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LONDON — It may not be advisable for patients with a history of myocardial infarction and preserved left ventricular function to discontinue long-term beta-blocker therapy, warn investigators.

In the randomized ABYSS trial, although there was no difference in death, MI, or stroke between patients who discontinued and those who continued taking beta-blockers, those who stopped taking the drugs had a higher rate of cardiovascular hospitalization.

Discontinuation was also associated with an increase in blood pressure and heart rate, without any improvement in quality of life.

“We thought we would be able to withdraw beta-blockers safely and that this would result in improved quality of life, but our trial results suggest this is not the case,” said lead investigator Johanne Silvain, MD, PhD, from Pitié-Salpêtrière University Hospital in Paris, who presented the ABYSS findings here at the European Society of Cardiology (ESC) Congress. 

The results, which were simultaneously published online in The New England Journal of Medicine, call into question current guidelines, which suggest that beta-blockers may be discontinued after 1 year in certain patient groups.

Beta-blockers have long been considered the standard of care for patients after MI, but trials showing the benefit of these drugs were conducted before the modern era of myocardial reperfusion and pharmacotherapy, which have led to sharp decreases in the risk for heart failure and for death after MI, Dr. Silvain explained. 

This has led to questions about the add-on benefits of lifelong beta-blocker treatment for patients with MI and a preserved left ventricular ejection fraction and no other primary indication for beta-blocker therapy.
 

The ABYSS Trial

To explore this issue, the open-label, non-inferiority ABYSS trial randomly assigned 3698 patients with a history of MI to the discontinuation or continuation of beta-blocker treatment. All study participants had a left ventricular ejection fraction of at least 40%, were receiving long-term beta-blocker treatment, and had experienced no cardiovascular event in the previous 6 months. 

At a median follow-up of 3 years, the primary endpoint — a composite of death, MI, stroke, and hospitalization for cardiovascular reasons — occurred more often in the discontinuation group than in the continuation group (23.8% vs 21.1%; hazard ratio, 1.16; 95% CI, 1.01-1.33). This did not meet the criteria for non-inferiority of discontinuation, compared with continuation, of beta-blocker therapy (P for non-inferiority = .44).

The difference in event rates between the two groups was driven by cardiovascular hospitalizations, which occurred more often in the discontinuation group than in the continuation group (18.9% vs 16.6%).

Other key results showed that there was no difference in quality of life between the two groups.

However, 6 months after randomization, there were increases in blood pressure and heart rate in the discontinuation group. Systolic blood pressure increased by 3.7 mm Hg and diastolic blood pressure increased by 3.9 mm Hg. Resting heart rate increased by 9.8 beats per minute.

“We were not able to show the non-inferiority of stopping beta-blockers in terms of cardiovascular events, [but we] showed a safety signal with this strategy of an increase in blood pressure and heart rate, with no improvement in quality of life,” Dr. Sylvain said.

“While recent guidelines suggest it may be reasonable to stop beta-blockers in this population, after these results, I will not be stopping these drugs if they are being well tolerated,” he said.

Sylvain said he was surprised that there was not an improvement in quality of life in the group that discontinued beta-blockers. “We are always told that beta-blockers have many side effects, so we expected to see an improvement in quality of life in the patients who stopped these drugs.”

One possible reason for the lack of improvement in quality of life is that the trial participants had been taking beta-blockers for several years. “We may have, therefore, selected patients who tolerate these drugs quite well. Those who had tolerance issues had probably already stopped taking them,” he explained.

In addition, the patient population had relatively high quality-of-life scores at baseline. “They were well treated and the therapies they were taking were well tolerated, so maybe it is difficult to improve quality of life further,” he said.
 

The REDUCE-AMI Trial

The ABYSS results appear at first to differ from results from the recent REDUCE-AMI trial, which failed to show the superiority of beta-blocker therapy, compared with no beta-blocker therapy, in acute MI patients with preserved ejection fraction.

But the REDUCE-AMI primary endpoint was a composite of death from any cause or new myocardial infarction; it did not include cardiovascular hospitalization, which was the main driver of the difference in outcomes in the ABYSS study, Dr. Sylvain pointed out.

“We showed an increase in coronary cases of hospitalization with stopping beta-blockers, and you have to remember that beta-blockers were developed to reduce coronary disease,” he said.
 

‘Slightly Inconclusive’

Jane Armitage, MBBS, University of Oxford, England, the ABYSS discussant for the ESC HOTLINE session, pointed out some limitations of the study, which led her to report that the result was “slightly inconclusive.” 

The open-label design may have allowed some bias regarding the cardiovascular hospitalization endpoint, she said.

“The decision whether to admit a patient to [the] hospital is somewhat subjective and could be influenced by a physician’s knowledge of treatment allocation. That is why, ideally, we prefer blinded trials. I think there are questions there,” she explained.

She also questioned whether the non-inferiority margin could have been increased, given the higher-than-expected event rate.

More data on this issue will come from several trials that are currently ongoing, Dr. Armitage said.

The ABYSS and REDUCE-AMI trials together suggest that it is safe, with respect to serious cardiac events, to stop beta-blocker treatment in MI patients with preserved ejection fraction, writes Tomas Jernberg, MD, PhD, from the Karolinska Institute in Stockholm, Sweden, in an accompanying editorial.

However, “because of the anti-ischemic effects of beta-blockers, an interruption may increase the risk of recurrent angina and the need for rehospitalization,” he adds.

“It is prudent to wait for the results of additional ongoing trials of beta-blockers involving patients with MI and a preserved left ventricular ejection fraction before definitively updating guidelines,” Dr. Jernberg concludes.

The ABYSS trial was funded by the French Ministry of Health and the ACTION Study Group. Dr. Sylvain, Dr. Armitage, and Dr. Jernberg report no relevant financial relationships.

A version of this article appeared on Medscape.com.

LONDON — It may not be advisable for patients with a history of myocardial infarction and preserved left ventricular function to discontinue long-term beta-blocker therapy, warn investigators.

In the randomized ABYSS trial, although there was no difference in death, MI, or stroke between patients who discontinued and those who continued taking beta-blockers, those who stopped taking the drugs had a higher rate of cardiovascular hospitalization.

Discontinuation was also associated with an increase in blood pressure and heart rate, without any improvement in quality of life.

“We thought we would be able to withdraw beta-blockers safely and that this would result in improved quality of life, but our trial results suggest this is not the case,” said lead investigator Johanne Silvain, MD, PhD, from Pitié-Salpêtrière University Hospital in Paris, who presented the ABYSS findings here at the European Society of Cardiology (ESC) Congress. 

The results, which were simultaneously published online in The New England Journal of Medicine, call into question current guidelines, which suggest that beta-blockers may be discontinued after 1 year in certain patient groups.

Beta-blockers have long been considered the standard of care for patients after MI, but trials showing the benefit of these drugs were conducted before the modern era of myocardial reperfusion and pharmacotherapy, which have led to sharp decreases in the risk for heart failure and for death after MI, Dr. Silvain explained. 

This has led to questions about the add-on benefits of lifelong beta-blocker treatment for patients with MI and a preserved left ventricular ejection fraction and no other primary indication for beta-blocker therapy.
 

The ABYSS Trial

To explore this issue, the open-label, non-inferiority ABYSS trial randomly assigned 3698 patients with a history of MI to the discontinuation or continuation of beta-blocker treatment. All study participants had a left ventricular ejection fraction of at least 40%, were receiving long-term beta-blocker treatment, and had experienced no cardiovascular event in the previous 6 months. 

At a median follow-up of 3 years, the primary endpoint — a composite of death, MI, stroke, and hospitalization for cardiovascular reasons — occurred more often in the discontinuation group than in the continuation group (23.8% vs 21.1%; hazard ratio, 1.16; 95% CI, 1.01-1.33). This did not meet the criteria for non-inferiority of discontinuation, compared with continuation, of beta-blocker therapy (P for non-inferiority = .44).

The difference in event rates between the two groups was driven by cardiovascular hospitalizations, which occurred more often in the discontinuation group than in the continuation group (18.9% vs 16.6%).

Other key results showed that there was no difference in quality of life between the two groups.

However, 6 months after randomization, there were increases in blood pressure and heart rate in the discontinuation group. Systolic blood pressure increased by 3.7 mm Hg and diastolic blood pressure increased by 3.9 mm Hg. Resting heart rate increased by 9.8 beats per minute.

“We were not able to show the non-inferiority of stopping beta-blockers in terms of cardiovascular events, [but we] showed a safety signal with this strategy of an increase in blood pressure and heart rate, with no improvement in quality of life,” Dr. Sylvain said.

“While recent guidelines suggest it may be reasonable to stop beta-blockers in this population, after these results, I will not be stopping these drugs if they are being well tolerated,” he said.

Sylvain said he was surprised that there was not an improvement in quality of life in the group that discontinued beta-blockers. “We are always told that beta-blockers have many side effects, so we expected to see an improvement in quality of life in the patients who stopped these drugs.”

One possible reason for the lack of improvement in quality of life is that the trial participants had been taking beta-blockers for several years. “We may have, therefore, selected patients who tolerate these drugs quite well. Those who had tolerance issues had probably already stopped taking them,” he explained.

In addition, the patient population had relatively high quality-of-life scores at baseline. “They were well treated and the therapies they were taking were well tolerated, so maybe it is difficult to improve quality of life further,” he said.
 

The REDUCE-AMI Trial

The ABYSS results appear at first to differ from results from the recent REDUCE-AMI trial, which failed to show the superiority of beta-blocker therapy, compared with no beta-blocker therapy, in acute MI patients with preserved ejection fraction.

But the REDUCE-AMI primary endpoint was a composite of death from any cause or new myocardial infarction; it did not include cardiovascular hospitalization, which was the main driver of the difference in outcomes in the ABYSS study, Dr. Sylvain pointed out.

“We showed an increase in coronary cases of hospitalization with stopping beta-blockers, and you have to remember that beta-blockers were developed to reduce coronary disease,” he said.
 

‘Slightly Inconclusive’

Jane Armitage, MBBS, University of Oxford, England, the ABYSS discussant for the ESC HOTLINE session, pointed out some limitations of the study, which led her to report that the result was “slightly inconclusive.” 

The open-label design may have allowed some bias regarding the cardiovascular hospitalization endpoint, she said.

“The decision whether to admit a patient to [the] hospital is somewhat subjective and could be influenced by a physician’s knowledge of treatment allocation. That is why, ideally, we prefer blinded trials. I think there are questions there,” she explained.

She also questioned whether the non-inferiority margin could have been increased, given the higher-than-expected event rate.

More data on this issue will come from several trials that are currently ongoing, Dr. Armitage said.

The ABYSS and REDUCE-AMI trials together suggest that it is safe, with respect to serious cardiac events, to stop beta-blocker treatment in MI patients with preserved ejection fraction, writes Tomas Jernberg, MD, PhD, from the Karolinska Institute in Stockholm, Sweden, in an accompanying editorial.

However, “because of the anti-ischemic effects of beta-blockers, an interruption may increase the risk of recurrent angina and the need for rehospitalization,” he adds.

“It is prudent to wait for the results of additional ongoing trials of beta-blockers involving patients with MI and a preserved left ventricular ejection fraction before definitively updating guidelines,” Dr. Jernberg concludes.

The ABYSS trial was funded by the French Ministry of Health and the ACTION Study Group. Dr. Sylvain, Dr. Armitage, and Dr. Jernberg report no relevant financial relationships.

A version of this article appeared on Medscape.com.

LONDON — It may not be advisable for patients with a history of myocardial infarction and preserved left ventricular function to discontinue long-term beta-blocker therapy, warn investigators.

In the randomized ABYSS trial, although there was no difference in death, MI, or stroke between patients who discontinued and those who continued taking beta-blockers, those who stopped taking the drugs had a higher rate of cardiovascular hospitalization.

Discontinuation was also associated with an increase in blood pressure and heart rate, without any improvement in quality of life.

“We thought we would be able to withdraw beta-blockers safely and that this would result in improved quality of life, but our trial results suggest this is not the case,” said lead investigator Johanne Silvain, MD, PhD, from Pitié-Salpêtrière University Hospital in Paris, who presented the ABYSS findings here at the European Society of Cardiology (ESC) Congress. 

The results, which were simultaneously published online in The New England Journal of Medicine, call into question current guidelines, which suggest that beta-blockers may be discontinued after 1 year in certain patient groups.

Beta-blockers have long been considered the standard of care for patients after MI, but trials showing the benefit of these drugs were conducted before the modern era of myocardial reperfusion and pharmacotherapy, which have led to sharp decreases in the risk for heart failure and for death after MI, Dr. Silvain explained. 

This has led to questions about the add-on benefits of lifelong beta-blocker treatment for patients with MI and a preserved left ventricular ejection fraction and no other primary indication for beta-blocker therapy.
 

The ABYSS Trial

To explore this issue, the open-label, non-inferiority ABYSS trial randomly assigned 3698 patients with a history of MI to the discontinuation or continuation of beta-blocker treatment. All study participants had a left ventricular ejection fraction of at least 40%, were receiving long-term beta-blocker treatment, and had experienced no cardiovascular event in the previous 6 months. 

At a median follow-up of 3 years, the primary endpoint — a composite of death, MI, stroke, and hospitalization for cardiovascular reasons — occurred more often in the discontinuation group than in the continuation group (23.8% vs 21.1%; hazard ratio, 1.16; 95% CI, 1.01-1.33). This did not meet the criteria for non-inferiority of discontinuation, compared with continuation, of beta-blocker therapy (P for non-inferiority = .44).

The difference in event rates between the two groups was driven by cardiovascular hospitalizations, which occurred more often in the discontinuation group than in the continuation group (18.9% vs 16.6%).

Other key results showed that there was no difference in quality of life between the two groups.

However, 6 months after randomization, there were increases in blood pressure and heart rate in the discontinuation group. Systolic blood pressure increased by 3.7 mm Hg and diastolic blood pressure increased by 3.9 mm Hg. Resting heart rate increased by 9.8 beats per minute.

“We were not able to show the non-inferiority of stopping beta-blockers in terms of cardiovascular events, [but we] showed a safety signal with this strategy of an increase in blood pressure and heart rate, with no improvement in quality of life,” Dr. Sylvain said.

“While recent guidelines suggest it may be reasonable to stop beta-blockers in this population, after these results, I will not be stopping these drugs if they are being well tolerated,” he said.

Sylvain said he was surprised that there was not an improvement in quality of life in the group that discontinued beta-blockers. “We are always told that beta-blockers have many side effects, so we expected to see an improvement in quality of life in the patients who stopped these drugs.”

One possible reason for the lack of improvement in quality of life is that the trial participants had been taking beta-blockers for several years. “We may have, therefore, selected patients who tolerate these drugs quite well. Those who had tolerance issues had probably already stopped taking them,” he explained.

In addition, the patient population had relatively high quality-of-life scores at baseline. “They were well treated and the therapies they were taking were well tolerated, so maybe it is difficult to improve quality of life further,” he said.
 

The REDUCE-AMI Trial

The ABYSS results appear at first to differ from results from the recent REDUCE-AMI trial, which failed to show the superiority of beta-blocker therapy, compared with no beta-blocker therapy, in acute MI patients with preserved ejection fraction.

But the REDUCE-AMI primary endpoint was a composite of death from any cause or new myocardial infarction; it did not include cardiovascular hospitalization, which was the main driver of the difference in outcomes in the ABYSS study, Dr. Sylvain pointed out.

“We showed an increase in coronary cases of hospitalization with stopping beta-blockers, and you have to remember that beta-blockers were developed to reduce coronary disease,” he said.
 

‘Slightly Inconclusive’

Jane Armitage, MBBS, University of Oxford, England, the ABYSS discussant for the ESC HOTLINE session, pointed out some limitations of the study, which led her to report that the result was “slightly inconclusive.” 

The open-label design may have allowed some bias regarding the cardiovascular hospitalization endpoint, she said.

“The decision whether to admit a patient to [the] hospital is somewhat subjective and could be influenced by a physician’s knowledge of treatment allocation. That is why, ideally, we prefer blinded trials. I think there are questions there,” she explained.

She also questioned whether the non-inferiority margin could have been increased, given the higher-than-expected event rate.

More data on this issue will come from several trials that are currently ongoing, Dr. Armitage said.

The ABYSS and REDUCE-AMI trials together suggest that it is safe, with respect to serious cardiac events, to stop beta-blocker treatment in MI patients with preserved ejection fraction, writes Tomas Jernberg, MD, PhD, from the Karolinska Institute in Stockholm, Sweden, in an accompanying editorial.

However, “because of the anti-ischemic effects of beta-blockers, an interruption may increase the risk of recurrent angina and the need for rehospitalization,” he adds.

“It is prudent to wait for the results of additional ongoing trials of beta-blockers involving patients with MI and a preserved left ventricular ejection fraction before definitively updating guidelines,” Dr. Jernberg concludes.

The ABYSS trial was funded by the French Ministry of Health and the ACTION Study Group. Dr. Sylvain, Dr. Armitage, and Dr. Jernberg report no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

High-dose psilocybin is associated with greater relief from depressive symptoms than placebo or escitalopram, with no increased risk for severe adverse events, a new meta-analysis suggests.
 

METHODOLOGY:

• Researchers conducted a network meta-analysis to evaluate the comparative effectiveness of oral monotherapy with psychedelics versus escitalopram in patients with clinically diagnosed depression.
• The meta-analysis included 811 participants (mean age, 42.49 years; 54.2% women) with clinically diagnosed depression across 15 psychedelic trials and 1968 participants (mean age, 39.35 years; 62.5% women) across five escitalopram trials.
• Trials evaluated oral monotherapy with psychedelics (psilocybin, lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine [MDMA], and ayahuasca), fixed-dose escitalopram (up to 20 mg/d) versus placebo, and psychedelic versus escitalopram monotherapy.
• The primary outcome was a change in depressive symptoms from baseline.

TAKEAWAY:

• Placebo responses in antidepressant trials (mean difference, 3.79; 95% CI, 0.77-6.80) and extremely low-dose psilocybin (mean difference, 3.96; 95% CI, 0.61-7.17) were better than those in psychedelic trials.
• High-dose psilocybin (20 mg or more) performed better than placebo in the antidepressant trials (mean difference, > 3). However, when comparing high-dose psilocybin with the placebo used in antidepressant trials, the effect size was smaller. The standardized mean difference dropped from 0.88 to 0.31, indicating that the effect of high-dose psilocybin was similar to that of current antidepressants.
• High-dose psilocybin was associated with a greater response than escitalopram at 10 mg (4.66; 95% CI, 1.36-7.74) and 20 mg (4.69; 95% CI, 1.64-7.54).
• No interventions were associated with an increased risk for all-cause discontinuation or severe adverse events.

IN PRACTICE:

“Taken together, our study findings suggest that among psychedelic treatments, high-dose psilocybin is more likely to reach the minimal important difference for depressive symptoms in studies with adequate blinding design, while the effect size of psilocybin was similar to that of current antidepressant drugs, showing a mean standardized mean difference of 0.3,” the authors wrote.

SOURCE:

The study was led by Tien-Wei Hsu, MD, I-Shou University and Kaohsiung Medical University, Kaohsiung City, Taiwan. It was published online in The BMJ. 

LIMITATIONS:

The study did not assess long-term effects of the interventions. Participants in the MDMA trials were primarily diagnosed with posttraumatic stress disorder, which may not be representative of the general population with depressive symptoms. Moreover, the sample size of the psychedelic trials was small. Using extremely low-dose psychedelics as a reference group may have eliminated some pharmacologic effects as these doses cannot be considered a placebo.

DISCLOSURES:

The study was supported by grants from the National Science and Technology Council. The authors declared no financial relationships with any organizations outside the submitted work in the past 3 years. Full disclosures are available in the original article.

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:

High-dose psilocybin is associated with greater relief from depressive symptoms than placebo or escitalopram, with no increased risk for severe adverse events, a new meta-analysis suggests.
 

METHODOLOGY:

• Researchers conducted a network meta-analysis to evaluate the comparative effectiveness of oral monotherapy with psychedelics versus escitalopram in patients with clinically diagnosed depression.
• The meta-analysis included 811 participants (mean age, 42.49 years; 54.2% women) with clinically diagnosed depression across 15 psychedelic trials and 1968 participants (mean age, 39.35 years; 62.5% women) across five escitalopram trials.
• Trials evaluated oral monotherapy with psychedelics (psilocybin, lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine [MDMA], and ayahuasca), fixed-dose escitalopram (up to 20 mg/d) versus placebo, and psychedelic versus escitalopram monotherapy.
• The primary outcome was a change in depressive symptoms from baseline.

TAKEAWAY:

• Placebo responses in antidepressant trials (mean difference, 3.79; 95% CI, 0.77-6.80) and extremely low-dose psilocybin (mean difference, 3.96; 95% CI, 0.61-7.17) were better than those in psychedelic trials.
• High-dose psilocybin (20 mg or more) performed better than placebo in the antidepressant trials (mean difference, > 3). However, when comparing high-dose psilocybin with the placebo used in antidepressant trials, the effect size was smaller. The standardized mean difference dropped from 0.88 to 0.31, indicating that the effect of high-dose psilocybin was similar to that of current antidepressants.
• High-dose psilocybin was associated with a greater response than escitalopram at 10 mg (4.66; 95% CI, 1.36-7.74) and 20 mg (4.69; 95% CI, 1.64-7.54).
• No interventions were associated with an increased risk for all-cause discontinuation or severe adverse events.

IN PRACTICE:

“Taken together, our study findings suggest that among psychedelic treatments, high-dose psilocybin is more likely to reach the minimal important difference for depressive symptoms in studies with adequate blinding design, while the effect size of psilocybin was similar to that of current antidepressant drugs, showing a mean standardized mean difference of 0.3,” the authors wrote.

SOURCE:

The study was led by Tien-Wei Hsu, MD, I-Shou University and Kaohsiung Medical University, Kaohsiung City, Taiwan. It was published online in The BMJ. 

LIMITATIONS:

The study did not assess long-term effects of the interventions. Participants in the MDMA trials were primarily diagnosed with posttraumatic stress disorder, which may not be representative of the general population with depressive symptoms. Moreover, the sample size of the psychedelic trials was small. Using extremely low-dose psychedelics as a reference group may have eliminated some pharmacologic effects as these doses cannot be considered a placebo.

DISCLOSURES:

The study was supported by grants from the National Science and Technology Council. The authors declared no financial relationships with any organizations outside the submitted work in the past 3 years. Full disclosures are available in the original article.

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:

High-dose psilocybin is associated with greater relief from depressive symptoms than placebo or escitalopram, with no increased risk for severe adverse events, a new meta-analysis suggests.
 

METHODOLOGY:

• Researchers conducted a network meta-analysis to evaluate the comparative effectiveness of oral monotherapy with psychedelics versus escitalopram in patients with clinically diagnosed depression.
• The meta-analysis included 811 participants (mean age, 42.49 years; 54.2% women) with clinically diagnosed depression across 15 psychedelic trials and 1968 participants (mean age, 39.35 years; 62.5% women) across five escitalopram trials.
• Trials evaluated oral monotherapy with psychedelics (psilocybin, lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine [MDMA], and ayahuasca), fixed-dose escitalopram (up to 20 mg/d) versus placebo, and psychedelic versus escitalopram monotherapy.
• The primary outcome was a change in depressive symptoms from baseline.

TAKEAWAY:

• Placebo responses in antidepressant trials (mean difference, 3.79; 95% CI, 0.77-6.80) and extremely low-dose psilocybin (mean difference, 3.96; 95% CI, 0.61-7.17) were better than those in psychedelic trials.
• High-dose psilocybin (20 mg or more) performed better than placebo in the antidepressant trials (mean difference, > 3). However, when comparing high-dose psilocybin with the placebo used in antidepressant trials, the effect size was smaller. The standardized mean difference dropped from 0.88 to 0.31, indicating that the effect of high-dose psilocybin was similar to that of current antidepressants.
• High-dose psilocybin was associated with a greater response than escitalopram at 10 mg (4.66; 95% CI, 1.36-7.74) and 20 mg (4.69; 95% CI, 1.64-7.54).
• No interventions were associated with an increased risk for all-cause discontinuation or severe adverse events.

IN PRACTICE:

“Taken together, our study findings suggest that among psychedelic treatments, high-dose psilocybin is more likely to reach the minimal important difference for depressive symptoms in studies with adequate blinding design, while the effect size of psilocybin was similar to that of current antidepressant drugs, showing a mean standardized mean difference of 0.3,” the authors wrote.

SOURCE:

The study was led by Tien-Wei Hsu, MD, I-Shou University and Kaohsiung Medical University, Kaohsiung City, Taiwan. It was published online in The BMJ. 

LIMITATIONS:

The study did not assess long-term effects of the interventions. Participants in the MDMA trials were primarily diagnosed with posttraumatic stress disorder, which may not be representative of the general population with depressive symptoms. Moreover, the sample size of the psychedelic trials was small. Using extremely low-dose psychedelics as a reference group may have eliminated some pharmacologic effects as these doses cannot be considered a placebo.

DISCLOSURES:

The study was supported by grants from the National Science and Technology Council. The authors declared no financial relationships with any organizations outside the submitted work in the past 3 years. Full disclosures are available in the original article.

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.

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 imnews@mdedge.com.

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 imnews@mdedge.com.

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 imnews@mdedge.com.

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.

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.

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.

This discussion was recorded on July 12, 2024. This transcript has been edited for clarity. 

Robert D. Glatter, MD: Hi and welcome. I’m Dr. Robert Glatter, medical advisor for Medscape Emergency Medicine. I recently met an innovative young woman named Hannah Herbst while attending the annual Eagles EMS Conference in Fort Lauderdale, Florida. 

Hannah Herbst is a graduate of Florida Atlantic University, selected for Forbes 30 Under 30, and founder of a company called Golden Hour Medical. She has a background in IT and developed an automated pneumatic tourniquet known as AutoTQ, which we’re going to discuss at length here. 

Also joining us is Dr. Peter Antevy, a pediatric emergency physician and medical director for Davie Fire Rescue as well as Coral Springs Parkland Fire Rescue. Peter is a member of EMS Eagles Global Alliance and is highly involved in high-quality research in prehospital emergency care and is quite well known in Florida and nationally. 

Welcome to both of you. 

Hannah Herbst: Thank you very much. Very grateful to be here.

Dr. Glatter: Hannah, I’ll let you start by explaining what AutoTQ is and then compare that to a standard Combat Application Tourniquet (CAT).

Ms. Herbst: Thank you. Unfortunately, blood loss is a leading cause of preventable death and trauma. When there’s blood loss occurring from an arm or a leg, the easiest way to stop it is by applying a tourniquet, which is this compression type of device that you place above the site of bleeding, and it then applies a high amount of pressure to stop blood flow through the limb. 

Currently, tourniquets on the market have failure rates as high as 84%. This became very real to me back in 2018, when I became aware of mass casualty incidents when I was a student. I became interested in how we can reimagine the conventional tourniquet and try to make it something that’s very user-friendly, much like an automated external defibrillator (AED). 

My team and I developed AutoTQ, which is an automated tourniquet. You press one button to wake it up and one button to inflate it. It guides you through the process of placing it above the site of bleeding on a limb, which is a leading cause of tourniquet failure and being able to effectively administer treatment to a patient that may bleed out. 
 

Tourniquet Failure Rates

Dr. Glatter: In terms of tourniquet failure, how often do standard tourniquets fail, like the CAT combat-type tourniquet? 

Ms. Herbst: Unfortunately, they fail very frequently. There are several studies that have been conducted to evaluate this. Many of them occur immediately after training. They found failure rates between 80% and 90% for the current conventional CAT tourniquet immediately after training, which is very concerning. 

Dr. Glatter: In terms of failure, was it the windlass aspect of the tourniquet that failed? Or was it something related to the actual strap? Was that in any way detailed? 

Ms. Herbst: There are usually a few different failure points that have been found in the literature. One is placement. Many times, when you’re panicked, you don’t remember exactly how to place it. It should be placed high and tight above the bleed and not over a joint. 

The second problem is inadequate tightness. For a CAT tourniquet to be effective, you have to get it extremely tight on that first pull before the windlass is activated, and many times people don’t remember that in the stress of the moment. 

Dr. Glatter: Peter, in terms of tourniquet application by your medics in the field, certainly the CAT-type device has been in existence for quite a while. Hannah’s proposing a new iteration of how to do this, which is automated and simple. What is your take on such a device? And how did you learn about Hannah’s device? 

Peter M. Antevy, MD: We’ve been training on tourniquets ever since the military data showed that there was an extreme benefit in using them. We’ve been doing training for many years, including our police officers. What we’ve noticed is that every time we gather everyone together to show them how to place a tourniquet — and we have to do one-on-one sessions with them — it’s not a device that they can easily put on. These are police officers who had the training last year. 

Like Hannah said, most of the time they have a problem unraveling it and understanding how to actually place it. It’s easier on the arm than it is on the leg. You can imagine it would be harder to place it on your own leg, especially if you had an injury. Then, they don’t tighten it well enough, as Hannah just mentioned. In order for a tourniquet to really be placed properly, it’s going to hurt that person. Many people have that tendency not to want to tighten it as much as they can. 

Having said that, how I got into all of this is because I’m the medical director for Coral Springs and Parkland, and unfortunately, we had the 2018 Valentine’s Day murders that happened where we lost 17 adults and kids. However, 17 people were saved that day, and the credit goes to our police officers who had tourniquets or chest seals on before those patients were brought out to EMS. Many lives were saved by the tourniquet. 

If you look at the Boston Marathon massacre and many other events that have happened, I believe — and I’ve always believed — that tourniquets should be in the glove box of every citizen. It should be in every school room. They should be in buildings along with the AED. 

In my town of Davie, we were the first in the country to add an ordinance that required a Stop the Bleed kit in the AED cabinet, and those were required by buildings of certain sizes. In order to get this lifesaving device everywhere, I think it has to be put into local ordinance and supported by states and by the national folks, which they are doing. 
 

Trials Are Underway

Dr. Glatter: In terms of adoption of such a device, it certainly has to go through rigorous testing and maybe some trials. Hannah, where are you at with vetting this in terms of any type of trial? Has it been compared head to head with standard tourniquets? 

Ms. Herbst: Yes, we’re currently doing large amounts of field testing. We’re doing testing on emergency vehicles and in the surgical setting with different customers. In addition, we’re running pilot studies at different universities and with different organizations, including the military, to make sure that this device is effective. We’re evaluating cognitive offloading of people. We’re hoping to start that study later this year. We’re excited to be doing this in a variety of settings. 

We’re also testing the quality of it in different environmental conditions and under different atmospheric pressure. We’re doing everything we can to ensure the device is safe and effective. We’re excited to scale and fill our preorders and be able to develop this and deliver it to many people. 

Dr. Glatter: I was wondering if you could describe the actual device. There’s a brain part of it and then, obviously, the strap aspect of it. I was curious about contamination and reusability issues. 

Ms. Herbst: That’s a great question. One of the limitations of conventional tourniquets on the market is that they are single use, and often, it requires two tourniquets to stop a bleed, both of which have to be disposed of. 

With AutoTQ, we have a reusable component and a disposable component. I actually have one here that I can show you. We have a cover on it that says: Stop bleed, slide up and power on. You just pull this cover off and then you have a few simple commands. You have powering the device on. I’ll just click this button: Tighten strap above bleeding, then press inflate. It delivers audible instructions telling you exactly how to use the device. Then, you tighten it above your bleed on the limb, and you press the inflate button. Then it administers air into the cuff and stops the patient’s bleed. 
 

Tourniquet Conversion and Limb Salvage

Dr. Glatter: In terms of ischemia time, how can a device like this make it easier for us to know when to let the tourniquet down and allow some blood flow? Certainly, limb salvage is important, and we don’t want to have necrosis and so forth. 

Dr. Antevy: That’s a great question. The limb salvage rate when tourniquets have been used is 85%. When used correctly, you can really improve the outcomes for many patients. 

On the flip side of that, there’s something called tourniquet conversion. That’s exactly what you mentioned. It’s making sure that the tourniquet doesn’t stay on for too long of a time. If you can imagine a patient going to an outlying hospital where there’s no trauma center, and then that patient then has to be moved a couple hours to the trauma center, could you potentially have a tourniquet on for too long that then ends up causing the patient a bad outcome? The answer is yes.

I just had someone on my webinar recently describing the appropriate conversion techniques of tourniquets. You don’t find too much of that in the literature, but you really have to ensure that as you’re taking the tourniquet down, the bleeding is actually stopped. It’s not really recommended to take a tourniquet down if the patient was just acutely bleeding. 

However, imagine a situation where a tourniquet was put on incorrectly. Let’s say a patient got nervous and they just put it on a patient who didn’t really need it. You really have to understand how to evaluate that wound to be sure that, as you’re taking the tourniquet down slowly, the patient doesn’t rebleed again. 

There are two sides of the question, Rob. One is making sure it’s not on inappropriately. The second one is making sure it’s not on for too long, which ends up causing ischemia to that limb. 

Dr. Glatter: Hannah, does your device collect data on the number of hours or minutes that the tourniquet has been up and then automatically deflate it in some sense to allow for that improvement in limb salvage?

Ms. Herbst: That’s a great question, and I really appreciate your answer as well, Dr Antevy. Ischemia time is a very important and critical component of tourniquet use. This is something, when we were designing AutoTQ, that we took into high consideration. 

We found, when we evaluated AutoTQ vs a CAT tourniquet in a mannequin model, that AutoTQ can achieve cessation of hemorrhage at around 400 mm Hg of mercury, whereas CAT requires 700-800 mm Hg. Already our ischemia time is slightly extended just based on existing literature with pneumatic tourniquets because it can stop the bleed at a lower pressure, which causes less complications with the patient’s limb. 

There are different features that we build out for different customers, so depending on what people want, it is possible to deflate the tourniquet. However, typically, you’re at the hospital within 30 minutes. It’s quick to get them there, and then the physician can treat and take that tourniquet down in a supervised and controlled setting. 

Dr. Glatter: In terms of patients with obesity, do you have adjustable straps that will accommodate for that aspect? 

Ms. Herbst: Yes, we have different cuff sizes to accommodate different limbs.
 

Will AutoTQ Be Available to the Public?

Dr. Glatter: Peter, in terms of usability in the prehospital setting, where do you think this is going in the next 3-5 years? 

Dr. Antevy: I’ll start with the public safety sector of the United States, which is the one that is actually first on scene. Whether you’re talking about police officers or EMS, it would behoove us to have tourniquets everywhere. On all of my ambulances, across all of my agencies that I manage, we have quite a number of tourniquets. 

Obviously, cost is a factor, and I know that Hannah has done a great job of making that brain reusable. All we have to do is purchase the straps, which are effectively the same cost, I understand, as a typical tourniquet you would purchase. 

Moving forward though, however, I think that this has wide scalability to the public market, whether it be schools, office buildings, the glove box, and so on. It’s really impossible to teach somebody how to do this the right way, if you have to teach them how to put the strap on, tighten it correctly, and so on. If there was an easy way, like Hannah developed, of just putting it on and pushing a button, then I think that the outcomes and the scalability are much further beyond what we can do in EMS. I think there’s great value in both markets. 
 

The ‘AED of Bleeding’: Rechargeable and Reusable

Dr. Glatter: This is the AED of bleeding. You have a device here that has wide-scale interest, certainly from the public and private sector. 

Hannah, in terms of battery decay, how would that work out if it was in someone’s garage? Let’s just say someone purchased it and they hadn’t used it in 3 or 4 months. What type of decay are we looking at and can they rely on it? 

Ms. Herbst: AutoTQ is rechargeable by a USB-C port, and our battery lasts for a year. Once a year, you’ll get an email reminder that says: “Hey, please charge your AutoTQ and make sure it’s up to the battery level.” We do everything in our power to make sure that our consumers are checking their batteries and that they’re ready to go. 

Dr. Glatter: Is it heat and fire resistant? What, in terms of durability, does your device have? 

Ms. Herbst: Just like any other medical device, we come with manufacturer recommendations for the upper and lower bounds of temperature and different storage recommendations. All of that is in our instructions for use. 

Dr. Glatter: Peter, getting back to logistics. In terms of adoption, do you feel that, in the long term, this device will be something that we’re going to be seeing widely adopted just going forward? 

Dr. Antevy: I do, and I’ll tell you why. When you look at AED use in this country, the odds of someone actually getting an AED and using it correctly are still very low. Part of that is because it’s complicated for many people to do. Getting tourniquets everywhere is step No. 1, and I think the federal government and the Stop the Bleed program is really making that happen. 

We talked about ordinances, but ease of use, I think, is really the key. You have people who oftentimes have their child in cardiac arrest in front of them, and they won’t put two hands on their chest because they just are afraid of doing it. 

When you have a device that’s a tourniquet, that’s a single-button turn on and single-button inflate, I think that would make it much more likely that a person will use that device when they’re passing the scene of an accident, as an example. 

We’ve had many non–mass casualty incident events that have had tourniquets. We’ve had some media stories on them, where they’re just happening because someone got into a motor vehicle accident. It doesn’t have to be a school shooting. I think the tourniquets should be everywhere and should be easily used by everybody. 
 

Managing Pain 

Dr. Glatter: Regarding sedation, is there a need because of the pain involved with the application? How would you sedate a patient, pediatric or adult, who needs a tourniquet? 

Dr. Antevy: We always evaluate people’s pain. If the patient is an extremist, we’re just going to be managing and trying to get them back to life. Once somebody is stabilized and is exhibiting pain of any sort, even, for example, after we intubate somebody, we have to sedate them and provide them pain control because they have a piece of plastic in their trachea. 

It’s the same thing here for a tourniquet. These are painful, and we do have the appropriate medications on our vehicles to address that pain. Again, just simply the trauma itself is very painful. Yes, we do address that in EMS, and I would say most public agencies across this country would address pain appropriately. 
 

Training on Tourniquet Use

Dr. Glatter: Hannah, can you talk a little bit about public training types of approaches? How would you train a consumer who purchases this type of device?

Ms. Herbst: A huge part of our mission is making blood loss prevention and control training accessible to a wide variety of people. One way that we’re able to do that is through our online training platform. When you purchase an AutoTQ kit, you plug it into your computer, and it walks you through the process of using it. It lets you practice on your own limb and on your buddy’s limb, just to be able to effectively apply it. We think this will have huge impacts in making sure that people are prepared and ready to stop the bleed with AutoTQ. 

Dr. Glatter: Do you recommend people training once a month, in general, just to keep their skills up to use this? In the throes of a trauma and very chaotic situation, people sometimes lose their ability to think clearly and straightly. 

Ms. Herbst: One of the studies we’re conducting is a learning curve study to try to figure out how quickly these skills degrade over time. We know that with the windlass tourniquet, it degrades within moments of training. With AutoTQ, we think the learning curve will last much longer. That’s something we’re evaluating, but we recommend people train as often as they can. 

Dr. Antevy: Rob, if I can mention that there is a concept of just-in-time training. I think that with having the expectation that people are going to be training frequently, unfortunately, as many of us know, even with the AED as a perfect example, people don’t do that. 

Yes. I would agree that you have to train at least once a year, is what I would say. At my office, we have a 2-hour training that goes over all these different items once a year. 

The device itself should have the ability to allow you to figure out how to use it just in time, whether via video, or like Hannah’s device, by audio. I think that having both those things would make it more likely that the device be used when needed. 

People panic, and if they have a device that can talk to them or walk them through it, they will be much more likely to use it at that time.

 

Final Takeaways

Dr. Glatter: Any other final thoughts or a few pearls for listeners to take away? Hannah, I’ll start with you. 

Ms. Herbst: I’m very grateful for your time, and I’m very excited about the potential for AutoTQ. To me, it’s so exciting to see people preordering the device now. We’ve had people from school bus companies and small sports teams. I think, just like Dr Antevy said, tourniquets aren’t limited to mass casualty situations. Blood loss can happen anywhere and to anyone. 

Being able to equip people and serve them to better prepare them for this happening to themselves, their friends, or their family is just the honor of a lifetime. Thank you very much for covering the device and for having me today. 

Dr. Glatter: Of course, my pleasure. Peter? 

Dr. Antevy: The citizens of this country, and everyone who lives across the world, has started to understand that there are things that we expect from our people, from the community. We expect them to do CPR for cardiac arrest. We expect them to know how to use an EpiPen. We expect them to know how to use an AED, and we also expect them to know how to stop bleeding with a tourniquet. 

The American public has gotten to understand that these devices are very important. Having a device that’s easily used, that I can teach you in 10 seconds, that speaks to you — these are all things that make this product have great potential. I do look forward to the studies, not just the cadaver studies, but the real human studies. 

I know Hannah is really a phenom and has been doing all these things so that this product can be on the shelves of Walmart and CVS one day. I commend you, Hannah, for everything you’re doing and wishing you the best of luck. We’re here for you. 

Dr. Glatter: Same here. Congratulations on your innovative capability and what you’ve done to change the outcomes of bleeding related to penetrating trauma. Thank you so much.

Robert D. Glatter, MD, is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. He is a medical advisor for Medscape and hosts the Hot Topics in EM series. Hannah D. Herbst, BS, is a graduate of Florida Atlantic University, was selected for Forbes 30 Under 30, and is the founder/CEO of Golden Hour Medical. Peter M. Antevy, MD, is a pediatric emergency medicine physician and medical director for Davie Fire Rescue and Coral Springs–Parkland Fire Department in Florida. He is also a member of the EMS Eagles Global Alliance.



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

This discussion was recorded on July 12, 2024. This transcript has been edited for clarity. 

Robert D. Glatter, MD: Hi and welcome. I’m Dr. Robert Glatter, medical advisor for Medscape Emergency Medicine. I recently met an innovative young woman named Hannah Herbst while attending the annual Eagles EMS Conference in Fort Lauderdale, Florida. 

Hannah Herbst is a graduate of Florida Atlantic University, selected for Forbes 30 Under 30, and founder of a company called Golden Hour Medical. She has a background in IT and developed an automated pneumatic tourniquet known as AutoTQ, which we’re going to discuss at length here. 

Also joining us is Dr. Peter Antevy, a pediatric emergency physician and medical director for Davie Fire Rescue as well as Coral Springs Parkland Fire Rescue. Peter is a member of EMS Eagles Global Alliance and is highly involved in high-quality research in prehospital emergency care and is quite well known in Florida and nationally. 

Welcome to both of you. 

Hannah Herbst: Thank you very much. Very grateful to be here.

Dr. Glatter: Hannah, I’ll let you start by explaining what AutoTQ is and then compare that to a standard Combat Application Tourniquet (CAT).

Ms. Herbst: Thank you. Unfortunately, blood loss is a leading cause of preventable death and trauma. When there’s blood loss occurring from an arm or a leg, the easiest way to stop it is by applying a tourniquet, which is this compression type of device that you place above the site of bleeding, and it then applies a high amount of pressure to stop blood flow through the limb. 

Currently, tourniquets on the market have failure rates as high as 84%. This became very real to me back in 2018, when I became aware of mass casualty incidents when I was a student. I became interested in how we can reimagine the conventional tourniquet and try to make it something that’s very user-friendly, much like an automated external defibrillator (AED). 

My team and I developed AutoTQ, which is an automated tourniquet. You press one button to wake it up and one button to inflate it. It guides you through the process of placing it above the site of bleeding on a limb, which is a leading cause of tourniquet failure and being able to effectively administer treatment to a patient that may bleed out. 
 

Tourniquet Failure Rates

Dr. Glatter: In terms of tourniquet failure, how often do standard tourniquets fail, like the CAT combat-type tourniquet? 

Ms. Herbst: Unfortunately, they fail very frequently. There are several studies that have been conducted to evaluate this. Many of them occur immediately after training. They found failure rates between 80% and 90% for the current conventional CAT tourniquet immediately after training, which is very concerning. 

Dr. Glatter: In terms of failure, was it the windlass aspect of the tourniquet that failed? Or was it something related to the actual strap? Was that in any way detailed? 

Ms. Herbst: There are usually a few different failure points that have been found in the literature. One is placement. Many times, when you’re panicked, you don’t remember exactly how to place it. It should be placed high and tight above the bleed and not over a joint. 

The second problem is inadequate tightness. For a CAT tourniquet to be effective, you have to get it extremely tight on that first pull before the windlass is activated, and many times people don’t remember that in the stress of the moment. 

Dr. Glatter: Peter, in terms of tourniquet application by your medics in the field, certainly the CAT-type device has been in existence for quite a while. Hannah’s proposing a new iteration of how to do this, which is automated and simple. What is your take on such a device? And how did you learn about Hannah’s device? 

Peter M. Antevy, MD: We’ve been training on tourniquets ever since the military data showed that there was an extreme benefit in using them. We’ve been doing training for many years, including our police officers. What we’ve noticed is that every time we gather everyone together to show them how to place a tourniquet — and we have to do one-on-one sessions with them — it’s not a device that they can easily put on. These are police officers who had the training last year. 

Like Hannah said, most of the time they have a problem unraveling it and understanding how to actually place it. It’s easier on the arm than it is on the leg. You can imagine it would be harder to place it on your own leg, especially if you had an injury. Then, they don’t tighten it well enough, as Hannah just mentioned. In order for a tourniquet to really be placed properly, it’s going to hurt that person. Many people have that tendency not to want to tighten it as much as they can. 

Having said that, how I got into all of this is because I’m the medical director for Coral Springs and Parkland, and unfortunately, we had the 2018 Valentine’s Day murders that happened where we lost 17 adults and kids. However, 17 people were saved that day, and the credit goes to our police officers who had tourniquets or chest seals on before those patients were brought out to EMS. Many lives were saved by the tourniquet. 

If you look at the Boston Marathon massacre and many other events that have happened, I believe — and I’ve always believed — that tourniquets should be in the glove box of every citizen. It should be in every school room. They should be in buildings along with the AED. 

In my town of Davie, we were the first in the country to add an ordinance that required a Stop the Bleed kit in the AED cabinet, and those were required by buildings of certain sizes. In order to get this lifesaving device everywhere, I think it has to be put into local ordinance and supported by states and by the national folks, which they are doing. 
 

Trials Are Underway

Dr. Glatter: In terms of adoption of such a device, it certainly has to go through rigorous testing and maybe some trials. Hannah, where are you at with vetting this in terms of any type of trial? Has it been compared head to head with standard tourniquets? 

Ms. Herbst: Yes, we’re currently doing large amounts of field testing. We’re doing testing on emergency vehicles and in the surgical setting with different customers. In addition, we’re running pilot studies at different universities and with different organizations, including the military, to make sure that this device is effective. We’re evaluating cognitive offloading of people. We’re hoping to start that study later this year. We’re excited to be doing this in a variety of settings. 

We’re also testing the quality of it in different environmental conditions and under different atmospheric pressure. We’re doing everything we can to ensure the device is safe and effective. We’re excited to scale and fill our preorders and be able to develop this and deliver it to many people. 

Dr. Glatter: I was wondering if you could describe the actual device. There’s a brain part of it and then, obviously, the strap aspect of it. I was curious about contamination and reusability issues. 

Ms. Herbst: That’s a great question. One of the limitations of conventional tourniquets on the market is that they are single use, and often, it requires two tourniquets to stop a bleed, both of which have to be disposed of. 

With AutoTQ, we have a reusable component and a disposable component. I actually have one here that I can show you. We have a cover on it that says: Stop bleed, slide up and power on. You just pull this cover off and then you have a few simple commands. You have powering the device on. I’ll just click this button: Tighten strap above bleeding, then press inflate. It delivers audible instructions telling you exactly how to use the device. Then, you tighten it above your bleed on the limb, and you press the inflate button. Then it administers air into the cuff and stops the patient’s bleed. 
 

Tourniquet Conversion and Limb Salvage

Dr. Glatter: In terms of ischemia time, how can a device like this make it easier for us to know when to let the tourniquet down and allow some blood flow? Certainly, limb salvage is important, and we don’t want to have necrosis and so forth. 

Dr. Antevy: That’s a great question. The limb salvage rate when tourniquets have been used is 85%. When used correctly, you can really improve the outcomes for many patients. 

On the flip side of that, there’s something called tourniquet conversion. That’s exactly what you mentioned. It’s making sure that the tourniquet doesn’t stay on for too long of a time. If you can imagine a patient going to an outlying hospital where there’s no trauma center, and then that patient then has to be moved a couple hours to the trauma center, could you potentially have a tourniquet on for too long that then ends up causing the patient a bad outcome? The answer is yes.

I just had someone on my webinar recently describing the appropriate conversion techniques of tourniquets. You don’t find too much of that in the literature, but you really have to ensure that as you’re taking the tourniquet down, the bleeding is actually stopped. It’s not really recommended to take a tourniquet down if the patient was just acutely bleeding. 

However, imagine a situation where a tourniquet was put on incorrectly. Let’s say a patient got nervous and they just put it on a patient who didn’t really need it. You really have to understand how to evaluate that wound to be sure that, as you’re taking the tourniquet down slowly, the patient doesn’t rebleed again. 

There are two sides of the question, Rob. One is making sure it’s not on inappropriately. The second one is making sure it’s not on for too long, which ends up causing ischemia to that limb. 

Dr. Glatter: Hannah, does your device collect data on the number of hours or minutes that the tourniquet has been up and then automatically deflate it in some sense to allow for that improvement in limb salvage?

Ms. Herbst: That’s a great question, and I really appreciate your answer as well, Dr Antevy. Ischemia time is a very important and critical component of tourniquet use. This is something, when we were designing AutoTQ, that we took into high consideration. 

We found, when we evaluated AutoTQ vs a CAT tourniquet in a mannequin model, that AutoTQ can achieve cessation of hemorrhage at around 400 mm Hg of mercury, whereas CAT requires 700-800 mm Hg. Already our ischemia time is slightly extended just based on existing literature with pneumatic tourniquets because it can stop the bleed at a lower pressure, which causes less complications with the patient’s limb. 

There are different features that we build out for different customers, so depending on what people want, it is possible to deflate the tourniquet. However, typically, you’re at the hospital within 30 minutes. It’s quick to get them there, and then the physician can treat and take that tourniquet down in a supervised and controlled setting. 

Dr. Glatter: In terms of patients with obesity, do you have adjustable straps that will accommodate for that aspect? 

Ms. Herbst: Yes, we have different cuff sizes to accommodate different limbs.
 

Will AutoTQ Be Available to the Public?

Dr. Glatter: Peter, in terms of usability in the prehospital setting, where do you think this is going in the next 3-5 years? 

Dr. Antevy: I’ll start with the public safety sector of the United States, which is the one that is actually first on scene. Whether you’re talking about police officers or EMS, it would behoove us to have tourniquets everywhere. On all of my ambulances, across all of my agencies that I manage, we have quite a number of tourniquets. 

Obviously, cost is a factor, and I know that Hannah has done a great job of making that brain reusable. All we have to do is purchase the straps, which are effectively the same cost, I understand, as a typical tourniquet you would purchase. 

Moving forward though, however, I think that this has wide scalability to the public market, whether it be schools, office buildings, the glove box, and so on. It’s really impossible to teach somebody how to do this the right way, if you have to teach them how to put the strap on, tighten it correctly, and so on. If there was an easy way, like Hannah developed, of just putting it on and pushing a button, then I think that the outcomes and the scalability are much further beyond what we can do in EMS. I think there’s great value in both markets. 
 

The ‘AED of Bleeding’: Rechargeable and Reusable

Dr. Glatter: This is the AED of bleeding. You have a device here that has wide-scale interest, certainly from the public and private sector. 

Hannah, in terms of battery decay, how would that work out if it was in someone’s garage? Let’s just say someone purchased it and they hadn’t used it in 3 or 4 months. What type of decay are we looking at and can they rely on it? 

Ms. Herbst: AutoTQ is rechargeable by a USB-C port, and our battery lasts for a year. Once a year, you’ll get an email reminder that says: “Hey, please charge your AutoTQ and make sure it’s up to the battery level.” We do everything in our power to make sure that our consumers are checking their batteries and that they’re ready to go. 

Dr. Glatter: Is it heat and fire resistant? What, in terms of durability, does your device have? 

Ms. Herbst: Just like any other medical device, we come with manufacturer recommendations for the upper and lower bounds of temperature and different storage recommendations. All of that is in our instructions for use. 

Dr. Glatter: Peter, getting back to logistics. In terms of adoption, do you feel that, in the long term, this device will be something that we’re going to be seeing widely adopted just going forward? 

Dr. Antevy: I do, and I’ll tell you why. When you look at AED use in this country, the odds of someone actually getting an AED and using it correctly are still very low. Part of that is because it’s complicated for many people to do. Getting tourniquets everywhere is step No. 1, and I think the federal government and the Stop the Bleed program is really making that happen. 

We talked about ordinances, but ease of use, I think, is really the key. You have people who oftentimes have their child in cardiac arrest in front of them, and they won’t put two hands on their chest because they just are afraid of doing it. 

When you have a device that’s a tourniquet, that’s a single-button turn on and single-button inflate, I think that would make it much more likely that a person will use that device when they’re passing the scene of an accident, as an example. 

We’ve had many non–mass casualty incident events that have had tourniquets. We’ve had some media stories on them, where they’re just happening because someone got into a motor vehicle accident. It doesn’t have to be a school shooting. I think the tourniquets should be everywhere and should be easily used by everybody. 
 

Managing Pain 

Dr. Glatter: Regarding sedation, is there a need because of the pain involved with the application? How would you sedate a patient, pediatric or adult, who needs a tourniquet? 

Dr. Antevy: We always evaluate people’s pain. If the patient is an extremist, we’re just going to be managing and trying to get them back to life. Once somebody is stabilized and is exhibiting pain of any sort, even, for example, after we intubate somebody, we have to sedate them and provide them pain control because they have a piece of plastic in their trachea. 

It’s the same thing here for a tourniquet. These are painful, and we do have the appropriate medications on our vehicles to address that pain. Again, just simply the trauma itself is very painful. Yes, we do address that in EMS, and I would say most public agencies across this country would address pain appropriately. 
 

Training on Tourniquet Use

Dr. Glatter: Hannah, can you talk a little bit about public training types of approaches? How would you train a consumer who purchases this type of device?

Ms. Herbst: A huge part of our mission is making blood loss prevention and control training accessible to a wide variety of people. One way that we’re able to do that is through our online training platform. When you purchase an AutoTQ kit, you plug it into your computer, and it walks you through the process of using it. It lets you practice on your own limb and on your buddy’s limb, just to be able to effectively apply it. We think this will have huge impacts in making sure that people are prepared and ready to stop the bleed with AutoTQ. 

Dr. Glatter: Do you recommend people training once a month, in general, just to keep their skills up to use this? In the throes of a trauma and very chaotic situation, people sometimes lose their ability to think clearly and straightly. 

Ms. Herbst: One of the studies we’re conducting is a learning curve study to try to figure out how quickly these skills degrade over time. We know that with the windlass tourniquet, it degrades within moments of training. With AutoTQ, we think the learning curve will last much longer. That’s something we’re evaluating, but we recommend people train as often as they can. 

Dr. Antevy: Rob, if I can mention that there is a concept of just-in-time training. I think that with having the expectation that people are going to be training frequently, unfortunately, as many of us know, even with the AED as a perfect example, people don’t do that. 

Yes. I would agree that you have to train at least once a year, is what I would say. At my office, we have a 2-hour training that goes over all these different items once a year. 

The device itself should have the ability to allow you to figure out how to use it just in time, whether via video, or like Hannah’s device, by audio. I think that having both those things would make it more likely that the device be used when needed. 

People panic, and if they have a device that can talk to them or walk them through it, they will be much more likely to use it at that time.

 

Final Takeaways

Dr. Glatter: Any other final thoughts or a few pearls for listeners to take away? Hannah, I’ll start with you. 

Ms. Herbst: I’m very grateful for your time, and I’m very excited about the potential for AutoTQ. To me, it’s so exciting to see people preordering the device now. We’ve had people from school bus companies and small sports teams. I think, just like Dr Antevy said, tourniquets aren’t limited to mass casualty situations. Blood loss can happen anywhere and to anyone. 

Being able to equip people and serve them to better prepare them for this happening to themselves, their friends, or their family is just the honor of a lifetime. Thank you very much for covering the device and for having me today. 

Dr. Glatter: Of course, my pleasure. Peter? 

Dr. Antevy: The citizens of this country, and everyone who lives across the world, has started to understand that there are things that we expect from our people, from the community. We expect them to do CPR for cardiac arrest. We expect them to know how to use an EpiPen. We expect them to know how to use an AED, and we also expect them to know how to stop bleeding with a tourniquet. 

The American public has gotten to understand that these devices are very important. Having a device that’s easily used, that I can teach you in 10 seconds, that speaks to you — these are all things that make this product have great potential. I do look forward to the studies, not just the cadaver studies, but the real human studies. 

I know Hannah is really a phenom and has been doing all these things so that this product can be on the shelves of Walmart and CVS one day. I commend you, Hannah, for everything you’re doing and wishing you the best of luck. We’re here for you. 

Dr. Glatter: Same here. Congratulations on your innovative capability and what you’ve done to change the outcomes of bleeding related to penetrating trauma. Thank you so much.

Robert D. Glatter, MD, is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. He is a medical advisor for Medscape and hosts the Hot Topics in EM series. Hannah D. Herbst, BS, is a graduate of Florida Atlantic University, was selected for Forbes 30 Under 30, and is the founder/CEO of Golden Hour Medical. Peter M. Antevy, MD, is a pediatric emergency medicine physician and medical director for Davie Fire Rescue and Coral Springs–Parkland Fire Department in Florida. He is also a member of the EMS Eagles Global Alliance.



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

This discussion was recorded on July 12, 2024. This transcript has been edited for clarity. 

Robert D. Glatter, MD: Hi and welcome. I’m Dr. Robert Glatter, medical advisor for Medscape Emergency Medicine. I recently met an innovative young woman named Hannah Herbst while attending the annual Eagles EMS Conference in Fort Lauderdale, Florida. 

Hannah Herbst is a graduate of Florida Atlantic University, selected for Forbes 30 Under 30, and founder of a company called Golden Hour Medical. She has a background in IT and developed an automated pneumatic tourniquet known as AutoTQ, which we’re going to discuss at length here. 

Also joining us is Dr. Peter Antevy, a pediatric emergency physician and medical director for Davie Fire Rescue as well as Coral Springs Parkland Fire Rescue. Peter is a member of EMS Eagles Global Alliance and is highly involved in high-quality research in prehospital emergency care and is quite well known in Florida and nationally. 

Welcome to both of you. 

Hannah Herbst: Thank you very much. Very grateful to be here.

Dr. Glatter: Hannah, I’ll let you start by explaining what AutoTQ is and then compare that to a standard Combat Application Tourniquet (CAT).

Ms. Herbst: Thank you. Unfortunately, blood loss is a leading cause of preventable death and trauma. When there’s blood loss occurring from an arm or a leg, the easiest way to stop it is by applying a tourniquet, which is this compression type of device that you place above the site of bleeding, and it then applies a high amount of pressure to stop blood flow through the limb. 

Currently, tourniquets on the market have failure rates as high as 84%. This became very real to me back in 2018, when I became aware of mass casualty incidents when I was a student. I became interested in how we can reimagine the conventional tourniquet and try to make it something that’s very user-friendly, much like an automated external defibrillator (AED). 

My team and I developed AutoTQ, which is an automated tourniquet. You press one button to wake it up and one button to inflate it. It guides you through the process of placing it above the site of bleeding on a limb, which is a leading cause of tourniquet failure and being able to effectively administer treatment to a patient that may bleed out. 
 

Tourniquet Failure Rates

Dr. Glatter: In terms of tourniquet failure, how often do standard tourniquets fail, like the CAT combat-type tourniquet? 

Ms. Herbst: Unfortunately, they fail very frequently. There are several studies that have been conducted to evaluate this. Many of them occur immediately after training. They found failure rates between 80% and 90% for the current conventional CAT tourniquet immediately after training, which is very concerning. 

Dr. Glatter: In terms of failure, was it the windlass aspect of the tourniquet that failed? Or was it something related to the actual strap? Was that in any way detailed? 

Ms. Herbst: There are usually a few different failure points that have been found in the literature. One is placement. Many times, when you’re panicked, you don’t remember exactly how to place it. It should be placed high and tight above the bleed and not over a joint. 

The second problem is inadequate tightness. For a CAT tourniquet to be effective, you have to get it extremely tight on that first pull before the windlass is activated, and many times people don’t remember that in the stress of the moment. 

Dr. Glatter: Peter, in terms of tourniquet application by your medics in the field, certainly the CAT-type device has been in existence for quite a while. Hannah’s proposing a new iteration of how to do this, which is automated and simple. What is your take on such a device? And how did you learn about Hannah’s device? 

Peter M. Antevy, MD: We’ve been training on tourniquets ever since the military data showed that there was an extreme benefit in using them. We’ve been doing training for many years, including our police officers. What we’ve noticed is that every time we gather everyone together to show them how to place a tourniquet — and we have to do one-on-one sessions with them — it’s not a device that they can easily put on. These are police officers who had the training last year. 

Like Hannah said, most of the time they have a problem unraveling it and understanding how to actually place it. It’s easier on the arm than it is on the leg. You can imagine it would be harder to place it on your own leg, especially if you had an injury. Then, they don’t tighten it well enough, as Hannah just mentioned. In order for a tourniquet to really be placed properly, it’s going to hurt that person. Many people have that tendency not to want to tighten it as much as they can. 

Having said that, how I got into all of this is because I’m the medical director for Coral Springs and Parkland, and unfortunately, we had the 2018 Valentine’s Day murders that happened where we lost 17 adults and kids. However, 17 people were saved that day, and the credit goes to our police officers who had tourniquets or chest seals on before those patients were brought out to EMS. Many lives were saved by the tourniquet. 

If you look at the Boston Marathon massacre and many other events that have happened, I believe — and I’ve always believed — that tourniquets should be in the glove box of every citizen. It should be in every school room. They should be in buildings along with the AED. 

In my town of Davie, we were the first in the country to add an ordinance that required a Stop the Bleed kit in the AED cabinet, and those were required by buildings of certain sizes. In order to get this lifesaving device everywhere, I think it has to be put into local ordinance and supported by states and by the national folks, which they are doing. 
 

Trials Are Underway

Dr. Glatter: In terms of adoption of such a device, it certainly has to go through rigorous testing and maybe some trials. Hannah, where are you at with vetting this in terms of any type of trial? Has it been compared head to head with standard tourniquets? 

Ms. Herbst: Yes, we’re currently doing large amounts of field testing. We’re doing testing on emergency vehicles and in the surgical setting with different customers. In addition, we’re running pilot studies at different universities and with different organizations, including the military, to make sure that this device is effective. We’re evaluating cognitive offloading of people. We’re hoping to start that study later this year. We’re excited to be doing this in a variety of settings. 

We’re also testing the quality of it in different environmental conditions and under different atmospheric pressure. We’re doing everything we can to ensure the device is safe and effective. We’re excited to scale and fill our preorders and be able to develop this and deliver it to many people. 

Dr. Glatter: I was wondering if you could describe the actual device. There’s a brain part of it and then, obviously, the strap aspect of it. I was curious about contamination and reusability issues. 

Ms. Herbst: That’s a great question. One of the limitations of conventional tourniquets on the market is that they are single use, and often, it requires two tourniquets to stop a bleed, both of which have to be disposed of. 

With AutoTQ, we have a reusable component and a disposable component. I actually have one here that I can show you. We have a cover on it that says: Stop bleed, slide up and power on. You just pull this cover off and then you have a few simple commands. You have powering the device on. I’ll just click this button: Tighten strap above bleeding, then press inflate. It delivers audible instructions telling you exactly how to use the device. Then, you tighten it above your bleed on the limb, and you press the inflate button. Then it administers air into the cuff and stops the patient’s bleed. 
 

Tourniquet Conversion and Limb Salvage

Dr. Glatter: In terms of ischemia time, how can a device like this make it easier for us to know when to let the tourniquet down and allow some blood flow? Certainly, limb salvage is important, and we don’t want to have necrosis and so forth. 

Dr. Antevy: That’s a great question. The limb salvage rate when tourniquets have been used is 85%. When used correctly, you can really improve the outcomes for many patients. 

On the flip side of that, there’s something called tourniquet conversion. That’s exactly what you mentioned. It’s making sure that the tourniquet doesn’t stay on for too long of a time. If you can imagine a patient going to an outlying hospital where there’s no trauma center, and then that patient then has to be moved a couple hours to the trauma center, could you potentially have a tourniquet on for too long that then ends up causing the patient a bad outcome? The answer is yes.

I just had someone on my webinar recently describing the appropriate conversion techniques of tourniquets. You don’t find too much of that in the literature, but you really have to ensure that as you’re taking the tourniquet down, the bleeding is actually stopped. It’s not really recommended to take a tourniquet down if the patient was just acutely bleeding. 

However, imagine a situation where a tourniquet was put on incorrectly. Let’s say a patient got nervous and they just put it on a patient who didn’t really need it. You really have to understand how to evaluate that wound to be sure that, as you’re taking the tourniquet down slowly, the patient doesn’t rebleed again. 

There are two sides of the question, Rob. One is making sure it’s not on inappropriately. The second one is making sure it’s not on for too long, which ends up causing ischemia to that limb. 

Dr. Glatter: Hannah, does your device collect data on the number of hours or minutes that the tourniquet has been up and then automatically deflate it in some sense to allow for that improvement in limb salvage?

Ms. Herbst: That’s a great question, and I really appreciate your answer as well, Dr Antevy. Ischemia time is a very important and critical component of tourniquet use. This is something, when we were designing AutoTQ, that we took into high consideration. 

We found, when we evaluated AutoTQ vs a CAT tourniquet in a mannequin model, that AutoTQ can achieve cessation of hemorrhage at around 400 mm Hg of mercury, whereas CAT requires 700-800 mm Hg. Already our ischemia time is slightly extended just based on existing literature with pneumatic tourniquets because it can stop the bleed at a lower pressure, which causes less complications with the patient’s limb. 

There are different features that we build out for different customers, so depending on what people want, it is possible to deflate the tourniquet. However, typically, you’re at the hospital within 30 minutes. It’s quick to get them there, and then the physician can treat and take that tourniquet down in a supervised and controlled setting. 

Dr. Glatter: In terms of patients with obesity, do you have adjustable straps that will accommodate for that aspect? 

Ms. Herbst: Yes, we have different cuff sizes to accommodate different limbs.
 

Will AutoTQ Be Available to the Public?

Dr. Glatter: Peter, in terms of usability in the prehospital setting, where do you think this is going in the next 3-5 years? 

Dr. Antevy: I’ll start with the public safety sector of the United States, which is the one that is actually first on scene. Whether you’re talking about police officers or EMS, it would behoove us to have tourniquets everywhere. On all of my ambulances, across all of my agencies that I manage, we have quite a number of tourniquets. 

Obviously, cost is a factor, and I know that Hannah has done a great job of making that brain reusable. All we have to do is purchase the straps, which are effectively the same cost, I understand, as a typical tourniquet you would purchase. 

Moving forward though, however, I think that this has wide scalability to the public market, whether it be schools, office buildings, the glove box, and so on. It’s really impossible to teach somebody how to do this the right way, if you have to teach them how to put the strap on, tighten it correctly, and so on. If there was an easy way, like Hannah developed, of just putting it on and pushing a button, then I think that the outcomes and the scalability are much further beyond what we can do in EMS. I think there’s great value in both markets. 
 

The ‘AED of Bleeding’: Rechargeable and Reusable

Dr. Glatter: This is the AED of bleeding. You have a device here that has wide-scale interest, certainly from the public and private sector. 

Hannah, in terms of battery decay, how would that work out if it was in someone’s garage? Let’s just say someone purchased it and they hadn’t used it in 3 or 4 months. What type of decay are we looking at and can they rely on it? 

Ms. Herbst: AutoTQ is rechargeable by a USB-C port, and our battery lasts for a year. Once a year, you’ll get an email reminder that says: “Hey, please charge your AutoTQ and make sure it’s up to the battery level.” We do everything in our power to make sure that our consumers are checking their batteries and that they’re ready to go. 

Dr. Glatter: Is it heat and fire resistant? What, in terms of durability, does your device have? 

Ms. Herbst: Just like any other medical device, we come with manufacturer recommendations for the upper and lower bounds of temperature and different storage recommendations. All of that is in our instructions for use. 

Dr. Glatter: Peter, getting back to logistics. In terms of adoption, do you feel that, in the long term, this device will be something that we’re going to be seeing widely adopted just going forward? 

Dr. Antevy: I do, and I’ll tell you why. When you look at AED use in this country, the odds of someone actually getting an AED and using it correctly are still very low. Part of that is because it’s complicated for many people to do. Getting tourniquets everywhere is step No. 1, and I think the federal government and the Stop the Bleed program is really making that happen. 

We talked about ordinances, but ease of use, I think, is really the key. You have people who oftentimes have their child in cardiac arrest in front of them, and they won’t put two hands on their chest because they just are afraid of doing it. 

When you have a device that’s a tourniquet, that’s a single-button turn on and single-button inflate, I think that would make it much more likely that a person will use that device when they’re passing the scene of an accident, as an example. 

We’ve had many non–mass casualty incident events that have had tourniquets. We’ve had some media stories on them, where they’re just happening because someone got into a motor vehicle accident. It doesn’t have to be a school shooting. I think the tourniquets should be everywhere and should be easily used by everybody. 
 

Managing Pain 

Dr. Glatter: Regarding sedation, is there a need because of the pain involved with the application? How would you sedate a patient, pediatric or adult, who needs a tourniquet? 

Dr. Antevy: We always evaluate people’s pain. If the patient is an extremist, we’re just going to be managing and trying to get them back to life. Once somebody is stabilized and is exhibiting pain of any sort, even, for example, after we intubate somebody, we have to sedate them and provide them pain control because they have a piece of plastic in their trachea. 

It’s the same thing here for a tourniquet. These are painful, and we do have the appropriate medications on our vehicles to address that pain. Again, just simply the trauma itself is very painful. Yes, we do address that in EMS, and I would say most public agencies across this country would address pain appropriately. 
 

Training on Tourniquet Use

Dr. Glatter: Hannah, can you talk a little bit about public training types of approaches? How would you train a consumer who purchases this type of device?

Ms. Herbst: A huge part of our mission is making blood loss prevention and control training accessible to a wide variety of people. One way that we’re able to do that is through our online training platform. When you purchase an AutoTQ kit, you plug it into your computer, and it walks you through the process of using it. It lets you practice on your own limb and on your buddy’s limb, just to be able to effectively apply it. We think this will have huge impacts in making sure that people are prepared and ready to stop the bleed with AutoTQ. 

Dr. Glatter: Do you recommend people training once a month, in general, just to keep their skills up to use this? In the throes of a trauma and very chaotic situation, people sometimes lose their ability to think clearly and straightly. 

Ms. Herbst: One of the studies we’re conducting is a learning curve study to try to figure out how quickly these skills degrade over time. We know that with the windlass tourniquet, it degrades within moments of training. With AutoTQ, we think the learning curve will last much longer. That’s something we’re evaluating, but we recommend people train as often as they can. 

Dr. Antevy: Rob, if I can mention that there is a concept of just-in-time training. I think that with having the expectation that people are going to be training frequently, unfortunately, as many of us know, even with the AED as a perfect example, people don’t do that. 

Yes. I would agree that you have to train at least once a year, is what I would say. At my office, we have a 2-hour training that goes over all these different items once a year. 

The device itself should have the ability to allow you to figure out how to use it just in time, whether via video, or like Hannah’s device, by audio. I think that having both those things would make it more likely that the device be used when needed. 

People panic, and if they have a device that can talk to them or walk them through it, they will be much more likely to use it at that time.

 

Final Takeaways

Dr. Glatter: Any other final thoughts or a few pearls for listeners to take away? Hannah, I’ll start with you. 

Ms. Herbst: I’m very grateful for your time, and I’m very excited about the potential for AutoTQ. To me, it’s so exciting to see people preordering the device now. We’ve had people from school bus companies and small sports teams. I think, just like Dr Antevy said, tourniquets aren’t limited to mass casualty situations. Blood loss can happen anywhere and to anyone. 

Being able to equip people and serve them to better prepare them for this happening to themselves, their friends, or their family is just the honor of a lifetime. Thank you very much for covering the device and for having me today. 

Dr. Glatter: Of course, my pleasure. Peter? 

Dr. Antevy: The citizens of this country, and everyone who lives across the world, has started to understand that there are things that we expect from our people, from the community. We expect them to do CPR for cardiac arrest. We expect them to know how to use an EpiPen. We expect them to know how to use an AED, and we also expect them to know how to stop bleeding with a tourniquet. 

The American public has gotten to understand that these devices are very important. Having a device that’s easily used, that I can teach you in 10 seconds, that speaks to you — these are all things that make this product have great potential. I do look forward to the studies, not just the cadaver studies, but the real human studies. 

I know Hannah is really a phenom and has been doing all these things so that this product can be on the shelves of Walmart and CVS one day. I commend you, Hannah, for everything you’re doing and wishing you the best of luck. We’re here for you. 

Dr. Glatter: Same here. Congratulations on your innovative capability and what you’ve done to change the outcomes of bleeding related to penetrating trauma. Thank you so much.

Robert D. Glatter, MD, is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. He is a medical advisor for Medscape and hosts the Hot Topics in EM series. Hannah D. Herbst, BS, is a graduate of Florida Atlantic University, was selected for Forbes 30 Under 30, and is the founder/CEO of Golden Hour Medical. Peter M. Antevy, MD, is a pediatric emergency medicine physician and medical director for Davie Fire Rescue and Coral Springs–Parkland Fire Department in Florida. He is also a member of the EMS Eagles Global Alliance.



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

People over age 60 who drink alcohol regularly are at an increased risk of early death, particularly from cancer or issues related to the heart and blood vessels.

That’s according to the findings of a new, large study that was published in JAMA Network Openand build upon numerous other recent studies concluding that any amount of alcohol consumption is linked to significant health risks. That’s a change from decades of public health messaging suggesting that moderate alcohol intake (one or two drinks per day) wasn’t dangerous. Recently, experts have uncovered flaws in how researchers came to those earlier conclusions.

In this latest study, researchers in Spain analyzed health data for more than 135,000 people, all of whom were at least 60 years old, lived in the United Kingdom, and provided their health information to the UK Biobank database. The average age of people at the start of the analysis period was 64.

The researchers compared 12 years of health outcomes for occasional drinkers with those who averaged drinking at least some alcohol on a daily basis. The greatest health risks were seen between occasional drinkers and those whom the researchers labeled “high risk.” Occasional drinkers had less than about two drinks per week. The high-risk group included men who averaged nearly three drinks per day or more, and women who averaged about a drink and a half per day or more. The analysis showed that, compared with occasional drinking, high-risk drinking was linked to a 33% increased risk of early death, a 39% increased risk of dying from cancer, and a 21% increased risk of dying from problems with the heart and blood vessels.

More moderate drinking habits were also linked to an increased risk of early death and dying from cancer, and even just averaging about one drink or less daily was associated with an 11% higher risk of dying from cancer. Low and moderate drinkers were most at risk if they also had health problems or experienced socioeconomic factors like living in less affluent neighborhoods.

The findings also suggested the potential that mostly drinking wine, or drinking mostly with meals, may be lower risk, but the researchers called for further study on those topics since “it may mostly reflect the effect of healthier lifestyles, slower alcohol absorption, or nonalcoholic components of beverages.”

A recent Gallup poll showed that overall, Americans’ attitudes toward the health impacts of alcohol are changing, with 65% of young adults (ages 18-34) saying that drinking can have negative health effects. But just 39% of adults age 55 or older agreed that drinking is bad for a person’s health. The gap in perspectives between younger and older adults about drinking is the largest on record, Gallup reported.

The study investigators reported no conflicts of interest.

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

People over age 60 who drink alcohol regularly are at an increased risk of early death, particularly from cancer or issues related to the heart and blood vessels.

That’s according to the findings of a new, large study that was published in JAMA Network Openand build upon numerous other recent studies concluding that any amount of alcohol consumption is linked to significant health risks. That’s a change from decades of public health messaging suggesting that moderate alcohol intake (one or two drinks per day) wasn’t dangerous. Recently, experts have uncovered flaws in how researchers came to those earlier conclusions.

In this latest study, researchers in Spain analyzed health data for more than 135,000 people, all of whom were at least 60 years old, lived in the United Kingdom, and provided their health information to the UK Biobank database. The average age of people at the start of the analysis period was 64.

The researchers compared 12 years of health outcomes for occasional drinkers with those who averaged drinking at least some alcohol on a daily basis. The greatest health risks were seen between occasional drinkers and those whom the researchers labeled “high risk.” Occasional drinkers had less than about two drinks per week. The high-risk group included men who averaged nearly three drinks per day or more, and women who averaged about a drink and a half per day or more. The analysis showed that, compared with occasional drinking, high-risk drinking was linked to a 33% increased risk of early death, a 39% increased risk of dying from cancer, and a 21% increased risk of dying from problems with the heart and blood vessels.

More moderate drinking habits were also linked to an increased risk of early death and dying from cancer, and even just averaging about one drink or less daily was associated with an 11% higher risk of dying from cancer. Low and moderate drinkers were most at risk if they also had health problems or experienced socioeconomic factors like living in less affluent neighborhoods.

The findings also suggested the potential that mostly drinking wine, or drinking mostly with meals, may be lower risk, but the researchers called for further study on those topics since “it may mostly reflect the effect of healthier lifestyles, slower alcohol absorption, or nonalcoholic components of beverages.”

A recent Gallup poll showed that overall, Americans’ attitudes toward the health impacts of alcohol are changing, with 65% of young adults (ages 18-34) saying that drinking can have negative health effects. But just 39% of adults age 55 or older agreed that drinking is bad for a person’s health. The gap in perspectives between younger and older adults about drinking is the largest on record, Gallup reported.

The study investigators reported no conflicts of interest.

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

People over age 60 who drink alcohol regularly are at an increased risk of early death, particularly from cancer or issues related to the heart and blood vessels.

That’s according to the findings of a new, large study that was published in JAMA Network Openand build upon numerous other recent studies concluding that any amount of alcohol consumption is linked to significant health risks. That’s a change from decades of public health messaging suggesting that moderate alcohol intake (one or two drinks per day) wasn’t dangerous. Recently, experts have uncovered flaws in how researchers came to those earlier conclusions.

In this latest study, researchers in Spain analyzed health data for more than 135,000 people, all of whom were at least 60 years old, lived in the United Kingdom, and provided their health information to the UK Biobank database. The average age of people at the start of the analysis period was 64.

The researchers compared 12 years of health outcomes for occasional drinkers with those who averaged drinking at least some alcohol on a daily basis. The greatest health risks were seen between occasional drinkers and those whom the researchers labeled “high risk.” Occasional drinkers had less than about two drinks per week. The high-risk group included men who averaged nearly three drinks per day or more, and women who averaged about a drink and a half per day or more. The analysis showed that, compared with occasional drinking, high-risk drinking was linked to a 33% increased risk of early death, a 39% increased risk of dying from cancer, and a 21% increased risk of dying from problems with the heart and blood vessels.

More moderate drinking habits were also linked to an increased risk of early death and dying from cancer, and even just averaging about one drink or less daily was associated with an 11% higher risk of dying from cancer. Low and moderate drinkers were most at risk if they also had health problems or experienced socioeconomic factors like living in less affluent neighborhoods.

The findings also suggested the potential that mostly drinking wine, or drinking mostly with meals, may be lower risk, but the researchers called for further study on those topics since “it may mostly reflect the effect of healthier lifestyles, slower alcohol absorption, or nonalcoholic components of beverages.”

A recent Gallup poll showed that overall, Americans’ attitudes toward the health impacts of alcohol are changing, with 65% of young adults (ages 18-34) saying that drinking can have negative health effects. But just 39% of adults age 55 or older agreed that drinking is bad for a person’s health. The gap in perspectives between younger and older adults about drinking is the largest on record, Gallup reported.

The study investigators reported no conflicts of interest.

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