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FDA approves setmelanotide for obesity in Bardet-Biedl syndrome
The Food and Drug Administration has approved a supplemental indication for setmelanotide (Imcivree, Rhythm Pharmaceuticals) injection for chronic weight management in adults and pediatric patients age 6 and older with obesity due to Bardet-Biedl Syndrome (BBS).
Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, is the first FDA-approved therapy for BBS, a rare genetic disorder that impairs a hunger signal along the melanocortin-4 receptor (MC4R) pathway.
BBS affects an estimated 1,500-2,500 people in the United States.
Individuals with BBS typically have obesity that starts at age 1 along with insatiable hunger (hyperphagia). Available weight management options are generally unsuccessful.
Other symptoms may include retinal degeneration, reduced kidney function, or extra digits of the hands or feet.
Setmelanotide received priority review, orphan drug designation, and breakthrough designation for this new indication.
As previously reported, in November 2020, the FDA approved setmelanotide for weight management in adults and children as young as 6 years with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing – who also have impaired hunger signaling from the brain.
These individuals have a normal weight at birth but develop persistent, severe obesity within months due to hyperphagia.
The FDA approval of Imcivree for BBS “represents a significant milestone for Rhythm [Pharmaceuticals], validating our strategy of developing Imcivree for people with hyperphagia and severe obesity caused by rare MC4R-pathway diseases and allowing us to provide our precision therapy to an established community of patients living with BBS and their families who are eagerly awaiting a new treatment option,” said David Meeker, MD, chair, president and CEO of Rhythm, in a press release.
Safety, effectiveness in 66-week trial in 44 patients
The safety and effectiveness of setmelanotidewas evaluated in a 66-week phase 3 clinical trial that enrolled 44 patients age 6 and older who had a diagnosis of BBS and obesity – defined as a body mass index greater than or equal to 30 kg/m2 or greater than or equal to 97th percentile for pediatric patients.
After an initial 14-week, randomized, double-blind, placebo-controlled treatment period, patients entered a 52-week, open-label period.
The trial met its primary endpoint and all key secondary endpoints, with statistically significant reductions in weight and hunger at 52 weeks on therapy.
- After 52 weeks of treatment, patients taking setmelanotide lost, on average, 7.9% of their initial BMI.
- 61% of patients lost 5% or more of their initial BMI, and 39% lost 10% or more of their initial BMI.
- In the 14-week, placebo-controlled treatment, on average, BMI dropped by 4.6% in the 22 patients treated with the study drug and dropped 0.1% in the 22 patients treated with placebo.
- At 52 weeks, the 14 patients aged 12 and older who were able to self-report their hunger had a significant –2.1 mean change in hunger score.
Setmelanotide is associated with the following warnings and precautions:
- Spontaneous penile erections in males and sexual adverse reactions in females. Instruct males with erection lasting longer than 4 hours to seek emergency medical attention.
- Depression and suicidal ideation. Monitor patients for new onset or worsening depression or suicidal thoughts or behaviors. Consider discontinuing the drug if patients have suicidal thoughts or behaviors or clinically significant or persistent depression symptoms.
- Skin pigmentation and darkening of preexisting nevi (moles). Examine skin before and during treatment.
- Setmelanotide is not approved for use in neonates or infants. Serious and fatal adverse reactions including “gasping syndrome” can occur in neonates and low-birth-weight infants treated with benzyl alcohol-preserved drugs.
The most common adverse reactions (with an incidence greater than or equal to 20%) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection.
The FDA did not approve the company’s supplemental new drug application for setmelanotide in Alström syndrome.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved a supplemental indication for setmelanotide (Imcivree, Rhythm Pharmaceuticals) injection for chronic weight management in adults and pediatric patients age 6 and older with obesity due to Bardet-Biedl Syndrome (BBS).
Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, is the first FDA-approved therapy for BBS, a rare genetic disorder that impairs a hunger signal along the melanocortin-4 receptor (MC4R) pathway.
BBS affects an estimated 1,500-2,500 people in the United States.
Individuals with BBS typically have obesity that starts at age 1 along with insatiable hunger (hyperphagia). Available weight management options are generally unsuccessful.
Other symptoms may include retinal degeneration, reduced kidney function, or extra digits of the hands or feet.
Setmelanotide received priority review, orphan drug designation, and breakthrough designation for this new indication.
As previously reported, in November 2020, the FDA approved setmelanotide for weight management in adults and children as young as 6 years with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing – who also have impaired hunger signaling from the brain.
These individuals have a normal weight at birth but develop persistent, severe obesity within months due to hyperphagia.
The FDA approval of Imcivree for BBS “represents a significant milestone for Rhythm [Pharmaceuticals], validating our strategy of developing Imcivree for people with hyperphagia and severe obesity caused by rare MC4R-pathway diseases and allowing us to provide our precision therapy to an established community of patients living with BBS and their families who are eagerly awaiting a new treatment option,” said David Meeker, MD, chair, president and CEO of Rhythm, in a press release.
Safety, effectiveness in 66-week trial in 44 patients
The safety and effectiveness of setmelanotidewas evaluated in a 66-week phase 3 clinical trial that enrolled 44 patients age 6 and older who had a diagnosis of BBS and obesity – defined as a body mass index greater than or equal to 30 kg/m2 or greater than or equal to 97th percentile for pediatric patients.
After an initial 14-week, randomized, double-blind, placebo-controlled treatment period, patients entered a 52-week, open-label period.
The trial met its primary endpoint and all key secondary endpoints, with statistically significant reductions in weight and hunger at 52 weeks on therapy.
- After 52 weeks of treatment, patients taking setmelanotide lost, on average, 7.9% of their initial BMI.
- 61% of patients lost 5% or more of their initial BMI, and 39% lost 10% or more of their initial BMI.
- In the 14-week, placebo-controlled treatment, on average, BMI dropped by 4.6% in the 22 patients treated with the study drug and dropped 0.1% in the 22 patients treated with placebo.
- At 52 weeks, the 14 patients aged 12 and older who were able to self-report their hunger had a significant –2.1 mean change in hunger score.
Setmelanotide is associated with the following warnings and precautions:
- Spontaneous penile erections in males and sexual adverse reactions in females. Instruct males with erection lasting longer than 4 hours to seek emergency medical attention.
- Depression and suicidal ideation. Monitor patients for new onset or worsening depression or suicidal thoughts or behaviors. Consider discontinuing the drug if patients have suicidal thoughts or behaviors or clinically significant or persistent depression symptoms.
- Skin pigmentation and darkening of preexisting nevi (moles). Examine skin before and during treatment.
- Setmelanotide is not approved for use in neonates or infants. Serious and fatal adverse reactions including “gasping syndrome” can occur in neonates and low-birth-weight infants treated with benzyl alcohol-preserved drugs.
The most common adverse reactions (with an incidence greater than or equal to 20%) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection.
The FDA did not approve the company’s supplemental new drug application for setmelanotide in Alström syndrome.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved a supplemental indication for setmelanotide (Imcivree, Rhythm Pharmaceuticals) injection for chronic weight management in adults and pediatric patients age 6 and older with obesity due to Bardet-Biedl Syndrome (BBS).
Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, is the first FDA-approved therapy for BBS, a rare genetic disorder that impairs a hunger signal along the melanocortin-4 receptor (MC4R) pathway.
BBS affects an estimated 1,500-2,500 people in the United States.
Individuals with BBS typically have obesity that starts at age 1 along with insatiable hunger (hyperphagia). Available weight management options are generally unsuccessful.
Other symptoms may include retinal degeneration, reduced kidney function, or extra digits of the hands or feet.
Setmelanotide received priority review, orphan drug designation, and breakthrough designation for this new indication.
As previously reported, in November 2020, the FDA approved setmelanotide for weight management in adults and children as young as 6 years with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing – who also have impaired hunger signaling from the brain.
These individuals have a normal weight at birth but develop persistent, severe obesity within months due to hyperphagia.
The FDA approval of Imcivree for BBS “represents a significant milestone for Rhythm [Pharmaceuticals], validating our strategy of developing Imcivree for people with hyperphagia and severe obesity caused by rare MC4R-pathway diseases and allowing us to provide our precision therapy to an established community of patients living with BBS and their families who are eagerly awaiting a new treatment option,” said David Meeker, MD, chair, president and CEO of Rhythm, in a press release.
Safety, effectiveness in 66-week trial in 44 patients
The safety and effectiveness of setmelanotidewas evaluated in a 66-week phase 3 clinical trial that enrolled 44 patients age 6 and older who had a diagnosis of BBS and obesity – defined as a body mass index greater than or equal to 30 kg/m2 or greater than or equal to 97th percentile for pediatric patients.
After an initial 14-week, randomized, double-blind, placebo-controlled treatment period, patients entered a 52-week, open-label period.
The trial met its primary endpoint and all key secondary endpoints, with statistically significant reductions in weight and hunger at 52 weeks on therapy.
- After 52 weeks of treatment, patients taking setmelanotide lost, on average, 7.9% of their initial BMI.
- 61% of patients lost 5% or more of their initial BMI, and 39% lost 10% or more of their initial BMI.
- In the 14-week, placebo-controlled treatment, on average, BMI dropped by 4.6% in the 22 patients treated with the study drug and dropped 0.1% in the 22 patients treated with placebo.
- At 52 weeks, the 14 patients aged 12 and older who were able to self-report their hunger had a significant –2.1 mean change in hunger score.
Setmelanotide is associated with the following warnings and precautions:
- Spontaneous penile erections in males and sexual adverse reactions in females. Instruct males with erection lasting longer than 4 hours to seek emergency medical attention.
- Depression and suicidal ideation. Monitor patients for new onset or worsening depression or suicidal thoughts or behaviors. Consider discontinuing the drug if patients have suicidal thoughts or behaviors or clinically significant or persistent depression symptoms.
- Skin pigmentation and darkening of preexisting nevi (moles). Examine skin before and during treatment.
- Setmelanotide is not approved for use in neonates or infants. Serious and fatal adverse reactions including “gasping syndrome” can occur in neonates and low-birth-weight infants treated with benzyl alcohol-preserved drugs.
The most common adverse reactions (with an incidence greater than or equal to 20%) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection.
The FDA did not approve the company’s supplemental new drug application for setmelanotide in Alström syndrome.
A version of this article first appeared on Medscape.com.
Meta-analysis points to safety of acetylcholine coronary testing
Provocation testing with intracoronary acetylcholine is safe, particularly among Western patients, suggests a large systematic review that underscores the importance of functional coronary angiography to diagnose epicardial or microvascular spasm.
The results, derived from more than 12,000 patients in 16 studies, showed a 0.5% risk of major complications, defined as death, ventricular tachycardia/ventricular fibrillation, myocardial infarction, and shock requiring resuscitation.
Ventricular tachycardia/fibrillation were the most common events and mainly reported from two Japanese studies. There were no deaths.
Exploratory subgroup analyses revealed significantly fewer major complications in Western populations (0.0%; P for heterogeneity = .938), compared with Asian populations (2.3%; P for heterogeneity < .001).
The pooled positive vasospasm rate was also lower in Western versus Asian studies (37.9% vs. 50.7%; P for between-group heterogeneity = .010), as reported by the Microvascular Network in the Journal of the American College of Cardiology.
“If you look at the data between Asian studies versus others, mainly European or U.S. studies, primarily in Caucasian populations, it’s like zero percent history of major complications. So, it sounds extremely safe to do this testing in Caucasian populations,” Yuhei Kobayashi, MD, NewYork-Presbyterian Brooklyn Methodist Hospital, Weill Cornell Medicine, said.
Safety will need to be assessed in African Americans and other racial/ethnic groups, but “it makes us think we should end up testing more in the United States,” he told this news organization.
Intracoronary acetylcholine testing is daily practice in Japan but is limited in the United States and Europe to a few specialized centers due to safety concerns. Three deaths were reported in 1980 with intravenous ergonovine testing, whereas the safety of acetylcholine protocols has been studied largely in single-center retrospective studies, typically in Asian populations.
Growing recognition of myocardial infarction with nonobstructive coronary arteries (MINOCA) and ischemia with no obstructive coronary arteries (INOCA), however, is changing the landscape. In recent U.S. and European guidelines, intracoronary acetylcholine testing is indicated as a class 2a recommendation in MINOCA/INOCA.
“More and more institutions in Europe and the United States are starting to do acetylcholine testing, because now we know that chest pain isn’t necessarily coming from the blocked arteries,” Dr. Kobayashi said. “There are functional abnormalities, including coronary spasm, and if we diagnose it, we have appropriate medical regimens for this kind of disease.”
First safety meta-analysis
The present review and meta-analysis included 12,585 participants in 16 studies through November 2021. Of these, 63% were conducted in Western countries, and most were prospective studies published over the past decade in patients with MINOCA or INOCA.
Ten studies used the contemporary diagnostic criteria for epicardial spasm of at least 90% reduction in coronary diameter. Acetylcholine was administered into the left coronary artery at up to 100 mcg and 200 mcg in seven and six studies, respectively, and was used in the other three studies to assess endothelial function with a slower infusion of up to 36.4 mcg.
Major complications were significantly higher in studies following the contemporary diagnostic cutoff than in those using a lower cutoff of at least 75% diameter reduction (1.0% vs. 0.0%; P for between-group heterogeneity < .001).
The incidence of major complications was 0.2% with the slower infusion of up to 36.4 mcg, 0.8% with a maximum dose of 100 mcg, and 0.3% with a maximum dose of 200 mcg. The positive vasospasm rate was similar with the latter two protocols, at 46.3% and 41.4%, respectively.
Minor complications occurred in 3.3% of patients but were not detailed. They can include paroxysmal atrial fibrillation, ventricular ectopic beats, transient hypotension, and bradycardia requiring intervention.
As with major complications, minor complications were lower in studies using noncontemporary versus contemporary diagnostic cutoffs for epicardial spasm (1.8% vs. 4.7%) and in Western versus Asian populations (2.6% vs. 9.4%). Minor complications were similar between protocols with maximum doses of 100 mcg and 200 mcg (3.6% vs. 3.8%).
Dr. Kobayashi suggested that several factors may explain the racial differences, including previously reported smooth muscle hyperresponsiveness to provocation stimuli in Japanese patients and the inclusion of a wide range of patients in Japanese studies, such as those with obstructive coronary disease.
Japanese studies also used sequential acetylcholine injection into both the right and left coronaries, a faster injection speed of 20 seconds, and upfront placement of a temporary pacing catheter in case of acetylcholine-induced bradycardia, particularly with right coronary injection.
Although the protocol is largely settled in Japan, he said, provocation protocols need to be standardized because “depending on the country and depending on the institution, people are doing totally different things.”
A big step forward
Commenting on the study, C. Noel Bairey Merz, MD, from Cedars Sinai, Los Angeles, said it has “widespread relevance” because half of all coronary angiograms done invasively in the United States for suspected ischemia find no obstructive coronary disease. Left untreated, however, MINOCA has a 2.5% annual event rate, and a quarter of that is death.
“This is a big step forward with likely equal opportunity to improve women and men’s ischemic heart disease,” she said.
On the other hand, all studies were conducted at centers of excellence, so safety will need to be carefully watched as testing rolls out to more community care, Dr. Merz said. “And it always needs to be underscored that this is done by an interventional cardiologist because they’re familiar with wires that can dissect arteries, and they’re familiar with minor complications that could turn into major, if someone didn’t act appropriately.”
Dr. Merz also called for unifying protocols and the need to raise awareness within the general cardiology community to ask interventionalists for acetylcholine spasm testing. Randomized controlled data from within the WISE study and the CorMica study showed that diagnostic certainty leads to greater therapeutic certainty. “You do a much better job about who and how to treat,” she said.
There are also three ongoing randomized controlled trials – WARRIOR, MINOCA-BAT, and iCorMica – in the INOCA and MINOCA populations testing different treatment strategies for hard clinical outcomes like death and myocardial infarction.
“So in addition to this publication being guideline-forming for diagnosis, we anticipate in the next several years to have clinical trial evidence about therapeutics, again, for formulation of class 1 guidelines,” Dr. Merz said.
John Beltrame, BMBS, PhD, University of Adelaide, Australia, said the meta-analysis shows that intracoronary acetylcholine spasm testing is safe and should prompt greater adoption of invasive functional angiography.
Interventionalists are quite happy to do fractional flow reserve using intravenous adenosine to assess coronary microvascular dysfunction, he said, and “what we think is that functional angiography should test both – both the spasm as well as the microvasculature – and that will give us a clear direction because the treatments are slightly different when you’re treating the large arteries as compared to the microscopic arteries. It’s an important thing.”
Dr. Beltrame and colleagues further detail the benefits of comprehensive invasive functional angiography over structural angiography in a related editorial.
He also noted that the Coronary Vasomotion Disorders International Study Group published international diagnostic criteria for microvascular angina and that several protocols for acetylcholine spasm testing are in the works, including one from Australia. Australian investigators are also organizing an accreditation program for those performing the test.
“The protocol itself is relatively straightforward, but it’s not merely picking up a manual and following the instructions,” Dr. Beltrame said. “Just the same as when you train someone in angioplasty, you don’t just go out and do it. You need to develop some experience in it and so should be proctored.”
Dr. Kobayashi reported consulting agreements with Abbott Vascular. Coauthor disclosures are listed in the paper. Dr. Beltrame and colleagues have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Provocation testing with intracoronary acetylcholine is safe, particularly among Western patients, suggests a large systematic review that underscores the importance of functional coronary angiography to diagnose epicardial or microvascular spasm.
The results, derived from more than 12,000 patients in 16 studies, showed a 0.5% risk of major complications, defined as death, ventricular tachycardia/ventricular fibrillation, myocardial infarction, and shock requiring resuscitation.
Ventricular tachycardia/fibrillation were the most common events and mainly reported from two Japanese studies. There were no deaths.
Exploratory subgroup analyses revealed significantly fewer major complications in Western populations (0.0%; P for heterogeneity = .938), compared with Asian populations (2.3%; P for heterogeneity < .001).
The pooled positive vasospasm rate was also lower in Western versus Asian studies (37.9% vs. 50.7%; P for between-group heterogeneity = .010), as reported by the Microvascular Network in the Journal of the American College of Cardiology.
“If you look at the data between Asian studies versus others, mainly European or U.S. studies, primarily in Caucasian populations, it’s like zero percent history of major complications. So, it sounds extremely safe to do this testing in Caucasian populations,” Yuhei Kobayashi, MD, NewYork-Presbyterian Brooklyn Methodist Hospital, Weill Cornell Medicine, said.
Safety will need to be assessed in African Americans and other racial/ethnic groups, but “it makes us think we should end up testing more in the United States,” he told this news organization.
Intracoronary acetylcholine testing is daily practice in Japan but is limited in the United States and Europe to a few specialized centers due to safety concerns. Three deaths were reported in 1980 with intravenous ergonovine testing, whereas the safety of acetylcholine protocols has been studied largely in single-center retrospective studies, typically in Asian populations.
Growing recognition of myocardial infarction with nonobstructive coronary arteries (MINOCA) and ischemia with no obstructive coronary arteries (INOCA), however, is changing the landscape. In recent U.S. and European guidelines, intracoronary acetylcholine testing is indicated as a class 2a recommendation in MINOCA/INOCA.
“More and more institutions in Europe and the United States are starting to do acetylcholine testing, because now we know that chest pain isn’t necessarily coming from the blocked arteries,” Dr. Kobayashi said. “There are functional abnormalities, including coronary spasm, and if we diagnose it, we have appropriate medical regimens for this kind of disease.”
First safety meta-analysis
The present review and meta-analysis included 12,585 participants in 16 studies through November 2021. Of these, 63% were conducted in Western countries, and most were prospective studies published over the past decade in patients with MINOCA or INOCA.
Ten studies used the contemporary diagnostic criteria for epicardial spasm of at least 90% reduction in coronary diameter. Acetylcholine was administered into the left coronary artery at up to 100 mcg and 200 mcg in seven and six studies, respectively, and was used in the other three studies to assess endothelial function with a slower infusion of up to 36.4 mcg.
Major complications were significantly higher in studies following the contemporary diagnostic cutoff than in those using a lower cutoff of at least 75% diameter reduction (1.0% vs. 0.0%; P for between-group heterogeneity < .001).
The incidence of major complications was 0.2% with the slower infusion of up to 36.4 mcg, 0.8% with a maximum dose of 100 mcg, and 0.3% with a maximum dose of 200 mcg. The positive vasospasm rate was similar with the latter two protocols, at 46.3% and 41.4%, respectively.
Minor complications occurred in 3.3% of patients but were not detailed. They can include paroxysmal atrial fibrillation, ventricular ectopic beats, transient hypotension, and bradycardia requiring intervention.
As with major complications, minor complications were lower in studies using noncontemporary versus contemporary diagnostic cutoffs for epicardial spasm (1.8% vs. 4.7%) and in Western versus Asian populations (2.6% vs. 9.4%). Minor complications were similar between protocols with maximum doses of 100 mcg and 200 mcg (3.6% vs. 3.8%).
Dr. Kobayashi suggested that several factors may explain the racial differences, including previously reported smooth muscle hyperresponsiveness to provocation stimuli in Japanese patients and the inclusion of a wide range of patients in Japanese studies, such as those with obstructive coronary disease.
Japanese studies also used sequential acetylcholine injection into both the right and left coronaries, a faster injection speed of 20 seconds, and upfront placement of a temporary pacing catheter in case of acetylcholine-induced bradycardia, particularly with right coronary injection.
Although the protocol is largely settled in Japan, he said, provocation protocols need to be standardized because “depending on the country and depending on the institution, people are doing totally different things.”
A big step forward
Commenting on the study, C. Noel Bairey Merz, MD, from Cedars Sinai, Los Angeles, said it has “widespread relevance” because half of all coronary angiograms done invasively in the United States for suspected ischemia find no obstructive coronary disease. Left untreated, however, MINOCA has a 2.5% annual event rate, and a quarter of that is death.
“This is a big step forward with likely equal opportunity to improve women and men’s ischemic heart disease,” she said.
On the other hand, all studies were conducted at centers of excellence, so safety will need to be carefully watched as testing rolls out to more community care, Dr. Merz said. “And it always needs to be underscored that this is done by an interventional cardiologist because they’re familiar with wires that can dissect arteries, and they’re familiar with minor complications that could turn into major, if someone didn’t act appropriately.”
Dr. Merz also called for unifying protocols and the need to raise awareness within the general cardiology community to ask interventionalists for acetylcholine spasm testing. Randomized controlled data from within the WISE study and the CorMica study showed that diagnostic certainty leads to greater therapeutic certainty. “You do a much better job about who and how to treat,” she said.
There are also three ongoing randomized controlled trials – WARRIOR, MINOCA-BAT, and iCorMica – in the INOCA and MINOCA populations testing different treatment strategies for hard clinical outcomes like death and myocardial infarction.
“So in addition to this publication being guideline-forming for diagnosis, we anticipate in the next several years to have clinical trial evidence about therapeutics, again, for formulation of class 1 guidelines,” Dr. Merz said.
John Beltrame, BMBS, PhD, University of Adelaide, Australia, said the meta-analysis shows that intracoronary acetylcholine spasm testing is safe and should prompt greater adoption of invasive functional angiography.
Interventionalists are quite happy to do fractional flow reserve using intravenous adenosine to assess coronary microvascular dysfunction, he said, and “what we think is that functional angiography should test both – both the spasm as well as the microvasculature – and that will give us a clear direction because the treatments are slightly different when you’re treating the large arteries as compared to the microscopic arteries. It’s an important thing.”
Dr. Beltrame and colleagues further detail the benefits of comprehensive invasive functional angiography over structural angiography in a related editorial.
He also noted that the Coronary Vasomotion Disorders International Study Group published international diagnostic criteria for microvascular angina and that several protocols for acetylcholine spasm testing are in the works, including one from Australia. Australian investigators are also organizing an accreditation program for those performing the test.
“The protocol itself is relatively straightforward, but it’s not merely picking up a manual and following the instructions,” Dr. Beltrame said. “Just the same as when you train someone in angioplasty, you don’t just go out and do it. You need to develop some experience in it and so should be proctored.”
Dr. Kobayashi reported consulting agreements with Abbott Vascular. Coauthor disclosures are listed in the paper. Dr. Beltrame and colleagues have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Provocation testing with intracoronary acetylcholine is safe, particularly among Western patients, suggests a large systematic review that underscores the importance of functional coronary angiography to diagnose epicardial or microvascular spasm.
The results, derived from more than 12,000 patients in 16 studies, showed a 0.5% risk of major complications, defined as death, ventricular tachycardia/ventricular fibrillation, myocardial infarction, and shock requiring resuscitation.
Ventricular tachycardia/fibrillation were the most common events and mainly reported from two Japanese studies. There were no deaths.
Exploratory subgroup analyses revealed significantly fewer major complications in Western populations (0.0%; P for heterogeneity = .938), compared with Asian populations (2.3%; P for heterogeneity < .001).
The pooled positive vasospasm rate was also lower in Western versus Asian studies (37.9% vs. 50.7%; P for between-group heterogeneity = .010), as reported by the Microvascular Network in the Journal of the American College of Cardiology.
“If you look at the data between Asian studies versus others, mainly European or U.S. studies, primarily in Caucasian populations, it’s like zero percent history of major complications. So, it sounds extremely safe to do this testing in Caucasian populations,” Yuhei Kobayashi, MD, NewYork-Presbyterian Brooklyn Methodist Hospital, Weill Cornell Medicine, said.
Safety will need to be assessed in African Americans and other racial/ethnic groups, but “it makes us think we should end up testing more in the United States,” he told this news organization.
Intracoronary acetylcholine testing is daily practice in Japan but is limited in the United States and Europe to a few specialized centers due to safety concerns. Three deaths were reported in 1980 with intravenous ergonovine testing, whereas the safety of acetylcholine protocols has been studied largely in single-center retrospective studies, typically in Asian populations.
Growing recognition of myocardial infarction with nonobstructive coronary arteries (MINOCA) and ischemia with no obstructive coronary arteries (INOCA), however, is changing the landscape. In recent U.S. and European guidelines, intracoronary acetylcholine testing is indicated as a class 2a recommendation in MINOCA/INOCA.
“More and more institutions in Europe and the United States are starting to do acetylcholine testing, because now we know that chest pain isn’t necessarily coming from the blocked arteries,” Dr. Kobayashi said. “There are functional abnormalities, including coronary spasm, and if we diagnose it, we have appropriate medical regimens for this kind of disease.”
First safety meta-analysis
The present review and meta-analysis included 12,585 participants in 16 studies through November 2021. Of these, 63% were conducted in Western countries, and most were prospective studies published over the past decade in patients with MINOCA or INOCA.
Ten studies used the contemporary diagnostic criteria for epicardial spasm of at least 90% reduction in coronary diameter. Acetylcholine was administered into the left coronary artery at up to 100 mcg and 200 mcg in seven and six studies, respectively, and was used in the other three studies to assess endothelial function with a slower infusion of up to 36.4 mcg.
Major complications were significantly higher in studies following the contemporary diagnostic cutoff than in those using a lower cutoff of at least 75% diameter reduction (1.0% vs. 0.0%; P for between-group heterogeneity < .001).
The incidence of major complications was 0.2% with the slower infusion of up to 36.4 mcg, 0.8% with a maximum dose of 100 mcg, and 0.3% with a maximum dose of 200 mcg. The positive vasospasm rate was similar with the latter two protocols, at 46.3% and 41.4%, respectively.
Minor complications occurred in 3.3% of patients but were not detailed. They can include paroxysmal atrial fibrillation, ventricular ectopic beats, transient hypotension, and bradycardia requiring intervention.
As with major complications, minor complications were lower in studies using noncontemporary versus contemporary diagnostic cutoffs for epicardial spasm (1.8% vs. 4.7%) and in Western versus Asian populations (2.6% vs. 9.4%). Minor complications were similar between protocols with maximum doses of 100 mcg and 200 mcg (3.6% vs. 3.8%).
Dr. Kobayashi suggested that several factors may explain the racial differences, including previously reported smooth muscle hyperresponsiveness to provocation stimuli in Japanese patients and the inclusion of a wide range of patients in Japanese studies, such as those with obstructive coronary disease.
Japanese studies also used sequential acetylcholine injection into both the right and left coronaries, a faster injection speed of 20 seconds, and upfront placement of a temporary pacing catheter in case of acetylcholine-induced bradycardia, particularly with right coronary injection.
Although the protocol is largely settled in Japan, he said, provocation protocols need to be standardized because “depending on the country and depending on the institution, people are doing totally different things.”
A big step forward
Commenting on the study, C. Noel Bairey Merz, MD, from Cedars Sinai, Los Angeles, said it has “widespread relevance” because half of all coronary angiograms done invasively in the United States for suspected ischemia find no obstructive coronary disease. Left untreated, however, MINOCA has a 2.5% annual event rate, and a quarter of that is death.
“This is a big step forward with likely equal opportunity to improve women and men’s ischemic heart disease,” she said.
On the other hand, all studies were conducted at centers of excellence, so safety will need to be carefully watched as testing rolls out to more community care, Dr. Merz said. “And it always needs to be underscored that this is done by an interventional cardiologist because they’re familiar with wires that can dissect arteries, and they’re familiar with minor complications that could turn into major, if someone didn’t act appropriately.”
Dr. Merz also called for unifying protocols and the need to raise awareness within the general cardiology community to ask interventionalists for acetylcholine spasm testing. Randomized controlled data from within the WISE study and the CorMica study showed that diagnostic certainty leads to greater therapeutic certainty. “You do a much better job about who and how to treat,” she said.
There are also three ongoing randomized controlled trials – WARRIOR, MINOCA-BAT, and iCorMica – in the INOCA and MINOCA populations testing different treatment strategies for hard clinical outcomes like death and myocardial infarction.
“So in addition to this publication being guideline-forming for diagnosis, we anticipate in the next several years to have clinical trial evidence about therapeutics, again, for formulation of class 1 guidelines,” Dr. Merz said.
John Beltrame, BMBS, PhD, University of Adelaide, Australia, said the meta-analysis shows that intracoronary acetylcholine spasm testing is safe and should prompt greater adoption of invasive functional angiography.
Interventionalists are quite happy to do fractional flow reserve using intravenous adenosine to assess coronary microvascular dysfunction, he said, and “what we think is that functional angiography should test both – both the spasm as well as the microvasculature – and that will give us a clear direction because the treatments are slightly different when you’re treating the large arteries as compared to the microscopic arteries. It’s an important thing.”
Dr. Beltrame and colleagues further detail the benefits of comprehensive invasive functional angiography over structural angiography in a related editorial.
He also noted that the Coronary Vasomotion Disorders International Study Group published international diagnostic criteria for microvascular angina and that several protocols for acetylcholine spasm testing are in the works, including one from Australia. Australian investigators are also organizing an accreditation program for those performing the test.
“The protocol itself is relatively straightforward, but it’s not merely picking up a manual and following the instructions,” Dr. Beltrame said. “Just the same as when you train someone in angioplasty, you don’t just go out and do it. You need to develop some experience in it and so should be proctored.”
Dr. Kobayashi reported consulting agreements with Abbott Vascular. Coauthor disclosures are listed in the paper. Dr. Beltrame and colleagues have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
“How long, how long to sing this song?”
“My soul is in deep anguish. How long, Lord, how long?” – Psalm 6
. A once-common word in the 1800s, it fell steeply in popularity in the 20th century. Lately, I see it everywhere. It’s a beautiful word, capturing not only sorrow, but also weariness. It is also audacious, facing injustice and acknowledging that it ought not be this way, and communal, bearing witness to the shared hardship of being human. The Hebrew scriptures captured the experience of lament in the form of psalms, from the Greek, psalmoi or “words to accompany the music.” A few thousand years later, the words still resonate, especially in times of grief. “I am weary with my groaning; all the night make I my bed to swim; I water my couch with my tears.”
“Hair loss” is not the chief complaint you want to see when running behind in clinic – it’s never a 15-minute visit. A woman in her late 30s with wavy, light-brown hair that grew to her waistline was seated on the exam chair. When I sat across from her, I couldn’t see her scalp. No erythema or scale. No frontal band of hair loss. Just a bit thin everywhere. Perhaps another post-COVID telogen? This might be easy. I blew right by her mother, who was sitting in the corner of the room. Her black and white horizontal striped shirt seemed to match her gray and white hair. She looked worried.
Having perused my patient’s labs and done an exam, I announced that the diagnosis was telogen effluvium. “There are many possible causes, stress is a common one. Have you been under a lot of stress lately?” (The answer is always yes, thus providing a good foothold to climb out of a hair-loss visit). “Yes. My 1-year-old daughter died last year. She had choked on a cashew from a granola bar given by her sister.” I gasped and turned from her green eyes to her mom’s. Without saying a word, mom pleaded with me to help. “I don’t know what to say,” I said, “I’m so sorry.” Neither replied.
On the commute home that day I listened to a live recording of the U2 song, “40.” I had recently read about it in a touching essay about lament by Enuma Okoro of the Financial Times. I thought about my patient’s suffering and the brutal injustice of fate. It feels like it’s everywhere lately. Reporting from the events in Ukraine, Buffalo, Uvalde, Tulsa has put agonized faces like hers in the public square for us all to gape at and quietly mourn.
Even from a secular lens, it can be seen that a beauty of psalms is how they move from despair to hope. Prayers will be answered. Things will get better. Turn up the volume and feel the urgency and pathos Bono injects into your soul as he sings the refrain; “How long, how long? How long to sing this song?” In the live version we the audience take over for him. The words accompanying the music swell over the crowd. How much longer? How much more suffering? My patient’s hair will grow back. It will take years. All we can do is lament with her.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].
“My soul is in deep anguish. How long, Lord, how long?” – Psalm 6
. A once-common word in the 1800s, it fell steeply in popularity in the 20th century. Lately, I see it everywhere. It’s a beautiful word, capturing not only sorrow, but also weariness. It is also audacious, facing injustice and acknowledging that it ought not be this way, and communal, bearing witness to the shared hardship of being human. The Hebrew scriptures captured the experience of lament in the form of psalms, from the Greek, psalmoi or “words to accompany the music.” A few thousand years later, the words still resonate, especially in times of grief. “I am weary with my groaning; all the night make I my bed to swim; I water my couch with my tears.”
“Hair loss” is not the chief complaint you want to see when running behind in clinic – it’s never a 15-minute visit. A woman in her late 30s with wavy, light-brown hair that grew to her waistline was seated on the exam chair. When I sat across from her, I couldn’t see her scalp. No erythema or scale. No frontal band of hair loss. Just a bit thin everywhere. Perhaps another post-COVID telogen? This might be easy. I blew right by her mother, who was sitting in the corner of the room. Her black and white horizontal striped shirt seemed to match her gray and white hair. She looked worried.
Having perused my patient’s labs and done an exam, I announced that the diagnosis was telogen effluvium. “There are many possible causes, stress is a common one. Have you been under a lot of stress lately?” (The answer is always yes, thus providing a good foothold to climb out of a hair-loss visit). “Yes. My 1-year-old daughter died last year. She had choked on a cashew from a granola bar given by her sister.” I gasped and turned from her green eyes to her mom’s. Without saying a word, mom pleaded with me to help. “I don’t know what to say,” I said, “I’m so sorry.” Neither replied.
On the commute home that day I listened to a live recording of the U2 song, “40.” I had recently read about it in a touching essay about lament by Enuma Okoro of the Financial Times. I thought about my patient’s suffering and the brutal injustice of fate. It feels like it’s everywhere lately. Reporting from the events in Ukraine, Buffalo, Uvalde, Tulsa has put agonized faces like hers in the public square for us all to gape at and quietly mourn.
Even from a secular lens, it can be seen that a beauty of psalms is how they move from despair to hope. Prayers will be answered. Things will get better. Turn up the volume and feel the urgency and pathos Bono injects into your soul as he sings the refrain; “How long, how long? How long to sing this song?” In the live version we the audience take over for him. The words accompanying the music swell over the crowd. How much longer? How much more suffering? My patient’s hair will grow back. It will take years. All we can do is lament with her.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].
“My soul is in deep anguish. How long, Lord, how long?” – Psalm 6
. A once-common word in the 1800s, it fell steeply in popularity in the 20th century. Lately, I see it everywhere. It’s a beautiful word, capturing not only sorrow, but also weariness. It is also audacious, facing injustice and acknowledging that it ought not be this way, and communal, bearing witness to the shared hardship of being human. The Hebrew scriptures captured the experience of lament in the form of psalms, from the Greek, psalmoi or “words to accompany the music.” A few thousand years later, the words still resonate, especially in times of grief. “I am weary with my groaning; all the night make I my bed to swim; I water my couch with my tears.”
“Hair loss” is not the chief complaint you want to see when running behind in clinic – it’s never a 15-minute visit. A woman in her late 30s with wavy, light-brown hair that grew to her waistline was seated on the exam chair. When I sat across from her, I couldn’t see her scalp. No erythema or scale. No frontal band of hair loss. Just a bit thin everywhere. Perhaps another post-COVID telogen? This might be easy. I blew right by her mother, who was sitting in the corner of the room. Her black and white horizontal striped shirt seemed to match her gray and white hair. She looked worried.
Having perused my patient’s labs and done an exam, I announced that the diagnosis was telogen effluvium. “There are many possible causes, stress is a common one. Have you been under a lot of stress lately?” (The answer is always yes, thus providing a good foothold to climb out of a hair-loss visit). “Yes. My 1-year-old daughter died last year. She had choked on a cashew from a granola bar given by her sister.” I gasped and turned from her green eyes to her mom’s. Without saying a word, mom pleaded with me to help. “I don’t know what to say,” I said, “I’m so sorry.” Neither replied.
On the commute home that day I listened to a live recording of the U2 song, “40.” I had recently read about it in a touching essay about lament by Enuma Okoro of the Financial Times. I thought about my patient’s suffering and the brutal injustice of fate. It feels like it’s everywhere lately. Reporting from the events in Ukraine, Buffalo, Uvalde, Tulsa has put agonized faces like hers in the public square for us all to gape at and quietly mourn.
Even from a secular lens, it can be seen that a beauty of psalms is how they move from despair to hope. Prayers will be answered. Things will get better. Turn up the volume and feel the urgency and pathos Bono injects into your soul as he sings the refrain; “How long, how long? How long to sing this song?” In the live version we the audience take over for him. The words accompanying the music swell over the crowd. How much longer? How much more suffering? My patient’s hair will grow back. It will take years. All we can do is lament with her.
Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].
Heart failure: Medicare cost sharing may put quadruple therapy out of reach
Out-of-pocket (OOP) costs for Medicare enrollees receiving quadruple drug therapy for heart failure with reduced ejection fraction were “substantially higher than regimens limited to generically available medications,” according to a new analysis of prescription drug plans.
“Despite the clinical benefit of quadruple therapy” consisting of beta-blockers, angiotensin receptor-neprilysin inhibitors (ARNIs), mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 (SGLT2) inhibitors, “coverage was restricted primarily through cost sharing, and estimated annual OOP costs for beneficiaries were [over $2,000] per year under most plans,” wrote Kamil F. Faridi, MD, and associates. The findings were published in the Journal of the American College of Cardiology.
For just 1 month of quadruple drug therapy for heart failure with reduced ejection fraction (HFrEF), the estimated median OOP cost was $94 for individuals covered by a Medicare prescription drug plan during the second quarter of 2020, with the majority coming from the ARNI (median, $47) and the SGLT2 inhibitor (median, $45). Alternative HFrEF regimens were significantly less costly, ranging from $3 to $47 OOP, the investigators reported.
Almost all of the 4,068 plans participating in Medicare at that time covered quadruple therapy for HFrEF, but more than 99% restricted coverage by instituting cost sharing for medications at tier level 3 and above on the drug formularies. Such restrictions for ARNIs and SGLT2 inhibitors “might not be readily apparent to prescribing physicians,” wrote Dr. Faridi of Yale University, New Haven, Conn., and associates.
Other methods of regulating coverage were less common. Prior authorization of ARNIs was invoked by about a quarter of the plans, but none required authorization for any of the other drugs involved, and few plans used step therapy-requirements involving lower-cost alternatives, they noted.
“The use of cost sharing restricts access through high OOP costs for patients. Furthermore, these policies likely disadvantage relatively poorer patients (although the poorest Medicare patients will tend to be dual-enrolled in Medicaid and protected from cost sharing),” Jason H. Wasfy, MD, and Anna C. O’Kelly, MD, said in an accompanying editorial comment .
Since acceptable cost-effectiveness has been demonstrated for dapagliflozin, an SGLT1 inhibitor, and for the ARNIs, and because these medications have no generic equivalents, health plans should “use the discretion they have under Medicare Part D to reduce cost sharing for patients with HFrEF,” Dr. Wasfy and Dr. O’Kelly wrote, adding that the current study “demonstrates that without consensus on cost effectiveness from the societal perspective, costs can be imposed directly on patients in ways that slow uptake of cost-effective drugs.”
Data for all Medicare Advantage plans (n = 3,167) and standalone Part D plans (n = 901) came from the Medicare Prescription Drug Plan Formulary and Pricing Information Files. Annual OOP costs were estimated “using each phase of a 2020 Medicare part D standard benefit,” including deductible, standard coverage, coverage gap, and catastrophic coverage, the investigators explained.
Dr. Faridi and associates did not report any direct funding sources for their study. Dr Faridi received a grant from the National Institutes of Health outside the scope of the present work, and other investigators disclosed ties to the Food and Drug Administration, the Centers for Medicare and Medicaid Services, Johnson & Johnson, AstraZeneca, Boehringer Ingelheim, Amgen, Cytokinetics, and the Institute for Clinical and Economic Review.
Dr. Wasfy is supported by the American Heart Association and has received consulting fees from Pfizer and honoraria from the Institute for Clinical and Economic Review. Dr. O’Kelly has no relevant disclosures.
Out-of-pocket (OOP) costs for Medicare enrollees receiving quadruple drug therapy for heart failure with reduced ejection fraction were “substantially higher than regimens limited to generically available medications,” according to a new analysis of prescription drug plans.
“Despite the clinical benefit of quadruple therapy” consisting of beta-blockers, angiotensin receptor-neprilysin inhibitors (ARNIs), mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 (SGLT2) inhibitors, “coverage was restricted primarily through cost sharing, and estimated annual OOP costs for beneficiaries were [over $2,000] per year under most plans,” wrote Kamil F. Faridi, MD, and associates. The findings were published in the Journal of the American College of Cardiology.
For just 1 month of quadruple drug therapy for heart failure with reduced ejection fraction (HFrEF), the estimated median OOP cost was $94 for individuals covered by a Medicare prescription drug plan during the second quarter of 2020, with the majority coming from the ARNI (median, $47) and the SGLT2 inhibitor (median, $45). Alternative HFrEF regimens were significantly less costly, ranging from $3 to $47 OOP, the investigators reported.
Almost all of the 4,068 plans participating in Medicare at that time covered quadruple therapy for HFrEF, but more than 99% restricted coverage by instituting cost sharing for medications at tier level 3 and above on the drug formularies. Such restrictions for ARNIs and SGLT2 inhibitors “might not be readily apparent to prescribing physicians,” wrote Dr. Faridi of Yale University, New Haven, Conn., and associates.
Other methods of regulating coverage were less common. Prior authorization of ARNIs was invoked by about a quarter of the plans, but none required authorization for any of the other drugs involved, and few plans used step therapy-requirements involving lower-cost alternatives, they noted.
“The use of cost sharing restricts access through high OOP costs for patients. Furthermore, these policies likely disadvantage relatively poorer patients (although the poorest Medicare patients will tend to be dual-enrolled in Medicaid and protected from cost sharing),” Jason H. Wasfy, MD, and Anna C. O’Kelly, MD, said in an accompanying editorial comment .
Since acceptable cost-effectiveness has been demonstrated for dapagliflozin, an SGLT1 inhibitor, and for the ARNIs, and because these medications have no generic equivalents, health plans should “use the discretion they have under Medicare Part D to reduce cost sharing for patients with HFrEF,” Dr. Wasfy and Dr. O’Kelly wrote, adding that the current study “demonstrates that without consensus on cost effectiveness from the societal perspective, costs can be imposed directly on patients in ways that slow uptake of cost-effective drugs.”
Data for all Medicare Advantage plans (n = 3,167) and standalone Part D plans (n = 901) came from the Medicare Prescription Drug Plan Formulary and Pricing Information Files. Annual OOP costs were estimated “using each phase of a 2020 Medicare part D standard benefit,” including deductible, standard coverage, coverage gap, and catastrophic coverage, the investigators explained.
Dr. Faridi and associates did not report any direct funding sources for their study. Dr Faridi received a grant from the National Institutes of Health outside the scope of the present work, and other investigators disclosed ties to the Food and Drug Administration, the Centers for Medicare and Medicaid Services, Johnson & Johnson, AstraZeneca, Boehringer Ingelheim, Amgen, Cytokinetics, and the Institute for Clinical and Economic Review.
Dr. Wasfy is supported by the American Heart Association and has received consulting fees from Pfizer and honoraria from the Institute for Clinical and Economic Review. Dr. O’Kelly has no relevant disclosures.
Out-of-pocket (OOP) costs for Medicare enrollees receiving quadruple drug therapy for heart failure with reduced ejection fraction were “substantially higher than regimens limited to generically available medications,” according to a new analysis of prescription drug plans.
“Despite the clinical benefit of quadruple therapy” consisting of beta-blockers, angiotensin receptor-neprilysin inhibitors (ARNIs), mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 (SGLT2) inhibitors, “coverage was restricted primarily through cost sharing, and estimated annual OOP costs for beneficiaries were [over $2,000] per year under most plans,” wrote Kamil F. Faridi, MD, and associates. The findings were published in the Journal of the American College of Cardiology.
For just 1 month of quadruple drug therapy for heart failure with reduced ejection fraction (HFrEF), the estimated median OOP cost was $94 for individuals covered by a Medicare prescription drug plan during the second quarter of 2020, with the majority coming from the ARNI (median, $47) and the SGLT2 inhibitor (median, $45). Alternative HFrEF regimens were significantly less costly, ranging from $3 to $47 OOP, the investigators reported.
Almost all of the 4,068 plans participating in Medicare at that time covered quadruple therapy for HFrEF, but more than 99% restricted coverage by instituting cost sharing for medications at tier level 3 and above on the drug formularies. Such restrictions for ARNIs and SGLT2 inhibitors “might not be readily apparent to prescribing physicians,” wrote Dr. Faridi of Yale University, New Haven, Conn., and associates.
Other methods of regulating coverage were less common. Prior authorization of ARNIs was invoked by about a quarter of the plans, but none required authorization for any of the other drugs involved, and few plans used step therapy-requirements involving lower-cost alternatives, they noted.
“The use of cost sharing restricts access through high OOP costs for patients. Furthermore, these policies likely disadvantage relatively poorer patients (although the poorest Medicare patients will tend to be dual-enrolled in Medicaid and protected from cost sharing),” Jason H. Wasfy, MD, and Anna C. O’Kelly, MD, said in an accompanying editorial comment .
Since acceptable cost-effectiveness has been demonstrated for dapagliflozin, an SGLT1 inhibitor, and for the ARNIs, and because these medications have no generic equivalents, health plans should “use the discretion they have under Medicare Part D to reduce cost sharing for patients with HFrEF,” Dr. Wasfy and Dr. O’Kelly wrote, adding that the current study “demonstrates that without consensus on cost effectiveness from the societal perspective, costs can be imposed directly on patients in ways that slow uptake of cost-effective drugs.”
Data for all Medicare Advantage plans (n = 3,167) and standalone Part D plans (n = 901) came from the Medicare Prescription Drug Plan Formulary and Pricing Information Files. Annual OOP costs were estimated “using each phase of a 2020 Medicare part D standard benefit,” including deductible, standard coverage, coverage gap, and catastrophic coverage, the investigators explained.
Dr. Faridi and associates did not report any direct funding sources for their study. Dr Faridi received a grant from the National Institutes of Health outside the scope of the present work, and other investigators disclosed ties to the Food and Drug Administration, the Centers for Medicare and Medicaid Services, Johnson & Johnson, AstraZeneca, Boehringer Ingelheim, Amgen, Cytokinetics, and the Institute for Clinical and Economic Review.
Dr. Wasfy is supported by the American Heart Association and has received consulting fees from Pfizer and honoraria from the Institute for Clinical and Economic Review. Dr. O’Kelly has no relevant disclosures.
FROM THE JOURNAL Of the AMERICAN COLLEGE OF CARDIOLOGY
How we treat acute pain could be wrong
In a surprising discovery that flies in the face of conventional medicine,
The paper, published in Science Translational Medicine, suggests that inflammation, a normal part of injury recovery, helps resolve acute pain and prevents it from becoming chronic. Blocking that inflammation may interfere with this process, leading to harder-to-treat pain.
“What we’ve been doing for decades not only appears to be wrong, but appears to be 180 degrees wrong,” says senior study author Jeffrey Mogil, PhD, a professor in the department of psychology at McGill University in Montreal. “You should not be blocking inflammation. You should be letting inflammation happen. That’s what stops chronic pain.”
Inflammation: Nature’s pain reliever
Wanting to know why pain goes away for some but drags on (and on) for others, the researchers looked at pain mechanisms in both humans and mice. They found that a type of white blood cell known as a neutrophil seems to play a key role.
“In analyzing the genes of people suffering from lower back pain, we observed active changes in genes over time in people whose pain went away,” says Luda Diatchenko, PhD, a professor in the faculty of medicine and Canada excellence research chair in human pain genetics at McGill. “Changes in the blood cells and their activity seemed to be the most important factor, especially in cells called neutrophils.”
To test this link, the researchers blocked neutrophils in mice and found the pain lasted 2-10 times longer than normal. Anti-inflammatory drugs, despite providing short-term relief, had the same pain-prolonging effect – though injecting neutrophils into the mice seemed to keep that from happening.
The findings are supported by a separate analysis of 500,000 people in the United Kingdom that showed those taking anti-inflammatory drugs to treat their pain were more likely to have pain 2-10 years later.
“Inflammation occurs for a reason,” says Dr. Mogil, “and it looks like it’s dangerous to interfere with it.”
Rethinking how we treat pain
Neutrophils arrive early during inflammation, at the onset of injury – just when many of us reach for pain medication. This research suggests it might be better not to block inflammation, instead letting the neutrophils “do their thing.” Taking an analgesic that alleviates pain without blocking neutrophils, like acetaminophen, may be better than taking an anti-inflammatory drug or steroid, says Dr. Mogil.
Still, while the findings are compelling, clinical trials are needed to directly compare anti-inflammatory drugs to other painkillers, the researchers said. This research may also lay the groundwork for new drug development for chronic pain patients, Dr. Mogil says.
“Our data strongly suggests that neutrophils act like analgesics themselves, which is potentially useful in terms of analgesic development,” Dr. Mogil says. “And of course, we need new analgesics.”
A version of this article first appeared on WebMD.com.
In a surprising discovery that flies in the face of conventional medicine,
The paper, published in Science Translational Medicine, suggests that inflammation, a normal part of injury recovery, helps resolve acute pain and prevents it from becoming chronic. Blocking that inflammation may interfere with this process, leading to harder-to-treat pain.
“What we’ve been doing for decades not only appears to be wrong, but appears to be 180 degrees wrong,” says senior study author Jeffrey Mogil, PhD, a professor in the department of psychology at McGill University in Montreal. “You should not be blocking inflammation. You should be letting inflammation happen. That’s what stops chronic pain.”
Inflammation: Nature’s pain reliever
Wanting to know why pain goes away for some but drags on (and on) for others, the researchers looked at pain mechanisms in both humans and mice. They found that a type of white blood cell known as a neutrophil seems to play a key role.
“In analyzing the genes of people suffering from lower back pain, we observed active changes in genes over time in people whose pain went away,” says Luda Diatchenko, PhD, a professor in the faculty of medicine and Canada excellence research chair in human pain genetics at McGill. “Changes in the blood cells and their activity seemed to be the most important factor, especially in cells called neutrophils.”
To test this link, the researchers blocked neutrophils in mice and found the pain lasted 2-10 times longer than normal. Anti-inflammatory drugs, despite providing short-term relief, had the same pain-prolonging effect – though injecting neutrophils into the mice seemed to keep that from happening.
The findings are supported by a separate analysis of 500,000 people in the United Kingdom that showed those taking anti-inflammatory drugs to treat their pain were more likely to have pain 2-10 years later.
“Inflammation occurs for a reason,” says Dr. Mogil, “and it looks like it’s dangerous to interfere with it.”
Rethinking how we treat pain
Neutrophils arrive early during inflammation, at the onset of injury – just when many of us reach for pain medication. This research suggests it might be better not to block inflammation, instead letting the neutrophils “do their thing.” Taking an analgesic that alleviates pain without blocking neutrophils, like acetaminophen, may be better than taking an anti-inflammatory drug or steroid, says Dr. Mogil.
Still, while the findings are compelling, clinical trials are needed to directly compare anti-inflammatory drugs to other painkillers, the researchers said. This research may also lay the groundwork for new drug development for chronic pain patients, Dr. Mogil says.
“Our data strongly suggests that neutrophils act like analgesics themselves, which is potentially useful in terms of analgesic development,” Dr. Mogil says. “And of course, we need new analgesics.”
A version of this article first appeared on WebMD.com.
In a surprising discovery that flies in the face of conventional medicine,
The paper, published in Science Translational Medicine, suggests that inflammation, a normal part of injury recovery, helps resolve acute pain and prevents it from becoming chronic. Blocking that inflammation may interfere with this process, leading to harder-to-treat pain.
“What we’ve been doing for decades not only appears to be wrong, but appears to be 180 degrees wrong,” says senior study author Jeffrey Mogil, PhD, a professor in the department of psychology at McGill University in Montreal. “You should not be blocking inflammation. You should be letting inflammation happen. That’s what stops chronic pain.”
Inflammation: Nature’s pain reliever
Wanting to know why pain goes away for some but drags on (and on) for others, the researchers looked at pain mechanisms in both humans and mice. They found that a type of white blood cell known as a neutrophil seems to play a key role.
“In analyzing the genes of people suffering from lower back pain, we observed active changes in genes over time in people whose pain went away,” says Luda Diatchenko, PhD, a professor in the faculty of medicine and Canada excellence research chair in human pain genetics at McGill. “Changes in the blood cells and their activity seemed to be the most important factor, especially in cells called neutrophils.”
To test this link, the researchers blocked neutrophils in mice and found the pain lasted 2-10 times longer than normal. Anti-inflammatory drugs, despite providing short-term relief, had the same pain-prolonging effect – though injecting neutrophils into the mice seemed to keep that from happening.
The findings are supported by a separate analysis of 500,000 people in the United Kingdom that showed those taking anti-inflammatory drugs to treat their pain were more likely to have pain 2-10 years later.
“Inflammation occurs for a reason,” says Dr. Mogil, “and it looks like it’s dangerous to interfere with it.”
Rethinking how we treat pain
Neutrophils arrive early during inflammation, at the onset of injury – just when many of us reach for pain medication. This research suggests it might be better not to block inflammation, instead letting the neutrophils “do their thing.” Taking an analgesic that alleviates pain without blocking neutrophils, like acetaminophen, may be better than taking an anti-inflammatory drug or steroid, says Dr. Mogil.
Still, while the findings are compelling, clinical trials are needed to directly compare anti-inflammatory drugs to other painkillers, the researchers said. This research may also lay the groundwork for new drug development for chronic pain patients, Dr. Mogil says.
“Our data strongly suggests that neutrophils act like analgesics themselves, which is potentially useful in terms of analgesic development,” Dr. Mogil says. “And of course, we need new analgesics.”
A version of this article first appeared on WebMD.com.
FROM SCIENCE TRANSLATIONAL MEDICINE
Longer circadian rhythms linked to severe depression in teens
, according to results from a European study.
A range of psychiatric symptoms and conditions has been linked to sleep pathologies, wrote Liisa Kuula, PhD, of the University of Helsinki, Finland, and colleagues. Some research suggests that late circadian rhythms and irregular sleep patterns increase the risk for psychiatric conditions, but the association has not been well studied, especially in adolescents, although the onset of psychiatric problems often occurs at this age, they said.
In a study published in the Journal of Psychiatric Research (2022 Apr 4. doi: 10.1016/j.jpsychires.2022.03.056.), the investigators reviewed data from 342 adolescents who were part of SleepHelsinki! a large cohort study of delayed sleep phase disorder (DSPD) in adolescents. The mean age of the participants was 17.4 years, and 70% were female.
The participants completed the Mini International Neuropsychiatric Interview (MINI) and wore temperature loggers for 3 days to assess circadian rhythms. The primary outcome was the impact of circadian dynamics on different psychiatric problems. Delayed Sleep Phase (DSP) behavior was defined as going to sleep later than 1 a.m. at least three times a week.
Circadian length was determined through the temperature loggers worn for 3 days. Most participants also completed 1-week GeneActiv Original actigraphy measurements (wearing the actigraph for 1 week) and responded to the Morningness-Eveningness Questionnaire, which divided participants into three circadian preference groups: morning, intermediate, and evening. Sleep duration was calculated as total sleep time, sleep quality was estimated by sleep efficiency, and sleep timing was assessed by the midpoint of the sleep period.
Overall, the MINI interview results suggested that approximately one-third (36%) of the teens had at least one psychiatric problem, and 21% had comorbid conditions.
Severe depression was significantly associated with a longer circadian period (P = .002), while suicidality was significantly associated with a later midpoint and more irregular sleep (P = .007 for both).
Participants with agoraphobia slept longer than did those without, the researchers noted (P = .013). However, sleep duration was not significantly associated with other psychiatric conditions.
Manic episodes and psychotic disorders were associated with irregular sleep timing (P < .018 and P < .017, respectively).
When the researchers examined DSP and circadian preferences, they found that 21.5% of individuals with suicidality had characteristics of DSP, as did 21.5% of those with panic disorder.
Individuals with a preference for eveningness were significantly more likely to meet criteria for severe depression, panic disorder, generalized anxiety disorder, and obsessive-compulsive disorder than were those without a preference for eveningness, the researchers noted.
“Our findings are the first to encompass diverse circadian measures alongside an array of psychiatric symptoms in such a focused age range,” the researchers wrote in their discussion. The data reflect results from other studies and extend the likely role of circadian patterns in mental wellbeing, they said.
The study findings were limited by several factors including the lack of actual diagnoses from medical records and use of self-reported symptoms, the researchers noted. Other limitations included the lack of polysomnography data and small size of subgroups of the study sample.
However, the results were strengthened by the heterogenous study population and use of multiple measures to examine sleep and circadian rhythms, as well as consideration of personal circadian preferences, the researchers said.
“The importance of overall synchronization with environment is perhaps best highlighted by response to treatment: most psychopathologic symptoms benefit from sleep-targeted therapeutic approaches,” they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
, according to results from a European study.
A range of psychiatric symptoms and conditions has been linked to sleep pathologies, wrote Liisa Kuula, PhD, of the University of Helsinki, Finland, and colleagues. Some research suggests that late circadian rhythms and irregular sleep patterns increase the risk for psychiatric conditions, but the association has not been well studied, especially in adolescents, although the onset of psychiatric problems often occurs at this age, they said.
In a study published in the Journal of Psychiatric Research (2022 Apr 4. doi: 10.1016/j.jpsychires.2022.03.056.), the investigators reviewed data from 342 adolescents who were part of SleepHelsinki! a large cohort study of delayed sleep phase disorder (DSPD) in adolescents. The mean age of the participants was 17.4 years, and 70% were female.
The participants completed the Mini International Neuropsychiatric Interview (MINI) and wore temperature loggers for 3 days to assess circadian rhythms. The primary outcome was the impact of circadian dynamics on different psychiatric problems. Delayed Sleep Phase (DSP) behavior was defined as going to sleep later than 1 a.m. at least three times a week.
Circadian length was determined through the temperature loggers worn for 3 days. Most participants also completed 1-week GeneActiv Original actigraphy measurements (wearing the actigraph for 1 week) and responded to the Morningness-Eveningness Questionnaire, which divided participants into three circadian preference groups: morning, intermediate, and evening. Sleep duration was calculated as total sleep time, sleep quality was estimated by sleep efficiency, and sleep timing was assessed by the midpoint of the sleep period.
Overall, the MINI interview results suggested that approximately one-third (36%) of the teens had at least one psychiatric problem, and 21% had comorbid conditions.
Severe depression was significantly associated with a longer circadian period (P = .002), while suicidality was significantly associated with a later midpoint and more irregular sleep (P = .007 for both).
Participants with agoraphobia slept longer than did those without, the researchers noted (P = .013). However, sleep duration was not significantly associated with other psychiatric conditions.
Manic episodes and psychotic disorders were associated with irregular sleep timing (P < .018 and P < .017, respectively).
When the researchers examined DSP and circadian preferences, they found that 21.5% of individuals with suicidality had characteristics of DSP, as did 21.5% of those with panic disorder.
Individuals with a preference for eveningness were significantly more likely to meet criteria for severe depression, panic disorder, generalized anxiety disorder, and obsessive-compulsive disorder than were those without a preference for eveningness, the researchers noted.
“Our findings are the first to encompass diverse circadian measures alongside an array of psychiatric symptoms in such a focused age range,” the researchers wrote in their discussion. The data reflect results from other studies and extend the likely role of circadian patterns in mental wellbeing, they said.
The study findings were limited by several factors including the lack of actual diagnoses from medical records and use of self-reported symptoms, the researchers noted. Other limitations included the lack of polysomnography data and small size of subgroups of the study sample.
However, the results were strengthened by the heterogenous study population and use of multiple measures to examine sleep and circadian rhythms, as well as consideration of personal circadian preferences, the researchers said.
“The importance of overall synchronization with environment is perhaps best highlighted by response to treatment: most psychopathologic symptoms benefit from sleep-targeted therapeutic approaches,” they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
, according to results from a European study.
A range of psychiatric symptoms and conditions has been linked to sleep pathologies, wrote Liisa Kuula, PhD, of the University of Helsinki, Finland, and colleagues. Some research suggests that late circadian rhythms and irregular sleep patterns increase the risk for psychiatric conditions, but the association has not been well studied, especially in adolescents, although the onset of psychiatric problems often occurs at this age, they said.
In a study published in the Journal of Psychiatric Research (2022 Apr 4. doi: 10.1016/j.jpsychires.2022.03.056.), the investigators reviewed data from 342 adolescents who were part of SleepHelsinki! a large cohort study of delayed sleep phase disorder (DSPD) in adolescents. The mean age of the participants was 17.4 years, and 70% were female.
The participants completed the Mini International Neuropsychiatric Interview (MINI) and wore temperature loggers for 3 days to assess circadian rhythms. The primary outcome was the impact of circadian dynamics on different psychiatric problems. Delayed Sleep Phase (DSP) behavior was defined as going to sleep later than 1 a.m. at least three times a week.
Circadian length was determined through the temperature loggers worn for 3 days. Most participants also completed 1-week GeneActiv Original actigraphy measurements (wearing the actigraph for 1 week) and responded to the Morningness-Eveningness Questionnaire, which divided participants into three circadian preference groups: morning, intermediate, and evening. Sleep duration was calculated as total sleep time, sleep quality was estimated by sleep efficiency, and sleep timing was assessed by the midpoint of the sleep period.
Overall, the MINI interview results suggested that approximately one-third (36%) of the teens had at least one psychiatric problem, and 21% had comorbid conditions.
Severe depression was significantly associated with a longer circadian period (P = .002), while suicidality was significantly associated with a later midpoint and more irregular sleep (P = .007 for both).
Participants with agoraphobia slept longer than did those without, the researchers noted (P = .013). However, sleep duration was not significantly associated with other psychiatric conditions.
Manic episodes and psychotic disorders were associated with irregular sleep timing (P < .018 and P < .017, respectively).
When the researchers examined DSP and circadian preferences, they found that 21.5% of individuals with suicidality had characteristics of DSP, as did 21.5% of those with panic disorder.
Individuals with a preference for eveningness were significantly more likely to meet criteria for severe depression, panic disorder, generalized anxiety disorder, and obsessive-compulsive disorder than were those without a preference for eveningness, the researchers noted.
“Our findings are the first to encompass diverse circadian measures alongside an array of psychiatric symptoms in such a focused age range,” the researchers wrote in their discussion. The data reflect results from other studies and extend the likely role of circadian patterns in mental wellbeing, they said.
The study findings were limited by several factors including the lack of actual diagnoses from medical records and use of self-reported symptoms, the researchers noted. Other limitations included the lack of polysomnography data and small size of subgroups of the study sample.
However, the results were strengthened by the heterogenous study population and use of multiple measures to examine sleep and circadian rhythms, as well as consideration of personal circadian preferences, the researchers said.
“The importance of overall synchronization with environment is perhaps best highlighted by response to treatment: most psychopathologic symptoms benefit from sleep-targeted therapeutic approaches,” they concluded.
The study received no outside funding. The researchers had no financial conflicts to disclose.
FROM THE JOURNAL OF PSYCHIATRIC RESEARCH
Bariatric surgery can be a tool to relieve migraine
DENVER – , a neurologist told colleagues at the annual meeting of the American Headache Society. “There’s evidence-based medicine to support bariatric surgery, a lot of it, and the outcomes are actually pretty good,” said Jennifer McVige, MD, MA, of Dent Neurologic Institute in Buffalo, N.Y.
As Dr. McVige noted, research has linked obesity to migraine even after adjustment for comorbidities. A 2007 analysis of a survey of 30,215 participants, for example, found that “the proportion of subjects with severe headache pain increased with BMI, doubling in the morbidly obese relative to the normally weighted (odds ratio [OR] = 1.9).” And a 2011 study of 3,733 pregnant women found that risk of migraine increased in line with level of obesity: “obese women had a 1.48-fold increased odds of migraine (OR = 1.48; 95% confidence interval [CI], 1.12-1.96). Severely obese (OR = 2.07; 95% CI, 1.27-3.39) and morbidly obese (OR = 2.75; 95% CI, 1.60-4.70) had the highest odds of migraines.”
The link between obesity and headaches is unclear, she said, but there are hints at possible factors. For one, calcitonin gene-related peptide (CGRP) is increased in people with obesity and is an important factor in migraines. Additionally, nausea is quite common in people with migraine, suggesting a possible gut-brain interaction – or not.
“Nausea is associated with a lot of the medicines that we give patients with migraine. Is it the nausea that’s associated with the migraine medicine, or is nausea occurring at the end of the migraine?” she asked. “That’s always been kind of a conundrum for us.”
Whatever the case, she said, bariatric surgery appears to be helpful for patients with headache. Some studies have been small, but a 2021 analysis of 1,680 patients with migraine found that 55% experienced remission with no need for medication at 180 days post surgery. Women, older patients, and those taking more migraine medications were less likely to reach remission.
Research also suggests that bariatric surgery can relieve headache symptoms in patients with idiopathic intracranial hypertension.
Dr. McVige cautioned, however, that medical professionals must take special care when they talk to patients about their weight. “I’ve learned from conversations with my patients that they don’t like hearing ‘obese,’ or ‘fat,’ or ‘diet,’ or ‘losing weight.’ What they do like is ‘maybe we could try to find ways to be more healthy, to help your body to look the way that you would like it to look in the future. Let me help you. Maybe we can talk about nutrition. Maybe we can talk about exercise. Let’s talk about energy. Let’s talk about those types of things.’”
Unfortunately, there’s little research into how to have these conversations, Dr. McVige said. Still, “we need to be the first people to come forward and say, ‘This is a tough topic for me to talk about too. It makes me uncomfortable as well. I know you’re uncomfortable, but I have to talk to you because I care about you as a patient.’”
She also advised colleagues to not bring up weight right out of the gate. “It’s easier to say some of those things after you develop a relationship,” she said, “when they know you care about them.”
Dr. McVige reported multiple disclosures related to research funding and speaker fees.
DENVER – , a neurologist told colleagues at the annual meeting of the American Headache Society. “There’s evidence-based medicine to support bariatric surgery, a lot of it, and the outcomes are actually pretty good,” said Jennifer McVige, MD, MA, of Dent Neurologic Institute in Buffalo, N.Y.
As Dr. McVige noted, research has linked obesity to migraine even after adjustment for comorbidities. A 2007 analysis of a survey of 30,215 participants, for example, found that “the proportion of subjects with severe headache pain increased with BMI, doubling in the morbidly obese relative to the normally weighted (odds ratio [OR] = 1.9).” And a 2011 study of 3,733 pregnant women found that risk of migraine increased in line with level of obesity: “obese women had a 1.48-fold increased odds of migraine (OR = 1.48; 95% confidence interval [CI], 1.12-1.96). Severely obese (OR = 2.07; 95% CI, 1.27-3.39) and morbidly obese (OR = 2.75; 95% CI, 1.60-4.70) had the highest odds of migraines.”
The link between obesity and headaches is unclear, she said, but there are hints at possible factors. For one, calcitonin gene-related peptide (CGRP) is increased in people with obesity and is an important factor in migraines. Additionally, nausea is quite common in people with migraine, suggesting a possible gut-brain interaction – or not.
“Nausea is associated with a lot of the medicines that we give patients with migraine. Is it the nausea that’s associated with the migraine medicine, or is nausea occurring at the end of the migraine?” she asked. “That’s always been kind of a conundrum for us.”
Whatever the case, she said, bariatric surgery appears to be helpful for patients with headache. Some studies have been small, but a 2021 analysis of 1,680 patients with migraine found that 55% experienced remission with no need for medication at 180 days post surgery. Women, older patients, and those taking more migraine medications were less likely to reach remission.
Research also suggests that bariatric surgery can relieve headache symptoms in patients with idiopathic intracranial hypertension.
Dr. McVige cautioned, however, that medical professionals must take special care when they talk to patients about their weight. “I’ve learned from conversations with my patients that they don’t like hearing ‘obese,’ or ‘fat,’ or ‘diet,’ or ‘losing weight.’ What they do like is ‘maybe we could try to find ways to be more healthy, to help your body to look the way that you would like it to look in the future. Let me help you. Maybe we can talk about nutrition. Maybe we can talk about exercise. Let’s talk about energy. Let’s talk about those types of things.’”
Unfortunately, there’s little research into how to have these conversations, Dr. McVige said. Still, “we need to be the first people to come forward and say, ‘This is a tough topic for me to talk about too. It makes me uncomfortable as well. I know you’re uncomfortable, but I have to talk to you because I care about you as a patient.’”
She also advised colleagues to not bring up weight right out of the gate. “It’s easier to say some of those things after you develop a relationship,” she said, “when they know you care about them.”
Dr. McVige reported multiple disclosures related to research funding and speaker fees.
DENVER – , a neurologist told colleagues at the annual meeting of the American Headache Society. “There’s evidence-based medicine to support bariatric surgery, a lot of it, and the outcomes are actually pretty good,” said Jennifer McVige, MD, MA, of Dent Neurologic Institute in Buffalo, N.Y.
As Dr. McVige noted, research has linked obesity to migraine even after adjustment for comorbidities. A 2007 analysis of a survey of 30,215 participants, for example, found that “the proportion of subjects with severe headache pain increased with BMI, doubling in the morbidly obese relative to the normally weighted (odds ratio [OR] = 1.9).” And a 2011 study of 3,733 pregnant women found that risk of migraine increased in line with level of obesity: “obese women had a 1.48-fold increased odds of migraine (OR = 1.48; 95% confidence interval [CI], 1.12-1.96). Severely obese (OR = 2.07; 95% CI, 1.27-3.39) and morbidly obese (OR = 2.75; 95% CI, 1.60-4.70) had the highest odds of migraines.”
The link between obesity and headaches is unclear, she said, but there are hints at possible factors. For one, calcitonin gene-related peptide (CGRP) is increased in people with obesity and is an important factor in migraines. Additionally, nausea is quite common in people with migraine, suggesting a possible gut-brain interaction – or not.
“Nausea is associated with a lot of the medicines that we give patients with migraine. Is it the nausea that’s associated with the migraine medicine, or is nausea occurring at the end of the migraine?” she asked. “That’s always been kind of a conundrum for us.”
Whatever the case, she said, bariatric surgery appears to be helpful for patients with headache. Some studies have been small, but a 2021 analysis of 1,680 patients with migraine found that 55% experienced remission with no need for medication at 180 days post surgery. Women, older patients, and those taking more migraine medications were less likely to reach remission.
Research also suggests that bariatric surgery can relieve headache symptoms in patients with idiopathic intracranial hypertension.
Dr. McVige cautioned, however, that medical professionals must take special care when they talk to patients about their weight. “I’ve learned from conversations with my patients that they don’t like hearing ‘obese,’ or ‘fat,’ or ‘diet,’ or ‘losing weight.’ What they do like is ‘maybe we could try to find ways to be more healthy, to help your body to look the way that you would like it to look in the future. Let me help you. Maybe we can talk about nutrition. Maybe we can talk about exercise. Let’s talk about energy. Let’s talk about those types of things.’”
Unfortunately, there’s little research into how to have these conversations, Dr. McVige said. Still, “we need to be the first people to come forward and say, ‘This is a tough topic for me to talk about too. It makes me uncomfortable as well. I know you’re uncomfortable, but I have to talk to you because I care about you as a patient.’”
She also advised colleagues to not bring up weight right out of the gate. “It’s easier to say some of those things after you develop a relationship,” she said, “when they know you care about them.”
Dr. McVige reported multiple disclosures related to research funding and speaker fees.
AT AHS 2022
More Black mothers deliver by cesarean, not always by choice
When 29-year-old Sakeenah Fowler was pregnant with her first child, doctors kept a close watch. Ms. Fowler has lupus, high blood pressure, a history of blood clotting, and kidney problems that all could have endangered her or the health of her unborn baby.
She saw maternal-fetal specialists who could keep watch of her high-risk pregnancy, and she collected urine samples every 24 hours to make sure her kidneys were functioning properly from her home in Roebuck, S.C.
But the pregnancy ultimately proved uneventful; even her kidneys remained stable. So Ms. Fowler said she was shocked when her doctors ordered an emergency cesarean delivery after she had gone into active labor.
“I was already dilated all the way to 6 cm,” but the baby’s heart rate had decreased by a small amount, she says. “They thought it was best to just go ahead with a C-section.”
Ms. Fowler, who is Black, said she believes the surgical intervention was unnecessary and that she wasn’t given a chance to discuss her options for a vaginal childbirth.
“They already had it in their minds that I wasn’t going to make it through the pregnancy without any issues; then when I did, it was like they wanted to find something that made me have to have a C-section,” Ms. Fowler said. “It was close to the holidays; everybody was ready to go home. It was just like I was pushed to do what they wanted me to do.”
Ms. Fowler’s sense of a lack of choice is important beyond the measure of patient experience. While cesarean deliveries can be a lifeline for mother and baby, they can put up massive roadblocks to maternal and infant health when not necessary.
“The risk of hemorrhage, infection – on average, all of these go up when you have surgery instead of a vaginal delivery,” says Kimberly B. Glazer, PhD, a perinatal epidemiologist at the Icahn School of Medicine at Mount Sinai, New York.
“Birth is one of the most salient experiences you can have. People want to feel like their values and preferences – whatever they may be – were honored and respected. Even if the delivery goes a different way than you wanted, feeling like your values were taken into account is very important.”
More than 1 million women undergo cesarean deliveries in the United States every year, composing over 31% of all births in 2020, according to the Centers for Disease Control and Prevention.
The World Health Organization, meanwhile, recommends a rate of cesarean delivery of no more than 15% per region. Whether or not all the U.S. procedures were medically warranted is unclear, however.
Black women have higher odds of undergoing a cesarean: 36% undergo surgical deliveries annually, compared with about 30% of White women. Black women are also about three times more likely to die of pregnancy-related causes than White women.
Risk becomes reality
Ms. Fowler eventually developed an infection in her cesarean surgical wound, but her doctors initially insisted her alternating chills and fever were merely postpartum hormonal swings, she says.
“I thought something had to be wrong, but they just kept saying nothing was wrong,” she says.
By the time her doctors caught the infection, Ms. Fowler was readmitted to the hospital for several days of IV antibiotic therapy. The infection “almost got into my bloodstream and could have killed me,” she says.
While cesarean deliveries are associated with decreases in maternal, neonatal, and infant mortality, the benefits are only seen up to a certain threshold. The WHO, for instance, has reported that over the 15% threshold, that lower mortality benefit disappears.
“When medically necessary, cesarean delivery can improve outcomes for mother and baby. But the fact that cesarean section rates have increased in recent years without a corresponding improvement in health outcomes indicates overreliance on the procedure,” Dr. Glazer says.
Clinical discretion leads to biased judgment calls
Rates of cesarean deliveries are even higher among low-risk pregnancies in women of color than in White women. Between 2016 and 2019, the overall rate of cesarean deliveries for low-risk births was 23%, according to a recent analysis. But the rate was almost 18% higher among Black women than among White women (27% vs. 22%).
“When you see data about these subjective indications varying by race and ethnicity, I think that’s pointing us toward some answers,” Dr. Glazer says. “Once you adjust for all these measures, prepregnancy characteristics, and risk factors, the research identifies variation in quality and outcomes that is rooted in structural and systemic racism in health care, implicit bias from clinicians.”
Researchers investigating cesarean deliveries have found that Black women are more likely to undergo the surgery for reasons that are highly subjective, such as fetal distress.
“There is a huge range of how concerning a fetal heart rate can be, and some health providers might perform a C-section for only minor changes in the fetal heart rate, while others might wait until it is much worse,” said Rebecca Hamm, MD, an assistant professor of obstetrics and gynecology at the Perelman School of Medicine at the University of Pennsylvania.
At least some of the differences in care can be explained by where women deliver their babies, studies have shown. Women of color disproportionately deliver at hospitals with poorer quality outcomes for moms and babies.
Dealing with the aftermath
There can be costs that reverberate throughout the life of a mother, child, and their family as the result of surgical delivery.
“Cesarean sections cost a lot more,” says Jamila Taylor, PhD, director of health care reform and a senior fellow with The Century Foundation, a progressive policy think tank in Washington, D.C. The cost of a cesarean delivery averages about $17,000, compared with about $12,200 for a vaginal birth; for uninsured patients, surgical deliveries cost about $9,000 more than vaginal deliveries.
Dr. Taylor, who has studied the historical mistreatment of Black women in obstetrics, noted that this cost includes not just the bill for surgery but also a prolonged recovery time that is often spent in a hospital bed.
Beyond the detrimental effect that a large hospital bill for delivery and aftercare can have on families, other costs can crop up later. Infants delivered by cesarean surgery are more likely to develop an infection, breathing problems, and to spend time in the neonatal intensive care unit than babies born vaginally. Although studies suggest these outcomes may result from a medically necessary health concern that spurred the cesarean surgery, they often stem from the delivery itself.
Babies born surgically also miss out on the benefits of passing through the birth canal, such as supporting a newborn’s immune system and preparing their lungs to breathe oxygen after birth.
Most of the efforts to reduce inequities in maternal care are happening at the clinical level, aimed at both patients and providers, Dr. Taylor says.
“As advocates, we’re talking about how we can help Black women be advocates for themselves in the health care system – if the physician suggests a C-section, getting a second opinion, or walking through what a [surgical delivery] will mean and what their recovery will look like,” she says.
Women are also increasingly choosing non-hospital settings to deliver when possible, Dr. Taylor says. Including doulas or midwife practitioners in the maternal care team can reduce unnecessary cesarean deliveries among Black women, according to Camille Clare, MD, chair of the New York chapter of the American College of Obstetricians and Gynecologists.
Also, last year, race was removed from the vaginal birth after C-section (VBAC) calculator, which is used to gauge the safety of vaginal delivery in women with a history of surgical birth. The original calculator included race-based correction factors for Black women and Hispanic women. It predicted a lower likelihood of successful vaginal deliveries for women who already had a C-section and who identify as Black or Hispanic than for White women with otherwise identical characteristics, such as age, weight, and a history of cesarean delivery.
“Those are things that over time should reduce the high rates of cesarean section for Black women in particular,” Dr. Clare says.
In addition to embracing the updated calculator and including nurse-midwives and doulas in their obstetrics services, Penn Medicine, Philadelphia received a federal grant to study the impact of creating a standard plan for deliveries. This includes standardizing the induction of labor and any effect that might have on reducing C-section rates.
“This idea that biases lead to difference in decisionmaking, and that by standardizing practices we could address these differences – people were somewhat resistant at first,” Dr. Hamm says. “They didn’t believe there were differences in their practices.”
People struggle to recognize those differences, she says, and “it takes active participation in reducing disparities to make that happen.”
At the community level, Synergistic Sisters in Science (SIS), a group of maternal health experts and health equity advocates, is working on a project called PM3, to reduce maternal mortality through mobile technology.
The smartphone app will provide information for new moms to empower them to start conversations with health care providers. It also connects users to social support and resources. SIS is especially hoping to engage Black women living in rural areas.
“There is so much mistrust due to things like unnecessary C-sections and the fact that Black women feel they aren’t heard,” said Natalie Hernandez, PhD, executive director of the Center for Maternal Health Equity at Morehouse School of Medicine, Atlanta. “Here is a tool that gives a woman information that’s culturally centered, looks like her, and was informed by her voice.”
A version of this article first appeared on WebMD.com.
When 29-year-old Sakeenah Fowler was pregnant with her first child, doctors kept a close watch. Ms. Fowler has lupus, high blood pressure, a history of blood clotting, and kidney problems that all could have endangered her or the health of her unborn baby.
She saw maternal-fetal specialists who could keep watch of her high-risk pregnancy, and she collected urine samples every 24 hours to make sure her kidneys were functioning properly from her home in Roebuck, S.C.
But the pregnancy ultimately proved uneventful; even her kidneys remained stable. So Ms. Fowler said she was shocked when her doctors ordered an emergency cesarean delivery after she had gone into active labor.
“I was already dilated all the way to 6 cm,” but the baby’s heart rate had decreased by a small amount, she says. “They thought it was best to just go ahead with a C-section.”
Ms. Fowler, who is Black, said she believes the surgical intervention was unnecessary and that she wasn’t given a chance to discuss her options for a vaginal childbirth.
“They already had it in their minds that I wasn’t going to make it through the pregnancy without any issues; then when I did, it was like they wanted to find something that made me have to have a C-section,” Ms. Fowler said. “It was close to the holidays; everybody was ready to go home. It was just like I was pushed to do what they wanted me to do.”
Ms. Fowler’s sense of a lack of choice is important beyond the measure of patient experience. While cesarean deliveries can be a lifeline for mother and baby, they can put up massive roadblocks to maternal and infant health when not necessary.
“The risk of hemorrhage, infection – on average, all of these go up when you have surgery instead of a vaginal delivery,” says Kimberly B. Glazer, PhD, a perinatal epidemiologist at the Icahn School of Medicine at Mount Sinai, New York.
“Birth is one of the most salient experiences you can have. People want to feel like their values and preferences – whatever they may be – were honored and respected. Even if the delivery goes a different way than you wanted, feeling like your values were taken into account is very important.”
More than 1 million women undergo cesarean deliveries in the United States every year, composing over 31% of all births in 2020, according to the Centers for Disease Control and Prevention.
The World Health Organization, meanwhile, recommends a rate of cesarean delivery of no more than 15% per region. Whether or not all the U.S. procedures were medically warranted is unclear, however.
Black women have higher odds of undergoing a cesarean: 36% undergo surgical deliveries annually, compared with about 30% of White women. Black women are also about three times more likely to die of pregnancy-related causes than White women.
Risk becomes reality
Ms. Fowler eventually developed an infection in her cesarean surgical wound, but her doctors initially insisted her alternating chills and fever were merely postpartum hormonal swings, she says.
“I thought something had to be wrong, but they just kept saying nothing was wrong,” she says.
By the time her doctors caught the infection, Ms. Fowler was readmitted to the hospital for several days of IV antibiotic therapy. The infection “almost got into my bloodstream and could have killed me,” she says.
While cesarean deliveries are associated with decreases in maternal, neonatal, and infant mortality, the benefits are only seen up to a certain threshold. The WHO, for instance, has reported that over the 15% threshold, that lower mortality benefit disappears.
“When medically necessary, cesarean delivery can improve outcomes for mother and baby. But the fact that cesarean section rates have increased in recent years without a corresponding improvement in health outcomes indicates overreliance on the procedure,” Dr. Glazer says.
Clinical discretion leads to biased judgment calls
Rates of cesarean deliveries are even higher among low-risk pregnancies in women of color than in White women. Between 2016 and 2019, the overall rate of cesarean deliveries for low-risk births was 23%, according to a recent analysis. But the rate was almost 18% higher among Black women than among White women (27% vs. 22%).
“When you see data about these subjective indications varying by race and ethnicity, I think that’s pointing us toward some answers,” Dr. Glazer says. “Once you adjust for all these measures, prepregnancy characteristics, and risk factors, the research identifies variation in quality and outcomes that is rooted in structural and systemic racism in health care, implicit bias from clinicians.”
Researchers investigating cesarean deliveries have found that Black women are more likely to undergo the surgery for reasons that are highly subjective, such as fetal distress.
“There is a huge range of how concerning a fetal heart rate can be, and some health providers might perform a C-section for only minor changes in the fetal heart rate, while others might wait until it is much worse,” said Rebecca Hamm, MD, an assistant professor of obstetrics and gynecology at the Perelman School of Medicine at the University of Pennsylvania.
At least some of the differences in care can be explained by where women deliver their babies, studies have shown. Women of color disproportionately deliver at hospitals with poorer quality outcomes for moms and babies.
Dealing with the aftermath
There can be costs that reverberate throughout the life of a mother, child, and their family as the result of surgical delivery.
“Cesarean sections cost a lot more,” says Jamila Taylor, PhD, director of health care reform and a senior fellow with The Century Foundation, a progressive policy think tank in Washington, D.C. The cost of a cesarean delivery averages about $17,000, compared with about $12,200 for a vaginal birth; for uninsured patients, surgical deliveries cost about $9,000 more than vaginal deliveries.
Dr. Taylor, who has studied the historical mistreatment of Black women in obstetrics, noted that this cost includes not just the bill for surgery but also a prolonged recovery time that is often spent in a hospital bed.
Beyond the detrimental effect that a large hospital bill for delivery and aftercare can have on families, other costs can crop up later. Infants delivered by cesarean surgery are more likely to develop an infection, breathing problems, and to spend time in the neonatal intensive care unit than babies born vaginally. Although studies suggest these outcomes may result from a medically necessary health concern that spurred the cesarean surgery, they often stem from the delivery itself.
Babies born surgically also miss out on the benefits of passing through the birth canal, such as supporting a newborn’s immune system and preparing their lungs to breathe oxygen after birth.
Most of the efforts to reduce inequities in maternal care are happening at the clinical level, aimed at both patients and providers, Dr. Taylor says.
“As advocates, we’re talking about how we can help Black women be advocates for themselves in the health care system – if the physician suggests a C-section, getting a second opinion, or walking through what a [surgical delivery] will mean and what their recovery will look like,” she says.
Women are also increasingly choosing non-hospital settings to deliver when possible, Dr. Taylor says. Including doulas or midwife practitioners in the maternal care team can reduce unnecessary cesarean deliveries among Black women, according to Camille Clare, MD, chair of the New York chapter of the American College of Obstetricians and Gynecologists.
Also, last year, race was removed from the vaginal birth after C-section (VBAC) calculator, which is used to gauge the safety of vaginal delivery in women with a history of surgical birth. The original calculator included race-based correction factors for Black women and Hispanic women. It predicted a lower likelihood of successful vaginal deliveries for women who already had a C-section and who identify as Black or Hispanic than for White women with otherwise identical characteristics, such as age, weight, and a history of cesarean delivery.
“Those are things that over time should reduce the high rates of cesarean section for Black women in particular,” Dr. Clare says.
In addition to embracing the updated calculator and including nurse-midwives and doulas in their obstetrics services, Penn Medicine, Philadelphia received a federal grant to study the impact of creating a standard plan for deliveries. This includes standardizing the induction of labor and any effect that might have on reducing C-section rates.
“This idea that biases lead to difference in decisionmaking, and that by standardizing practices we could address these differences – people were somewhat resistant at first,” Dr. Hamm says. “They didn’t believe there were differences in their practices.”
People struggle to recognize those differences, she says, and “it takes active participation in reducing disparities to make that happen.”
At the community level, Synergistic Sisters in Science (SIS), a group of maternal health experts and health equity advocates, is working on a project called PM3, to reduce maternal mortality through mobile technology.
The smartphone app will provide information for new moms to empower them to start conversations with health care providers. It also connects users to social support and resources. SIS is especially hoping to engage Black women living in rural areas.
“There is so much mistrust due to things like unnecessary C-sections and the fact that Black women feel they aren’t heard,” said Natalie Hernandez, PhD, executive director of the Center for Maternal Health Equity at Morehouse School of Medicine, Atlanta. “Here is a tool that gives a woman information that’s culturally centered, looks like her, and was informed by her voice.”
A version of this article first appeared on WebMD.com.
When 29-year-old Sakeenah Fowler was pregnant with her first child, doctors kept a close watch. Ms. Fowler has lupus, high blood pressure, a history of blood clotting, and kidney problems that all could have endangered her or the health of her unborn baby.
She saw maternal-fetal specialists who could keep watch of her high-risk pregnancy, and she collected urine samples every 24 hours to make sure her kidneys were functioning properly from her home in Roebuck, S.C.
But the pregnancy ultimately proved uneventful; even her kidneys remained stable. So Ms. Fowler said she was shocked when her doctors ordered an emergency cesarean delivery after she had gone into active labor.
“I was already dilated all the way to 6 cm,” but the baby’s heart rate had decreased by a small amount, she says. “They thought it was best to just go ahead with a C-section.”
Ms. Fowler, who is Black, said she believes the surgical intervention was unnecessary and that she wasn’t given a chance to discuss her options for a vaginal childbirth.
“They already had it in their minds that I wasn’t going to make it through the pregnancy without any issues; then when I did, it was like they wanted to find something that made me have to have a C-section,” Ms. Fowler said. “It was close to the holidays; everybody was ready to go home. It was just like I was pushed to do what they wanted me to do.”
Ms. Fowler’s sense of a lack of choice is important beyond the measure of patient experience. While cesarean deliveries can be a lifeline for mother and baby, they can put up massive roadblocks to maternal and infant health when not necessary.
“The risk of hemorrhage, infection – on average, all of these go up when you have surgery instead of a vaginal delivery,” says Kimberly B. Glazer, PhD, a perinatal epidemiologist at the Icahn School of Medicine at Mount Sinai, New York.
“Birth is one of the most salient experiences you can have. People want to feel like their values and preferences – whatever they may be – were honored and respected. Even if the delivery goes a different way than you wanted, feeling like your values were taken into account is very important.”
More than 1 million women undergo cesarean deliveries in the United States every year, composing over 31% of all births in 2020, according to the Centers for Disease Control and Prevention.
The World Health Organization, meanwhile, recommends a rate of cesarean delivery of no more than 15% per region. Whether or not all the U.S. procedures were medically warranted is unclear, however.
Black women have higher odds of undergoing a cesarean: 36% undergo surgical deliveries annually, compared with about 30% of White women. Black women are also about three times more likely to die of pregnancy-related causes than White women.
Risk becomes reality
Ms. Fowler eventually developed an infection in her cesarean surgical wound, but her doctors initially insisted her alternating chills and fever were merely postpartum hormonal swings, she says.
“I thought something had to be wrong, but they just kept saying nothing was wrong,” she says.
By the time her doctors caught the infection, Ms. Fowler was readmitted to the hospital for several days of IV antibiotic therapy. The infection “almost got into my bloodstream and could have killed me,” she says.
While cesarean deliveries are associated with decreases in maternal, neonatal, and infant mortality, the benefits are only seen up to a certain threshold. The WHO, for instance, has reported that over the 15% threshold, that lower mortality benefit disappears.
“When medically necessary, cesarean delivery can improve outcomes for mother and baby. But the fact that cesarean section rates have increased in recent years without a corresponding improvement in health outcomes indicates overreliance on the procedure,” Dr. Glazer says.
Clinical discretion leads to biased judgment calls
Rates of cesarean deliveries are even higher among low-risk pregnancies in women of color than in White women. Between 2016 and 2019, the overall rate of cesarean deliveries for low-risk births was 23%, according to a recent analysis. But the rate was almost 18% higher among Black women than among White women (27% vs. 22%).
“When you see data about these subjective indications varying by race and ethnicity, I think that’s pointing us toward some answers,” Dr. Glazer says. “Once you adjust for all these measures, prepregnancy characteristics, and risk factors, the research identifies variation in quality and outcomes that is rooted in structural and systemic racism in health care, implicit bias from clinicians.”
Researchers investigating cesarean deliveries have found that Black women are more likely to undergo the surgery for reasons that are highly subjective, such as fetal distress.
“There is a huge range of how concerning a fetal heart rate can be, and some health providers might perform a C-section for only minor changes in the fetal heart rate, while others might wait until it is much worse,” said Rebecca Hamm, MD, an assistant professor of obstetrics and gynecology at the Perelman School of Medicine at the University of Pennsylvania.
At least some of the differences in care can be explained by where women deliver their babies, studies have shown. Women of color disproportionately deliver at hospitals with poorer quality outcomes for moms and babies.
Dealing with the aftermath
There can be costs that reverberate throughout the life of a mother, child, and their family as the result of surgical delivery.
“Cesarean sections cost a lot more,” says Jamila Taylor, PhD, director of health care reform and a senior fellow with The Century Foundation, a progressive policy think tank in Washington, D.C. The cost of a cesarean delivery averages about $17,000, compared with about $12,200 for a vaginal birth; for uninsured patients, surgical deliveries cost about $9,000 more than vaginal deliveries.
Dr. Taylor, who has studied the historical mistreatment of Black women in obstetrics, noted that this cost includes not just the bill for surgery but also a prolonged recovery time that is often spent in a hospital bed.
Beyond the detrimental effect that a large hospital bill for delivery and aftercare can have on families, other costs can crop up later. Infants delivered by cesarean surgery are more likely to develop an infection, breathing problems, and to spend time in the neonatal intensive care unit than babies born vaginally. Although studies suggest these outcomes may result from a medically necessary health concern that spurred the cesarean surgery, they often stem from the delivery itself.
Babies born surgically also miss out on the benefits of passing through the birth canal, such as supporting a newborn’s immune system and preparing their lungs to breathe oxygen after birth.
Most of the efforts to reduce inequities in maternal care are happening at the clinical level, aimed at both patients and providers, Dr. Taylor says.
“As advocates, we’re talking about how we can help Black women be advocates for themselves in the health care system – if the physician suggests a C-section, getting a second opinion, or walking through what a [surgical delivery] will mean and what their recovery will look like,” she says.
Women are also increasingly choosing non-hospital settings to deliver when possible, Dr. Taylor says. Including doulas or midwife practitioners in the maternal care team can reduce unnecessary cesarean deliveries among Black women, according to Camille Clare, MD, chair of the New York chapter of the American College of Obstetricians and Gynecologists.
Also, last year, race was removed from the vaginal birth after C-section (VBAC) calculator, which is used to gauge the safety of vaginal delivery in women with a history of surgical birth. The original calculator included race-based correction factors for Black women and Hispanic women. It predicted a lower likelihood of successful vaginal deliveries for women who already had a C-section and who identify as Black or Hispanic than for White women with otherwise identical characteristics, such as age, weight, and a history of cesarean delivery.
“Those are things that over time should reduce the high rates of cesarean section for Black women in particular,” Dr. Clare says.
In addition to embracing the updated calculator and including nurse-midwives and doulas in their obstetrics services, Penn Medicine, Philadelphia received a federal grant to study the impact of creating a standard plan for deliveries. This includes standardizing the induction of labor and any effect that might have on reducing C-section rates.
“This idea that biases lead to difference in decisionmaking, and that by standardizing practices we could address these differences – people were somewhat resistant at first,” Dr. Hamm says. “They didn’t believe there were differences in their practices.”
People struggle to recognize those differences, she says, and “it takes active participation in reducing disparities to make that happen.”
At the community level, Synergistic Sisters in Science (SIS), a group of maternal health experts and health equity advocates, is working on a project called PM3, to reduce maternal mortality through mobile technology.
The smartphone app will provide information for new moms to empower them to start conversations with health care providers. It also connects users to social support and resources. SIS is especially hoping to engage Black women living in rural areas.
“There is so much mistrust due to things like unnecessary C-sections and the fact that Black women feel they aren’t heard,” said Natalie Hernandez, PhD, executive director of the Center for Maternal Health Equity at Morehouse School of Medicine, Atlanta. “Here is a tool that gives a woman information that’s culturally centered, looks like her, and was informed by her voice.”
A version of this article first appeared on WebMD.com.
Food allergy test breakthrough: Less risk, more useful results
What would you do if you believed you had a serious health issue, but the best way to find out for sure might kill you?
That’s the reality for patients who wish to confirm or rule out a food allergy, says Sindy Tang, PhD, an associate professor of mechanical engineering at Stanford (Calif.) University.
And it’s the reason Dr. Tang and her colleagues are developing a food allergy test that’s not only safer, but also more reliable than today’s tests. In a paper in the journal Lab on a Chip, Dr. Tang and her colleagues outline the basis for this future test, which isolates a food allergy marker from the blood using a magnetic field.
How today’s food allergy tests fall short
The gold standard for food allergy diagnosis is something called the oral food challenge. That’s when the patient eats gradually increasing amounts of a problem food – say, peanuts – every 15 to 30 minutes to see if symptoms occur. This means highly allergic patients may risk anaphylaxis, an allergic reaction that causes inflammation so severe that breathing becomes restricted and blood pressure drops. Because of that, a clinical team must be at the ready with treatments like oxygen, epinephrine, or albuterol.
“The test is very accurate, but it’s also potentially unsafe and even fatal in rare cases,” Dr. Tang says. “That’s led to many sham tests advertised online that claim to use hair samples for food tests, but those are inaccurate and potentially dangerous, since they may give someone a false sense of confidence about a food they should avoid.”
Less risky tests are available, such as skin-prick tests – those involve scratching a small amount of the food into a patient’s arm – as well as blood tests that measure allergen-specific antibodies.
“Unfortunately, both of those are not that accurate and have high false-positive rates,” Dr. Tang says. “The best method is the oral food challenge, which many patients are afraid to do, not surprisingly.”
The future of food allergy testing: faster, safer, more reliable
In their study, the Stanford researchers focused on a type of white blood cell known as basophils, which release histamine when triggered by allergens. By using magnetic nanoparticles that bind to some blood cells but not basophils, they were able to separate basophils from the blood with a magnetic field in just 10 minutes.
Once isolated, the basophils are exposed to potential allergens. If they react, that’s a sign of an allergy.
Basophils have been isolated in labs before but not nearly this quickly and efficiently, Dr. Tang says.
“For true basophil activation, you need the blood to be fresh, which is challenging when you have to send it to a lab,” Dr. Tang says. “Being able to do this kind of test within a clinic or an in-house lab would be a big step forward.”
Next steps
While this represents a breakthrough in basophil activation testing, more research is needed to fully develop the system for clinical use. It must be standardized, automated, and miniaturized, the researchers say.
That said, the results give hope to those with food allergies that tomorrow’s gold-standard test will require only a blood sample without an emergency team standing by.
A version of this article first appeared on WebMD.com.
What would you do if you believed you had a serious health issue, but the best way to find out for sure might kill you?
That’s the reality for patients who wish to confirm or rule out a food allergy, says Sindy Tang, PhD, an associate professor of mechanical engineering at Stanford (Calif.) University.
And it’s the reason Dr. Tang and her colleagues are developing a food allergy test that’s not only safer, but also more reliable than today’s tests. In a paper in the journal Lab on a Chip, Dr. Tang and her colleagues outline the basis for this future test, which isolates a food allergy marker from the blood using a magnetic field.
How today’s food allergy tests fall short
The gold standard for food allergy diagnosis is something called the oral food challenge. That’s when the patient eats gradually increasing amounts of a problem food – say, peanuts – every 15 to 30 minutes to see if symptoms occur. This means highly allergic patients may risk anaphylaxis, an allergic reaction that causes inflammation so severe that breathing becomes restricted and blood pressure drops. Because of that, a clinical team must be at the ready with treatments like oxygen, epinephrine, or albuterol.
“The test is very accurate, but it’s also potentially unsafe and even fatal in rare cases,” Dr. Tang says. “That’s led to many sham tests advertised online that claim to use hair samples for food tests, but those are inaccurate and potentially dangerous, since they may give someone a false sense of confidence about a food they should avoid.”
Less risky tests are available, such as skin-prick tests – those involve scratching a small amount of the food into a patient’s arm – as well as blood tests that measure allergen-specific antibodies.
“Unfortunately, both of those are not that accurate and have high false-positive rates,” Dr. Tang says. “The best method is the oral food challenge, which many patients are afraid to do, not surprisingly.”
The future of food allergy testing: faster, safer, more reliable
In their study, the Stanford researchers focused on a type of white blood cell known as basophils, which release histamine when triggered by allergens. By using magnetic nanoparticles that bind to some blood cells but not basophils, they were able to separate basophils from the blood with a magnetic field in just 10 minutes.
Once isolated, the basophils are exposed to potential allergens. If they react, that’s a sign of an allergy.
Basophils have been isolated in labs before but not nearly this quickly and efficiently, Dr. Tang says.
“For true basophil activation, you need the blood to be fresh, which is challenging when you have to send it to a lab,” Dr. Tang says. “Being able to do this kind of test within a clinic or an in-house lab would be a big step forward.”
Next steps
While this represents a breakthrough in basophil activation testing, more research is needed to fully develop the system for clinical use. It must be standardized, automated, and miniaturized, the researchers say.
That said, the results give hope to those with food allergies that tomorrow’s gold-standard test will require only a blood sample without an emergency team standing by.
A version of this article first appeared on WebMD.com.
What would you do if you believed you had a serious health issue, but the best way to find out for sure might kill you?
That’s the reality for patients who wish to confirm or rule out a food allergy, says Sindy Tang, PhD, an associate professor of mechanical engineering at Stanford (Calif.) University.
And it’s the reason Dr. Tang and her colleagues are developing a food allergy test that’s not only safer, but also more reliable than today’s tests. In a paper in the journal Lab on a Chip, Dr. Tang and her colleagues outline the basis for this future test, which isolates a food allergy marker from the blood using a magnetic field.
How today’s food allergy tests fall short
The gold standard for food allergy diagnosis is something called the oral food challenge. That’s when the patient eats gradually increasing amounts of a problem food – say, peanuts – every 15 to 30 minutes to see if symptoms occur. This means highly allergic patients may risk anaphylaxis, an allergic reaction that causes inflammation so severe that breathing becomes restricted and blood pressure drops. Because of that, a clinical team must be at the ready with treatments like oxygen, epinephrine, or albuterol.
“The test is very accurate, but it’s also potentially unsafe and even fatal in rare cases,” Dr. Tang says. “That’s led to many sham tests advertised online that claim to use hair samples for food tests, but those are inaccurate and potentially dangerous, since they may give someone a false sense of confidence about a food they should avoid.”
Less risky tests are available, such as skin-prick tests – those involve scratching a small amount of the food into a patient’s arm – as well as blood tests that measure allergen-specific antibodies.
“Unfortunately, both of those are not that accurate and have high false-positive rates,” Dr. Tang says. “The best method is the oral food challenge, which many patients are afraid to do, not surprisingly.”
The future of food allergy testing: faster, safer, more reliable
In their study, the Stanford researchers focused on a type of white blood cell known as basophils, which release histamine when triggered by allergens. By using magnetic nanoparticles that bind to some blood cells but not basophils, they were able to separate basophils from the blood with a magnetic field in just 10 minutes.
Once isolated, the basophils are exposed to potential allergens. If they react, that’s a sign of an allergy.
Basophils have been isolated in labs before but not nearly this quickly and efficiently, Dr. Tang says.
“For true basophil activation, you need the blood to be fresh, which is challenging when you have to send it to a lab,” Dr. Tang says. “Being able to do this kind of test within a clinic or an in-house lab would be a big step forward.”
Next steps
While this represents a breakthrough in basophil activation testing, more research is needed to fully develop the system for clinical use. It must be standardized, automated, and miniaturized, the researchers say.
That said, the results give hope to those with food allergies that tomorrow’s gold-standard test will require only a blood sample without an emergency team standing by.
A version of this article first appeared on WebMD.com.
A unique care model for comorbid depression, PTSD
“We know there are strains on the mental health care system, and sometimes something as simple as getting to see a psychiatrist can be incredibly challenging,” coinvestigator Zachary Zuschlag, MD, staff psychiatrist at the James A. Haley Veterans’ Hospital and assistant professor at the University of South Florida, both in Tampa, said in an interview.
“So, a model that encourages primary care doctors, together with consultation from us [psychiatrists] to effectively treat these patients in a more proactive way, is very beneficial,” Dr. Zuschlag said.
The findings were presented at the American Society of Clinical Psychopharmacology annual meeting.
Common bedfellows
Dr. Zuschlag noted that comorbid PTSD and depression is common, but it is often considered too complex to be managed in a primary care setting.
Although treating these patients can be challenging, Dr. Zuschlag, who also heads his Veterans Administration facility’s antidepressant monitoring program (ADM), said that when he started the program for this patient population, he used “a much more inclusive model and welcomed these patients even if they had co-occurring issues.”
“Anecdotally, we had seen that our patients with [depression and] co-occurring PTSD appeared to be doing as well as their peers without PTSD, and we just wanted to look at it more systematically,” he added.
The ADM program is specifically designed for psychopharmacologic management of depression and anxiety in the primary care setting. It involves an interdisciplinary team of RN care managers, consulting psychiatrists, psychologists, and primary care physicians. Patients in primary care clinics deemed likely to benefit from psychiatric medications can be enrolled and followed in the program.
The program consists of structured, protocol-based telephone contacts from the RN care managers at scheduled intervals, usually every 3-4 weeks, said Dr. Zuschlag.
During calls, information is collected via evidence-based mental health symptomatic assessment scales. The consulting psychiatrists use this and other information to help guide treatment and coordinate with patients’ primary care physicians to adjust the treatment plan, including medication changes and additional psychotherapy.
To determine the program’s efficacy the investigators retrospectively reviewed all patients enrolled in the ADM program during its first 10 months. Of the 433 program participants, 112 (26%) were identified with active PTSD symptoms at baseline. Another 43 patients had a prior diagnosis of PTSD.
Program completion rates for the cohort with PTSD did not differ from that of the cohort without PTSD.
Overall, mean improvements in depression and anxiety symptoms were evidenced by changes in Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder Assessment-7 (GAD-7) scores of 44% and 43%, respectively.
No differences in mean reduction in symptoms of depression were observed when comparing those with no history of PTSD with those with any history of PTSD (–6.16 vs. –5.42; P = .3244) or with those with active PTSD symptoms (–6.16 vs. –5.54; P = .4543).
Similarly, for anxiety, a mean reduction of –5.61 on the GAD-7 score was observed for the cohort without PTSD, compared with –4.99 in the cohort with any history of PTSD and –5.35 in the cohort with active PTSD symptoms. Again, these differences were nonsignificant.
Dr. Zuschlag noted that the VA setting is unique, with a lot of resources available to conduct such a program as ADM.
“Care management programs that are multidisciplinary are very effective and, in our experience, those who have completed the program do exceptionally well. The patients love it because there is a lot of contact between them and their various care providers,” he said.
A model for other settings?
Commenting on the study, Nagy A. Youssef, MD, PhD, professor of psychiatry and director of clinical research at Ohio State University, Columbus, called the results “interesting.”
“Treating patients with comorbid mild to moderate depression and current or past PTSD within the primary care setting using a care management program could be a model for other VA hospitals as well as in non-VA settings,” said Dr. Youssef, who was not part of the study.
Dr. Youssef noted that not only was there no difference in symptomatic improvement between the depression-plus-PTSD and depression-only groups, but program completion rates did not differ.
This further emphasizes “the potential utility of this approach in initial patient treatment, especially with limited mental health resources and the need to help more patients,” he said.
Dr. Zuschlag and Dr. Youssef report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
“We know there are strains on the mental health care system, and sometimes something as simple as getting to see a psychiatrist can be incredibly challenging,” coinvestigator Zachary Zuschlag, MD, staff psychiatrist at the James A. Haley Veterans’ Hospital and assistant professor at the University of South Florida, both in Tampa, said in an interview.
“So, a model that encourages primary care doctors, together with consultation from us [psychiatrists] to effectively treat these patients in a more proactive way, is very beneficial,” Dr. Zuschlag said.
The findings were presented at the American Society of Clinical Psychopharmacology annual meeting.
Common bedfellows
Dr. Zuschlag noted that comorbid PTSD and depression is common, but it is often considered too complex to be managed in a primary care setting.
Although treating these patients can be challenging, Dr. Zuschlag, who also heads his Veterans Administration facility’s antidepressant monitoring program (ADM), said that when he started the program for this patient population, he used “a much more inclusive model and welcomed these patients even if they had co-occurring issues.”
“Anecdotally, we had seen that our patients with [depression and] co-occurring PTSD appeared to be doing as well as their peers without PTSD, and we just wanted to look at it more systematically,” he added.
The ADM program is specifically designed for psychopharmacologic management of depression and anxiety in the primary care setting. It involves an interdisciplinary team of RN care managers, consulting psychiatrists, psychologists, and primary care physicians. Patients in primary care clinics deemed likely to benefit from psychiatric medications can be enrolled and followed in the program.
The program consists of structured, protocol-based telephone contacts from the RN care managers at scheduled intervals, usually every 3-4 weeks, said Dr. Zuschlag.
During calls, information is collected via evidence-based mental health symptomatic assessment scales. The consulting psychiatrists use this and other information to help guide treatment and coordinate with patients’ primary care physicians to adjust the treatment plan, including medication changes and additional psychotherapy.
To determine the program’s efficacy the investigators retrospectively reviewed all patients enrolled in the ADM program during its first 10 months. Of the 433 program participants, 112 (26%) were identified with active PTSD symptoms at baseline. Another 43 patients had a prior diagnosis of PTSD.
Program completion rates for the cohort with PTSD did not differ from that of the cohort without PTSD.
Overall, mean improvements in depression and anxiety symptoms were evidenced by changes in Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder Assessment-7 (GAD-7) scores of 44% and 43%, respectively.
No differences in mean reduction in symptoms of depression were observed when comparing those with no history of PTSD with those with any history of PTSD (–6.16 vs. –5.42; P = .3244) or with those with active PTSD symptoms (–6.16 vs. –5.54; P = .4543).
Similarly, for anxiety, a mean reduction of –5.61 on the GAD-7 score was observed for the cohort without PTSD, compared with –4.99 in the cohort with any history of PTSD and –5.35 in the cohort with active PTSD symptoms. Again, these differences were nonsignificant.
Dr. Zuschlag noted that the VA setting is unique, with a lot of resources available to conduct such a program as ADM.
“Care management programs that are multidisciplinary are very effective and, in our experience, those who have completed the program do exceptionally well. The patients love it because there is a lot of contact between them and their various care providers,” he said.
A model for other settings?
Commenting on the study, Nagy A. Youssef, MD, PhD, professor of psychiatry and director of clinical research at Ohio State University, Columbus, called the results “interesting.”
“Treating patients with comorbid mild to moderate depression and current or past PTSD within the primary care setting using a care management program could be a model for other VA hospitals as well as in non-VA settings,” said Dr. Youssef, who was not part of the study.
Dr. Youssef noted that not only was there no difference in symptomatic improvement between the depression-plus-PTSD and depression-only groups, but program completion rates did not differ.
This further emphasizes “the potential utility of this approach in initial patient treatment, especially with limited mental health resources and the need to help more patients,” he said.
Dr. Zuschlag and Dr. Youssef report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
“We know there are strains on the mental health care system, and sometimes something as simple as getting to see a psychiatrist can be incredibly challenging,” coinvestigator Zachary Zuschlag, MD, staff psychiatrist at the James A. Haley Veterans’ Hospital and assistant professor at the University of South Florida, both in Tampa, said in an interview.
“So, a model that encourages primary care doctors, together with consultation from us [psychiatrists] to effectively treat these patients in a more proactive way, is very beneficial,” Dr. Zuschlag said.
The findings were presented at the American Society of Clinical Psychopharmacology annual meeting.
Common bedfellows
Dr. Zuschlag noted that comorbid PTSD and depression is common, but it is often considered too complex to be managed in a primary care setting.
Although treating these patients can be challenging, Dr. Zuschlag, who also heads his Veterans Administration facility’s antidepressant monitoring program (ADM), said that when he started the program for this patient population, he used “a much more inclusive model and welcomed these patients even if they had co-occurring issues.”
“Anecdotally, we had seen that our patients with [depression and] co-occurring PTSD appeared to be doing as well as their peers without PTSD, and we just wanted to look at it more systematically,” he added.
The ADM program is specifically designed for psychopharmacologic management of depression and anxiety in the primary care setting. It involves an interdisciplinary team of RN care managers, consulting psychiatrists, psychologists, and primary care physicians. Patients in primary care clinics deemed likely to benefit from psychiatric medications can be enrolled and followed in the program.
The program consists of structured, protocol-based telephone contacts from the RN care managers at scheduled intervals, usually every 3-4 weeks, said Dr. Zuschlag.
During calls, information is collected via evidence-based mental health symptomatic assessment scales. The consulting psychiatrists use this and other information to help guide treatment and coordinate with patients’ primary care physicians to adjust the treatment plan, including medication changes and additional psychotherapy.
To determine the program’s efficacy the investigators retrospectively reviewed all patients enrolled in the ADM program during its first 10 months. Of the 433 program participants, 112 (26%) were identified with active PTSD symptoms at baseline. Another 43 patients had a prior diagnosis of PTSD.
Program completion rates for the cohort with PTSD did not differ from that of the cohort without PTSD.
Overall, mean improvements in depression and anxiety symptoms were evidenced by changes in Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder Assessment-7 (GAD-7) scores of 44% and 43%, respectively.
No differences in mean reduction in symptoms of depression were observed when comparing those with no history of PTSD with those with any history of PTSD (–6.16 vs. –5.42; P = .3244) or with those with active PTSD symptoms (–6.16 vs. –5.54; P = .4543).
Similarly, for anxiety, a mean reduction of –5.61 on the GAD-7 score was observed for the cohort without PTSD, compared with –4.99 in the cohort with any history of PTSD and –5.35 in the cohort with active PTSD symptoms. Again, these differences were nonsignificant.
Dr. Zuschlag noted that the VA setting is unique, with a lot of resources available to conduct such a program as ADM.
“Care management programs that are multidisciplinary are very effective and, in our experience, those who have completed the program do exceptionally well. The patients love it because there is a lot of contact between them and their various care providers,” he said.
A model for other settings?
Commenting on the study, Nagy A. Youssef, MD, PhD, professor of psychiatry and director of clinical research at Ohio State University, Columbus, called the results “interesting.”
“Treating patients with comorbid mild to moderate depression and current or past PTSD within the primary care setting using a care management program could be a model for other VA hospitals as well as in non-VA settings,” said Dr. Youssef, who was not part of the study.
Dr. Youssef noted that not only was there no difference in symptomatic improvement between the depression-plus-PTSD and depression-only groups, but program completion rates did not differ.
This further emphasizes “the potential utility of this approach in initial patient treatment, especially with limited mental health resources and the need to help more patients,” he said.
Dr. Zuschlag and Dr. Youssef report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ASCP 2022