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Confirmed: Intermittent use of benzodiazepines is the safest option
BARCELONA – results of a large-scale study show.
Investigators matched more than 57,000 chronic benzodiazepine users with nearly 114,000 intermittent users and found that, at 1 year, chronic users had an 8% increased risk for emergency department visits and/or hospitalizations for falls.
Chronic users also had a 25% increased risk for hip fracture, a 4% raised risk for ED visits and/or hospitalizations for any reason, and a 23% increased risk for death.
Study investigator Simon J.C. Davies, MD, PhD, MSc, Centre for Addiction & Mental Health, Toronto, said that the research shows that, where possible, patients older than 65 years with anxiety or insomnia who are taking benzodiazepines should not stay on these medications continuously.
However, he acknowledged that, “in practical terms, there will be some who can’t change or do not want to change” their treatment.
The findings were presented at the annual meeting of the European College of Neuropsychopharmacology.
Wide range of adverse outcomes
The authors noted that benzodiazepines are used to treat anxiety and insomnia but are associated with a range of adverse outcomes, including falls, fractures, cognitive impairment, and mortality as well as tolerance and dose escalation.
“These risks are especially relevant in older adults,” they added, noting that some guidelines recommend avoiding the drugs in this population, whereas other suggest short-term benzodiazepine use for a maximum of 4 weeks.
Despite this, “benzodiazepines are widely prescribed in older adults.” One study showed that almost 15% of adults aged 65 years or older received at least one benzodiazepine prescription.
Moreover, chronic use is more common in older versus younger patients.
Benzodiazepine use among older adults “used to be higher,” Dr. Davies said in an interview, at around 20%, but the “numbers have come down,” partly because of the introduction of benzodiazepine-like sleep medications but also because of educational efforts.
“There are certainly campaigns in Ontario to educate physicians,” Dr. Davies said, “but I think more broadly people are aware of the activity of these drugs, and the tolerance and other issues.”
To compare the risk associated with chronic versus intermittent use of benzodiazepines in older adults, the team performed a population-based cohort study using linked health care databases in Ontario.
They focused on adults aged 65 years or older with a first benzodiazepine prescription after at least 1 year without taking the drugs.
Chronic benzodiazepine use was defined as 120 days of prescriptions over the first 180 days after the index prescription. Patients who met these criteria were matched with intermittent users in a 2:1 ratio by age and sex.
Patients were then propensity matched using 24 variables, including health system use in the year prior to the index prescription, clinical diagnoses, prior psychiatric health system use, falls, and income level.
The team identified 57,072 chronic benzodiazepine users and 312,468 intermittent users, of whom, 57,041 and 113,839, respectively, were propensity matched.
As expected, chronic users were prescribed benzodiazepines for more days than were the intermittent users over both the initial 180-day exposure period, at 141 days versus 33 days, and again during a further 180-day follow-up period, at 181 days versus 19 days.
Over the follow-up period, the daily lorazepam dose-equivalents of chronic users four times that of intermittent users.
Hospitalizations and/or ED visits for falls were higher among patients in the chronic benzodiazepine group, at 4.6% versus 3.2% in those who took the drugs intermittently.
After adjusting for benzodiazepine dose, the team found that chronic benzodiazepine use was associated with a significant increase in the risk for falls leading to hospital presentation over the 360-day study period, compared with intermittent use (hazard ratio, 1.08; P = .0124).
Sex differences
In addition, chronic use was linked to a significantly increased risk for hip fracture (HR, 1.25; P = .0095), and long-term care admission (HR, 1.32; P < .0001).
There was also a significant increase in ED visits and/or hospitalizations for any reason with chronic benzodiazepine use versus intermittent use (HR, 1.04; P = .0007), and an increase in the risk for death (HR, 1.23; P < .0001).
A nonsignificant increased risk for wrist fracture was also associated with chronic use of benzodiazepines (HR, 1.02; P = .8683).
Further analysis revealed some sex differences. For instance, men had a marked increase in the risk for hip fracture with chronic use (HR, 1.50; P = .0154), whereas the risk was not significant in women (HR, 1.16; P = .1332). In addition, mortality risk associated with chronic use was higher in men than in women (HR, 1.39; P < .0001 vs. HR, 1.10; P = .2245).
The decision to discontinue chronic benzodiazepine use can be challenging, said Dr. Davies. “If you’re advising people to stop, what happens to the treatment of their anxiety?”
He said that there are many other treatment options for anxiety that don’t come with tolerance or risk for addiction.
“My position would be that intermittent use is perfectly acceptable while you bide your time to explore other treatments. They may be pharmacological; they may, of course, be lifestyle changes, psychotherapies, and so on,” said Dr. Davies.
If, however, patients feel that chronic benzodiazepine use is their only option, this research informs that decision by quantifying the risks.
“We’ve always known that there was a problem, but there haven’t been high-quality epidemiological studies like this that allowed us to say what the numbers are,” said Dr. Davies.
Confirmatory research
In a comment, Christoph U. Correll, MD, professor of psychiatry at Hofstra University, Hempstead, N.Y., noted that the risk associated with benzodiazepine use, especially in older people, has been demonstrated repeatedly.
“In that context, it is not surprising that less continuous exposure to an established risk factor attenuates the risk for these adverse outcomes,” he said.
Dr. Correll, who was not involved in the study pointed out there is nevertheless a “risk of residual confounding by indication.”
In other words, “people with intermittent benzodiazepine use may have less severe underlying illness and better healthy lifestyle behaviors than those requiring chronic benzodiazepine administration.”
Also commenting on the research, Christian Vinkers, MD, PhD, psychiatrist and professor of stress and resilience, Amsterdam University Medical Centre, said that it confirms “once again that long-term benzodiazepine use should not be encouraged.”
“The risk of falls, as well as cognitive side effects and impaired driving skills, with the risk of road accidents, make chronic overuse of benzodiazepines a public health issue. Of course, there is a small group of patients who should have access to long-term use, but it is reasonable to assume that this group is currently too large,” he added.
The study was funded through a grant from the University of Toronto Department of Psychiatry Excellence Funds. No relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
BARCELONA – results of a large-scale study show.
Investigators matched more than 57,000 chronic benzodiazepine users with nearly 114,000 intermittent users and found that, at 1 year, chronic users had an 8% increased risk for emergency department visits and/or hospitalizations for falls.
Chronic users also had a 25% increased risk for hip fracture, a 4% raised risk for ED visits and/or hospitalizations for any reason, and a 23% increased risk for death.
Study investigator Simon J.C. Davies, MD, PhD, MSc, Centre for Addiction & Mental Health, Toronto, said that the research shows that, where possible, patients older than 65 years with anxiety or insomnia who are taking benzodiazepines should not stay on these medications continuously.
However, he acknowledged that, “in practical terms, there will be some who can’t change or do not want to change” their treatment.
The findings were presented at the annual meeting of the European College of Neuropsychopharmacology.
Wide range of adverse outcomes
The authors noted that benzodiazepines are used to treat anxiety and insomnia but are associated with a range of adverse outcomes, including falls, fractures, cognitive impairment, and mortality as well as tolerance and dose escalation.
“These risks are especially relevant in older adults,” they added, noting that some guidelines recommend avoiding the drugs in this population, whereas other suggest short-term benzodiazepine use for a maximum of 4 weeks.
Despite this, “benzodiazepines are widely prescribed in older adults.” One study showed that almost 15% of adults aged 65 years or older received at least one benzodiazepine prescription.
Moreover, chronic use is more common in older versus younger patients.
Benzodiazepine use among older adults “used to be higher,” Dr. Davies said in an interview, at around 20%, but the “numbers have come down,” partly because of the introduction of benzodiazepine-like sleep medications but also because of educational efforts.
“There are certainly campaigns in Ontario to educate physicians,” Dr. Davies said, “but I think more broadly people are aware of the activity of these drugs, and the tolerance and other issues.”
To compare the risk associated with chronic versus intermittent use of benzodiazepines in older adults, the team performed a population-based cohort study using linked health care databases in Ontario.
They focused on adults aged 65 years or older with a first benzodiazepine prescription after at least 1 year without taking the drugs.
Chronic benzodiazepine use was defined as 120 days of prescriptions over the first 180 days after the index prescription. Patients who met these criteria were matched with intermittent users in a 2:1 ratio by age and sex.
Patients were then propensity matched using 24 variables, including health system use in the year prior to the index prescription, clinical diagnoses, prior psychiatric health system use, falls, and income level.
The team identified 57,072 chronic benzodiazepine users and 312,468 intermittent users, of whom, 57,041 and 113,839, respectively, were propensity matched.
As expected, chronic users were prescribed benzodiazepines for more days than were the intermittent users over both the initial 180-day exposure period, at 141 days versus 33 days, and again during a further 180-day follow-up period, at 181 days versus 19 days.
Over the follow-up period, the daily lorazepam dose-equivalents of chronic users four times that of intermittent users.
Hospitalizations and/or ED visits for falls were higher among patients in the chronic benzodiazepine group, at 4.6% versus 3.2% in those who took the drugs intermittently.
After adjusting for benzodiazepine dose, the team found that chronic benzodiazepine use was associated with a significant increase in the risk for falls leading to hospital presentation over the 360-day study period, compared with intermittent use (hazard ratio, 1.08; P = .0124).
Sex differences
In addition, chronic use was linked to a significantly increased risk for hip fracture (HR, 1.25; P = .0095), and long-term care admission (HR, 1.32; P < .0001).
There was also a significant increase in ED visits and/or hospitalizations for any reason with chronic benzodiazepine use versus intermittent use (HR, 1.04; P = .0007), and an increase in the risk for death (HR, 1.23; P < .0001).
A nonsignificant increased risk for wrist fracture was also associated with chronic use of benzodiazepines (HR, 1.02; P = .8683).
Further analysis revealed some sex differences. For instance, men had a marked increase in the risk for hip fracture with chronic use (HR, 1.50; P = .0154), whereas the risk was not significant in women (HR, 1.16; P = .1332). In addition, mortality risk associated with chronic use was higher in men than in women (HR, 1.39; P < .0001 vs. HR, 1.10; P = .2245).
The decision to discontinue chronic benzodiazepine use can be challenging, said Dr. Davies. “If you’re advising people to stop, what happens to the treatment of their anxiety?”
He said that there are many other treatment options for anxiety that don’t come with tolerance or risk for addiction.
“My position would be that intermittent use is perfectly acceptable while you bide your time to explore other treatments. They may be pharmacological; they may, of course, be lifestyle changes, psychotherapies, and so on,” said Dr. Davies.
If, however, patients feel that chronic benzodiazepine use is their only option, this research informs that decision by quantifying the risks.
“We’ve always known that there was a problem, but there haven’t been high-quality epidemiological studies like this that allowed us to say what the numbers are,” said Dr. Davies.
Confirmatory research
In a comment, Christoph U. Correll, MD, professor of psychiatry at Hofstra University, Hempstead, N.Y., noted that the risk associated with benzodiazepine use, especially in older people, has been demonstrated repeatedly.
“In that context, it is not surprising that less continuous exposure to an established risk factor attenuates the risk for these adverse outcomes,” he said.
Dr. Correll, who was not involved in the study pointed out there is nevertheless a “risk of residual confounding by indication.”
In other words, “people with intermittent benzodiazepine use may have less severe underlying illness and better healthy lifestyle behaviors than those requiring chronic benzodiazepine administration.”
Also commenting on the research, Christian Vinkers, MD, PhD, psychiatrist and professor of stress and resilience, Amsterdam University Medical Centre, said that it confirms “once again that long-term benzodiazepine use should not be encouraged.”
“The risk of falls, as well as cognitive side effects and impaired driving skills, with the risk of road accidents, make chronic overuse of benzodiazepines a public health issue. Of course, there is a small group of patients who should have access to long-term use, but it is reasonable to assume that this group is currently too large,” he added.
The study was funded through a grant from the University of Toronto Department of Psychiatry Excellence Funds. No relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
BARCELONA – results of a large-scale study show.
Investigators matched more than 57,000 chronic benzodiazepine users with nearly 114,000 intermittent users and found that, at 1 year, chronic users had an 8% increased risk for emergency department visits and/or hospitalizations for falls.
Chronic users also had a 25% increased risk for hip fracture, a 4% raised risk for ED visits and/or hospitalizations for any reason, and a 23% increased risk for death.
Study investigator Simon J.C. Davies, MD, PhD, MSc, Centre for Addiction & Mental Health, Toronto, said that the research shows that, where possible, patients older than 65 years with anxiety or insomnia who are taking benzodiazepines should not stay on these medications continuously.
However, he acknowledged that, “in practical terms, there will be some who can’t change or do not want to change” their treatment.
The findings were presented at the annual meeting of the European College of Neuropsychopharmacology.
Wide range of adverse outcomes
The authors noted that benzodiazepines are used to treat anxiety and insomnia but are associated with a range of adverse outcomes, including falls, fractures, cognitive impairment, and mortality as well as tolerance and dose escalation.
“These risks are especially relevant in older adults,” they added, noting that some guidelines recommend avoiding the drugs in this population, whereas other suggest short-term benzodiazepine use for a maximum of 4 weeks.
Despite this, “benzodiazepines are widely prescribed in older adults.” One study showed that almost 15% of adults aged 65 years or older received at least one benzodiazepine prescription.
Moreover, chronic use is more common in older versus younger patients.
Benzodiazepine use among older adults “used to be higher,” Dr. Davies said in an interview, at around 20%, but the “numbers have come down,” partly because of the introduction of benzodiazepine-like sleep medications but also because of educational efforts.
“There are certainly campaigns in Ontario to educate physicians,” Dr. Davies said, “but I think more broadly people are aware of the activity of these drugs, and the tolerance and other issues.”
To compare the risk associated with chronic versus intermittent use of benzodiazepines in older adults, the team performed a population-based cohort study using linked health care databases in Ontario.
They focused on adults aged 65 years or older with a first benzodiazepine prescription after at least 1 year without taking the drugs.
Chronic benzodiazepine use was defined as 120 days of prescriptions over the first 180 days after the index prescription. Patients who met these criteria were matched with intermittent users in a 2:1 ratio by age and sex.
Patients were then propensity matched using 24 variables, including health system use in the year prior to the index prescription, clinical diagnoses, prior psychiatric health system use, falls, and income level.
The team identified 57,072 chronic benzodiazepine users and 312,468 intermittent users, of whom, 57,041 and 113,839, respectively, were propensity matched.
As expected, chronic users were prescribed benzodiazepines for more days than were the intermittent users over both the initial 180-day exposure period, at 141 days versus 33 days, and again during a further 180-day follow-up period, at 181 days versus 19 days.
Over the follow-up period, the daily lorazepam dose-equivalents of chronic users four times that of intermittent users.
Hospitalizations and/or ED visits for falls were higher among patients in the chronic benzodiazepine group, at 4.6% versus 3.2% in those who took the drugs intermittently.
After adjusting for benzodiazepine dose, the team found that chronic benzodiazepine use was associated with a significant increase in the risk for falls leading to hospital presentation over the 360-day study period, compared with intermittent use (hazard ratio, 1.08; P = .0124).
Sex differences
In addition, chronic use was linked to a significantly increased risk for hip fracture (HR, 1.25; P = .0095), and long-term care admission (HR, 1.32; P < .0001).
There was also a significant increase in ED visits and/or hospitalizations for any reason with chronic benzodiazepine use versus intermittent use (HR, 1.04; P = .0007), and an increase in the risk for death (HR, 1.23; P < .0001).
A nonsignificant increased risk for wrist fracture was also associated with chronic use of benzodiazepines (HR, 1.02; P = .8683).
Further analysis revealed some sex differences. For instance, men had a marked increase in the risk for hip fracture with chronic use (HR, 1.50; P = .0154), whereas the risk was not significant in women (HR, 1.16; P = .1332). In addition, mortality risk associated with chronic use was higher in men than in women (HR, 1.39; P < .0001 vs. HR, 1.10; P = .2245).
The decision to discontinue chronic benzodiazepine use can be challenging, said Dr. Davies. “If you’re advising people to stop, what happens to the treatment of their anxiety?”
He said that there are many other treatment options for anxiety that don’t come with tolerance or risk for addiction.
“My position would be that intermittent use is perfectly acceptable while you bide your time to explore other treatments. They may be pharmacological; they may, of course, be lifestyle changes, psychotherapies, and so on,” said Dr. Davies.
If, however, patients feel that chronic benzodiazepine use is their only option, this research informs that decision by quantifying the risks.
“We’ve always known that there was a problem, but there haven’t been high-quality epidemiological studies like this that allowed us to say what the numbers are,” said Dr. Davies.
Confirmatory research
In a comment, Christoph U. Correll, MD, professor of psychiatry at Hofstra University, Hempstead, N.Y., noted that the risk associated with benzodiazepine use, especially in older people, has been demonstrated repeatedly.
“In that context, it is not surprising that less continuous exposure to an established risk factor attenuates the risk for these adverse outcomes,” he said.
Dr. Correll, who was not involved in the study pointed out there is nevertheless a “risk of residual confounding by indication.”
In other words, “people with intermittent benzodiazepine use may have less severe underlying illness and better healthy lifestyle behaviors than those requiring chronic benzodiazepine administration.”
Also commenting on the research, Christian Vinkers, MD, PhD, psychiatrist and professor of stress and resilience, Amsterdam University Medical Centre, said that it confirms “once again that long-term benzodiazepine use should not be encouraged.”
“The risk of falls, as well as cognitive side effects and impaired driving skills, with the risk of road accidents, make chronic overuse of benzodiazepines a public health issue. Of course, there is a small group of patients who should have access to long-term use, but it is reasonable to assume that this group is currently too large,” he added.
The study was funded through a grant from the University of Toronto Department of Psychiatry Excellence Funds. No relevant financial relationships were declared.
A version of this article first appeared on Medscape.com.
AT ECNP 2023
Esketamine bests quetiapine for severe depression in head-to-head trial
BARCELONA – (TRD), results of a large, multicenter, head-to-head phase 3 trial show.
Results from the ESCAPE-TRD study, which included 675 participants with TRD, show that esketamine was associated with significantly increased rates of both depression and functional remission, compared with quetiapine.
More than 675 patients were randomly assigned to receive one of the two drugs along with ongoing treatment with an SSRI or a serotonin-norepinephrine reuptake inhibitor (SNRI).
Esketamine increased remission rates at 2 and 8 months over quetiapine by 72% and raised functional remission rates at 8 months by 88% while decreasing adverse event rates.
The findings were presented at the annual meeting of the European College of Neuropsychopharmacology and were published online in the New England Journal of Medicine.
New hope
The results provide “some hope for our patients suffering from TRD, which, given the data, is somewhat of a misnomer,” said study investigator Andreas Reif, MD, professor of psychiatry, psychosomatic medicine, and psychotherapy, University Hospital Frankfurt–Goethe University, Frankfurt am Main, Germany, and president-elect of the ECNP.
“These patients are not resistant, they just have resistance to monoaminergic drugs,” he added. Esketamine, he said, is a “new weapon in our armamentarium.”
Dr. Reif said TRD is a serious condition that affects approximately 20%-30% of those with major depressive disorder and has “substantial impact” on patients’ lives, including quality of life and level of functioning.
“We know that esketamine nasal spray is effective in TRD. However, up to now, there were only placebo-controlled trials in addition to ongoing antidepressant treatment,” Dr. Reif noted. Consequently, he added, a head-to-head comparison with an active agent with proven efficacy was “urgently needed.”
For the trial, patients from 171 sites in 24 countries with TRD, defined as a less than 25% improvement in symptoms with two or more consecutive treatments of adequate dosage and duration, were randomly assigned to receive esketamine nasal spray (n = 336) or quetiapine (n = 340) extended release together with ongoing SSRI or SNRI therapy.
Both esketamine and quetiapine were flexibly dosed. The primary endpoint was rates of remission at week 8 on the Montgomery-Åsberg Depression Rating Scale (MADRS). After week 8, patients entered a maintenance phase that lasted to week 32.
Dr. Reif said the study population was representative of a typical TRD population.
The average duration of the current depression episode was more than 5 years, and the average MADRS score was above 30.
Key findings
Results showed that those who received esketamine in combination with an SSRI or SNRI experienced a significantly higher rate of remission at week 8, compared with those treated with quetiapine (27.1% vs. 17.6%; P = .003). This equated to an adjusted odds ratio for remission of 1.74 (P = .003).
Use of esketamine was also associated with a higher rate of remission at week 8, and patients remained relapse free at week 32 (21.7% vs. 14.1% with quetiapine; odds ratio, 1.72; P = .008).
At every time point through the study, the proportion of patients experiencing remission was significantly greater with esketamine than with quetiapine. The absolute rate of remission at week 32 was 55.0%, versus 37.0% (P < .001).
Dr. Reif noted that the definition of remission used in the study was a MADRS score of less than or equal to 10, but if the “more lenient” definition of less than or equal to 12, which has been used previously, were to be applied, the absolute remission rates would rise to 65.1%, versus 46.7%.
Dr. Reif also presented results on functional remission rates beyond 32 weeks – data that were not included in the study as published in NEJM.
While remission rates increased over time in both study arms, the functional remission rate at week 32 was, again, significantly higher with esketamine than with quetiapine (38.1% vs. 25.0%; OR, 1.88; P < .001).
The safety data revealed no new signals, Dr. Reif said. Use of esketamine was associated with a lower rate of treatment-emergent adverse events that led to treatment discontinuation, at 4.2% vs. 11.0% with quetiapine.
Among patients given the ketamine-derived drug, there were lower rates of nervous system disorders, and there were no incidences of weight gain, fatigue, or hangover.
Dr. Reif said the results show that esketamine nasal spray was superior to quetiapine in achieving remission over time and that it “greatly improves patients’ functional impairment” while achieving “generally lower” adverse event rates.
He added that they are currently running a significant number of secondary analyses “to give us a better grasp of which patient benefits most” from esketamine therapy over quetiapine. The results may potentially be used to guide patient selection.
‘Tremendous advance’
Session co-chair Mark Weiser, MD, chairman at the department of psychiatry, Tel Aviv (Israel) University, said in an interview that the results are “very exciting” and offer “further proof of a tremendous advance in our field.”
Dr. Weiser, who was not involved in the study, added that demonstrating functional improvement with esketamine was key.
“It’s great to improve symptoms,” he said, “but to have patients show an improvement in their functionality is really the bottom line of this. Not only do you feel better, but you function better, and that’s of extreme importance and makes us feel very optimistic about the future.”
Josep Antoni Ramos-Quiroga, MD, PhD, head of psychiatry, Vall Hebron University Hospital and Autonomous University of Barcelona, welcomed the findings.
“The results of this study show the superior response and safety of esketamine nasal spray when compared with quetiapine,” he said in a release. “This gives people with treatment-resistant depression more safe treatment options.”
The study was funded by Janssen EMEA. Dr. Reif has relationships with Boehringer Ingelheim, COMPASS, Janssen Pharmaceuticals, LivaNova USA, Medice, Saga Therapeutics, and Shire. Other authors have disclosed numerous relationships with industry.
A version of this article first appeared on Medscape.com.
BARCELONA – (TRD), results of a large, multicenter, head-to-head phase 3 trial show.
Results from the ESCAPE-TRD study, which included 675 participants with TRD, show that esketamine was associated with significantly increased rates of both depression and functional remission, compared with quetiapine.
More than 675 patients were randomly assigned to receive one of the two drugs along with ongoing treatment with an SSRI or a serotonin-norepinephrine reuptake inhibitor (SNRI).
Esketamine increased remission rates at 2 and 8 months over quetiapine by 72% and raised functional remission rates at 8 months by 88% while decreasing adverse event rates.
The findings were presented at the annual meeting of the European College of Neuropsychopharmacology and were published online in the New England Journal of Medicine.
New hope
The results provide “some hope for our patients suffering from TRD, which, given the data, is somewhat of a misnomer,” said study investigator Andreas Reif, MD, professor of psychiatry, psychosomatic medicine, and psychotherapy, University Hospital Frankfurt–Goethe University, Frankfurt am Main, Germany, and president-elect of the ECNP.
“These patients are not resistant, they just have resistance to monoaminergic drugs,” he added. Esketamine, he said, is a “new weapon in our armamentarium.”
Dr. Reif said TRD is a serious condition that affects approximately 20%-30% of those with major depressive disorder and has “substantial impact” on patients’ lives, including quality of life and level of functioning.
“We know that esketamine nasal spray is effective in TRD. However, up to now, there were only placebo-controlled trials in addition to ongoing antidepressant treatment,” Dr. Reif noted. Consequently, he added, a head-to-head comparison with an active agent with proven efficacy was “urgently needed.”
For the trial, patients from 171 sites in 24 countries with TRD, defined as a less than 25% improvement in symptoms with two or more consecutive treatments of adequate dosage and duration, were randomly assigned to receive esketamine nasal spray (n = 336) or quetiapine (n = 340) extended release together with ongoing SSRI or SNRI therapy.
Both esketamine and quetiapine were flexibly dosed. The primary endpoint was rates of remission at week 8 on the Montgomery-Åsberg Depression Rating Scale (MADRS). After week 8, patients entered a maintenance phase that lasted to week 32.
Dr. Reif said the study population was representative of a typical TRD population.
The average duration of the current depression episode was more than 5 years, and the average MADRS score was above 30.
Key findings
Results showed that those who received esketamine in combination with an SSRI or SNRI experienced a significantly higher rate of remission at week 8, compared with those treated with quetiapine (27.1% vs. 17.6%; P = .003). This equated to an adjusted odds ratio for remission of 1.74 (P = .003).
Use of esketamine was also associated with a higher rate of remission at week 8, and patients remained relapse free at week 32 (21.7% vs. 14.1% with quetiapine; odds ratio, 1.72; P = .008).
At every time point through the study, the proportion of patients experiencing remission was significantly greater with esketamine than with quetiapine. The absolute rate of remission at week 32 was 55.0%, versus 37.0% (P < .001).
Dr. Reif noted that the definition of remission used in the study was a MADRS score of less than or equal to 10, but if the “more lenient” definition of less than or equal to 12, which has been used previously, were to be applied, the absolute remission rates would rise to 65.1%, versus 46.7%.
Dr. Reif also presented results on functional remission rates beyond 32 weeks – data that were not included in the study as published in NEJM.
While remission rates increased over time in both study arms, the functional remission rate at week 32 was, again, significantly higher with esketamine than with quetiapine (38.1% vs. 25.0%; OR, 1.88; P < .001).
The safety data revealed no new signals, Dr. Reif said. Use of esketamine was associated with a lower rate of treatment-emergent adverse events that led to treatment discontinuation, at 4.2% vs. 11.0% with quetiapine.
Among patients given the ketamine-derived drug, there were lower rates of nervous system disorders, and there were no incidences of weight gain, fatigue, or hangover.
Dr. Reif said the results show that esketamine nasal spray was superior to quetiapine in achieving remission over time and that it “greatly improves patients’ functional impairment” while achieving “generally lower” adverse event rates.
He added that they are currently running a significant number of secondary analyses “to give us a better grasp of which patient benefits most” from esketamine therapy over quetiapine. The results may potentially be used to guide patient selection.
‘Tremendous advance’
Session co-chair Mark Weiser, MD, chairman at the department of psychiatry, Tel Aviv (Israel) University, said in an interview that the results are “very exciting” and offer “further proof of a tremendous advance in our field.”
Dr. Weiser, who was not involved in the study, added that demonstrating functional improvement with esketamine was key.
“It’s great to improve symptoms,” he said, “but to have patients show an improvement in their functionality is really the bottom line of this. Not only do you feel better, but you function better, and that’s of extreme importance and makes us feel very optimistic about the future.”
Josep Antoni Ramos-Quiroga, MD, PhD, head of psychiatry, Vall Hebron University Hospital and Autonomous University of Barcelona, welcomed the findings.
“The results of this study show the superior response and safety of esketamine nasal spray when compared with quetiapine,” he said in a release. “This gives people with treatment-resistant depression more safe treatment options.”
The study was funded by Janssen EMEA. Dr. Reif has relationships with Boehringer Ingelheim, COMPASS, Janssen Pharmaceuticals, LivaNova USA, Medice, Saga Therapeutics, and Shire. Other authors have disclosed numerous relationships with industry.
A version of this article first appeared on Medscape.com.
BARCELONA – (TRD), results of a large, multicenter, head-to-head phase 3 trial show.
Results from the ESCAPE-TRD study, which included 675 participants with TRD, show that esketamine was associated with significantly increased rates of both depression and functional remission, compared with quetiapine.
More than 675 patients were randomly assigned to receive one of the two drugs along with ongoing treatment with an SSRI or a serotonin-norepinephrine reuptake inhibitor (SNRI).
Esketamine increased remission rates at 2 and 8 months over quetiapine by 72% and raised functional remission rates at 8 months by 88% while decreasing adverse event rates.
The findings were presented at the annual meeting of the European College of Neuropsychopharmacology and were published online in the New England Journal of Medicine.
New hope
The results provide “some hope for our patients suffering from TRD, which, given the data, is somewhat of a misnomer,” said study investigator Andreas Reif, MD, professor of psychiatry, psychosomatic medicine, and psychotherapy, University Hospital Frankfurt–Goethe University, Frankfurt am Main, Germany, and president-elect of the ECNP.
“These patients are not resistant, they just have resistance to monoaminergic drugs,” he added. Esketamine, he said, is a “new weapon in our armamentarium.”
Dr. Reif said TRD is a serious condition that affects approximately 20%-30% of those with major depressive disorder and has “substantial impact” on patients’ lives, including quality of life and level of functioning.
“We know that esketamine nasal spray is effective in TRD. However, up to now, there were only placebo-controlled trials in addition to ongoing antidepressant treatment,” Dr. Reif noted. Consequently, he added, a head-to-head comparison with an active agent with proven efficacy was “urgently needed.”
For the trial, patients from 171 sites in 24 countries with TRD, defined as a less than 25% improvement in symptoms with two or more consecutive treatments of adequate dosage and duration, were randomly assigned to receive esketamine nasal spray (n = 336) or quetiapine (n = 340) extended release together with ongoing SSRI or SNRI therapy.
Both esketamine and quetiapine were flexibly dosed. The primary endpoint was rates of remission at week 8 on the Montgomery-Åsberg Depression Rating Scale (MADRS). After week 8, patients entered a maintenance phase that lasted to week 32.
Dr. Reif said the study population was representative of a typical TRD population.
The average duration of the current depression episode was more than 5 years, and the average MADRS score was above 30.
Key findings
Results showed that those who received esketamine in combination with an SSRI or SNRI experienced a significantly higher rate of remission at week 8, compared with those treated with quetiapine (27.1% vs. 17.6%; P = .003). This equated to an adjusted odds ratio for remission of 1.74 (P = .003).
Use of esketamine was also associated with a higher rate of remission at week 8, and patients remained relapse free at week 32 (21.7% vs. 14.1% with quetiapine; odds ratio, 1.72; P = .008).
At every time point through the study, the proportion of patients experiencing remission was significantly greater with esketamine than with quetiapine. The absolute rate of remission at week 32 was 55.0%, versus 37.0% (P < .001).
Dr. Reif noted that the definition of remission used in the study was a MADRS score of less than or equal to 10, but if the “more lenient” definition of less than or equal to 12, which has been used previously, were to be applied, the absolute remission rates would rise to 65.1%, versus 46.7%.
Dr. Reif also presented results on functional remission rates beyond 32 weeks – data that were not included in the study as published in NEJM.
While remission rates increased over time in both study arms, the functional remission rate at week 32 was, again, significantly higher with esketamine than with quetiapine (38.1% vs. 25.0%; OR, 1.88; P < .001).
The safety data revealed no new signals, Dr. Reif said. Use of esketamine was associated with a lower rate of treatment-emergent adverse events that led to treatment discontinuation, at 4.2% vs. 11.0% with quetiapine.
Among patients given the ketamine-derived drug, there were lower rates of nervous system disorders, and there were no incidences of weight gain, fatigue, or hangover.
Dr. Reif said the results show that esketamine nasal spray was superior to quetiapine in achieving remission over time and that it “greatly improves patients’ functional impairment” while achieving “generally lower” adverse event rates.
He added that they are currently running a significant number of secondary analyses “to give us a better grasp of which patient benefits most” from esketamine therapy over quetiapine. The results may potentially be used to guide patient selection.
‘Tremendous advance’
Session co-chair Mark Weiser, MD, chairman at the department of psychiatry, Tel Aviv (Israel) University, said in an interview that the results are “very exciting” and offer “further proof of a tremendous advance in our field.”
Dr. Weiser, who was not involved in the study, added that demonstrating functional improvement with esketamine was key.
“It’s great to improve symptoms,” he said, “but to have patients show an improvement in their functionality is really the bottom line of this. Not only do you feel better, but you function better, and that’s of extreme importance and makes us feel very optimistic about the future.”
Josep Antoni Ramos-Quiroga, MD, PhD, head of psychiatry, Vall Hebron University Hospital and Autonomous University of Barcelona, welcomed the findings.
“The results of this study show the superior response and safety of esketamine nasal spray when compared with quetiapine,” he said in a release. “This gives people with treatment-resistant depression more safe treatment options.”
The study was funded by Janssen EMEA. Dr. Reif has relationships with Boehringer Ingelheim, COMPASS, Janssen Pharmaceuticals, LivaNova USA, Medice, Saga Therapeutics, and Shire. Other authors have disclosed numerous relationships with industry.
A version of this article first appeared on Medscape.com.
AT ECNP 2023
Are they ‘antiobesity medications’ or ‘weight-loss drugs’?
A simple Google search for the terms “weight-loss pens,” “weight-loss drugs,” and “weight-loss medications” displays seven times more results than a search for terms like “antiobesity medications,” “antiobesity drugs,” or “drugs (or medications) to treat obesity.” The same search applied to academic databases yields the opposite results: fewer than 500 results for “weight-loss drugs/agents/medications” and 19,000 results for “antiobesity agents,” for example.
To highlight the importance of the language used to talk about obesity treatment, researchers affiliated with the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Association for the Study of Obesity and Metabolic Syndrome (ABESO) released a statement on the subject at the Brazilian Congress of Update in Endocrinology and Metabolism 2023. On the basis of the study by the ABESO and the SBEM, the statement proposes abandoning the use of the term “weight-loss medications” in scientific publications and, most importantly, in the media.
“Put together, we believe that the common use of the term ‘weight-loss medications’ by media and the public, as well as by doctors and the scientific community, contributes to stigma, and certainly that language matters,” study author Paulo Augusto Carvalho Miranda, MD, PhD, chair of SBEM, said in an interview.
“When we refer to these medications as ‘weight-loss drugs,’ we are using derogatory terms to refer to medications that were extensively studied before their launch onto the market and approved by a regulatory authority to treat a disease called obesity,” said study author Márcio Mancini, MD, PhD, deputy chair of the SBEM’s Obesity Department.
Beyond semantics
Another article published by this news organization presents the initiative of a global task force comprising 60 leaders in the clinical management of obesity, who proposed a new name for the disease. According to the leader of the project, Francesco Rubino, MD, “The word is so stigmatized, with so much misunderstanding and misperception, that some might say the only solution is to change the name.” Following this same logic, the authors of the Brazilian study believe that changing how we refer to medications may improve perceptions of health care professionals and patients toward prevention and treatment strategies for obesity.
According to Dr. Miranda, the first step is “remembering that how we refer to people, diseases, and treatments makes all the difference, especially in situations like obesity, a stigmatized disease loaded with misconceptions. It is not merely an issue of semantics, but also an issue of reducing the stigma surrounding the subject.”
According to Dr. Miranda, the primary purpose of the statement is to highlight the uniqueness of the situation and the importance of encouraging the use of the expressions “antiobesity medications” and “medications to treat obesity” to help reduce the stigma and improve adherence and persistence in obesity treatment.
Impact in practice
The statement also emphasizes that obesity pharmacotherapy is widely underused in patients with obesity and that, in the United States, it is prescribed only for approximately 3% of adults with the disease. Weight management programs for this patient population stress implementing lifestyle changes, and only 1.1% of participants are prescribed medications.
According to the statement, the term “weight-loss medications” contributes to the concept that their use has an aesthetic goal and can be consumed by anyone who desires to lose weight.
In addition to ensuring the correct use of language, Dr. Mancini adds that it is essential for doctors to seek and present pharmacologic treatment for obesity as something that will improve patient health. This means stressing that obesity can be controlled with a 10% loss in body weight, just as other chronic diseases, such as diabetes, can be controlled. Moreover, it is important to point out that medications also have a crucial role in optimizing weight maintenance in the long term.
Another issue Dr. Mancini raised is the prejudice that many doctors have against people with obesity. Health professionals should recognize they are also subject to weight bias and that the way they communicate with patients could have a profound effect on health-related outcomes.
“The stigma surrounding obesity can lead to bullying, even in the patient’s home by their relatives; this is very common. Weight stigma is so strong that it hinders patient health and decreases the likelihood of the patient seeking specialized care,” Dr. Mancini warned.
According to the authors, it is of utmost importance to understand that an individual should not be defined by his or disease (as by the use of the terms “obese” or “diabetic”) but rather understood to live with this disease (“individual with obesity” or “with diabetes”). Dr. Mancini suggests the following strategies that health care professionals can adopt while caring for patients with obesity:
- Speak to patients with empathy and respect, avoiding the use of judgmental words.
- Ask if they would like to discuss the “weight issue,” “BMI issue,” terms that are better received by the public, instead of saying “excess fat” or “excess weight.”
- If the patient agrees to talk about the subject, reinforce that this is a chronic health problem that requires longterm treatment and give him or her short, medium, and longterm options.
Lastly, the authors highlighted the importance of differentiating between regulatory agency–approved medications and over-the-counter drugs and supplements that are often sold as “weight-loss agents” and are responsible for an unacceptably high rate of emergency visits.
This article was translated from the Medscape Portuguese Edition. A version appeared on Medscape.com.
A simple Google search for the terms “weight-loss pens,” “weight-loss drugs,” and “weight-loss medications” displays seven times more results than a search for terms like “antiobesity medications,” “antiobesity drugs,” or “drugs (or medications) to treat obesity.” The same search applied to academic databases yields the opposite results: fewer than 500 results for “weight-loss drugs/agents/medications” and 19,000 results for “antiobesity agents,” for example.
To highlight the importance of the language used to talk about obesity treatment, researchers affiliated with the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Association for the Study of Obesity and Metabolic Syndrome (ABESO) released a statement on the subject at the Brazilian Congress of Update in Endocrinology and Metabolism 2023. On the basis of the study by the ABESO and the SBEM, the statement proposes abandoning the use of the term “weight-loss medications” in scientific publications and, most importantly, in the media.
“Put together, we believe that the common use of the term ‘weight-loss medications’ by media and the public, as well as by doctors and the scientific community, contributes to stigma, and certainly that language matters,” study author Paulo Augusto Carvalho Miranda, MD, PhD, chair of SBEM, said in an interview.
“When we refer to these medications as ‘weight-loss drugs,’ we are using derogatory terms to refer to medications that were extensively studied before their launch onto the market and approved by a regulatory authority to treat a disease called obesity,” said study author Márcio Mancini, MD, PhD, deputy chair of the SBEM’s Obesity Department.
Beyond semantics
Another article published by this news organization presents the initiative of a global task force comprising 60 leaders in the clinical management of obesity, who proposed a new name for the disease. According to the leader of the project, Francesco Rubino, MD, “The word is so stigmatized, with so much misunderstanding and misperception, that some might say the only solution is to change the name.” Following this same logic, the authors of the Brazilian study believe that changing how we refer to medications may improve perceptions of health care professionals and patients toward prevention and treatment strategies for obesity.
According to Dr. Miranda, the first step is “remembering that how we refer to people, diseases, and treatments makes all the difference, especially in situations like obesity, a stigmatized disease loaded with misconceptions. It is not merely an issue of semantics, but also an issue of reducing the stigma surrounding the subject.”
According to Dr. Miranda, the primary purpose of the statement is to highlight the uniqueness of the situation and the importance of encouraging the use of the expressions “antiobesity medications” and “medications to treat obesity” to help reduce the stigma and improve adherence and persistence in obesity treatment.
Impact in practice
The statement also emphasizes that obesity pharmacotherapy is widely underused in patients with obesity and that, in the United States, it is prescribed only for approximately 3% of adults with the disease. Weight management programs for this patient population stress implementing lifestyle changes, and only 1.1% of participants are prescribed medications.
According to the statement, the term “weight-loss medications” contributes to the concept that their use has an aesthetic goal and can be consumed by anyone who desires to lose weight.
In addition to ensuring the correct use of language, Dr. Mancini adds that it is essential for doctors to seek and present pharmacologic treatment for obesity as something that will improve patient health. This means stressing that obesity can be controlled with a 10% loss in body weight, just as other chronic diseases, such as diabetes, can be controlled. Moreover, it is important to point out that medications also have a crucial role in optimizing weight maintenance in the long term.
Another issue Dr. Mancini raised is the prejudice that many doctors have against people with obesity. Health professionals should recognize they are also subject to weight bias and that the way they communicate with patients could have a profound effect on health-related outcomes.
“The stigma surrounding obesity can lead to bullying, even in the patient’s home by their relatives; this is very common. Weight stigma is so strong that it hinders patient health and decreases the likelihood of the patient seeking specialized care,” Dr. Mancini warned.
According to the authors, it is of utmost importance to understand that an individual should not be defined by his or disease (as by the use of the terms “obese” or “diabetic”) but rather understood to live with this disease (“individual with obesity” or “with diabetes”). Dr. Mancini suggests the following strategies that health care professionals can adopt while caring for patients with obesity:
- Speak to patients with empathy and respect, avoiding the use of judgmental words.
- Ask if they would like to discuss the “weight issue,” “BMI issue,” terms that are better received by the public, instead of saying “excess fat” or “excess weight.”
- If the patient agrees to talk about the subject, reinforce that this is a chronic health problem that requires longterm treatment and give him or her short, medium, and longterm options.
Lastly, the authors highlighted the importance of differentiating between regulatory agency–approved medications and over-the-counter drugs and supplements that are often sold as “weight-loss agents” and are responsible for an unacceptably high rate of emergency visits.
This article was translated from the Medscape Portuguese Edition. A version appeared on Medscape.com.
A simple Google search for the terms “weight-loss pens,” “weight-loss drugs,” and “weight-loss medications” displays seven times more results than a search for terms like “antiobesity medications,” “antiobesity drugs,” or “drugs (or medications) to treat obesity.” The same search applied to academic databases yields the opposite results: fewer than 500 results for “weight-loss drugs/agents/medications” and 19,000 results for “antiobesity agents,” for example.
To highlight the importance of the language used to talk about obesity treatment, researchers affiliated with the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Association for the Study of Obesity and Metabolic Syndrome (ABESO) released a statement on the subject at the Brazilian Congress of Update in Endocrinology and Metabolism 2023. On the basis of the study by the ABESO and the SBEM, the statement proposes abandoning the use of the term “weight-loss medications” in scientific publications and, most importantly, in the media.
“Put together, we believe that the common use of the term ‘weight-loss medications’ by media and the public, as well as by doctors and the scientific community, contributes to stigma, and certainly that language matters,” study author Paulo Augusto Carvalho Miranda, MD, PhD, chair of SBEM, said in an interview.
“When we refer to these medications as ‘weight-loss drugs,’ we are using derogatory terms to refer to medications that were extensively studied before their launch onto the market and approved by a regulatory authority to treat a disease called obesity,” said study author Márcio Mancini, MD, PhD, deputy chair of the SBEM’s Obesity Department.
Beyond semantics
Another article published by this news organization presents the initiative of a global task force comprising 60 leaders in the clinical management of obesity, who proposed a new name for the disease. According to the leader of the project, Francesco Rubino, MD, “The word is so stigmatized, with so much misunderstanding and misperception, that some might say the only solution is to change the name.” Following this same logic, the authors of the Brazilian study believe that changing how we refer to medications may improve perceptions of health care professionals and patients toward prevention and treatment strategies for obesity.
According to Dr. Miranda, the first step is “remembering that how we refer to people, diseases, and treatments makes all the difference, especially in situations like obesity, a stigmatized disease loaded with misconceptions. It is not merely an issue of semantics, but also an issue of reducing the stigma surrounding the subject.”
According to Dr. Miranda, the primary purpose of the statement is to highlight the uniqueness of the situation and the importance of encouraging the use of the expressions “antiobesity medications” and “medications to treat obesity” to help reduce the stigma and improve adherence and persistence in obesity treatment.
Impact in practice
The statement also emphasizes that obesity pharmacotherapy is widely underused in patients with obesity and that, in the United States, it is prescribed only for approximately 3% of adults with the disease. Weight management programs for this patient population stress implementing lifestyle changes, and only 1.1% of participants are prescribed medications.
According to the statement, the term “weight-loss medications” contributes to the concept that their use has an aesthetic goal and can be consumed by anyone who desires to lose weight.
In addition to ensuring the correct use of language, Dr. Mancini adds that it is essential for doctors to seek and present pharmacologic treatment for obesity as something that will improve patient health. This means stressing that obesity can be controlled with a 10% loss in body weight, just as other chronic diseases, such as diabetes, can be controlled. Moreover, it is important to point out that medications also have a crucial role in optimizing weight maintenance in the long term.
Another issue Dr. Mancini raised is the prejudice that many doctors have against people with obesity. Health professionals should recognize they are also subject to weight bias and that the way they communicate with patients could have a profound effect on health-related outcomes.
“The stigma surrounding obesity can lead to bullying, even in the patient’s home by their relatives; this is very common. Weight stigma is so strong that it hinders patient health and decreases the likelihood of the patient seeking specialized care,” Dr. Mancini warned.
According to the authors, it is of utmost importance to understand that an individual should not be defined by his or disease (as by the use of the terms “obese” or “diabetic”) but rather understood to live with this disease (“individual with obesity” or “with diabetes”). Dr. Mancini suggests the following strategies that health care professionals can adopt while caring for patients with obesity:
- Speak to patients with empathy and respect, avoiding the use of judgmental words.
- Ask if they would like to discuss the “weight issue,” “BMI issue,” terms that are better received by the public, instead of saying “excess fat” or “excess weight.”
- If the patient agrees to talk about the subject, reinforce that this is a chronic health problem that requires longterm treatment and give him or her short, medium, and longterm options.
Lastly, the authors highlighted the importance of differentiating between regulatory agency–approved medications and over-the-counter drugs and supplements that are often sold as “weight-loss agents” and are responsible for an unacceptably high rate of emergency visits.
This article was translated from the Medscape Portuguese Edition. A version appeared on Medscape.com.
Nonsurgical option for more large thyroid nodule patients?
WASHINGTON – , compared with only those that were.
While more research is needed, “the risk of false negative FNA results for large nodules may not be as high as reported in previous studies if you include patients who do not have indication for surgery, such as compressive symptoms, suspicious ultrasound features, etc.,” senior author Tracy Tylee, MD, an associate professor of endocrinology at the University of Washington, Seattle, said in an interview.
The implication is that nonsurgical options such as radiofrequency ablation may be appropriate for more patients than realized, she added.
“Clinicians should consider following these patients more conservatively, either with a second FNA to confirm [the] nodule is benign or with ultrasound follow-up for 5 years with intervention only if [there are] significant changes on imaging,” she said.
The findings were presented at the annual meeting of the American Thyroid Association.
Concerns about nodules over 4 cm having high false negative rates
Management of large thyroid nodules over 4 cm that are classified as Bethesda II, indicative of being benign, is complicated by concerns of false negatives in such cases. While the false negative rate for thyroid nodules in general is approximately 3%, the rate for large nodules over 4 cm has been reported as high as 35%.
Importantly, however, most studies evaluating the issue only involve patients who have received thyroid surgery, whereas most benign nodules are not referred for surgery.
“This may overestimate the false negative FNA biopsy risk for this group,” first author Melbin Thomas, MD, also of the University of Washington, said in her talk.
To better assess the false negative rate in the broader context of large nodules that did and did not undergo surgery, Dr. Thomas and her colleagues conducted a retrospective chart review of all patients undergoing FNA biopsy at her center between 2008 and 2014 for thyroid nodules larger than 4 cm and initially classified as Bethesda II, or benign.
With a follow-up of up to 10 years, nodules were considered accurately benign if they showed benign pathology on surgical resection, if they remained benign based on repeat FNA biopsy with Bethesda II results, or if there were no changes on imaging characteristics on ultrasound after at least 2 years.
Overall, 47 nodules over 4 cm and Bethesda II cytology were included, with an average follow-up of 5 years (range 2.2-9.7 years).
Of the nodules, 23 were treated with surgery, two of which were determined to have been malignant (8.7%) and, hence, false negatives. Nine of the nodules had repeat FNA, with none found to be malignant, and 15 received repeat ultrasound, also with no malignancies.
Overall, the false negative rate including all patients was 4.3%.
“False negative FNA biopsy results were not markedly elevated if nodules greater than 4 cm are evaluated, but rates were considerably higher if limited to surgical patients,” Dr. Thomas said.
Clinicians may be compelled to perform more aggressive surgery on large but benign thyroid nodules for a number of reasons, Dr. Tylee noted.
“A concern is that we may discontinue follow-up on these larger nodules and fail to diagnose a cancer early on, before there has been extrathyroidal extension or lymph node metastases,” she said.
In such cases, patients could wind up presenting at a higher stage of disease and require more intensive therapy.
However, with a low false negative rate overall, “all of this can increase the long-term health care costs and anxiety for patients, so having a better understanding of the true benign rate for large nodules is important,” she concluded.
Commenting on the research, Rodis D. Paparodis, MD, chief of Endocrinology, Diabetes, and Metabolism Clinics, in Patras, Greece, said the findings underscore that, as a surgical procedure, “thyroidectomy should be used cautiously, only when the benefit outweighs the risk.”
In his own previous multicenter study, Dr. Paparodis conducted a review of nearly 2,500 thyroidectomies that were performed based on size or longterm slow growth despite preoperative benign FNA findings. The results showed that only 1.9% of patients had any form of thyroid cancer in the nodule that had led to surgery; however, multiple other significant cancers were often present in other locations in the gland.
“Therefore, we suggest that careful sonographic evaluation of all thyroid nodules is warranted prior to deciding and planning the extent of surgical management for multinodular goiter,” he told this news organization.
“In addition, FNA of all suspicious nodules is required as well, to avoid unnecessary surprises in surgical pathology.”
Dr. Tylee, Dr. Thomas, and Dr. Paparodis report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
WASHINGTON – , compared with only those that were.
While more research is needed, “the risk of false negative FNA results for large nodules may not be as high as reported in previous studies if you include patients who do not have indication for surgery, such as compressive symptoms, suspicious ultrasound features, etc.,” senior author Tracy Tylee, MD, an associate professor of endocrinology at the University of Washington, Seattle, said in an interview.
The implication is that nonsurgical options such as radiofrequency ablation may be appropriate for more patients than realized, she added.
“Clinicians should consider following these patients more conservatively, either with a second FNA to confirm [the] nodule is benign or with ultrasound follow-up for 5 years with intervention only if [there are] significant changes on imaging,” she said.
The findings were presented at the annual meeting of the American Thyroid Association.
Concerns about nodules over 4 cm having high false negative rates
Management of large thyroid nodules over 4 cm that are classified as Bethesda II, indicative of being benign, is complicated by concerns of false negatives in such cases. While the false negative rate for thyroid nodules in general is approximately 3%, the rate for large nodules over 4 cm has been reported as high as 35%.
Importantly, however, most studies evaluating the issue only involve patients who have received thyroid surgery, whereas most benign nodules are not referred for surgery.
“This may overestimate the false negative FNA biopsy risk for this group,” first author Melbin Thomas, MD, also of the University of Washington, said in her talk.
To better assess the false negative rate in the broader context of large nodules that did and did not undergo surgery, Dr. Thomas and her colleagues conducted a retrospective chart review of all patients undergoing FNA biopsy at her center between 2008 and 2014 for thyroid nodules larger than 4 cm and initially classified as Bethesda II, or benign.
With a follow-up of up to 10 years, nodules were considered accurately benign if they showed benign pathology on surgical resection, if they remained benign based on repeat FNA biopsy with Bethesda II results, or if there were no changes on imaging characteristics on ultrasound after at least 2 years.
Overall, 47 nodules over 4 cm and Bethesda II cytology were included, with an average follow-up of 5 years (range 2.2-9.7 years).
Of the nodules, 23 were treated with surgery, two of which were determined to have been malignant (8.7%) and, hence, false negatives. Nine of the nodules had repeat FNA, with none found to be malignant, and 15 received repeat ultrasound, also with no malignancies.
Overall, the false negative rate including all patients was 4.3%.
“False negative FNA biopsy results were not markedly elevated if nodules greater than 4 cm are evaluated, but rates were considerably higher if limited to surgical patients,” Dr. Thomas said.
Clinicians may be compelled to perform more aggressive surgery on large but benign thyroid nodules for a number of reasons, Dr. Tylee noted.
“A concern is that we may discontinue follow-up on these larger nodules and fail to diagnose a cancer early on, before there has been extrathyroidal extension or lymph node metastases,” she said.
In such cases, patients could wind up presenting at a higher stage of disease and require more intensive therapy.
However, with a low false negative rate overall, “all of this can increase the long-term health care costs and anxiety for patients, so having a better understanding of the true benign rate for large nodules is important,” she concluded.
Commenting on the research, Rodis D. Paparodis, MD, chief of Endocrinology, Diabetes, and Metabolism Clinics, in Patras, Greece, said the findings underscore that, as a surgical procedure, “thyroidectomy should be used cautiously, only when the benefit outweighs the risk.”
In his own previous multicenter study, Dr. Paparodis conducted a review of nearly 2,500 thyroidectomies that were performed based on size or longterm slow growth despite preoperative benign FNA findings. The results showed that only 1.9% of patients had any form of thyroid cancer in the nodule that had led to surgery; however, multiple other significant cancers were often present in other locations in the gland.
“Therefore, we suggest that careful sonographic evaluation of all thyroid nodules is warranted prior to deciding and planning the extent of surgical management for multinodular goiter,” he told this news organization.
“In addition, FNA of all suspicious nodules is required as well, to avoid unnecessary surprises in surgical pathology.”
Dr. Tylee, Dr. Thomas, and Dr. Paparodis report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
WASHINGTON – , compared with only those that were.
While more research is needed, “the risk of false negative FNA results for large nodules may not be as high as reported in previous studies if you include patients who do not have indication for surgery, such as compressive symptoms, suspicious ultrasound features, etc.,” senior author Tracy Tylee, MD, an associate professor of endocrinology at the University of Washington, Seattle, said in an interview.
The implication is that nonsurgical options such as radiofrequency ablation may be appropriate for more patients than realized, she added.
“Clinicians should consider following these patients more conservatively, either with a second FNA to confirm [the] nodule is benign or with ultrasound follow-up for 5 years with intervention only if [there are] significant changes on imaging,” she said.
The findings were presented at the annual meeting of the American Thyroid Association.
Concerns about nodules over 4 cm having high false negative rates
Management of large thyroid nodules over 4 cm that are classified as Bethesda II, indicative of being benign, is complicated by concerns of false negatives in such cases. While the false negative rate for thyroid nodules in general is approximately 3%, the rate for large nodules over 4 cm has been reported as high as 35%.
Importantly, however, most studies evaluating the issue only involve patients who have received thyroid surgery, whereas most benign nodules are not referred for surgery.
“This may overestimate the false negative FNA biopsy risk for this group,” first author Melbin Thomas, MD, also of the University of Washington, said in her talk.
To better assess the false negative rate in the broader context of large nodules that did and did not undergo surgery, Dr. Thomas and her colleagues conducted a retrospective chart review of all patients undergoing FNA biopsy at her center between 2008 and 2014 for thyroid nodules larger than 4 cm and initially classified as Bethesda II, or benign.
With a follow-up of up to 10 years, nodules were considered accurately benign if they showed benign pathology on surgical resection, if they remained benign based on repeat FNA biopsy with Bethesda II results, or if there were no changes on imaging characteristics on ultrasound after at least 2 years.
Overall, 47 nodules over 4 cm and Bethesda II cytology were included, with an average follow-up of 5 years (range 2.2-9.7 years).
Of the nodules, 23 were treated with surgery, two of which were determined to have been malignant (8.7%) and, hence, false negatives. Nine of the nodules had repeat FNA, with none found to be malignant, and 15 received repeat ultrasound, also with no malignancies.
Overall, the false negative rate including all patients was 4.3%.
“False negative FNA biopsy results were not markedly elevated if nodules greater than 4 cm are evaluated, but rates were considerably higher if limited to surgical patients,” Dr. Thomas said.
Clinicians may be compelled to perform more aggressive surgery on large but benign thyroid nodules for a number of reasons, Dr. Tylee noted.
“A concern is that we may discontinue follow-up on these larger nodules and fail to diagnose a cancer early on, before there has been extrathyroidal extension or lymph node metastases,” she said.
In such cases, patients could wind up presenting at a higher stage of disease and require more intensive therapy.
However, with a low false negative rate overall, “all of this can increase the long-term health care costs and anxiety for patients, so having a better understanding of the true benign rate for large nodules is important,” she concluded.
Commenting on the research, Rodis D. Paparodis, MD, chief of Endocrinology, Diabetes, and Metabolism Clinics, in Patras, Greece, said the findings underscore that, as a surgical procedure, “thyroidectomy should be used cautiously, only when the benefit outweighs the risk.”
In his own previous multicenter study, Dr. Paparodis conducted a review of nearly 2,500 thyroidectomies that were performed based on size or longterm slow growth despite preoperative benign FNA findings. The results showed that only 1.9% of patients had any form of thyroid cancer in the nodule that had led to surgery; however, multiple other significant cancers were often present in other locations in the gland.
“Therefore, we suggest that careful sonographic evaluation of all thyroid nodules is warranted prior to deciding and planning the extent of surgical management for multinodular goiter,” he told this news organization.
“In addition, FNA of all suspicious nodules is required as well, to avoid unnecessary surprises in surgical pathology.”
Dr. Tylee, Dr. Thomas, and Dr. Paparodis report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ATA 2023
Biologics linked to fewer hospitalizations after asthma exacerbation
In a real-world study of asthma patients,
The data fill a gap, according to Sushan Gupta, MD, who presented the results at the annual meeting of the American College of Chest Physicians. “There’s some ample real-world data that shows that biologics reduce the incidence of asthma exacerbation, but the data regarding what happens after an exacerbation is still lacking, especially real-world data,” said Dr. Gupta, who is a resident at Carle Foundation Hospital in Champaign, Ill.
The findings were encouraging. “Patients with severe asthma on biologics fare well even after an exacerbation event, which includes a reduced incidence of hospitalization, ICU admission, and need for mechanical ventilation. We did not have any patient in the biologic group that required intubation, so that is pretty significant as compared to other patients who did not receive biologics,” said Dr. Gupta.
The results weren’t surprising, but underscore the benefits of biologics, according to Brittany Duchene, MD, who moderated the session where the results were presented. “I think it reinforced that they’re really good drugs,” said Dr. Duchene, who is a pulmonary critical care physician at Northeastern Vermont Regional Hospital, St. Johnsbury.
Although the study was retrospective, it suggests that the threshold for initiating biologics could potentially be lowered for patients with uncontrolled asthma despite adequate use of inhalers, according to Dr. Gupta. “Should that threshold be lower, and would that improve the overall morbidity and eventually the health care cost of utilization? Our study does not prove any of those data, but moving forward that data will also come out.”
Dr. Duchene noted that the accumulating scientific and clinical data for biologics is “really, really strong.” She also speculated that biologics could be used increasingly in the acute setting, which she admitted is a controversial topic. “I think there’s going to be a lot more push to early initiation, and you can see from the [new] study that it decreased a lot of hospitalizations.”
Dr. Gupta emphasized the need for prospective studies, and Dr. Duchene agreed that any such change would need to be patient centric, considering the diversity of available biologics. “It depends what their true issue is. The broader the biologic [mechanism of action], probably the more success you’ll have. I’ve found there’s not a pure allergic or a pure eosinophilic asthma patient. They’re usually more a combination.”
Some key questions remain about biologics treatment, especially in the long term. These include when a patient should be switched from one biologic to another, and whether biologic treatment should be continued over the patient’s lifetime and potential long-term side effects. “I think that data is still evolving and will come to us with time,” said Dr. Gupta.
The researchers analyzed retrospective data from 316 asthma patients treated with biologics and 9,645 treated with nonbiologic therapy between February 2018 and February 2023 at a tertiary care teaching hospital in the Midwest. There was a higher proportion of females in the biologics (69.7%) and nonbiologics groups (63.8%, P = .032), but there was no significant difference in the proportion of Whites in the biologics and nonbiologics groups (78.2% vs. 74.3%, P = .103).
The lack of a difference in racial groups was a surprise, according to Dr. Duchene, especially since other studies have noted disparities in biologic therapy among asthma patients.
Among the biologics group, 0.9% were hospitalized during the study period, compared with 6.5% of the nonbiologics group (P = .00006). They also had fewer ICU visits (0.3% vs. 1.8%; P = .04).
Dr. Gupta’s team attempted to subdivide the data by individual biologic, but there was no statistical significance in outcomes between biologics, perhaps because of the relatively small sample size.
Dr. Gupta noted that his group’s results are generally similar to other studies, including a U.S. study that found a decrease in exacerbation rates after staring or switching biologics and a slightly higher prevalence of biologics use among White patients (77% of biologic users versus 71% of nonbiologics users). A study in southwestern England found fewer ED visits and hospitalizations among patients on biologics.
Dr. Gupta and Dr. Duchene have no relevant financial disclosures.
In a real-world study of asthma patients,
The data fill a gap, according to Sushan Gupta, MD, who presented the results at the annual meeting of the American College of Chest Physicians. “There’s some ample real-world data that shows that biologics reduce the incidence of asthma exacerbation, but the data regarding what happens after an exacerbation is still lacking, especially real-world data,” said Dr. Gupta, who is a resident at Carle Foundation Hospital in Champaign, Ill.
The findings were encouraging. “Patients with severe asthma on biologics fare well even after an exacerbation event, which includes a reduced incidence of hospitalization, ICU admission, and need for mechanical ventilation. We did not have any patient in the biologic group that required intubation, so that is pretty significant as compared to other patients who did not receive biologics,” said Dr. Gupta.
The results weren’t surprising, but underscore the benefits of biologics, according to Brittany Duchene, MD, who moderated the session where the results were presented. “I think it reinforced that they’re really good drugs,” said Dr. Duchene, who is a pulmonary critical care physician at Northeastern Vermont Regional Hospital, St. Johnsbury.
Although the study was retrospective, it suggests that the threshold for initiating biologics could potentially be lowered for patients with uncontrolled asthma despite adequate use of inhalers, according to Dr. Gupta. “Should that threshold be lower, and would that improve the overall morbidity and eventually the health care cost of utilization? Our study does not prove any of those data, but moving forward that data will also come out.”
Dr. Duchene noted that the accumulating scientific and clinical data for biologics is “really, really strong.” She also speculated that biologics could be used increasingly in the acute setting, which she admitted is a controversial topic. “I think there’s going to be a lot more push to early initiation, and you can see from the [new] study that it decreased a lot of hospitalizations.”
Dr. Gupta emphasized the need for prospective studies, and Dr. Duchene agreed that any such change would need to be patient centric, considering the diversity of available biologics. “It depends what their true issue is. The broader the biologic [mechanism of action], probably the more success you’ll have. I’ve found there’s not a pure allergic or a pure eosinophilic asthma patient. They’re usually more a combination.”
Some key questions remain about biologics treatment, especially in the long term. These include when a patient should be switched from one biologic to another, and whether biologic treatment should be continued over the patient’s lifetime and potential long-term side effects. “I think that data is still evolving and will come to us with time,” said Dr. Gupta.
The researchers analyzed retrospective data from 316 asthma patients treated with biologics and 9,645 treated with nonbiologic therapy between February 2018 and February 2023 at a tertiary care teaching hospital in the Midwest. There was a higher proportion of females in the biologics (69.7%) and nonbiologics groups (63.8%, P = .032), but there was no significant difference in the proportion of Whites in the biologics and nonbiologics groups (78.2% vs. 74.3%, P = .103).
The lack of a difference in racial groups was a surprise, according to Dr. Duchene, especially since other studies have noted disparities in biologic therapy among asthma patients.
Among the biologics group, 0.9% were hospitalized during the study period, compared with 6.5% of the nonbiologics group (P = .00006). They also had fewer ICU visits (0.3% vs. 1.8%; P = .04).
Dr. Gupta’s team attempted to subdivide the data by individual biologic, but there was no statistical significance in outcomes between biologics, perhaps because of the relatively small sample size.
Dr. Gupta noted that his group’s results are generally similar to other studies, including a U.S. study that found a decrease in exacerbation rates after staring or switching biologics and a slightly higher prevalence of biologics use among White patients (77% of biologic users versus 71% of nonbiologics users). A study in southwestern England found fewer ED visits and hospitalizations among patients on biologics.
Dr. Gupta and Dr. Duchene have no relevant financial disclosures.
In a real-world study of asthma patients,
The data fill a gap, according to Sushan Gupta, MD, who presented the results at the annual meeting of the American College of Chest Physicians. “There’s some ample real-world data that shows that biologics reduce the incidence of asthma exacerbation, but the data regarding what happens after an exacerbation is still lacking, especially real-world data,” said Dr. Gupta, who is a resident at Carle Foundation Hospital in Champaign, Ill.
The findings were encouraging. “Patients with severe asthma on biologics fare well even after an exacerbation event, which includes a reduced incidence of hospitalization, ICU admission, and need for mechanical ventilation. We did not have any patient in the biologic group that required intubation, so that is pretty significant as compared to other patients who did not receive biologics,” said Dr. Gupta.
The results weren’t surprising, but underscore the benefits of biologics, according to Brittany Duchene, MD, who moderated the session where the results were presented. “I think it reinforced that they’re really good drugs,” said Dr. Duchene, who is a pulmonary critical care physician at Northeastern Vermont Regional Hospital, St. Johnsbury.
Although the study was retrospective, it suggests that the threshold for initiating biologics could potentially be lowered for patients with uncontrolled asthma despite adequate use of inhalers, according to Dr. Gupta. “Should that threshold be lower, and would that improve the overall morbidity and eventually the health care cost of utilization? Our study does not prove any of those data, but moving forward that data will also come out.”
Dr. Duchene noted that the accumulating scientific and clinical data for biologics is “really, really strong.” She also speculated that biologics could be used increasingly in the acute setting, which she admitted is a controversial topic. “I think there’s going to be a lot more push to early initiation, and you can see from the [new] study that it decreased a lot of hospitalizations.”
Dr. Gupta emphasized the need for prospective studies, and Dr. Duchene agreed that any such change would need to be patient centric, considering the diversity of available biologics. “It depends what their true issue is. The broader the biologic [mechanism of action], probably the more success you’ll have. I’ve found there’s not a pure allergic or a pure eosinophilic asthma patient. They’re usually more a combination.”
Some key questions remain about biologics treatment, especially in the long term. These include when a patient should be switched from one biologic to another, and whether biologic treatment should be continued over the patient’s lifetime and potential long-term side effects. “I think that data is still evolving and will come to us with time,” said Dr. Gupta.
The researchers analyzed retrospective data from 316 asthma patients treated with biologics and 9,645 treated with nonbiologic therapy between February 2018 and February 2023 at a tertiary care teaching hospital in the Midwest. There was a higher proportion of females in the biologics (69.7%) and nonbiologics groups (63.8%, P = .032), but there was no significant difference in the proportion of Whites in the biologics and nonbiologics groups (78.2% vs. 74.3%, P = .103).
The lack of a difference in racial groups was a surprise, according to Dr. Duchene, especially since other studies have noted disparities in biologic therapy among asthma patients.
Among the biologics group, 0.9% were hospitalized during the study period, compared with 6.5% of the nonbiologics group (P = .00006). They also had fewer ICU visits (0.3% vs. 1.8%; P = .04).
Dr. Gupta’s team attempted to subdivide the data by individual biologic, but there was no statistical significance in outcomes between biologics, perhaps because of the relatively small sample size.
Dr. Gupta noted that his group’s results are generally similar to other studies, including a U.S. study that found a decrease in exacerbation rates after staring or switching biologics and a slightly higher prevalence of biologics use among White patients (77% of biologic users versus 71% of nonbiologics users). A study in southwestern England found fewer ED visits and hospitalizations among patients on biologics.
Dr. Gupta and Dr. Duchene have no relevant financial disclosures.
FROM CHEST 2023
Running vs. meds for depression: Is there a clear winner?
BARCELONA – However, running provides greater physical health benefits while adherence is greater with drug treatment.
“Both interventions helped with the depression to around the same extent,” study presenter Brenda W.J.H. Penninx, PhD, professor of psychiatric epidemiology at the VU University Medical Center in Amsterdam said in a release.
However, medication “generally had worse impact on body weight, heart rate variability, and blood pressure, whereas running therapy led to improved effect on general fitness and heart rate,” Dr. Penninx added.
The findings were presented at the annual congress of the European College of Neuropsychopharmacology and recently published in the Journal of Affective Disorders.
Research gap
Previous research suggests exercise interventions can have a therapeutic effect equivalent to antidepressants, but their impact on physical health has been “poorly examined in a psychiatric population, the investigators note.
The authors note that depressive and anxiety disorders “cause immense suffering by compromising both mental and physical health,” and the need for effective treatments is “pressing.”
Although antidepressant medication is considered a “standard first-line treatment” alongside psychotherapy, the drugs are “not effective for all and [are] often associated with side effects.”
The Mood Treatment with Antidepressant or Running (MOTAR) study was a partially randomized pragmatic trial in adults with depression and/or anxiety disorder, as determined using the DSM-IV algorithms with the Composite International Diagnostic Interview (CIDI).
The 16-week intervention study included 141 patients with depression and/or anxiety. The mean age was 38.2 years and 58% were women. Participants were offered a choice of treatment: 16 weeks of treatment with the selective serotonin reuptake inhibitor (SSRI) escitalopram (Lexapro) or a 16-week group-based running therapy.
Patients without a strong preference for treatment allocation were randomly assigned to either antidepressant medication or running therapy, while those unwilling to be randomized were allocated to their preferred intervention.
A total of 22 patients were randomly assigned to receive antidepressant treatment and 13 to running therapy. A total of 36 participants chose antidepressant treatment, while 83 chose the running therapy.
Running therapy involved 16 weeks of supervised 45-minute outdoor running sessions to a target of two to three sessions per week, in line with U.S. Centers for Disease Control and Prevention/American College of Sports Medicine recommendations.
Physical health benefits
Treatment adherence in the antidepressant group, defined as still using treatment at the posttreatment assessment, was 82.2% vs. 52.1% among running therapy participants, where adherence was specified as completing more than 22 sessions.
Remission was defined as no longer meeting the criteria of a current depressive or anxiety disorder via CIDI at week 16.
On intention-to-treat analysis, this requirement was met by 44.8% of patients taking antidepressants and 43.3% of those in the running therapy group (P = .88).
However, running therapy patients showed significant improvements in weight (P = .001), waist circumference (P = .011), systolic and diastolic blood pressure (P = .011 and P = .002, respectively), heart rate (P = .033), and heart rate variability (P = .006).
The investigators note the more favorable physical health changes in the running therapy group were attributable to “larger improvements in the running therapy group but also due to larger deterioration in the antidepressant group.”
Antidepressants are generally safe and effective and work for most people, said Dr. Penninx. She also noted that untreated depression leads to worse outcomes, so “antidepressants are generally a good choice.”
Nevertheless, she said, “we need to extend our treatment arsenal as not all patients respond to antidepressants or are willing to take them.”
The study’s results, she added, suggest that “implementing exercise therapy is something we should take much more seriously, as it could be a good, and maybe even better, choice for some of our patients.”
Francesca Cirulli, PhD, senior researcher and group leader at the National Institute of Health, Rome, said in an interview that the study is notable because it is one of the first to prospectively measure the effects of antidepressants and running on physical health.
Dr. Cirulli suggested that running therapy could be tried ahead of treatment with antidepressants if patients prefer physical exercise and can adhere to it. However, she said, the findings also suggest that an increase in physical activity should accompany treatment with antidepressant medications.
Overall, Dr. Cirulli said “the message should not be that everyone can be helped by running and antidepressants are bad,” but rather “these are both helpful, but not excellent, interventions against depression.”
‘Important limitations’
In a comment, Eduard Vieta, MD, PhD, chair of the department of psychiatry and psychology at the University of Barcelona Hospital Clinic, noted the study has “very important limitations.”
Among the limitations: the inclusion of nonrandomized patients who received the treatment of their choice, causing obvious bias and the “lack of binding and power issues” over the number of patients enrolled.
Dr. Vieta also said that the results “seem obvious, because it is known that exercise improves physical health.”
The trial therefore shows, “if you can find people who are able to do exercise while depressed and adhere to it, those would benefit from that practice,” he noted.
Also commenting on the research, Eric Ruhe, MD, PhD, Radboud University Medical Center, Nijmegen, the Netherlands, said the results are confirmatory and “again show physical health can influence mental health.”
However, Dr. Ruhe underlined, while it is “common practice” to allow patients to follow their treatment preference and is “understandable from a pragmatic point of view,” the group comparison may be “biased,” compared with a “truly randomized study.”
“For example, patients in the antidepressant group were more depressed, which might be associated with less chance of persisting engagement in the exercises,” he said. “So, we have to be careful not to overinterpret the comparisons between groups, which the authors acknowledge properly.”
Turning to the difference in adherence between the two interventions, Dr. Ruhe said the results show adopting, and adhering to, a lifestyle habit is more difficult than taking a pill.
“This is not exclusively found in psychiatry, indicating that we also have to focus on how to improve compliance to healthy behavior. This could have tremendous impact on health care more generally, but also on psychiatric diseases,” Dr. Ruhe said.
The MOTAR study was funded by a NWO-VICI grant. Funding for the inflammatory markers was provided by ZonMw: The Netherlands Organization for Health Research and Development. The study authors and clinicians interviewed for this story declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BARCELONA – However, running provides greater physical health benefits while adherence is greater with drug treatment.
“Both interventions helped with the depression to around the same extent,” study presenter Brenda W.J.H. Penninx, PhD, professor of psychiatric epidemiology at the VU University Medical Center in Amsterdam said in a release.
However, medication “generally had worse impact on body weight, heart rate variability, and blood pressure, whereas running therapy led to improved effect on general fitness and heart rate,” Dr. Penninx added.
The findings were presented at the annual congress of the European College of Neuropsychopharmacology and recently published in the Journal of Affective Disorders.
Research gap
Previous research suggests exercise interventions can have a therapeutic effect equivalent to antidepressants, but their impact on physical health has been “poorly examined in a psychiatric population, the investigators note.
The authors note that depressive and anxiety disorders “cause immense suffering by compromising both mental and physical health,” and the need for effective treatments is “pressing.”
Although antidepressant medication is considered a “standard first-line treatment” alongside psychotherapy, the drugs are “not effective for all and [are] often associated with side effects.”
The Mood Treatment with Antidepressant or Running (MOTAR) study was a partially randomized pragmatic trial in adults with depression and/or anxiety disorder, as determined using the DSM-IV algorithms with the Composite International Diagnostic Interview (CIDI).
The 16-week intervention study included 141 patients with depression and/or anxiety. The mean age was 38.2 years and 58% were women. Participants were offered a choice of treatment: 16 weeks of treatment with the selective serotonin reuptake inhibitor (SSRI) escitalopram (Lexapro) or a 16-week group-based running therapy.
Patients without a strong preference for treatment allocation were randomly assigned to either antidepressant medication or running therapy, while those unwilling to be randomized were allocated to their preferred intervention.
A total of 22 patients were randomly assigned to receive antidepressant treatment and 13 to running therapy. A total of 36 participants chose antidepressant treatment, while 83 chose the running therapy.
Running therapy involved 16 weeks of supervised 45-minute outdoor running sessions to a target of two to three sessions per week, in line with U.S. Centers for Disease Control and Prevention/American College of Sports Medicine recommendations.
Physical health benefits
Treatment adherence in the antidepressant group, defined as still using treatment at the posttreatment assessment, was 82.2% vs. 52.1% among running therapy participants, where adherence was specified as completing more than 22 sessions.
Remission was defined as no longer meeting the criteria of a current depressive or anxiety disorder via CIDI at week 16.
On intention-to-treat analysis, this requirement was met by 44.8% of patients taking antidepressants and 43.3% of those in the running therapy group (P = .88).
However, running therapy patients showed significant improvements in weight (P = .001), waist circumference (P = .011), systolic and diastolic blood pressure (P = .011 and P = .002, respectively), heart rate (P = .033), and heart rate variability (P = .006).
The investigators note the more favorable physical health changes in the running therapy group were attributable to “larger improvements in the running therapy group but also due to larger deterioration in the antidepressant group.”
Antidepressants are generally safe and effective and work for most people, said Dr. Penninx. She also noted that untreated depression leads to worse outcomes, so “antidepressants are generally a good choice.”
Nevertheless, she said, “we need to extend our treatment arsenal as not all patients respond to antidepressants or are willing to take them.”
The study’s results, she added, suggest that “implementing exercise therapy is something we should take much more seriously, as it could be a good, and maybe even better, choice for some of our patients.”
Francesca Cirulli, PhD, senior researcher and group leader at the National Institute of Health, Rome, said in an interview that the study is notable because it is one of the first to prospectively measure the effects of antidepressants and running on physical health.
Dr. Cirulli suggested that running therapy could be tried ahead of treatment with antidepressants if patients prefer physical exercise and can adhere to it. However, she said, the findings also suggest that an increase in physical activity should accompany treatment with antidepressant medications.
Overall, Dr. Cirulli said “the message should not be that everyone can be helped by running and antidepressants are bad,” but rather “these are both helpful, but not excellent, interventions against depression.”
‘Important limitations’
In a comment, Eduard Vieta, MD, PhD, chair of the department of psychiatry and psychology at the University of Barcelona Hospital Clinic, noted the study has “very important limitations.”
Among the limitations: the inclusion of nonrandomized patients who received the treatment of their choice, causing obvious bias and the “lack of binding and power issues” over the number of patients enrolled.
Dr. Vieta also said that the results “seem obvious, because it is known that exercise improves physical health.”
The trial therefore shows, “if you can find people who are able to do exercise while depressed and adhere to it, those would benefit from that practice,” he noted.
Also commenting on the research, Eric Ruhe, MD, PhD, Radboud University Medical Center, Nijmegen, the Netherlands, said the results are confirmatory and “again show physical health can influence mental health.”
However, Dr. Ruhe underlined, while it is “common practice” to allow patients to follow their treatment preference and is “understandable from a pragmatic point of view,” the group comparison may be “biased,” compared with a “truly randomized study.”
“For example, patients in the antidepressant group were more depressed, which might be associated with less chance of persisting engagement in the exercises,” he said. “So, we have to be careful not to overinterpret the comparisons between groups, which the authors acknowledge properly.”
Turning to the difference in adherence between the two interventions, Dr. Ruhe said the results show adopting, and adhering to, a lifestyle habit is more difficult than taking a pill.
“This is not exclusively found in psychiatry, indicating that we also have to focus on how to improve compliance to healthy behavior. This could have tremendous impact on health care more generally, but also on psychiatric diseases,” Dr. Ruhe said.
The MOTAR study was funded by a NWO-VICI grant. Funding for the inflammatory markers was provided by ZonMw: The Netherlands Organization for Health Research and Development. The study authors and clinicians interviewed for this story declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
BARCELONA – However, running provides greater physical health benefits while adherence is greater with drug treatment.
“Both interventions helped with the depression to around the same extent,” study presenter Brenda W.J.H. Penninx, PhD, professor of psychiatric epidemiology at the VU University Medical Center in Amsterdam said in a release.
However, medication “generally had worse impact on body weight, heart rate variability, and blood pressure, whereas running therapy led to improved effect on general fitness and heart rate,” Dr. Penninx added.
The findings were presented at the annual congress of the European College of Neuropsychopharmacology and recently published in the Journal of Affective Disorders.
Research gap
Previous research suggests exercise interventions can have a therapeutic effect equivalent to antidepressants, but their impact on physical health has been “poorly examined in a psychiatric population, the investigators note.
The authors note that depressive and anxiety disorders “cause immense suffering by compromising both mental and physical health,” and the need for effective treatments is “pressing.”
Although antidepressant medication is considered a “standard first-line treatment” alongside psychotherapy, the drugs are “not effective for all and [are] often associated with side effects.”
The Mood Treatment with Antidepressant or Running (MOTAR) study was a partially randomized pragmatic trial in adults with depression and/or anxiety disorder, as determined using the DSM-IV algorithms with the Composite International Diagnostic Interview (CIDI).
The 16-week intervention study included 141 patients with depression and/or anxiety. The mean age was 38.2 years and 58% were women. Participants were offered a choice of treatment: 16 weeks of treatment with the selective serotonin reuptake inhibitor (SSRI) escitalopram (Lexapro) or a 16-week group-based running therapy.
Patients without a strong preference for treatment allocation were randomly assigned to either antidepressant medication or running therapy, while those unwilling to be randomized were allocated to their preferred intervention.
A total of 22 patients were randomly assigned to receive antidepressant treatment and 13 to running therapy. A total of 36 participants chose antidepressant treatment, while 83 chose the running therapy.
Running therapy involved 16 weeks of supervised 45-minute outdoor running sessions to a target of two to three sessions per week, in line with U.S. Centers for Disease Control and Prevention/American College of Sports Medicine recommendations.
Physical health benefits
Treatment adherence in the antidepressant group, defined as still using treatment at the posttreatment assessment, was 82.2% vs. 52.1% among running therapy participants, where adherence was specified as completing more than 22 sessions.
Remission was defined as no longer meeting the criteria of a current depressive or anxiety disorder via CIDI at week 16.
On intention-to-treat analysis, this requirement was met by 44.8% of patients taking antidepressants and 43.3% of those in the running therapy group (P = .88).
However, running therapy patients showed significant improvements in weight (P = .001), waist circumference (P = .011), systolic and diastolic blood pressure (P = .011 and P = .002, respectively), heart rate (P = .033), and heart rate variability (P = .006).
The investigators note the more favorable physical health changes in the running therapy group were attributable to “larger improvements in the running therapy group but also due to larger deterioration in the antidepressant group.”
Antidepressants are generally safe and effective and work for most people, said Dr. Penninx. She also noted that untreated depression leads to worse outcomes, so “antidepressants are generally a good choice.”
Nevertheless, she said, “we need to extend our treatment arsenal as not all patients respond to antidepressants or are willing to take them.”
The study’s results, she added, suggest that “implementing exercise therapy is something we should take much more seriously, as it could be a good, and maybe even better, choice for some of our patients.”
Francesca Cirulli, PhD, senior researcher and group leader at the National Institute of Health, Rome, said in an interview that the study is notable because it is one of the first to prospectively measure the effects of antidepressants and running on physical health.
Dr. Cirulli suggested that running therapy could be tried ahead of treatment with antidepressants if patients prefer physical exercise and can adhere to it. However, she said, the findings also suggest that an increase in physical activity should accompany treatment with antidepressant medications.
Overall, Dr. Cirulli said “the message should not be that everyone can be helped by running and antidepressants are bad,” but rather “these are both helpful, but not excellent, interventions against depression.”
‘Important limitations’
In a comment, Eduard Vieta, MD, PhD, chair of the department of psychiatry and psychology at the University of Barcelona Hospital Clinic, noted the study has “very important limitations.”
Among the limitations: the inclusion of nonrandomized patients who received the treatment of their choice, causing obvious bias and the “lack of binding and power issues” over the number of patients enrolled.
Dr. Vieta also said that the results “seem obvious, because it is known that exercise improves physical health.”
The trial therefore shows, “if you can find people who are able to do exercise while depressed and adhere to it, those would benefit from that practice,” he noted.
Also commenting on the research, Eric Ruhe, MD, PhD, Radboud University Medical Center, Nijmegen, the Netherlands, said the results are confirmatory and “again show physical health can influence mental health.”
However, Dr. Ruhe underlined, while it is “common practice” to allow patients to follow their treatment preference and is “understandable from a pragmatic point of view,” the group comparison may be “biased,” compared with a “truly randomized study.”
“For example, patients in the antidepressant group were more depressed, which might be associated with less chance of persisting engagement in the exercises,” he said. “So, we have to be careful not to overinterpret the comparisons between groups, which the authors acknowledge properly.”
Turning to the difference in adherence between the two interventions, Dr. Ruhe said the results show adopting, and adhering to, a lifestyle habit is more difficult than taking a pill.
“This is not exclusively found in psychiatry, indicating that we also have to focus on how to improve compliance to healthy behavior. This could have tremendous impact on health care more generally, but also on psychiatric diseases,” Dr. Ruhe said.
The MOTAR study was funded by a NWO-VICI grant. Funding for the inflammatory markers was provided by ZonMw: The Netherlands Organization for Health Research and Development. The study authors and clinicians interviewed for this story declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ECNP 2023
Nintedanib dose reductions in IPF may do no harm
HONOLULU – nintedanib (Ofev) for patients with idiopathic pulmonary fibrosis (IPF) who can’t tolerate the full 150-mg twice-daily dose.
An analysis of data from a large administrative claims database showed that there were no significant differences in either all-cause mortality or hospitalization rates between patients with IPF treated at the full 150-mg twice-daily dose and those treated with a reduced twice-daily dose of 100 mg nintedanib.
Although the results need to be confirmed by additional prospective and registry studies, they suggest that patients with IPF can still fare just as well with a reduced-dose nintedanib regimen, ideally with fewer gastrointestinal side effects such as diarrhea, reported Andrew Limper, MD, of the Mayo Clinic in Rochester, Minn.
“At least on this preliminary data you could ... rest assured,” Dr. Limper told his colleagues in an oral abstract session at the American College of Chest Physicians (CHEST) 2023 annual meeting.
“This is not definitive proof, I’m not making more out of this than it is, but we all put people on 100 mg twice daily because their guts don’t tolerate it; they live in the bathroom and they don’t want to live that way,” Dr. Limper said.
Hard to take
Nintedanib is approved in the United States for the treatment of IPF, chronic fibrosing interstitial lung diseases (ILD) with a progressive phenotype, and systemic sclerosis-associated ILD. For IPF, the standard dose established in randomized clinical trials is 150 mg twice daily.
However, nintedanib is associated with a number of side effects, including hepatic and other gastrointestinal toxicities, arterial thromboembolic events, and proteinuria within the nephrotic range. As a result, clinicians often reduce the dose to 100 mg twice daily, but there is a lack of data to indicate whether it’s safe to do so or if efficacy will be compromised.
To see whether dose reductions might result in poorer outcomes for patients with IPF, Dr. Limper and colleagues analyzed data from the OptumLabs Data Warehouse, a large administrative claims database, to compare outcomes for patients treated with IPF at either the 150-mg or 100-mg twice-daily doses.
They used propensity-score matching to account for differences among individuals according to age, sex, race/ethnicity, residence, insurance type, additional medication use, oxygen use, smoking status, health care use, and comorbidities. The final cohort included 346 patients in each dosing group.
There was no difference between the dosing groups for the primary outcome of all-cause mortality at 18 months, with a nonsignificant hazard ratio of 0.65 (P = .313), and no significant difference over 24 months in risk of hospitalization, with a hazard ratio of 0.98 (P = .899).
“This is not randomized controlled data; I doubt that [nintedanib maker Boehringer Ingelheim] is ever going to do a 150 vs. 100 milligram head-to-head trial, but it does give us some ground to start to look at this,” Dr. Limper said.
Not so sure
Session comoderator Misbah Baqir, MBBS, also from the Mayo Clinic, told this news organization that she would need to see more data from prospective studies using endpoints other than mortality before she could be convinced that nintedanib dose reductions do not adversely affect efficacy. She was not involved in the study.
“I feel that the endpoint should be different, either it should be forced vital capacity change, quality of life, or something else. The problem with a database study is that you don’t have everything in it. You have to play with what you have, and you don’t have forced vital capacity. You have to go into the charts to get it,” she said.
It would be more helpful to objectively compare, for example, diarrhea episodes or other adverse events to see whether they were significantly reduced with the 100-mg dose, she added.
In an interview, Dr. Limper said that he and his colleagues plan to gather additional observational data including the newly available Medicare fee-for-service data set, registry data, and other sources.
“If we get all of that, and it really still looks compelling – and that’s an if – then I think that would be the foothold to go back to the manufacturer and say, ‘Hey, maybe you ought to think about doing a prospective trial to prove it with lung function and other endpoints such as 6-minute walks,’ ” he said.
The study was supported by a grant from Three Lakes Foundation. Dr. Limper and Dr. Baqir have disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
HONOLULU – nintedanib (Ofev) for patients with idiopathic pulmonary fibrosis (IPF) who can’t tolerate the full 150-mg twice-daily dose.
An analysis of data from a large administrative claims database showed that there were no significant differences in either all-cause mortality or hospitalization rates between patients with IPF treated at the full 150-mg twice-daily dose and those treated with a reduced twice-daily dose of 100 mg nintedanib.
Although the results need to be confirmed by additional prospective and registry studies, they suggest that patients with IPF can still fare just as well with a reduced-dose nintedanib regimen, ideally with fewer gastrointestinal side effects such as diarrhea, reported Andrew Limper, MD, of the Mayo Clinic in Rochester, Minn.
“At least on this preliminary data you could ... rest assured,” Dr. Limper told his colleagues in an oral abstract session at the American College of Chest Physicians (CHEST) 2023 annual meeting.
“This is not definitive proof, I’m not making more out of this than it is, but we all put people on 100 mg twice daily because their guts don’t tolerate it; they live in the bathroom and they don’t want to live that way,” Dr. Limper said.
Hard to take
Nintedanib is approved in the United States for the treatment of IPF, chronic fibrosing interstitial lung diseases (ILD) with a progressive phenotype, and systemic sclerosis-associated ILD. For IPF, the standard dose established in randomized clinical trials is 150 mg twice daily.
However, nintedanib is associated with a number of side effects, including hepatic and other gastrointestinal toxicities, arterial thromboembolic events, and proteinuria within the nephrotic range. As a result, clinicians often reduce the dose to 100 mg twice daily, but there is a lack of data to indicate whether it’s safe to do so or if efficacy will be compromised.
To see whether dose reductions might result in poorer outcomes for patients with IPF, Dr. Limper and colleagues analyzed data from the OptumLabs Data Warehouse, a large administrative claims database, to compare outcomes for patients treated with IPF at either the 150-mg or 100-mg twice-daily doses.
They used propensity-score matching to account for differences among individuals according to age, sex, race/ethnicity, residence, insurance type, additional medication use, oxygen use, smoking status, health care use, and comorbidities. The final cohort included 346 patients in each dosing group.
There was no difference between the dosing groups for the primary outcome of all-cause mortality at 18 months, with a nonsignificant hazard ratio of 0.65 (P = .313), and no significant difference over 24 months in risk of hospitalization, with a hazard ratio of 0.98 (P = .899).
“This is not randomized controlled data; I doubt that [nintedanib maker Boehringer Ingelheim] is ever going to do a 150 vs. 100 milligram head-to-head trial, but it does give us some ground to start to look at this,” Dr. Limper said.
Not so sure
Session comoderator Misbah Baqir, MBBS, also from the Mayo Clinic, told this news organization that she would need to see more data from prospective studies using endpoints other than mortality before she could be convinced that nintedanib dose reductions do not adversely affect efficacy. She was not involved in the study.
“I feel that the endpoint should be different, either it should be forced vital capacity change, quality of life, or something else. The problem with a database study is that you don’t have everything in it. You have to play with what you have, and you don’t have forced vital capacity. You have to go into the charts to get it,” she said.
It would be more helpful to objectively compare, for example, diarrhea episodes or other adverse events to see whether they were significantly reduced with the 100-mg dose, she added.
In an interview, Dr. Limper said that he and his colleagues plan to gather additional observational data including the newly available Medicare fee-for-service data set, registry data, and other sources.
“If we get all of that, and it really still looks compelling – and that’s an if – then I think that would be the foothold to go back to the manufacturer and say, ‘Hey, maybe you ought to think about doing a prospective trial to prove it with lung function and other endpoints such as 6-minute walks,’ ” he said.
The study was supported by a grant from Three Lakes Foundation. Dr. Limper and Dr. Baqir have disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
HONOLULU – nintedanib (Ofev) for patients with idiopathic pulmonary fibrosis (IPF) who can’t tolerate the full 150-mg twice-daily dose.
An analysis of data from a large administrative claims database showed that there were no significant differences in either all-cause mortality or hospitalization rates between patients with IPF treated at the full 150-mg twice-daily dose and those treated with a reduced twice-daily dose of 100 mg nintedanib.
Although the results need to be confirmed by additional prospective and registry studies, they suggest that patients with IPF can still fare just as well with a reduced-dose nintedanib regimen, ideally with fewer gastrointestinal side effects such as diarrhea, reported Andrew Limper, MD, of the Mayo Clinic in Rochester, Minn.
“At least on this preliminary data you could ... rest assured,” Dr. Limper told his colleagues in an oral abstract session at the American College of Chest Physicians (CHEST) 2023 annual meeting.
“This is not definitive proof, I’m not making more out of this than it is, but we all put people on 100 mg twice daily because their guts don’t tolerate it; they live in the bathroom and they don’t want to live that way,” Dr. Limper said.
Hard to take
Nintedanib is approved in the United States for the treatment of IPF, chronic fibrosing interstitial lung diseases (ILD) with a progressive phenotype, and systemic sclerosis-associated ILD. For IPF, the standard dose established in randomized clinical trials is 150 mg twice daily.
However, nintedanib is associated with a number of side effects, including hepatic and other gastrointestinal toxicities, arterial thromboembolic events, and proteinuria within the nephrotic range. As a result, clinicians often reduce the dose to 100 mg twice daily, but there is a lack of data to indicate whether it’s safe to do so or if efficacy will be compromised.
To see whether dose reductions might result in poorer outcomes for patients with IPF, Dr. Limper and colleagues analyzed data from the OptumLabs Data Warehouse, a large administrative claims database, to compare outcomes for patients treated with IPF at either the 150-mg or 100-mg twice-daily doses.
They used propensity-score matching to account for differences among individuals according to age, sex, race/ethnicity, residence, insurance type, additional medication use, oxygen use, smoking status, health care use, and comorbidities. The final cohort included 346 patients in each dosing group.
There was no difference between the dosing groups for the primary outcome of all-cause mortality at 18 months, with a nonsignificant hazard ratio of 0.65 (P = .313), and no significant difference over 24 months in risk of hospitalization, with a hazard ratio of 0.98 (P = .899).
“This is not randomized controlled data; I doubt that [nintedanib maker Boehringer Ingelheim] is ever going to do a 150 vs. 100 milligram head-to-head trial, but it does give us some ground to start to look at this,” Dr. Limper said.
Not so sure
Session comoderator Misbah Baqir, MBBS, also from the Mayo Clinic, told this news organization that she would need to see more data from prospective studies using endpoints other than mortality before she could be convinced that nintedanib dose reductions do not adversely affect efficacy. She was not involved in the study.
“I feel that the endpoint should be different, either it should be forced vital capacity change, quality of life, or something else. The problem with a database study is that you don’t have everything in it. You have to play with what you have, and you don’t have forced vital capacity. You have to go into the charts to get it,” she said.
It would be more helpful to objectively compare, for example, diarrhea episodes or other adverse events to see whether they were significantly reduced with the 100-mg dose, she added.
In an interview, Dr. Limper said that he and his colleagues plan to gather additional observational data including the newly available Medicare fee-for-service data set, registry data, and other sources.
“If we get all of that, and it really still looks compelling – and that’s an if – then I think that would be the foothold to go back to the manufacturer and say, ‘Hey, maybe you ought to think about doing a prospective trial to prove it with lung function and other endpoints such as 6-minute walks,’ ” he said.
The study was supported by a grant from Three Lakes Foundation. Dr. Limper and Dr. Baqir have disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
AT CHEST 2023
Are women and men with rheumatism treated equally?
LEIPZIG, GERMANY – Women eat more healthily, visit their physician more often, and accept offers of prophylactic treatment more frequently than their male counterparts. Nevertheless, they are generally diagnosed with a rheumatic disease much later. “With systemic sclerosis for example, diagnosis occurs a whole year later than for male patients,” said Uta Kiltz, MD, senior physician at the Ruhrgebiet Rheumatism Center in Bochum, Germany, at a press conference for the annual congress of the German Society for Rheumatology.
In addition, certain markers and antibodies can be detected earlier in men’s blood – for example in systemic sclerosis. “What’s more, women exhibit a more diverse array of symptoms, which can make an unequivocal diagnosis difficult,” Dr. Kiltz explained.
Differences between the sexes in terms of disease progression and clinical presentation have been described for most rheumatic diseases. Roughly speaking, women often exhibit a much wider range of symptoms and report a higher disease burden, whereas men tend to experience a more severe progression of the disease.
Comorbidities also occur at different rates between the sexes. Whereas women with rheumatoid arthritis suffer more frequently from osteoporosis and depression, men are more likely to develop cardiovascular diseases and diabetes.
Gender-sensitive approach
Like Dr. Kiltz, Susanna Späthling-Mestekemper, MD, PhD, of the Munich-Pasing (Germany) Rheumatology Practice, also advocates a gender-sensitive approach to diagnosis and therapy. Dr. Späthling-Mestekemper referred to this during the conference, stating that women are still treated more poorly than men. The difference in treatment quality results from gaps in knowledge in the following areas:
- Sex-specific differences in the diagnosis and therapy of rheumatic diseases and in basic and clinical research
- Sex-specific differences in communication between male and female patients and between male and female physicians.
Dr. Späthling-Mestekemper used axial spondyloarthritis (axSpA) as a “prominent example” of false diagnoses. “Men more commonly fulfill the modified New York criteria – involvement of the axial skeleton, the lumbar spine, and increasing radiological progression.”
In contrast, women with axSpA exhibit the following differences:
- It is more likely for the cervical spine to be affected.
- Women are more likely to suffer from peripheral joint involvement.
- They suffer more from whole body pain.
- They have fatigue and exhaustion.
- They exhibit fewer humoral signs of inflammation (lower C-reactive protein).
- They are rarely HLA-B27 positive.
“We also have to completely rethink how we make the diagnosis in women,” said Dr. Späthling-Mestekemper. The current approach leads to women with axSpA being diagnosed much later than men. “Depending on the study, the difference can range from 7 months to 2 years,” according to Dr. Späthling-Mestekemper.
A 2018 Spanish study reported that the most common incorrect diagnoses in women with axSpA were sciatica, osteoarthritis, and fibromyalgia.
However, it is not just in axSpA that there are significant differences between men and women. There is evidence that women with systemic lupus erythematosus suffer more from musculoskeletal symptoms, while men with lupus exhibit more severe organ involvement (especially more serositis and nephritis).
For systemic sclerosis, women have the higher survival rate. They also exhibit skin involvement more frequently. Men, however, are more likely to have organ involvement, especially with the lungs.
TNF blockers
Using the example of axSpA, Dr. Späthling-Mestekemper also showed that men and women respond differently to tumor necrosis factor (TNF) blocker therapy. “The duration of therapy with TNF blockers is shorter for women: 33.4 months versus 44.9 months. They respond less to this therapy; they stop and change more frequently.”
Data from March 2023 show that, in contrast, there is no evidence of a difference in response to Janus kinase inhibitor treatment.
The presence of enthesitis has been discussed as one reason for the worse response to TNF blockers in women, since they have it more often than men do. “In fact, a better response to TNF blockers is associated with HLA-B27 positivity, with the absence of enthesitis and with TNF blocker naivety. In women, higher fat-mass index could also play a part, or even abdominal weight gain, which also increases in women after menopause,” said Dr. Späthling-Mestekemper.
She mentioned the following other potential reasons for a delayed therapy response to biological drugs in women:
- Genetic, physical, or hormonal causes
- Widespread pain or fibromyalgia
- Late diagnosis or late application of therapy, which lowers the chances of remission.
Even the science itself has shown the following sex-specific shortcomings:
- Disregarding sex-specific differences in animal-experimental studies (which, until recently, were only conducted in male mice to avoid hormone fluctuations)
- Women in clinical studies are still underrepresented: only 37% of the populations in phase 3 studies are women; 64% of studies do not describe any sex-specific differences
- Most of the data come from epidemiological analyses (not from basic research)
- Gaps in medical textbooks
Communication differences
Female patients are looking for explanations, whereas male patients describe specific symptoms. Female physicians talk, while male physicians treat. They sound like stereotypes, but they have been substantiated in multiple studies, said Dr. Späthling-Mestekemper. In general, the study results show that male patients behave in the following ways:
- Describe their symptoms in terms of specifics
- Do not like to admit having mental health issues
- Are three to five times more likely to commit suicide because of depression than women
On the other hand, female patients behave in the following ways:
- Look for an explanation for their symptoms
- Often do not have their physical symptoms taken seriously
- Are often pushed in a psychosomatic direction.
Female physicians focus on the following questions:
- Prevention, communication, shared decision-making, open-ended questions, “positive” discussions, patient self-management (chronic diseases such as diabetes: female physicians are better at reaching the therapy goals set by the ADA guidelines than male physicians)
- Psychosocial situations: consultations last 1 minute longer (10%).
Male physicians focus on the following questions:
- Medical history
- Physical examination (cardiac catheterizations after a heart attack are arranged much more commonly by male rather than female physicians)
- Diagnostics
Recognition and training
A large-scale surgical study in 2021 made a few waves. The study analyzed whether it makes a difference if women are operated on by men or by women. The results showed that women who had been operated on by men exhibited a higher level of risk after the surgery, compared with men who had been operated on by men or by women. The risk took the following forms:
- 15% higher risk for a worse surgery result
- 16% higher risk for complications
- 11% higher risk for repeat hospitalization
- 20% higher risk for a longer period of hospitalization
- 32% higher risk for mortality
The study authors provided the following potential reasons for these differences:
- Male physicians underestimate the severity of symptoms in their female patients
- Women are less comfortable indicating their postoperative pain to a male physician
- Different working style and treatment decisions between female and male physicians
- Unconsciously incorporated role patterns and preconceptions
“Our potential solutions are recognition and training. We need a personalized style of medicine; we need to have a closer look. We owe our male and female patients as much,” said Dr. Späthling-Mestekemper.
This article was translated from the Medscape German Edition and a version appeared on Medscape.com.
LEIPZIG, GERMANY – Women eat more healthily, visit their physician more often, and accept offers of prophylactic treatment more frequently than their male counterparts. Nevertheless, they are generally diagnosed with a rheumatic disease much later. “With systemic sclerosis for example, diagnosis occurs a whole year later than for male patients,” said Uta Kiltz, MD, senior physician at the Ruhrgebiet Rheumatism Center in Bochum, Germany, at a press conference for the annual congress of the German Society for Rheumatology.
In addition, certain markers and antibodies can be detected earlier in men’s blood – for example in systemic sclerosis. “What’s more, women exhibit a more diverse array of symptoms, which can make an unequivocal diagnosis difficult,” Dr. Kiltz explained.
Differences between the sexes in terms of disease progression and clinical presentation have been described for most rheumatic diseases. Roughly speaking, women often exhibit a much wider range of symptoms and report a higher disease burden, whereas men tend to experience a more severe progression of the disease.
Comorbidities also occur at different rates between the sexes. Whereas women with rheumatoid arthritis suffer more frequently from osteoporosis and depression, men are more likely to develop cardiovascular diseases and diabetes.
Gender-sensitive approach
Like Dr. Kiltz, Susanna Späthling-Mestekemper, MD, PhD, of the Munich-Pasing (Germany) Rheumatology Practice, also advocates a gender-sensitive approach to diagnosis and therapy. Dr. Späthling-Mestekemper referred to this during the conference, stating that women are still treated more poorly than men. The difference in treatment quality results from gaps in knowledge in the following areas:
- Sex-specific differences in the diagnosis and therapy of rheumatic diseases and in basic and clinical research
- Sex-specific differences in communication between male and female patients and between male and female physicians.
Dr. Späthling-Mestekemper used axial spondyloarthritis (axSpA) as a “prominent example” of false diagnoses. “Men more commonly fulfill the modified New York criteria – involvement of the axial skeleton, the lumbar spine, and increasing radiological progression.”
In contrast, women with axSpA exhibit the following differences:
- It is more likely for the cervical spine to be affected.
- Women are more likely to suffer from peripheral joint involvement.
- They suffer more from whole body pain.
- They have fatigue and exhaustion.
- They exhibit fewer humoral signs of inflammation (lower C-reactive protein).
- They are rarely HLA-B27 positive.
“We also have to completely rethink how we make the diagnosis in women,” said Dr. Späthling-Mestekemper. The current approach leads to women with axSpA being diagnosed much later than men. “Depending on the study, the difference can range from 7 months to 2 years,” according to Dr. Späthling-Mestekemper.
A 2018 Spanish study reported that the most common incorrect diagnoses in women with axSpA were sciatica, osteoarthritis, and fibromyalgia.
However, it is not just in axSpA that there are significant differences between men and women. There is evidence that women with systemic lupus erythematosus suffer more from musculoskeletal symptoms, while men with lupus exhibit more severe organ involvement (especially more serositis and nephritis).
For systemic sclerosis, women have the higher survival rate. They also exhibit skin involvement more frequently. Men, however, are more likely to have organ involvement, especially with the lungs.
TNF blockers
Using the example of axSpA, Dr. Späthling-Mestekemper also showed that men and women respond differently to tumor necrosis factor (TNF) blocker therapy. “The duration of therapy with TNF blockers is shorter for women: 33.4 months versus 44.9 months. They respond less to this therapy; they stop and change more frequently.”
Data from March 2023 show that, in contrast, there is no evidence of a difference in response to Janus kinase inhibitor treatment.
The presence of enthesitis has been discussed as one reason for the worse response to TNF blockers in women, since they have it more often than men do. “In fact, a better response to TNF blockers is associated with HLA-B27 positivity, with the absence of enthesitis and with TNF blocker naivety. In women, higher fat-mass index could also play a part, or even abdominal weight gain, which also increases in women after menopause,” said Dr. Späthling-Mestekemper.
She mentioned the following other potential reasons for a delayed therapy response to biological drugs in women:
- Genetic, physical, or hormonal causes
- Widespread pain or fibromyalgia
- Late diagnosis or late application of therapy, which lowers the chances of remission.
Even the science itself has shown the following sex-specific shortcomings:
- Disregarding sex-specific differences in animal-experimental studies (which, until recently, were only conducted in male mice to avoid hormone fluctuations)
- Women in clinical studies are still underrepresented: only 37% of the populations in phase 3 studies are women; 64% of studies do not describe any sex-specific differences
- Most of the data come from epidemiological analyses (not from basic research)
- Gaps in medical textbooks
Communication differences
Female patients are looking for explanations, whereas male patients describe specific symptoms. Female physicians talk, while male physicians treat. They sound like stereotypes, but they have been substantiated in multiple studies, said Dr. Späthling-Mestekemper. In general, the study results show that male patients behave in the following ways:
- Describe their symptoms in terms of specifics
- Do not like to admit having mental health issues
- Are three to five times more likely to commit suicide because of depression than women
On the other hand, female patients behave in the following ways:
- Look for an explanation for their symptoms
- Often do not have their physical symptoms taken seriously
- Are often pushed in a psychosomatic direction.
Female physicians focus on the following questions:
- Prevention, communication, shared decision-making, open-ended questions, “positive” discussions, patient self-management (chronic diseases such as diabetes: female physicians are better at reaching the therapy goals set by the ADA guidelines than male physicians)
- Psychosocial situations: consultations last 1 minute longer (10%).
Male physicians focus on the following questions:
- Medical history
- Physical examination (cardiac catheterizations after a heart attack are arranged much more commonly by male rather than female physicians)
- Diagnostics
Recognition and training
A large-scale surgical study in 2021 made a few waves. The study analyzed whether it makes a difference if women are operated on by men or by women. The results showed that women who had been operated on by men exhibited a higher level of risk after the surgery, compared with men who had been operated on by men or by women. The risk took the following forms:
- 15% higher risk for a worse surgery result
- 16% higher risk for complications
- 11% higher risk for repeat hospitalization
- 20% higher risk for a longer period of hospitalization
- 32% higher risk for mortality
The study authors provided the following potential reasons for these differences:
- Male physicians underestimate the severity of symptoms in their female patients
- Women are less comfortable indicating their postoperative pain to a male physician
- Different working style and treatment decisions between female and male physicians
- Unconsciously incorporated role patterns and preconceptions
“Our potential solutions are recognition and training. We need a personalized style of medicine; we need to have a closer look. We owe our male and female patients as much,” said Dr. Späthling-Mestekemper.
This article was translated from the Medscape German Edition and a version appeared on Medscape.com.
LEIPZIG, GERMANY – Women eat more healthily, visit their physician more often, and accept offers of prophylactic treatment more frequently than their male counterparts. Nevertheless, they are generally diagnosed with a rheumatic disease much later. “With systemic sclerosis for example, diagnosis occurs a whole year later than for male patients,” said Uta Kiltz, MD, senior physician at the Ruhrgebiet Rheumatism Center in Bochum, Germany, at a press conference for the annual congress of the German Society for Rheumatology.
In addition, certain markers and antibodies can be detected earlier in men’s blood – for example in systemic sclerosis. “What’s more, women exhibit a more diverse array of symptoms, which can make an unequivocal diagnosis difficult,” Dr. Kiltz explained.
Differences between the sexes in terms of disease progression and clinical presentation have been described for most rheumatic diseases. Roughly speaking, women often exhibit a much wider range of symptoms and report a higher disease burden, whereas men tend to experience a more severe progression of the disease.
Comorbidities also occur at different rates between the sexes. Whereas women with rheumatoid arthritis suffer more frequently from osteoporosis and depression, men are more likely to develop cardiovascular diseases and diabetes.
Gender-sensitive approach
Like Dr. Kiltz, Susanna Späthling-Mestekemper, MD, PhD, of the Munich-Pasing (Germany) Rheumatology Practice, also advocates a gender-sensitive approach to diagnosis and therapy. Dr. Späthling-Mestekemper referred to this during the conference, stating that women are still treated more poorly than men. The difference in treatment quality results from gaps in knowledge in the following areas:
- Sex-specific differences in the diagnosis and therapy of rheumatic diseases and in basic and clinical research
- Sex-specific differences in communication between male and female patients and between male and female physicians.
Dr. Späthling-Mestekemper used axial spondyloarthritis (axSpA) as a “prominent example” of false diagnoses. “Men more commonly fulfill the modified New York criteria – involvement of the axial skeleton, the lumbar spine, and increasing radiological progression.”
In contrast, women with axSpA exhibit the following differences:
- It is more likely for the cervical spine to be affected.
- Women are more likely to suffer from peripheral joint involvement.
- They suffer more from whole body pain.
- They have fatigue and exhaustion.
- They exhibit fewer humoral signs of inflammation (lower C-reactive protein).
- They are rarely HLA-B27 positive.
“We also have to completely rethink how we make the diagnosis in women,” said Dr. Späthling-Mestekemper. The current approach leads to women with axSpA being diagnosed much later than men. “Depending on the study, the difference can range from 7 months to 2 years,” according to Dr. Späthling-Mestekemper.
A 2018 Spanish study reported that the most common incorrect diagnoses in women with axSpA were sciatica, osteoarthritis, and fibromyalgia.
However, it is not just in axSpA that there are significant differences between men and women. There is evidence that women with systemic lupus erythematosus suffer more from musculoskeletal symptoms, while men with lupus exhibit more severe organ involvement (especially more serositis and nephritis).
For systemic sclerosis, women have the higher survival rate. They also exhibit skin involvement more frequently. Men, however, are more likely to have organ involvement, especially with the lungs.
TNF blockers
Using the example of axSpA, Dr. Späthling-Mestekemper also showed that men and women respond differently to tumor necrosis factor (TNF) blocker therapy. “The duration of therapy with TNF blockers is shorter for women: 33.4 months versus 44.9 months. They respond less to this therapy; they stop and change more frequently.”
Data from March 2023 show that, in contrast, there is no evidence of a difference in response to Janus kinase inhibitor treatment.
The presence of enthesitis has been discussed as one reason for the worse response to TNF blockers in women, since they have it more often than men do. “In fact, a better response to TNF blockers is associated with HLA-B27 positivity, with the absence of enthesitis and with TNF blocker naivety. In women, higher fat-mass index could also play a part, or even abdominal weight gain, which also increases in women after menopause,” said Dr. Späthling-Mestekemper.
She mentioned the following other potential reasons for a delayed therapy response to biological drugs in women:
- Genetic, physical, or hormonal causes
- Widespread pain or fibromyalgia
- Late diagnosis or late application of therapy, which lowers the chances of remission.
Even the science itself has shown the following sex-specific shortcomings:
- Disregarding sex-specific differences in animal-experimental studies (which, until recently, were only conducted in male mice to avoid hormone fluctuations)
- Women in clinical studies are still underrepresented: only 37% of the populations in phase 3 studies are women; 64% of studies do not describe any sex-specific differences
- Most of the data come from epidemiological analyses (not from basic research)
- Gaps in medical textbooks
Communication differences
Female patients are looking for explanations, whereas male patients describe specific symptoms. Female physicians talk, while male physicians treat. They sound like stereotypes, but they have been substantiated in multiple studies, said Dr. Späthling-Mestekemper. In general, the study results show that male patients behave in the following ways:
- Describe their symptoms in terms of specifics
- Do not like to admit having mental health issues
- Are three to five times more likely to commit suicide because of depression than women
On the other hand, female patients behave in the following ways:
- Look for an explanation for their symptoms
- Often do not have their physical symptoms taken seriously
- Are often pushed in a psychosomatic direction.
Female physicians focus on the following questions:
- Prevention, communication, shared decision-making, open-ended questions, “positive” discussions, patient self-management (chronic diseases such as diabetes: female physicians are better at reaching the therapy goals set by the ADA guidelines than male physicians)
- Psychosocial situations: consultations last 1 minute longer (10%).
Male physicians focus on the following questions:
- Medical history
- Physical examination (cardiac catheterizations after a heart attack are arranged much more commonly by male rather than female physicians)
- Diagnostics
Recognition and training
A large-scale surgical study in 2021 made a few waves. The study analyzed whether it makes a difference if women are operated on by men or by women. The results showed that women who had been operated on by men exhibited a higher level of risk after the surgery, compared with men who had been operated on by men or by women. The risk took the following forms:
- 15% higher risk for a worse surgery result
- 16% higher risk for complications
- 11% higher risk for repeat hospitalization
- 20% higher risk for a longer period of hospitalization
- 32% higher risk for mortality
The study authors provided the following potential reasons for these differences:
- Male physicians underestimate the severity of symptoms in their female patients
- Women are less comfortable indicating their postoperative pain to a male physician
- Different working style and treatment decisions between female and male physicians
- Unconsciously incorporated role patterns and preconceptions
“Our potential solutions are recognition and training. We need a personalized style of medicine; we need to have a closer look. We owe our male and female patients as much,” said Dr. Späthling-Mestekemper.
This article was translated from the Medscape German Edition and a version appeared on Medscape.com.
AT THE GERMAN RHEUMATOLOGY CONGRESS 2023
New hyperglycemia emergency guidance updates DKA definition
HAMBURG, GERMANY – along with many other updates to the last statement on the topic, published 14 years ago.
Based on extensive literature reviews and observations of current trends, the new document – due to be published soon – will cover diagnosis and management of the two most serious acute hyperglycemic emergencies seen in adults, DKA and hyperosmolar hyperglycemic state (HHS).
New to the 2023 version will be a strong emphasis on the excess morbidity and mortality risks associated with the increasingly common “hybrid” presentation of the two conditions together, now seen in about a third of cases.
The new report will also more strongly urge clinicians to investigate why the person experienced the emergency.
While new-onset diabetes and infection are recognized precipitating causes for DKA, insulin omission related to finances, mental health, and social determinants should be identified, and patients directed to appropriate resources, said experts previewing the upcoming new report at the annual meeting of the European Association for the Study of Diabetes.
“The challenge is, although we were making progress for a long time in terms of those hyperglycemic crises, we’ve really plateaued and there are still people being admitted in large numbers, and when you look more globally even more so,” said American Diabetes Association Chief Science and Medical Officer Robert A. Gabbay, MD, PhD.
The new consensus report will be jointly endorsed by the ADA, the EASD, the American Association of Clinical Endocrinology, the Diabetes Technology Society, and the Joint British Diabetes Societies for Inpatient Care. The previous consensus statement on the subject was published in 2009 by the ADA alone.
New DKA and HHS definitions reflect emerging trends
The statement will revise the definition of DKA, partly spurred by the increasing occurrence and recognition of euglycemic ketoacidosis arising from the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors. For all patients with hyperglycemic crisis, the hyperglycemia cutoff is now lowered to 200 mg/dL (11.1 mmol/L) from the previous 250 mg/dL.
However, the glucose cutoff has been removed entirely for people with a history of diabetes.
“Both of these changes are recognizing the wide range of glucose levels at the presence of DKA. Approximately 10% of DKA occurs with euglycemia or near-normoglycemia,” noted coauthor Shivani Misra, MD, PhD, senior clinical lecturer and honorary consultant in Metabolic Medicine at Imperial College, London.
For assessing ketosis in DKA, the new statement strongly recommends use of beta-hydroxybutyrate – either via point-of-care test or serum level measured in a laboratory – with a low cutoff of ≥ 3.0 mmol/L. Alternatively, a urine ketone strip value of 2+ or greater can be used.
However, beta-hydroxybutyrate testing is more widely available now than it was in 2009 and is strongly preferred over urine ketone measurement because it’s the predominant ketone during acidosis. Moreover, urine acetoacetate – measured by the strips – paradoxically increases during resolution of DKA, and drug interferences can occur with urine ketone measurement, Dr. Misra noted.
Metabolic acidosis is now defined as a pH < 7.3 and/or a bicarbonate concentration < 18 mmol/L, up from 15 in some prior guidelines including the United Kingdom’s. Also, anion gap has been removed from the main definition but, the document will say, can still be used in settings where ketone testing is unavailable.
As previously, the new statement will classify DKA by mild, moderate, and severe but now for the first time there are recommendations of care for each of those levels, as well as for HHS.
For HHS, the glucose cutoff of ≥ 600 mg/dL will stay the same. But now, the effective serum osmolality has been lowered from > 320 to > 300 mOsml/L to account for the effect of dehydration, along with an alternative criteria of total serum osmolality > 320 mOsm/L. The same two changes as with DKA for both ketones and acidosis have also been included for HHS.
Asked to comment, session audience member and independent diabetes industry consultant Charles Alexander, MD, told this news organization, “I liked the proposal to eliminate the anion gap in decision-making and to focus on measurement of blood ketones, principally beta-hydroxybutyrate, in the diagnosis of DKA and monitoring the effect of treatment.
“If someone is on an SGLT2 inhibitor, there is no need to look at blood glucose levels, which may be normal or near normal in the setting of DKA.”
But Dr. Alexander thinks that they should have eliminated glucose levels entirely as part of the DKA/HHS definition even for people without diabetes.
“The problem is that medical education for many years has taught us that DKA is a condition of high blood glucose, but it may not be. It is good that they said blood glucose levels were not important if the patient had a history of diabetes. However, a glucose of 200mg/dL may not be low enough if someone is on an SGLT2 inhibitor. There needs to be a much lower threshold for measuring blood ketones in anyone with nausea, vomiting, and abdominal pain, regardless of the blood glucose level.”
Acute management: IV fluids, insulin, and potassium
Like the 2009 statement, the new one will include detailed management flowcharts for DKA and HHS, but this time in color. This new statement includes individual algorithms for management with intravenous fluids, insulin, and potassium. Bicarbonate has been removed and relegated to a note at the bottom saying that it should only be considered if pH is < 7.0.
Under fluid treatment, the new statement offers more information about using crystalloids to treat dehydration and a recommendation to add dextrose to IV fluid therapy as a substrate when the glucose drops below 250 mg/dL, in order to prevent hypoglycemia. For euglycemic DKA, the recommendation is to include dextrose and normal saline simultaneously.
And for the first time, subcutaneous rather than IV insulin is considered acceptable for mild, but not moderate or severe, DKA.
Two options are suggested for IV insulin in HHS: The fluid can be given first and low-dose fixed-rate insulin infusion added, or fluids and insulin can be given at the same time.
Criteria for resolution of DKA are a venous pH of ≥ 7.3 or bicarbonate > 18 mmol/L, ketones < 0.6 mmol/L, and glucose ideally < 200 mg/dL (11.0 mmol/L). For HHS, resolution is suggested when the measured or calculated serum osmolality falls to < 300 mosm/kg, blood glucose is < 250mg/dL (13.9 mmol/L), urine output > 0.5 mL/kg/hour, and cognitive status is improved.
The statement also will provide detailed recommended options for transitioning from IV to subcutaneous insulin, but defers to clinical judgment for deciding when the patient can be discharged. The initiation or continuation of SGLT2 inhibitors is not recommended at any time during hospitalization for hyperglycemic crises.
Mitigating complications, preventing recurrence
In addition to listing potential complications of treating hyperglycemic crises, just as the 2009 statement did, the new one will offer mitigation strategies for some of the more common ones. For preventing hypoglycemia, frequent blood glucose monitoring is advised along with adding dextrose to the IV fluids when glucose drops below 250 mg/dL.
For prevention of hypokalemia, which occurs in about half of patients treated for DKA and HHS, the statement recommends potassium monitoring every 4 hours and replacement added to fluids.
Acute kidney injury, also occurring in about half of people treated for DKA and/or HHS, usually resolves with hydration. Daily renal function monitoring is advised.
Preventing recurrence: Many factors beyond clinical
Prevention of recurrence with readmission for DKA and/or HHS, occurring in up to 22% of U.S. patients within 30 days, entails close follow-up within 2-4 weeks after discharge (including via telemedicine), and assessment of possible causes, including mental health disorders and social determinants of health.
Appropriate education should be provided, including “structured education” involving problem-solving, sick day rules, injection techniques, a review of insulin doses, consideration of continuous glucose monitoring (CGM), and home ketone testing.
Patients should be provided with an adequate supply of insulin and durable diabetes equipment, along with contact information for health care professionals who can assist them. Social service professionals can be helpful for patients who lack reliable access.
Dr. Gabbay told this news organization, “The eye-opening thing is we tend to typically think of DKA as how people tend to get diagnosed with diabetes and, yes, that’s true, but that’s only a minority of people. Those might be preventable by early screening, but all these other people and the number of recurrent episodes, that’s an area where it’s really a failure of the system where we can do better in ensuring that doesn’t happen.”
Education is only part of it, he stressed. “It’s not just an intelligence thing. It’s social factors, and there can be complex psychological issues and mental health issues. We need to screen for those things when we see someone coming back the second, third, fifth, or sixth time. We’ve all seen that. Just educating them to take their insulin is not the answer. …You’ve got to ask the questions and engage them to go a little deeper.”
Dr. Gabbay is an employee of the ADA. Dr. Alexander has reported being a nonpaid advisor for diaTribe and a consultant for Kinexum. Dr. Misra has received speaker fees from Sanofi and ABCD and an investigator-initiated research grant from Dexcom, and is a trustee for the Diabetes Research and Wellness Foundation in the United Kingdom.
A version of this article appeared on Medscape.com.
HAMBURG, GERMANY – along with many other updates to the last statement on the topic, published 14 years ago.
Based on extensive literature reviews and observations of current trends, the new document – due to be published soon – will cover diagnosis and management of the two most serious acute hyperglycemic emergencies seen in adults, DKA and hyperosmolar hyperglycemic state (HHS).
New to the 2023 version will be a strong emphasis on the excess morbidity and mortality risks associated with the increasingly common “hybrid” presentation of the two conditions together, now seen in about a third of cases.
The new report will also more strongly urge clinicians to investigate why the person experienced the emergency.
While new-onset diabetes and infection are recognized precipitating causes for DKA, insulin omission related to finances, mental health, and social determinants should be identified, and patients directed to appropriate resources, said experts previewing the upcoming new report at the annual meeting of the European Association for the Study of Diabetes.
“The challenge is, although we were making progress for a long time in terms of those hyperglycemic crises, we’ve really plateaued and there are still people being admitted in large numbers, and when you look more globally even more so,” said American Diabetes Association Chief Science and Medical Officer Robert A. Gabbay, MD, PhD.
The new consensus report will be jointly endorsed by the ADA, the EASD, the American Association of Clinical Endocrinology, the Diabetes Technology Society, and the Joint British Diabetes Societies for Inpatient Care. The previous consensus statement on the subject was published in 2009 by the ADA alone.
New DKA and HHS definitions reflect emerging trends
The statement will revise the definition of DKA, partly spurred by the increasing occurrence and recognition of euglycemic ketoacidosis arising from the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors. For all patients with hyperglycemic crisis, the hyperglycemia cutoff is now lowered to 200 mg/dL (11.1 mmol/L) from the previous 250 mg/dL.
However, the glucose cutoff has been removed entirely for people with a history of diabetes.
“Both of these changes are recognizing the wide range of glucose levels at the presence of DKA. Approximately 10% of DKA occurs with euglycemia or near-normoglycemia,” noted coauthor Shivani Misra, MD, PhD, senior clinical lecturer and honorary consultant in Metabolic Medicine at Imperial College, London.
For assessing ketosis in DKA, the new statement strongly recommends use of beta-hydroxybutyrate – either via point-of-care test or serum level measured in a laboratory – with a low cutoff of ≥ 3.0 mmol/L. Alternatively, a urine ketone strip value of 2+ or greater can be used.
However, beta-hydroxybutyrate testing is more widely available now than it was in 2009 and is strongly preferred over urine ketone measurement because it’s the predominant ketone during acidosis. Moreover, urine acetoacetate – measured by the strips – paradoxically increases during resolution of DKA, and drug interferences can occur with urine ketone measurement, Dr. Misra noted.
Metabolic acidosis is now defined as a pH < 7.3 and/or a bicarbonate concentration < 18 mmol/L, up from 15 in some prior guidelines including the United Kingdom’s. Also, anion gap has been removed from the main definition but, the document will say, can still be used in settings where ketone testing is unavailable.
As previously, the new statement will classify DKA by mild, moderate, and severe but now for the first time there are recommendations of care for each of those levels, as well as for HHS.
For HHS, the glucose cutoff of ≥ 600 mg/dL will stay the same. But now, the effective serum osmolality has been lowered from > 320 to > 300 mOsml/L to account for the effect of dehydration, along with an alternative criteria of total serum osmolality > 320 mOsm/L. The same two changes as with DKA for both ketones and acidosis have also been included for HHS.
Asked to comment, session audience member and independent diabetes industry consultant Charles Alexander, MD, told this news organization, “I liked the proposal to eliminate the anion gap in decision-making and to focus on measurement of blood ketones, principally beta-hydroxybutyrate, in the diagnosis of DKA and monitoring the effect of treatment.
“If someone is on an SGLT2 inhibitor, there is no need to look at blood glucose levels, which may be normal or near normal in the setting of DKA.”
But Dr. Alexander thinks that they should have eliminated glucose levels entirely as part of the DKA/HHS definition even for people without diabetes.
“The problem is that medical education for many years has taught us that DKA is a condition of high blood glucose, but it may not be. It is good that they said blood glucose levels were not important if the patient had a history of diabetes. However, a glucose of 200mg/dL may not be low enough if someone is on an SGLT2 inhibitor. There needs to be a much lower threshold for measuring blood ketones in anyone with nausea, vomiting, and abdominal pain, regardless of the blood glucose level.”
Acute management: IV fluids, insulin, and potassium
Like the 2009 statement, the new one will include detailed management flowcharts for DKA and HHS, but this time in color. This new statement includes individual algorithms for management with intravenous fluids, insulin, and potassium. Bicarbonate has been removed and relegated to a note at the bottom saying that it should only be considered if pH is < 7.0.
Under fluid treatment, the new statement offers more information about using crystalloids to treat dehydration and a recommendation to add dextrose to IV fluid therapy as a substrate when the glucose drops below 250 mg/dL, in order to prevent hypoglycemia. For euglycemic DKA, the recommendation is to include dextrose and normal saline simultaneously.
And for the first time, subcutaneous rather than IV insulin is considered acceptable for mild, but not moderate or severe, DKA.
Two options are suggested for IV insulin in HHS: The fluid can be given first and low-dose fixed-rate insulin infusion added, or fluids and insulin can be given at the same time.
Criteria for resolution of DKA are a venous pH of ≥ 7.3 or bicarbonate > 18 mmol/L, ketones < 0.6 mmol/L, and glucose ideally < 200 mg/dL (11.0 mmol/L). For HHS, resolution is suggested when the measured or calculated serum osmolality falls to < 300 mosm/kg, blood glucose is < 250mg/dL (13.9 mmol/L), urine output > 0.5 mL/kg/hour, and cognitive status is improved.
The statement also will provide detailed recommended options for transitioning from IV to subcutaneous insulin, but defers to clinical judgment for deciding when the patient can be discharged. The initiation or continuation of SGLT2 inhibitors is not recommended at any time during hospitalization for hyperglycemic crises.
Mitigating complications, preventing recurrence
In addition to listing potential complications of treating hyperglycemic crises, just as the 2009 statement did, the new one will offer mitigation strategies for some of the more common ones. For preventing hypoglycemia, frequent blood glucose monitoring is advised along with adding dextrose to the IV fluids when glucose drops below 250 mg/dL.
For prevention of hypokalemia, which occurs in about half of patients treated for DKA and HHS, the statement recommends potassium monitoring every 4 hours and replacement added to fluids.
Acute kidney injury, also occurring in about half of people treated for DKA and/or HHS, usually resolves with hydration. Daily renal function monitoring is advised.
Preventing recurrence: Many factors beyond clinical
Prevention of recurrence with readmission for DKA and/or HHS, occurring in up to 22% of U.S. patients within 30 days, entails close follow-up within 2-4 weeks after discharge (including via telemedicine), and assessment of possible causes, including mental health disorders and social determinants of health.
Appropriate education should be provided, including “structured education” involving problem-solving, sick day rules, injection techniques, a review of insulin doses, consideration of continuous glucose monitoring (CGM), and home ketone testing.
Patients should be provided with an adequate supply of insulin and durable diabetes equipment, along with contact information for health care professionals who can assist them. Social service professionals can be helpful for patients who lack reliable access.
Dr. Gabbay told this news organization, “The eye-opening thing is we tend to typically think of DKA as how people tend to get diagnosed with diabetes and, yes, that’s true, but that’s only a minority of people. Those might be preventable by early screening, but all these other people and the number of recurrent episodes, that’s an area where it’s really a failure of the system where we can do better in ensuring that doesn’t happen.”
Education is only part of it, he stressed. “It’s not just an intelligence thing. It’s social factors, and there can be complex psychological issues and mental health issues. We need to screen for those things when we see someone coming back the second, third, fifth, or sixth time. We’ve all seen that. Just educating them to take their insulin is not the answer. …You’ve got to ask the questions and engage them to go a little deeper.”
Dr. Gabbay is an employee of the ADA. Dr. Alexander has reported being a nonpaid advisor for diaTribe and a consultant for Kinexum. Dr. Misra has received speaker fees from Sanofi and ABCD and an investigator-initiated research grant from Dexcom, and is a trustee for the Diabetes Research and Wellness Foundation in the United Kingdom.
A version of this article appeared on Medscape.com.
HAMBURG, GERMANY – along with many other updates to the last statement on the topic, published 14 years ago.
Based on extensive literature reviews and observations of current trends, the new document – due to be published soon – will cover diagnosis and management of the two most serious acute hyperglycemic emergencies seen in adults, DKA and hyperosmolar hyperglycemic state (HHS).
New to the 2023 version will be a strong emphasis on the excess morbidity and mortality risks associated with the increasingly common “hybrid” presentation of the two conditions together, now seen in about a third of cases.
The new report will also more strongly urge clinicians to investigate why the person experienced the emergency.
While new-onset diabetes and infection are recognized precipitating causes for DKA, insulin omission related to finances, mental health, and social determinants should be identified, and patients directed to appropriate resources, said experts previewing the upcoming new report at the annual meeting of the European Association for the Study of Diabetes.
“The challenge is, although we were making progress for a long time in terms of those hyperglycemic crises, we’ve really plateaued and there are still people being admitted in large numbers, and when you look more globally even more so,” said American Diabetes Association Chief Science and Medical Officer Robert A. Gabbay, MD, PhD.
The new consensus report will be jointly endorsed by the ADA, the EASD, the American Association of Clinical Endocrinology, the Diabetes Technology Society, and the Joint British Diabetes Societies for Inpatient Care. The previous consensus statement on the subject was published in 2009 by the ADA alone.
New DKA and HHS definitions reflect emerging trends
The statement will revise the definition of DKA, partly spurred by the increasing occurrence and recognition of euglycemic ketoacidosis arising from the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors. For all patients with hyperglycemic crisis, the hyperglycemia cutoff is now lowered to 200 mg/dL (11.1 mmol/L) from the previous 250 mg/dL.
However, the glucose cutoff has been removed entirely for people with a history of diabetes.
“Both of these changes are recognizing the wide range of glucose levels at the presence of DKA. Approximately 10% of DKA occurs with euglycemia or near-normoglycemia,” noted coauthor Shivani Misra, MD, PhD, senior clinical lecturer and honorary consultant in Metabolic Medicine at Imperial College, London.
For assessing ketosis in DKA, the new statement strongly recommends use of beta-hydroxybutyrate – either via point-of-care test or serum level measured in a laboratory – with a low cutoff of ≥ 3.0 mmol/L. Alternatively, a urine ketone strip value of 2+ or greater can be used.
However, beta-hydroxybutyrate testing is more widely available now than it was in 2009 and is strongly preferred over urine ketone measurement because it’s the predominant ketone during acidosis. Moreover, urine acetoacetate – measured by the strips – paradoxically increases during resolution of DKA, and drug interferences can occur with urine ketone measurement, Dr. Misra noted.
Metabolic acidosis is now defined as a pH < 7.3 and/or a bicarbonate concentration < 18 mmol/L, up from 15 in some prior guidelines including the United Kingdom’s. Also, anion gap has been removed from the main definition but, the document will say, can still be used in settings where ketone testing is unavailable.
As previously, the new statement will classify DKA by mild, moderate, and severe but now for the first time there are recommendations of care for each of those levels, as well as for HHS.
For HHS, the glucose cutoff of ≥ 600 mg/dL will stay the same. But now, the effective serum osmolality has been lowered from > 320 to > 300 mOsml/L to account for the effect of dehydration, along with an alternative criteria of total serum osmolality > 320 mOsm/L. The same two changes as with DKA for both ketones and acidosis have also been included for HHS.
Asked to comment, session audience member and independent diabetes industry consultant Charles Alexander, MD, told this news organization, “I liked the proposal to eliminate the anion gap in decision-making and to focus on measurement of blood ketones, principally beta-hydroxybutyrate, in the diagnosis of DKA and monitoring the effect of treatment.
“If someone is on an SGLT2 inhibitor, there is no need to look at blood glucose levels, which may be normal or near normal in the setting of DKA.”
But Dr. Alexander thinks that they should have eliminated glucose levels entirely as part of the DKA/HHS definition even for people without diabetes.
“The problem is that medical education for many years has taught us that DKA is a condition of high blood glucose, but it may not be. It is good that they said blood glucose levels were not important if the patient had a history of diabetes. However, a glucose of 200mg/dL may not be low enough if someone is on an SGLT2 inhibitor. There needs to be a much lower threshold for measuring blood ketones in anyone with nausea, vomiting, and abdominal pain, regardless of the blood glucose level.”
Acute management: IV fluids, insulin, and potassium
Like the 2009 statement, the new one will include detailed management flowcharts for DKA and HHS, but this time in color. This new statement includes individual algorithms for management with intravenous fluids, insulin, and potassium. Bicarbonate has been removed and relegated to a note at the bottom saying that it should only be considered if pH is < 7.0.
Under fluid treatment, the new statement offers more information about using crystalloids to treat dehydration and a recommendation to add dextrose to IV fluid therapy as a substrate when the glucose drops below 250 mg/dL, in order to prevent hypoglycemia. For euglycemic DKA, the recommendation is to include dextrose and normal saline simultaneously.
And for the first time, subcutaneous rather than IV insulin is considered acceptable for mild, but not moderate or severe, DKA.
Two options are suggested for IV insulin in HHS: The fluid can be given first and low-dose fixed-rate insulin infusion added, or fluids and insulin can be given at the same time.
Criteria for resolution of DKA are a venous pH of ≥ 7.3 or bicarbonate > 18 mmol/L, ketones < 0.6 mmol/L, and glucose ideally < 200 mg/dL (11.0 mmol/L). For HHS, resolution is suggested when the measured or calculated serum osmolality falls to < 300 mosm/kg, blood glucose is < 250mg/dL (13.9 mmol/L), urine output > 0.5 mL/kg/hour, and cognitive status is improved.
The statement also will provide detailed recommended options for transitioning from IV to subcutaneous insulin, but defers to clinical judgment for deciding when the patient can be discharged. The initiation or continuation of SGLT2 inhibitors is not recommended at any time during hospitalization for hyperglycemic crises.
Mitigating complications, preventing recurrence
In addition to listing potential complications of treating hyperglycemic crises, just as the 2009 statement did, the new one will offer mitigation strategies for some of the more common ones. For preventing hypoglycemia, frequent blood glucose monitoring is advised along with adding dextrose to the IV fluids when glucose drops below 250 mg/dL.
For prevention of hypokalemia, which occurs in about half of patients treated for DKA and HHS, the statement recommends potassium monitoring every 4 hours and replacement added to fluids.
Acute kidney injury, also occurring in about half of people treated for DKA and/or HHS, usually resolves with hydration. Daily renal function monitoring is advised.
Preventing recurrence: Many factors beyond clinical
Prevention of recurrence with readmission for DKA and/or HHS, occurring in up to 22% of U.S. patients within 30 days, entails close follow-up within 2-4 weeks after discharge (including via telemedicine), and assessment of possible causes, including mental health disorders and social determinants of health.
Appropriate education should be provided, including “structured education” involving problem-solving, sick day rules, injection techniques, a review of insulin doses, consideration of continuous glucose monitoring (CGM), and home ketone testing.
Patients should be provided with an adequate supply of insulin and durable diabetes equipment, along with contact information for health care professionals who can assist them. Social service professionals can be helpful for patients who lack reliable access.
Dr. Gabbay told this news organization, “The eye-opening thing is we tend to typically think of DKA as how people tend to get diagnosed with diabetes and, yes, that’s true, but that’s only a minority of people. Those might be preventable by early screening, but all these other people and the number of recurrent episodes, that’s an area where it’s really a failure of the system where we can do better in ensuring that doesn’t happen.”
Education is only part of it, he stressed. “It’s not just an intelligence thing. It’s social factors, and there can be complex psychological issues and mental health issues. We need to screen for those things when we see someone coming back the second, third, fifth, or sixth time. We’ve all seen that. Just educating them to take their insulin is not the answer. …You’ve got to ask the questions and engage them to go a little deeper.”
Dr. Gabbay is an employee of the ADA. Dr. Alexander has reported being a nonpaid advisor for diaTribe and a consultant for Kinexum. Dr. Misra has received speaker fees from Sanofi and ABCD and an investigator-initiated research grant from Dexcom, and is a trustee for the Diabetes Research and Wellness Foundation in the United Kingdom.
A version of this article appeared on Medscape.com.
AT EASD 2023
Spreading out daily meals and snacks may boost heart failure survival
CLEVELAND – , an observational study suggests.
The new findings, based primarily on 15 years of data from the National Health and Nutrition Examination Survey (NHANES), may argue against time-restricted diet interventions like intermittent fasting for patients with HF, researchers say.
The study’s nearly 1,000 participants on medical therapy for HF reported a mean daily eating window of 11 hours and daily average of four “eating occasions,” defined as meals or snacks of at least 50 kcal.
A daily eating window of 11 or more hours, compared with less than 11 hours, corresponded to a greater than 40% drop in risk for CV mortality (P = .013) over 5-6 years, reported Hayley E. Billingsley, RD, CEP, Virginia Commonwealth University, Richmond, Va,, at the annual scientific meeting of the Heart Failure Society of America.
The analysis adjusted for caloric intake, daily number of eating occasions, body mass index (BMI), history of CV disease and cancer, diabetes, and a slew of other potential confounders.
Prior evidence, mostly from healthy people, has suggested that extended fasting during the day is associated with less physical activity, Ms. Billingsley said in an interview. So it may be that people with HF who spread out their calorie intake are more active throughout the day.
A longer time window for eating, therefore, may have indirect metabolic benefits and help preserve their lean body mass, possibly reducing CV risk in a patient group at risk for muscle wasting.
The findings add to earlier evidence from Ms. Billingsley’s center that suggests that expanded daily time windows for eating, especially later final food rather than earlier first food, may help boost CV fitness for patients with obesity and HF with preserved ejection fraction.
Intermittent fasting and other practices involving the timing of food intake have been studied for weight loss and metabolic health in mostly healthy people and patients with diabetes, she noted. “But it’s really underexplored in people with established cardiovascular disease.”
On the basis of admittedly “very preliminary” findings, it may be that some patients should not shorten their daily time windows for eating or engage in intermittent fasting, Ms. Billingsley said. It’s probably worth considering, before the approach is recommended, “what their risk is for malnutrition or sarcopenia.”
The current study included 991 persons who entered the NHANES database from 2003 to 2018. The patients self-identified as having HF, reported taking medications commonly prescribed in HF, and provided at least two “reliable” dietary recalls.
The average age of the patients was 68 years, and they had had HF for a mean of 9.5 years; 47% were women, three-fourths were White persons, two thirds had dyslipidemia, and a quarter had a history of cancer.
On average, their first eating occasion of the day was at about 8:30 a.m., and the last occasion was at about 7:30 p.m., for a time window of about 11 hours; daily calorie consumption averaged about 1,830 kcal.
About 52% died over the mean follow-up of 69 months; about 44% of deaths were from CV causes.
In a model adjusted for demographics, BMI, smoking status, times of eating occasions, CV disease, diabetes, and cancer history, the all-cause mortality hazard ratio for time windows ≥ 11 hours vs. < 11 hours was 0.236 (95% confidence interval, 0.07-0.715; P = .011).
The reduction was no longer significant on further adjustment for duration of HF, a score reflecting difficulty walking, nightly hours of sleep (which averaged 7.2 hours), daily number of eating occasions, and caloric intake, Ms. Billingsley reported.
But in the fully adjusted analysis, the HR for CV mortality for the longer vs. shorter time window was 0.368 (95% CI, 0.169-0.803; P = .013).
The issue deserves further exploration in a randomized trial, Ms. Billingsley proposed, perhaps one in which patients with HF wear accelerometers to track daily activity levels. “We’d love to do a pilot study of extending their eating window that really digs into what the mechanism of any benefit might be if we assign them to a longer time window and whether it’s related to physical activity.”
Ms. Billingsley reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
CLEVELAND – , an observational study suggests.
The new findings, based primarily on 15 years of data from the National Health and Nutrition Examination Survey (NHANES), may argue against time-restricted diet interventions like intermittent fasting for patients with HF, researchers say.
The study’s nearly 1,000 participants on medical therapy for HF reported a mean daily eating window of 11 hours and daily average of four “eating occasions,” defined as meals or snacks of at least 50 kcal.
A daily eating window of 11 or more hours, compared with less than 11 hours, corresponded to a greater than 40% drop in risk for CV mortality (P = .013) over 5-6 years, reported Hayley E. Billingsley, RD, CEP, Virginia Commonwealth University, Richmond, Va,, at the annual scientific meeting of the Heart Failure Society of America.
The analysis adjusted for caloric intake, daily number of eating occasions, body mass index (BMI), history of CV disease and cancer, diabetes, and a slew of other potential confounders.
Prior evidence, mostly from healthy people, has suggested that extended fasting during the day is associated with less physical activity, Ms. Billingsley said in an interview. So it may be that people with HF who spread out their calorie intake are more active throughout the day.
A longer time window for eating, therefore, may have indirect metabolic benefits and help preserve their lean body mass, possibly reducing CV risk in a patient group at risk for muscle wasting.
The findings add to earlier evidence from Ms. Billingsley’s center that suggests that expanded daily time windows for eating, especially later final food rather than earlier first food, may help boost CV fitness for patients with obesity and HF with preserved ejection fraction.
Intermittent fasting and other practices involving the timing of food intake have been studied for weight loss and metabolic health in mostly healthy people and patients with diabetes, she noted. “But it’s really underexplored in people with established cardiovascular disease.”
On the basis of admittedly “very preliminary” findings, it may be that some patients should not shorten their daily time windows for eating or engage in intermittent fasting, Ms. Billingsley said. It’s probably worth considering, before the approach is recommended, “what their risk is for malnutrition or sarcopenia.”
The current study included 991 persons who entered the NHANES database from 2003 to 2018. The patients self-identified as having HF, reported taking medications commonly prescribed in HF, and provided at least two “reliable” dietary recalls.
The average age of the patients was 68 years, and they had had HF for a mean of 9.5 years; 47% were women, three-fourths were White persons, two thirds had dyslipidemia, and a quarter had a history of cancer.
On average, their first eating occasion of the day was at about 8:30 a.m., and the last occasion was at about 7:30 p.m., for a time window of about 11 hours; daily calorie consumption averaged about 1,830 kcal.
About 52% died over the mean follow-up of 69 months; about 44% of deaths were from CV causes.
In a model adjusted for demographics, BMI, smoking status, times of eating occasions, CV disease, diabetes, and cancer history, the all-cause mortality hazard ratio for time windows ≥ 11 hours vs. < 11 hours was 0.236 (95% confidence interval, 0.07-0.715; P = .011).
The reduction was no longer significant on further adjustment for duration of HF, a score reflecting difficulty walking, nightly hours of sleep (which averaged 7.2 hours), daily number of eating occasions, and caloric intake, Ms. Billingsley reported.
But in the fully adjusted analysis, the HR for CV mortality for the longer vs. shorter time window was 0.368 (95% CI, 0.169-0.803; P = .013).
The issue deserves further exploration in a randomized trial, Ms. Billingsley proposed, perhaps one in which patients with HF wear accelerometers to track daily activity levels. “We’d love to do a pilot study of extending their eating window that really digs into what the mechanism of any benefit might be if we assign them to a longer time window and whether it’s related to physical activity.”
Ms. Billingsley reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
CLEVELAND – , an observational study suggests.
The new findings, based primarily on 15 years of data from the National Health and Nutrition Examination Survey (NHANES), may argue against time-restricted diet interventions like intermittent fasting for patients with HF, researchers say.
The study’s nearly 1,000 participants on medical therapy for HF reported a mean daily eating window of 11 hours and daily average of four “eating occasions,” defined as meals or snacks of at least 50 kcal.
A daily eating window of 11 or more hours, compared with less than 11 hours, corresponded to a greater than 40% drop in risk for CV mortality (P = .013) over 5-6 years, reported Hayley E. Billingsley, RD, CEP, Virginia Commonwealth University, Richmond, Va,, at the annual scientific meeting of the Heart Failure Society of America.
The analysis adjusted for caloric intake, daily number of eating occasions, body mass index (BMI), history of CV disease and cancer, diabetes, and a slew of other potential confounders.
Prior evidence, mostly from healthy people, has suggested that extended fasting during the day is associated with less physical activity, Ms. Billingsley said in an interview. So it may be that people with HF who spread out their calorie intake are more active throughout the day.
A longer time window for eating, therefore, may have indirect metabolic benefits and help preserve their lean body mass, possibly reducing CV risk in a patient group at risk for muscle wasting.
The findings add to earlier evidence from Ms. Billingsley’s center that suggests that expanded daily time windows for eating, especially later final food rather than earlier first food, may help boost CV fitness for patients with obesity and HF with preserved ejection fraction.
Intermittent fasting and other practices involving the timing of food intake have been studied for weight loss and metabolic health in mostly healthy people and patients with diabetes, she noted. “But it’s really underexplored in people with established cardiovascular disease.”
On the basis of admittedly “very preliminary” findings, it may be that some patients should not shorten their daily time windows for eating or engage in intermittent fasting, Ms. Billingsley said. It’s probably worth considering, before the approach is recommended, “what their risk is for malnutrition or sarcopenia.”
The current study included 991 persons who entered the NHANES database from 2003 to 2018. The patients self-identified as having HF, reported taking medications commonly prescribed in HF, and provided at least two “reliable” dietary recalls.
The average age of the patients was 68 years, and they had had HF for a mean of 9.5 years; 47% were women, three-fourths were White persons, two thirds had dyslipidemia, and a quarter had a history of cancer.
On average, their first eating occasion of the day was at about 8:30 a.m., and the last occasion was at about 7:30 p.m., for a time window of about 11 hours; daily calorie consumption averaged about 1,830 kcal.
About 52% died over the mean follow-up of 69 months; about 44% of deaths were from CV causes.
In a model adjusted for demographics, BMI, smoking status, times of eating occasions, CV disease, diabetes, and cancer history, the all-cause mortality hazard ratio for time windows ≥ 11 hours vs. < 11 hours was 0.236 (95% confidence interval, 0.07-0.715; P = .011).
The reduction was no longer significant on further adjustment for duration of HF, a score reflecting difficulty walking, nightly hours of sleep (which averaged 7.2 hours), daily number of eating occasions, and caloric intake, Ms. Billingsley reported.
But in the fully adjusted analysis, the HR for CV mortality for the longer vs. shorter time window was 0.368 (95% CI, 0.169-0.803; P = .013).
The issue deserves further exploration in a randomized trial, Ms. Billingsley proposed, perhaps one in which patients with HF wear accelerometers to track daily activity levels. “We’d love to do a pilot study of extending their eating window that really digs into what the mechanism of any benefit might be if we assign them to a longer time window and whether it’s related to physical activity.”
Ms. Billingsley reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
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