Cardiology News

Treatment for chronic hypertension in pregnancy with labetalol showed no significant differences in maternal or neonatal outcomes, compared with treatment with nifedipine, new research indicates.

The open-label, multicenter, randomized CHAP (Chronic Hypertension in Pregnancy) trial showed that treating mild chronic hypertension was better than delaying treatment until severe hypertension developed, but still unclear was whether, or to what extent, the choice of first-line treatment affected outcomes.

Researchers, led by Ayodeji A. Sanusi, MD, MPH, with the Division of Maternal and Fetal Medicine at the University of Alabama at Birmingham, conducted a secondary analysis of CHAP to compare the primary treatments. Mild chronic hypertension in the study was defined as blood pressure of 140-159/90-104 mmHg before 20 weeks of gestation.
 

Three Comparisons

Three comparisons were performed in 2292 participants based on medications prescribed at enrollment: 720 (31.4%) received labetalol; 417 (18.2%) initially received nifedipine; and 1155 (50.4%) had standard care. Labetalol was compared with standard care; nifedipine was compared with standard care; and labetalol was compared with nifedipine.

The primary outcome was occurrence of superimposed preeclampsia with severe features; preterm birth before 35 weeks of gestation; placental abruption; or fetal or neonatal death. The key secondary outcome was a small-for-gestational age neonate. Researchers also compared adverse effects between groups.

Among the results were the following:

• The primary outcome occurred in 30.1% in the labetalol group; 31.2% in the nifedipine group; and 37% in the standard care group.
• Risk of the primary outcome was lower among those receiving treatment. For labetalol vs standard care, the adjusted relative risk (RR) was 0.82; 95% confidence interval (CI), 0.72-0.94. For nifedipine vs standard care, the adjusted RR was 0.84; 95% CI, 0.71-0.99. There was no significant difference in risk when labetalol was compared with nifedipine (adjusted RR, 0.98; 95% CI, 0.82-1.18).
• There were no significant differences in numbers of small-for-gestational age neonates or serious adverse events between those who received labetalol and those using nifedipine.

Any adverse events were significantly more common with nifedipine, compared with labetalol (35.7% vs 28.3%, P = .009), and with nifedipine, compared with standard care (35.7% vs 26.3%, P = .0003). Adverse event rates were not significantly higher with labetalol when compared with standard care (28.3% vs 26.3%, P = .34). The most frequently reported adverse events were headache, medication intolerance, dizziness, nausea, dyspepsia, neonatal jaundice, and vomiting.

“Thus, labetalol compared with nifedipine appeared to have fewer adverse events and to be better tolerated,” the authors write. They note that labetalol, a third-generation mixed alpha- and beta-adrenergic antagonist, is contraindicated for those who have obstructive pulmonary disease and nifedipine, a dihydropyridine calcium channel blocker, is contraindicated in people with tachycardia.

The authors write that their results align with other studies that have not found differences between labetalol and nifedipine. “[O]ur findings support the use of either labetalol or nifedipine as initial first-line agents for the management of mild chronic hypertension in pregnancy to reduce the risk of adverse maternal and other perinatal outcomes with no increased risk of fetal harm,” the authors write.

Dr. Sanusi reports no relevant financial relationships. Full coauthor disclosures are available with the full text of the paper.

Treatment for chronic hypertension in pregnancy with labetalol showed no significant differences in maternal or neonatal outcomes, compared with treatment with nifedipine, new research indicates.

The open-label, multicenter, randomized CHAP (Chronic Hypertension in Pregnancy) trial showed that treating mild chronic hypertension was better than delaying treatment until severe hypertension developed, but still unclear was whether, or to what extent, the choice of first-line treatment affected outcomes.

Researchers, led by Ayodeji A. Sanusi, MD, MPH, with the Division of Maternal and Fetal Medicine at the University of Alabama at Birmingham, conducted a secondary analysis of CHAP to compare the primary treatments. Mild chronic hypertension in the study was defined as blood pressure of 140-159/90-104 mmHg before 20 weeks of gestation.
 

Three Comparisons

Three comparisons were performed in 2292 participants based on medications prescribed at enrollment: 720 (31.4%) received labetalol; 417 (18.2%) initially received nifedipine; and 1155 (50.4%) had standard care. Labetalol was compared with standard care; nifedipine was compared with standard care; and labetalol was compared with nifedipine.

The primary outcome was occurrence of superimposed preeclampsia with severe features; preterm birth before 35 weeks of gestation; placental abruption; or fetal or neonatal death. The key secondary outcome was a small-for-gestational age neonate. Researchers also compared adverse effects between groups.

Among the results were the following:

• The primary outcome occurred in 30.1% in the labetalol group; 31.2% in the nifedipine group; and 37% in the standard care group.
• Risk of the primary outcome was lower among those receiving treatment. For labetalol vs standard care, the adjusted relative risk (RR) was 0.82; 95% confidence interval (CI), 0.72-0.94. For nifedipine vs standard care, the adjusted RR was 0.84; 95% CI, 0.71-0.99. There was no significant difference in risk when labetalol was compared with nifedipine (adjusted RR, 0.98; 95% CI, 0.82-1.18).
• There were no significant differences in numbers of small-for-gestational age neonates or serious adverse events between those who received labetalol and those using nifedipine.

Any adverse events were significantly more common with nifedipine, compared with labetalol (35.7% vs 28.3%, P = .009), and with nifedipine, compared with standard care (35.7% vs 26.3%, P = .0003). Adverse event rates were not significantly higher with labetalol when compared with standard care (28.3% vs 26.3%, P = .34). The most frequently reported adverse events were headache, medication intolerance, dizziness, nausea, dyspepsia, neonatal jaundice, and vomiting.

“Thus, labetalol compared with nifedipine appeared to have fewer adverse events and to be better tolerated,” the authors write. They note that labetalol, a third-generation mixed alpha- and beta-adrenergic antagonist, is contraindicated for those who have obstructive pulmonary disease and nifedipine, a dihydropyridine calcium channel blocker, is contraindicated in people with tachycardia.

The authors write that their results align with other studies that have not found differences between labetalol and nifedipine. “[O]ur findings support the use of either labetalol or nifedipine as initial first-line agents for the management of mild chronic hypertension in pregnancy to reduce the risk of adverse maternal and other perinatal outcomes with no increased risk of fetal harm,” the authors write.

Dr. Sanusi reports no relevant financial relationships. Full coauthor disclosures are available with the full text of the paper.

Treatment for chronic hypertension in pregnancy with labetalol showed no significant differences in maternal or neonatal outcomes, compared with treatment with nifedipine, new research indicates.

The open-label, multicenter, randomized CHAP (Chronic Hypertension in Pregnancy) trial showed that treating mild chronic hypertension was better than delaying treatment until severe hypertension developed, but still unclear was whether, or to what extent, the choice of first-line treatment affected outcomes.

Researchers, led by Ayodeji A. Sanusi, MD, MPH, with the Division of Maternal and Fetal Medicine at the University of Alabama at Birmingham, conducted a secondary analysis of CHAP to compare the primary treatments. Mild chronic hypertension in the study was defined as blood pressure of 140-159/90-104 mmHg before 20 weeks of gestation.
 

Three Comparisons

Three comparisons were performed in 2292 participants based on medications prescribed at enrollment: 720 (31.4%) received labetalol; 417 (18.2%) initially received nifedipine; and 1155 (50.4%) had standard care. Labetalol was compared with standard care; nifedipine was compared with standard care; and labetalol was compared with nifedipine.

The primary outcome was occurrence of superimposed preeclampsia with severe features; preterm birth before 35 weeks of gestation; placental abruption; or fetal or neonatal death. The key secondary outcome was a small-for-gestational age neonate. Researchers also compared adverse effects between groups.

Among the results were the following:

• The primary outcome occurred in 30.1% in the labetalol group; 31.2% in the nifedipine group; and 37% in the standard care group.
• Risk of the primary outcome was lower among those receiving treatment. For labetalol vs standard care, the adjusted relative risk (RR) was 0.82; 95% confidence interval (CI), 0.72-0.94. For nifedipine vs standard care, the adjusted RR was 0.84; 95% CI, 0.71-0.99. There was no significant difference in risk when labetalol was compared with nifedipine (adjusted RR, 0.98; 95% CI, 0.82-1.18).
• There were no significant differences in numbers of small-for-gestational age neonates or serious adverse events between those who received labetalol and those using nifedipine.

Any adverse events were significantly more common with nifedipine, compared with labetalol (35.7% vs 28.3%, P = .009), and with nifedipine, compared with standard care (35.7% vs 26.3%, P = .0003). Adverse event rates were not significantly higher with labetalol when compared with standard care (28.3% vs 26.3%, P = .34). The most frequently reported adverse events were headache, medication intolerance, dizziness, nausea, dyspepsia, neonatal jaundice, and vomiting.

“Thus, labetalol compared with nifedipine appeared to have fewer adverse events and to be better tolerated,” the authors write. They note that labetalol, a third-generation mixed alpha- and beta-adrenergic antagonist, is contraindicated for those who have obstructive pulmonary disease and nifedipine, a dihydropyridine calcium channel blocker, is contraindicated in people with tachycardia.

The authors write that their results align with other studies that have not found differences between labetalol and nifedipine. “[O]ur findings support the use of either labetalol or nifedipine as initial first-line agents for the management of mild chronic hypertension in pregnancy to reduce the risk of adverse maternal and other perinatal outcomes with no increased risk of fetal harm,” the authors write.

Dr. Sanusi reports no relevant financial relationships. Full coauthor disclosures are available with the full text of the paper.

Two hospitals in California in recent months have been cited by state inspectors for allowing certified registered nurse anesthetists (CRNAs) to practice beyond their scope, leading to one hospital temporarily stopping use of CRNAs in surgeries.

In one case, a CRNA changed a physician’s order from general anesthesia to spinal anesthesia for a patient who later became unresponsive and had to be transferred to another hospital, according to The Modesto Bee.

The unusual situation highlights the ongoing, often contentious debate about the proper role of CRNAs in surgery amid widely varying state scope of practice laws.

Elizabeth Bamgbose, CRNA, past president of the California Association of Nurse Anesthetists (CANA), said that the absence of CRNAs at Doctors Medical Center (DMC) in Modesto, California, had led to the cancellation of hundreds of procedures. It was an unnecessary step, she said.

“It’s unfortunate that a single surveyor has taken it upon themselves to reinterpret state regulations and redefine a practice that was efficient and safe,” said Ms. Bamgbose, a member of the CANA practice committee.

In late May, the California Department of Public Health (CDPH) issued an “immediate jeopardy” warning about DMC of Modesto. The state agency, like its counterparts in other states, acts on behalf of the Centers for Medicare and Medicaid Services (CMS) in surveying healthcare facilities. CMS defines immediate jeopardy as “a situation in which entity noncompliance has placed the health and safety of recipients in its care at risk for serious injury, serious harm, serious impairment, or death.”

The administrative warning comes with fines and requires the facility to submit an action plan to remediate the situation. The state determines through a follow-up survey whether the plan is sufficient for the facility to avoid being dropped from participation in Medicare and Medicaid.

Before the immediate jeopardy action was taken against DMC, the state had issued three previous such warnings in 2024, according to the CDPH enforcement actions dashboard.
 

CRNA Claims to Be in Charge

Stanislaus Surgical Hospital in Modesto, California, was the first facility to attract CDPH attention. It reportedly was cited in August 2023 and January 2024 surveys for a number of violations of the CMS conditions of participation, including allowing nurse anesthetists to practice beyond their scope.

According to The Modesto Bee, CDPH issued an “immediate jeopardy” order for Stanislaus in January.

The paper reported that state regulators took issue with a CRNA claiming to be the lead manager of the hospital’s anesthesia group, referring to herself as the “chief CRNA.”

Jennifer Banek, MSN, CRNA, a member of the American Association of Nurse Anesthesiology board, declined comment on the Stanislaus hospital but said that “it would not be unusual for a nurse anesthetist to serve as a leader, especially (for a) rural or underserved population.”

In April, CMS informed Stanislaus it was being terminated from Medicare, but several Congressional representatives from the Modesto area asked CMS to reconsider. The agency eventually reversed the sanction, The Modesto Bee reported.

CDPH subsequently cited DMC for CRNA scope of practice issues. A department spokesman said that CDPH teams went to DMC “to investigate practices that may not be compliant with state and federal requirements.” The agency declined to comment further until its investigations were complete.

CDPH is monitoring DMC to ensure the hospital complies with state requirements and will return for an unannounced follow-up survey “so it can provide safe, high-quality care to patients that need it,” the spokesperson said.

Although DMC would not confirm it on the record, the immediate jeopardy order led to the removal of all CRNAs, according to Ms. Banek, Ms. Bamgbose, and The Modesto Bee.

The hospital said in a statement that it is working with CDPH to address its concerns and will await a follow-up survey. “Our hospital will continue to fully participate in the Medicare and Medicaid programs during this process.”
 

Scope of Practice Confusion?

Federal and state laws and hospital bylaws all prescribe what falls within the scope of practice for a CRNA, but uncertainty remains.

Twenty-five states — including California — have legally opted out of the federal CMS requirement that a physician supervise CRNAs.

But that does not supersede state laws or hospital bylaws governing practice, said American Society of Anesthesiologists (ASA) president Ronald Harter, MD.

Five states — Alaska, Delaware, Montana, New Hampshire, and Oregon — have laws that allow nurse anesthetists to practice without physician oversight or involvement, said Dr. Harter, professor of anesthesiology at The Ohio State University Wexner Medical Center in Columbus, Ohio.

“There’s a lot of various opinions on what exactly constitutes scope of practice of a nurse anesthetist,” Dr. Harter said. “The vast majority of them work under the direction of an anesthesiologist, and in those settings, it’s typically very clear to everybody who performs what tasks within the care team,” he said.

It’s less common for nurse anesthetists to work totally independent of physician oversight, he said.

Ms. Bamgbose, however, said there is no California statute requiring physician supervision of CRNAs.

The ASA maintains that CRNAs should always be under the supervision of a physician, which can be an anesthesiologist, obstetrician, gastroenterologist, surgeon, or other physician conducting a procedure. An anesthesiologist does not necessarily have to be physically on site, but in those circumstances, the physician conducting the procedure would be, said Dr. Harter.

Nurse anesthetists are “excellent advanced practice nurses,” Dr. Harter said. “But they haven’t been to medical school; they haven’t conducted a residency in anesthesiology. [They] don’t have the medical knowledge and skills that are required to manage the medical problems that patients either bring to the OR with them or that can arise during the time that they’re under anesthesia.”
 

Filling a Gap

Nurse anesthetists see things differently.

CRNAs, by virtue of their certification, can “practice to the full extent and to the full scope, which is complete service of anesthesia,” said Ms. Bamgbose. “You can practice independently of anyone, any type of supervision,” she said.

She acknowledges that “the bylaws of any institution will govern the scope at which any healthcare professional can practice at that institution.”

Most nurse anesthetists see themselves as independent practitioners.

Seventy-five percent of CRNAs who responded to a 2023 Medscape Medical News survey said they practice independently. But even Ms. Banek said that often, the meaning of “independent” is in the eye of the beholder. “It could mean different things to various providers, especially depending on the state that they are residing in,” she said.

Ms. Banek and Ms. Bamgbose said that CRNAs can help fill a gap in anesthesiology services in underserved areas.

The Bureau of Labor Statistics estimates there are currently 32,530 anesthesiologists in the United States, with California employing the largest number, at about 5300. The Association of American Medical Colleges estimated the number at 42,263 in 2022. But the federal Health Resources and Services Administration projects a shortage of 6300 anesthesiologists over the next 15 years.

Some 61,000 CRNAs are currently practicing, with 2400 graduating each year. They are required to be board-certified and are recredentialed every 4 years. By 2025, all will be required to have a doctoral degree. Most have already achieved that status, said Ms. Banek.

“Nurse anesthetists provide care predominantly to rural and underserved areas,” she said, adding, “In many rural hospitals across the country and in all three branches of the military, CRNAs practice autonomously.”

There are 3000 CRNAs in California, said Ms. Bamgbose. Nurse anesthetists are the only anesthesiology professionals in four of 58 California counties, she said.

Ms. Banek said she had heard that some 200 cases were canceled in 1 week at DMC due to the lack of CRNAs. Having physician supervision, which she called redundant, “is really creating a barrier to care,” she said.

“We have countless state and national studies that show the safety and efficacy of our practice,” said Ms. Bamgbose. “To interrupt that care ... is incredibly disruptive to the system.”

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

Two hospitals in California in recent months have been cited by state inspectors for allowing certified registered nurse anesthetists (CRNAs) to practice beyond their scope, leading to one hospital temporarily stopping use of CRNAs in surgeries.

In one case, a CRNA changed a physician’s order from general anesthesia to spinal anesthesia for a patient who later became unresponsive and had to be transferred to another hospital, according to The Modesto Bee.

The unusual situation highlights the ongoing, often contentious debate about the proper role of CRNAs in surgery amid widely varying state scope of practice laws.

Elizabeth Bamgbose, CRNA, past president of the California Association of Nurse Anesthetists (CANA), said that the absence of CRNAs at Doctors Medical Center (DMC) in Modesto, California, had led to the cancellation of hundreds of procedures. It was an unnecessary step, she said.

“It’s unfortunate that a single surveyor has taken it upon themselves to reinterpret state regulations and redefine a practice that was efficient and safe,” said Ms. Bamgbose, a member of the CANA practice committee.

In late May, the California Department of Public Health (CDPH) issued an “immediate jeopardy” warning about DMC of Modesto. The state agency, like its counterparts in other states, acts on behalf of the Centers for Medicare and Medicaid Services (CMS) in surveying healthcare facilities. CMS defines immediate jeopardy as “a situation in which entity noncompliance has placed the health and safety of recipients in its care at risk for serious injury, serious harm, serious impairment, or death.”

The administrative warning comes with fines and requires the facility to submit an action plan to remediate the situation. The state determines through a follow-up survey whether the plan is sufficient for the facility to avoid being dropped from participation in Medicare and Medicaid.

Before the immediate jeopardy action was taken against DMC, the state had issued three previous such warnings in 2024, according to the CDPH enforcement actions dashboard.
 

CRNA Claims to Be in Charge

Stanislaus Surgical Hospital in Modesto, California, was the first facility to attract CDPH attention. It reportedly was cited in August 2023 and January 2024 surveys for a number of violations of the CMS conditions of participation, including allowing nurse anesthetists to practice beyond their scope.

According to The Modesto Bee, CDPH issued an “immediate jeopardy” order for Stanislaus in January.

The paper reported that state regulators took issue with a CRNA claiming to be the lead manager of the hospital’s anesthesia group, referring to herself as the “chief CRNA.”

Jennifer Banek, MSN, CRNA, a member of the American Association of Nurse Anesthesiology board, declined comment on the Stanislaus hospital but said that “it would not be unusual for a nurse anesthetist to serve as a leader, especially (for a) rural or underserved population.”

In April, CMS informed Stanislaus it was being terminated from Medicare, but several Congressional representatives from the Modesto area asked CMS to reconsider. The agency eventually reversed the sanction, The Modesto Bee reported.

CDPH subsequently cited DMC for CRNA scope of practice issues. A department spokesman said that CDPH teams went to DMC “to investigate practices that may not be compliant with state and federal requirements.” The agency declined to comment further until its investigations were complete.

CDPH is monitoring DMC to ensure the hospital complies with state requirements and will return for an unannounced follow-up survey “so it can provide safe, high-quality care to patients that need it,” the spokesperson said.

Although DMC would not confirm it on the record, the immediate jeopardy order led to the removal of all CRNAs, according to Ms. Banek, Ms. Bamgbose, and The Modesto Bee.

The hospital said in a statement that it is working with CDPH to address its concerns and will await a follow-up survey. “Our hospital will continue to fully participate in the Medicare and Medicaid programs during this process.”
 

Scope of Practice Confusion?

Federal and state laws and hospital bylaws all prescribe what falls within the scope of practice for a CRNA, but uncertainty remains.

Twenty-five states — including California — have legally opted out of the federal CMS requirement that a physician supervise CRNAs.

But that does not supersede state laws or hospital bylaws governing practice, said American Society of Anesthesiologists (ASA) president Ronald Harter, MD.

Five states — Alaska, Delaware, Montana, New Hampshire, and Oregon — have laws that allow nurse anesthetists to practice without physician oversight or involvement, said Dr. Harter, professor of anesthesiology at The Ohio State University Wexner Medical Center in Columbus, Ohio.

“There’s a lot of various opinions on what exactly constitutes scope of practice of a nurse anesthetist,” Dr. Harter said. “The vast majority of them work under the direction of an anesthesiologist, and in those settings, it’s typically very clear to everybody who performs what tasks within the care team,” he said.

It’s less common for nurse anesthetists to work totally independent of physician oversight, he said.

Ms. Bamgbose, however, said there is no California statute requiring physician supervision of CRNAs.

The ASA maintains that CRNAs should always be under the supervision of a physician, which can be an anesthesiologist, obstetrician, gastroenterologist, surgeon, or other physician conducting a procedure. An anesthesiologist does not necessarily have to be physically on site, but in those circumstances, the physician conducting the procedure would be, said Dr. Harter.

Nurse anesthetists are “excellent advanced practice nurses,” Dr. Harter said. “But they haven’t been to medical school; they haven’t conducted a residency in anesthesiology. [They] don’t have the medical knowledge and skills that are required to manage the medical problems that patients either bring to the OR with them or that can arise during the time that they’re under anesthesia.”
 

Filling a Gap

Nurse anesthetists see things differently.

CRNAs, by virtue of their certification, can “practice to the full extent and to the full scope, which is complete service of anesthesia,” said Ms. Bamgbose. “You can practice independently of anyone, any type of supervision,” she said.

She acknowledges that “the bylaws of any institution will govern the scope at which any healthcare professional can practice at that institution.”

Most nurse anesthetists see themselves as independent practitioners.

Seventy-five percent of CRNAs who responded to a 2023 Medscape Medical News survey said they practice independently. But even Ms. Banek said that often, the meaning of “independent” is in the eye of the beholder. “It could mean different things to various providers, especially depending on the state that they are residing in,” she said.

Ms. Banek and Ms. Bamgbose said that CRNAs can help fill a gap in anesthesiology services in underserved areas.

The Bureau of Labor Statistics estimates there are currently 32,530 anesthesiologists in the United States, with California employing the largest number, at about 5300. The Association of American Medical Colleges estimated the number at 42,263 in 2022. But the federal Health Resources and Services Administration projects a shortage of 6300 anesthesiologists over the next 15 years.

Some 61,000 CRNAs are currently practicing, with 2400 graduating each year. They are required to be board-certified and are recredentialed every 4 years. By 2025, all will be required to have a doctoral degree. Most have already achieved that status, said Ms. Banek.

“Nurse anesthetists provide care predominantly to rural and underserved areas,” she said, adding, “In many rural hospitals across the country and in all three branches of the military, CRNAs practice autonomously.”

There are 3000 CRNAs in California, said Ms. Bamgbose. Nurse anesthetists are the only anesthesiology professionals in four of 58 California counties, she said.

Ms. Banek said she had heard that some 200 cases were canceled in 1 week at DMC due to the lack of CRNAs. Having physician supervision, which she called redundant, “is really creating a barrier to care,” she said.

“We have countless state and national studies that show the safety and efficacy of our practice,” said Ms. Bamgbose. “To interrupt that care ... is incredibly disruptive to the system.”

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

Two hospitals in California in recent months have been cited by state inspectors for allowing certified registered nurse anesthetists (CRNAs) to practice beyond their scope, leading to one hospital temporarily stopping use of CRNAs in surgeries.

In one case, a CRNA changed a physician’s order from general anesthesia to spinal anesthesia for a patient who later became unresponsive and had to be transferred to another hospital, according to The Modesto Bee.

The unusual situation highlights the ongoing, often contentious debate about the proper role of CRNAs in surgery amid widely varying state scope of practice laws.

Elizabeth Bamgbose, CRNA, past president of the California Association of Nurse Anesthetists (CANA), said that the absence of CRNAs at Doctors Medical Center (DMC) in Modesto, California, had led to the cancellation of hundreds of procedures. It was an unnecessary step, she said.

“It’s unfortunate that a single surveyor has taken it upon themselves to reinterpret state regulations and redefine a practice that was efficient and safe,” said Ms. Bamgbose, a member of the CANA practice committee.

In late May, the California Department of Public Health (CDPH) issued an “immediate jeopardy” warning about DMC of Modesto. The state agency, like its counterparts in other states, acts on behalf of the Centers for Medicare and Medicaid Services (CMS) in surveying healthcare facilities. CMS defines immediate jeopardy as “a situation in which entity noncompliance has placed the health and safety of recipients in its care at risk for serious injury, serious harm, serious impairment, or death.”

The administrative warning comes with fines and requires the facility to submit an action plan to remediate the situation. The state determines through a follow-up survey whether the plan is sufficient for the facility to avoid being dropped from participation in Medicare and Medicaid.

Before the immediate jeopardy action was taken against DMC, the state had issued three previous such warnings in 2024, according to the CDPH enforcement actions dashboard.
 

CRNA Claims to Be in Charge

Stanislaus Surgical Hospital in Modesto, California, was the first facility to attract CDPH attention. It reportedly was cited in August 2023 and January 2024 surveys for a number of violations of the CMS conditions of participation, including allowing nurse anesthetists to practice beyond their scope.

According to The Modesto Bee, CDPH issued an “immediate jeopardy” order for Stanislaus in January.

The paper reported that state regulators took issue with a CRNA claiming to be the lead manager of the hospital’s anesthesia group, referring to herself as the “chief CRNA.”

Jennifer Banek, MSN, CRNA, a member of the American Association of Nurse Anesthesiology board, declined comment on the Stanislaus hospital but said that “it would not be unusual for a nurse anesthetist to serve as a leader, especially (for a) rural or underserved population.”

In April, CMS informed Stanislaus it was being terminated from Medicare, but several Congressional representatives from the Modesto area asked CMS to reconsider. The agency eventually reversed the sanction, The Modesto Bee reported.

CDPH subsequently cited DMC for CRNA scope of practice issues. A department spokesman said that CDPH teams went to DMC “to investigate practices that may not be compliant with state and federal requirements.” The agency declined to comment further until its investigations were complete.

CDPH is monitoring DMC to ensure the hospital complies with state requirements and will return for an unannounced follow-up survey “so it can provide safe, high-quality care to patients that need it,” the spokesperson said.

Although DMC would not confirm it on the record, the immediate jeopardy order led to the removal of all CRNAs, according to Ms. Banek, Ms. Bamgbose, and The Modesto Bee.

The hospital said in a statement that it is working with CDPH to address its concerns and will await a follow-up survey. “Our hospital will continue to fully participate in the Medicare and Medicaid programs during this process.”
 

Scope of Practice Confusion?

Federal and state laws and hospital bylaws all prescribe what falls within the scope of practice for a CRNA, but uncertainty remains.

Twenty-five states — including California — have legally opted out of the federal CMS requirement that a physician supervise CRNAs.

But that does not supersede state laws or hospital bylaws governing practice, said American Society of Anesthesiologists (ASA) president Ronald Harter, MD.

Five states — Alaska, Delaware, Montana, New Hampshire, and Oregon — have laws that allow nurse anesthetists to practice without physician oversight or involvement, said Dr. Harter, professor of anesthesiology at The Ohio State University Wexner Medical Center in Columbus, Ohio.

“There’s a lot of various opinions on what exactly constitutes scope of practice of a nurse anesthetist,” Dr. Harter said. “The vast majority of them work under the direction of an anesthesiologist, and in those settings, it’s typically very clear to everybody who performs what tasks within the care team,” he said.

It’s less common for nurse anesthetists to work totally independent of physician oversight, he said.

Ms. Bamgbose, however, said there is no California statute requiring physician supervision of CRNAs.

The ASA maintains that CRNAs should always be under the supervision of a physician, which can be an anesthesiologist, obstetrician, gastroenterologist, surgeon, or other physician conducting a procedure. An anesthesiologist does not necessarily have to be physically on site, but in those circumstances, the physician conducting the procedure would be, said Dr. Harter.

Nurse anesthetists are “excellent advanced practice nurses,” Dr. Harter said. “But they haven’t been to medical school; they haven’t conducted a residency in anesthesiology. [They] don’t have the medical knowledge and skills that are required to manage the medical problems that patients either bring to the OR with them or that can arise during the time that they’re under anesthesia.”
 

Filling a Gap

Nurse anesthetists see things differently.

CRNAs, by virtue of their certification, can “practice to the full extent and to the full scope, which is complete service of anesthesia,” said Ms. Bamgbose. “You can practice independently of anyone, any type of supervision,” she said.

She acknowledges that “the bylaws of any institution will govern the scope at which any healthcare professional can practice at that institution.”

Most nurse anesthetists see themselves as independent practitioners.

Seventy-five percent of CRNAs who responded to a 2023 Medscape Medical News survey said they practice independently. But even Ms. Banek said that often, the meaning of “independent” is in the eye of the beholder. “It could mean different things to various providers, especially depending on the state that they are residing in,” she said.

Ms. Banek and Ms. Bamgbose said that CRNAs can help fill a gap in anesthesiology services in underserved areas.

The Bureau of Labor Statistics estimates there are currently 32,530 anesthesiologists in the United States, with California employing the largest number, at about 5300. The Association of American Medical Colleges estimated the number at 42,263 in 2022. But the federal Health Resources and Services Administration projects a shortage of 6300 anesthesiologists over the next 15 years.

Some 61,000 CRNAs are currently practicing, with 2400 graduating each year. They are required to be board-certified and are recredentialed every 4 years. By 2025, all will be required to have a doctoral degree. Most have already achieved that status, said Ms. Banek.

“Nurse anesthetists provide care predominantly to rural and underserved areas,” she said, adding, “In many rural hospitals across the country and in all three branches of the military, CRNAs practice autonomously.”

There are 3000 CRNAs in California, said Ms. Bamgbose. Nurse anesthetists are the only anesthesiology professionals in four of 58 California counties, she said.

Ms. Banek said she had heard that some 200 cases were canceled in 1 week at DMC due to the lack of CRNAs. Having physician supervision, which she called redundant, “is really creating a barrier to care,” she said.

“We have countless state and national studies that show the safety and efficacy of our practice,” said Ms. Bamgbose. “To interrupt that care ... is incredibly disruptive to the system.”

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

SAN DIEGO – Researchers are unraveling the complex relationship between cardiovascular (CV)- and stroke-related outcomes in migraine with, and without, aura.

Early results of one study suggest that aura increases the risk for major adverse cerebrovascular and CV events (MACE) in those with migraine, and that this risk is particularly high in men.

“We confirmed that aura increases the risk for these cerebrovascular and cardiovascular outcomes in people with migraine and that there’s an increased risk of these MACE events in men with migraine,” said study investigator Gina Dumkrieger, PhD, principal data science analyst and assistant professor of neurology, Mayo Clinic, Phoenix, Arizona.

The findings were presented at the annual meeting of the American Headache Society.
 

Few Data on Migraine and Stroke Risk

The extent to which migraine increases the risk for stroke CV outcomes has not been extensively studied.

“We’re trying to find out whether migraine-related factors make it more likely that you’re going to have one of these events,” said Dr. Dumkrieger. “Knowing a particular factor increases the risk is something patients and medical providers would want to know.”

Using Mayo Clinic electronic health records, which cover all three sites (Florida, Minnesota, and Arizona), researchers identified individuals with migraine using diagnostic codes. They also looked at data on sex, race, and the presence of aura.

They investigated whether a history of MACE risk factors — including atrial fibrillation, diabetes, hyperlipidemia, hypertension, and tobacco use — affected risk and the potential interaction of aura with these risk factors.

MACE events included cerebral infarction, intracerebral hemorrhage, and acute myocardial infarction.

The analysis included 130,126 participants (80% women, 95% White individuals). Of these, 6% experienced a MACE event, and 94% did not.

“We confirmed that aura does increase the risk for a MACE event, and all of the known risk factors that we included were also significant,” said Dr. Dumkrieger.

Odds ratios (ORs) were 3.82 for atrial fibrillation, 3.11 for hypertension, and 3.06 for hyperlipidemia.

It was surprising, said Dr. Dumkrieger, that male sex was tied to an increased risk for a MACE event (OR, 1.40). “This is not something that was known before,” she said.

The link between migraine and ischemic stroke, particularly with aura, was stronger in women — particularly young women.

Investigators also found an interaction between male sex and aura, when it comes to MACE outcomes, said Dr. Dumkrieger. “Males in general are at higher risk, and people with aura are at higher risk. Males with aura are also at higher risk, but maybe not as much as you would think they would be. It’s not a purely additive thing. This is something we need to look into more,” she said. 

The study also revealed an interaction between aura and hypertension as well as aura and tobacco use, but here too, it was not an additive risk, said Dr. Dumkrieger. However, she added, the presence of aura does not moderate the risk for hyperlipidemia, diabetes, or atrial fibrillation.

The research also showed a significant interaction between male sex and Black race which was additive. “There’s apparently increased risk if you are male and Black or African American that’s greater than what you would expect. We should be especially concerned about these individuals,” she said.
 

Unanswered Questions

The current analysis is part of a larger study that will more closely examine these relationships. “We want to learn, for example, why aura moderates some of the risk factors but not others,” said Dr. Dumkrieger.

The researchers also plan to investigate other migraine features, including headache frequency, and headache sensations such as pulsating or throbbing.

Dr. Dumkrieger was an investigator of another study, also presented at the AHS meeting, that’s investigating the role of migraine-specific features and imaging results in the complex interrelationship between migraine and MACE risk.

That study, which also used the Mayo Clinic electronic health record data, included 60,454 migraine patients diagnosed with migraine after 2010.

Researchers divided participants into those with a MACE outcome (1107) and those without such an outcome (59,347) after at least 2 years of follow-up. They created a propensity cohort of individuals matched for age and risk factors for MACE outcome.

The final cohort consisted of 575 patients with and 652 patients without MACE outcome.

One of the most interesting early results from this study was that those with a MACE outcome had significantly more white matter hyperintensities than those with no MACE outcome, at 64% versus 51%, respectively. 

This and other findings need to be validated in a different cohort with an electronic health records database from another institution. In future, the team plans to focus on identifying specific migraine features and medications and their relative contributions to MACE risk in migraine patients.

Yet another study featured at the AHS meeting confirmed the increased risk for stroke among migraine patients using a large database with over 410,000 subjects.

Results showed stroke was more than three times more common in those with a migraine diagnosis than in those without (risk ratio, [RR] 3.23; P < .001). The RR for hemorrhagic stroke (3.15) was comparable with that of ischemic stroke (3.20).

The overall stroke RR for chronic migraine versus controls without migraine was 3.68 (P < .001). The RR for migraine with aura versus migraine without aura was 1.37 (P < .001).
 

Useful Data

Commenting on the research, Juliana VanderPluym, MD, a headache specialist at the Mayo Clinic, Phoenix, Arizona, described this new information as “very useful.”

The fact that there are more white matter lesions on MRI scans in migraine patients with MACE needs further exploration, said Dr. VanderPluym.

“Understanding how much of that relates to migraine, how much relates to other comorbid conditions, and what this all means together, is very important, particularly because MACE can be life-threatening and life-altering,” she added.

Learning how migraine medications may impact MACE risk is also something that needs to be examined in greater depth, she said. “I would think that migraines that are controlled might have a different risk for MACE than uncontrolled migraine,” she said.

The investigators reported no relevant financial conflicts of interest.

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

SAN DIEGO – Researchers are unraveling the complex relationship between cardiovascular (CV)- and stroke-related outcomes in migraine with, and without, aura.

Early results of one study suggest that aura increases the risk for major adverse cerebrovascular and CV events (MACE) in those with migraine, and that this risk is particularly high in men.

“We confirmed that aura increases the risk for these cerebrovascular and cardiovascular outcomes in people with migraine and that there’s an increased risk of these MACE events in men with migraine,” said study investigator Gina Dumkrieger, PhD, principal data science analyst and assistant professor of neurology, Mayo Clinic, Phoenix, Arizona.

The findings were presented at the annual meeting of the American Headache Society.
 

Few Data on Migraine and Stroke Risk

The extent to which migraine increases the risk for stroke CV outcomes has not been extensively studied.

“We’re trying to find out whether migraine-related factors make it more likely that you’re going to have one of these events,” said Dr. Dumkrieger. “Knowing a particular factor increases the risk is something patients and medical providers would want to know.”

Using Mayo Clinic electronic health records, which cover all three sites (Florida, Minnesota, and Arizona), researchers identified individuals with migraine using diagnostic codes. They also looked at data on sex, race, and the presence of aura.

They investigated whether a history of MACE risk factors — including atrial fibrillation, diabetes, hyperlipidemia, hypertension, and tobacco use — affected risk and the potential interaction of aura with these risk factors.

MACE events included cerebral infarction, intracerebral hemorrhage, and acute myocardial infarction.

The analysis included 130,126 participants (80% women, 95% White individuals). Of these, 6% experienced a MACE event, and 94% did not.

“We confirmed that aura does increase the risk for a MACE event, and all of the known risk factors that we included were also significant,” said Dr. Dumkrieger.

Odds ratios (ORs) were 3.82 for atrial fibrillation, 3.11 for hypertension, and 3.06 for hyperlipidemia.

It was surprising, said Dr. Dumkrieger, that male sex was tied to an increased risk for a MACE event (OR, 1.40). “This is not something that was known before,” she said.

The link between migraine and ischemic stroke, particularly with aura, was stronger in women — particularly young women.

Investigators also found an interaction between male sex and aura, when it comes to MACE outcomes, said Dr. Dumkrieger. “Males in general are at higher risk, and people with aura are at higher risk. Males with aura are also at higher risk, but maybe not as much as you would think they would be. It’s not a purely additive thing. This is something we need to look into more,” she said. 

The study also revealed an interaction between aura and hypertension as well as aura and tobacco use, but here too, it was not an additive risk, said Dr. Dumkrieger. However, she added, the presence of aura does not moderate the risk for hyperlipidemia, diabetes, or atrial fibrillation.

The research also showed a significant interaction between male sex and Black race which was additive. “There’s apparently increased risk if you are male and Black or African American that’s greater than what you would expect. We should be especially concerned about these individuals,” she said.
 

Unanswered Questions

The current analysis is part of a larger study that will more closely examine these relationships. “We want to learn, for example, why aura moderates some of the risk factors but not others,” said Dr. Dumkrieger.

The researchers also plan to investigate other migraine features, including headache frequency, and headache sensations such as pulsating or throbbing.

Dr. Dumkrieger was an investigator of another study, also presented at the AHS meeting, that’s investigating the role of migraine-specific features and imaging results in the complex interrelationship between migraine and MACE risk.

That study, which also used the Mayo Clinic electronic health record data, included 60,454 migraine patients diagnosed with migraine after 2010.

Researchers divided participants into those with a MACE outcome (1107) and those without such an outcome (59,347) after at least 2 years of follow-up. They created a propensity cohort of individuals matched for age and risk factors for MACE outcome.

The final cohort consisted of 575 patients with and 652 patients without MACE outcome.

One of the most interesting early results from this study was that those with a MACE outcome had significantly more white matter hyperintensities than those with no MACE outcome, at 64% versus 51%, respectively. 

This and other findings need to be validated in a different cohort with an electronic health records database from another institution. In future, the team plans to focus on identifying specific migraine features and medications and their relative contributions to MACE risk in migraine patients.

Yet another study featured at the AHS meeting confirmed the increased risk for stroke among migraine patients using a large database with over 410,000 subjects.

Results showed stroke was more than three times more common in those with a migraine diagnosis than in those without (risk ratio, [RR] 3.23; P < .001). The RR for hemorrhagic stroke (3.15) was comparable with that of ischemic stroke (3.20).

The overall stroke RR for chronic migraine versus controls without migraine was 3.68 (P < .001). The RR for migraine with aura versus migraine without aura was 1.37 (P < .001).
 

Useful Data

Commenting on the research, Juliana VanderPluym, MD, a headache specialist at the Mayo Clinic, Phoenix, Arizona, described this new information as “very useful.”

The fact that there are more white matter lesions on MRI scans in migraine patients with MACE needs further exploration, said Dr. VanderPluym.

“Understanding how much of that relates to migraine, how much relates to other comorbid conditions, and what this all means together, is very important, particularly because MACE can be life-threatening and life-altering,” she added.

Learning how migraine medications may impact MACE risk is also something that needs to be examined in greater depth, she said. “I would think that migraines that are controlled might have a different risk for MACE than uncontrolled migraine,” she said.

The investigators reported no relevant financial conflicts of interest.

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

SAN DIEGO – Researchers are unraveling the complex relationship between cardiovascular (CV)- and stroke-related outcomes in migraine with, and without, aura.

Early results of one study suggest that aura increases the risk for major adverse cerebrovascular and CV events (MACE) in those with migraine, and that this risk is particularly high in men.

“We confirmed that aura increases the risk for these cerebrovascular and cardiovascular outcomes in people with migraine and that there’s an increased risk of these MACE events in men with migraine,” said study investigator Gina Dumkrieger, PhD, principal data science analyst and assistant professor of neurology, Mayo Clinic, Phoenix, Arizona.

The findings were presented at the annual meeting of the American Headache Society.
 

Few Data on Migraine and Stroke Risk

The extent to which migraine increases the risk for stroke CV outcomes has not been extensively studied.

“We’re trying to find out whether migraine-related factors make it more likely that you’re going to have one of these events,” said Dr. Dumkrieger. “Knowing a particular factor increases the risk is something patients and medical providers would want to know.”

Using Mayo Clinic electronic health records, which cover all three sites (Florida, Minnesota, and Arizona), researchers identified individuals with migraine using diagnostic codes. They also looked at data on sex, race, and the presence of aura.

They investigated whether a history of MACE risk factors — including atrial fibrillation, diabetes, hyperlipidemia, hypertension, and tobacco use — affected risk and the potential interaction of aura with these risk factors.

MACE events included cerebral infarction, intracerebral hemorrhage, and acute myocardial infarction.

The analysis included 130,126 participants (80% women, 95% White individuals). Of these, 6% experienced a MACE event, and 94% did not.

“We confirmed that aura does increase the risk for a MACE event, and all of the known risk factors that we included were also significant,” said Dr. Dumkrieger.

Odds ratios (ORs) were 3.82 for atrial fibrillation, 3.11 for hypertension, and 3.06 for hyperlipidemia.

It was surprising, said Dr. Dumkrieger, that male sex was tied to an increased risk for a MACE event (OR, 1.40). “This is not something that was known before,” she said.

The link between migraine and ischemic stroke, particularly with aura, was stronger in women — particularly young women.

Investigators also found an interaction between male sex and aura, when it comes to MACE outcomes, said Dr. Dumkrieger. “Males in general are at higher risk, and people with aura are at higher risk. Males with aura are also at higher risk, but maybe not as much as you would think they would be. It’s not a purely additive thing. This is something we need to look into more,” she said. 

The study also revealed an interaction between aura and hypertension as well as aura and tobacco use, but here too, it was not an additive risk, said Dr. Dumkrieger. However, she added, the presence of aura does not moderate the risk for hyperlipidemia, diabetes, or atrial fibrillation.

The research also showed a significant interaction between male sex and Black race which was additive. “There’s apparently increased risk if you are male and Black or African American that’s greater than what you would expect. We should be especially concerned about these individuals,” she said.
 

Unanswered Questions

The current analysis is part of a larger study that will more closely examine these relationships. “We want to learn, for example, why aura moderates some of the risk factors but not others,” said Dr. Dumkrieger.

The researchers also plan to investigate other migraine features, including headache frequency, and headache sensations such as pulsating or throbbing.

Dr. Dumkrieger was an investigator of another study, also presented at the AHS meeting, that’s investigating the role of migraine-specific features and imaging results in the complex interrelationship between migraine and MACE risk.

That study, which also used the Mayo Clinic electronic health record data, included 60,454 migraine patients diagnosed with migraine after 2010.

Researchers divided participants into those with a MACE outcome (1107) and those without such an outcome (59,347) after at least 2 years of follow-up. They created a propensity cohort of individuals matched for age and risk factors for MACE outcome.

The final cohort consisted of 575 patients with and 652 patients without MACE outcome.

One of the most interesting early results from this study was that those with a MACE outcome had significantly more white matter hyperintensities than those with no MACE outcome, at 64% versus 51%, respectively. 

This and other findings need to be validated in a different cohort with an electronic health records database from another institution. In future, the team plans to focus on identifying specific migraine features and medications and their relative contributions to MACE risk in migraine patients.

Yet another study featured at the AHS meeting confirmed the increased risk for stroke among migraine patients using a large database with over 410,000 subjects.

Results showed stroke was more than three times more common in those with a migraine diagnosis than in those without (risk ratio, [RR] 3.23; P < .001). The RR for hemorrhagic stroke (3.15) was comparable with that of ischemic stroke (3.20).

The overall stroke RR for chronic migraine versus controls without migraine was 3.68 (P < .001). The RR for migraine with aura versus migraine without aura was 1.37 (P < .001).
 

Useful Data

Commenting on the research, Juliana VanderPluym, MD, a headache specialist at the Mayo Clinic, Phoenix, Arizona, described this new information as “very useful.”

The fact that there are more white matter lesions on MRI scans in migraine patients with MACE needs further exploration, said Dr. VanderPluym.

“Understanding how much of that relates to migraine, how much relates to other comorbid conditions, and what this all means together, is very important, particularly because MACE can be life-threatening and life-altering,” she added.

Learning how migraine medications may impact MACE risk is also something that needs to be examined in greater depth, she said. “I would think that migraines that are controlled might have a different risk for MACE than uncontrolled migraine,” she said.

The investigators reported no relevant financial conflicts of interest.

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

LYON, France – Lerodalcibep, a novel, third-generation anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, helps high-risk patients already receiving maximally tolerated statins to achieve guideline lipid targets, reported investigators.

In the randomized, placebo-controlled LIBerate-CVD trial of more than 900 patients, lerodalcibep led to reductions from baseline in low-density lipoprotein (LDL) cholesterol levels of more than 60%.

“We believe that lerodalcibep offers a novel, effective alternative to current PCSK9 inhibitors for patients with cardiovascular disease or at very high risk for cardiovascular disease,” said Evan Stein, MD, PhD, chief scientific officer and cofounder of LIB Therapeutics in Chicago, who presented the findings at the European Atherosclerosis Society (EAS) 2024.

Moreover, it leads to “substantial additional LDL cholesterol reductions on top of existing oral agents” and allows more than 90% of patients to achieve the latest European Society of Cardiology (ESC) guideline targets, he said.

Lerodalcibep has “tolerability and safety similar to placebo,” Dr. Stein said, and requires only “a small monthly injection, which takes about 12 seconds.”

“The drug doesn’t require refrigeration” and is “stable, so far, over 9 months,” he reported.

The latest data “confirm the efficacy of lerodalcibep,” said Giuseppe Danilo Norata, PhD, from the Department of Pharmacological and Biomolecular Sciences at the University of Milan, Milan, Italy, who was not involved in the study.

The LDL cholesterol reduction in this phase 3 trial is “in line with what was observed in LIBerate-FH,” and the high proportion of patients achieving their LDL cholesterol target is “impressive,” he added.
 

Effective and Well Tolerated

The safety results are “suggestive of a drug that is well tolerated, with injection-site reactions being the only remarkable adverse event increased in the treatment group,” Dr. Norata reported.

Only a “limited number” of patients developed neutralizing antidrug antibodies, which did not affect the efficacy of lerodalcibep. However, “given that the therapy is expected to be administered for years,” a longer analysis is needed to exclude the concern that a small percentage of neutralizing antidrug antibodies could reduce the efficacy, he said.

If approved, lerodalcibep could end up as a first-line option in the treatment pathway for high-risk cardiovascular disease because the efficacy “is similar to that of other injectable PCSK9 inhibitors,” he said, adding that its position in the market will “largely depend on the price.”

As the mechanism of action is similar to that of other monoclonal antibodies, “there is no pharmacological rationale to use it after another PSCK9 inhibitor,” he explained.

Lerodalcibep is a small recombinant fusion protein that combines a PCSK9-binding domain with human serum albumin.

The binding domain blocks the interaction between PCSK9 and the LDL cholesterol receptor, and the albumin linkage increases the half-life to 12-15 days, allowing low-volume injections to be given every 4 weeks.

A prior phase 2 study suggested that lerodalcibep substantially decreases LDL cholesterol levels in patients already taking maximally tolerated statins. The 300-mg dose was associated with an average reduction from baseline in LDL cholesterol levels of 77% over 12 weeks, whereas free PCSK9 levels decreased by 88%.

The current phase 3 study enrolled individuals at 65 centers in 100 countries who had or were at a very high risk for cardiovascular disease and who had an LDL cholesterol level of ≥ 1.8 mmol/L despite being on maximally tolerated statins.

Study participants were randomized in a 2:1 ratio to receive monthly subcutaneous lerodalcibep (n = 614) or placebo (n = 308) for 52 weeks and were assessed for the co-primary endpoints of the percentage change in LDL cholesterol levels from baseline to week 52 and the mean of levels at weeks 50 and 52.

The mean age was similar in the lerodalcibep and placebo groups (63.3 vs 64.5 years), as were the proportion of female (30% vs 30%) and White (80% vs 79%) participants.

The vast majority of participants in the lerodalcibep and placebo groups had a documented cardiovascular event (85.3% vs 86.4%) and were receiving secondary prevention, and 87% and 82%, respectively, were receiving a statin (any dose).

In a modified intention-to-treat analysis, the mean placebo-adjusted reduction in LDL cholesterol levels from baseline with lerodalcibep was 62% at week 52 (P < .0001), and the mean of levels at weeks 50 and 52 was 69.4% (P < .0001).

Similar results were seen in a per protocol analysis and an intention-to-treat analysis with imputation, which is a US Food and Drug Administration measure introduced in 2021 that assumes patients who discontinue the study treatment have an outcome similar to that in the placebo patients.

Moreover, 98.2% of patients in the lerodalcibep group achieved the ESC and European Atherosclerosis Society recommended reduction in LDL cholesterol levels of ≥ 50%, whereas only 8.8% in the placebo group did.
 

Hitting the LDL Cholesterol Target

More patients in the lerodalcibep group than in the placebo group achieved the LDL cholesterol target of < 1.4 mmol/L (95.3% vs 18.5%), and more patients in the lerodalcibep group achieved both that target and the ≥ 50% target (94.5% and 6.8%).

Lerodalcibep was also associated with significant reductions from baseline in levels of non–high-density lipoprotein (HDL) cholesterol, apolipoprotein B, very LDL cholesterol, and triglycerides, as well as an increase in HDL cholesterol levels (P < .0001 for all).

In terms of safety, lerodalcibep was associated with an adverse event rate leading to withdrawal similar to that seen with placebo (4.2% vs 3.6%), and 15.9% and 14.8% of patients, respectively, experienced at least one serious adverse event.

In-stent restenosis occurred more often in the lerodalcibep group than in the placebo group (5.4% vs 2.0%).

The study drug was associated with low levels of transient and sporadic antidrug antibodies and a low rate of neutralizing antidrug antibodies (0.9%), which were not associated with restenosis, a reduction in free PCSK9 levels, or the ability of lerodalcibep to lower LDL cholesterol levels.

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

LYON, France – Lerodalcibep, a novel, third-generation anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, helps high-risk patients already receiving maximally tolerated statins to achieve guideline lipid targets, reported investigators.

In the randomized, placebo-controlled LIBerate-CVD trial of more than 900 patients, lerodalcibep led to reductions from baseline in low-density lipoprotein (LDL) cholesterol levels of more than 60%.

“We believe that lerodalcibep offers a novel, effective alternative to current PCSK9 inhibitors for patients with cardiovascular disease or at very high risk for cardiovascular disease,” said Evan Stein, MD, PhD, chief scientific officer and cofounder of LIB Therapeutics in Chicago, who presented the findings at the European Atherosclerosis Society (EAS) 2024.

Moreover, it leads to “substantial additional LDL cholesterol reductions on top of existing oral agents” and allows more than 90% of patients to achieve the latest European Society of Cardiology (ESC) guideline targets, he said.

Lerodalcibep has “tolerability and safety similar to placebo,” Dr. Stein said, and requires only “a small monthly injection, which takes about 12 seconds.”

“The drug doesn’t require refrigeration” and is “stable, so far, over 9 months,” he reported.

The latest data “confirm the efficacy of lerodalcibep,” said Giuseppe Danilo Norata, PhD, from the Department of Pharmacological and Biomolecular Sciences at the University of Milan, Milan, Italy, who was not involved in the study.

The LDL cholesterol reduction in this phase 3 trial is “in line with what was observed in LIBerate-FH,” and the high proportion of patients achieving their LDL cholesterol target is “impressive,” he added.
 

Effective and Well Tolerated

The safety results are “suggestive of a drug that is well tolerated, with injection-site reactions being the only remarkable adverse event increased in the treatment group,” Dr. Norata reported.

Only a “limited number” of patients developed neutralizing antidrug antibodies, which did not affect the efficacy of lerodalcibep. However, “given that the therapy is expected to be administered for years,” a longer analysis is needed to exclude the concern that a small percentage of neutralizing antidrug antibodies could reduce the efficacy, he said.

If approved, lerodalcibep could end up as a first-line option in the treatment pathway for high-risk cardiovascular disease because the efficacy “is similar to that of other injectable PCSK9 inhibitors,” he said, adding that its position in the market will “largely depend on the price.”

As the mechanism of action is similar to that of other monoclonal antibodies, “there is no pharmacological rationale to use it after another PSCK9 inhibitor,” he explained.

Lerodalcibep is a small recombinant fusion protein that combines a PCSK9-binding domain with human serum albumin.

The binding domain blocks the interaction between PCSK9 and the LDL cholesterol receptor, and the albumin linkage increases the half-life to 12-15 days, allowing low-volume injections to be given every 4 weeks.

A prior phase 2 study suggested that lerodalcibep substantially decreases LDL cholesterol levels in patients already taking maximally tolerated statins. The 300-mg dose was associated with an average reduction from baseline in LDL cholesterol levels of 77% over 12 weeks, whereas free PCSK9 levels decreased by 88%.

The current phase 3 study enrolled individuals at 65 centers in 100 countries who had or were at a very high risk for cardiovascular disease and who had an LDL cholesterol level of ≥ 1.8 mmol/L despite being on maximally tolerated statins.

Study participants were randomized in a 2:1 ratio to receive monthly subcutaneous lerodalcibep (n = 614) or placebo (n = 308) for 52 weeks and were assessed for the co-primary endpoints of the percentage change in LDL cholesterol levels from baseline to week 52 and the mean of levels at weeks 50 and 52.

The mean age was similar in the lerodalcibep and placebo groups (63.3 vs 64.5 years), as were the proportion of female (30% vs 30%) and White (80% vs 79%) participants.

The vast majority of participants in the lerodalcibep and placebo groups had a documented cardiovascular event (85.3% vs 86.4%) and were receiving secondary prevention, and 87% and 82%, respectively, were receiving a statin (any dose).

In a modified intention-to-treat analysis, the mean placebo-adjusted reduction in LDL cholesterol levels from baseline with lerodalcibep was 62% at week 52 (P < .0001), and the mean of levels at weeks 50 and 52 was 69.4% (P < .0001).

Similar results were seen in a per protocol analysis and an intention-to-treat analysis with imputation, which is a US Food and Drug Administration measure introduced in 2021 that assumes patients who discontinue the study treatment have an outcome similar to that in the placebo patients.

Moreover, 98.2% of patients in the lerodalcibep group achieved the ESC and European Atherosclerosis Society recommended reduction in LDL cholesterol levels of ≥ 50%, whereas only 8.8% in the placebo group did.
 

Hitting the LDL Cholesterol Target

More patients in the lerodalcibep group than in the placebo group achieved the LDL cholesterol target of < 1.4 mmol/L (95.3% vs 18.5%), and more patients in the lerodalcibep group achieved both that target and the ≥ 50% target (94.5% and 6.8%).

Lerodalcibep was also associated with significant reductions from baseline in levels of non–high-density lipoprotein (HDL) cholesterol, apolipoprotein B, very LDL cholesterol, and triglycerides, as well as an increase in HDL cholesterol levels (P < .0001 for all).

In terms of safety, lerodalcibep was associated with an adverse event rate leading to withdrawal similar to that seen with placebo (4.2% vs 3.6%), and 15.9% and 14.8% of patients, respectively, experienced at least one serious adverse event.

In-stent restenosis occurred more often in the lerodalcibep group than in the placebo group (5.4% vs 2.0%).

The study drug was associated with low levels of transient and sporadic antidrug antibodies and a low rate of neutralizing antidrug antibodies (0.9%), which were not associated with restenosis, a reduction in free PCSK9 levels, or the ability of lerodalcibep to lower LDL cholesterol levels.

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

LYON, France – Lerodalcibep, a novel, third-generation anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, helps high-risk patients already receiving maximally tolerated statins to achieve guideline lipid targets, reported investigators.

In the randomized, placebo-controlled LIBerate-CVD trial of more than 900 patients, lerodalcibep led to reductions from baseline in low-density lipoprotein (LDL) cholesterol levels of more than 60%.

“We believe that lerodalcibep offers a novel, effective alternative to current PCSK9 inhibitors for patients with cardiovascular disease or at very high risk for cardiovascular disease,” said Evan Stein, MD, PhD, chief scientific officer and cofounder of LIB Therapeutics in Chicago, who presented the findings at the European Atherosclerosis Society (EAS) 2024.

Moreover, it leads to “substantial additional LDL cholesterol reductions on top of existing oral agents” and allows more than 90% of patients to achieve the latest European Society of Cardiology (ESC) guideline targets, he said.

Lerodalcibep has “tolerability and safety similar to placebo,” Dr. Stein said, and requires only “a small monthly injection, which takes about 12 seconds.”

“The drug doesn’t require refrigeration” and is “stable, so far, over 9 months,” he reported.

The latest data “confirm the efficacy of lerodalcibep,” said Giuseppe Danilo Norata, PhD, from the Department of Pharmacological and Biomolecular Sciences at the University of Milan, Milan, Italy, who was not involved in the study.

The LDL cholesterol reduction in this phase 3 trial is “in line with what was observed in LIBerate-FH,” and the high proportion of patients achieving their LDL cholesterol target is “impressive,” he added.
 

Effective and Well Tolerated

The safety results are “suggestive of a drug that is well tolerated, with injection-site reactions being the only remarkable adverse event increased in the treatment group,” Dr. Norata reported.

Only a “limited number” of patients developed neutralizing antidrug antibodies, which did not affect the efficacy of lerodalcibep. However, “given that the therapy is expected to be administered for years,” a longer analysis is needed to exclude the concern that a small percentage of neutralizing antidrug antibodies could reduce the efficacy, he said.

If approved, lerodalcibep could end up as a first-line option in the treatment pathway for high-risk cardiovascular disease because the efficacy “is similar to that of other injectable PCSK9 inhibitors,” he said, adding that its position in the market will “largely depend on the price.”

As the mechanism of action is similar to that of other monoclonal antibodies, “there is no pharmacological rationale to use it after another PSCK9 inhibitor,” he explained.

Lerodalcibep is a small recombinant fusion protein that combines a PCSK9-binding domain with human serum albumin.

The binding domain blocks the interaction between PCSK9 and the LDL cholesterol receptor, and the albumin linkage increases the half-life to 12-15 days, allowing low-volume injections to be given every 4 weeks.

A prior phase 2 study suggested that lerodalcibep substantially decreases LDL cholesterol levels in patients already taking maximally tolerated statins. The 300-mg dose was associated with an average reduction from baseline in LDL cholesterol levels of 77% over 12 weeks, whereas free PCSK9 levels decreased by 88%.

The current phase 3 study enrolled individuals at 65 centers in 100 countries who had or were at a very high risk for cardiovascular disease and who had an LDL cholesterol level of ≥ 1.8 mmol/L despite being on maximally tolerated statins.

Study participants were randomized in a 2:1 ratio to receive monthly subcutaneous lerodalcibep (n = 614) or placebo (n = 308) for 52 weeks and were assessed for the co-primary endpoints of the percentage change in LDL cholesterol levels from baseline to week 52 and the mean of levels at weeks 50 and 52.

The mean age was similar in the lerodalcibep and placebo groups (63.3 vs 64.5 years), as were the proportion of female (30% vs 30%) and White (80% vs 79%) participants.

The vast majority of participants in the lerodalcibep and placebo groups had a documented cardiovascular event (85.3% vs 86.4%) and were receiving secondary prevention, and 87% and 82%, respectively, were receiving a statin (any dose).

In a modified intention-to-treat analysis, the mean placebo-adjusted reduction in LDL cholesterol levels from baseline with lerodalcibep was 62% at week 52 (P < .0001), and the mean of levels at weeks 50 and 52 was 69.4% (P < .0001).

Similar results were seen in a per protocol analysis and an intention-to-treat analysis with imputation, which is a US Food and Drug Administration measure introduced in 2021 that assumes patients who discontinue the study treatment have an outcome similar to that in the placebo patients.

Moreover, 98.2% of patients in the lerodalcibep group achieved the ESC and European Atherosclerosis Society recommended reduction in LDL cholesterol levels of ≥ 50%, whereas only 8.8% in the placebo group did.
 

Hitting the LDL Cholesterol Target

More patients in the lerodalcibep group than in the placebo group achieved the LDL cholesterol target of < 1.4 mmol/L (95.3% vs 18.5%), and more patients in the lerodalcibep group achieved both that target and the ≥ 50% target (94.5% and 6.8%).

Lerodalcibep was also associated with significant reductions from baseline in levels of non–high-density lipoprotein (HDL) cholesterol, apolipoprotein B, very LDL cholesterol, and triglycerides, as well as an increase in HDL cholesterol levels (P < .0001 for all).

In terms of safety, lerodalcibep was associated with an adverse event rate leading to withdrawal similar to that seen with placebo (4.2% vs 3.6%), and 15.9% and 14.8% of patients, respectively, experienced at least one serious adverse event.

In-stent restenosis occurred more often in the lerodalcibep group than in the placebo group (5.4% vs 2.0%).

The study drug was associated with low levels of transient and sporadic antidrug antibodies and a low rate of neutralizing antidrug antibodies (0.9%), which were not associated with restenosis, a reduction in free PCSK9 levels, or the ability of lerodalcibep to lower LDL cholesterol levels.

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

TOPLINE:

An experimental pancreatic gene therapy given to a mouse model of obesity as a one-time, single-dose treatment showed improvements in body composition and fasting glucose comparable with those achieved with the glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide, without the reversal of fat-loss and glycemia improvements that are a key concern with the withdrawal of GLP-1 receptor agonist drugs.

METHODOLOGY:

• The adeno-associated virus–based GLP-1 pancreatic gene therapy is designed to induce durable islet production of GLP-1 peptides that could, in theory, negate the need for regular injections or dosing of conventional GLP-1 receptor agonist drugs.
• With initial preclinical research showing benefits in Yucatan pigs, the authors tested the pancreatic gene therapy in mice representing a validated model of diet-induced obesity.
• The mice were randomized to receive either a single-dose administration of the pancreatic gene therapy (n = 10), daily subcutaneous semaglutide injections (n = 10; 10 nmol/kg/d for 4 weeks), pancreatic gene therapy placebo (n = 8), or a semaglutide placebo (n = 8).
• The gene therapy is designed to be delivered directly to the pancreas with a needle puncture, using a proprietary endoscopic delivery method that is similar to procedures commonly performed by gastrointestinal endoscopists, limiting systemic exposure.
• At 4 weeks, semaglutide was discontinued, and 5 of the 10 mice in that group were randomized to the gene therapy, while the other 5 received placebo.

TAKEAWAY:

• At week 4, the pancreatic gene therapy arm had a reduction in fat mass of 21%, compared with 16% with semaglutide (P < .05; both P < .0001 vs placebo)
• The pancreatic gene therapy and semaglutide groups each preserved lean mass, with a loss of only 5% of body weight (both P < .0001 vs placebo).
• At week 8, mice withdrawn from semaglutide had nearly a full reversal of the fat and lean mass losses observed at 4 weeks, returning to within 1% and 2% below baseline, respectively, while the semaglutide-withdrawn mice treated with gene therapy maintained a fat reduction of 17% (P < .01) and lean mass of 5% (P < .0001).
• Significant improvements in fasting glucose were observed in the gene therapy and semaglutide-treated mice at week 4 (both 18%; P < .0001).
• While semaglutide-withdrawal resulted in a rebound of fasting glucose to baseline at week 8, those who had initially received gene therapy or were switched over to the therapy maintained fasting glucose reductions of 21% and 22% at 8 weeks (P < .0001 and P < .001), respectively.
• No indications of pancreatic inflammation or injury were observed in any of the groups.

IN PRACTICE:

The results suggest the therapy could represent “a reliable, ‘off ramp’ from chronic GLP-1 drugs that allows people to maintain the weight loss and blood sugar benefits, even as they stop taking these medicines,” said first author Harith Rajagopalan, MD, PhD, cofounder and chief executive officer of Fractyl Health, which is developing the gene therapy, in a press statement issued by the company.

The therapy is being developed as a candidate for the treatment of type 2 diabetes and plans are underway for the first in-human study in type 2 diabetes in 2025, Dr. Rajagopalan noted while presenting the results at the American Diabetes Association (ADA)’s 84th scientific sessions.
 

SOURCE:

The study was presented on June 23, 2024, at the annual meeting of the ADA’s 84th scientific sessions (Abstract #261-OR).

LIMITATIONS:

The pancreatic gene therapy is in early development and has not been assessed by any regulatory body for investigational or commercial use.

Asked by an audience member at the ADA presentation if the therapy would be reversible if complications were to arise, Dr. Rajagopalan responded that “there are ways to tune this effect in order to prevent complications from occurring, which we will discuss in due course.”

Also asked about the potential for a positive feedback loop with GLP-1 signaling and insulin signaling, Dr. Rajagopalan noted that “I don’t believe that we have seen any evidence of that risk so far. One could hypothesize, but we have not seen anything [in that regard] that would be a cause for concern.”
 

DISCLOSURES:

The study was funded by Fractyl Health, and Dr. Rajagopalan and the authors declared being employees and stockholders/shareholders of the company.

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

TOPLINE:

An experimental pancreatic gene therapy given to a mouse model of obesity as a one-time, single-dose treatment showed improvements in body composition and fasting glucose comparable with those achieved with the glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide, without the reversal of fat-loss and glycemia improvements that are a key concern with the withdrawal of GLP-1 receptor agonist drugs.

METHODOLOGY:

• The adeno-associated virus–based GLP-1 pancreatic gene therapy is designed to induce durable islet production of GLP-1 peptides that could, in theory, negate the need for regular injections or dosing of conventional GLP-1 receptor agonist drugs.
• With initial preclinical research showing benefits in Yucatan pigs, the authors tested the pancreatic gene therapy in mice representing a validated model of diet-induced obesity.
• The mice were randomized to receive either a single-dose administration of the pancreatic gene therapy (n = 10), daily subcutaneous semaglutide injections (n = 10; 10 nmol/kg/d for 4 weeks), pancreatic gene therapy placebo (n = 8), or a semaglutide placebo (n = 8).
• The gene therapy is designed to be delivered directly to the pancreas with a needle puncture, using a proprietary endoscopic delivery method that is similar to procedures commonly performed by gastrointestinal endoscopists, limiting systemic exposure.
• At 4 weeks, semaglutide was discontinued, and 5 of the 10 mice in that group were randomized to the gene therapy, while the other 5 received placebo.

TAKEAWAY:

• At week 4, the pancreatic gene therapy arm had a reduction in fat mass of 21%, compared with 16% with semaglutide (P < .05; both P < .0001 vs placebo)
• The pancreatic gene therapy and semaglutide groups each preserved lean mass, with a loss of only 5% of body weight (both P < .0001 vs placebo).
• At week 8, mice withdrawn from semaglutide had nearly a full reversal of the fat and lean mass losses observed at 4 weeks, returning to within 1% and 2% below baseline, respectively, while the semaglutide-withdrawn mice treated with gene therapy maintained a fat reduction of 17% (P < .01) and lean mass of 5% (P < .0001).
• Significant improvements in fasting glucose were observed in the gene therapy and semaglutide-treated mice at week 4 (both 18%; P < .0001).
• While semaglutide-withdrawal resulted in a rebound of fasting glucose to baseline at week 8, those who had initially received gene therapy or were switched over to the therapy maintained fasting glucose reductions of 21% and 22% at 8 weeks (P < .0001 and P < .001), respectively.
• No indications of pancreatic inflammation or injury were observed in any of the groups.

IN PRACTICE:

The results suggest the therapy could represent “a reliable, ‘off ramp’ from chronic GLP-1 drugs that allows people to maintain the weight loss and blood sugar benefits, even as they stop taking these medicines,” said first author Harith Rajagopalan, MD, PhD, cofounder and chief executive officer of Fractyl Health, which is developing the gene therapy, in a press statement issued by the company.

The therapy is being developed as a candidate for the treatment of type 2 diabetes and plans are underway for the first in-human study in type 2 diabetes in 2025, Dr. Rajagopalan noted while presenting the results at the American Diabetes Association (ADA)’s 84th scientific sessions.
 

SOURCE:

The study was presented on June 23, 2024, at the annual meeting of the ADA’s 84th scientific sessions (Abstract #261-OR).

LIMITATIONS:

The pancreatic gene therapy is in early development and has not been assessed by any regulatory body for investigational or commercial use.

Asked by an audience member at the ADA presentation if the therapy would be reversible if complications were to arise, Dr. Rajagopalan responded that “there are ways to tune this effect in order to prevent complications from occurring, which we will discuss in due course.”

Also asked about the potential for a positive feedback loop with GLP-1 signaling and insulin signaling, Dr. Rajagopalan noted that “I don’t believe that we have seen any evidence of that risk so far. One could hypothesize, but we have not seen anything [in that regard] that would be a cause for concern.”
 

DISCLOSURES:

The study was funded by Fractyl Health, and Dr. Rajagopalan and the authors declared being employees and stockholders/shareholders of the company.

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

TOPLINE:

An experimental pancreatic gene therapy given to a mouse model of obesity as a one-time, single-dose treatment showed improvements in body composition and fasting glucose comparable with those achieved with the glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide, without the reversal of fat-loss and glycemia improvements that are a key concern with the withdrawal of GLP-1 receptor agonist drugs.

METHODOLOGY:

• The adeno-associated virus–based GLP-1 pancreatic gene therapy is designed to induce durable islet production of GLP-1 peptides that could, in theory, negate the need for regular injections or dosing of conventional GLP-1 receptor agonist drugs.
• With initial preclinical research showing benefits in Yucatan pigs, the authors tested the pancreatic gene therapy in mice representing a validated model of diet-induced obesity.
• The mice were randomized to receive either a single-dose administration of the pancreatic gene therapy (n = 10), daily subcutaneous semaglutide injections (n = 10; 10 nmol/kg/d for 4 weeks), pancreatic gene therapy placebo (n = 8), or a semaglutide placebo (n = 8).
• The gene therapy is designed to be delivered directly to the pancreas with a needle puncture, using a proprietary endoscopic delivery method that is similar to procedures commonly performed by gastrointestinal endoscopists, limiting systemic exposure.
• At 4 weeks, semaglutide was discontinued, and 5 of the 10 mice in that group were randomized to the gene therapy, while the other 5 received placebo.

TAKEAWAY:

• At week 4, the pancreatic gene therapy arm had a reduction in fat mass of 21%, compared with 16% with semaglutide (P < .05; both P < .0001 vs placebo)
• The pancreatic gene therapy and semaglutide groups each preserved lean mass, with a loss of only 5% of body weight (both P < .0001 vs placebo).
• At week 8, mice withdrawn from semaglutide had nearly a full reversal of the fat and lean mass losses observed at 4 weeks, returning to within 1% and 2% below baseline, respectively, while the semaglutide-withdrawn mice treated with gene therapy maintained a fat reduction of 17% (P < .01) and lean mass of 5% (P < .0001).
• Significant improvements in fasting glucose were observed in the gene therapy and semaglutide-treated mice at week 4 (both 18%; P < .0001).
• While semaglutide-withdrawal resulted in a rebound of fasting glucose to baseline at week 8, those who had initially received gene therapy or were switched over to the therapy maintained fasting glucose reductions of 21% and 22% at 8 weeks (P < .0001 and P < .001), respectively.
• No indications of pancreatic inflammation or injury were observed in any of the groups.

IN PRACTICE:

The results suggest the therapy could represent “a reliable, ‘off ramp’ from chronic GLP-1 drugs that allows people to maintain the weight loss and blood sugar benefits, even as they stop taking these medicines,” said first author Harith Rajagopalan, MD, PhD, cofounder and chief executive officer of Fractyl Health, which is developing the gene therapy, in a press statement issued by the company.

The therapy is being developed as a candidate for the treatment of type 2 diabetes and plans are underway for the first in-human study in type 2 diabetes in 2025, Dr. Rajagopalan noted while presenting the results at the American Diabetes Association (ADA)’s 84th scientific sessions.
 

SOURCE:

The study was presented on June 23, 2024, at the annual meeting of the ADA’s 84th scientific sessions (Abstract #261-OR).

LIMITATIONS:

The pancreatic gene therapy is in early development and has not been assessed by any regulatory body for investigational or commercial use.

Asked by an audience member at the ADA presentation if the therapy would be reversible if complications were to arise, Dr. Rajagopalan responded that “there are ways to tune this effect in order to prevent complications from occurring, which we will discuss in due course.”

Also asked about the potential for a positive feedback loop with GLP-1 signaling and insulin signaling, Dr. Rajagopalan noted that “I don’t believe that we have seen any evidence of that risk so far. One could hypothesize, but we have not seen anything [in that regard] that would be a cause for concern.”
 

DISCLOSURES:

The study was funded by Fractyl Health, and Dr. Rajagopalan and the authors declared being employees and stockholders/shareholders of the company.

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

Adults older than 50 years who report experiencing persistently high levels of loneliness have a 56% increased risk for stroke, a new study showed.

The increased stroke risk did not apply to individuals who reported experiencing situational loneliness, a finding that investigators believe bolsters the hypothesis that chronic loneliness is driving the association.

“Our findings suggest that individuals who experience chronic loneliness are at higher risk for incident stroke,” lead investigator Yenee Soh, ScD, research associate of social and behavioral sciences in the Harvard T.H. Chan School of Public Health, Boston, told this news organization. “It is important to routinely assess loneliness, as the consequences may be worse if unidentified and/or ignored.”

The findings were published online in eClinicalMedicine.
 

Significant, Chronic Health Consequences

Exacerbated by the COVID-19 pandemic, loneliness is at an all-time high. A 2023 Surgeon General’s report highlighted the fact that loneliness and social isolation are linked to significant and chronic health consequences.

Previous research has linked loneliness to cardiovascular disease, yet few studies have examined the association between loneliness and stroke risk. The current study is one of the first to examine the association between changes in loneliness and stroke risk over time.

Using data from the 2006-2018 Health and Retirement Study, researchers assessed the link between loneliness and incident stroke over time. Between 2006 and 2008, 12,161 study participants, who were all older than 50 years with no history of stroke, responded to questions from the Revised UCLA Loneliness Scale. From these responses, researchers created summary loneliness scores.

Four years later, from 2010 to 2012, the 8936 remaining study participants responded to the same 20 questions again. Based on loneliness scores across the two time points, participants were divided into four groups:

• Consistently low (those who scored low on the loneliness scale at both baseline and follow-up).
• Remitting (those who scored high at baseline and low at follow-up).
• Recent onset (those who scored low at baseline and high at follow-up).
• Consistently high (those who scored high at both baseline and follow-up).

Incident stroke was determined by participant report and medical record data.

Among participants whose loneliness was measured at baseline only, 1237 strokes occurred during the 2006-2018 follow-up period. Among those who provided two loneliness assessments over time, 601 strokes occurred during the follow-up period.

Even after adjusting for social isolation, depressive symptoms, physical activity, body mass index, and other health conditions, investigators found that participants who reported being lonely at baseline only had a 25% increased stroke risk, compared with those who did not report being lonely at baseline (hazard ratio [HR], 1.25; 95% confidence interval (CI), 1.06-1.47).

Participants who reported having consistently high loneliness across both time points had a 56% increased risk for incident stroke vs those who did not report loneliness at both time points after adjusting for social isolation and depression (HR, 1.56; 95% CI, 1.11-2.18).

The researchers did not investigate any of the underlying issues that may contribute to the association between loneliness and stroke risk, but speculated there may be physiological factors at play. These could include inflammation caused by increased hypothalamic pituitary-adrenocortical activity, behavioral factors such as poor medication adherence, smoking and/or alcohol use, and psychosocial issues.

Those who experience chronic loneliness may represent individuals that are unable to develop or maintain satisfying social relationships, which may result in longer-term interpersonal difficulties, Dr. Soh noted.

“Since loneliness is a highly subjective experience, seeking help to address and intervene to address a patient’s specific personal needs is important. It’s important to distinguish loneliness from social isolation,” said Dr. Soh.

She added that “by screening for loneliness and providing care or referring patients to relevant behavioral healthcare providers, clinicians can play a crucial role in addressing loneliness and its associated health risks early on to help reduce the population burden of loneliness.”
 

Progressive Research

Commenting on the findings for this news organization, Elaine Jones, MD, medical director of Access TeleCare, who was not involved in the research, applauded the investigators for “advancing the topic by looking at the chronicity aspect of loneliness.”

She said more research is needed to investigate loneliness as a stroke risk factor and noted that there may be something inherently different among respondents who reported loneliness at both study time points.

“Personality types may play a role here. We know people with positive attitudes and outlooks can do better in challenging health situations than people who are negative in their attitudes, regardless of depression. Perhaps those who feel lonely initially decided to do something about it and join groups, take up a hobby, or re-engage with family or friends. Perhaps the people who are chronically lonely don’t, or can’t, do this,” Dr. Jones said.

Chronic loneliness can cause stress, she added, “and we know that stress chemicals and hormones can be harmful to health over long durations of time.”

The study was funded by the National Institute on Aging. There were no conflicts of interest noted.

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

Adults older than 50 years who report experiencing persistently high levels of loneliness have a 56% increased risk for stroke, a new study showed.

The increased stroke risk did not apply to individuals who reported experiencing situational loneliness, a finding that investigators believe bolsters the hypothesis that chronic loneliness is driving the association.

“Our findings suggest that individuals who experience chronic loneliness are at higher risk for incident stroke,” lead investigator Yenee Soh, ScD, research associate of social and behavioral sciences in the Harvard T.H. Chan School of Public Health, Boston, told this news organization. “It is important to routinely assess loneliness, as the consequences may be worse if unidentified and/or ignored.”

The findings were published online in eClinicalMedicine.
 

Significant, Chronic Health Consequences

Exacerbated by the COVID-19 pandemic, loneliness is at an all-time high. A 2023 Surgeon General’s report highlighted the fact that loneliness and social isolation are linked to significant and chronic health consequences.

Previous research has linked loneliness to cardiovascular disease, yet few studies have examined the association between loneliness and stroke risk. The current study is one of the first to examine the association between changes in loneliness and stroke risk over time.

Using data from the 2006-2018 Health and Retirement Study, researchers assessed the link between loneliness and incident stroke over time. Between 2006 and 2008, 12,161 study participants, who were all older than 50 years with no history of stroke, responded to questions from the Revised UCLA Loneliness Scale. From these responses, researchers created summary loneliness scores.

Four years later, from 2010 to 2012, the 8936 remaining study participants responded to the same 20 questions again. Based on loneliness scores across the two time points, participants were divided into four groups:

• Consistently low (those who scored low on the loneliness scale at both baseline and follow-up).
• Remitting (those who scored high at baseline and low at follow-up).
• Recent onset (those who scored low at baseline and high at follow-up).
• Consistently high (those who scored high at both baseline and follow-up).

Incident stroke was determined by participant report and medical record data.

Among participants whose loneliness was measured at baseline only, 1237 strokes occurred during the 2006-2018 follow-up period. Among those who provided two loneliness assessments over time, 601 strokes occurred during the follow-up period.

Even after adjusting for social isolation, depressive symptoms, physical activity, body mass index, and other health conditions, investigators found that participants who reported being lonely at baseline only had a 25% increased stroke risk, compared with those who did not report being lonely at baseline (hazard ratio [HR], 1.25; 95% confidence interval (CI), 1.06-1.47).

Participants who reported having consistently high loneliness across both time points had a 56% increased risk for incident stroke vs those who did not report loneliness at both time points after adjusting for social isolation and depression (HR, 1.56; 95% CI, 1.11-2.18).

The researchers did not investigate any of the underlying issues that may contribute to the association between loneliness and stroke risk, but speculated there may be physiological factors at play. These could include inflammation caused by increased hypothalamic pituitary-adrenocortical activity, behavioral factors such as poor medication adherence, smoking and/or alcohol use, and psychosocial issues.

Those who experience chronic loneliness may represent individuals that are unable to develop or maintain satisfying social relationships, which may result in longer-term interpersonal difficulties, Dr. Soh noted.

“Since loneliness is a highly subjective experience, seeking help to address and intervene to address a patient’s specific personal needs is important. It’s important to distinguish loneliness from social isolation,” said Dr. Soh.

She added that “by screening for loneliness and providing care or referring patients to relevant behavioral healthcare providers, clinicians can play a crucial role in addressing loneliness and its associated health risks early on to help reduce the population burden of loneliness.”
 

Progressive Research

Commenting on the findings for this news organization, Elaine Jones, MD, medical director of Access TeleCare, who was not involved in the research, applauded the investigators for “advancing the topic by looking at the chronicity aspect of loneliness.”

She said more research is needed to investigate loneliness as a stroke risk factor and noted that there may be something inherently different among respondents who reported loneliness at both study time points.

“Personality types may play a role here. We know people with positive attitudes and outlooks can do better in challenging health situations than people who are negative in their attitudes, regardless of depression. Perhaps those who feel lonely initially decided to do something about it and join groups, take up a hobby, or re-engage with family or friends. Perhaps the people who are chronically lonely don’t, or can’t, do this,” Dr. Jones said.

Chronic loneliness can cause stress, she added, “and we know that stress chemicals and hormones can be harmful to health over long durations of time.”

The study was funded by the National Institute on Aging. There were no conflicts of interest noted.

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

Adults older than 50 years who report experiencing persistently high levels of loneliness have a 56% increased risk for stroke, a new study showed.

The increased stroke risk did not apply to individuals who reported experiencing situational loneliness, a finding that investigators believe bolsters the hypothesis that chronic loneliness is driving the association.

“Our findings suggest that individuals who experience chronic loneliness are at higher risk for incident stroke,” lead investigator Yenee Soh, ScD, research associate of social and behavioral sciences in the Harvard T.H. Chan School of Public Health, Boston, told this news organization. “It is important to routinely assess loneliness, as the consequences may be worse if unidentified and/or ignored.”

The findings were published online in eClinicalMedicine.
 

Significant, Chronic Health Consequences

Exacerbated by the COVID-19 pandemic, loneliness is at an all-time high. A 2023 Surgeon General’s report highlighted the fact that loneliness and social isolation are linked to significant and chronic health consequences.

Previous research has linked loneliness to cardiovascular disease, yet few studies have examined the association between loneliness and stroke risk. The current study is one of the first to examine the association between changes in loneliness and stroke risk over time.

Using data from the 2006-2018 Health and Retirement Study, researchers assessed the link between loneliness and incident stroke over time. Between 2006 and 2008, 12,161 study participants, who were all older than 50 years with no history of stroke, responded to questions from the Revised UCLA Loneliness Scale. From these responses, researchers created summary loneliness scores.

Four years later, from 2010 to 2012, the 8936 remaining study participants responded to the same 20 questions again. Based on loneliness scores across the two time points, participants were divided into four groups:

• Consistently low (those who scored low on the loneliness scale at both baseline and follow-up).
• Remitting (those who scored high at baseline and low at follow-up).
• Recent onset (those who scored low at baseline and high at follow-up).
• Consistently high (those who scored high at both baseline and follow-up).

Incident stroke was determined by participant report and medical record data.

Among participants whose loneliness was measured at baseline only, 1237 strokes occurred during the 2006-2018 follow-up period. Among those who provided two loneliness assessments over time, 601 strokes occurred during the follow-up period.

Even after adjusting for social isolation, depressive symptoms, physical activity, body mass index, and other health conditions, investigators found that participants who reported being lonely at baseline only had a 25% increased stroke risk, compared with those who did not report being lonely at baseline (hazard ratio [HR], 1.25; 95% confidence interval (CI), 1.06-1.47).

Participants who reported having consistently high loneliness across both time points had a 56% increased risk for incident stroke vs those who did not report loneliness at both time points after adjusting for social isolation and depression (HR, 1.56; 95% CI, 1.11-2.18).

The researchers did not investigate any of the underlying issues that may contribute to the association between loneliness and stroke risk, but speculated there may be physiological factors at play. These could include inflammation caused by increased hypothalamic pituitary-adrenocortical activity, behavioral factors such as poor medication adherence, smoking and/or alcohol use, and psychosocial issues.

Those who experience chronic loneliness may represent individuals that are unable to develop or maintain satisfying social relationships, which may result in longer-term interpersonal difficulties, Dr. Soh noted.

“Since loneliness is a highly subjective experience, seeking help to address and intervene to address a patient’s specific personal needs is important. It’s important to distinguish loneliness from social isolation,” said Dr. Soh.

She added that “by screening for loneliness and providing care or referring patients to relevant behavioral healthcare providers, clinicians can play a crucial role in addressing loneliness and its associated health risks early on to help reduce the population burden of loneliness.”
 

Progressive Research

Commenting on the findings for this news organization, Elaine Jones, MD, medical director of Access TeleCare, who was not involved in the research, applauded the investigators for “advancing the topic by looking at the chronicity aspect of loneliness.”

She said more research is needed to investigate loneliness as a stroke risk factor and noted that there may be something inherently different among respondents who reported loneliness at both study time points.

“Personality types may play a role here. We know people with positive attitudes and outlooks can do better in challenging health situations than people who are negative in their attitudes, regardless of depression. Perhaps those who feel lonely initially decided to do something about it and join groups, take up a hobby, or re-engage with family or friends. Perhaps the people who are chronically lonely don’t, or can’t, do this,” Dr. Jones said.

Chronic loneliness can cause stress, she added, “and we know that stress chemicals and hormones can be harmful to health over long durations of time.”

The study was funded by the National Institute on Aging. There were no conflicts of interest noted.

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

Halifax, Nova Scotia; American Samoa; Queens, New York; Lansing, Michigan; Gurugram, India. I often ask patients where they’re from. Practicing in San Diego, the answers are a geography lesson. People from around the world come here. I sometimes add the more interesting question: How’d you end up here? Many took the three highways to San Diego: the Navy, the defense industry (like General Dynamics), or followed a partner. My Queens patient had a better answer: Super Bowl XXII. On Sunday, Jan. 31st, 1988, the Redskins played the Broncos in San Diego. John Elway and the Broncos lost, but it didn’t matter. “I was scrapin’ the ice off my windshield that Monday morning when I thought, that’s it. I’m done! I drove to the garage where I worked and quit on the spot. Then I drove home and packed my bags.”

In a paper on how to make life decisions, this guy would be Exhibit A: “Don’t overthink it.” That approach might not be suitable for everyone, or for every decision. It might actually be an example of how not to make life decisions (more on that later). But, is there a best way to go about making big life decisions?

The first treatise on this subject was a paper by one Franklin, Ben in 1772. Providing advice to a friend on how to make a career decision, Franklin argued: “My way is to divide half a sheet of paper by a line into two columns; writing over the one Pro and over the other Con.” This “moral algebra” as he called it was a framework to put rigor to a messy, organic problem.

wrawecihokilospeslofriphohobuchibiletutawrospepehophastephechewrubrelopadrocosleswobislimimumesoclupiuiposwocihistithophabru

The flaw in this method is that in the end you have two lists. Then what? Do the length of the lists decide? What if some factors are more important? Well, let’s add tools to help. You could use a spreadsheet and assign weights to each variable. Then sum the values and choose based on that. So if “not scraping ice off your windshield” is twice as important as “doubling your rent,” then you’ve got your answer. But what if you aren’t good at estimating how important things are? Actually, most of us are pretty awful at assigning weights to life variables – having bags of money is the consummate example. Seems important, but because of habituation, it turns out to not be sustainable. Note Exhibit B, our wealthy neighbor who owns a Lambo and G-Wagen (AMG squared, of course), who just parked a Cybertruck in his driveway. Realizing the risk of depending on peoples’ flawed judgment, companies instead use statistical modeling called bootstrap aggregating to “vote” on the weights for variables in a prediction. If you aren’t sure how important a new Rivian or walking to the beach would be, a model can answer that for you! It’s a bit disconcerting, I know. I mean, how can a model know what we’d like? Wait, isn’t that how Netflix picks stuff for you? Exactly.

Ok, so why don’t we just ask our friendly personal AI? “OK, ChatGPT, given what you know about me, where can I have it all?” Alas, here we slam into a glass wall. It seems the answer is out there but even our life-changing magical AI tools fail us. Mathematically, it is impossible to have it all. An illustrative example of this is called the economic “impossible trinity problem.” Even the most sophisticated algorithm cannot find an optional solution to some trinities such as fixed foreign exchange rate, free capital movement, and an independent monetary policy. Economists have concluded you must trade off one to have the other two. Impossible trinities are common in economics and in life. Armistead Maupin in his “Tales of the City” codifies it as Mona’s Law, the essence of which is: You cannot have the perfect job, the perfect partner, and the perfect house at the same time. (See Exhibit C, one Tom Brady).

[embed:render:related:node:267456]

This brings me to my final point, hard decisions are matters of the heart and experiencing life is the best way to understand its beautiful chaos. If making rash judgments is ill-advised and using technology cannot solve all problems (try asking your AI buddy for the square root of 2 as a fraction) what tools can we use? Maybe try reading more novels. They allow us to experience multiple lifetimes in a short time, which is what we need to learn what matters. Reading Dorothea’s choice at the end of “Middlemarch” is a nice example. Should she give up Lowick Manor and marry the penniless Ladislaw or keep it and use her wealth to help others? Seeing her struggle helps us understand how to answer questions like: Should I give up my academic practice or marry that guy or move to Texas? These cannot be reduced to arithmetic. The only way to know is to know as much of life as possible.

My last visit with my Queens patient was our last together. He’s divorced and moving from San Diego to Gallatin, Tennessee. “I’ve paid my last taxes to California, Doc. I decided that’s it, I’m done!” Perhaps he should have read “The Grapes of Wrath” before he set out for California in the first place.

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 dermnews@mdedge.com.

Halifax, Nova Scotia; American Samoa; Queens, New York; Lansing, Michigan; Gurugram, India. I often ask patients where they’re from. Practicing in San Diego, the answers are a geography lesson. People from around the world come here. I sometimes add the more interesting question: How’d you end up here? Many took the three highways to San Diego: the Navy, the defense industry (like General Dynamics), or followed a partner. My Queens patient had a better answer: Super Bowl XXII. On Sunday, Jan. 31st, 1988, the Redskins played the Broncos in San Diego. John Elway and the Broncos lost, but it didn’t matter. “I was scrapin’ the ice off my windshield that Monday morning when I thought, that’s it. I’m done! I drove to the garage where I worked and quit on the spot. Then I drove home and packed my bags.”

In a paper on how to make life decisions, this guy would be Exhibit A: “Don’t overthink it.” That approach might not be suitable for everyone, or for every decision. It might actually be an example of how not to make life decisions (more on that later). But, is there a best way to go about making big life decisions?

The first treatise on this subject was a paper by one Franklin, Ben in 1772. Providing advice to a friend on how to make a career decision, Franklin argued: “My way is to divide half a sheet of paper by a line into two columns; writing over the one Pro and over the other Con.” This “moral algebra” as he called it was a framework to put rigor to a messy, organic problem.

wrawecihokilospeslofriphohobuchibiletutawrospepehophastephechewrubrelopadrocosleswobislimimumesoclupiuiposwocihistithophabru

The flaw in this method is that in the end you have two lists. Then what? Do the length of the lists decide? What if some factors are more important? Well, let’s add tools to help. You could use a spreadsheet and assign weights to each variable. Then sum the values and choose based on that. So if “not scraping ice off your windshield” is twice as important as “doubling your rent,” then you’ve got your answer. But what if you aren’t good at estimating how important things are? Actually, most of us are pretty awful at assigning weights to life variables – having bags of money is the consummate example. Seems important, but because of habituation, it turns out to not be sustainable. Note Exhibit B, our wealthy neighbor who owns a Lambo and G-Wagen (AMG squared, of course), who just parked a Cybertruck in his driveway. Realizing the risk of depending on peoples’ flawed judgment, companies instead use statistical modeling called bootstrap aggregating to “vote” on the weights for variables in a prediction. If you aren’t sure how important a new Rivian or walking to the beach would be, a model can answer that for you! It’s a bit disconcerting, I know. I mean, how can a model know what we’d like? Wait, isn’t that how Netflix picks stuff for you? Exactly.

Ok, so why don’t we just ask our friendly personal AI? “OK, ChatGPT, given what you know about me, where can I have it all?” Alas, here we slam into a glass wall. It seems the answer is out there but even our life-changing magical AI tools fail us. Mathematically, it is impossible to have it all. An illustrative example of this is called the economic “impossible trinity problem.” Even the most sophisticated algorithm cannot find an optional solution to some trinities such as fixed foreign exchange rate, free capital movement, and an independent monetary policy. Economists have concluded you must trade off one to have the other two. Impossible trinities are common in economics and in life. Armistead Maupin in his “Tales of the City” codifies it as Mona’s Law, the essence of which is: You cannot have the perfect job, the perfect partner, and the perfect house at the same time. (See Exhibit C, one Tom Brady).

[embed:render:related:node:267456]

This brings me to my final point, hard decisions are matters of the heart and experiencing life is the best way to understand its beautiful chaos. If making rash judgments is ill-advised and using technology cannot solve all problems (try asking your AI buddy for the square root of 2 as a fraction) what tools can we use? Maybe try reading more novels. They allow us to experience multiple lifetimes in a short time, which is what we need to learn what matters. Reading Dorothea’s choice at the end of “Middlemarch” is a nice example. Should she give up Lowick Manor and marry the penniless Ladislaw or keep it and use her wealth to help others? Seeing her struggle helps us understand how to answer questions like: Should I give up my academic practice or marry that guy or move to Texas? These cannot be reduced to arithmetic. The only way to know is to know as much of life as possible.

My last visit with my Queens patient was our last together. He’s divorced and moving from San Diego to Gallatin, Tennessee. “I’ve paid my last taxes to California, Doc. I decided that’s it, I’m done!” Perhaps he should have read “The Grapes of Wrath” before he set out for California in the first place.

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 dermnews@mdedge.com.

Halifax, Nova Scotia; American Samoa; Queens, New York; Lansing, Michigan; Gurugram, India. I often ask patients where they’re from. Practicing in San Diego, the answers are a geography lesson. People from around the world come here. I sometimes add the more interesting question: How’d you end up here? Many took the three highways to San Diego: the Navy, the defense industry (like General Dynamics), or followed a partner. My Queens patient had a better answer: Super Bowl XXII. On Sunday, Jan. 31st, 1988, the Redskins played the Broncos in San Diego. John Elway and the Broncos lost, but it didn’t matter. “I was scrapin’ the ice off my windshield that Monday morning when I thought, that’s it. I’m done! I drove to the garage where I worked and quit on the spot. Then I drove home and packed my bags.”

In a paper on how to make life decisions, this guy would be Exhibit A: “Don’t overthink it.” That approach might not be suitable for everyone, or for every decision. It might actually be an example of how not to make life decisions (more on that later). But, is there a best way to go about making big life decisions?

The first treatise on this subject was a paper by one Franklin, Ben in 1772. Providing advice to a friend on how to make a career decision, Franklin argued: “My way is to divide half a sheet of paper by a line into two columns; writing over the one Pro and over the other Con.” This “moral algebra” as he called it was a framework to put rigor to a messy, organic problem.

wrawecihokilospeslofriphohobuchibiletutawrospepehophastephechewrubrelopadrocosleswobislimimumesoclupiuiposwocihistithophabru

The flaw in this method is that in the end you have two lists. Then what? Do the length of the lists decide? What if some factors are more important? Well, let’s add tools to help. You could use a spreadsheet and assign weights to each variable. Then sum the values and choose based on that. So if “not scraping ice off your windshield” is twice as important as “doubling your rent,” then you’ve got your answer. But what if you aren’t good at estimating how important things are? Actually, most of us are pretty awful at assigning weights to life variables – having bags of money is the consummate example. Seems important, but because of habituation, it turns out to not be sustainable. Note Exhibit B, our wealthy neighbor who owns a Lambo and G-Wagen (AMG squared, of course), who just parked a Cybertruck in his driveway. Realizing the risk of depending on peoples’ flawed judgment, companies instead use statistical modeling called bootstrap aggregating to “vote” on the weights for variables in a prediction. If you aren’t sure how important a new Rivian or walking to the beach would be, a model can answer that for you! It’s a bit disconcerting, I know. I mean, how can a model know what we’d like? Wait, isn’t that how Netflix picks stuff for you? Exactly.

Ok, so why don’t we just ask our friendly personal AI? “OK, ChatGPT, given what you know about me, where can I have it all?” Alas, here we slam into a glass wall. It seems the answer is out there but even our life-changing magical AI tools fail us. Mathematically, it is impossible to have it all. An illustrative example of this is called the economic “impossible trinity problem.” Even the most sophisticated algorithm cannot find an optional solution to some trinities such as fixed foreign exchange rate, free capital movement, and an independent monetary policy. Economists have concluded you must trade off one to have the other two. Impossible trinities are common in economics and in life. Armistead Maupin in his “Tales of the City” codifies it as Mona’s Law, the essence of which is: You cannot have the perfect job, the perfect partner, and the perfect house at the same time. (See Exhibit C, one Tom Brady).

[embed:render:related:node:267456]

This brings me to my final point, hard decisions are matters of the heart and experiencing life is the best way to understand its beautiful chaos. If making rash judgments is ill-advised and using technology cannot solve all problems (try asking your AI buddy for the square root of 2 as a fraction) what tools can we use? Maybe try reading more novels. They allow us to experience multiple lifetimes in a short time, which is what we need to learn what matters. Reading Dorothea’s choice at the end of “Middlemarch” is a nice example. Should she give up Lowick Manor and marry the penniless Ladislaw or keep it and use her wealth to help others? Seeing her struggle helps us understand how to answer questions like: Should I give up my academic practice or marry that guy or move to Texas? These cannot be reduced to arithmetic. The only way to know is to know as much of life as possible.

My last visit with my Queens patient was our last together. He’s divorced and moving from San Diego to Gallatin, Tennessee. “I’ve paid my last taxes to California, Doc. I decided that’s it, I’m done!” Perhaps he should have read “The Grapes of Wrath” before he set out for California in the first place.

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 dermnews@mdedge.com.

TOPLINE:

A new analysis showed that preeclampsia is associated with an increased risk for young-onset dementia.

METHODOLOGY:

• Researchers analyzed data from the French Conception study, a nationwide prospective cohort study of more than 1.9 million pregnancies.
• Mothers were followed for an average of 9 years.

TAKEAWAY:

• Nearly 3% of the mothers had preeclampsia, and 128 developed young-onset dementia.
• Preeclampsia was associated with a 2.65-fold increased risk for young-onset dementia after adjusting for obesity, diabetes, smoking, drug or alcohol addiction, and social deprivation.
• The risk was greater when preeclampsia occurred before 34 weeks of gestation (hazard ratio [HR], 4.15) or was superimposed on chronic hypertension (HR, 4.76).
• Prior research has found an association between preeclampsia and vascular dementia, but this analysis “is the first to show an increase in early-onset dementia risk,” the authors of the study wrote.

IN PRACTICE:

“Individuals who have had preeclampsia should be reassured that young-onset dementia remains a very rare condition. Their absolute risk increases only imperceptibly,” Stephen Tong, PhD, and Roxanne Hastie, PhD, both with the University of Melbourne, Melbourne, Australia, wrote in a related commentary about the findings.

“Individuals who have been affected by preeclampsia in a prior pregnancy might instead focus on reducing their risk of developing the many chronic health ailments that are far more common,” they added. “Although it is yet to be proven in clinical trials, it is plausible that after an episode of preeclampsia, adopting a healthy lifestyle may improve vascular health and reduce the risk of many serious cardiovascular conditions.”

SOURCE:

Valérie Olié, PhD, of the Santé Publique France in Saint-Maurice, France, was the corresponding author on the paper. The research letter was published online in JAMA Network Open.

LIMITATIONS:

The investigators relied on hospital records to identify cases of dementia, which may have led to underestimation of incidence of the disease.

DISCLOSURES:

The study was funded by the French Hypertension Society, the French Hypertension Research Foundation, and the French Cardiology Federation. A co-author disclosed personal fees from pharmaceutical companies.

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

TOPLINE:

A new analysis showed that preeclampsia is associated with an increased risk for young-onset dementia.

METHODOLOGY:

• Researchers analyzed data from the French Conception study, a nationwide prospective cohort study of more than 1.9 million pregnancies.
• Mothers were followed for an average of 9 years.

TAKEAWAY:

• Nearly 3% of the mothers had preeclampsia, and 128 developed young-onset dementia.
• Preeclampsia was associated with a 2.65-fold increased risk for young-onset dementia after adjusting for obesity, diabetes, smoking, drug or alcohol addiction, and social deprivation.
• The risk was greater when preeclampsia occurred before 34 weeks of gestation (hazard ratio [HR], 4.15) or was superimposed on chronic hypertension (HR, 4.76).
• Prior research has found an association between preeclampsia and vascular dementia, but this analysis “is the first to show an increase in early-onset dementia risk,” the authors of the study wrote.

IN PRACTICE:

“Individuals who have had preeclampsia should be reassured that young-onset dementia remains a very rare condition. Their absolute risk increases only imperceptibly,” Stephen Tong, PhD, and Roxanne Hastie, PhD, both with the University of Melbourne, Melbourne, Australia, wrote in a related commentary about the findings.

“Individuals who have been affected by preeclampsia in a prior pregnancy might instead focus on reducing their risk of developing the many chronic health ailments that are far more common,” they added. “Although it is yet to be proven in clinical trials, it is plausible that after an episode of preeclampsia, adopting a healthy lifestyle may improve vascular health and reduce the risk of many serious cardiovascular conditions.”

SOURCE:

Valérie Olié, PhD, of the Santé Publique France in Saint-Maurice, France, was the corresponding author on the paper. The research letter was published online in JAMA Network Open.

LIMITATIONS:

The investigators relied on hospital records to identify cases of dementia, which may have led to underestimation of incidence of the disease.

DISCLOSURES:

The study was funded by the French Hypertension Society, the French Hypertension Research Foundation, and the French Cardiology Federation. A co-author disclosed personal fees from pharmaceutical companies.

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

TOPLINE:

A new analysis showed that preeclampsia is associated with an increased risk for young-onset dementia.

METHODOLOGY:

• Researchers analyzed data from the French Conception study, a nationwide prospective cohort study of more than 1.9 million pregnancies.
• Mothers were followed for an average of 9 years.

TAKEAWAY:

• Nearly 3% of the mothers had preeclampsia, and 128 developed young-onset dementia.
• Preeclampsia was associated with a 2.65-fold increased risk for young-onset dementia after adjusting for obesity, diabetes, smoking, drug or alcohol addiction, and social deprivation.
• The risk was greater when preeclampsia occurred before 34 weeks of gestation (hazard ratio [HR], 4.15) or was superimposed on chronic hypertension (HR, 4.76).
• Prior research has found an association between preeclampsia and vascular dementia, but this analysis “is the first to show an increase in early-onset dementia risk,” the authors of the study wrote.

IN PRACTICE:

“Individuals who have had preeclampsia should be reassured that young-onset dementia remains a very rare condition. Their absolute risk increases only imperceptibly,” Stephen Tong, PhD, and Roxanne Hastie, PhD, both with the University of Melbourne, Melbourne, Australia, wrote in a related commentary about the findings.

“Individuals who have been affected by preeclampsia in a prior pregnancy might instead focus on reducing their risk of developing the many chronic health ailments that are far more common,” they added. “Although it is yet to be proven in clinical trials, it is plausible that after an episode of preeclampsia, adopting a healthy lifestyle may improve vascular health and reduce the risk of many serious cardiovascular conditions.”

SOURCE:

Valérie Olié, PhD, of the Santé Publique France in Saint-Maurice, France, was the corresponding author on the paper. The research letter was published online in JAMA Network Open.

LIMITATIONS:

The investigators relied on hospital records to identify cases of dementia, which may have led to underestimation of incidence of the disease.

DISCLOSURES:

The study was funded by the French Hypertension Society, the French Hypertension Research Foundation, and the French Cardiology Federation. A co-author disclosed personal fees from pharmaceutical companies.

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

The Centers for Medicare & Medicaid Services (CMS) has announced the conclusion of a program that provided billions in early Medicare payments to those affected by the Change Healthcare/UnitedHealth Group cyberattack last winter. The Accelerated and Advance Payment program, which began in early March to assist hospitals and practices facing significant reimbursement delays, will stop accepting applications after July 12, 2024.

CMS reported that the program advanced more than $2.55 billion in Medicare payments to > 4200 Part A providers, including hospitals, and more than $717.18 million in payments to Part B suppliers such as physicians, nonphysician practitioners, and durable medical equipment suppliers.

According to CMS, the Medicare billing system is now functioning properly, and 96% of the early payments have been recovered. The advances were to represent ≤ 30 days of typical claims payments in a 3-month period of 2023, with full repayment expected within 90 days through “automatic recoupment from Medicare claims” — no extensions allowed.

The agency took a victory lap regarding its response. “In the face of one of the most widespread cyberattacks on the US health care industry, CMS promptly took action to get providers and suppliers access to the funds they needed to continue providing patients with vital care,” CMS Administrator Chiquita Brooks-LaSure said in a statement. “Our efforts helped minimize the disruptive fallout from this incident, and we will remain vigilant to be ready to address future events.”

Ongoing Concerns from Health Care Organizations

Ben Teicher, an American Hospital Association spokesman, said that the organization hopes that CMS will be responsive if there’s more need for action after the advance payment program expires. The organization represents about 5000 hospitals, health care systems, and other providers.

“Our members report that the aftereffects of this event will likely be felt throughout the remainder of the year,” he said. According to Teicher, hospitals remain concerned about their ability to process claims and appeal denials, the safety of reconnecting to cyber services, and access to information needed to bill patients and reconcile payments.

In addition, hospitals are concerned about “financial support to mitigate the considerable costs incurred as a result of the cyberattack,” he said.

Charlene MacDonald, executive vice-president of public affairs at the Federation of American Hospitals, which represents more than 1000 for-profit hospitals, sent a statement to this news organization that said some providers “are still feeling the effects of care denials and delays caused by insurer inaction.

“We appreciate that the Administration acted within its authority to support providers during this unprecedented crisis and blunt these devastating impacts, especially because a vast majority of managed care companies failed to step up to the plate,” she said. “It is now time to shift our focus to holding plans accountable for using tactics to delay and deny needed patient care.”

Cyberattack Impact and Response

The ransom-based cyberattack against Change Healthcare/UnitedHealth Group targeted an electronic data interchange clearing house processing payer reimbursement systems, disrupting cash flows at hospitals and medical practices, and affecting patient access to prescriptions and life-saving therapy.

Change Healthcare — part of the UnitedHealth Group subsidiary Optum — processes half of all medical claims, according to a Department of Justice lawsuit. The American Hospital Association described the cyberattack as “the most significant and consequential incident of its kind” in US history.

By late March, UnitedHealth Group said nearly all medical and pharmacy claims were processing properly, while a deputy secretary of the US Department of Health & Human Services told clinicians that officials were focusing on the last group of clinicians who were facing cash-flow problems.

Still, a senior advisor with CMS told providers at that time that “we have heard from so many providers over the last several weeks who are really struggling to make ends meet right now or who are worried that they will not be able to make payroll in the weeks to come.”

Randy Dotinga is a freelance health/medical reporter and board member of the Association of Health Care Journalists.

A version of this article appeared on Medscape.com.

The Centers for Medicare & Medicaid Services (CMS) has announced the conclusion of a program that provided billions in early Medicare payments to those affected by the Change Healthcare/UnitedHealth Group cyberattack last winter. The Accelerated and Advance Payment program, which began in early March to assist hospitals and practices facing significant reimbursement delays, will stop accepting applications after July 12, 2024.

CMS reported that the program advanced more than $2.55 billion in Medicare payments to > 4200 Part A providers, including hospitals, and more than $717.18 million in payments to Part B suppliers such as physicians, nonphysician practitioners, and durable medical equipment suppliers.

According to CMS, the Medicare billing system is now functioning properly, and 96% of the early payments have been recovered. The advances were to represent ≤ 30 days of typical claims payments in a 3-month period of 2023, with full repayment expected within 90 days through “automatic recoupment from Medicare claims” — no extensions allowed.

The agency took a victory lap regarding its response. “In the face of one of the most widespread cyberattacks on the US health care industry, CMS promptly took action to get providers and suppliers access to the funds they needed to continue providing patients with vital care,” CMS Administrator Chiquita Brooks-LaSure said in a statement. “Our efforts helped minimize the disruptive fallout from this incident, and we will remain vigilant to be ready to address future events.”

Ongoing Concerns from Health Care Organizations

Ben Teicher, an American Hospital Association spokesman, said that the organization hopes that CMS will be responsive if there’s more need for action after the advance payment program expires. The organization represents about 5000 hospitals, health care systems, and other providers.

“Our members report that the aftereffects of this event will likely be felt throughout the remainder of the year,” he said. According to Teicher, hospitals remain concerned about their ability to process claims and appeal denials, the safety of reconnecting to cyber services, and access to information needed to bill patients and reconcile payments.

In addition, hospitals are concerned about “financial support to mitigate the considerable costs incurred as a result of the cyberattack,” he said.

Charlene MacDonald, executive vice-president of public affairs at the Federation of American Hospitals, which represents more than 1000 for-profit hospitals, sent a statement to this news organization that said some providers “are still feeling the effects of care denials and delays caused by insurer inaction.

“We appreciate that the Administration acted within its authority to support providers during this unprecedented crisis and blunt these devastating impacts, especially because a vast majority of managed care companies failed to step up to the plate,” she said. “It is now time to shift our focus to holding plans accountable for using tactics to delay and deny needed patient care.”

Cyberattack Impact and Response

The ransom-based cyberattack against Change Healthcare/UnitedHealth Group targeted an electronic data interchange clearing house processing payer reimbursement systems, disrupting cash flows at hospitals and medical practices, and affecting patient access to prescriptions and life-saving therapy.

Change Healthcare — part of the UnitedHealth Group subsidiary Optum — processes half of all medical claims, according to a Department of Justice lawsuit. The American Hospital Association described the cyberattack as “the most significant and consequential incident of its kind” in US history.

By late March, UnitedHealth Group said nearly all medical and pharmacy claims were processing properly, while a deputy secretary of the US Department of Health & Human Services told clinicians that officials were focusing on the last group of clinicians who were facing cash-flow problems.

Still, a senior advisor with CMS told providers at that time that “we have heard from so many providers over the last several weeks who are really struggling to make ends meet right now or who are worried that they will not be able to make payroll in the weeks to come.”

Randy Dotinga is a freelance health/medical reporter and board member of the Association of Health Care Journalists.

A version of this article appeared on Medscape.com.

The Centers for Medicare & Medicaid Services (CMS) has announced the conclusion of a program that provided billions in early Medicare payments to those affected by the Change Healthcare/UnitedHealth Group cyberattack last winter. The Accelerated and Advance Payment program, which began in early March to assist hospitals and practices facing significant reimbursement delays, will stop accepting applications after July 12, 2024.

CMS reported that the program advanced more than $2.55 billion in Medicare payments to > 4200 Part A providers, including hospitals, and more than $717.18 million in payments to Part B suppliers such as physicians, nonphysician practitioners, and durable medical equipment suppliers.

According to CMS, the Medicare billing system is now functioning properly, and 96% of the early payments have been recovered. The advances were to represent ≤ 30 days of typical claims payments in a 3-month period of 2023, with full repayment expected within 90 days through “automatic recoupment from Medicare claims” — no extensions allowed.

The agency took a victory lap regarding its response. “In the face of one of the most widespread cyberattacks on the US health care industry, CMS promptly took action to get providers and suppliers access to the funds they needed to continue providing patients with vital care,” CMS Administrator Chiquita Brooks-LaSure said in a statement. “Our efforts helped minimize the disruptive fallout from this incident, and we will remain vigilant to be ready to address future events.”

Ongoing Concerns from Health Care Organizations

Ben Teicher, an American Hospital Association spokesman, said that the organization hopes that CMS will be responsive if there’s more need for action after the advance payment program expires. The organization represents about 5000 hospitals, health care systems, and other providers.

“Our members report that the aftereffects of this event will likely be felt throughout the remainder of the year,” he said. According to Teicher, hospitals remain concerned about their ability to process claims and appeal denials, the safety of reconnecting to cyber services, and access to information needed to bill patients and reconcile payments.

In addition, hospitals are concerned about “financial support to mitigate the considerable costs incurred as a result of the cyberattack,” he said.

Charlene MacDonald, executive vice-president of public affairs at the Federation of American Hospitals, which represents more than 1000 for-profit hospitals, sent a statement to this news organization that said some providers “are still feeling the effects of care denials and delays caused by insurer inaction.

“We appreciate that the Administration acted within its authority to support providers during this unprecedented crisis and blunt these devastating impacts, especially because a vast majority of managed care companies failed to step up to the plate,” she said. “It is now time to shift our focus to holding plans accountable for using tactics to delay and deny needed patient care.”

Cyberattack Impact and Response

The ransom-based cyberattack against Change Healthcare/UnitedHealth Group targeted an electronic data interchange clearing house processing payer reimbursement systems, disrupting cash flows at hospitals and medical practices, and affecting patient access to prescriptions and life-saving therapy.

Change Healthcare — part of the UnitedHealth Group subsidiary Optum — processes half of all medical claims, according to a Department of Justice lawsuit. The American Hospital Association described the cyberattack as “the most significant and consequential incident of its kind” in US history.

By late March, UnitedHealth Group said nearly all medical and pharmacy claims were processing properly, while a deputy secretary of the US Department of Health & Human Services told clinicians that officials were focusing on the last group of clinicians who were facing cash-flow problems.

Still, a senior advisor with CMS told providers at that time that “we have heard from so many providers over the last several weeks who are really struggling to make ends meet right now or who are worried that they will not be able to make payroll in the weeks to come.”

Randy Dotinga is a freelance health/medical reporter and board member of the Association of Health Care Journalists.

A version of this article appeared on Medscape.com.

Glucagon-like peptide 1 (GLP-1) receptor agonists such as semaglutide (marketed as Ozempic and Rybelsus for type 2 diabetes and as Wegovy for obesity) slow down digestion and curb hunger by working on the brain’s dopamine reward center. They are prescribed to promote weight loss, metabolic health in type 2 diabetes, and heart health in coronary artery disease.

Semaglutide can be prescribed in two forms: the brand-name version, which is approved and confirmed as safe and effective by the US Food and Drug Administration (FDA), and the versions that can be obtained from a compounding pharmacy. Compounding pharmacies are permitted by the FDA to produce what is “ essentially a copy” of approved medications when there’s an official shortage, which is currently the case with semaglutide and other GLP-1 receptor agonists.

Patients are often drawn to compounding pharmacies for pricing-related reasons. If semaglutide is prescribed for a clear indication like diabetes and is covered by insurance, the brand-name version is commonly dispensed. However, if it’s not covered, patients need to pay out of pocket for branded versions, which carry a monthly cost of $1000 or more. Alternatively, their doctors can prescribe compounded semaglutide, which some telehealth companies advertise at costs of approximately $150-$300 per month.
 

Potential Issues With Compounded Semaglutide 

Compounding pharmacies produce drugs from raw materials containing active pharmaceutical ingredients (APIs). Although compounders use many of the same ingredients found in brand-name medications, for drugs like semaglutide, they may opt for specific salts that are not identical to those involved in the production of the standard versions. These salts are typically reserved for research purposes and may not be suitable for general use.

In late 2023, the FDA issued a letter asking the public to exercise caution when using compounded products containing semaglutide or semaglutide salts. This was followed in January 2024 by an FDA communication citing adverse events reported with the use of compounded semaglutide and advising patients to avoid these versions if an approved form of the drug is available.
 

Compound Pharmacies: A Closer Look 

Compounding pharmacies have exploded in popularity in the past several decades. The compounding pharmacy market is expected to grow at 7.8% per year over the next decade. 

Historically, compounding pharmacies have filled a niche for specialty vitamins for intravenous administration as well as chemotherapy medications. They also offer controlled substances, such as ketamine lozenges and nasal sprays, which are unavailable or are in short supply from traditional manufacturers.

Compounding pharmacies fall into two categories. First are compounding pharmacies covered under Section 503A of the Federal Food, Drug and Cosmetic Act; these drugs are neither tested nor monitored. Such facilities do not have to report adverse events to the FDA. The second category is Section 503B outsourcing facilities. These pharmacies choose to be tested by, to be inspected by, and to report adverse events to the FDA. 
 

The FDA’s Latest Update on This Issue

This news organization contacted the FDA for an update on the adverse events reported about compounded semaglutide. From August 8, 2021, to March 31, 2024, they received more than 20,000 adverse events reports for FDA-approved semaglutide. Comparatively, there were 210 adverse events reported on compounded semaglutide products. 

The FDA went on to describe that many of the adverse events reported were consistent with known reactions in the labeling, like nausea, diarrhea, and headache. Yet, they added that, “the FDA is unable to determine how, or if, other factors may have contributed to these adverse events, such as differences in ingredients and formulation between FDA-approved and compounded semaglutide products.” They also noted there was variation in the data quality in the reports they have received, which came only from 503B compounding pharmacies.

In conclusion, given the concerns about compounded semaglutide, it is prudent for the prescribing physicians as well as the patients taking the medication to know that risks are “higher” according to the FDA. We eagerly await more specific information from the FDA to better understand reported adverse events. 
 

How to Help Patients Receive Safe Compounded Semaglutide 

For clinicians considering prescribing semaglutide from compounding pharmacies, there are several questions worth asking, according to the Alliance for Pharmacy Compounding. First, find out whether the pharmacy complies with United States Pharmacopeia compounding standards and whether they source their APIs from FDA-registered facilities, the latter being required by federal law. It’s also important to ensure that these facilities undergo periodic third-party testing to verify medication purity and dosing. 

Ask whether the pharmacy is accredited by the Pharmacy Compounding Accreditation Board (PCAB). Accreditation from the PCAB means that pharmacies have been assessed for processes related to continuous quality improvement. In addition, ask whether the pharmacy is designated as a 503B compounder and if not, why.

Finally, interviewing the pharmacist themselves can provide useful information about staffing, training, and their methods of preparing medications. For example, if they are preparing a sterile eye drop, it is important to ask about sterility testing.

Jesse M. Pines, MD, MBA, MSCE, is a clinical professor of emergency medicine at George Washington University in Washington, and a professor in the department of emergency medicine at Drexel University College of Medicine in Philadelphia, Pennsylvania. Dr. Pines is also the chief of clinical innovation at US Acute Care Solutions in Canton, Ohio. Robert D. Glatter, MD, is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. Dr. Pines reported conflicts of interest with CSL Behring and Abbott Point-of-Care. Dr. Glatter reported no relevant conflicts of interest.
 

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

Glucagon-like peptide 1 (GLP-1) receptor agonists such as semaglutide (marketed as Ozempic and Rybelsus for type 2 diabetes and as Wegovy for obesity) slow down digestion and curb hunger by working on the brain’s dopamine reward center. They are prescribed to promote weight loss, metabolic health in type 2 diabetes, and heart health in coronary artery disease.

Semaglutide can be prescribed in two forms: the brand-name version, which is approved and confirmed as safe and effective by the US Food and Drug Administration (FDA), and the versions that can be obtained from a compounding pharmacy. Compounding pharmacies are permitted by the FDA to produce what is “ essentially a copy” of approved medications when there’s an official shortage, which is currently the case with semaglutide and other GLP-1 receptor agonists.

Patients are often drawn to compounding pharmacies for pricing-related reasons. If semaglutide is prescribed for a clear indication like diabetes and is covered by insurance, the brand-name version is commonly dispensed. However, if it’s not covered, patients need to pay out of pocket for branded versions, which carry a monthly cost of $1000 or more. Alternatively, their doctors can prescribe compounded semaglutide, which some telehealth companies advertise at costs of approximately $150-$300 per month.
 

Potential Issues With Compounded Semaglutide 

Compounding pharmacies produce drugs from raw materials containing active pharmaceutical ingredients (APIs). Although compounders use many of the same ingredients found in brand-name medications, for drugs like semaglutide, they may opt for specific salts that are not identical to those involved in the production of the standard versions. These salts are typically reserved for research purposes and may not be suitable for general use.

In late 2023, the FDA issued a letter asking the public to exercise caution when using compounded products containing semaglutide or semaglutide salts. This was followed in January 2024 by an FDA communication citing adverse events reported with the use of compounded semaglutide and advising patients to avoid these versions if an approved form of the drug is available.
 

Compound Pharmacies: A Closer Look 

Compounding pharmacies have exploded in popularity in the past several decades. The compounding pharmacy market is expected to grow at 7.8% per year over the next decade. 

Historically, compounding pharmacies have filled a niche for specialty vitamins for intravenous administration as well as chemotherapy medications. They also offer controlled substances, such as ketamine lozenges and nasal sprays, which are unavailable or are in short supply from traditional manufacturers.

Compounding pharmacies fall into two categories. First are compounding pharmacies covered under Section 503A of the Federal Food, Drug and Cosmetic Act; these drugs are neither tested nor monitored. Such facilities do not have to report adverse events to the FDA. The second category is Section 503B outsourcing facilities. These pharmacies choose to be tested by, to be inspected by, and to report adverse events to the FDA. 
 

The FDA’s Latest Update on This Issue

This news organization contacted the FDA for an update on the adverse events reported about compounded semaglutide. From August 8, 2021, to March 31, 2024, they received more than 20,000 adverse events reports for FDA-approved semaglutide. Comparatively, there were 210 adverse events reported on compounded semaglutide products. 

The FDA went on to describe that many of the adverse events reported were consistent with known reactions in the labeling, like nausea, diarrhea, and headache. Yet, they added that, “the FDA is unable to determine how, or if, other factors may have contributed to these adverse events, such as differences in ingredients and formulation between FDA-approved and compounded semaglutide products.” They also noted there was variation in the data quality in the reports they have received, which came only from 503B compounding pharmacies.

In conclusion, given the concerns about compounded semaglutide, it is prudent for the prescribing physicians as well as the patients taking the medication to know that risks are “higher” according to the FDA. We eagerly await more specific information from the FDA to better understand reported adverse events. 
 

How to Help Patients Receive Safe Compounded Semaglutide 

For clinicians considering prescribing semaglutide from compounding pharmacies, there are several questions worth asking, according to the Alliance for Pharmacy Compounding. First, find out whether the pharmacy complies with United States Pharmacopeia compounding standards and whether they source their APIs from FDA-registered facilities, the latter being required by federal law. It’s also important to ensure that these facilities undergo periodic third-party testing to verify medication purity and dosing. 

Ask whether the pharmacy is accredited by the Pharmacy Compounding Accreditation Board (PCAB). Accreditation from the PCAB means that pharmacies have been assessed for processes related to continuous quality improvement. In addition, ask whether the pharmacy is designated as a 503B compounder and if not, why.

Finally, interviewing the pharmacist themselves can provide useful information about staffing, training, and their methods of preparing medications. For example, if they are preparing a sterile eye drop, it is important to ask about sterility testing.

Jesse M. Pines, MD, MBA, MSCE, is a clinical professor of emergency medicine at George Washington University in Washington, and a professor in the department of emergency medicine at Drexel University College of Medicine in Philadelphia, Pennsylvania. Dr. Pines is also the chief of clinical innovation at US Acute Care Solutions in Canton, Ohio. Robert D. Glatter, MD, is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. Dr. Pines reported conflicts of interest with CSL Behring and Abbott Point-of-Care. Dr. Glatter reported no relevant conflicts of interest.
 

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

Glucagon-like peptide 1 (GLP-1) receptor agonists such as semaglutide (marketed as Ozempic and Rybelsus for type 2 diabetes and as Wegovy for obesity) slow down digestion and curb hunger by working on the brain’s dopamine reward center. They are prescribed to promote weight loss, metabolic health in type 2 diabetes, and heart health in coronary artery disease.

Semaglutide can be prescribed in two forms: the brand-name version, which is approved and confirmed as safe and effective by the US Food and Drug Administration (FDA), and the versions that can be obtained from a compounding pharmacy. Compounding pharmacies are permitted by the FDA to produce what is “ essentially a copy” of approved medications when there’s an official shortage, which is currently the case with semaglutide and other GLP-1 receptor agonists.

Patients are often drawn to compounding pharmacies for pricing-related reasons. If semaglutide is prescribed for a clear indication like diabetes and is covered by insurance, the brand-name version is commonly dispensed. However, if it’s not covered, patients need to pay out of pocket for branded versions, which carry a monthly cost of $1000 or more. Alternatively, their doctors can prescribe compounded semaglutide, which some telehealth companies advertise at costs of approximately $150-$300 per month.
 

Potential Issues With Compounded Semaglutide 

Compounding pharmacies produce drugs from raw materials containing active pharmaceutical ingredients (APIs). Although compounders use many of the same ingredients found in brand-name medications, for drugs like semaglutide, they may opt for specific salts that are not identical to those involved in the production of the standard versions. These salts are typically reserved for research purposes and may not be suitable for general use.

In late 2023, the FDA issued a letter asking the public to exercise caution when using compounded products containing semaglutide or semaglutide salts. This was followed in January 2024 by an FDA communication citing adverse events reported with the use of compounded semaglutide and advising patients to avoid these versions if an approved form of the drug is available.
 

Compound Pharmacies: A Closer Look 

Compounding pharmacies have exploded in popularity in the past several decades. The compounding pharmacy market is expected to grow at 7.8% per year over the next decade. 

Historically, compounding pharmacies have filled a niche for specialty vitamins for intravenous administration as well as chemotherapy medications. They also offer controlled substances, such as ketamine lozenges and nasal sprays, which are unavailable or are in short supply from traditional manufacturers.

Compounding pharmacies fall into two categories. First are compounding pharmacies covered under Section 503A of the Federal Food, Drug and Cosmetic Act; these drugs are neither tested nor monitored. Such facilities do not have to report adverse events to the FDA. The second category is Section 503B outsourcing facilities. These pharmacies choose to be tested by, to be inspected by, and to report adverse events to the FDA. 
 

The FDA’s Latest Update on This Issue

This news organization contacted the FDA for an update on the adverse events reported about compounded semaglutide. From August 8, 2021, to March 31, 2024, they received more than 20,000 adverse events reports for FDA-approved semaglutide. Comparatively, there were 210 adverse events reported on compounded semaglutide products. 

The FDA went on to describe that many of the adverse events reported were consistent with known reactions in the labeling, like nausea, diarrhea, and headache. Yet, they added that, “the FDA is unable to determine how, or if, other factors may have contributed to these adverse events, such as differences in ingredients and formulation between FDA-approved and compounded semaglutide products.” They also noted there was variation in the data quality in the reports they have received, which came only from 503B compounding pharmacies.

In conclusion, given the concerns about compounded semaglutide, it is prudent for the prescribing physicians as well as the patients taking the medication to know that risks are “higher” according to the FDA. We eagerly await more specific information from the FDA to better understand reported adverse events. 
 

How to Help Patients Receive Safe Compounded Semaglutide 

For clinicians considering prescribing semaglutide from compounding pharmacies, there are several questions worth asking, according to the Alliance for Pharmacy Compounding. First, find out whether the pharmacy complies with United States Pharmacopeia compounding standards and whether they source their APIs from FDA-registered facilities, the latter being required by federal law. It’s also important to ensure that these facilities undergo periodic third-party testing to verify medication purity and dosing. 

Ask whether the pharmacy is accredited by the Pharmacy Compounding Accreditation Board (PCAB). Accreditation from the PCAB means that pharmacies have been assessed for processes related to continuous quality improvement. In addition, ask whether the pharmacy is designated as a 503B compounder and if not, why.

Finally, interviewing the pharmacist themselves can provide useful information about staffing, training, and their methods of preparing medications. For example, if they are preparing a sterile eye drop, it is important to ask about sterility testing.

Jesse M. Pines, MD, MBA, MSCE, is a clinical professor of emergency medicine at George Washington University in Washington, and a professor in the department of emergency medicine at Drexel University College of Medicine in Philadelphia, Pennsylvania. Dr. Pines is also the chief of clinical innovation at US Acute Care Solutions in Canton, Ohio. Robert D. Glatter, MD, is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. Dr. Pines reported conflicts of interest with CSL Behring and Abbott Point-of-Care. Dr. Glatter reported no relevant conflicts of interest.
 

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