In December, in what’s known as the “Take Care of Maya” case, a Florida jury returned a record $261 million verdict against Johns Hopkins All Children’s Hospital, St. Petersburg, Florida, for its treatment of a young patient and her family after an emergency room visit.

A month earlier, in New York, a jury ordered Westchester Medical Center Health Network to pay $120 million to a patient and his family following delayed stroke care that resulted in brain damage.

Mega malpractice awards like these are rising against physicians and hospitals around the country, according to new data from TransRe, an international reinsurance company that tracks large verdicts.

“2023 blew away every record previously set among high medical malpractice verdicts,” said Richard Henderson, senior vice president for TransRe. “If we look at the 50 largest verdicts in 2023 and average them out, we have a higher monetary amount than any other year.”

In 2023, there were 57 medical malpractice verdicts of $10 million or more in the United States, the data showed. Slightly more than half of those reached $25 million or more.

From 2012 to 2022, verdicts of $10 million or more ranged from 34 in 2013 to 52 in 2022, TransRe research found.

While New York, Illinois, and Florida typically saw the highest dollar verdicts in previous years, so-called “nuclear” verdicts now occur in states like Utah and Georgia where they once were uncommon, said Robert E. White Jr., president of TDC Group and The Doctors Company, a national medical liability insurer for physicians.

A rollback of tort reforms across the country is one contributor, he said. For example, Georgia’s cap on noneconomic damages is among those that have been ruled unconstitutional by courts. Utah’s cap on noneconomic damages still stands, but the limit was deemed unconstitutional in wrongful death cases. In 2019, a portion of Utah›s pre-litigation panel process was also struck down by the state’s Supreme Court.

“We used to be able to predict where these high verdicts would occur,” Mr. White said. “We can’t predict it anymore.”

Research shows a majority of malpractice cases are dropped or settled before trial, and claims that go before juries usually end in doctors’ favor. Plaintiffs’ attorneys cite large jury verdicts in similar cases to induce settlements and higher payouts, Mr. White said.

And while mega verdicts rarely stick, they can have lasting effects on future claims. The awards lead to larger settlement demands from plaintiffs and drive up the cost to resolve claims, according to Mr. Henderson and Mr. White.

“Verdicts are the yardstick by which all settlements are measured,” Mr. White said. “That’s where the damage is done.” The prospect of a mega verdict can make insurers leery of fighting some malpractice cases and motivate them to offer bigger settlements to stay out of the courtroom, he added.

Why Are Juries Awarding Higher Verdicts?

There’s no single reason for the rise in nuclear verdicts, Mr. Henderson said.

One theory is that plaintiffs’ attorneys held back on resolving high-dollar cases during the COVID pandemic and let loose with high-demand claims when courts returned to normal, he said.

Another theory is that people emerged from the pandemic angrier.

“Whether it was political dynamics, masking [mandates], or differences in opinions, people came out of it angry, and generally speaking, you don’t want an angry jury,” Mr. Henderson said. “For a while, there was the halo effect, where health professionals were seen as heroes. That went away, and all of a sudden [they] became ‘the bad guys.’ ”

“People are angry at the healthcare system, and this anger manifests itself in [liability] suits,” added Bill Burns, vice president of research for the Medical Professional Liability Association, an industry group for medical liability insurers.

Hospital and medical group consolidation also reduces the personal connection juries may have with healthcare providers, Mr. Burns said.

“Healthcare has become a big business, and the corporatization of medicine now puts companies on the stand and not your local community hospital or your family doctor that you have known since birth,” he said.

Plaintiffs’ attorneys also deploy tactics that can prompt higher verdicts, Mr. White said. They may tell a jury that the provider or hospital is a threat to the community and that awarding a large verdict will deter others in the healthcare community from repeating the same actions.

Juries may then want to punish the defendant in addition to assessing damages for economic harm or pain and suffering, Mr. White said.

“I am concerned that jurors are trying to right social wrongs rather than judging cases on the facts presented to them,” added Mike Stinson, vice president for policy and legal affairs for the Medical Professional Liability Association.

Third-party litigation financing also can lead to mega verdicts. That’s an emerging practice in which companies unrelated to a lawsuit provide capital to plaintiffs in return for a portion of any financial award. The firms essentially “invest” in the litigation.

“What this does is provide an additional financial backdrop for plaintiffs,” Mr. Henderson said. “It allows them to dig in harder on cases. They can hold out for higher numbers, and if nothing else, it can prolong litigation.”

Do High Awards Actually Stick?

Multimillion-dollar verdicts may grab headlines, but do plaintiffs actually receive them?

Rarely, said TransRe, which tracks the final outcomes of verdicts. In many cases, large verdicts are reduced on appeal.

In the Maya case, which involved child protection authorities, a judge later lowered the damages against Johns Hopkins All Children’s Hospital by $47.5 million.

A federal judge in October, for example, rejected a record $110 million medical malpractice award in Minnesota, reducing it to $10 million. The district judge ruled the award was “shockingly excessive” and that the plaintiff should either accept the $10 million award or retry the case.

After a verdict is awarded, the defendant typically challenges the award, and the case goes through the appellate pipeline, Mr. Henderson explained. A judge may reduce some elements of the verdict, he said, but more often, the plaintiff and defendant agree on a compromised figure.

Seattle medical liability defense attorney Jennifer Crisera has experienced this firsthand. She recalled a recent case where a plaintiff’s attorney demanded what she describes as an unreasonable amount to settle a claim. Ms. Crisera did not want to give exact numbers but said the plaintiff made an 8-figure demand and the defense offered a low 7-figure range.

“My impression was that plaintiff’s counsel believed that they could get a nuclear verdict from the jury, so they kept their settlement demand artificially high,” she said. “The division between the numbers was way too high. Ultimately, we had to let a jury decide the value.”

The plaintiff won the case, and the verdict was much less than the settlement demand, she said. Even so, the defense incurred trial costs, and the health provider was forced to endure the emotional stress of a trial that could have been avoided, Ms. Crisera said.

Higher medical malpractice premiums are another consequence of massive awards.

Premium rates are associated with how much insurers pay on average for cases and how frequently they are making payouts, Mr. White said.

Medical liability insurance premiums for physicians have steadily increased since 2019, according to data from the Medical Liability Monitor, a national publication that analyzes liability insurance premiums. The Monitor studies insurance premium data from insurers that cover internists, general surgeons, and obstetrician-gynecologists.

From 2019 to 2023, average premium rates for physicians increased between 1.1% and 3% each year in states without patient compensation funds, according to Monitor data.

“Nuclear verdicts are a real driver of the industry’s underwriting losses and remain top of mind for every malpractice insurance company,” said Michael Matray, editor for the Medical Liability Monitor. “Responses to this year’s rate survey questionnaire indicate that most responding companies have experienced an increase in claims greater than $1 million and claims greater than $5 million during the past 2 years.”

However, increases vary widely by region and among counties. In Montgomery County, Alabama, for instance, premiums for internists rose by 24% from 2022 to 2023, from $8,231 to $10,240. Premiums for Montgomery County general surgeons rose by 11.9% from 2022 to 2023, from $30,761 to $34,426, according to survey data.

In several counties in Illinois (Adams, Knox, Peoria, and Rock Island), premiums for some internists rose by 15% from $24,041 to $27,783, and premiums for some surgeons increased by 27% from $60,202 to $76,461, according to survey data. Some internists in Catoosa County, Georgia, meanwhile, paid $17,831 in 2023, up from $16,313 in 2022. Some surgeons in Catoosa County paid $65,616 in 2023, up from $60,032 in 2022. Inflation could be one factor behind higher liability premium rates. Claim severity is a key driver of higher premium rates, Mr. White added.

“We have not seen stability in claims severity,” he said. “It is continuing to go up and, in all likelihood, it will drive [premium] rates up further from this point.”
 

A version of this article appeared on Medscape.com.

In December, in what’s known as the “Take Care of Maya” case, a Florida jury returned a record $261 million verdict against Johns Hopkins All Children’s Hospital, St. Petersburg, Florida, for its treatment of a young patient and her family after an emergency room visit.

A month earlier, in New York, a jury ordered Westchester Medical Center Health Network to pay $120 million to a patient and his family following delayed stroke care that resulted in brain damage.

Mega malpractice awards like these are rising against physicians and hospitals around the country, according to new data from TransRe, an international reinsurance company that tracks large verdicts.

“2023 blew away every record previously set among high medical malpractice verdicts,” said Richard Henderson, senior vice president for TransRe. “If we look at the 50 largest verdicts in 2023 and average them out, we have a higher monetary amount than any other year.”

In 2023, there were 57 medical malpractice verdicts of $10 million or more in the United States, the data showed. Slightly more than half of those reached $25 million or more.

From 2012 to 2022, verdicts of $10 million or more ranged from 34 in 2013 to 52 in 2022, TransRe research found.

While New York, Illinois, and Florida typically saw the highest dollar verdicts in previous years, so-called “nuclear” verdicts now occur in states like Utah and Georgia where they once were uncommon, said Robert E. White Jr., president of TDC Group and The Doctors Company, a national medical liability insurer for physicians.

A rollback of tort reforms across the country is one contributor, he said. For example, Georgia’s cap on noneconomic damages is among those that have been ruled unconstitutional by courts. Utah’s cap on noneconomic damages still stands, but the limit was deemed unconstitutional in wrongful death cases. In 2019, a portion of Utah›s pre-litigation panel process was also struck down by the state’s Supreme Court.

“We used to be able to predict where these high verdicts would occur,” Mr. White said. “We can’t predict it anymore.”

Research shows a majority of malpractice cases are dropped or settled before trial, and claims that go before juries usually end in doctors’ favor. Plaintiffs’ attorneys cite large jury verdicts in similar cases to induce settlements and higher payouts, Mr. White said.

And while mega verdicts rarely stick, they can have lasting effects on future claims. The awards lead to larger settlement demands from plaintiffs and drive up the cost to resolve claims, according to Mr. Henderson and Mr. White.

“Verdicts are the yardstick by which all settlements are measured,” Mr. White said. “That’s where the damage is done.” The prospect of a mega verdict can make insurers leery of fighting some malpractice cases and motivate them to offer bigger settlements to stay out of the courtroom, he added.

Why Are Juries Awarding Higher Verdicts?

There’s no single reason for the rise in nuclear verdicts, Mr. Henderson said.

One theory is that plaintiffs’ attorneys held back on resolving high-dollar cases during the COVID pandemic and let loose with high-demand claims when courts returned to normal, he said.

Another theory is that people emerged from the pandemic angrier.

“Whether it was political dynamics, masking [mandates], or differences in opinions, people came out of it angry, and generally speaking, you don’t want an angry jury,” Mr. Henderson said. “For a while, there was the halo effect, where health professionals were seen as heroes. That went away, and all of a sudden [they] became ‘the bad guys.’ ”

“People are angry at the healthcare system, and this anger manifests itself in [liability] suits,” added Bill Burns, vice president of research for the Medical Professional Liability Association, an industry group for medical liability insurers.

Hospital and medical group consolidation also reduces the personal connection juries may have with healthcare providers, Mr. Burns said.

“Healthcare has become a big business, and the corporatization of medicine now puts companies on the stand and not your local community hospital or your family doctor that you have known since birth,” he said.

Plaintiffs’ attorneys also deploy tactics that can prompt higher verdicts, Mr. White said. They may tell a jury that the provider or hospital is a threat to the community and that awarding a large verdict will deter others in the healthcare community from repeating the same actions.

Juries may then want to punish the defendant in addition to assessing damages for economic harm or pain and suffering, Mr. White said.

“I am concerned that jurors are trying to right social wrongs rather than judging cases on the facts presented to them,” added Mike Stinson, vice president for policy and legal affairs for the Medical Professional Liability Association.

Third-party litigation financing also can lead to mega verdicts. That’s an emerging practice in which companies unrelated to a lawsuit provide capital to plaintiffs in return for a portion of any financial award. The firms essentially “invest” in the litigation.

“What this does is provide an additional financial backdrop for plaintiffs,” Mr. Henderson said. “It allows them to dig in harder on cases. They can hold out for higher numbers, and if nothing else, it can prolong litigation.”

Do High Awards Actually Stick?

Multimillion-dollar verdicts may grab headlines, but do plaintiffs actually receive them?

Rarely, said TransRe, which tracks the final outcomes of verdicts. In many cases, large verdicts are reduced on appeal.

In the Maya case, which involved child protection authorities, a judge later lowered the damages against Johns Hopkins All Children’s Hospital by $47.5 million.

A federal judge in October, for example, rejected a record $110 million medical malpractice award in Minnesota, reducing it to $10 million. The district judge ruled the award was “shockingly excessive” and that the plaintiff should either accept the $10 million award or retry the case.

After a verdict is awarded, the defendant typically challenges the award, and the case goes through the appellate pipeline, Mr. Henderson explained. A judge may reduce some elements of the verdict, he said, but more often, the plaintiff and defendant agree on a compromised figure.

Seattle medical liability defense attorney Jennifer Crisera has experienced this firsthand. She recalled a recent case where a plaintiff’s attorney demanded what she describes as an unreasonable amount to settle a claim. Ms. Crisera did not want to give exact numbers but said the plaintiff made an 8-figure demand and the defense offered a low 7-figure range.

“My impression was that plaintiff’s counsel believed that they could get a nuclear verdict from the jury, so they kept their settlement demand artificially high,” she said. “The division between the numbers was way too high. Ultimately, we had to let a jury decide the value.”

The plaintiff won the case, and the verdict was much less than the settlement demand, she said. Even so, the defense incurred trial costs, and the health provider was forced to endure the emotional stress of a trial that could have been avoided, Ms. Crisera said.

Higher medical malpractice premiums are another consequence of massive awards.

Premium rates are associated with how much insurers pay on average for cases and how frequently they are making payouts, Mr. White said.

Medical liability insurance premiums for physicians have steadily increased since 2019, according to data from the Medical Liability Monitor, a national publication that analyzes liability insurance premiums. The Monitor studies insurance premium data from insurers that cover internists, general surgeons, and obstetrician-gynecologists.

From 2019 to 2023, average premium rates for physicians increased between 1.1% and 3% each year in states without patient compensation funds, according to Monitor data.

“Nuclear verdicts are a real driver of the industry’s underwriting losses and remain top of mind for every malpractice insurance company,” said Michael Matray, editor for the Medical Liability Monitor. “Responses to this year’s rate survey questionnaire indicate that most responding companies have experienced an increase in claims greater than $1 million and claims greater than $5 million during the past 2 years.”

However, increases vary widely by region and among counties. In Montgomery County, Alabama, for instance, premiums for internists rose by 24% from 2022 to 2023, from $8,231 to $10,240. Premiums for Montgomery County general surgeons rose by 11.9% from 2022 to 2023, from $30,761 to $34,426, according to survey data.

In several counties in Illinois (Adams, Knox, Peoria, and Rock Island), premiums for some internists rose by 15% from $24,041 to $27,783, and premiums for some surgeons increased by 27% from $60,202 to $76,461, according to survey data. Some internists in Catoosa County, Georgia, meanwhile, paid $17,831 in 2023, up from $16,313 in 2022. Some surgeons in Catoosa County paid $65,616 in 2023, up from $60,032 in 2022. Inflation could be one factor behind higher liability premium rates. Claim severity is a key driver of higher premium rates, Mr. White added.

“We have not seen stability in claims severity,” he said. “It is continuing to go up and, in all likelihood, it will drive [premium] rates up further from this point.”
 

A version of this article appeared on Medscape.com.

In December, in what’s known as the “Take Care of Maya” case, a Florida jury returned a record $261 million verdict against Johns Hopkins All Children’s Hospital, St. Petersburg, Florida, for its treatment of a young patient and her family after an emergency room visit.

A month earlier, in New York, a jury ordered Westchester Medical Center Health Network to pay $120 million to a patient and his family following delayed stroke care that resulted in brain damage.

Mega malpractice awards like these are rising against physicians and hospitals around the country, according to new data from TransRe, an international reinsurance company that tracks large verdicts.

“2023 blew away every record previously set among high medical malpractice verdicts,” said Richard Henderson, senior vice president for TransRe. “If we look at the 50 largest verdicts in 2023 and average them out, we have a higher monetary amount than any other year.”

In 2023, there were 57 medical malpractice verdicts of $10 million or more in the United States, the data showed. Slightly more than half of those reached $25 million or more.

From 2012 to 2022, verdicts of $10 million or more ranged from 34 in 2013 to 52 in 2022, TransRe research found.

While New York, Illinois, and Florida typically saw the highest dollar verdicts in previous years, so-called “nuclear” verdicts now occur in states like Utah and Georgia where they once were uncommon, said Robert E. White Jr., president of TDC Group and The Doctors Company, a national medical liability insurer for physicians.

A rollback of tort reforms across the country is one contributor, he said. For example, Georgia’s cap on noneconomic damages is among those that have been ruled unconstitutional by courts. Utah’s cap on noneconomic damages still stands, but the limit was deemed unconstitutional in wrongful death cases. In 2019, a portion of Utah›s pre-litigation panel process was also struck down by the state’s Supreme Court.

“We used to be able to predict where these high verdicts would occur,” Mr. White said. “We can’t predict it anymore.”

Research shows a majority of malpractice cases are dropped or settled before trial, and claims that go before juries usually end in doctors’ favor. Plaintiffs’ attorneys cite large jury verdicts in similar cases to induce settlements and higher payouts, Mr. White said.

And while mega verdicts rarely stick, they can have lasting effects on future claims. The awards lead to larger settlement demands from plaintiffs and drive up the cost to resolve claims, according to Mr. Henderson and Mr. White.

“Verdicts are the yardstick by which all settlements are measured,” Mr. White said. “That’s where the damage is done.” The prospect of a mega verdict can make insurers leery of fighting some malpractice cases and motivate them to offer bigger settlements to stay out of the courtroom, he added.

Why Are Juries Awarding Higher Verdicts?

There’s no single reason for the rise in nuclear verdicts, Mr. Henderson said.

One theory is that plaintiffs’ attorneys held back on resolving high-dollar cases during the COVID pandemic and let loose with high-demand claims when courts returned to normal, he said.

Another theory is that people emerged from the pandemic angrier.

“Whether it was political dynamics, masking [mandates], or differences in opinions, people came out of it angry, and generally speaking, you don’t want an angry jury,” Mr. Henderson said. “For a while, there was the halo effect, where health professionals were seen as heroes. That went away, and all of a sudden [they] became ‘the bad guys.’ ”

“People are angry at the healthcare system, and this anger manifests itself in [liability] suits,” added Bill Burns, vice president of research for the Medical Professional Liability Association, an industry group for medical liability insurers.

Hospital and medical group consolidation also reduces the personal connection juries may have with healthcare providers, Mr. Burns said.

“Healthcare has become a big business, and the corporatization of medicine now puts companies on the stand and not your local community hospital or your family doctor that you have known since birth,” he said.

Plaintiffs’ attorneys also deploy tactics that can prompt higher verdicts, Mr. White said. They may tell a jury that the provider or hospital is a threat to the community and that awarding a large verdict will deter others in the healthcare community from repeating the same actions.

Juries may then want to punish the defendant in addition to assessing damages for economic harm or pain and suffering, Mr. White said.

“I am concerned that jurors are trying to right social wrongs rather than judging cases on the facts presented to them,” added Mike Stinson, vice president for policy and legal affairs for the Medical Professional Liability Association.

Third-party litigation financing also can lead to mega verdicts. That’s an emerging practice in which companies unrelated to a lawsuit provide capital to plaintiffs in return for a portion of any financial award. The firms essentially “invest” in the litigation.

“What this does is provide an additional financial backdrop for plaintiffs,” Mr. Henderson said. “It allows them to dig in harder on cases. They can hold out for higher numbers, and if nothing else, it can prolong litigation.”

Do High Awards Actually Stick?

Multimillion-dollar verdicts may grab headlines, but do plaintiffs actually receive them?

Rarely, said TransRe, which tracks the final outcomes of verdicts. In many cases, large verdicts are reduced on appeal.

In the Maya case, which involved child protection authorities, a judge later lowered the damages against Johns Hopkins All Children’s Hospital by $47.5 million.

A federal judge in October, for example, rejected a record $110 million medical malpractice award in Minnesota, reducing it to $10 million. The district judge ruled the award was “shockingly excessive” and that the plaintiff should either accept the $10 million award or retry the case.

After a verdict is awarded, the defendant typically challenges the award, and the case goes through the appellate pipeline, Mr. Henderson explained. A judge may reduce some elements of the verdict, he said, but more often, the plaintiff and defendant agree on a compromised figure.

Seattle medical liability defense attorney Jennifer Crisera has experienced this firsthand. She recalled a recent case where a plaintiff’s attorney demanded what she describes as an unreasonable amount to settle a claim. Ms. Crisera did not want to give exact numbers but said the plaintiff made an 8-figure demand and the defense offered a low 7-figure range.

“My impression was that plaintiff’s counsel believed that they could get a nuclear verdict from the jury, so they kept their settlement demand artificially high,” she said. “The division between the numbers was way too high. Ultimately, we had to let a jury decide the value.”

The plaintiff won the case, and the verdict was much less than the settlement demand, she said. Even so, the defense incurred trial costs, and the health provider was forced to endure the emotional stress of a trial that could have been avoided, Ms. Crisera said.

Higher medical malpractice premiums are another consequence of massive awards.

Premium rates are associated with how much insurers pay on average for cases and how frequently they are making payouts, Mr. White said.

Medical liability insurance premiums for physicians have steadily increased since 2019, according to data from the Medical Liability Monitor, a national publication that analyzes liability insurance premiums. The Monitor studies insurance premium data from insurers that cover internists, general surgeons, and obstetrician-gynecologists.

From 2019 to 2023, average premium rates for physicians increased between 1.1% and 3% each year in states without patient compensation funds, according to Monitor data.

“Nuclear verdicts are a real driver of the industry’s underwriting losses and remain top of mind for every malpractice insurance company,” said Michael Matray, editor for the Medical Liability Monitor. “Responses to this year’s rate survey questionnaire indicate that most responding companies have experienced an increase in claims greater than $1 million and claims greater than $5 million during the past 2 years.”

However, increases vary widely by region and among counties. In Montgomery County, Alabama, for instance, premiums for internists rose by 24% from 2022 to 2023, from $8,231 to $10,240. Premiums for Montgomery County general surgeons rose by 11.9% from 2022 to 2023, from $30,761 to $34,426, according to survey data.

In several counties in Illinois (Adams, Knox, Peoria, and Rock Island), premiums for some internists rose by 15% from $24,041 to $27,783, and premiums for some surgeons increased by 27% from $60,202 to $76,461, according to survey data. Some internists in Catoosa County, Georgia, meanwhile, paid $17,831 in 2023, up from $16,313 in 2022. Some surgeons in Catoosa County paid $65,616 in 2023, up from $60,032 in 2022. Inflation could be one factor behind higher liability premium rates. Claim severity is a key driver of higher premium rates, Mr. White added.

“We have not seen stability in claims severity,” he said. “It is continuing to go up and, in all likelihood, it will drive [premium] rates up further from this point.”
 

A version of this article appeared on Medscape.com.

A new study added heart failure with preserved ejection fraction (HFpEF) to the growing list of cardiovascular conditions linked to clonal hematopoiesis of indeterminate potential (CHIP), which already includes atherosclerotic cardiovascular disease (ASCVD).

But what exactly is CHIP, and what is its potential value in CVD risk and management?

CHIP is an age-related condition marked by clonal expansion of blood stem cells with leukemia-associated mutations in individuals without evidence of hematologic malignancy. CHIP is estimated to affect about 10% of people aged 70 years and older.

First described as a risk factor for hematologic, particularly myeloid, malignant neoplasms, CHIP has recently emerged as a novel CVD risk factor.

CHIP gives rise to proinflammatory immune cells, which can exacerbate ASCVD and may induce or accelerate HF.

“The association between CHIP and HFpEF may be particularly relevant, given that the prevalence of HFpEF is rising due to the progressive aging of the population,” said José J. Fuster, PhD, coordinator for the program on novel mechanisms of atherosclerosis, Spanish National Center for Cardiovascular Research, Madrid.

Yet previous studies examining CHIP and HF have either focused on overall HF without distinguishing HF subtypes of preserved vs reduced ejection fraction, or have examined its prognostic significance in the setting of established HF, rather than the development of future HF.

To help fill the gap, Boston-based researchers recently evaluated associations of CHIP and the two most common gene-specific CHIP subtypes (TET2 and DNMT3A CHIP) with incident HFpEF and HF with reduced ejection fraction (HFrEF).

In two racially diverse cohorts with a total of 8090 adults, TET2 CHIP was independently associated with > twofold higher risk of incident HFpEF. By contrast, there were no significant associations of CHIP with incident HFrEF.

“Our study’s fundings suggest that previously described associations between CHIP and future development of heart failure may be driven primarily by HFpEF,” said Michael Honigberg, MD, with the Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston.

In addition, the “clearest signal for an association with HF was observed for TET2 CHIP, the second-most common subtype of CHIP in the population. This finding aligns with a recently published study that reported relative enrichment of TET2 CHIP in a small human HFpEF cohort,” Dr. Honigberg said.

Dr. Fuster said the connection between CHIP and aging “enhances the potential clinical relevance of this study, as CHIP is frequent in elderly individuals and, therefore, may contribute to the pathophysiology of HFpEF in a high proportion of patients.”

He cautioned, however, that the findings need to be validated in other studies.

“In addition, there is a growing recognition that the effects of CHIP are heterogeneous, as mutations in different genes have different effects on cardiovascular and act through different mechanisms. Additional studies will be needed to dissect gene-specific effects in HFpEF. It will also be important to explore whether CHIP influences the clinical progression of the disease,” Dr. Fuster said.

Targeted Treatment?

Dr. Honigberg said the findings may aid in the development of new targeted-treatment strategies for at least the subset of patients with HFpEF.

Based on multiple lines of evidence, the mechanism linking TET2 CHIP to CVD appears to be heightened inflammation, he explained.

For example, in a substudy of the CANTOS trial, patients with atherosclerosis and TET2 CHIP who received canakinumab appeared to derive “outsized benefit” in preventing CV events compared with the overall trial population, Dr. Honigberg said.

“HFpEF is a particularly challenging disease with limited effective therapies. Our findings support the premise that targeted anti-inflammatory therapies may prevent and/or treat HFpEF driven by TET2 CHIP. Of course, this hypothesis will require testing in prospective randomized trials,” Dr. Honigberg said.

“The field of CHIP has developed rapidly, and it is an exciting area of research,” Dr. Fuster added. “However, I personally believe that much work lies ahead before it is ready for prime time in the clinical setting.

“Although the link between CHIP and CVD is solid, we still lack evidence-based interventions to mitigate the elevated CVD risk associated with these mutations. In the absence of effective interventions, the added value of screening for CHIP as a risk factor may be limited,” Dr. Fuster noted.

“For instance, in the setting of HFpEF, we don’t really know whether CHIP mutation carriers may respond favorably to contemporary HF medications or may require new personalized approaches. Additional research and, eventually, clinical trials, are needed,” he added. 

Dr. Honigberg has disclosed relationships with Genentech, Miga Health, CRISPR Therapeutics, and Comanche Biopharma. Dr. Fuster has no relevant disclosures.
 

A version of this article appeared on Medscape.com.

A new study added heart failure with preserved ejection fraction (HFpEF) to the growing list of cardiovascular conditions linked to clonal hematopoiesis of indeterminate potential (CHIP), which already includes atherosclerotic cardiovascular disease (ASCVD).

But what exactly is CHIP, and what is its potential value in CVD risk and management?

CHIP is an age-related condition marked by clonal expansion of blood stem cells with leukemia-associated mutations in individuals without evidence of hematologic malignancy. CHIP is estimated to affect about 10% of people aged 70 years and older.

First described as a risk factor for hematologic, particularly myeloid, malignant neoplasms, CHIP has recently emerged as a novel CVD risk factor.

CHIP gives rise to proinflammatory immune cells, which can exacerbate ASCVD and may induce or accelerate HF.

“The association between CHIP and HFpEF may be particularly relevant, given that the prevalence of HFpEF is rising due to the progressive aging of the population,” said José J. Fuster, PhD, coordinator for the program on novel mechanisms of atherosclerosis, Spanish National Center for Cardiovascular Research, Madrid.

Yet previous studies examining CHIP and HF have either focused on overall HF without distinguishing HF subtypes of preserved vs reduced ejection fraction, or have examined its prognostic significance in the setting of established HF, rather than the development of future HF.

To help fill the gap, Boston-based researchers recently evaluated associations of CHIP and the two most common gene-specific CHIP subtypes (TET2 and DNMT3A CHIP) with incident HFpEF and HF with reduced ejection fraction (HFrEF).

In two racially diverse cohorts with a total of 8090 adults, TET2 CHIP was independently associated with > twofold higher risk of incident HFpEF. By contrast, there were no significant associations of CHIP with incident HFrEF.

“Our study’s fundings suggest that previously described associations between CHIP and future development of heart failure may be driven primarily by HFpEF,” said Michael Honigberg, MD, with the Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston.

In addition, the “clearest signal for an association with HF was observed for TET2 CHIP, the second-most common subtype of CHIP in the population. This finding aligns with a recently published study that reported relative enrichment of TET2 CHIP in a small human HFpEF cohort,” Dr. Honigberg said.

Dr. Fuster said the connection between CHIP and aging “enhances the potential clinical relevance of this study, as CHIP is frequent in elderly individuals and, therefore, may contribute to the pathophysiology of HFpEF in a high proportion of patients.”

He cautioned, however, that the findings need to be validated in other studies.

“In addition, there is a growing recognition that the effects of CHIP are heterogeneous, as mutations in different genes have different effects on cardiovascular and act through different mechanisms. Additional studies will be needed to dissect gene-specific effects in HFpEF. It will also be important to explore whether CHIP influences the clinical progression of the disease,” Dr. Fuster said.

Targeted Treatment?

Dr. Honigberg said the findings may aid in the development of new targeted-treatment strategies for at least the subset of patients with HFpEF.

Based on multiple lines of evidence, the mechanism linking TET2 CHIP to CVD appears to be heightened inflammation, he explained.

For example, in a substudy of the CANTOS trial, patients with atherosclerosis and TET2 CHIP who received canakinumab appeared to derive “outsized benefit” in preventing CV events compared with the overall trial population, Dr. Honigberg said.

“HFpEF is a particularly challenging disease with limited effective therapies. Our findings support the premise that targeted anti-inflammatory therapies may prevent and/or treat HFpEF driven by TET2 CHIP. Of course, this hypothesis will require testing in prospective randomized trials,” Dr. Honigberg said.

“The field of CHIP has developed rapidly, and it is an exciting area of research,” Dr. Fuster added. “However, I personally believe that much work lies ahead before it is ready for prime time in the clinical setting.

“Although the link between CHIP and CVD is solid, we still lack evidence-based interventions to mitigate the elevated CVD risk associated with these mutations. In the absence of effective interventions, the added value of screening for CHIP as a risk factor may be limited,” Dr. Fuster noted.

“For instance, in the setting of HFpEF, we don’t really know whether CHIP mutation carriers may respond favorably to contemporary HF medications or may require new personalized approaches. Additional research and, eventually, clinical trials, are needed,” he added. 

Dr. Honigberg has disclosed relationships with Genentech, Miga Health, CRISPR Therapeutics, and Comanche Biopharma. Dr. Fuster has no relevant disclosures.
 

A version of this article appeared on Medscape.com.

A new study added heart failure with preserved ejection fraction (HFpEF) to the growing list of cardiovascular conditions linked to clonal hematopoiesis of indeterminate potential (CHIP), which already includes atherosclerotic cardiovascular disease (ASCVD).

But what exactly is CHIP, and what is its potential value in CVD risk and management?

CHIP is an age-related condition marked by clonal expansion of blood stem cells with leukemia-associated mutations in individuals without evidence of hematologic malignancy. CHIP is estimated to affect about 10% of people aged 70 years and older.

First described as a risk factor for hematologic, particularly myeloid, malignant neoplasms, CHIP has recently emerged as a novel CVD risk factor.

CHIP gives rise to proinflammatory immune cells, which can exacerbate ASCVD and may induce or accelerate HF.

“The association between CHIP and HFpEF may be particularly relevant, given that the prevalence of HFpEF is rising due to the progressive aging of the population,” said José J. Fuster, PhD, coordinator for the program on novel mechanisms of atherosclerosis, Spanish National Center for Cardiovascular Research, Madrid.

Yet previous studies examining CHIP and HF have either focused on overall HF without distinguishing HF subtypes of preserved vs reduced ejection fraction, or have examined its prognostic significance in the setting of established HF, rather than the development of future HF.

To help fill the gap, Boston-based researchers recently evaluated associations of CHIP and the two most common gene-specific CHIP subtypes (TET2 and DNMT3A CHIP) with incident HFpEF and HF with reduced ejection fraction (HFrEF).

In two racially diverse cohorts with a total of 8090 adults, TET2 CHIP was independently associated with > twofold higher risk of incident HFpEF. By contrast, there were no significant associations of CHIP with incident HFrEF.

“Our study’s fundings suggest that previously described associations between CHIP and future development of heart failure may be driven primarily by HFpEF,” said Michael Honigberg, MD, with the Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston.

In addition, the “clearest signal for an association with HF was observed for TET2 CHIP, the second-most common subtype of CHIP in the population. This finding aligns with a recently published study that reported relative enrichment of TET2 CHIP in a small human HFpEF cohort,” Dr. Honigberg said.

Dr. Fuster said the connection between CHIP and aging “enhances the potential clinical relevance of this study, as CHIP is frequent in elderly individuals and, therefore, may contribute to the pathophysiology of HFpEF in a high proportion of patients.”

He cautioned, however, that the findings need to be validated in other studies.

“In addition, there is a growing recognition that the effects of CHIP are heterogeneous, as mutations in different genes have different effects on cardiovascular and act through different mechanisms. Additional studies will be needed to dissect gene-specific effects in HFpEF. It will also be important to explore whether CHIP influences the clinical progression of the disease,” Dr. Fuster said.

Targeted Treatment?

Dr. Honigberg said the findings may aid in the development of new targeted-treatment strategies for at least the subset of patients with HFpEF.

Based on multiple lines of evidence, the mechanism linking TET2 CHIP to CVD appears to be heightened inflammation, he explained.

For example, in a substudy of the CANTOS trial, patients with atherosclerosis and TET2 CHIP who received canakinumab appeared to derive “outsized benefit” in preventing CV events compared with the overall trial population, Dr. Honigberg said.

“HFpEF is a particularly challenging disease with limited effective therapies. Our findings support the premise that targeted anti-inflammatory therapies may prevent and/or treat HFpEF driven by TET2 CHIP. Of course, this hypothesis will require testing in prospective randomized trials,” Dr. Honigberg said.

“The field of CHIP has developed rapidly, and it is an exciting area of research,” Dr. Fuster added. “However, I personally believe that much work lies ahead before it is ready for prime time in the clinical setting.

“Although the link between CHIP and CVD is solid, we still lack evidence-based interventions to mitigate the elevated CVD risk associated with these mutations. In the absence of effective interventions, the added value of screening for CHIP as a risk factor may be limited,” Dr. Fuster noted.

“For instance, in the setting of HFpEF, we don’t really know whether CHIP mutation carriers may respond favorably to contemporary HF medications or may require new personalized approaches. Additional research and, eventually, clinical trials, are needed,” he added. 

Dr. Honigberg has disclosed relationships with Genentech, Miga Health, CRISPR Therapeutics, and Comanche Biopharma. Dr. Fuster has no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Black women who develop high blood pressure before age 35 have a threefold increased risk of having a midlife stroke, new observational data suggested.

The Black Women’s Health Study, which has followed 59,000 participants in the United States since the 1990s, also showed that those who develop hypertension before age 45 have twice the risk of suffering a stroke.

“The really concerning thing about this data is the high proportion of young Black women who had high blood pressure and are suffering strokes relatively early in life,” the study’s lead author, Hugo J. Aparicio, MD, associate professor of neurology at Boston University Chobanian & Avedisian School of Medicine, told this news organization. “This can lead to a burden of disability in relatively young women who may be at the prime of their life, pursuing careers and looking after family.”

Dr. Aparicio will present the data in full at the International Stroke Conference 2024 to be held in Phoenix, Arizona, Feb. 7-9.

He explained that while there has been good progress in reducing stroke rates in older people over the past decades, there is a concerning observation from multiple datasets showing that stroke rates in midlife have been plateauing or even increasing in recent years.

“For Black women specifically, there is a concern, as we know this group has higher rates of raised blood pressure and stroke overall,” said Dr. Aparicio. “We were interested in looking at whether the onset of hypertension at an earlier age in this group is one of the reasons for the increased stroke risk in midlife.”

The researchers analyzed data from the Black Women’s Health Study, a prospective study of 59,000 Black women from across the United States. The baseline year for this analysis, which included 46,754 stroke-free participants younger than age 65 (mean age, 42 years), was the 1999 questionnaire.

History of hypertension, defined as physician-diagnosed hypertension with the use of an antihypertensive medication, and of stroke occurrence was determined by self-report. It has been shown in previous studies that these self-reported data on incidence of hypertension in this dataset are highly reliable, Dr. Aparicio noted.

At baseline, 10.5% of participants aged 45-64 years had hypertension. Stroke occurred in 3.2% of individuals over a mean follow-up of 17 years.

Black women with hypertension before age 45 had a higher risk for midlife stroke (hazard ratio [HR], 2.23; 95% CI, 1.79-2.78), after adjustment for age, neighborhood socioeconomic status, residence in Stroke Belt, smoking, body mass index, and diabetes than women with no history of hypertension.

The risk was also increased with hypertension at midlife ages 45-64 years (HR, 1.69; 95% CI, 1.47-1.95) and was highest among those with hypertension at ages 24-34 years (HR, 3.15; 95% CI, 1.92-5.16).

“Our results show that among young Black women, those with hypertension have a much higher stroke risk than those without hypertension, even if they are taking antihypertensive medication,” Dr. Aparicio said. “This underscores how potent hypertension is as a risk factor for stroke.”

He concluded that both individuals and doctors need to realize that hypertension and stroke are not problems of the elderly exclusively.

“These are conditions that need to be addressed very early in life. This is even more important for Black women, as they are a high-risk group. They need to pay attention to blood pressure numbers early in life — ideally from adolescence — to catch levels before they become too elevated,” Dr. Aparicio said.

“We also need to address lifestyle changes including diet, physical activity, sleep habits, and address other cardiovascular risk factors such as cholesterol and body mass index, so we can prevent strokes from occurring,” he added. “At the policy level, we need to advocate, provide and fund primary prevention measures, and enable earlier screening and better treatment.”

The Role of Psychosocial Stressors

Commenting on the study, the American Heart Association immediate past president, Michelle A. Albert, MD, professor of medicine at the University of California, San Francisco, emphasized the importance of regular primary care appointments to screen for high blood pressure and other cardiovascular risk factors.

She pointed out that one of the contributing factors that may increase the risk for Black women is their disproportionate experience of psychosocial stressors and chronic cumulative stress.

This could include stress related to financial issues, racism and other forms of bias, the neighborhood environment, and having to take care of multiple generations of family with limited resources.

“These are some of the things that are less talked about as going into the heightened risk for many cardiovascular risk factors, including hypertension, very early in life for Black women that we need to bring to the forefront of conversations,” Dr. Albert said.

“These stressors not only impact hypertension onset but also they impact one’s ability to be able to seek help, and once the help is sought, to be able to sustain the therapies recommended and the interventions recommended,” she added.

The authors reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Black women who develop high blood pressure before age 35 have a threefold increased risk of having a midlife stroke, new observational data suggested.

The Black Women’s Health Study, which has followed 59,000 participants in the United States since the 1990s, also showed that those who develop hypertension before age 45 have twice the risk of suffering a stroke.

“The really concerning thing about this data is the high proportion of young Black women who had high blood pressure and are suffering strokes relatively early in life,” the study’s lead author, Hugo J. Aparicio, MD, associate professor of neurology at Boston University Chobanian & Avedisian School of Medicine, told this news organization. “This can lead to a burden of disability in relatively young women who may be at the prime of their life, pursuing careers and looking after family.”

Dr. Aparicio will present the data in full at the International Stroke Conference 2024 to be held in Phoenix, Arizona, Feb. 7-9.

He explained that while there has been good progress in reducing stroke rates in older people over the past decades, there is a concerning observation from multiple datasets showing that stroke rates in midlife have been plateauing or even increasing in recent years.

“For Black women specifically, there is a concern, as we know this group has higher rates of raised blood pressure and stroke overall,” said Dr. Aparicio. “We were interested in looking at whether the onset of hypertension at an earlier age in this group is one of the reasons for the increased stroke risk in midlife.”

The researchers analyzed data from the Black Women’s Health Study, a prospective study of 59,000 Black women from across the United States. The baseline year for this analysis, which included 46,754 stroke-free participants younger than age 65 (mean age, 42 years), was the 1999 questionnaire.

History of hypertension, defined as physician-diagnosed hypertension with the use of an antihypertensive medication, and of stroke occurrence was determined by self-report. It has been shown in previous studies that these self-reported data on incidence of hypertension in this dataset are highly reliable, Dr. Aparicio noted.

At baseline, 10.5% of participants aged 45-64 years had hypertension. Stroke occurred in 3.2% of individuals over a mean follow-up of 17 years.

Black women with hypertension before age 45 had a higher risk for midlife stroke (hazard ratio [HR], 2.23; 95% CI, 1.79-2.78), after adjustment for age, neighborhood socioeconomic status, residence in Stroke Belt, smoking, body mass index, and diabetes than women with no history of hypertension.

The risk was also increased with hypertension at midlife ages 45-64 years (HR, 1.69; 95% CI, 1.47-1.95) and was highest among those with hypertension at ages 24-34 years (HR, 3.15; 95% CI, 1.92-5.16).

“Our results show that among young Black women, those with hypertension have a much higher stroke risk than those without hypertension, even if they are taking antihypertensive medication,” Dr. Aparicio said. “This underscores how potent hypertension is as a risk factor for stroke.”

He concluded that both individuals and doctors need to realize that hypertension and stroke are not problems of the elderly exclusively.

“These are conditions that need to be addressed very early in life. This is even more important for Black women, as they are a high-risk group. They need to pay attention to blood pressure numbers early in life — ideally from adolescence — to catch levels before they become too elevated,” Dr. Aparicio said.

“We also need to address lifestyle changes including diet, physical activity, sleep habits, and address other cardiovascular risk factors such as cholesterol and body mass index, so we can prevent strokes from occurring,” he added. “At the policy level, we need to advocate, provide and fund primary prevention measures, and enable earlier screening and better treatment.”

The Role of Psychosocial Stressors

Commenting on the study, the American Heart Association immediate past president, Michelle A. Albert, MD, professor of medicine at the University of California, San Francisco, emphasized the importance of regular primary care appointments to screen for high blood pressure and other cardiovascular risk factors.

She pointed out that one of the contributing factors that may increase the risk for Black women is their disproportionate experience of psychosocial stressors and chronic cumulative stress.

This could include stress related to financial issues, racism and other forms of bias, the neighborhood environment, and having to take care of multiple generations of family with limited resources.

“These are some of the things that are less talked about as going into the heightened risk for many cardiovascular risk factors, including hypertension, very early in life for Black women that we need to bring to the forefront of conversations,” Dr. Albert said.

“These stressors not only impact hypertension onset but also they impact one’s ability to be able to seek help, and once the help is sought, to be able to sustain the therapies recommended and the interventions recommended,” she added.

The authors reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Black women who develop high blood pressure before age 35 have a threefold increased risk of having a midlife stroke, new observational data suggested.

The Black Women’s Health Study, which has followed 59,000 participants in the United States since the 1990s, also showed that those who develop hypertension before age 45 have twice the risk of suffering a stroke.

“The really concerning thing about this data is the high proportion of young Black women who had high blood pressure and are suffering strokes relatively early in life,” the study’s lead author, Hugo J. Aparicio, MD, associate professor of neurology at Boston University Chobanian & Avedisian School of Medicine, told this news organization. “This can lead to a burden of disability in relatively young women who may be at the prime of their life, pursuing careers and looking after family.”

Dr. Aparicio will present the data in full at the International Stroke Conference 2024 to be held in Phoenix, Arizona, Feb. 7-9.

He explained that while there has been good progress in reducing stroke rates in older people over the past decades, there is a concerning observation from multiple datasets showing that stroke rates in midlife have been plateauing or even increasing in recent years.

“For Black women specifically, there is a concern, as we know this group has higher rates of raised blood pressure and stroke overall,” said Dr. Aparicio. “We were interested in looking at whether the onset of hypertension at an earlier age in this group is one of the reasons for the increased stroke risk in midlife.”

The researchers analyzed data from the Black Women’s Health Study, a prospective study of 59,000 Black women from across the United States. The baseline year for this analysis, which included 46,754 stroke-free participants younger than age 65 (mean age, 42 years), was the 1999 questionnaire.

History of hypertension, defined as physician-diagnosed hypertension with the use of an antihypertensive medication, and of stroke occurrence was determined by self-report. It has been shown in previous studies that these self-reported data on incidence of hypertension in this dataset are highly reliable, Dr. Aparicio noted.

At baseline, 10.5% of participants aged 45-64 years had hypertension. Stroke occurred in 3.2% of individuals over a mean follow-up of 17 years.

Black women with hypertension before age 45 had a higher risk for midlife stroke (hazard ratio [HR], 2.23; 95% CI, 1.79-2.78), after adjustment for age, neighborhood socioeconomic status, residence in Stroke Belt, smoking, body mass index, and diabetes than women with no history of hypertension.

The risk was also increased with hypertension at midlife ages 45-64 years (HR, 1.69; 95% CI, 1.47-1.95) and was highest among those with hypertension at ages 24-34 years (HR, 3.15; 95% CI, 1.92-5.16).

“Our results show that among young Black women, those with hypertension have a much higher stroke risk than those without hypertension, even if they are taking antihypertensive medication,” Dr. Aparicio said. “This underscores how potent hypertension is as a risk factor for stroke.”

He concluded that both individuals and doctors need to realize that hypertension and stroke are not problems of the elderly exclusively.

“These are conditions that need to be addressed very early in life. This is even more important for Black women, as they are a high-risk group. They need to pay attention to blood pressure numbers early in life — ideally from adolescence — to catch levels before they become too elevated,” Dr. Aparicio said.

“We also need to address lifestyle changes including diet, physical activity, sleep habits, and address other cardiovascular risk factors such as cholesterol and body mass index, so we can prevent strokes from occurring,” he added. “At the policy level, we need to advocate, provide and fund primary prevention measures, and enable earlier screening and better treatment.”

The Role of Psychosocial Stressors

Commenting on the study, the American Heart Association immediate past president, Michelle A. Albert, MD, professor of medicine at the University of California, San Francisco, emphasized the importance of regular primary care appointments to screen for high blood pressure and other cardiovascular risk factors.

She pointed out that one of the contributing factors that may increase the risk for Black women is their disproportionate experience of psychosocial stressors and chronic cumulative stress.

This could include stress related to financial issues, racism and other forms of bias, the neighborhood environment, and having to take care of multiple generations of family with limited resources.

“These are some of the things that are less talked about as going into the heightened risk for many cardiovascular risk factors, including hypertension, very early in life for Black women that we need to bring to the forefront of conversations,” Dr. Albert said.

“These stressors not only impact hypertension onset but also they impact one’s ability to be able to seek help, and once the help is sought, to be able to sustain the therapies recommended and the interventions recommended,” she added.

The authors reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

A significant gap in our understanding of eosinophilic esophagitis (EoE) lies in how environmental factors, such as allergens or food, influence the response to proton pump inhibitor (PPI) therapy. While PPI achieve histologic remission in approximately 50% of patients, the response in the remaining 50% remains unclear. Addressing this, Muftah and colleagues conducted a study to evaluate the relationship between environmental and food allergies and PPI response in newly diagnosed EoE patients.

Between 2012 and 2016, adult patients newly diagnosed with EoE were tested for environmental and food allergies. Following diagnosis, patients participated in an 8-week trial of twice-daily PPI therapy. The treatment's effectiveness was assessed through repeated upper endoscopies with esophageal biopsies.

The study's primary outcome was the histologic remission of EoE, defined as a decrease in eosinophils to < 15 eosinophils/high-powered field (eos/hpf) in all esophageal biopsy samples during repeat endoscopy. Out of 61 patients, 21 achieved histologic remission, while 40 were classified as having PPI-nonresponding EoE. Among PPI-nonresponding EoE patients, positive food allergen testing was significantly more prevalent compared with PPI-responding EoE patients (82.5% vs 42.9%; P = .0003). Additionally, patients with >10 positive environmental allergen tests were significantly less likely to be PPI-responding EoE patients than those with <10 positive results (21% vs 53.9%; P = .03). A similar trend was observed in patients with >5 positive environmental allergens.

This study is not without limitations. It may exhibit a selection bias toward more severe cases and has a relatively small sample size, affecting its statistical power and generalizability.

This research supports the idea of more tailored management for EoE patients, focusing on their allergen profile, potentially leading to more effective treatment strategies and reducing unnecessary PPI trials. The statistically significant results pave the way for further research, providing an additional tool to predict PPI responsiveness and prevent delays in achieving remission.

Clinicians should consider patient characteristics, particularly positive food allergen tests, that might affect treatment response. More studies are needed, however, to understand the effect of environmental allergies on PPI response fully. A notable finding is that specific aeroallergens, such as oak, birch, Hormodendrum mold, dust mite (Dermatophagoides pteronyssinus), tree mix, and grass mix allergens, are associated with a lack of PPI response. This raises questions about whether exposure to these allergens during peak seasons could worsen PPI response in allergic EoE patients.

Key takeaways from this study include: (1) the importance of integrating allergen testing in EoE patients, especially those unresponsive to standard PPI therapy or suspected as having allergic phenotypes; (2) the need to monitor and adjust therapy based on clinical and histologic responses; and (3) the necessity of staying abreast of emerging research in this area.

EoE diagnosis presents unique challenges, particularly when patients exhibit exclusive distal esophageal eosinophilia or when discrepancies arise between endoscopic and histologic findings. Eosinophil-derived neurotoxin (EDN), a molecule previously studied for its role in monitoring allergy-mediated inflammatory diseases such as asthma and eczema, can shed light on these diagnostic difficulties.

Thomas and coworkers conducted a retrospective study in which they reviewed 231 pediatric patients, obtaining a minimum of four biopsies from at least two different levels of the esophagus. The study aimed to evaluate whether EDN concentrations, determined through esophageal epithelial brushing at the time of biopsy, could serve as an adjunctive diagnostic tool for EoE.

EDN levels proved sensitive (84.4%) and specific (94.6%) in evaluating active EoE when several measures of EoE were used in patients with active EoE compared with those with inactive EoE and the control group. Previous studies at the same institution had found EDN useful for differentiating EoE patients from non-EoE patients. Moreover, an EDN concentration > 10 μg/mL, when collected through esophageal epithelial brushing, was highly sensitive (97%) and specific (89%) for active EoE. This finding suggests the potential for using EDN as a biochemical marker, enhancing diagnostic accuracy and reducing the need for additional interventions in complex cases.

EDN as a biomarker could be invaluable for distinguishing difficult cases, such as those involving distal eosinophilia, active vs nonactive EoE, or non-EoE conditions, such as gastroesophageal reflux disease. Of note, lower EDN levels were observed in pediatric EoE patients who responded to PPI, suggesting EDN's potential utility in predicting PPI responsiveness. Incorporating the measurement of eosinophilic activity could add a new dimension to existing criteria, equipping clinicians with more precise diagnostic tools and reducing the reliance on multiple procedures. This approach would strengthen the correlation between symptomatic, endoscopic, and histologic data.

The study by Jensen and colleagues sheds light on a crucial aspect of EoE management: the psychosocial burden. A recent EoE diagnosis can be associated with increased symptom burden, somatization, and anxiety in patients and families, underscoring the need for a multidisciplinary approach to patient care that considers both physical and mental health. To date, numerous studies have focused on understanding the disease, its follow-up, and treatment. However, there has been limited exploration of the psychosocial burden and patient-associated factors in EoE.

In this context, this team aimed to enhance our understanding of the burden of EoE by evaluating psychosocial comorbidities, such as disordered sleep, anxiety, and somatization, in a pediatric population with EoE. The study included 87 patients of age 8-18 years who completed validated assessments during routine clinic visits, encompassing EoE symptoms (Pediatric Eosinophilic Esophagitis Symptom Scores, PEESSv2.0), quality of life (PedsQL-EoE), anxiety state and trait (State-Trait Anxiety Inventory for Children, STAI-C), somatization (Children's Somatic Symptoms Inventory-24, CSSI-24), and sleep-disordered breathing (University of Michigan Pediatric Sleep Questionnaire, PSQ).

The mean age of the participants was 12.8 years, highlighting the importance of addressing psychosocial distress in this age group, which undergoes crucial developmental stages. Most patients (82%, 71) had been diagnosed with EoE at least 12 months prior, and 60% (52) were treated with multiple approaches. Additionally, 34% (29) had undergone seven or more esophagogastroduodenoscopies, and nearly one third (33%, 27) had experienced a gastrointestinal-related emergency department visit. These factors potentially increase patient stress due to the continuous need for repeat procedures and hospital visits. An intriguing finding was that patients with shorter disease durations (6-12 months since diagnosis) experienced higher symptom burdens (P = .03). Patients with public insurance had less favorable scores for sleep-disordered breathing (P = .01).

Significantly, patients with neurodevelopmental comorbidities had higher scores for somatic symptoms, trait anxiety, and sleep-disordered breathing, and lower quality-of-life scores, compared with those without such comorbidities (P < .01 for all), suggesting that patients with neurodevelopmental issues might particularly benefit from tailored treatments addressing these aspects of the disease. Furthermore, patients with shorter disease durations since diagnosis exhibited higher somatic symptoms and trait anxiety (both P < .01). The study also revealed that patients with fewer esophagogastroduodenoscopies (1-3) had higher somatic symptom scores (P < .01), state anxiety (P = .02), and trait anxiety (P = .03). EoE-associated symptom burden was significantly correlated with increased somatic symptoms (0.34; 95% CI 0.23-0.45) and decreased quality of life (-0.42; 95% CI -0.59 to -0.25). Concerns about eating food and EoE-associated symptoms were both linked to the EoE-associated symptom burden.

This study has several limitations, including a relatively small sample size, which decreases the power and limits inferences for smaller groups within the sample. There was also an imbalance in gender distribution, with only 26% of patients being female, potentially limiting the generalizability of the findings. Moreover, the study included only EoE patients, lacking a control group for comparison to the general pediatric population.

Highlighting a significant aspect of pediatric EoE treatment, this study illuminates an area that might affect patients' long-term quality of life. It underscores the need for multidisciplinary care for EoE patients, where mental health professionals, such as psychologists or psychiatrists, can play a vital role in improving mental health through early identification and intervention for anxiety and somatization disorders. They can also provide education for patients and families on coping strategies. Peer support groups for children and adolescents could be another beneficial tool, allowing them to share experiences and reduce feelings of isolation.

Physicians who treat chronic diseases such as EoE should consider psychosocial factors, as they can affect both physical and mental quality of life. Using screening tools (such as PEESSv2.0, PedsQL-EoE, STAI-C, CSSI-24, or PSQ) during clinic visits can facilitate a more comprehensive evaluation.

A significant gap in our understanding of eosinophilic esophagitis (EoE) lies in how environmental factors, such as allergens or food, influence the response to proton pump inhibitor (PPI) therapy. While PPI achieve histologic remission in approximately 50% of patients, the response in the remaining 50% remains unclear. Addressing this, Muftah and colleagues conducted a study to evaluate the relationship between environmental and food allergies and PPI response in newly diagnosed EoE patients.

Between 2012 and 2016, adult patients newly diagnosed with EoE were tested for environmental and food allergies. Following diagnosis, patients participated in an 8-week trial of twice-daily PPI therapy. The treatment's effectiveness was assessed through repeated upper endoscopies with esophageal biopsies.

The study's primary outcome was the histologic remission of EoE, defined as a decrease in eosinophils to < 15 eosinophils/high-powered field (eos/hpf) in all esophageal biopsy samples during repeat endoscopy. Out of 61 patients, 21 achieved histologic remission, while 40 were classified as having PPI-nonresponding EoE. Among PPI-nonresponding EoE patients, positive food allergen testing was significantly more prevalent compared with PPI-responding EoE patients (82.5% vs 42.9%; P = .0003). Additionally, patients with >10 positive environmental allergen tests were significantly less likely to be PPI-responding EoE patients than those with <10 positive results (21% vs 53.9%; P = .03). A similar trend was observed in patients with >5 positive environmental allergens.

This study is not without limitations. It may exhibit a selection bias toward more severe cases and has a relatively small sample size, affecting its statistical power and generalizability.

This research supports the idea of more tailored management for EoE patients, focusing on their allergen profile, potentially leading to more effective treatment strategies and reducing unnecessary PPI trials. The statistically significant results pave the way for further research, providing an additional tool to predict PPI responsiveness and prevent delays in achieving remission.

Clinicians should consider patient characteristics, particularly positive food allergen tests, that might affect treatment response. More studies are needed, however, to understand the effect of environmental allergies on PPI response fully. A notable finding is that specific aeroallergens, such as oak, birch, Hormodendrum mold, dust mite (Dermatophagoides pteronyssinus), tree mix, and grass mix allergens, are associated with a lack of PPI response. This raises questions about whether exposure to these allergens during peak seasons could worsen PPI response in allergic EoE patients.

Key takeaways from this study include: (1) the importance of integrating allergen testing in EoE patients, especially those unresponsive to standard PPI therapy or suspected as having allergic phenotypes; (2) the need to monitor and adjust therapy based on clinical and histologic responses; and (3) the necessity of staying abreast of emerging research in this area.

EoE diagnosis presents unique challenges, particularly when patients exhibit exclusive distal esophageal eosinophilia or when discrepancies arise between endoscopic and histologic findings. Eosinophil-derived neurotoxin (EDN), a molecule previously studied for its role in monitoring allergy-mediated inflammatory diseases such as asthma and eczema, can shed light on these diagnostic difficulties.

Thomas and coworkers conducted a retrospective study in which they reviewed 231 pediatric patients, obtaining a minimum of four biopsies from at least two different levels of the esophagus. The study aimed to evaluate whether EDN concentrations, determined through esophageal epithelial brushing at the time of biopsy, could serve as an adjunctive diagnostic tool for EoE.

EDN levels proved sensitive (84.4%) and specific (94.6%) in evaluating active EoE when several measures of EoE were used in patients with active EoE compared with those with inactive EoE and the control group. Previous studies at the same institution had found EDN useful for differentiating EoE patients from non-EoE patients. Moreover, an EDN concentration > 10 μg/mL, when collected through esophageal epithelial brushing, was highly sensitive (97%) and specific (89%) for active EoE. This finding suggests the potential for using EDN as a biochemical marker, enhancing diagnostic accuracy and reducing the need for additional interventions in complex cases.

EDN as a biomarker could be invaluable for distinguishing difficult cases, such as those involving distal eosinophilia, active vs nonactive EoE, or non-EoE conditions, such as gastroesophageal reflux disease. Of note, lower EDN levels were observed in pediatric EoE patients who responded to PPI, suggesting EDN's potential utility in predicting PPI responsiveness. Incorporating the measurement of eosinophilic activity could add a new dimension to existing criteria, equipping clinicians with more precise diagnostic tools and reducing the reliance on multiple procedures. This approach would strengthen the correlation between symptomatic, endoscopic, and histologic data.

The study by Jensen and colleagues sheds light on a crucial aspect of EoE management: the psychosocial burden. A recent EoE diagnosis can be associated with increased symptom burden, somatization, and anxiety in patients and families, underscoring the need for a multidisciplinary approach to patient care that considers both physical and mental health. To date, numerous studies have focused on understanding the disease, its follow-up, and treatment. However, there has been limited exploration of the psychosocial burden and patient-associated factors in EoE.

In this context, this team aimed to enhance our understanding of the burden of EoE by evaluating psychosocial comorbidities, such as disordered sleep, anxiety, and somatization, in a pediatric population with EoE. The study included 87 patients of age 8-18 years who completed validated assessments during routine clinic visits, encompassing EoE symptoms (Pediatric Eosinophilic Esophagitis Symptom Scores, PEESSv2.0), quality of life (PedsQL-EoE), anxiety state and trait (State-Trait Anxiety Inventory for Children, STAI-C), somatization (Children's Somatic Symptoms Inventory-24, CSSI-24), and sleep-disordered breathing (University of Michigan Pediatric Sleep Questionnaire, PSQ).

The mean age of the participants was 12.8 years, highlighting the importance of addressing psychosocial distress in this age group, which undergoes crucial developmental stages. Most patients (82%, 71) had been diagnosed with EoE at least 12 months prior, and 60% (52) were treated with multiple approaches. Additionally, 34% (29) had undergone seven or more esophagogastroduodenoscopies, and nearly one third (33%, 27) had experienced a gastrointestinal-related emergency department visit. These factors potentially increase patient stress due to the continuous need for repeat procedures and hospital visits. An intriguing finding was that patients with shorter disease durations (6-12 months since diagnosis) experienced higher symptom burdens (P = .03). Patients with public insurance had less favorable scores for sleep-disordered breathing (P = .01).

Significantly, patients with neurodevelopmental comorbidities had higher scores for somatic symptoms, trait anxiety, and sleep-disordered breathing, and lower quality-of-life scores, compared with those without such comorbidities (P < .01 for all), suggesting that patients with neurodevelopmental issues might particularly benefit from tailored treatments addressing these aspects of the disease. Furthermore, patients with shorter disease durations since diagnosis exhibited higher somatic symptoms and trait anxiety (both P < .01). The study also revealed that patients with fewer esophagogastroduodenoscopies (1-3) had higher somatic symptom scores (P < .01), state anxiety (P = .02), and trait anxiety (P = .03). EoE-associated symptom burden was significantly correlated with increased somatic symptoms (0.34; 95% CI 0.23-0.45) and decreased quality of life (-0.42; 95% CI -0.59 to -0.25). Concerns about eating food and EoE-associated symptoms were both linked to the EoE-associated symptom burden.

This study has several limitations, including a relatively small sample size, which decreases the power and limits inferences for smaller groups within the sample. There was also an imbalance in gender distribution, with only 26% of patients being female, potentially limiting the generalizability of the findings. Moreover, the study included only EoE patients, lacking a control group for comparison to the general pediatric population.

Highlighting a significant aspect of pediatric EoE treatment, this study illuminates an area that might affect patients' long-term quality of life. It underscores the need for multidisciplinary care for EoE patients, where mental health professionals, such as psychologists or psychiatrists, can play a vital role in improving mental health through early identification and intervention for anxiety and somatization disorders. They can also provide education for patients and families on coping strategies. Peer support groups for children and adolescents could be another beneficial tool, allowing them to share experiences and reduce feelings of isolation.

Physicians who treat chronic diseases such as EoE should consider psychosocial factors, as they can affect both physical and mental quality of life. Using screening tools (such as PEESSv2.0, PedsQL-EoE, STAI-C, CSSI-24, or PSQ) during clinic visits can facilitate a more comprehensive evaluation.

A significant gap in our understanding of eosinophilic esophagitis (EoE) lies in how environmental factors, such as allergens or food, influence the response to proton pump inhibitor (PPI) therapy. While PPI achieve histologic remission in approximately 50% of patients, the response in the remaining 50% remains unclear. Addressing this, Muftah and colleagues conducted a study to evaluate the relationship between environmental and food allergies and PPI response in newly diagnosed EoE patients.

Between 2012 and 2016, adult patients newly diagnosed with EoE were tested for environmental and food allergies. Following diagnosis, patients participated in an 8-week trial of twice-daily PPI therapy. The treatment's effectiveness was assessed through repeated upper endoscopies with esophageal biopsies.

The study's primary outcome was the histologic remission of EoE, defined as a decrease in eosinophils to < 15 eosinophils/high-powered field (eos/hpf) in all esophageal biopsy samples during repeat endoscopy. Out of 61 patients, 21 achieved histologic remission, while 40 were classified as having PPI-nonresponding EoE. Among PPI-nonresponding EoE patients, positive food allergen testing was significantly more prevalent compared with PPI-responding EoE patients (82.5% vs 42.9%; P = .0003). Additionally, patients with >10 positive environmental allergen tests were significantly less likely to be PPI-responding EoE patients than those with <10 positive results (21% vs 53.9%; P = .03). A similar trend was observed in patients with >5 positive environmental allergens.

This study is not without limitations. It may exhibit a selection bias toward more severe cases and has a relatively small sample size, affecting its statistical power and generalizability.

This research supports the idea of more tailored management for EoE patients, focusing on their allergen profile, potentially leading to more effective treatment strategies and reducing unnecessary PPI trials. The statistically significant results pave the way for further research, providing an additional tool to predict PPI responsiveness and prevent delays in achieving remission.

Clinicians should consider patient characteristics, particularly positive food allergen tests, that might affect treatment response. More studies are needed, however, to understand the effect of environmental allergies on PPI response fully. A notable finding is that specific aeroallergens, such as oak, birch, Hormodendrum mold, dust mite (Dermatophagoides pteronyssinus), tree mix, and grass mix allergens, are associated with a lack of PPI response. This raises questions about whether exposure to these allergens during peak seasons could worsen PPI response in allergic EoE patients.

Key takeaways from this study include: (1) the importance of integrating allergen testing in EoE patients, especially those unresponsive to standard PPI therapy or suspected as having allergic phenotypes; (2) the need to monitor and adjust therapy based on clinical and histologic responses; and (3) the necessity of staying abreast of emerging research in this area.

EoE diagnosis presents unique challenges, particularly when patients exhibit exclusive distal esophageal eosinophilia or when discrepancies arise between endoscopic and histologic findings. Eosinophil-derived neurotoxin (EDN), a molecule previously studied for its role in monitoring allergy-mediated inflammatory diseases such as asthma and eczema, can shed light on these diagnostic difficulties.

Thomas and coworkers conducted a retrospective study in which they reviewed 231 pediatric patients, obtaining a minimum of four biopsies from at least two different levels of the esophagus. The study aimed to evaluate whether EDN concentrations, determined through esophageal epithelial brushing at the time of biopsy, could serve as an adjunctive diagnostic tool for EoE.

EDN levels proved sensitive (84.4%) and specific (94.6%) in evaluating active EoE when several measures of EoE were used in patients with active EoE compared with those with inactive EoE and the control group. Previous studies at the same institution had found EDN useful for differentiating EoE patients from non-EoE patients. Moreover, an EDN concentration > 10 μg/mL, when collected through esophageal epithelial brushing, was highly sensitive (97%) and specific (89%) for active EoE. This finding suggests the potential for using EDN as a biochemical marker, enhancing diagnostic accuracy and reducing the need for additional interventions in complex cases.

EDN as a biomarker could be invaluable for distinguishing difficult cases, such as those involving distal eosinophilia, active vs nonactive EoE, or non-EoE conditions, such as gastroesophageal reflux disease. Of note, lower EDN levels were observed in pediatric EoE patients who responded to PPI, suggesting EDN's potential utility in predicting PPI responsiveness. Incorporating the measurement of eosinophilic activity could add a new dimension to existing criteria, equipping clinicians with more precise diagnostic tools and reducing the reliance on multiple procedures. This approach would strengthen the correlation between symptomatic, endoscopic, and histologic data.

The study by Jensen and colleagues sheds light on a crucial aspect of EoE management: the psychosocial burden. A recent EoE diagnosis can be associated with increased symptom burden, somatization, and anxiety in patients and families, underscoring the need for a multidisciplinary approach to patient care that considers both physical and mental health. To date, numerous studies have focused on understanding the disease, its follow-up, and treatment. However, there has been limited exploration of the psychosocial burden and patient-associated factors in EoE.

In this context, this team aimed to enhance our understanding of the burden of EoE by evaluating psychosocial comorbidities, such as disordered sleep, anxiety, and somatization, in a pediatric population with EoE. The study included 87 patients of age 8-18 years who completed validated assessments during routine clinic visits, encompassing EoE symptoms (Pediatric Eosinophilic Esophagitis Symptom Scores, PEESSv2.0), quality of life (PedsQL-EoE), anxiety state and trait (State-Trait Anxiety Inventory for Children, STAI-C), somatization (Children's Somatic Symptoms Inventory-24, CSSI-24), and sleep-disordered breathing (University of Michigan Pediatric Sleep Questionnaire, PSQ).

The mean age of the participants was 12.8 years, highlighting the importance of addressing psychosocial distress in this age group, which undergoes crucial developmental stages. Most patients (82%, 71) had been diagnosed with EoE at least 12 months prior, and 60% (52) were treated with multiple approaches. Additionally, 34% (29) had undergone seven or more esophagogastroduodenoscopies, and nearly one third (33%, 27) had experienced a gastrointestinal-related emergency department visit. These factors potentially increase patient stress due to the continuous need for repeat procedures and hospital visits. An intriguing finding was that patients with shorter disease durations (6-12 months since diagnosis) experienced higher symptom burdens (P = .03). Patients with public insurance had less favorable scores for sleep-disordered breathing (P = .01).

Significantly, patients with neurodevelopmental comorbidities had higher scores for somatic symptoms, trait anxiety, and sleep-disordered breathing, and lower quality-of-life scores, compared with those without such comorbidities (P < .01 for all), suggesting that patients with neurodevelopmental issues might particularly benefit from tailored treatments addressing these aspects of the disease. Furthermore, patients with shorter disease durations since diagnosis exhibited higher somatic symptoms and trait anxiety (both P < .01). The study also revealed that patients with fewer esophagogastroduodenoscopies (1-3) had higher somatic symptom scores (P < .01), state anxiety (P = .02), and trait anxiety (P = .03). EoE-associated symptom burden was significantly correlated with increased somatic symptoms (0.34; 95% CI 0.23-0.45) and decreased quality of life (-0.42; 95% CI -0.59 to -0.25). Concerns about eating food and EoE-associated symptoms were both linked to the EoE-associated symptom burden.

This study has several limitations, including a relatively small sample size, which decreases the power and limits inferences for smaller groups within the sample. There was also an imbalance in gender distribution, with only 26% of patients being female, potentially limiting the generalizability of the findings. Moreover, the study included only EoE patients, lacking a control group for comparison to the general pediatric population.

Highlighting a significant aspect of pediatric EoE treatment, this study illuminates an area that might affect patients' long-term quality of life. It underscores the need for multidisciplinary care for EoE patients, where mental health professionals, such as psychologists or psychiatrists, can play a vital role in improving mental health through early identification and intervention for anxiety and somatization disorders. They can also provide education for patients and families on coping strategies. Peer support groups for children and adolescents could be another beneficial tool, allowing them to share experiences and reduce feelings of isolation.

Physicians who treat chronic diseases such as EoE should consider psychosocial factors, as they can affect both physical and mental quality of life. Using screening tools (such as PEESSv2.0, PedsQL-EoE, STAI-C, CSSI-24, or PSQ) during clinic visits can facilitate a more comprehensive evaluation.

The authors of a study published in the December 2023 issue of the Scandinavian Journal of Gastroenterology analyzed data to examine the potential link between gut microbiota and migraine. According to the statistical analysis, the researchers found that "a greater abundance of genus Lactobacillus was associated with a higher risk of migraine and a higher abundance of family Prevotellaceae was related to a decreased risk of migraine." Furthermore, they noted that these gut microbial patterns could be due to a genetic predisposition. The authors suggested that stool sampling could potentially be helpful in the diagnosis of migraine, and that measures to modify gut microbiota in the context of migraine therapy could be identified with future research.

While it is not clear whether migraine is a cause or effect of these alterations, or whether there is another confounding variable, the idea of using diet as a means of reducing migraine risk would be appealing for many patients. This offers hope, but it also leaves a window open for exaggeration and excessive reliance on certain foods or supplements before reliable links are established.

Further examining the genetic factors that might play a role in migraine, a large Korean data analysis published in the December 2023 issue of Epidemiology and Health described a link between migraine and Parkinson's disease. The researchers included 214,193 patients with migraine and 5,879,711 individuals without migraine. According to the statistical analysis, the patients who had migraine with aura showed a 1.35-fold higher risk for Parkinson's disease than individuals without migraine. However, the researchers did not note a statistically significant difference between the risk for Parkinson's disease among patients who had migraine without aura and individuals without migraine.

They also examined other factors, and noted that among individuals with migraine, those who had preexisting dyslipidemia had a higher risk for Parkinson's disease than those who did not have dyslipidemia. Other factors that were not correlated with an association between migraine and Parkinson's disease included cardiovascular risk factors, hypertension, diabetes, smoking status, and high body mass index.

The study authors noted that factors associated with the activity of calcitonin gene-related peptide (CGRP), which is known to play a significant role in the pathophysiology of migraine, could play a role in the link between migraine and Parkinson's disease. They pointed to previous studies that found evidence of elevated CGRP levels in the cerebrospinal fluid of patients with Parkinson's disease as possible evidence of a pathophysiologic link.

An earlier commentary, published in the April 2020 issue of Headache, suggested an implication of CGRP antagonists in the development of neurodegenerative disorders such as Parkinson's disease. The commentary authors noted that previous research correlated midlife migraine to late-life parkinsonism, suggesting a conceivable common pathology, which could include a genetic or environmental predisposition.^[1] They also noted that studies suggest a possible link between CGRP and multiple system atrophy, a parkinsonian disorder.^[1] They considered the possibility that one of the ways that CGRP could contribute to these disorders is through its role in the recruitment of inflammatory mediators, which can alter the function of nicotinic receptors in the dopaminergic system in Parkinson's disease pathogenesis.^[2]

Recent research published in the December 2023 issue of Headache suggests that CGRP responsiveness in migraine therapy could be mediated by genetics. The study included 198 patients who had been typed for genes involved in CGRP signaling or pharmacologic response and were given genetic and polygenic risk scores. Responders were defined as patients who experienced ≥ 50% reduction in migraine days per month at 5.7-month follow-up.

The analysis revealed an association between nonresponder status and rs12615320-G in RAMP1, a gene that encodes a component of high-affinity CGRP receptors, which increased the risk for nonresponder status. The researchers also identified an association between nonresponder status and rs4680-A in COMT, a gene that has been associated with lower COMT enzymatic activity, chronic pain/fibromyalgia, and a "worrier" phenotype. Nonresponders also had a lower mean genetic risk score than responders. These genetic associations could help identify which patients would be most likely to benefit from anti-CGRP therapies.

Given that CGRP responsiveness may have a genetic component, it is possible that one of the contributors to the link between migraine and Parkinson's disease could lie in patients' genetic predisposition to CGRP activity. Yet, the association between these two common conditions is not thoroughly established, and the role of CGRP in the pathogenesis of Parkinson's disease is not fully validated. Nevertheless, the new developments in treatments that modify CGRP activity could have implications beyond migraine.

Additional References

1. Alexoudi A, Deftereos S. CGRP antagonists: side effects and potential Parkinson's disease development. Headache. 2020;60:789-790. doi: 10.1111/head.13770 Source

2. Blumenfeld A, Durham PL, Feoktistov A, et al. Hypervigilance, allostatic load, and migraine prevention: Antibodies to CGRP or receptor. Neurol Ther. 2021;10:469-497. doi:10.1007/s40120-021-00250-7 Source

The authors of a study published in the December 2023 issue of the Scandinavian Journal of Gastroenterology analyzed data to examine the potential link between gut microbiota and migraine. According to the statistical analysis, the researchers found that "a greater abundance of genus Lactobacillus was associated with a higher risk of migraine and a higher abundance of family Prevotellaceae was related to a decreased risk of migraine." Furthermore, they noted that these gut microbial patterns could be due to a genetic predisposition. The authors suggested that stool sampling could potentially be helpful in the diagnosis of migraine, and that measures to modify gut microbiota in the context of migraine therapy could be identified with future research.

While it is not clear whether migraine is a cause or effect of these alterations, or whether there is another confounding variable, the idea of using diet as a means of reducing migraine risk would be appealing for many patients. This offers hope, but it also leaves a window open for exaggeration and excessive reliance on certain foods or supplements before reliable links are established.

Further examining the genetic factors that might play a role in migraine, a large Korean data analysis published in the December 2023 issue of Epidemiology and Health described a link between migraine and Parkinson's disease. The researchers included 214,193 patients with migraine and 5,879,711 individuals without migraine. According to the statistical analysis, the patients who had migraine with aura showed a 1.35-fold higher risk for Parkinson's disease than individuals without migraine. However, the researchers did not note a statistically significant difference between the risk for Parkinson's disease among patients who had migraine without aura and individuals without migraine.

They also examined other factors, and noted that among individuals with migraine, those who had preexisting dyslipidemia had a higher risk for Parkinson's disease than those who did not have dyslipidemia. Other factors that were not correlated with an association between migraine and Parkinson's disease included cardiovascular risk factors, hypertension, diabetes, smoking status, and high body mass index.

The study authors noted that factors associated with the activity of calcitonin gene-related peptide (CGRP), which is known to play a significant role in the pathophysiology of migraine, could play a role in the link between migraine and Parkinson's disease. They pointed to previous studies that found evidence of elevated CGRP levels in the cerebrospinal fluid of patients with Parkinson's disease as possible evidence of a pathophysiologic link.

An earlier commentary, published in the April 2020 issue of Headache, suggested an implication of CGRP antagonists in the development of neurodegenerative disorders such as Parkinson's disease. The commentary authors noted that previous research correlated midlife migraine to late-life parkinsonism, suggesting a conceivable common pathology, which could include a genetic or environmental predisposition.^[1] They also noted that studies suggest a possible link between CGRP and multiple system atrophy, a parkinsonian disorder.^[1] They considered the possibility that one of the ways that CGRP could contribute to these disorders is through its role in the recruitment of inflammatory mediators, which can alter the function of nicotinic receptors in the dopaminergic system in Parkinson's disease pathogenesis.^[2]

Recent research published in the December 2023 issue of Headache suggests that CGRP responsiveness in migraine therapy could be mediated by genetics. The study included 198 patients who had been typed for genes involved in CGRP signaling or pharmacologic response and were given genetic and polygenic risk scores. Responders were defined as patients who experienced ≥ 50% reduction in migraine days per month at 5.7-month follow-up.

The analysis revealed an association between nonresponder status and rs12615320-G in RAMP1, a gene that encodes a component of high-affinity CGRP receptors, which increased the risk for nonresponder status. The researchers also identified an association between nonresponder status and rs4680-A in COMT, a gene that has been associated with lower COMT enzymatic activity, chronic pain/fibromyalgia, and a "worrier" phenotype. Nonresponders also had a lower mean genetic risk score than responders. These genetic associations could help identify which patients would be most likely to benefit from anti-CGRP therapies.

Given that CGRP responsiveness may have a genetic component, it is possible that one of the contributors to the link between migraine and Parkinson's disease could lie in patients' genetic predisposition to CGRP activity. Yet, the association between these two common conditions is not thoroughly established, and the role of CGRP in the pathogenesis of Parkinson's disease is not fully validated. Nevertheless, the new developments in treatments that modify CGRP activity could have implications beyond migraine.

Additional References

1. Alexoudi A, Deftereos S. CGRP antagonists: side effects and potential Parkinson's disease development. Headache. 2020;60:789-790. doi: 10.1111/head.13770 Source

2. Blumenfeld A, Durham PL, Feoktistov A, et al. Hypervigilance, allostatic load, and migraine prevention: Antibodies to CGRP or receptor. Neurol Ther. 2021;10:469-497. doi:10.1007/s40120-021-00250-7 Source

The authors of a study published in the December 2023 issue of the Scandinavian Journal of Gastroenterology analyzed data to examine the potential link between gut microbiota and migraine. According to the statistical analysis, the researchers found that "a greater abundance of genus Lactobacillus was associated with a higher risk of migraine and a higher abundance of family Prevotellaceae was related to a decreased risk of migraine." Furthermore, they noted that these gut microbial patterns could be due to a genetic predisposition. The authors suggested that stool sampling could potentially be helpful in the diagnosis of migraine, and that measures to modify gut microbiota in the context of migraine therapy could be identified with future research.

While it is not clear whether migraine is a cause or effect of these alterations, or whether there is another confounding variable, the idea of using diet as a means of reducing migraine risk would be appealing for many patients. This offers hope, but it also leaves a window open for exaggeration and excessive reliance on certain foods or supplements before reliable links are established.

Further examining the genetic factors that might play a role in migraine, a large Korean data analysis published in the December 2023 issue of Epidemiology and Health described a link between migraine and Parkinson's disease. The researchers included 214,193 patients with migraine and 5,879,711 individuals without migraine. According to the statistical analysis, the patients who had migraine with aura showed a 1.35-fold higher risk for Parkinson's disease than individuals without migraine. However, the researchers did not note a statistically significant difference between the risk for Parkinson's disease among patients who had migraine without aura and individuals without migraine.

They also examined other factors, and noted that among individuals with migraine, those who had preexisting dyslipidemia had a higher risk for Parkinson's disease than those who did not have dyslipidemia. Other factors that were not correlated with an association between migraine and Parkinson's disease included cardiovascular risk factors, hypertension, diabetes, smoking status, and high body mass index.

The study authors noted that factors associated with the activity of calcitonin gene-related peptide (CGRP), which is known to play a significant role in the pathophysiology of migraine, could play a role in the link between migraine and Parkinson's disease. They pointed to previous studies that found evidence of elevated CGRP levels in the cerebrospinal fluid of patients with Parkinson's disease as possible evidence of a pathophysiologic link.

An earlier commentary, published in the April 2020 issue of Headache, suggested an implication of CGRP antagonists in the development of neurodegenerative disorders such as Parkinson's disease. The commentary authors noted that previous research correlated midlife migraine to late-life parkinsonism, suggesting a conceivable common pathology, which could include a genetic or environmental predisposition.^[1] They also noted that studies suggest a possible link between CGRP and multiple system atrophy, a parkinsonian disorder.^[1] They considered the possibility that one of the ways that CGRP could contribute to these disorders is through its role in the recruitment of inflammatory mediators, which can alter the function of nicotinic receptors in the dopaminergic system in Parkinson's disease pathogenesis.^[2]

Recent research published in the December 2023 issue of Headache suggests that CGRP responsiveness in migraine therapy could be mediated by genetics. The study included 198 patients who had been typed for genes involved in CGRP signaling or pharmacologic response and were given genetic and polygenic risk scores. Responders were defined as patients who experienced ≥ 50% reduction in migraine days per month at 5.7-month follow-up.

The analysis revealed an association between nonresponder status and rs12615320-G in RAMP1, a gene that encodes a component of high-affinity CGRP receptors, which increased the risk for nonresponder status. The researchers also identified an association between nonresponder status and rs4680-A in COMT, a gene that has been associated with lower COMT enzymatic activity, chronic pain/fibromyalgia, and a "worrier" phenotype. Nonresponders also had a lower mean genetic risk score than responders. These genetic associations could help identify which patients would be most likely to benefit from anti-CGRP therapies.

Given that CGRP responsiveness may have a genetic component, it is possible that one of the contributors to the link between migraine and Parkinson's disease could lie in patients' genetic predisposition to CGRP activity. Yet, the association between these two common conditions is not thoroughly established, and the role of CGRP in the pathogenesis of Parkinson's disease is not fully validated. Nevertheless, the new developments in treatments that modify CGRP activity could have implications beyond migraine.

Additional References

1. Alexoudi A, Deftereos S. CGRP antagonists: side effects and potential Parkinson's disease development. Headache. 2020;60:789-790. doi: 10.1111/head.13770 Source

2. Blumenfeld A, Durham PL, Feoktistov A, et al. Hypervigilance, allostatic load, and migraine prevention: Antibodies to CGRP or receptor. Neurol Ther. 2021;10:469-497. doi:10.1007/s40120-021-00250-7 Source

The National Rosacea Society (NRS) has launched a new Seal of Acceptance program to help patients and physicians identify skin care and cosmetic products that are appropriate for sensitive and redness-prone skin in people who have rosacea, according to a press release from the NRS.

The seal is meant to be a resource to easily identify skin care products and cosmetic products that have been evaluated as unlikely to cause rosacea flares or skin irritation, according to the press release.

Surveys conducted by the NRS indicate that 92% of rosacea patients report burning, stinging, or itching on their skin, 66% identified specific skin products as triggers for their symptoms, and 84% were “very interested” in skin care guidance.

National Rosacea Society

Patients and clinicians can find a searchable list of currently approved products in the Seal of Acceptance section of the NRS website. New skin care and cosmetic products will be added to the list of those with the Seal of Acceptance on an ongoing basis.

Products under consideration to earn the Seal of Acceptance must be free of ingredients that can cause skin barrier disruption, flushing, burning, itching, or other unwanted neurosensory stimulation, according to the press release.

Each accepted product also must pass clinical testing to confirm safety and low risk for irritation and sensitization for individuals with rosacea. Applications for the Seal of Acceptance are reviewed anonymously by an independent panel of dermatologists. The NRS created the program under the guidance of Zoe D. Draelos, MD, a clinical and research dermatologist in High Point, North Carolina, who also serves on the NRS board of directors.

More information about products carrying the seal and how companies can apply to have their products considered to carry the seal is available at rosacea.org/seal-of-acceptance/.

The National Rosacea Society (NRS) has launched a new Seal of Acceptance program to help patients and physicians identify skin care and cosmetic products that are appropriate for sensitive and redness-prone skin in people who have rosacea, according to a press release from the NRS.

The seal is meant to be a resource to easily identify skin care products and cosmetic products that have been evaluated as unlikely to cause rosacea flares or skin irritation, according to the press release.

Surveys conducted by the NRS indicate that 92% of rosacea patients report burning, stinging, or itching on their skin, 66% identified specific skin products as triggers for their symptoms, and 84% were “very interested” in skin care guidance.

National Rosacea Society

Patients and clinicians can find a searchable list of currently approved products in the Seal of Acceptance section of the NRS website. New skin care and cosmetic products will be added to the list of those with the Seal of Acceptance on an ongoing basis.

Products under consideration to earn the Seal of Acceptance must be free of ingredients that can cause skin barrier disruption, flushing, burning, itching, or other unwanted neurosensory stimulation, according to the press release.

Each accepted product also must pass clinical testing to confirm safety and low risk for irritation and sensitization for individuals with rosacea. Applications for the Seal of Acceptance are reviewed anonymously by an independent panel of dermatologists. The NRS created the program under the guidance of Zoe D. Draelos, MD, a clinical and research dermatologist in High Point, North Carolina, who also serves on the NRS board of directors.

More information about products carrying the seal and how companies can apply to have their products considered to carry the seal is available at rosacea.org/seal-of-acceptance/.

The National Rosacea Society (NRS) has launched a new Seal of Acceptance program to help patients and physicians identify skin care and cosmetic products that are appropriate for sensitive and redness-prone skin in people who have rosacea, according to a press release from the NRS.

The seal is meant to be a resource to easily identify skin care products and cosmetic products that have been evaluated as unlikely to cause rosacea flares or skin irritation, according to the press release.

Surveys conducted by the NRS indicate that 92% of rosacea patients report burning, stinging, or itching on their skin, 66% identified specific skin products as triggers for their symptoms, and 84% were “very interested” in skin care guidance.

National Rosacea Society

Patients and clinicians can find a searchable list of currently approved products in the Seal of Acceptance section of the NRS website. New skin care and cosmetic products will be added to the list of those with the Seal of Acceptance on an ongoing basis.

Products under consideration to earn the Seal of Acceptance must be free of ingredients that can cause skin barrier disruption, flushing, burning, itching, or other unwanted neurosensory stimulation, according to the press release.

Each accepted product also must pass clinical testing to confirm safety and low risk for irritation and sensitization for individuals with rosacea. Applications for the Seal of Acceptance are reviewed anonymously by an independent panel of dermatologists. The NRS created the program under the guidance of Zoe D. Draelos, MD, a clinical and research dermatologist in High Point, North Carolina, who also serves on the NRS board of directors.

More information about products carrying the seal and how companies can apply to have their products considered to carry the seal is available at rosacea.org/seal-of-acceptance/.

This transcript has been edited for clarity.

There’s never been anything like the revolution in the treatment of obesity that we are now living through. Historically, there’s always been calorie counting and diets. Now, after a burst of interest in gastric bypass surgery, we have the amazing world of injectables. We all have heard about Ozempic, Mounjaro, and Wegovy.

These are being used by millions of Americans at this point, some on prescription for conditions like diabetes and some to bring about weight loss in prediabetes, or in some instances — as is often seen on American television — weight control or weight loss by people who just want to look better. Celebrities getting behind these injectables has really powered an explosion of use.

There still are ethical issues out there for practitioners. For one thing, there are some forms of semaglutide, a key ingredient in some of these injectables, that are made by compounding pharmacies. They’re not the name-brand prescription injectables made by large companies. They’re brewed up, if you will, by a specialty pharmacy trying to mimic the ingredient.

What we’ve seen in recent weeks is an explosion of overdoses. When a person uses one of these compounding pharmacies, usually in association with a spa or sometimes online sales of weight loss injectables, they’re not always certain about how to dose themselves, how much to give, and what to take. They could misread the instructions. The more that it’s up to them to determine the dose, the more there’s risk for error. Reports show as much as 1500% increases in poisoning of people who took, instead of a 10th of a milliliter, 10 mL of these compounded versions of the injectable drugs.

Everybody needs to be alert, and not only for adverse events from the prescription injectables. It is important to track that, make sure that people aren’t getting into trouble, and have contact with the FDA if you have a patient who reports some kind of adverse event they attribute to injectables.

It’s important to realize that there’s this generic, cheaper path, but it’s a more dangerous path. People need to know this if they’re going to try that route. Doctors should be aware of it. People should be ready to call the poison control center number in their area to make sure that they know what to do if they overdose on this stuff.

My own inclination is to try to discourage its use. I think it’s still too dangerous to have people self-dosing with ingredients that really are not yet FDA approved in terms of knowing that they’ve been tested in clinical trials.

The other big issue, aside from this Wild West world outside of prescribed injectables, is what to say to people who are obese or trying to manage their weight. I think people need to know all their options. It’s pretty easy to just say, “Let’s put you on one of these injectables” and prescribe it. For one thing, they may not be able to get it; there’s such huge demand that there are some shortages out there.

People may be better off trying to manage weight with diet, calorie counting, or lifestyle changes. After all, you could stay on these drugs forever to maintain your weight, but it’s not cheap. We don’t really know the long-term consequences of decades-long use of these drugs.

I think people should hear their options and maybe try something less invasive to begin with. If that doesn’t work, then move on to the injectables. It isn’t so clear to me — given the cost, some of the unknowns of long-term use, and some of the dangers of people sneaking around and trying to get things cheaper on the side — that going straight to injectables is our best answer.

I do think doctors should talk about weight with their patients, carefully, with the patient’s consent. Make sure there’s no stigma. Make sure we’re not doing anything to raise anxiety as we talk about this condition. After all, it is seen as a disease.

Then, maybe enter your way gradually into interventions, seeing if lifestyle change is possible. It’s cheap and easier to implement: better diet, better exercise, or calorie counting. Some people succeed. When they don’t, we should move on, but realize that we’ve got the equivalent of a black market. We need to encourage patients, if they use injectable weight loss drugs, to tell doctors so that they can be on alert about the dangers and risks of overdose.

Dr. Caplan is Director, Division of Medical Ethics, New York University Langone Medical Center, New York City. He disclosed an unpaid position with Johnson & Johnson’s Panel for Compassionate Drug Use, and serves as a contributing author and advisor for Medscape.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

There’s never been anything like the revolution in the treatment of obesity that we are now living through. Historically, there’s always been calorie counting and diets. Now, after a burst of interest in gastric bypass surgery, we have the amazing world of injectables. We all have heard about Ozempic, Mounjaro, and Wegovy.

These are being used by millions of Americans at this point, some on prescription for conditions like diabetes and some to bring about weight loss in prediabetes, or in some instances — as is often seen on American television — weight control or weight loss by people who just want to look better. Celebrities getting behind these injectables has really powered an explosion of use.

There still are ethical issues out there for practitioners. For one thing, there are some forms of semaglutide, a key ingredient in some of these injectables, that are made by compounding pharmacies. They’re not the name-brand prescription injectables made by large companies. They’re brewed up, if you will, by a specialty pharmacy trying to mimic the ingredient.

What we’ve seen in recent weeks is an explosion of overdoses. When a person uses one of these compounding pharmacies, usually in association with a spa or sometimes online sales of weight loss injectables, they’re not always certain about how to dose themselves, how much to give, and what to take. They could misread the instructions. The more that it’s up to them to determine the dose, the more there’s risk for error. Reports show as much as 1500% increases in poisoning of people who took, instead of a 10th of a milliliter, 10 mL of these compounded versions of the injectable drugs.

Everybody needs to be alert, and not only for adverse events from the prescription injectables. It is important to track that, make sure that people aren’t getting into trouble, and have contact with the FDA if you have a patient who reports some kind of adverse event they attribute to injectables.

It’s important to realize that there’s this generic, cheaper path, but it’s a more dangerous path. People need to know this if they’re going to try that route. Doctors should be aware of it. People should be ready to call the poison control center number in their area to make sure that they know what to do if they overdose on this stuff.

My own inclination is to try to discourage its use. I think it’s still too dangerous to have people self-dosing with ingredients that really are not yet FDA approved in terms of knowing that they’ve been tested in clinical trials.

The other big issue, aside from this Wild West world outside of prescribed injectables, is what to say to people who are obese or trying to manage their weight. I think people need to know all their options. It’s pretty easy to just say, “Let’s put you on one of these injectables” and prescribe it. For one thing, they may not be able to get it; there’s such huge demand that there are some shortages out there.

People may be better off trying to manage weight with diet, calorie counting, or lifestyle changes. After all, you could stay on these drugs forever to maintain your weight, but it’s not cheap. We don’t really know the long-term consequences of decades-long use of these drugs.

I think people should hear their options and maybe try something less invasive to begin with. If that doesn’t work, then move on to the injectables. It isn’t so clear to me — given the cost, some of the unknowns of long-term use, and some of the dangers of people sneaking around and trying to get things cheaper on the side — that going straight to injectables is our best answer.

I do think doctors should talk about weight with their patients, carefully, with the patient’s consent. Make sure there’s no stigma. Make sure we’re not doing anything to raise anxiety as we talk about this condition. After all, it is seen as a disease.

Then, maybe enter your way gradually into interventions, seeing if lifestyle change is possible. It’s cheap and easier to implement: better diet, better exercise, or calorie counting. Some people succeed. When they don’t, we should move on, but realize that we’ve got the equivalent of a black market. We need to encourage patients, if they use injectable weight loss drugs, to tell doctors so that they can be on alert about the dangers and risks of overdose.

Dr. Caplan is Director, Division of Medical Ethics, New York University Langone Medical Center, New York City. He disclosed an unpaid position with Johnson & Johnson’s Panel for Compassionate Drug Use, and serves as a contributing author and advisor for Medscape.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

There’s never been anything like the revolution in the treatment of obesity that we are now living through. Historically, there’s always been calorie counting and diets. Now, after a burst of interest in gastric bypass surgery, we have the amazing world of injectables. We all have heard about Ozempic, Mounjaro, and Wegovy.

These are being used by millions of Americans at this point, some on prescription for conditions like diabetes and some to bring about weight loss in prediabetes, or in some instances — as is often seen on American television — weight control or weight loss by people who just want to look better. Celebrities getting behind these injectables has really powered an explosion of use.

There still are ethical issues out there for practitioners. For one thing, there are some forms of semaglutide, a key ingredient in some of these injectables, that are made by compounding pharmacies. They’re not the name-brand prescription injectables made by large companies. They’re brewed up, if you will, by a specialty pharmacy trying to mimic the ingredient.

What we’ve seen in recent weeks is an explosion of overdoses. When a person uses one of these compounding pharmacies, usually in association with a spa or sometimes online sales of weight loss injectables, they’re not always certain about how to dose themselves, how much to give, and what to take. They could misread the instructions. The more that it’s up to them to determine the dose, the more there’s risk for error. Reports show as much as 1500% increases in poisoning of people who took, instead of a 10th of a milliliter, 10 mL of these compounded versions of the injectable drugs.

Everybody needs to be alert, and not only for adverse events from the prescription injectables. It is important to track that, make sure that people aren’t getting into trouble, and have contact with the FDA if you have a patient who reports some kind of adverse event they attribute to injectables.

It’s important to realize that there’s this generic, cheaper path, but it’s a more dangerous path. People need to know this if they’re going to try that route. Doctors should be aware of it. People should be ready to call the poison control center number in their area to make sure that they know what to do if they overdose on this stuff.

My own inclination is to try to discourage its use. I think it’s still too dangerous to have people self-dosing with ingredients that really are not yet FDA approved in terms of knowing that they’ve been tested in clinical trials.

The other big issue, aside from this Wild West world outside of prescribed injectables, is what to say to people who are obese or trying to manage their weight. I think people need to know all their options. It’s pretty easy to just say, “Let’s put you on one of these injectables” and prescribe it. For one thing, they may not be able to get it; there’s such huge demand that there are some shortages out there.

People may be better off trying to manage weight with diet, calorie counting, or lifestyle changes. After all, you could stay on these drugs forever to maintain your weight, but it’s not cheap. We don’t really know the long-term consequences of decades-long use of these drugs.

I think people should hear their options and maybe try something less invasive to begin with. If that doesn’t work, then move on to the injectables. It isn’t so clear to me — given the cost, some of the unknowns of long-term use, and some of the dangers of people sneaking around and trying to get things cheaper on the side — that going straight to injectables is our best answer.

I do think doctors should talk about weight with their patients, carefully, with the patient’s consent. Make sure there’s no stigma. Make sure we’re not doing anything to raise anxiety as we talk about this condition. After all, it is seen as a disease.

Then, maybe enter your way gradually into interventions, seeing if lifestyle change is possible. It’s cheap and easier to implement: better diet, better exercise, or calorie counting. Some people succeed. When they don’t, we should move on, but realize that we’ve got the equivalent of a black market. We need to encourage patients, if they use injectable weight loss drugs, to tell doctors so that they can be on alert about the dangers and risks of overdose.

Dr. Caplan is Director, Division of Medical Ethics, New York University Langone Medical Center, New York City. He disclosed an unpaid position with Johnson & Johnson’s Panel for Compassionate Drug Use, and serves as a contributing author and advisor for Medscape.

A version of this article appeared on Medscape.com.

It’s 2 a.m. and my phone wakes me up with a start. My patient, Christine Z*, is vomiting uncontrollably, and Dr Google has diagnosed her with acute pancreatitis from semaglutide (Wegovy). Ten hours, several imaging studies, one blood draw, and many bags of fluids later, the verdict is in: Christine is alarmingly constipated. In fact, her entire large intestine is packed to the brim with stool. In residency, we called this diagnosis FOS, and I’ll leave it to your imagination to figure out what it stands for.

In retrospect, Christine mentions that upon raising her Wegovy dose, her bowel movements had become increasingly smaller and infrequent. This begs the question: How can practitioners help offset side effects through dietary changes, and while we are at it, what other dietary advice is prudent at treatment onset?

Proper nutrition always starts with drinking copious amounts of water. In general, I recommend a minimum of 64 ounces of water daily in patients taking incretins such as semaglutide (Wegovy for weight loss, Ozempic and Rybelsus for type 2 diabetes) or tirzepatide (Zepbound for weight loss, Mounjaro for type 2 diabetes). While these medications don’t directly dehydrate patients, they can increase the risk for dehydration due to severe nausea. Drinking copious amounts of water can prevent dehydration, preserve kidney function, and minimize fatigue and dizziness. In addition, fluids help soften bowel movements, making them easier to pass.

Occasionally incretins make it so easy for patients to drop pounds that their eating patterns become sloppier — more sweets and simple carbohydrates. I recommend a realistic and low glycemic index meal plan. While no foods are strictly contraindicated, processed, high-sugar, and fatty foods are likely to worsen side effects like nausea and gastrointestinal distress. Similarly, alcohol not only worsens nausea, but it’s also likely to exacerbate reflux by relaxing the sphincter that separates the stomach from the esophagus.

The next most important dietary advice is consuming sufficient fiber. In the majority of patients, increasing fiber intake relieves constipation. There are two types of fiber: soluble and insoluble. In practical terms, most fiber-rich foods contain a mixture of these two types. The general recommendation is 38 g/d for men and 25 g/d for women. The caveat to this advice is that a minority of patients, such as those with irritable bowel syndrome, may develop worsening constipation with increasing fiber.

To minimize side effects, some patients find it useful to eat five small meals throughout the day rather than three larger meals. In addition, I recommend eating slowly and stopping before the point of satiety. Finally, because weight loss of any kind is inevitably associated with muscle loss, I stress the importance of adequate protein. In general, I advise 25-30 g of protein per meal.

Christine eventually restarted her Wegovy after recovering from her grueling night in the emergency room. As this was her second go-around on Wegovy, she dug out my “guide to preventing side effects of incretins” and followed it to a T. So far, she’s feeling great.

*The patient’s name has been changed.
 

A version of this article appeared on Medscape.com.

It’s 2 a.m. and my phone wakes me up with a start. My patient, Christine Z*, is vomiting uncontrollably, and Dr Google has diagnosed her with acute pancreatitis from semaglutide (Wegovy). Ten hours, several imaging studies, one blood draw, and many bags of fluids later, the verdict is in: Christine is alarmingly constipated. In fact, her entire large intestine is packed to the brim with stool. In residency, we called this diagnosis FOS, and I’ll leave it to your imagination to figure out what it stands for.

In retrospect, Christine mentions that upon raising her Wegovy dose, her bowel movements had become increasingly smaller and infrequent. This begs the question: How can practitioners help offset side effects through dietary changes, and while we are at it, what other dietary advice is prudent at treatment onset?

Proper nutrition always starts with drinking copious amounts of water. In general, I recommend a minimum of 64 ounces of water daily in patients taking incretins such as semaglutide (Wegovy for weight loss, Ozempic and Rybelsus for type 2 diabetes) or tirzepatide (Zepbound for weight loss, Mounjaro for type 2 diabetes). While these medications don’t directly dehydrate patients, they can increase the risk for dehydration due to severe nausea. Drinking copious amounts of water can prevent dehydration, preserve kidney function, and minimize fatigue and dizziness. In addition, fluids help soften bowel movements, making them easier to pass.

Occasionally incretins make it so easy for patients to drop pounds that their eating patterns become sloppier — more sweets and simple carbohydrates. I recommend a realistic and low glycemic index meal plan. While no foods are strictly contraindicated, processed, high-sugar, and fatty foods are likely to worsen side effects like nausea and gastrointestinal distress. Similarly, alcohol not only worsens nausea, but it’s also likely to exacerbate reflux by relaxing the sphincter that separates the stomach from the esophagus.

The next most important dietary advice is consuming sufficient fiber. In the majority of patients, increasing fiber intake relieves constipation. There are two types of fiber: soluble and insoluble. In practical terms, most fiber-rich foods contain a mixture of these two types. The general recommendation is 38 g/d for men and 25 g/d for women. The caveat to this advice is that a minority of patients, such as those with irritable bowel syndrome, may develop worsening constipation with increasing fiber.

To minimize side effects, some patients find it useful to eat five small meals throughout the day rather than three larger meals. In addition, I recommend eating slowly and stopping before the point of satiety. Finally, because weight loss of any kind is inevitably associated with muscle loss, I stress the importance of adequate protein. In general, I advise 25-30 g of protein per meal.

Christine eventually restarted her Wegovy after recovering from her grueling night in the emergency room. As this was her second go-around on Wegovy, she dug out my “guide to preventing side effects of incretins” and followed it to a T. So far, she’s feeling great.

*The patient’s name has been changed.
 

A version of this article appeared on Medscape.com.

It’s 2 a.m. and my phone wakes me up with a start. My patient, Christine Z*, is vomiting uncontrollably, and Dr Google has diagnosed her with acute pancreatitis from semaglutide (Wegovy). Ten hours, several imaging studies, one blood draw, and many bags of fluids later, the verdict is in: Christine is alarmingly constipated. In fact, her entire large intestine is packed to the brim with stool. In residency, we called this diagnosis FOS, and I’ll leave it to your imagination to figure out what it stands for.

In retrospect, Christine mentions that upon raising her Wegovy dose, her bowel movements had become increasingly smaller and infrequent. This begs the question: How can practitioners help offset side effects through dietary changes, and while we are at it, what other dietary advice is prudent at treatment onset?

Proper nutrition always starts with drinking copious amounts of water. In general, I recommend a minimum of 64 ounces of water daily in patients taking incretins such as semaglutide (Wegovy for weight loss, Ozempic and Rybelsus for type 2 diabetes) or tirzepatide (Zepbound for weight loss, Mounjaro for type 2 diabetes). While these medications don’t directly dehydrate patients, they can increase the risk for dehydration due to severe nausea. Drinking copious amounts of water can prevent dehydration, preserve kidney function, and minimize fatigue and dizziness. In addition, fluids help soften bowel movements, making them easier to pass.

Occasionally incretins make it so easy for patients to drop pounds that their eating patterns become sloppier — more sweets and simple carbohydrates. I recommend a realistic and low glycemic index meal plan. While no foods are strictly contraindicated, processed, high-sugar, and fatty foods are likely to worsen side effects like nausea and gastrointestinal distress. Similarly, alcohol not only worsens nausea, but it’s also likely to exacerbate reflux by relaxing the sphincter that separates the stomach from the esophagus.

The next most important dietary advice is consuming sufficient fiber. In the majority of patients, increasing fiber intake relieves constipation. There are two types of fiber: soluble and insoluble. In practical terms, most fiber-rich foods contain a mixture of these two types. The general recommendation is 38 g/d for men and 25 g/d for women. The caveat to this advice is that a minority of patients, such as those with irritable bowel syndrome, may develop worsening constipation with increasing fiber.

To minimize side effects, some patients find it useful to eat five small meals throughout the day rather than three larger meals. In addition, I recommend eating slowly and stopping before the point of satiety. Finally, because weight loss of any kind is inevitably associated with muscle loss, I stress the importance of adequate protein. In general, I advise 25-30 g of protein per meal.

Christine eventually restarted her Wegovy after recovering from her grueling night in the emergency room. As this was her second go-around on Wegovy, she dug out my “guide to preventing side effects of incretins” and followed it to a T. So far, she’s feeling great.

*The patient’s name has been changed.
 

A version of this article appeared on Medscape.com.

The United States Medical Licensing Examination (USMLE) program is invalidating scores attained by some examinees after an investigation revealed a pattern of anomalous exam performance associated with test-takers from Nepal. 

In a January 31 announcement, the USMLE program said that officials are in the process of notifying examinees with results in question and that the examinees will be required to take validation exams. The program did not offer further details about its investigation or how the questionable performance was identified. 

“The USMLE program regularly monitors and analyzes examinees’ test performances for unusual score patterns or variations, and other information that could raise questions about the validity of an examinee’s results,” the program said in a statement. “Highly irregular patterns can be indicative of prior unauthorized access to secure exam content.”

Some medical graduates say the action against students cheating on the USMLE is long overdue. 

The selling and buying of USMLE questions online have become rampant in recent years, particularly by groups within the international medical graduate (IMG) community, according to multiple IMGs who shared their concerns with this news organization. Sellers operate under pseudonyms across social media platforms and charge anywhere from $300 to $2000 for questions, Medscape research shows. 

Facebook posts often advertise questions for sale, said Saqib Gul, MD, an IMG from Pakistan who has voiced concerns about the practice on social media. 

“People make up fake profiles and tell others to [direct message] them for recalls,” he told this news organization. “There was a dedicated Facebook page that was doing this. In other cases, a couple of friends that took the exam remember a certain number of questions and write them down after the test.”

Ahmad Ozair, MD, an IMG from Lucknow, Uttar Pradesh, India, said that he has come across many groups online sharing or selling USMLE recalls. He first became suspicious when he saw several students, all from a few medical schools in Nepal, posting on social media about scoring in the 270 and 280-plus range. 

“The statistical probability that you would have three or more candidates in the same year, scoring in the 99th percentile worldwide, belonging to a small geographical area is extremely low.” 

Dr. Ozair, who now is studying public health at Johns Hopkins University in Baltimore, said that the issue is important for “all stakeholders” who care about patient safety: “Would you want a doctor who has cheated on the medical licensing exam to take care of you?” 

In an interview, USMLE program spokesman Joe Knickrehm said that the program relies on multiple processes to detect and respond to claims that exam integrity is being compromised. The process includes monitoring performance data, an anonymous tip line for reporting suspicious behavior, and a thorough investigative process. 

“The USMLE program regularly monitors social media channels for comments relating to exam security and irregular behavior and will initiate an investigation if warranted,” Mr. Knickrehm told this news organization. “ The covert nature of this activity does not lend itself to a definitive statement regarding whether the problem has increased or decreased in recent years.” 

Mr. Knickrehm said that the program’s STOPit app allows people to report suspicious behavior electronically to the USMLE program. Since its launch in 2021, the program has received more than 80 tips per year through the app, according to Mr. Knickrehm. Security violations are investigated by USMLE staff and reviewed by the USMLE Committee for Individualized Review (CIR). Anyone found to have engaged in irregular behavior by the CIR for activities undermining exam integrity are typically barred from access to the USMLE for multiple years. 
 

How Easy Is It to Buy Recalls?

Two years ago, Dr B was approached by a former study partner who had just completed Step 2 of the USMLE. She asked whether Dr B wanted to buy recalled questions to help her pass. 

“She paid this guy almost $2000 for recalls and told me if I pay this money, he’ll give me the recalls,” said Dr B, who asked to remain anonymous for fear of being associated with students cheating on the USMLE. “I told her I was not interested, and she said the guy would lower the price. I broke contact with her.”

Dr B, an IMG from Pakistan, was appalled. But she said that the episode was not the first time she has come across groups selling USMLE recalls or heard peers brag about having access to exam content. 

“I am baffled at how many [groups] post on social media and brazenly advertise their ‘services,’” she told this news organization. “No one arrests them, their customers go on to score abnormally high on the boards, making it unachievable for people who take the honest route, plus giving IMGs a bad rep.” 

Groups offering recalls are easily findable on sites such as Telegram and Signal. Telegram is a cloud-based messaging app that focuses on security, and Signal is an encrypted messaging service. 

The website recallmastery.com purports to offer a range of USMLE recall packages, from a free, unsorted version to Step 1 and Step 2 packages that include “fresh updates,” and sections with “mostly repeated topics. Prices range from the free version to the $799 VIP package. 

Another site called MedPox.com boasts 2024 Step 2 recalls, advertising “ actual exam questions to get HIGH scores.” The website’s owner states that the recalls were collected “by my friends,” and to message the them to be added to the “recalls group.”

A reporter was able to easily download a free version of alleged USMLE questions and answers from recallmastery.com. The document was a combination of typed and handwritten notes about medical questions, with red circles around recalled answers. 

J. Bryan Carmody, MD, who blogs about medical education, reviewed a copy of the document. He said that the content appeared “credible” and was in fact recalled USMLE questions. However, the extent of which the question stem was recalled was incomplete at best, and there was little production value to the document, said Dr. Carmody, a nephrologist and associate professor of pediatrics at the Eastern Virgina Medical School in Norfolk. 

The person selling the recall packages states on the website that the free version is not organized or sorted, but it allows viewers to “see how this works before paying for premium recalls.” 

Mr. Knickrehm said that the program could not comment on the document, but that “whenever the USMLE program receives or locates information about a potential security violation, we investigate and take necessary action.” 

When asked about the specific websites noted above, Knickrehm said that the program routinely monitors a wide array of websites, message boards, and chat rooms for USMLE-related materials. Though many sites advertise having USMLE recalls for sale, it’s more likely they are selling non-USMLE content, he said. 

Using past content to cheat on medical exams is an old problem. In 2010, for example, the American Board of Internal Medicine suspended 139 physicians after they were caught cheating on the board exams. The scandal involved a vast cheating ring that included physicians memorizing questions and reproducing them after the tests. The board later sued a gastroenterologist for her part in the scandal. 

In 2012, a CNN investigation exposed doctors who were memorizing test questions and creating sophisticated recall banks to cheat on radiology boards. The Association of American Medical Colleges sued a medical student in 2017 for attempting to secretly record content on the MCAT using spyglasses. 

In recent years, Dr. Carmody said that he has received multiple messages and screenshots from concerned students and residents who were offered or encountered recalls. 

“One thing that’s unclear is how legitimate the claims are,” he said. “Many of these recalls may be faulty or outdated. It could be someone who took the exam yesterday and has a photographic memory or it could be some sparsely recalled or mis-recalled information. Unless you’re willing to pay these people, you can’t inspect the quality, or even if you did, you wouldn’t know if the information was current or not.”
 

‘As an IMG, There Is So Much at Stake’

Whether recall sellers — and those buying them — are more frequently IMGs has fostered heated debate on social media. 

On a Reddit thread devoted to IMG issues, posters expressed frustration about being bombarded with recall advertisements and unwanted messages about buying USMLE questions while trying to find study materials. One poster called the practices a “huge slap to all those IMGs who are struggling day and night, just to get a good score.”

In an X thread about the same subject, however, some self-described IMGs took offense to claims that IMGs might score higher because they have access to recalls. The allegations are “incendiary” and “malign hardworking IMGs,” posters wrote.

When Dr. Gul spoke out online about the “biopsy” culture, he received multiple private messages from fellow IMGs telling him to remove his comments, he said. 

“I received a lot of backlash on social media,” he told this news organization. “Some IMGs asked me to take down my posts because they thought I was making IMGs look bad, and it might prompt authorities to take action or shut down international examination centers for IMGs.”

Most of the IMGs who spoke to this news organization were afraid to be publicly identified. Several IMG advocates and IMG associations contacted for the story did not respond. One medical education expert said that his institution advised him to “steer clear” of commenting because the issue was “controversial.” 

“As an IMG, there is so much at stake,” Dr B said. “Any association with shady operations like these is an absolute suicide. I’m personally afraid of any repercussions of the sort.”

USMLE officials declined to comment on whether the buying or selling of recalls appears to be more prevalent among the IMG community, saying it is “difficult to generalize this behavior as ‘prevalent’ simply due to the clandestine nature of this activity.”
 

Cheat-Proofing the USMLE

The USMLE program has taken several steps intended to prevent cheating, but more needs to be done, medical education advocates say. 

For example, Dr. Carmody called the recent change in the attempt limit for taking USMLE exams from six to four times a good move. 

“The reality is, if you’re taking a USMLE exam five-plus times, you’re far more likely to be memorizing questions and selling them for shady test prep operations than you are to be legitimately pursuing U.S. residency training or licensure,” he wrote on X. 

The 2022 move to make USMLE Step 1 pass or fail is another positive change, said Dr. Gul, who added that US programs should also put less weight on test scores and focus more on clinical experience. 

“Many programs in the US prioritize scores rather than clinical experiences in home countries,” he said. “If program directors would remove these criteria, probably the cheating practices would stop. Clinical practice matters. When a doctor gets matched, they have to be good at seeing and treating patients, not just good at sitting in front of a screen and taking an exam.”

Turning over questions more rapidly would help curb the practices, Dr. Carmody said. Another strategy is using math techniques to identify unusual deviations that suggest cheating, he said. 

A blueprint for the strategy was created after a cheating scandal involving Canada’s Medical Council of Canada Qualifying Examination (MCCQE) in 2004. After learning which questions were circulated, MCCQE administrators evaluated exams by comparing answers of compromised questions with the answers of noncompromised questions. 

“For a person who was not cheating, the error of performance should be pretty similar on those two groups of questions,” Dr. Carmody said. “But if you were given the questions in advance, you might have very poor performance on questions that had not been compromised, and very high performance on those that had been compromised. That disparity is very unlikely to occur just by chance alone.” 

Based on his research, Dr. Ozair is working on an academic review paper about cheating on the USMLE and on the Medical Council of Canada Qualification Examination. He said that he hopes the paper will raise more awareness about the problem and drive more action. 

He and others interviewed for this story shared that the websites they’ve reported to the USMLE program are still active and offering recalls to buyers. 

“Even if they are not actually offering something tangible or true, appearance matters,” Dr. Ozair said. “I think it’s worth the USMLE sending cease and desist letters and getting these websites taken down. This would restore faith in the process and underscore that this issue is being taken seriously.”
 

A version of this article appeared on Medscape.com.

The United States Medical Licensing Examination (USMLE) program is invalidating scores attained by some examinees after an investigation revealed a pattern of anomalous exam performance associated with test-takers from Nepal. 

In a January 31 announcement, the USMLE program said that officials are in the process of notifying examinees with results in question and that the examinees will be required to take validation exams. The program did not offer further details about its investigation or how the questionable performance was identified. 

“The USMLE program regularly monitors and analyzes examinees’ test performances for unusual score patterns or variations, and other information that could raise questions about the validity of an examinee’s results,” the program said in a statement. “Highly irregular patterns can be indicative of prior unauthorized access to secure exam content.”

Some medical graduates say the action against students cheating on the USMLE is long overdue. 

The selling and buying of USMLE questions online have become rampant in recent years, particularly by groups within the international medical graduate (IMG) community, according to multiple IMGs who shared their concerns with this news organization. Sellers operate under pseudonyms across social media platforms and charge anywhere from $300 to $2000 for questions, Medscape research shows. 

Facebook posts often advertise questions for sale, said Saqib Gul, MD, an IMG from Pakistan who has voiced concerns about the practice on social media. 

“People make up fake profiles and tell others to [direct message] them for recalls,” he told this news organization. “There was a dedicated Facebook page that was doing this. In other cases, a couple of friends that took the exam remember a certain number of questions and write them down after the test.”

Ahmad Ozair, MD, an IMG from Lucknow, Uttar Pradesh, India, said that he has come across many groups online sharing or selling USMLE recalls. He first became suspicious when he saw several students, all from a few medical schools in Nepal, posting on social media about scoring in the 270 and 280-plus range. 

“The statistical probability that you would have three or more candidates in the same year, scoring in the 99th percentile worldwide, belonging to a small geographical area is extremely low.” 

Dr. Ozair, who now is studying public health at Johns Hopkins University in Baltimore, said that the issue is important for “all stakeholders” who care about patient safety: “Would you want a doctor who has cheated on the medical licensing exam to take care of you?” 

In an interview, USMLE program spokesman Joe Knickrehm said that the program relies on multiple processes to detect and respond to claims that exam integrity is being compromised. The process includes monitoring performance data, an anonymous tip line for reporting suspicious behavior, and a thorough investigative process. 

“The USMLE program regularly monitors social media channels for comments relating to exam security and irregular behavior and will initiate an investigation if warranted,” Mr. Knickrehm told this news organization. “ The covert nature of this activity does not lend itself to a definitive statement regarding whether the problem has increased or decreased in recent years.” 

Mr. Knickrehm said that the program’s STOPit app allows people to report suspicious behavior electronically to the USMLE program. Since its launch in 2021, the program has received more than 80 tips per year through the app, according to Mr. Knickrehm. Security violations are investigated by USMLE staff and reviewed by the USMLE Committee for Individualized Review (CIR). Anyone found to have engaged in irregular behavior by the CIR for activities undermining exam integrity are typically barred from access to the USMLE for multiple years. 
 

How Easy Is It to Buy Recalls?

Two years ago, Dr B was approached by a former study partner who had just completed Step 2 of the USMLE. She asked whether Dr B wanted to buy recalled questions to help her pass. 

“She paid this guy almost $2000 for recalls and told me if I pay this money, he’ll give me the recalls,” said Dr B, who asked to remain anonymous for fear of being associated with students cheating on the USMLE. “I told her I was not interested, and she said the guy would lower the price. I broke contact with her.”

Dr B, an IMG from Pakistan, was appalled. But she said that the episode was not the first time she has come across groups selling USMLE recalls or heard peers brag about having access to exam content. 

“I am baffled at how many [groups] post on social media and brazenly advertise their ‘services,’” she told this news organization. “No one arrests them, their customers go on to score abnormally high on the boards, making it unachievable for people who take the honest route, plus giving IMGs a bad rep.” 

Groups offering recalls are easily findable on sites such as Telegram and Signal. Telegram is a cloud-based messaging app that focuses on security, and Signal is an encrypted messaging service. 

The website recallmastery.com purports to offer a range of USMLE recall packages, from a free, unsorted version to Step 1 and Step 2 packages that include “fresh updates,” and sections with “mostly repeated topics. Prices range from the free version to the $799 VIP package. 

Another site called MedPox.com boasts 2024 Step 2 recalls, advertising “ actual exam questions to get HIGH scores.” The website’s owner states that the recalls were collected “by my friends,” and to message the them to be added to the “recalls group.”

A reporter was able to easily download a free version of alleged USMLE questions and answers from recallmastery.com. The document was a combination of typed and handwritten notes about medical questions, with red circles around recalled answers. 

J. Bryan Carmody, MD, who blogs about medical education, reviewed a copy of the document. He said that the content appeared “credible” and was in fact recalled USMLE questions. However, the extent of which the question stem was recalled was incomplete at best, and there was little production value to the document, said Dr. Carmody, a nephrologist and associate professor of pediatrics at the Eastern Virgina Medical School in Norfolk. 

The person selling the recall packages states on the website that the free version is not organized or sorted, but it allows viewers to “see how this works before paying for premium recalls.” 

Mr. Knickrehm said that the program could not comment on the document, but that “whenever the USMLE program receives or locates information about a potential security violation, we investigate and take necessary action.” 

When asked about the specific websites noted above, Knickrehm said that the program routinely monitors a wide array of websites, message boards, and chat rooms for USMLE-related materials. Though many sites advertise having USMLE recalls for sale, it’s more likely they are selling non-USMLE content, he said. 

Using past content to cheat on medical exams is an old problem. In 2010, for example, the American Board of Internal Medicine suspended 139 physicians after they were caught cheating on the board exams. The scandal involved a vast cheating ring that included physicians memorizing questions and reproducing them after the tests. The board later sued a gastroenterologist for her part in the scandal. 

In 2012, a CNN investigation exposed doctors who were memorizing test questions and creating sophisticated recall banks to cheat on radiology boards. The Association of American Medical Colleges sued a medical student in 2017 for attempting to secretly record content on the MCAT using spyglasses. 

In recent years, Dr. Carmody said that he has received multiple messages and screenshots from concerned students and residents who were offered or encountered recalls. 

“One thing that’s unclear is how legitimate the claims are,” he said. “Many of these recalls may be faulty or outdated. It could be someone who took the exam yesterday and has a photographic memory or it could be some sparsely recalled or mis-recalled information. Unless you’re willing to pay these people, you can’t inspect the quality, or even if you did, you wouldn’t know if the information was current or not.”
 

‘As an IMG, There Is So Much at Stake’

Whether recall sellers — and those buying them — are more frequently IMGs has fostered heated debate on social media. 

On a Reddit thread devoted to IMG issues, posters expressed frustration about being bombarded with recall advertisements and unwanted messages about buying USMLE questions while trying to find study materials. One poster called the practices a “huge slap to all those IMGs who are struggling day and night, just to get a good score.”

In an X thread about the same subject, however, some self-described IMGs took offense to claims that IMGs might score higher because they have access to recalls. The allegations are “incendiary” and “malign hardworking IMGs,” posters wrote.

When Dr. Gul spoke out online about the “biopsy” culture, he received multiple private messages from fellow IMGs telling him to remove his comments, he said. 

“I received a lot of backlash on social media,” he told this news organization. “Some IMGs asked me to take down my posts because they thought I was making IMGs look bad, and it might prompt authorities to take action or shut down international examination centers for IMGs.”

Most of the IMGs who spoke to this news organization were afraid to be publicly identified. Several IMG advocates and IMG associations contacted for the story did not respond. One medical education expert said that his institution advised him to “steer clear” of commenting because the issue was “controversial.” 

“As an IMG, there is so much at stake,” Dr B said. “Any association with shady operations like these is an absolute suicide. I’m personally afraid of any repercussions of the sort.”

USMLE officials declined to comment on whether the buying or selling of recalls appears to be more prevalent among the IMG community, saying it is “difficult to generalize this behavior as ‘prevalent’ simply due to the clandestine nature of this activity.”
 

Cheat-Proofing the USMLE

The USMLE program has taken several steps intended to prevent cheating, but more needs to be done, medical education advocates say. 

For example, Dr. Carmody called the recent change in the attempt limit for taking USMLE exams from six to four times a good move. 

“The reality is, if you’re taking a USMLE exam five-plus times, you’re far more likely to be memorizing questions and selling them for shady test prep operations than you are to be legitimately pursuing U.S. residency training or licensure,” he wrote on X. 

The 2022 move to make USMLE Step 1 pass or fail is another positive change, said Dr. Gul, who added that US programs should also put less weight on test scores and focus more on clinical experience. 

“Many programs in the US prioritize scores rather than clinical experiences in home countries,” he said. “If program directors would remove these criteria, probably the cheating practices would stop. Clinical practice matters. When a doctor gets matched, they have to be good at seeing and treating patients, not just good at sitting in front of a screen and taking an exam.”

Turning over questions more rapidly would help curb the practices, Dr. Carmody said. Another strategy is using math techniques to identify unusual deviations that suggest cheating, he said. 

A blueprint for the strategy was created after a cheating scandal involving Canada’s Medical Council of Canada Qualifying Examination (MCCQE) in 2004. After learning which questions were circulated, MCCQE administrators evaluated exams by comparing answers of compromised questions with the answers of noncompromised questions. 

“For a person who was not cheating, the error of performance should be pretty similar on those two groups of questions,” Dr. Carmody said. “But if you were given the questions in advance, you might have very poor performance on questions that had not been compromised, and very high performance on those that had been compromised. That disparity is very unlikely to occur just by chance alone.” 

Based on his research, Dr. Ozair is working on an academic review paper about cheating on the USMLE and on the Medical Council of Canada Qualification Examination. He said that he hopes the paper will raise more awareness about the problem and drive more action. 

He and others interviewed for this story shared that the websites they’ve reported to the USMLE program are still active and offering recalls to buyers. 

“Even if they are not actually offering something tangible or true, appearance matters,” Dr. Ozair said. “I think it’s worth the USMLE sending cease and desist letters and getting these websites taken down. This would restore faith in the process and underscore that this issue is being taken seriously.”
 

A version of this article appeared on Medscape.com.

The United States Medical Licensing Examination (USMLE) program is invalidating scores attained by some examinees after an investigation revealed a pattern of anomalous exam performance associated with test-takers from Nepal. 

In a January 31 announcement, the USMLE program said that officials are in the process of notifying examinees with results in question and that the examinees will be required to take validation exams. The program did not offer further details about its investigation or how the questionable performance was identified. 

“The USMLE program regularly monitors and analyzes examinees’ test performances for unusual score patterns or variations, and other information that could raise questions about the validity of an examinee’s results,” the program said in a statement. “Highly irregular patterns can be indicative of prior unauthorized access to secure exam content.”

Some medical graduates say the action against students cheating on the USMLE is long overdue. 

The selling and buying of USMLE questions online have become rampant in recent years, particularly by groups within the international medical graduate (IMG) community, according to multiple IMGs who shared their concerns with this news organization. Sellers operate under pseudonyms across social media platforms and charge anywhere from $300 to $2000 for questions, Medscape research shows. 

Facebook posts often advertise questions for sale, said Saqib Gul, MD, an IMG from Pakistan who has voiced concerns about the practice on social media. 

“People make up fake profiles and tell others to [direct message] them for recalls,” he told this news organization. “There was a dedicated Facebook page that was doing this. In other cases, a couple of friends that took the exam remember a certain number of questions and write them down after the test.”

Ahmad Ozair, MD, an IMG from Lucknow, Uttar Pradesh, India, said that he has come across many groups online sharing or selling USMLE recalls. He first became suspicious when he saw several students, all from a few medical schools in Nepal, posting on social media about scoring in the 270 and 280-plus range. 

“The statistical probability that you would have three or more candidates in the same year, scoring in the 99th percentile worldwide, belonging to a small geographical area is extremely low.” 

Dr. Ozair, who now is studying public health at Johns Hopkins University in Baltimore, said that the issue is important for “all stakeholders” who care about patient safety: “Would you want a doctor who has cheated on the medical licensing exam to take care of you?” 

In an interview, USMLE program spokesman Joe Knickrehm said that the program relies on multiple processes to detect and respond to claims that exam integrity is being compromised. The process includes monitoring performance data, an anonymous tip line for reporting suspicious behavior, and a thorough investigative process. 

“The USMLE program regularly monitors social media channels for comments relating to exam security and irregular behavior and will initiate an investigation if warranted,” Mr. Knickrehm told this news organization. “ The covert nature of this activity does not lend itself to a definitive statement regarding whether the problem has increased or decreased in recent years.” 

Mr. Knickrehm said that the program’s STOPit app allows people to report suspicious behavior electronically to the USMLE program. Since its launch in 2021, the program has received more than 80 tips per year through the app, according to Mr. Knickrehm. Security violations are investigated by USMLE staff and reviewed by the USMLE Committee for Individualized Review (CIR). Anyone found to have engaged in irregular behavior by the CIR for activities undermining exam integrity are typically barred from access to the USMLE for multiple years. 
 

How Easy Is It to Buy Recalls?

Two years ago, Dr B was approached by a former study partner who had just completed Step 2 of the USMLE. She asked whether Dr B wanted to buy recalled questions to help her pass. 

“She paid this guy almost $2000 for recalls and told me if I pay this money, he’ll give me the recalls,” said Dr B, who asked to remain anonymous for fear of being associated with students cheating on the USMLE. “I told her I was not interested, and she said the guy would lower the price. I broke contact with her.”

Dr B, an IMG from Pakistan, was appalled. But she said that the episode was not the first time she has come across groups selling USMLE recalls or heard peers brag about having access to exam content. 

“I am baffled at how many [groups] post on social media and brazenly advertise their ‘services,’” she told this news organization. “No one arrests them, their customers go on to score abnormally high on the boards, making it unachievable for people who take the honest route, plus giving IMGs a bad rep.” 

Groups offering recalls are easily findable on sites such as Telegram and Signal. Telegram is a cloud-based messaging app that focuses on security, and Signal is an encrypted messaging service. 

The website recallmastery.com purports to offer a range of USMLE recall packages, from a free, unsorted version to Step 1 and Step 2 packages that include “fresh updates,” and sections with “mostly repeated topics. Prices range from the free version to the $799 VIP package. 

Another site called MedPox.com boasts 2024 Step 2 recalls, advertising “ actual exam questions to get HIGH scores.” The website’s owner states that the recalls were collected “by my friends,” and to message the them to be added to the “recalls group.”

A reporter was able to easily download a free version of alleged USMLE questions and answers from recallmastery.com. The document was a combination of typed and handwritten notes about medical questions, with red circles around recalled answers. 

J. Bryan Carmody, MD, who blogs about medical education, reviewed a copy of the document. He said that the content appeared “credible” and was in fact recalled USMLE questions. However, the extent of which the question stem was recalled was incomplete at best, and there was little production value to the document, said Dr. Carmody, a nephrologist and associate professor of pediatrics at the Eastern Virgina Medical School in Norfolk. 

The person selling the recall packages states on the website that the free version is not organized or sorted, but it allows viewers to “see how this works before paying for premium recalls.” 

Mr. Knickrehm said that the program could not comment on the document, but that “whenever the USMLE program receives or locates information about a potential security violation, we investigate and take necessary action.” 

When asked about the specific websites noted above, Knickrehm said that the program routinely monitors a wide array of websites, message boards, and chat rooms for USMLE-related materials. Though many sites advertise having USMLE recalls for sale, it’s more likely they are selling non-USMLE content, he said. 

Using past content to cheat on medical exams is an old problem. In 2010, for example, the American Board of Internal Medicine suspended 139 physicians after they were caught cheating on the board exams. The scandal involved a vast cheating ring that included physicians memorizing questions and reproducing them after the tests. The board later sued a gastroenterologist for her part in the scandal. 

In 2012, a CNN investigation exposed doctors who were memorizing test questions and creating sophisticated recall banks to cheat on radiology boards. The Association of American Medical Colleges sued a medical student in 2017 for attempting to secretly record content on the MCAT using spyglasses. 

In recent years, Dr. Carmody said that he has received multiple messages and screenshots from concerned students and residents who were offered or encountered recalls. 

“One thing that’s unclear is how legitimate the claims are,” he said. “Many of these recalls may be faulty or outdated. It could be someone who took the exam yesterday and has a photographic memory or it could be some sparsely recalled or mis-recalled information. Unless you’re willing to pay these people, you can’t inspect the quality, or even if you did, you wouldn’t know if the information was current or not.”
 

‘As an IMG, There Is So Much at Stake’

Whether recall sellers — and those buying them — are more frequently IMGs has fostered heated debate on social media. 

On a Reddit thread devoted to IMG issues, posters expressed frustration about being bombarded with recall advertisements and unwanted messages about buying USMLE questions while trying to find study materials. One poster called the practices a “huge slap to all those IMGs who are struggling day and night, just to get a good score.”

In an X thread about the same subject, however, some self-described IMGs took offense to claims that IMGs might score higher because they have access to recalls. The allegations are “incendiary” and “malign hardworking IMGs,” posters wrote.

When Dr. Gul spoke out online about the “biopsy” culture, he received multiple private messages from fellow IMGs telling him to remove his comments, he said. 

“I received a lot of backlash on social media,” he told this news organization. “Some IMGs asked me to take down my posts because they thought I was making IMGs look bad, and it might prompt authorities to take action or shut down international examination centers for IMGs.”

Most of the IMGs who spoke to this news organization were afraid to be publicly identified. Several IMG advocates and IMG associations contacted for the story did not respond. One medical education expert said that his institution advised him to “steer clear” of commenting because the issue was “controversial.” 

“As an IMG, there is so much at stake,” Dr B said. “Any association with shady operations like these is an absolute suicide. I’m personally afraid of any repercussions of the sort.”

USMLE officials declined to comment on whether the buying or selling of recalls appears to be more prevalent among the IMG community, saying it is “difficult to generalize this behavior as ‘prevalent’ simply due to the clandestine nature of this activity.”
 

Cheat-Proofing the USMLE

The USMLE program has taken several steps intended to prevent cheating, but more needs to be done, medical education advocates say. 

For example, Dr. Carmody called the recent change in the attempt limit for taking USMLE exams from six to four times a good move. 

“The reality is, if you’re taking a USMLE exam five-plus times, you’re far more likely to be memorizing questions and selling them for shady test prep operations than you are to be legitimately pursuing U.S. residency training or licensure,” he wrote on X. 

The 2022 move to make USMLE Step 1 pass or fail is another positive change, said Dr. Gul, who added that US programs should also put less weight on test scores and focus more on clinical experience. 

“Many programs in the US prioritize scores rather than clinical experiences in home countries,” he said. “If program directors would remove these criteria, probably the cheating practices would stop. Clinical practice matters. When a doctor gets matched, they have to be good at seeing and treating patients, not just good at sitting in front of a screen and taking an exam.”

Turning over questions more rapidly would help curb the practices, Dr. Carmody said. Another strategy is using math techniques to identify unusual deviations that suggest cheating, he said. 

A blueprint for the strategy was created after a cheating scandal involving Canada’s Medical Council of Canada Qualifying Examination (MCCQE) in 2004. After learning which questions were circulated, MCCQE administrators evaluated exams by comparing answers of compromised questions with the answers of noncompromised questions. 

“For a person who was not cheating, the error of performance should be pretty similar on those two groups of questions,” Dr. Carmody said. “But if you were given the questions in advance, you might have very poor performance on questions that had not been compromised, and very high performance on those that had been compromised. That disparity is very unlikely to occur just by chance alone.” 

Based on his research, Dr. Ozair is working on an academic review paper about cheating on the USMLE and on the Medical Council of Canada Qualification Examination. He said that he hopes the paper will raise more awareness about the problem and drive more action. 

He and others interviewed for this story shared that the websites they’ve reported to the USMLE program are still active and offering recalls to buyers. 

“Even if they are not actually offering something tangible or true, appearance matters,” Dr. Ozair said. “I think it’s worth the USMLE sending cease and desist letters and getting these websites taken down. This would restore faith in the process and underscore that this issue is being taken seriously.”
 

A version of this article appeared on Medscape.com.

Men with cardiorespiratory fitness (CRF) who increased their CRF by more than 3% had a significantly lower risk of prostate cancer incidence, a large Swedish study found.

The prospective analysis, published in the British Journal of Sports Medicine, done in a cohort of nearly 58,000, was conducted by Kate A. Bolam, PhD, a clinical exercise physiologist at the Swedish School of Sport and Health Sciences in Stockholm.

“The findings suggest that physicians could work toward supporting patients to understand what types of activities could improve their fitness and ways they can incorporate these activities into their lives in an enjoyable way, or at the very least refer patients on to an exercise specialist,” Dr. Bolam said in an interview.

Grouped by baseline CRF, the association between change in absolute CRF and prostate cancer incidence was significant only for participants with a moderate baseline CRF. Moreover, changes in both absolute and relative CRF were not associated with prostate cancer mortality.

The lack of mortality significance may be due to the relatively few deaths from prostate cancer in the cohort, Dr. Bolam said. “It may be we weren’t powered to detect anything with such low numbers. And it’s not likely men will die from prostate cancer but more likely from more common chronic diseases such as heart disease.” The authors noted that unlike the case with other common cancers, there are relatively few preventable risk factors with strong evidence for reducing overall prostate cancer risk. “Aside from developmental factors, being diagnosed with overweight or obesity are the main risk factors for developing advanced prostate cancer, but insufficient evidence exists to extend this conclusion to non-advanced prostate cancer,” they wrote.

There is evidence, however, that exercise reduces all-cause mortality risk across many cancer types, including prostate.
 

Study details

The cohort was drawn from Swedish national health-profile database figures from 1982 to 2019. Participants completed an occupational health profile assessment including at least two valid CRF tests on a cycle ergometer. During a mean follow-up of 6.7 years, 592 (1%) of 57,652 men (mean age 41.3 years, standard deviation 10.55) were diagnosed with prostate cancer, and in 46 (.08%) prostate cancer was the primary cause of death.

An increase in absolute CRF (as a percentage of liters per minute of cardiac output) was associated with a reduced incidence risk, with a hazard ratio of 0.98 (95% CI, 0.96-0.99). Grouping participants as having increased (+3%), stable (±3%), or decreased (−3%) CRF, the investigators found increased fitness was associated with an HR for prostate cancer incidence of 0.65 (95% CI, 0.49-0.86), vs decreased fitness.

According to the authors, this and similar investigations of mechanisms behind physical activity benefits will lead to more targeted prevention recommendations. The results highlight the importance of encouraging the general public to increase CRF or reach moderate fitness levels, Dr. Bolam’s group wrote. The group is planning a similar study in breast cancer.

This study was funded by the Swedish Cancer Society. The authors declared no competing interests.

Men with cardiorespiratory fitness (CRF) who increased their CRF by more than 3% had a significantly lower risk of prostate cancer incidence, a large Swedish study found.

The prospective analysis, published in the British Journal of Sports Medicine, done in a cohort of nearly 58,000, was conducted by Kate A. Bolam, PhD, a clinical exercise physiologist at the Swedish School of Sport and Health Sciences in Stockholm.

“The findings suggest that physicians could work toward supporting patients to understand what types of activities could improve their fitness and ways they can incorporate these activities into their lives in an enjoyable way, or at the very least refer patients on to an exercise specialist,” Dr. Bolam said in an interview.

Grouped by baseline CRF, the association between change in absolute CRF and prostate cancer incidence was significant only for participants with a moderate baseline CRF. Moreover, changes in both absolute and relative CRF were not associated with prostate cancer mortality.

The lack of mortality significance may be due to the relatively few deaths from prostate cancer in the cohort, Dr. Bolam said. “It may be we weren’t powered to detect anything with such low numbers. And it’s not likely men will die from prostate cancer but more likely from more common chronic diseases such as heart disease.” The authors noted that unlike the case with other common cancers, there are relatively few preventable risk factors with strong evidence for reducing overall prostate cancer risk. “Aside from developmental factors, being diagnosed with overweight or obesity are the main risk factors for developing advanced prostate cancer, but insufficient evidence exists to extend this conclusion to non-advanced prostate cancer,” they wrote.

There is evidence, however, that exercise reduces all-cause mortality risk across many cancer types, including prostate.
 

Study details

The cohort was drawn from Swedish national health-profile database figures from 1982 to 2019. Participants completed an occupational health profile assessment including at least two valid CRF tests on a cycle ergometer. During a mean follow-up of 6.7 years, 592 (1%) of 57,652 men (mean age 41.3 years, standard deviation 10.55) were diagnosed with prostate cancer, and in 46 (.08%) prostate cancer was the primary cause of death.

An increase in absolute CRF (as a percentage of liters per minute of cardiac output) was associated with a reduced incidence risk, with a hazard ratio of 0.98 (95% CI, 0.96-0.99). Grouping participants as having increased (+3%), stable (±3%), or decreased (−3%) CRF, the investigators found increased fitness was associated with an HR for prostate cancer incidence of 0.65 (95% CI, 0.49-0.86), vs decreased fitness.

According to the authors, this and similar investigations of mechanisms behind physical activity benefits will lead to more targeted prevention recommendations. The results highlight the importance of encouraging the general public to increase CRF or reach moderate fitness levels, Dr. Bolam’s group wrote. The group is planning a similar study in breast cancer.

This study was funded by the Swedish Cancer Society. The authors declared no competing interests.

Men with cardiorespiratory fitness (CRF) who increased their CRF by more than 3% had a significantly lower risk of prostate cancer incidence, a large Swedish study found.

The prospective analysis, published in the British Journal of Sports Medicine, done in a cohort of nearly 58,000, was conducted by Kate A. Bolam, PhD, a clinical exercise physiologist at the Swedish School of Sport and Health Sciences in Stockholm.

“The findings suggest that physicians could work toward supporting patients to understand what types of activities could improve their fitness and ways they can incorporate these activities into their lives in an enjoyable way, or at the very least refer patients on to an exercise specialist,” Dr. Bolam said in an interview.

Grouped by baseline CRF, the association between change in absolute CRF and prostate cancer incidence was significant only for participants with a moderate baseline CRF. Moreover, changes in both absolute and relative CRF were not associated with prostate cancer mortality.

The lack of mortality significance may be due to the relatively few deaths from prostate cancer in the cohort, Dr. Bolam said. “It may be we weren’t powered to detect anything with such low numbers. And it’s not likely men will die from prostate cancer but more likely from more common chronic diseases such as heart disease.” The authors noted that unlike the case with other common cancers, there are relatively few preventable risk factors with strong evidence for reducing overall prostate cancer risk. “Aside from developmental factors, being diagnosed with overweight or obesity are the main risk factors for developing advanced prostate cancer, but insufficient evidence exists to extend this conclusion to non-advanced prostate cancer,” they wrote.

There is evidence, however, that exercise reduces all-cause mortality risk across many cancer types, including prostate.
 

Study details

The cohort was drawn from Swedish national health-profile database figures from 1982 to 2019. Participants completed an occupational health profile assessment including at least two valid CRF tests on a cycle ergometer. During a mean follow-up of 6.7 years, 592 (1%) of 57,652 men (mean age 41.3 years, standard deviation 10.55) were diagnosed with prostate cancer, and in 46 (.08%) prostate cancer was the primary cause of death.

An increase in absolute CRF (as a percentage of liters per minute of cardiac output) was associated with a reduced incidence risk, with a hazard ratio of 0.98 (95% CI, 0.96-0.99). Grouping participants as having increased (+3%), stable (±3%), or decreased (−3%) CRF, the investigators found increased fitness was associated with an HR for prostate cancer incidence of 0.65 (95% CI, 0.49-0.86), vs decreased fitness.

According to the authors, this and similar investigations of mechanisms behind physical activity benefits will lead to more targeted prevention recommendations. The results highlight the importance of encouraging the general public to increase CRF or reach moderate fitness levels, Dr. Bolam’s group wrote. The group is planning a similar study in breast cancer.

This study was funded by the Swedish Cancer Society. The authors declared no competing interests.