancer (15.5%), and prostate cancer (44.8%).
• The primary outcome was acute toxicities, including new malignancies and deaths, within 6 months of initiating SBRT.
• Overall, 527 (35.9%) patients received concomitant systemic treatment and 828 (56%) had de novo oligometastatic disease.

TAKEAWAY:

• Overall, though, only eight patients (0.5%) experienced acute SBRT-related toxicity of grade 3 and above within 6 months; two events, however, were fatal (pneumonitis and cerebral hemorrhage), and both occurred in patients with NSCLC.
• The other six grade 3 events included one instance of each of the following: empyema, pneumonia, radiation pneumonitis, radiation skin injury, decreased appetite, and bone pain. Two of these events occurred in patients with NSCLC, two in patients with breast cancer, one in patients with colorectal cancer, and one in patients with prostate cancer.
• New primary malignancies were reported in 13 (0.9%) patients, which included bladder cancer (n = 3), nonmelanoma skin cancer (n = 3), and leukemia (n = 1).
• Overall, 43 (2.9%) patients died within 6 months, most from their primary cancer (58.1%).

IN PRACTICE:

Low rates of early acute toxicities reported in this real-world study help confirm the safety of SBRT in the treatment of oligometastases, the authors concluded. However, “some anatomical sites might be associated with an increased risk of even severe or fatal toxicities.”

SOURCE:

The study, led by Filippo Alongi, Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Cancer Care Center, Negrar di Valpolicella, Italy, and University of Brescia, also in Italy, was published online in Radiotherapy & Oncology .

LIMITATIONS:

Some limitations of the study include the nonrandomized design and potential variability in patient selection criteria, treatment doses, and schedules.

DISCLOSURES:

The study did not receive any funding support. Two authors declared receiving speaker or lecture honoraria or consultation fees from various sources.

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 first appeared on Medscape.com.

TOPLINE:

Stereotactic body radiotherapy (SBRT) is a safe treatment option for patients with oligometastatic cancer, with only 0.5% of patients experiencing severe acute toxicities within 6 months, according to a large real-world analysis.

METHODOLOGY:

• Advances in cancer imaging have helped identify more patients with oligometastatic disease. Although the standard treatment approach typically involves systemic therapy such as chemotherapy and immunotherapy, SBRT has increasingly become an option for these patients. However, the toxicities associated with SBRT remain less clear.
• OligoCare, a European, prospective, registry-based, single-arm observational study, aims to provide real-world outcomes among patients with oligometastatic cancer who received SBRT. In this analysis, the researchers evaluated early toxicities among 1468 patients with different primary cancers — non–small cell lung cancer (NSCLC; 19.7%), colorectal cancer (20%), breast cancer (15.5%), and prostate cancer (44.8%).
• The primary outcome was acute toxicities, including new malignancies and deaths, within 6 months of initiating SBRT.
• Overall, 527 (35.9%) patients received concomitant systemic treatment and 828 (56%) had de novo oligometastatic disease.

TAKEAWAY:

• Overall, though, only eight patients (0.5%) experienced acute SBRT-related toxicity of grade 3 and above within 6 months; two events, however, were fatal (pneumonitis and cerebral hemorrhage), and both occurred in patients with NSCLC.
• The other six grade 3 events included one instance of each of the following: empyema, pneumonia, radiation pneumonitis, radiation skin injury, decreased appetite, and bone pain. Two of these events occurred in patients with NSCLC, two in patients with breast cancer, one in patients with colorectal cancer, and one in patients with prostate cancer.
• New primary malignancies were reported in 13 (0.9%) patients, which included bladder cancer (n = 3), nonmelanoma skin cancer (n = 3), and leukemia (n = 1).
• Overall, 43 (2.9%) patients died within 6 months, most from their primary cancer (58.1%).

IN PRACTICE:

Low rates of early acute toxicities reported in this real-world study help confirm the safety of SBRT in the treatment of oligometastases, the authors concluded. However, “some anatomical sites might be associated with an increased risk of even severe or fatal toxicities.”

SOURCE:

The study, led by Filippo Alongi, Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Cancer Care Center, Negrar di Valpolicella, Italy, and University of Brescia, also in Italy, was published online in Radiotherapy & Oncology .

LIMITATIONS:

Some limitations of the study include the nonrandomized design and potential variability in patient selection criteria, treatment doses, and schedules.

DISCLOSURES:

The study did not receive any funding support. Two authors declared receiving speaker or lecture honoraria or consultation fees from various sources.

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 first appeared on Medscape.com.

TOPLINE: