Moving in a very different direction from past coronary stent designs, a new device that is being characterized as bioadaptable, as opposed to bioabsorbable, was noninferior to a widely used drug-eluting stent, and associated with several unique vessel functional improvements at 12 months in a randomized controlled trial.

“The device restored vessel motion, which we think is the reason that we saw plaque stabilization and regression,” reported Shigero Saito, MD, director of the catheterization laboratory at Shonan Kamakura (Japan) General Hospital.

The principal features of the bioadaptable design are cobalt-chromium metal helical strands to provide indefinite scaffolding support coupled with a biodegradable sirolimus-containing poly(D,L-lacti-co-glycolic acid) (PLGA) topcoat and a biodegradable poly-L-lactic acid (PLLA) bottom coat to “uncage” the vessel once these materials are resorbed, said Dr. Saito.

Twelve-month data from the randomized BIOADAPTOR trial, presented as a late breaker at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions, provide the first evidence that this uncaging of the vessel is an advantage.

Compared head-to-head in a contemporary drug-eluting stent (DES) in a randomized trial, the bioadaptable stent, as predicted in prior studies, “improved hemodynamics and supported plaque stabilization and positive remodeling,” said Dr. Saito.

In BIOADAPTOR, 445 patients in Japan, Germany, Belgium, and New Zealand were randomized to the novel stent, called DynamX, or to the Resolute Onyx. The trial has a planned follow-up of 5 years.

While the primary endpoint at 12 months was noninferiority for target lesion failure (TLF), it was a series of secondary imaging endpoints that suggest an important impact of uncaging the vessel. This includes better vessel function potentially relevant to resistance to restenosis.

As a result of numerically lower TLF in the DynamX group (1.8% vs. 2.8%), the new device easily demonstrated noninferiority at a high level of significance (P < .001). A numerical advantage for most events, including cardiovascular death (0% vs. 0.9%) and target-vessel myocardial infarction (1.4% vs. 1.9%), favored the novel device, but event rates were low in both arms and none of these differences were statistically significant.

However, the secondary imaging analyses at 12 months suggested major differences between the two devices from “uncaging” the vessel.

These differences included a highly significant improvement at 12 months in vessel pulsatility (P < .001) within the DynamX stent relative to the Onyx stent in all measured segments (proximal, mid, and distal).

In addition, compliance remained suppressed relative to both the proximal (P < .001) and distal (P < .001) vessels of patients fitted with Onyx device. Conversely, there was no significant relative difference in this measure among those fitted with the DynamX device.

At 12 months, the plaque volume change behind the stent of noncalcified lesions increased 9% in the Onyx group but was reduced 4% in the DynamX group (P = .028).

While there was a 13% gain overall in percent diameter stenosis within the stent of patients receiving the DynamX device, it was consistently lower than that observed in the Onyx group. This difference was only a trend overall (12.7% vs. 17.3%; P = .051), but the advantage reached significance, favoring DynamX, for the left anterior descending (LAD) artery (12.1% vs. 19.0%; P = .006), small vessels (13.0% vs. 18.3%; P = .045), and long lesions (13.0% vs. 22.9%; P = .008).

The same relative advantage for DynamX was seen on late lumen loss at 6 months. In this case, the overall advantage of DynamX (0.09 vs. 0.25; P = .038) did reach significance, and there was an advantage for the LAD (–0.02 vs. 0.24; P = .007) and long lesions (–0.06 vs. 0.38; P = .016). The difference did not reach significance for small vessels (0.08 vs. 0.26; P = .121).

All of these advantages on the secondary endpoints can be directly attributed to the effect of uncaging the vessel, according to Dr. Saito, who said this new design “addresses the shortcomings” of both previous drug-eluting and biodegradable stents.

Pointing out that the nonplateauing of late events has persisted regardless of stent design after “more than 20 years of innovation in design and materials,” Dr. Saito said all current stents have weaknesses. While biodegradable stents have not improved long-term outcomes relative to DES “as a result of loss of long-term vessel dynamic support,” DES are flawed due to “permanent caging of the vessel and loss of vessel motion and function.”

This novel hybrid design, employing both metal and biodegradable components, “is a completely different concept,” said Ron Waksman, MD, associate director, division of cardiology, Medstar Hospital Center, Washington. He was particularly impressed by the improvements in pulsatility and compliance in target vessels along with the favorable effects on plaque volume.

“The reduction in plaque volume is something we have not seen before. Usually we see the opposite,” Dr. Waksman said.

“Clearly, the Bioadaptor device is not a me-too stent,” he said. He was not surprised that there was no difference in hard outcomes given both the small sample size and the fact that the advantages of uncaging the vessel are likely to accrue over time.

“We need to look at what happens after 1 year. We still have not seen the potential of this device,” he said, adding he was “impressed” by the features of this novel concept. However, he suggested the advantages remain theoretical from the clinical standpoint, advising Dr. Saito that “you still need to demonstrate the clinical benefits.”

Dr. Saito reports a financial relationship with Elixir Medical, which funded the BIOADAPTOR trial. Dr. Waksman reports financial relationships with 19 pharmaceutical companies including those that manufacture cardiovascular stents.

Moving in a very different direction from past coronary stent designs, a new device that is being characterized as bioadaptable, as opposed to bioabsorbable, was noninferior to a widely used drug-eluting stent, and associated with several unique vessel functional improvements at 12 months in a randomized controlled trial.

“The device restored vessel motion, which we think is the reason that we saw plaque stabilization and regression,” reported Shigero Saito, MD, director of the catheterization laboratory at Shonan Kamakura (Japan) General Hospital.

The principal features of the bioadaptable design are cobalt-chromium metal helical strands to provide indefinite scaffolding support coupled with a biodegradable sirolimus-containing poly(D,L-lacti-co-glycolic acid) (PLGA) topcoat and a biodegradable poly-L-lactic acid (PLLA) bottom coat to “uncage” the vessel once these materials are resorbed, said Dr. Saito.

Twelve-month data from the randomized BIOADAPTOR trial, presented as a late breaker at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions, provide the first evidence that this uncaging of the vessel is an advantage.

Compared head-to-head in a contemporary drug-eluting stent (DES) in a randomized trial, the bioadaptable stent, as predicted in prior studies, “improved hemodynamics and supported plaque stabilization and positive remodeling,” said Dr. Saito.

In BIOADAPTOR, 445 patients in Japan, Germany, Belgium, and New Zealand were randomized to the novel stent, called DynamX, or to the Resolute Onyx. The trial has a planned follow-up of 5 years.

While the primary endpoint at 12 months was noninferiority for target lesion failure (TLF), it was a series of secondary imaging endpoints that suggest an important impact of uncaging the vessel. This includes better vessel function potentially relevant to resistance to restenosis.

As a result of numerically lower TLF in the DynamX group (1.8% vs. 2.8%), the new device easily demonstrated noninferiority at a high level of significance (P < .001). A numerical advantage for most events, including cardiovascular death (0% vs. 0.9%) and target-vessel myocardial infarction (1.4% vs. 1.9%), favored the novel device, but event rates were low in both arms and none of these differences were statistically significant.

However, the secondary imaging analyses at 12 months suggested major differences between the two devices from “uncaging” the vessel.

These differences included a highly significant improvement at 12 months in vessel pulsatility (P < .001) within the DynamX stent relative to the Onyx stent in all measured segments (proximal, mid, and distal).

In addition, compliance remained suppressed relative to both the proximal (P < .001) and distal (P < .001) vessels of patients fitted with Onyx device. Conversely, there was no significant relative difference in this measure among those fitted with the DynamX device.

At 12 months, the plaque volume change behind the stent of noncalcified lesions increased 9% in the Onyx group but was reduced 4% in the DynamX group (P = .028).

While there was a 13% gain overall in percent diameter stenosis within the stent of patients receiving the DynamX device, it was consistently lower than that observed in the Onyx group. This difference was only a trend overall (12.7% vs. 17.3%; P = .051), but the advantage reached significance, favoring DynamX, for the left anterior descending (LAD) artery (12.1% vs. 19.0%; P = .006), small vessels (13.0% vs. 18.3%; P = .045), and long lesions (13.0% vs. 22.9%; P = .008).

The same relative advantage for DynamX was seen on late lumen loss at 6 months. In this case, the overall advantage of DynamX (0.09 vs. 0.25; P = .038) did reach significance, and there was an advantage for the LAD (–0.02 vs. 0.24; P = .007) and long lesions (–0.06 vs. 0.38; P = .016). The difference did not reach significance for small vessels (0.08 vs. 0.26; P = .121).

All of these advantages on the secondary endpoints can be directly attributed to the effect of uncaging the vessel, according to Dr. Saito, who said this new design “addresses the shortcomings” of both previous drug-eluting and biodegradable stents.

Pointing out that the nonplateauing of late events has persisted regardless of stent design after “more than 20 years of innovation in design and materials,” Dr. Saito said all current stents have weaknesses. While biodegradable stents have not improved long-term outcomes relative to DES “as a result of loss of long-term vessel dynamic support,” DES are flawed due to “permanent caging of the vessel and loss of vessel motion and function.”

This novel hybrid design, employing both metal and biodegradable components, “is a completely different concept,” said Ron Waksman, MD, associate director, division of cardiology, Medstar Hospital Center, Washington. He was particularly impressed by the improvements in pulsatility and compliance in target vessels along with the favorable effects on plaque volume.

“The reduction in plaque volume is something we have not seen before. Usually we see the opposite,” Dr. Waksman said.

“Clearly, the Bioadaptor device is not a me-too stent,” he said. He was not surprised that there was no difference in hard outcomes given both the small sample size and the fact that the advantages of uncaging the vessel are likely to accrue over time.

“We need to look at what happens after 1 year. We still have not seen the potential of this device,” he said, adding he was “impressed” by the features of this novel concept. However, he suggested the advantages remain theoretical from the clinical standpoint, advising Dr. Saito that “you still need to demonstrate the clinical benefits.”

Dr. Saito reports a financial relationship with Elixir Medical, which funded the BIOADAPTOR trial. Dr. Waksman reports financial relationships with 19 pharmaceutical companies including those that manufacture cardiovascular stents.

Moving in a very different direction from past coronary stent designs, a new device that is being characterized as bioadaptable, as opposed to bioabsorbable, was noninferior to a widely used drug-eluting stent, and associated with several unique vessel functional improvements at 12 months in a randomized controlled trial.

“The device restored vessel motion, which we think is the reason that we saw plaque stabilization and regression,” reported Shigero Saito, MD, director of the catheterization laboratory at Shonan Kamakura (Japan) General Hospital.

The principal features of the bioadaptable design are cobalt-chromium metal helical strands to provide indefinite scaffolding support coupled with a biodegradable sirolimus-containing poly(D,L-lacti-co-glycolic acid) (PLGA) topcoat and a biodegradable poly-L-lactic acid (PLLA) bottom coat to “uncage” the vessel once these materials are resorbed, said Dr. Saito.

Twelve-month data from the randomized BIOADAPTOR trial, presented as a late breaker at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions, provide the first evidence that this uncaging of the vessel is an advantage.

Compared head-to-head in a contemporary drug-eluting stent (DES) in a randomized trial, the bioadaptable stent, as predicted in prior studies, “improved hemodynamics and supported plaque stabilization and positive remodeling,” said Dr. Saito.

In BIOADAPTOR, 445 patients in Japan, Germany, Belgium, and New Zealand were randomized to the novel stent, called DynamX, or to the Resolute Onyx. The trial has a planned follow-up of 5 years.

While the primary endpoint at 12 months was noninferiority for target lesion failure (TLF), it was a series of secondary imaging endpoints that suggest an important impact of uncaging the vessel. This includes better vessel function potentially relevant to resistance to restenosis.

As a result of numerically lower TLF in the DynamX group (1.8% vs. 2.8%), the new device easily demonstrated noninferiority at a high level of significance (P < .001). A numerical advantage for most events, including cardiovascular death (0% vs. 0.9%) and target-vessel myocardial infarction (1.4% vs. 1.9%), favored the novel device, but event rates were low in both arms and none of these differences were statistically significant.

However, the secondary imaging analyses at 12 months suggested major differences between the two devices from “uncaging” the vessel.

These differences included a highly significant improvement at 12 months in vessel pulsatility (P < .001) within the DynamX stent relative to the Onyx stent in all measured segments (proximal, mid, and distal).

In addition, compliance remained suppressed relative to both the proximal (P < .001) and distal (P < .001) vessels of patients fitted with Onyx device. Conversely, there was no significant relative difference in this measure among those fitted with the DynamX device.

At 12 months, the plaque volume change behind the stent of noncalcified lesions increased 9% in the Onyx group but was reduced 4% in the DynamX group (P = .028).

While there was a 13% gain overall in percent diameter stenosis within the stent of patients receiving the DynamX device, it was consistently lower than that observed in the Onyx group. This difference was only a trend overall (12.7% vs. 17.3%; P = .051), but the advantage reached significance, favoring DynamX, for the left anterior descending (LAD) artery (12.1% vs. 19.0%; P = .006), small vessels (13.0% vs. 18.3%; P = .045), and long lesions (13.0% vs. 22.9%; P = .008).

The same relative advantage for DynamX was seen on late lumen loss at 6 months. In this case, the overall advantage of DynamX (0.09 vs. 0.25; P = .038) did reach significance, and there was an advantage for the LAD (–0.02 vs. 0.24; P = .007) and long lesions (–0.06 vs. 0.38; P = .016). The difference did not reach significance for small vessels (0.08 vs. 0.26; P = .121).

All of these advantages on the secondary endpoints can be directly attributed to the effect of uncaging the vessel, according to Dr. Saito, who said this new design “addresses the shortcomings” of both previous drug-eluting and biodegradable stents.

Pointing out that the nonplateauing of late events has persisted regardless of stent design after “more than 20 years of innovation in design and materials,” Dr. Saito said all current stents have weaknesses. While biodegradable stents have not improved long-term outcomes relative to DES “as a result of loss of long-term vessel dynamic support,” DES are flawed due to “permanent caging of the vessel and loss of vessel motion and function.”

This novel hybrid design, employing both metal and biodegradable components, “is a completely different concept,” said Ron Waksman, MD, associate director, division of cardiology, Medstar Hospital Center, Washington. He was particularly impressed by the improvements in pulsatility and compliance in target vessels along with the favorable effects on plaque volume.

“The reduction in plaque volume is something we have not seen before. Usually we see the opposite,” Dr. Waksman said.

“Clearly, the Bioadaptor device is not a me-too stent,” he said. He was not surprised that there was no difference in hard outcomes given both the small sample size and the fact that the advantages of uncaging the vessel are likely to accrue over time.

“We need to look at what happens after 1 year. We still have not seen the potential of this device,” he said, adding he was “impressed” by the features of this novel concept. However, he suggested the advantages remain theoretical from the clinical standpoint, advising Dr. Saito that “you still need to demonstrate the clinical benefits.”

Dr. Saito reports a financial relationship with Elixir Medical, which funded the BIOADAPTOR trial. Dr. Waksman reports financial relationships with 19 pharmaceutical companies including those that manufacture cardiovascular stents.

CLEVELAND – With early diagnosis an ongoing complex target for axial spondyloarthritis (axSpA), new research may help to answer where the biggest delays lie.

Gregory McDermott, MD, a research fellow at Brigham and Women’s Hospital in Boston, led a pilot study with data from Mass General Brigham electronic health records. He shared top results at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN) , where addressing delay in diagnosis was a major theme.

Included in the cohort were 554 patients who had three ICD-9 or ICD-10 codes and an imaging report of sacroiliitis, ankylosis, or syndesmophytes, and were screened via manual chart review for modified New York and Assessment of Spondyloarthritis International Society criteria.

The average diagnostic delay for axSpA was 6.8 years in this study (median, 3.8 years), relatively consistent with findings in previous studies globally, and the average age of onset was 29.5.

The researchers also factored in history of specialty care for back pain (orthopedics, physical medicine and rehabilitation, pain medicine) or extra-articular manifestations (ophthalmology, dermatology, gastroenterology) before axSpA diagnosis. Other factors included smoking and insurance status, along with age, sex, race, and other demographic data.

The results showed shorter delays in diagnosing axSpA were associated with older age at symptom onset and peripheral arthritis, whereas longer delays (more than 4 years) were associated with a history of uveitis, ankylosing spondylitis at diagnosis, and being among those in the 80-99th percentile on the social vulnerability index (SVI). The SVI includes U.S. census data on factors including housing type, household composition and disability status, employment status, minority status, non-English speaking, educational attainment, transportation, and mean income level.
 

Notable uveitis finding

Dr. McDermott said the team was surprised by the association between having had uveitis and delayed axSpA diagnosis.

Among patients with uveitis, 12% had a short delay from symptom onset to axSpA diagnosis of 0-1 years, but more than twice that percentage (27%) had a delay of more than 4 years (P < .001).

“We thought the finding related to uveitis was interesting and potentially clinically meaningful as 27% of axSpA patients in our cohort with more than 4 years of diagnostic delay sought ophthalmology care prior to their diagnosis, [compared with 13% of patients with a diagnosis within 1 year],” Dr. McDermott said. “This practice setting in particular may be a place where we can intervene with simple screening or increased education in order to get people appropriately referred to rheumatology care.”

Longer delays can lead to more functional impairment, radiographic progression, and work disability, as well as poorer quality of life, increased depression, and higher unemployment and health care costs, Dr. McDermott said.
 

Patients may miss key treatment window

Maureen Dubreuil, MD, MSc, assistant professor at Boston University and a rheumatologist with the VA Boston Healthcare System, who was not part of the study, said: “This study addressed a critically important problem in the field – that diagnosis of axSpA is delayed by 7 years, which is much longer than the average time to diagnosis for other forms of arthritis, such as rheumatoid arthritis, which is under 6 months.

“It is critical that diagnostic delay is reduced in axSpA because undiagnosed individuals may miss an important window of opportunity to receive treatment that prevents permanent structural damage and functional declines. This work, if confirmed in other data, would allow development of interventions to improve timely evaluation of individuals with chronic back pain who may have axSpA, particularly among those with within lower socioeconomic strata, and those who are older or have uveitis.”
 

Study tests screening tool

Among the ideas proposed for reducing the delay was a referral strategy with a screening tool.

Swetha Alexander, MD, a rheumatology fellow at the University of Utah, Salt Lake City, who presented her team’s poster, noted that, in the United States, patients with chronic back pain often come first to a primary care doctor or another specialty and not to a rheumatologist.

As an internal medicine resident at Yale University, New Haven, Conn., Dr. Alexander and colleagues there conducted the Finding Axial Spondyloarthritis (FaxSpA) study to test whether patient self-referral or referral by other physicians, guided by answers to a screening tool, could help to speed the process of getting patients more likely to have axSpA to a rheumatologist.

Dr. Alexander said they found that using the screening tool was better than having no referral strategy, explaining that screening helped diagnose about 34% of the study population with axSpA, whereas if a patient came in with chronic back pain to a primary care physician without any screening and ultimately to a rheumatologist, “you’re only capturing about 20%,” she said, citing estimates in the literature.
 

Questions may need rewording

However, the researchers found that patient interpretation of the screening questions was different depending on whether they were answering online or directly from a rheumatologist’s in-person questions. For more success, Dr. Alexander said, the questions may need to be reworded or more education may be needed for both patients and physicians to get more valid information.

For instance, she said, when the screening tool asks about inflammation, the patient may assume the physician is asking about pain and answer one way, but when a rheumatologist asks the question a slightly different way in the clinic, the patient may give a different answer.
 

First questions in portal, on social media

In the screening intervention (called A-tool) patients first answered three questions via the MyChart portal or Facebook. If they answered all three questions positively, they would move on to another round of questions and the answers would decide whether they would be eligible to come into the rheumatologist to get evaluated for axSpA.

At the study visit, rheumatologists asked the same questions as the online A-tool, which focus on SpA features with reasonable sensitivity and specificity for axSpA (no labs or imaging included). Clinicians’ judgment was considered the gold standard for diagnosis of axSpA.

The authors reported that 1,274 patients answered questions with the screening tool via Facebook (50%) and MyChart (50%) from April 2019 to February 2022. Among the responders, 507 (40%) were eligible for a rheumatologist visit.

As of May 2022, 100 patients were enrolled. Of the enrolled patients, 86 patients completed all the study procedures, including study visit, labs, and imaging (x-ray and MRI of the pelvis). Of the 86 patients, 29 (34%) were diagnosed with axSpA.

The tool appears to help narrow the chronic back pain patients who need to be seen by a rheumatologist for potential axSpA, Dr. Alexander said, which may help to speed diagnosis and also save time and resources.

Dr. McDermott, Dr. Dubreuil, and Dr. Alexander reported no relevant financial relationships. The FaxSpA study was supported with funding from Novartis and the Spondylitis Association of America.

CLEVELAND – With early diagnosis an ongoing complex target for axial spondyloarthritis (axSpA), new research may help to answer where the biggest delays lie.

Gregory McDermott, MD, a research fellow at Brigham and Women’s Hospital in Boston, led a pilot study with data from Mass General Brigham electronic health records. He shared top results at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN) , where addressing delay in diagnosis was a major theme.

Included in the cohort were 554 patients who had three ICD-9 or ICD-10 codes and an imaging report of sacroiliitis, ankylosis, or syndesmophytes, and were screened via manual chart review for modified New York and Assessment of Spondyloarthritis International Society criteria.

The average diagnostic delay for axSpA was 6.8 years in this study (median, 3.8 years), relatively consistent with findings in previous studies globally, and the average age of onset was 29.5.

The researchers also factored in history of specialty care for back pain (orthopedics, physical medicine and rehabilitation, pain medicine) or extra-articular manifestations (ophthalmology, dermatology, gastroenterology) before axSpA diagnosis. Other factors included smoking and insurance status, along with age, sex, race, and other demographic data.

The results showed shorter delays in diagnosing axSpA were associated with older age at symptom onset and peripheral arthritis, whereas longer delays (more than 4 years) were associated with a history of uveitis, ankylosing spondylitis at diagnosis, and being among those in the 80-99th percentile on the social vulnerability index (SVI). The SVI includes U.S. census data on factors including housing type, household composition and disability status, employment status, minority status, non-English speaking, educational attainment, transportation, and mean income level.
 

Notable uveitis finding

Dr. McDermott said the team was surprised by the association between having had uveitis and delayed axSpA diagnosis.

Among patients with uveitis, 12% had a short delay from symptom onset to axSpA diagnosis of 0-1 years, but more than twice that percentage (27%) had a delay of more than 4 years (P < .001).

“We thought the finding related to uveitis was interesting and potentially clinically meaningful as 27% of axSpA patients in our cohort with more than 4 years of diagnostic delay sought ophthalmology care prior to their diagnosis, [compared with 13% of patients with a diagnosis within 1 year],” Dr. McDermott said. “This practice setting in particular may be a place where we can intervene with simple screening or increased education in order to get people appropriately referred to rheumatology care.”

Longer delays can lead to more functional impairment, radiographic progression, and work disability, as well as poorer quality of life, increased depression, and higher unemployment and health care costs, Dr. McDermott said.
 

Patients may miss key treatment window

Maureen Dubreuil, MD, MSc, assistant professor at Boston University and a rheumatologist with the VA Boston Healthcare System, who was not part of the study, said: “This study addressed a critically important problem in the field – that diagnosis of axSpA is delayed by 7 years, which is much longer than the average time to diagnosis for other forms of arthritis, such as rheumatoid arthritis, which is under 6 months.

“It is critical that diagnostic delay is reduced in axSpA because undiagnosed individuals may miss an important window of opportunity to receive treatment that prevents permanent structural damage and functional declines. This work, if confirmed in other data, would allow development of interventions to improve timely evaluation of individuals with chronic back pain who may have axSpA, particularly among those with within lower socioeconomic strata, and those who are older or have uveitis.”
 

Study tests screening tool

Among the ideas proposed for reducing the delay was a referral strategy with a screening tool.

Swetha Alexander, MD, a rheumatology fellow at the University of Utah, Salt Lake City, who presented her team’s poster, noted that, in the United States, patients with chronic back pain often come first to a primary care doctor or another specialty and not to a rheumatologist.

As an internal medicine resident at Yale University, New Haven, Conn., Dr. Alexander and colleagues there conducted the Finding Axial Spondyloarthritis (FaxSpA) study to test whether patient self-referral or referral by other physicians, guided by answers to a screening tool, could help to speed the process of getting patients more likely to have axSpA to a rheumatologist.

Dr. Alexander said they found that using the screening tool was better than having no referral strategy, explaining that screening helped diagnose about 34% of the study population with axSpA, whereas if a patient came in with chronic back pain to a primary care physician without any screening and ultimately to a rheumatologist, “you’re only capturing about 20%,” she said, citing estimates in the literature.
 

Questions may need rewording

However, the researchers found that patient interpretation of the screening questions was different depending on whether they were answering online or directly from a rheumatologist’s in-person questions. For more success, Dr. Alexander said, the questions may need to be reworded or more education may be needed for both patients and physicians to get more valid information.

For instance, she said, when the screening tool asks about inflammation, the patient may assume the physician is asking about pain and answer one way, but when a rheumatologist asks the question a slightly different way in the clinic, the patient may give a different answer.
 

First questions in portal, on social media

In the screening intervention (called A-tool) patients first answered three questions via the MyChart portal or Facebook. If they answered all three questions positively, they would move on to another round of questions and the answers would decide whether they would be eligible to come into the rheumatologist to get evaluated for axSpA.

At the study visit, rheumatologists asked the same questions as the online A-tool, which focus on SpA features with reasonable sensitivity and specificity for axSpA (no labs or imaging included). Clinicians’ judgment was considered the gold standard for diagnosis of axSpA.

The authors reported that 1,274 patients answered questions with the screening tool via Facebook (50%) and MyChart (50%) from April 2019 to February 2022. Among the responders, 507 (40%) were eligible for a rheumatologist visit.

As of May 2022, 100 patients were enrolled. Of the enrolled patients, 86 patients completed all the study procedures, including study visit, labs, and imaging (x-ray and MRI of the pelvis). Of the 86 patients, 29 (34%) were diagnosed with axSpA.

The tool appears to help narrow the chronic back pain patients who need to be seen by a rheumatologist for potential axSpA, Dr. Alexander said, which may help to speed diagnosis and also save time and resources.

Dr. McDermott, Dr. Dubreuil, and Dr. Alexander reported no relevant financial relationships. The FaxSpA study was supported with funding from Novartis and the Spondylitis Association of America.

CLEVELAND – With early diagnosis an ongoing complex target for axial spondyloarthritis (axSpA), new research may help to answer where the biggest delays lie.

Gregory McDermott, MD, a research fellow at Brigham and Women’s Hospital in Boston, led a pilot study with data from Mass General Brigham electronic health records. He shared top results at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN) , where addressing delay in diagnosis was a major theme.

Included in the cohort were 554 patients who had three ICD-9 or ICD-10 codes and an imaging report of sacroiliitis, ankylosis, or syndesmophytes, and were screened via manual chart review for modified New York and Assessment of Spondyloarthritis International Society criteria.

The average diagnostic delay for axSpA was 6.8 years in this study (median, 3.8 years), relatively consistent with findings in previous studies globally, and the average age of onset was 29.5.

The researchers also factored in history of specialty care for back pain (orthopedics, physical medicine and rehabilitation, pain medicine) or extra-articular manifestations (ophthalmology, dermatology, gastroenterology) before axSpA diagnosis. Other factors included smoking and insurance status, along with age, sex, race, and other demographic data.

The results showed shorter delays in diagnosing axSpA were associated with older age at symptom onset and peripheral arthritis, whereas longer delays (more than 4 years) were associated with a history of uveitis, ankylosing spondylitis at diagnosis, and being among those in the 80-99th percentile on the social vulnerability index (SVI). The SVI includes U.S. census data on factors including housing type, household composition and disability status, employment status, minority status, non-English speaking, educational attainment, transportation, and mean income level.
 

Notable uveitis finding

Dr. McDermott said the team was surprised by the association between having had uveitis and delayed axSpA diagnosis.

Among patients with uveitis, 12% had a short delay from symptom onset to axSpA diagnosis of 0-1 years, but more than twice that percentage (27%) had a delay of more than 4 years (P < .001).

“We thought the finding related to uveitis was interesting and potentially clinically meaningful as 27% of axSpA patients in our cohort with more than 4 years of diagnostic delay sought ophthalmology care prior to their diagnosis, [compared with 13% of patients with a diagnosis within 1 year],” Dr. McDermott said. “This practice setting in particular may be a place where we can intervene with simple screening or increased education in order to get people appropriately referred to rheumatology care.”

Longer delays can lead to more functional impairment, radiographic progression, and work disability, as well as poorer quality of life, increased depression, and higher unemployment and health care costs, Dr. McDermott said.
 

Patients may miss key treatment window

Maureen Dubreuil, MD, MSc, assistant professor at Boston University and a rheumatologist with the VA Boston Healthcare System, who was not part of the study, said: “This study addressed a critically important problem in the field – that diagnosis of axSpA is delayed by 7 years, which is much longer than the average time to diagnosis for other forms of arthritis, such as rheumatoid arthritis, which is under 6 months.

“It is critical that diagnostic delay is reduced in axSpA because undiagnosed individuals may miss an important window of opportunity to receive treatment that prevents permanent structural damage and functional declines. This work, if confirmed in other data, would allow development of interventions to improve timely evaluation of individuals with chronic back pain who may have axSpA, particularly among those with within lower socioeconomic strata, and those who are older or have uveitis.”
 

Study tests screening tool

Among the ideas proposed for reducing the delay was a referral strategy with a screening tool.

Swetha Alexander, MD, a rheumatology fellow at the University of Utah, Salt Lake City, who presented her team’s poster, noted that, in the United States, patients with chronic back pain often come first to a primary care doctor or another specialty and not to a rheumatologist.

As an internal medicine resident at Yale University, New Haven, Conn., Dr. Alexander and colleagues there conducted the Finding Axial Spondyloarthritis (FaxSpA) study to test whether patient self-referral or referral by other physicians, guided by answers to a screening tool, could help to speed the process of getting patients more likely to have axSpA to a rheumatologist.

Dr. Alexander said they found that using the screening tool was better than having no referral strategy, explaining that screening helped diagnose about 34% of the study population with axSpA, whereas if a patient came in with chronic back pain to a primary care physician without any screening and ultimately to a rheumatologist, “you’re only capturing about 20%,” she said, citing estimates in the literature.
 

Questions may need rewording

However, the researchers found that patient interpretation of the screening questions was different depending on whether they were answering online or directly from a rheumatologist’s in-person questions. For more success, Dr. Alexander said, the questions may need to be reworded or more education may be needed for both patients and physicians to get more valid information.

For instance, she said, when the screening tool asks about inflammation, the patient may assume the physician is asking about pain and answer one way, but when a rheumatologist asks the question a slightly different way in the clinic, the patient may give a different answer.
 

First questions in portal, on social media

In the screening intervention (called A-tool) patients first answered three questions via the MyChart portal or Facebook. If they answered all three questions positively, they would move on to another round of questions and the answers would decide whether they would be eligible to come into the rheumatologist to get evaluated for axSpA.

At the study visit, rheumatologists asked the same questions as the online A-tool, which focus on SpA features with reasonable sensitivity and specificity for axSpA (no labs or imaging included). Clinicians’ judgment was considered the gold standard for diagnosis of axSpA.

The authors reported that 1,274 patients answered questions with the screening tool via Facebook (50%) and MyChart (50%) from April 2019 to February 2022. Among the responders, 507 (40%) were eligible for a rheumatologist visit.

As of May 2022, 100 patients were enrolled. Of the enrolled patients, 86 patients completed all the study procedures, including study visit, labs, and imaging (x-ray and MRI of the pelvis). Of the 86 patients, 29 (34%) were diagnosed with axSpA.

The tool appears to help narrow the chronic back pain patients who need to be seen by a rheumatologist for potential axSpA, Dr. Alexander said, which may help to speed diagnosis and also save time and resources.

Dr. McDermott, Dr. Dubreuil, and Dr. Alexander reported no relevant financial relationships. The FaxSpA study was supported with funding from Novartis and the Spondylitis Association of America.

In what may be the first randomized trial to compare coronary intervention access using the distal or proximal radial arteries, researchers have found no significant differences between the two in hand function a year after the procedure.

The distal radial artery (DRA) access point is just below the thumb on the inside of the wrist. The proximal radial artery (PRA) entry is in the inside lower forearm above the wrist.

“There has been growing interest in the use of distal radial access given its ease of hemostasis, lower incidence of radial artery occlusions, as well as the more ergonomic favorable setup for a left radial access, which is typically utilized in patients with prior CABG who undergo a cardiac catheterization when used as alternative to femoral artery access,” Karim Al-Azizi, MD, of Texas A&M University, an interventional cardiologist and associate program director of the cardiology fellowship at  Baylor Scott & White Health, in Plano, Tex., said in an interview.

Baylor Scott &amp; White

Dr Al-Azizi presented the late-breaking 1-year results of the DIPRA–for Distal vs. Proximal Radial Artery–study at the Society for Cardiovascular Angiography & Interventions annual scientific sessions. The 30-day results of the DIPRA trial were presented in 2022 at this meeting.

Dr. Al-Azizi said DIPRA is the first randomized, controlled trial comparing hand function outcomes with the two approaches. “I think the biggest question for most investigators and most practitioners is that, is this safe on the hand? Are we doing the right thing by going into the radial artery in the anatomical snuff box in proximity to the radial nerve and would that affect motor function?” he said. “And it does not seem like it from a head-to-head comparison of proximal versus distal access.”

The DIPRA study randomized 300 patients 1:1 to cardiac catheterization through either the distal or proximal access. Of those, 216 completed 1-year follow-up, 112 randomized to DRA and 104 to PRA.

The study used three metrics to evaluate hand function: hand-grip strength; pinch test, which measured the strength of a pinch between the thumb and index finger; and QuickDASH, an abbreviated version of the Disabilities of the Arm, Shoulder, and Hand questionnaire, in which participants self-evaluate their hand function. Study protocol mandated that operators use ultrasound guidance for DRA access.

The 1-year results of all three measures showed no significant difference in change of hand function from baseline between the two groups. The composite average score change was –0.07 (–0.41, 0.44) for the DRA patients and –0.03. (–0.36, 0.44) for the PRA group (P = .59).

One-year change for the specific hand function measures for DRA and PRA, respectively, were: hand grip, 0.7 (–3, 4.5) vs. 1.3 (–2, 4.3) kg (P = .57); pinch grip, –0.1 (–1.1, 1) vs. –0.3 (–1, 0.7) kg (P = .66); and none for change in the QuickDASH score (–6.6, 2.3 vs. –4.6, 2.9) points (P = .58).

Outcomes at intervention were also similar. Bleeding incidence was 0% and 1.4% (P = .25) in the respective groups. Successful RA access was achieved in 96.7% and 98% (P = .72).

Baseline characteristics were balanced between the two groups: 75% were male; mean age was 66.6 ± 9.6 years; 32% had diabetes; 77% had hypertension; and 19% had a previous percutaneous coronary intervention.

One key strength of the DIPRA study Dr. Al-Azizi noted is that it included some investigators who were at the early stage of the learning curve with the procedure. A limitation is that it didn’t evaluate hand numbness or tingling, but hand sensory testing is “very subjective,” he said. “To avoid confusion, we decided to go with the more repeatable questionnaire rather than a sensation or sensory test,” he added.

The next step for his research team is to conduct a meta-analysis of studies that have evaluated DRA and PRA, Dr. Al-Azizi said.
 

‘Slow to the party’

U.S. interventional cardiologists have been “slow to the party” in adopting radial artery access for PCI, said David A. Cox, MD, of Sanger Heart and Vascular Institute in Charlotte, N.C., and SCAI communications committee chair. Even now uptake is low, compared with the rest of the world, he said.

“I can tell you what patients care about: Did you have to stick my groin?” he said at a SCAI press conference. “What they just want to know is that there are no issues with hand function.”

Some patients who need fine motor hand function would still opt for femoral access, he said.

“Are we looking at the right metric?” he asked Dr. Al-Azizi. “It took a long time to get American doctors to stick the radial, so why would I want to learn distal radial artery if I’m really pretty good at proximal and if it’s not inferior?”

Dr. Al-Azizi noted that previous studies showed a trend toward a lower incidence of radial artery occlusion (RAO) with DRA access. It also better preserves the renal arteries for dialysis and CABG, he said.

“The metric that would move the needle,” Dr. Cox noted, “is if you had radial artery occlusion rates vs. snuff box occlusion rates, and we don’t have that rate.”

Dr. Al-Azizi has no relevant financial disclosures. Dr. Cox disclosed financial relationships with Medtronic.

In what may be the first randomized trial to compare coronary intervention access using the distal or proximal radial arteries, researchers have found no significant differences between the two in hand function a year after the procedure.

The distal radial artery (DRA) access point is just below the thumb on the inside of the wrist. The proximal radial artery (PRA) entry is in the inside lower forearm above the wrist.

“There has been growing interest in the use of distal radial access given its ease of hemostasis, lower incidence of radial artery occlusions, as well as the more ergonomic favorable setup for a left radial access, which is typically utilized in patients with prior CABG who undergo a cardiac catheterization when used as alternative to femoral artery access,” Karim Al-Azizi, MD, of Texas A&M University, an interventional cardiologist and associate program director of the cardiology fellowship at  Baylor Scott & White Health, in Plano, Tex., said in an interview.

Baylor Scott &amp; White

Dr Al-Azizi presented the late-breaking 1-year results of the DIPRA–for Distal vs. Proximal Radial Artery–study at the Society for Cardiovascular Angiography & Interventions annual scientific sessions. The 30-day results of the DIPRA trial were presented in 2022 at this meeting.

Dr. Al-Azizi said DIPRA is the first randomized, controlled trial comparing hand function outcomes with the two approaches. “I think the biggest question for most investigators and most practitioners is that, is this safe on the hand? Are we doing the right thing by going into the radial artery in the anatomical snuff box in proximity to the radial nerve and would that affect motor function?” he said. “And it does not seem like it from a head-to-head comparison of proximal versus distal access.”

The DIPRA study randomized 300 patients 1:1 to cardiac catheterization through either the distal or proximal access. Of those, 216 completed 1-year follow-up, 112 randomized to DRA and 104 to PRA.

The study used three metrics to evaluate hand function: hand-grip strength; pinch test, which measured the strength of a pinch between the thumb and index finger; and QuickDASH, an abbreviated version of the Disabilities of the Arm, Shoulder, and Hand questionnaire, in which participants self-evaluate their hand function. Study protocol mandated that operators use ultrasound guidance for DRA access.

The 1-year results of all three measures showed no significant difference in change of hand function from baseline between the two groups. The composite average score change was –0.07 (–0.41, 0.44) for the DRA patients and –0.03. (–0.36, 0.44) for the PRA group (P = .59).

One-year change for the specific hand function measures for DRA and PRA, respectively, were: hand grip, 0.7 (–3, 4.5) vs. 1.3 (–2, 4.3) kg (P = .57); pinch grip, –0.1 (–1.1, 1) vs. –0.3 (–1, 0.7) kg (P = .66); and none for change in the QuickDASH score (–6.6, 2.3 vs. –4.6, 2.9) points (P = .58).

Outcomes at intervention were also similar. Bleeding incidence was 0% and 1.4% (P = .25) in the respective groups. Successful RA access was achieved in 96.7% and 98% (P = .72).

Baseline characteristics were balanced between the two groups: 75% were male; mean age was 66.6 ± 9.6 years; 32% had diabetes; 77% had hypertension; and 19% had a previous percutaneous coronary intervention.

One key strength of the DIPRA study Dr. Al-Azizi noted is that it included some investigators who were at the early stage of the learning curve with the procedure. A limitation is that it didn’t evaluate hand numbness or tingling, but hand sensory testing is “very subjective,” he said. “To avoid confusion, we decided to go with the more repeatable questionnaire rather than a sensation or sensory test,” he added.

The next step for his research team is to conduct a meta-analysis of studies that have evaluated DRA and PRA, Dr. Al-Azizi said.
 

‘Slow to the party’

U.S. interventional cardiologists have been “slow to the party” in adopting radial artery access for PCI, said David A. Cox, MD, of Sanger Heart and Vascular Institute in Charlotte, N.C., and SCAI communications committee chair. Even now uptake is low, compared with the rest of the world, he said.

“I can tell you what patients care about: Did you have to stick my groin?” he said at a SCAI press conference. “What they just want to know is that there are no issues with hand function.”

Some patients who need fine motor hand function would still opt for femoral access, he said.

“Are we looking at the right metric?” he asked Dr. Al-Azizi. “It took a long time to get American doctors to stick the radial, so why would I want to learn distal radial artery if I’m really pretty good at proximal and if it’s not inferior?”

Dr. Al-Azizi noted that previous studies showed a trend toward a lower incidence of radial artery occlusion (RAO) with DRA access. It also better preserves the renal arteries for dialysis and CABG, he said.

“The metric that would move the needle,” Dr. Cox noted, “is if you had radial artery occlusion rates vs. snuff box occlusion rates, and we don’t have that rate.”

Dr. Al-Azizi has no relevant financial disclosures. Dr. Cox disclosed financial relationships with Medtronic.

In what may be the first randomized trial to compare coronary intervention access using the distal or proximal radial arteries, researchers have found no significant differences between the two in hand function a year after the procedure.

The distal radial artery (DRA) access point is just below the thumb on the inside of the wrist. The proximal radial artery (PRA) entry is in the inside lower forearm above the wrist.

“There has been growing interest in the use of distal radial access given its ease of hemostasis, lower incidence of radial artery occlusions, as well as the more ergonomic favorable setup for a left radial access, which is typically utilized in patients with prior CABG who undergo a cardiac catheterization when used as alternative to femoral artery access,” Karim Al-Azizi, MD, of Texas A&M University, an interventional cardiologist and associate program director of the cardiology fellowship at  Baylor Scott & White Health, in Plano, Tex., said in an interview.

Baylor Scott &amp; White

Dr Al-Azizi presented the late-breaking 1-year results of the DIPRA–for Distal vs. Proximal Radial Artery–study at the Society for Cardiovascular Angiography & Interventions annual scientific sessions. The 30-day results of the DIPRA trial were presented in 2022 at this meeting.

Dr. Al-Azizi said DIPRA is the first randomized, controlled trial comparing hand function outcomes with the two approaches. “I think the biggest question for most investigators and most practitioners is that, is this safe on the hand? Are we doing the right thing by going into the radial artery in the anatomical snuff box in proximity to the radial nerve and would that affect motor function?” he said. “And it does not seem like it from a head-to-head comparison of proximal versus distal access.”

The DIPRA study randomized 300 patients 1:1 to cardiac catheterization through either the distal or proximal access. Of those, 216 completed 1-year follow-up, 112 randomized to DRA and 104 to PRA.

The study used three metrics to evaluate hand function: hand-grip strength; pinch test, which measured the strength of a pinch between the thumb and index finger; and QuickDASH, an abbreviated version of the Disabilities of the Arm, Shoulder, and Hand questionnaire, in which participants self-evaluate their hand function. Study protocol mandated that operators use ultrasound guidance for DRA access.

The 1-year results of all three measures showed no significant difference in change of hand function from baseline between the two groups. The composite average score change was –0.07 (–0.41, 0.44) for the DRA patients and –0.03. (–0.36, 0.44) for the PRA group (P = .59).

One-year change for the specific hand function measures for DRA and PRA, respectively, were: hand grip, 0.7 (–3, 4.5) vs. 1.3 (–2, 4.3) kg (P = .57); pinch grip, –0.1 (–1.1, 1) vs. –0.3 (–1, 0.7) kg (P = .66); and none for change in the QuickDASH score (–6.6, 2.3 vs. –4.6, 2.9) points (P = .58).

Outcomes at intervention were also similar. Bleeding incidence was 0% and 1.4% (P = .25) in the respective groups. Successful RA access was achieved in 96.7% and 98% (P = .72).

Baseline characteristics were balanced between the two groups: 75% were male; mean age was 66.6 ± 9.6 years; 32% had diabetes; 77% had hypertension; and 19% had a previous percutaneous coronary intervention.

One key strength of the DIPRA study Dr. Al-Azizi noted is that it included some investigators who were at the early stage of the learning curve with the procedure. A limitation is that it didn’t evaluate hand numbness or tingling, but hand sensory testing is “very subjective,” he said. “To avoid confusion, we decided to go with the more repeatable questionnaire rather than a sensation or sensory test,” he added.

The next step for his research team is to conduct a meta-analysis of studies that have evaluated DRA and PRA, Dr. Al-Azizi said.
 

‘Slow to the party’

U.S. interventional cardiologists have been “slow to the party” in adopting radial artery access for PCI, said David A. Cox, MD, of Sanger Heart and Vascular Institute in Charlotte, N.C., and SCAI communications committee chair. Even now uptake is low, compared with the rest of the world, he said.

“I can tell you what patients care about: Did you have to stick my groin?” he said at a SCAI press conference. “What they just want to know is that there are no issues with hand function.”

Some patients who need fine motor hand function would still opt for femoral access, he said.

“Are we looking at the right metric?” he asked Dr. Al-Azizi. “It took a long time to get American doctors to stick the radial, so why would I want to learn distal radial artery if I’m really pretty good at proximal and if it’s not inferior?”

Dr. Al-Azizi noted that previous studies showed a trend toward a lower incidence of radial artery occlusion (RAO) with DRA access. It also better preserves the renal arteries for dialysis and CABG, he said.

“The metric that would move the needle,” Dr. Cox noted, “is if you had radial artery occlusion rates vs. snuff box occlusion rates, and we don’t have that rate.”

Dr. Al-Azizi has no relevant financial disclosures. Dr. Cox disclosed financial relationships with Medtronic.

Patients with arginine vasopressin deficiency (AVD) appear to also be deficient in oxytocin, the “love hormone,” suggesting a possible pathway for treating the psychological symptoms associated with the illness.
 

Formerly known as central diabetes insipidus, AVD is a rare neuroendocrine condition in which fluid isn’t regulated, leading to polydipsia and polyuria. The vasopressin receptor 2 agonist desmopressin treats those symptoms, but patients often also experience psychopathological problems, such as increased anxiety, depression, and emotional withdrawal.

It has been hypothesized that those symptoms are caused by a concurrent deficiency of the so-called “love hormone” oxytocin, given the anatomic proximity of vasopressin and oxytocin production in the brain.

Now, for the first time, researchers have demonstrated evidence of that phenomenon using 3,4-methylenedioxymethamphetamine (MDMA, also known as “ecstasy”) to provoke oxytocin release. In individuals without AVD, use of MDMA resulted in large increases in plasma oxytocin concentrations, whereas there was very little response among those with AVD, suggesting that the latter patients were deficient in oxytocin.

“These findings are suggestive of a new hypothalamic–pituitary disease entity and contribute to deepening our understanding of oxytocin as a key hormone in centrally generated socioemotional effects, as reflected by reduced prosocial, empathic, and anxiolytic effects in patients with an oxytocin deficiency,” Cihan Atila, MD, of the University of Basel (Switzerland), and colleagues wrote.

“Future studies should evaluate whether oxytocin replacement therapy can alleviate residual symptoms related to oxytocin deficiency in patients with [AVD],” they added.

The findings, from a single-center study of 15 patients with AVD and 15 healthy control persons, were published online in The Lancet Diabetes and Endocrinology.

“Atila and colleagues provide compelling evidence for a clinically relevant oxytocin deficiency in this population of patients, which appears to be at least partly responsible for the associated increase in psychopathological findings,” say Mirela Diana Ilie, MD, an endocrinologist in training at the National Institute of Endocrinology, Bucharest, Romania, and Gérald Raverot, MD, professor of endocrinology at Lyon (France) University Hospital, France, in an accompanying editorial.

“From a therapeutic viewpoint, the findings ... pave the way to intervention studies assessing the effect of intranasal oxytocin in patients with [AVD] and better clinical care for these patients,” they add.

However, Dr. Ilie and Dr. Raverot urged caution for a variety of reasons, including the fact that, thus far, only one patient with arginine vasopressin deficiency has been administered oxytocin on a long-term basis. They suggested further studies to answer many pertinent questions, such as what the appropriate doses and frequency of oxytocin administration are, whether the dose should remain constant or be increased during stress or particular acute situations, whether long-term administration is suitable for all patients regardless of the extent of oxytocin deficiency, and how follow-up should be conducted.

“Answering these questions seems all the more important considering that oxytocin therapy has shown conflicting results when administered for psychiatric disorders,” said Dr. Ilie and Dr. Raverot.

In the meantime, “independent of the potential use of oxytocin, given the frequent and important psychological burden of [AVD], clinicians should screen patients for psychological comorbidities and should not hesitate to refer them to appropriate psychological and psychiatric care,” the editorialists wrote.
 

Eightfold increase in plasma oxytocin levels in patients vs. control persons

The 15 AVD patients and 15 matched healthy control persons were recruited between Feb. 1, 2021, and May 1, 2022. Of those with AVD, eight had an isolated posterior pituitary dysfunction, and seven had a combined pituitary dysfunction. The patients had significantly higher scores on measures of anxiety, alexithymia, and depression, and self-reported mental health was lower, compared with control persons.

All participants were randomly assigned to receive either a single oral dose of MDMA 100 mg or placebo in the first experimental session and the opposite treatment in a second session. There was a 2-week washout period in between.

Median oxytocin concentrations at baseline were 77 pg/mL in the healthy control persons and peaked after MDMA stimulation to 624 pg/mL after 180 minutes, with a maximum of 659 pg/mL. In contrast, among the patients with AVD, baseline oxytocin levels were 60 pg/mL and peaked to just 92 pg/mL after 150 minutes, with a maximum change in concentration of 66 pg/mL.

In response to MDMA, there was an eightfold increase in plasma oxytocin area under the curve among the control persons versus no notable increase in the patients with AVD.

The net incremental oxytocin area under the curve after MDMA administration was 82% higher among control persons than patients (P < .0001).

The MDMA-induced increase in oxytocin was associated with reduced anxiety scores among the control persons but not the AVD patients. Similar results were seen for subjective prosocial and empathic effects.

The most frequently reported adverse effects of the MDMA provocation in both groups were fatigue, lack of appetite, and dry mouth, all of which occurred in more than half of participants.

“These findings contradict the previous theory that oxytocin stimulation has only a secondary role in the effects of MDMA. Our results, by contrast, suggest a paradigm shift and underline the importance of oxytocin as a key feature of the effects of MDMA,” Dr. Atila and colleagues concluded.

Dr. Atila, Dr. Ilie, and Dr. Raverot have disclosed no relevant financial relationships. One study coauthor owns stock in MiniMed.

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

Patients with arginine vasopressin deficiency (AVD) appear to also be deficient in oxytocin, the “love hormone,” suggesting a possible pathway for treating the psychological symptoms associated with the illness.
 

Formerly known as central diabetes insipidus, AVD is a rare neuroendocrine condition in which fluid isn’t regulated, leading to polydipsia and polyuria. The vasopressin receptor 2 agonist desmopressin treats those symptoms, but patients often also experience psychopathological problems, such as increased anxiety, depression, and emotional withdrawal.

It has been hypothesized that those symptoms are caused by a concurrent deficiency of the so-called “love hormone” oxytocin, given the anatomic proximity of vasopressin and oxytocin production in the brain.

Now, for the first time, researchers have demonstrated evidence of that phenomenon using 3,4-methylenedioxymethamphetamine (MDMA, also known as “ecstasy”) to provoke oxytocin release. In individuals without AVD, use of MDMA resulted in large increases in plasma oxytocin concentrations, whereas there was very little response among those with AVD, suggesting that the latter patients were deficient in oxytocin.

“These findings are suggestive of a new hypothalamic–pituitary disease entity and contribute to deepening our understanding of oxytocin as a key hormone in centrally generated socioemotional effects, as reflected by reduced prosocial, empathic, and anxiolytic effects in patients with an oxytocin deficiency,” Cihan Atila, MD, of the University of Basel (Switzerland), and colleagues wrote.

“Future studies should evaluate whether oxytocin replacement therapy can alleviate residual symptoms related to oxytocin deficiency in patients with [AVD],” they added.

The findings, from a single-center study of 15 patients with AVD and 15 healthy control persons, were published online in The Lancet Diabetes and Endocrinology.

“Atila and colleagues provide compelling evidence for a clinically relevant oxytocin deficiency in this population of patients, which appears to be at least partly responsible for the associated increase in psychopathological findings,” say Mirela Diana Ilie, MD, an endocrinologist in training at the National Institute of Endocrinology, Bucharest, Romania, and Gérald Raverot, MD, professor of endocrinology at Lyon (France) University Hospital, France, in an accompanying editorial.

“From a therapeutic viewpoint, the findings ... pave the way to intervention studies assessing the effect of intranasal oxytocin in patients with [AVD] and better clinical care for these patients,” they add.

However, Dr. Ilie and Dr. Raverot urged caution for a variety of reasons, including the fact that, thus far, only one patient with arginine vasopressin deficiency has been administered oxytocin on a long-term basis. They suggested further studies to answer many pertinent questions, such as what the appropriate doses and frequency of oxytocin administration are, whether the dose should remain constant or be increased during stress or particular acute situations, whether long-term administration is suitable for all patients regardless of the extent of oxytocin deficiency, and how follow-up should be conducted.

“Answering these questions seems all the more important considering that oxytocin therapy has shown conflicting results when administered for psychiatric disorders,” said Dr. Ilie and Dr. Raverot.

In the meantime, “independent of the potential use of oxytocin, given the frequent and important psychological burden of [AVD], clinicians should screen patients for psychological comorbidities and should not hesitate to refer them to appropriate psychological and psychiatric care,” the editorialists wrote.
 

Eightfold increase in plasma oxytocin levels in patients vs. control persons

The 15 AVD patients and 15 matched healthy control persons were recruited between Feb. 1, 2021, and May 1, 2022. Of those with AVD, eight had an isolated posterior pituitary dysfunction, and seven had a combined pituitary dysfunction. The patients had significantly higher scores on measures of anxiety, alexithymia, and depression, and self-reported mental health was lower, compared with control persons.

All participants were randomly assigned to receive either a single oral dose of MDMA 100 mg or placebo in the first experimental session and the opposite treatment in a second session. There was a 2-week washout period in between.

Median oxytocin concentrations at baseline were 77 pg/mL in the healthy control persons and peaked after MDMA stimulation to 624 pg/mL after 180 minutes, with a maximum of 659 pg/mL. In contrast, among the patients with AVD, baseline oxytocin levels were 60 pg/mL and peaked to just 92 pg/mL after 150 minutes, with a maximum change in concentration of 66 pg/mL.

In response to MDMA, there was an eightfold increase in plasma oxytocin area under the curve among the control persons versus no notable increase in the patients with AVD.

The net incremental oxytocin area under the curve after MDMA administration was 82% higher among control persons than patients (P < .0001).

The MDMA-induced increase in oxytocin was associated with reduced anxiety scores among the control persons but not the AVD patients. Similar results were seen for subjective prosocial and empathic effects.

The most frequently reported adverse effects of the MDMA provocation in both groups were fatigue, lack of appetite, and dry mouth, all of which occurred in more than half of participants.

“These findings contradict the previous theory that oxytocin stimulation has only a secondary role in the effects of MDMA. Our results, by contrast, suggest a paradigm shift and underline the importance of oxytocin as a key feature of the effects of MDMA,” Dr. Atila and colleagues concluded.

Dr. Atila, Dr. Ilie, and Dr. Raverot have disclosed no relevant financial relationships. One study coauthor owns stock in MiniMed.

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

Patients with arginine vasopressin deficiency (AVD) appear to also be deficient in oxytocin, the “love hormone,” suggesting a possible pathway for treating the psychological symptoms associated with the illness.
 

Formerly known as central diabetes insipidus, AVD is a rare neuroendocrine condition in which fluid isn’t regulated, leading to polydipsia and polyuria. The vasopressin receptor 2 agonist desmopressin treats those symptoms, but patients often also experience psychopathological problems, such as increased anxiety, depression, and emotional withdrawal.

It has been hypothesized that those symptoms are caused by a concurrent deficiency of the so-called “love hormone” oxytocin, given the anatomic proximity of vasopressin and oxytocin production in the brain.

Now, for the first time, researchers have demonstrated evidence of that phenomenon using 3,4-methylenedioxymethamphetamine (MDMA, also known as “ecstasy”) to provoke oxytocin release. In individuals without AVD, use of MDMA resulted in large increases in plasma oxytocin concentrations, whereas there was very little response among those with AVD, suggesting that the latter patients were deficient in oxytocin.

“These findings are suggestive of a new hypothalamic–pituitary disease entity and contribute to deepening our understanding of oxytocin as a key hormone in centrally generated socioemotional effects, as reflected by reduced prosocial, empathic, and anxiolytic effects in patients with an oxytocin deficiency,” Cihan Atila, MD, of the University of Basel (Switzerland), and colleagues wrote.

“Future studies should evaluate whether oxytocin replacement therapy can alleviate residual symptoms related to oxytocin deficiency in patients with [AVD],” they added.

The findings, from a single-center study of 15 patients with AVD and 15 healthy control persons, were published online in The Lancet Diabetes and Endocrinology.

“Atila and colleagues provide compelling evidence for a clinically relevant oxytocin deficiency in this population of patients, which appears to be at least partly responsible for the associated increase in psychopathological findings,” say Mirela Diana Ilie, MD, an endocrinologist in training at the National Institute of Endocrinology, Bucharest, Romania, and Gérald Raverot, MD, professor of endocrinology at Lyon (France) University Hospital, France, in an accompanying editorial.

“From a therapeutic viewpoint, the findings ... pave the way to intervention studies assessing the effect of intranasal oxytocin in patients with [AVD] and better clinical care for these patients,” they add.

However, Dr. Ilie and Dr. Raverot urged caution for a variety of reasons, including the fact that, thus far, only one patient with arginine vasopressin deficiency has been administered oxytocin on a long-term basis. They suggested further studies to answer many pertinent questions, such as what the appropriate doses and frequency of oxytocin administration are, whether the dose should remain constant or be increased during stress or particular acute situations, whether long-term administration is suitable for all patients regardless of the extent of oxytocin deficiency, and how follow-up should be conducted.

“Answering these questions seems all the more important considering that oxytocin therapy has shown conflicting results when administered for psychiatric disorders,” said Dr. Ilie and Dr. Raverot.

In the meantime, “independent of the potential use of oxytocin, given the frequent and important psychological burden of [AVD], clinicians should screen patients for psychological comorbidities and should not hesitate to refer them to appropriate psychological and psychiatric care,” the editorialists wrote.
 

Eightfold increase in plasma oxytocin levels in patients vs. control persons

The 15 AVD patients and 15 matched healthy control persons were recruited between Feb. 1, 2021, and May 1, 2022. Of those with AVD, eight had an isolated posterior pituitary dysfunction, and seven had a combined pituitary dysfunction. The patients had significantly higher scores on measures of anxiety, alexithymia, and depression, and self-reported mental health was lower, compared with control persons.

All participants were randomly assigned to receive either a single oral dose of MDMA 100 mg or placebo in the first experimental session and the opposite treatment in a second session. There was a 2-week washout period in between.

Median oxytocin concentrations at baseline were 77 pg/mL in the healthy control persons and peaked after MDMA stimulation to 624 pg/mL after 180 minutes, with a maximum of 659 pg/mL. In contrast, among the patients with AVD, baseline oxytocin levels were 60 pg/mL and peaked to just 92 pg/mL after 150 minutes, with a maximum change in concentration of 66 pg/mL.

In response to MDMA, there was an eightfold increase in plasma oxytocin area under the curve among the control persons versus no notable increase in the patients with AVD.

The net incremental oxytocin area under the curve after MDMA administration was 82% higher among control persons than patients (P < .0001).

The MDMA-induced increase in oxytocin was associated with reduced anxiety scores among the control persons but not the AVD patients. Similar results were seen for subjective prosocial and empathic effects.

The most frequently reported adverse effects of the MDMA provocation in both groups were fatigue, lack of appetite, and dry mouth, all of which occurred in more than half of participants.

“These findings contradict the previous theory that oxytocin stimulation has only a secondary role in the effects of MDMA. Our results, by contrast, suggest a paradigm shift and underline the importance of oxytocin as a key feature of the effects of MDMA,” Dr. Atila and colleagues concluded.

Dr. Atila, Dr. Ilie, and Dr. Raverot have disclosed no relevant financial relationships. One study coauthor owns stock in MiniMed.

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

BALTIMORE – A single 60-mg daily dose of nifedipine appeared similarly effective as taking a 30-mg dose twice daily for treating hypertensive disorders in pregnancy, according to research presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.*

Isabelle Band

The findings suggest that starting patients on a once-daily 60-mg dose is therefore reasonable, Isabelle Band, BA, a medical student at the Icahn School of Medicine at Mount Sinai, New York, told attendees. Ms. Band said in an interview that there does not appear to be a consensus on the standard of care for nifedipine dosing regimen in this population but that previous in vitro studies have shown increased metabolism of nifedipine in a physiologic state that mimics pregnancy.

“I’ve spoken to some colleagues here who say that they frequently have this debate of which dosing regimen to go with,” Ms. Band said. “I was pleasantly surprised that there was no significant difference between the two dosing regimens because once-daily dosing is less burdensome for patients and will likely improve compliance and convenience for patients.” An additional benefit of once-daily dosing relates to payers because anecdotal reports suggest insurance companies do not tend to approve twice-daily dosing as readily as once-daily dosing, Ms. Band added.

Ms. Band and her colleagues conducted a retrospective chart review of all patients with hypertensive disorders of pregnancy who were admitted to the Mount Sinai Health System between Jan. 1, 2015, and April 30, 2021, and were prescribed nifedipine in a once-daily (60-mg) or twice-daily (two 30-mg) dose. They excluded patients with renal disease and those already taking hypertensives prior to admission.

Among 237 patients who met the criteria, 59% received 60 mg in a twice-daily 30-mg dose, and 41% received 60 mg in a once-daily dose. Among patients requiring an up titration, two-thirds (67%) needed an increase in the nifedipine dose – the most common adjustment – and 20.7% needed both an increase in nifedipine and an additional medication.

The researchers observed no statistically significant differences in the proportion of patients who required a dose increase or an additional antihypertensive in the group taking the twice-daily dose (33.8%) or those receiving the once-daily dose (35.7%). This finding remained statistically insignificant after controlling for gestational diabetes, delivery mode, administration of Lasix, and receipt of emergency antihypertensive treatment (P = .71). The time that passed before patients needed a dose increase was also statistically similar between the groups: 24.3 hours in the twice-daily group and 24 hours in the once-daily group (P = .49).

There were no statistically significant differences in the need for a dose increase or an additional hypertensive agent based on race, ethnicity, body mass index, or history of preeclampsia as well. However, 24.5% of those taking the once-daily dosage had a history of preeclampsia, compared with 7.2% of those taking the twice-daily dosage (P < .001). Further, the median number of prior pregnancies was two in the twice-daily group versus three in the once-daily group (P = .002).

The authors found no significant difference between the two dosing groups in the need for emergency hypertensive treatment after reaching the study dose or in readmission for blood pressure control. In the twice-daily group, 21.6% of patients needed emergency antihypertensive treatment, compared with 14.3% in the once-daily group (P = .19). Readmission was necessary for 7.2% of the twice-daily group and 6.1% of the once-daily group (P > .99).

A subgroup analysis compared those who started nifedipine antepartum and those who started it post partum, but again, no significant difference in the dosing regimens existed.

Michael Ruma, MD, a maternal-fetal medicine specialist at Perinatal Associates of New Mexico in Albuquerque, was not involved in the study and said he welcomed the results.

“We have too many choices in medicine, so we need to just simplify the plan of attack,” reducing the number of things that clinicians need to think about, Dr. Ruma said in an interview. “A singular dose is always easiest for the patient, always easier for nursing staff, and usually, if you can optimize the dosing, that’s the best approach.”

Annabeth Brewton, MD, a resident at University of Tennessee, Knoxville, agreed, adding that new parents already have a lot going on immediately post partum.

“They’re going to be breastfeeding, they’re not sleeping, they’re going to forget to take that [second] dose,” Dr. Brewton said.

Ms. Band and Dr. Brewton had no disclosures. Dr. Ruma reported consulting and speaking for Hologic and consulting for Philips Ultrasound.

Correction, 5/24/23: An earlier version of this article misstated the daily doses of nifedipine. The study compared a single 60-mg daily dose with a 30-mg dose taken twice daily.  

BALTIMORE – A single 60-mg daily dose of nifedipine appeared similarly effective as taking a 30-mg dose twice daily for treating hypertensive disorders in pregnancy, according to research presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.*

Isabelle Band

The findings suggest that starting patients on a once-daily 60-mg dose is therefore reasonable, Isabelle Band, BA, a medical student at the Icahn School of Medicine at Mount Sinai, New York, told attendees. Ms. Band said in an interview that there does not appear to be a consensus on the standard of care for nifedipine dosing regimen in this population but that previous in vitro studies have shown increased metabolism of nifedipine in a physiologic state that mimics pregnancy.

“I’ve spoken to some colleagues here who say that they frequently have this debate of which dosing regimen to go with,” Ms. Band said. “I was pleasantly surprised that there was no significant difference between the two dosing regimens because once-daily dosing is less burdensome for patients and will likely improve compliance and convenience for patients.” An additional benefit of once-daily dosing relates to payers because anecdotal reports suggest insurance companies do not tend to approve twice-daily dosing as readily as once-daily dosing, Ms. Band added.

Ms. Band and her colleagues conducted a retrospective chart review of all patients with hypertensive disorders of pregnancy who were admitted to the Mount Sinai Health System between Jan. 1, 2015, and April 30, 2021, and were prescribed nifedipine in a once-daily (60-mg) or twice-daily (two 30-mg) dose. They excluded patients with renal disease and those already taking hypertensives prior to admission.

Among 237 patients who met the criteria, 59% received 60 mg in a twice-daily 30-mg dose, and 41% received 60 mg in a once-daily dose. Among patients requiring an up titration, two-thirds (67%) needed an increase in the nifedipine dose – the most common adjustment – and 20.7% needed both an increase in nifedipine and an additional medication.

The researchers observed no statistically significant differences in the proportion of patients who required a dose increase or an additional antihypertensive in the group taking the twice-daily dose (33.8%) or those receiving the once-daily dose (35.7%). This finding remained statistically insignificant after controlling for gestational diabetes, delivery mode, administration of Lasix, and receipt of emergency antihypertensive treatment (P = .71). The time that passed before patients needed a dose increase was also statistically similar between the groups: 24.3 hours in the twice-daily group and 24 hours in the once-daily group (P = .49).

There were no statistically significant differences in the need for a dose increase or an additional hypertensive agent based on race, ethnicity, body mass index, or history of preeclampsia as well. However, 24.5% of those taking the once-daily dosage had a history of preeclampsia, compared with 7.2% of those taking the twice-daily dosage (P < .001). Further, the median number of prior pregnancies was two in the twice-daily group versus three in the once-daily group (P = .002).

The authors found no significant difference between the two dosing groups in the need for emergency hypertensive treatment after reaching the study dose or in readmission for blood pressure control. In the twice-daily group, 21.6% of patients needed emergency antihypertensive treatment, compared with 14.3% in the once-daily group (P = .19). Readmission was necessary for 7.2% of the twice-daily group and 6.1% of the once-daily group (P > .99).

A subgroup analysis compared those who started nifedipine antepartum and those who started it post partum, but again, no significant difference in the dosing regimens existed.

Michael Ruma, MD, a maternal-fetal medicine specialist at Perinatal Associates of New Mexico in Albuquerque, was not involved in the study and said he welcomed the results.

“We have too many choices in medicine, so we need to just simplify the plan of attack,” reducing the number of things that clinicians need to think about, Dr. Ruma said in an interview. “A singular dose is always easiest for the patient, always easier for nursing staff, and usually, if you can optimize the dosing, that’s the best approach.”

Annabeth Brewton, MD, a resident at University of Tennessee, Knoxville, agreed, adding that new parents already have a lot going on immediately post partum.

“They’re going to be breastfeeding, they’re not sleeping, they’re going to forget to take that [second] dose,” Dr. Brewton said.

Ms. Band and Dr. Brewton had no disclosures. Dr. Ruma reported consulting and speaking for Hologic and consulting for Philips Ultrasound.

Correction, 5/24/23: An earlier version of this article misstated the daily doses of nifedipine. The study compared a single 60-mg daily dose with a 30-mg dose taken twice daily.  

BALTIMORE – A single 60-mg daily dose of nifedipine appeared similarly effective as taking a 30-mg dose twice daily for treating hypertensive disorders in pregnancy, according to research presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.*

Isabelle Band

The findings suggest that starting patients on a once-daily 60-mg dose is therefore reasonable, Isabelle Band, BA, a medical student at the Icahn School of Medicine at Mount Sinai, New York, told attendees. Ms. Band said in an interview that there does not appear to be a consensus on the standard of care for nifedipine dosing regimen in this population but that previous in vitro studies have shown increased metabolism of nifedipine in a physiologic state that mimics pregnancy.

“I’ve spoken to some colleagues here who say that they frequently have this debate of which dosing regimen to go with,” Ms. Band said. “I was pleasantly surprised that there was no significant difference between the two dosing regimens because once-daily dosing is less burdensome for patients and will likely improve compliance and convenience for patients.” An additional benefit of once-daily dosing relates to payers because anecdotal reports suggest insurance companies do not tend to approve twice-daily dosing as readily as once-daily dosing, Ms. Band added.

Ms. Band and her colleagues conducted a retrospective chart review of all patients with hypertensive disorders of pregnancy who were admitted to the Mount Sinai Health System between Jan. 1, 2015, and April 30, 2021, and were prescribed nifedipine in a once-daily (60-mg) or twice-daily (two 30-mg) dose. They excluded patients with renal disease and those already taking hypertensives prior to admission.

Among 237 patients who met the criteria, 59% received 60 mg in a twice-daily 30-mg dose, and 41% received 60 mg in a once-daily dose. Among patients requiring an up titration, two-thirds (67%) needed an increase in the nifedipine dose – the most common adjustment – and 20.7% needed both an increase in nifedipine and an additional medication.

The researchers observed no statistically significant differences in the proportion of patients who required a dose increase or an additional antihypertensive in the group taking the twice-daily dose (33.8%) or those receiving the once-daily dose (35.7%). This finding remained statistically insignificant after controlling for gestational diabetes, delivery mode, administration of Lasix, and receipt of emergency antihypertensive treatment (P = .71). The time that passed before patients needed a dose increase was also statistically similar between the groups: 24.3 hours in the twice-daily group and 24 hours in the once-daily group (P = .49).

There were no statistically significant differences in the need for a dose increase or an additional hypertensive agent based on race, ethnicity, body mass index, or history of preeclampsia as well. However, 24.5% of those taking the once-daily dosage had a history of preeclampsia, compared with 7.2% of those taking the twice-daily dosage (P < .001). Further, the median number of prior pregnancies was two in the twice-daily group versus three in the once-daily group (P = .002).

The authors found no significant difference between the two dosing groups in the need for emergency hypertensive treatment after reaching the study dose or in readmission for blood pressure control. In the twice-daily group, 21.6% of patients needed emergency antihypertensive treatment, compared with 14.3% in the once-daily group (P = .19). Readmission was necessary for 7.2% of the twice-daily group and 6.1% of the once-daily group (P > .99).

A subgroup analysis compared those who started nifedipine antepartum and those who started it post partum, but again, no significant difference in the dosing regimens existed.

Michael Ruma, MD, a maternal-fetal medicine specialist at Perinatal Associates of New Mexico in Albuquerque, was not involved in the study and said he welcomed the results.

“We have too many choices in medicine, so we need to just simplify the plan of attack,” reducing the number of things that clinicians need to think about, Dr. Ruma said in an interview. “A singular dose is always easiest for the patient, always easier for nursing staff, and usually, if you can optimize the dosing, that’s the best approach.”

Annabeth Brewton, MD, a resident at University of Tennessee, Knoxville, agreed, adding that new parents already have a lot going on immediately post partum.

“They’re going to be breastfeeding, they’re not sleeping, they’re going to forget to take that [second] dose,” Dr. Brewton said.

Ms. Band and Dr. Brewton had no disclosures. Dr. Ruma reported consulting and speaking for Hologic and consulting for Philips Ultrasound.

Correction, 5/24/23: An earlier version of this article misstated the daily doses of nifedipine. The study compared a single 60-mg daily dose with a 30-mg dose taken twice daily.  

Use of a machine-learning model that incorporates information from a single troponin test as well as other clinical data was superior to current practice as an aid to the diagnosis of myocardial infarction in the emergency department in a new study.

“Our results suggest that by using this machine-learning model, compared to the currently recommended approach, we could double the proportion of patients who are identified correctly as having a low probability of an MI on arrival to enable immediate discharge and free up space in the emergency department,” senior author Nicholas L. Mills, MD, University of Edinburgh, Scotland, said in an interview.

“And, perhaps even more importantly, use of this model could also increase the proportion of patients who are correctly identified as at a high probability of having an MI,” he added.

The study was published online in Nature Medicine.

The authors explained that at present, the likelihood of an MI diagnosis for patients presenting to the emergency department with chest pain is based on a fixed troponin threshold in serial tests at specific time points, but there are several problems with this approach.

First, a fixed troponin threshold is generally used for all patients, which does not account for age, sex, or comorbidities that are known to influence cardiac troponin concentrations. Second, the need to perform tests at specific time points for serial testing can be challenging in busy emergency departments.

And third, patients are categorized as being at low, intermediate, or high risk of MI on the basis of troponin thresholds alone, and the test does not take into account other important factors, such as the time of symptom onset or findings on the electrocardiogram.

“Our current practice of using the same threshold to rule in and rule out an MI for everyone, regardless of whether they are an 18-year-old female without a history of heart disease or an 85-year-old male with known heart failure, doesn’t perform well, and there’s a significant risk of misdiagnosis. There is also a high likelihood for inequalities in care, particularly between men and women,” Dr. Mills said.

The current study evaluated whether use of a machine learning model known as CoDE-ACS to guide decision-making could overcome some of these challenges.

The machine learning model assesses the whole spectrum of troponin levels as a continuous variable (rather than use of a single threshold) and turns this measurement into a probability that an individual patient is having an MI after accounting for other factors, including age, sex, comorbidities, and time from symptom onset.

For the current study, the CoDE-ACS model was trained in 10,000 patients with suspected acute coronary syndrome (ACS) who presented to 10 hospitals in Scotland as part of the High-STEACS trial evaluating the implementation of a high-sensitivity cardiac troponin I assay. The results were then validated in another 10,000 patients from six countries around the world.

“Using this model, the patient can have a troponin test on arrival at the emergency department. The other information on age, sex, clinical history, and time since symptom onset is keyed in, and it gives a probability on a scale of 0–100 as to whether the patient is having an MI,” Dr. Mills noted.

“It also has the capacity to incorporate more information over time. So, if there is a second troponin measurement made, then the model automatically refines the probability score,” he added.

The current study showed that use of the CoDE-ACS model identified more patients at presentation as having a low probability of having an MI than fixed cardiac troponin thresholds (61% vs. 27%) with a similar negative predictive value.

It also identified fewer patients as having a high probability of having an MI (10% vs. 16%) with a greater positive predictive value.

Among patients who were identified as having a low probability of MI, the rate of cardiac death was lower than the rate among those with intermediate or high probability at 30 days (0.1% vs. 0.5% and 1.8%) and 1 year (0.3% vs. 2.8% and 4.2%).

“The results show that the machine learning model doubles the proportion of patients who can be discharged with a single test compared to the current practice of using the threshold approach. It really is a game changer in terms of its potential to improve health efficiency,” Dr. Mills said.

In terms of ruling patients in as possibly having an MI, he pointed out that troponin levels are increased in patients with a wide range of other conditions, including heart failure, kidney failure, and atrial fibrillation.

“When using the threshold approach, only one in four patients with an elevated troponin level will actually be having an MI, and that leads to confusion,” he said. “This model takes into consideration these other conditions and so it can correctly identify three out of four patients with a high probability of having an MI. We can therefore be more confident that it is appropriate to refer those patients to cardiology and save a lot of potentially unnecessary investigations and treatments in the others.”

Dr. Mills said the model also seems to work when assessing patients early on.

“Around one-third of patients present within 3 hours of symptom onset, and actually these are a high-risk group because people who have genuine cardiac pain are normally extremely uncomfortable and tend to present quickly. Current guidelines require that we do two tests in all these individuals, but this new model incorporates the time of symptom onset into its estimates of probability and therefore allows us to rule out patients even when they present very early.”

He reported that a second test is required in only one in five patients – those whose first test indicated intermediate probability.

“The second test allows us to refine the probability further, allowing us to rule another half of those patients out. We are then left with a small proportion of patients – about 1 in 10 – who remain of intermediate probability and will require additional clinical judgment.”
 

Should improve inequities in MI diagnosis

Dr. Mills said the CoDE-ACS model will improve current inequities in MI diagnosis, because of which MI is underrecognized in women and younger people.

“Women have troponin concentrations that are half those of men, and although sex-specific troponin thresholds are recommended in the guidelines, they are not widely used. This automatically leads to underrecognition of heart disease in women. But this new machine learning model performs identically in men and women because it has been trained to recognize the different normal levels in men and women,” he explained.

“It will also help us not to underdiagnose MI in younger people who often have a less classical presentation of MI, and they also generally have very low concentrations of troponin, so any increase in troponin way below the current diagnostic threshold may be very relevant to their risk,” he added.

The researchers are planning a randomized trial of the new model to demonstrate the impact it could have on equality of care and overcrowding in the emergency department. In the trial, patients will be randomly assigned to undergo decision-making on the basis of troponin thresholds (current practice) or to undergo decision-making through the CoDE-ACS model.

“The hope is that this trial will show reductions in unnecessary hospital admissions and length of stay in the emergency department,” Dr. Mills said. Results are expected sometime next year.

“This algorithm is very well trained. It has learned on 20,000 patients, so it has a lot more experience than I have, and I have been a professor of cardiology for 20 years,” Dr. Mills said.

He said he believes these models will get even smarter in the future as more data are added.

“I think the future for good decision-making in emergency care will be informed by clinical decision support from well-trained machine learning algorithms and they will help us guide not just the diagnosis of MI but also heart failure and other important cardiac conditions,” he said.
 

‘Elegant and exciting’ data

Commenting on the study, John W. McEvoy, MB, University of Galway, Ireland, said: “These are elegant and exciting data; however, the inputs into the machine learning algorithm include all the necessary information to actually diagnose MI. So why predict MI, when a human diagnosis can just be made directly? The answer to this question may depend on whether we trust machines more than humans.”

Dr. Mills noted that clinical judgment will always be an important part of MI diagnosis.

“Currently, using the troponin threshold approach, experienced clinicians will be able to nuance the results, but invariably, there is disagreement on this, and this can be a major source of tension within clinical care. By providing more individualized information, this will help enormously in the decision-making process,” he said.

“This model is not about replacing clinical decision-making. It’s more about augmenting decision-making and giving clinicians guidance to be able to improve efficiency and reduce inequality,” he added.

The study was funded with support from the National Institute for Health Research and NHSX, the British Heart Foundation, and Wellcome Leap. Dr. Mills has received honoraria or consultancy from Abbott Diagnostics, Roche Diagnostics, Siemens Healthineers, and LumiraDx. He is employed by the University of Edinburgh, which has filed a patent on the Collaboration for the Diagnosis and Evaluation of Acute Coronary Syndrome score.
 

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

Use of a machine-learning model that incorporates information from a single troponin test as well as other clinical data was superior to current practice as an aid to the diagnosis of myocardial infarction in the emergency department in a new study.

“Our results suggest that by using this machine-learning model, compared to the currently recommended approach, we could double the proportion of patients who are identified correctly as having a low probability of an MI on arrival to enable immediate discharge and free up space in the emergency department,” senior author Nicholas L. Mills, MD, University of Edinburgh, Scotland, said in an interview.

“And, perhaps even more importantly, use of this model could also increase the proportion of patients who are correctly identified as at a high probability of having an MI,” he added.

The study was published online in Nature Medicine.

The authors explained that at present, the likelihood of an MI diagnosis for patients presenting to the emergency department with chest pain is based on a fixed troponin threshold in serial tests at specific time points, but there are several problems with this approach.

First, a fixed troponin threshold is generally used for all patients, which does not account for age, sex, or comorbidities that are known to influence cardiac troponin concentrations. Second, the need to perform tests at specific time points for serial testing can be challenging in busy emergency departments.

And third, patients are categorized as being at low, intermediate, or high risk of MI on the basis of troponin thresholds alone, and the test does not take into account other important factors, such as the time of symptom onset or findings on the electrocardiogram.

“Our current practice of using the same threshold to rule in and rule out an MI for everyone, regardless of whether they are an 18-year-old female without a history of heart disease or an 85-year-old male with known heart failure, doesn’t perform well, and there’s a significant risk of misdiagnosis. There is also a high likelihood for inequalities in care, particularly between men and women,” Dr. Mills said.

The current study evaluated whether use of a machine learning model known as CoDE-ACS to guide decision-making could overcome some of these challenges.

The machine learning model assesses the whole spectrum of troponin levels as a continuous variable (rather than use of a single threshold) and turns this measurement into a probability that an individual patient is having an MI after accounting for other factors, including age, sex, comorbidities, and time from symptom onset.

For the current study, the CoDE-ACS model was trained in 10,000 patients with suspected acute coronary syndrome (ACS) who presented to 10 hospitals in Scotland as part of the High-STEACS trial evaluating the implementation of a high-sensitivity cardiac troponin I assay. The results were then validated in another 10,000 patients from six countries around the world.

“Using this model, the patient can have a troponin test on arrival at the emergency department. The other information on age, sex, clinical history, and time since symptom onset is keyed in, and it gives a probability on a scale of 0–100 as to whether the patient is having an MI,” Dr. Mills noted.

“It also has the capacity to incorporate more information over time. So, if there is a second troponin measurement made, then the model automatically refines the probability score,” he added.

The current study showed that use of the CoDE-ACS model identified more patients at presentation as having a low probability of having an MI than fixed cardiac troponin thresholds (61% vs. 27%) with a similar negative predictive value.

It also identified fewer patients as having a high probability of having an MI (10% vs. 16%) with a greater positive predictive value.

Among patients who were identified as having a low probability of MI, the rate of cardiac death was lower than the rate among those with intermediate or high probability at 30 days (0.1% vs. 0.5% and 1.8%) and 1 year (0.3% vs. 2.8% and 4.2%).

“The results show that the machine learning model doubles the proportion of patients who can be discharged with a single test compared to the current practice of using the threshold approach. It really is a game changer in terms of its potential to improve health efficiency,” Dr. Mills said.

In terms of ruling patients in as possibly having an MI, he pointed out that troponin levels are increased in patients with a wide range of other conditions, including heart failure, kidney failure, and atrial fibrillation.

“When using the threshold approach, only one in four patients with an elevated troponin level will actually be having an MI, and that leads to confusion,” he said. “This model takes into consideration these other conditions and so it can correctly identify three out of four patients with a high probability of having an MI. We can therefore be more confident that it is appropriate to refer those patients to cardiology and save a lot of potentially unnecessary investigations and treatments in the others.”

Dr. Mills said the model also seems to work when assessing patients early on.

“Around one-third of patients present within 3 hours of symptom onset, and actually these are a high-risk group because people who have genuine cardiac pain are normally extremely uncomfortable and tend to present quickly. Current guidelines require that we do two tests in all these individuals, but this new model incorporates the time of symptom onset into its estimates of probability and therefore allows us to rule out patients even when they present very early.”

He reported that a second test is required in only one in five patients – those whose first test indicated intermediate probability.

“The second test allows us to refine the probability further, allowing us to rule another half of those patients out. We are then left with a small proportion of patients – about 1 in 10 – who remain of intermediate probability and will require additional clinical judgment.”
 

Should improve inequities in MI diagnosis

Dr. Mills said the CoDE-ACS model will improve current inequities in MI diagnosis, because of which MI is underrecognized in women and younger people.

“Women have troponin concentrations that are half those of men, and although sex-specific troponin thresholds are recommended in the guidelines, they are not widely used. This automatically leads to underrecognition of heart disease in women. But this new machine learning model performs identically in men and women because it has been trained to recognize the different normal levels in men and women,” he explained.

“It will also help us not to underdiagnose MI in younger people who often have a less classical presentation of MI, and they also generally have very low concentrations of troponin, so any increase in troponin way below the current diagnostic threshold may be very relevant to their risk,” he added.

The researchers are planning a randomized trial of the new model to demonstrate the impact it could have on equality of care and overcrowding in the emergency department. In the trial, patients will be randomly assigned to undergo decision-making on the basis of troponin thresholds (current practice) or to undergo decision-making through the CoDE-ACS model.

“The hope is that this trial will show reductions in unnecessary hospital admissions and length of stay in the emergency department,” Dr. Mills said. Results are expected sometime next year.

“This algorithm is very well trained. It has learned on 20,000 patients, so it has a lot more experience than I have, and I have been a professor of cardiology for 20 years,” Dr. Mills said.

He said he believes these models will get even smarter in the future as more data are added.

“I think the future for good decision-making in emergency care will be informed by clinical decision support from well-trained machine learning algorithms and they will help us guide not just the diagnosis of MI but also heart failure and other important cardiac conditions,” he said.
 

‘Elegant and exciting’ data

Commenting on the study, John W. McEvoy, MB, University of Galway, Ireland, said: “These are elegant and exciting data; however, the inputs into the machine learning algorithm include all the necessary information to actually diagnose MI. So why predict MI, when a human diagnosis can just be made directly? The answer to this question may depend on whether we trust machines more than humans.”

Dr. Mills noted that clinical judgment will always be an important part of MI diagnosis.

“Currently, using the troponin threshold approach, experienced clinicians will be able to nuance the results, but invariably, there is disagreement on this, and this can be a major source of tension within clinical care. By providing more individualized information, this will help enormously in the decision-making process,” he said.

“This model is not about replacing clinical decision-making. It’s more about augmenting decision-making and giving clinicians guidance to be able to improve efficiency and reduce inequality,” he added.

The study was funded with support from the National Institute for Health Research and NHSX, the British Heart Foundation, and Wellcome Leap. Dr. Mills has received honoraria or consultancy from Abbott Diagnostics, Roche Diagnostics, Siemens Healthineers, and LumiraDx. He is employed by the University of Edinburgh, which has filed a patent on the Collaboration for the Diagnosis and Evaluation of Acute Coronary Syndrome score.
 

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

Use of a machine-learning model that incorporates information from a single troponin test as well as other clinical data was superior to current practice as an aid to the diagnosis of myocardial infarction in the emergency department in a new study.

“Our results suggest that by using this machine-learning model, compared to the currently recommended approach, we could double the proportion of patients who are identified correctly as having a low probability of an MI on arrival to enable immediate discharge and free up space in the emergency department,” senior author Nicholas L. Mills, MD, University of Edinburgh, Scotland, said in an interview.

“And, perhaps even more importantly, use of this model could also increase the proportion of patients who are correctly identified as at a high probability of having an MI,” he added.

The study was published online in Nature Medicine.

The authors explained that at present, the likelihood of an MI diagnosis for patients presenting to the emergency department with chest pain is based on a fixed troponin threshold in serial tests at specific time points, but there are several problems with this approach.

First, a fixed troponin threshold is generally used for all patients, which does not account for age, sex, or comorbidities that are known to influence cardiac troponin concentrations. Second, the need to perform tests at specific time points for serial testing can be challenging in busy emergency departments.

And third, patients are categorized as being at low, intermediate, or high risk of MI on the basis of troponin thresholds alone, and the test does not take into account other important factors, such as the time of symptom onset or findings on the electrocardiogram.

“Our current practice of using the same threshold to rule in and rule out an MI for everyone, regardless of whether they are an 18-year-old female without a history of heart disease or an 85-year-old male with known heart failure, doesn’t perform well, and there’s a significant risk of misdiagnosis. There is also a high likelihood for inequalities in care, particularly between men and women,” Dr. Mills said.

The current study evaluated whether use of a machine learning model known as CoDE-ACS to guide decision-making could overcome some of these challenges.

The machine learning model assesses the whole spectrum of troponin levels as a continuous variable (rather than use of a single threshold) and turns this measurement into a probability that an individual patient is having an MI after accounting for other factors, including age, sex, comorbidities, and time from symptom onset.

For the current study, the CoDE-ACS model was trained in 10,000 patients with suspected acute coronary syndrome (ACS) who presented to 10 hospitals in Scotland as part of the High-STEACS trial evaluating the implementation of a high-sensitivity cardiac troponin I assay. The results were then validated in another 10,000 patients from six countries around the world.

“Using this model, the patient can have a troponin test on arrival at the emergency department. The other information on age, sex, clinical history, and time since symptom onset is keyed in, and it gives a probability on a scale of 0–100 as to whether the patient is having an MI,” Dr. Mills noted.

“It also has the capacity to incorporate more information over time. So, if there is a second troponin measurement made, then the model automatically refines the probability score,” he added.

The current study showed that use of the CoDE-ACS model identified more patients at presentation as having a low probability of having an MI than fixed cardiac troponin thresholds (61% vs. 27%) with a similar negative predictive value.

It also identified fewer patients as having a high probability of having an MI (10% vs. 16%) with a greater positive predictive value.

Among patients who were identified as having a low probability of MI, the rate of cardiac death was lower than the rate among those with intermediate or high probability at 30 days (0.1% vs. 0.5% and 1.8%) and 1 year (0.3% vs. 2.8% and 4.2%).

“The results show that the machine learning model doubles the proportion of patients who can be discharged with a single test compared to the current practice of using the threshold approach. It really is a game changer in terms of its potential to improve health efficiency,” Dr. Mills said.

In terms of ruling patients in as possibly having an MI, he pointed out that troponin levels are increased in patients with a wide range of other conditions, including heart failure, kidney failure, and atrial fibrillation.

“When using the threshold approach, only one in four patients with an elevated troponin level will actually be having an MI, and that leads to confusion,” he said. “This model takes into consideration these other conditions and so it can correctly identify three out of four patients with a high probability of having an MI. We can therefore be more confident that it is appropriate to refer those patients to cardiology and save a lot of potentially unnecessary investigations and treatments in the others.”

Dr. Mills said the model also seems to work when assessing patients early on.

“Around one-third of patients present within 3 hours of symptom onset, and actually these are a high-risk group because people who have genuine cardiac pain are normally extremely uncomfortable and tend to present quickly. Current guidelines require that we do two tests in all these individuals, but this new model incorporates the time of symptom onset into its estimates of probability and therefore allows us to rule out patients even when they present very early.”

He reported that a second test is required in only one in five patients – those whose first test indicated intermediate probability.

“The second test allows us to refine the probability further, allowing us to rule another half of those patients out. We are then left with a small proportion of patients – about 1 in 10 – who remain of intermediate probability and will require additional clinical judgment.”
 

Should improve inequities in MI diagnosis

Dr. Mills said the CoDE-ACS model will improve current inequities in MI diagnosis, because of which MI is underrecognized in women and younger people.

“Women have troponin concentrations that are half those of men, and although sex-specific troponin thresholds are recommended in the guidelines, they are not widely used. This automatically leads to underrecognition of heart disease in women. But this new machine learning model performs identically in men and women because it has been trained to recognize the different normal levels in men and women,” he explained.

“It will also help us not to underdiagnose MI in younger people who often have a less classical presentation of MI, and they also generally have very low concentrations of troponin, so any increase in troponin way below the current diagnostic threshold may be very relevant to their risk,” he added.

The researchers are planning a randomized trial of the new model to demonstrate the impact it could have on equality of care and overcrowding in the emergency department. In the trial, patients will be randomly assigned to undergo decision-making on the basis of troponin thresholds (current practice) or to undergo decision-making through the CoDE-ACS model.

“The hope is that this trial will show reductions in unnecessary hospital admissions and length of stay in the emergency department,” Dr. Mills said. Results are expected sometime next year.

“This algorithm is very well trained. It has learned on 20,000 patients, so it has a lot more experience than I have, and I have been a professor of cardiology for 20 years,” Dr. Mills said.

He said he believes these models will get even smarter in the future as more data are added.

“I think the future for good decision-making in emergency care will be informed by clinical decision support from well-trained machine learning algorithms and they will help us guide not just the diagnosis of MI but also heart failure and other important cardiac conditions,” he said.
 

‘Elegant and exciting’ data

Commenting on the study, John W. McEvoy, MB, University of Galway, Ireland, said: “These are elegant and exciting data; however, the inputs into the machine learning algorithm include all the necessary information to actually diagnose MI. So why predict MI, when a human diagnosis can just be made directly? The answer to this question may depend on whether we trust machines more than humans.”

Dr. Mills noted that clinical judgment will always be an important part of MI diagnosis.

“Currently, using the troponin threshold approach, experienced clinicians will be able to nuance the results, but invariably, there is disagreement on this, and this can be a major source of tension within clinical care. By providing more individualized information, this will help enormously in the decision-making process,” he said.

“This model is not about replacing clinical decision-making. It’s more about augmenting decision-making and giving clinicians guidance to be able to improve efficiency and reduce inequality,” he added.

The study was funded with support from the National Institute for Health Research and NHSX, the British Heart Foundation, and Wellcome Leap. Dr. Mills has received honoraria or consultancy from Abbott Diagnostics, Roche Diagnostics, Siemens Healthineers, and LumiraDx. He is employed by the University of Edinburgh, which has filed a patent on the Collaboration for the Diagnosis and Evaluation of Acute Coronary Syndrome score.
 

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

A multicenter study published in JAMA Pediatrics indicates that an elevated proportion of children and adolescents around the world, particularly girls or those with high body mass index (BMI), experience disordered eating. The high figures are concerning from a public health perspective and highlight the need to implement strategies for preventing eating disorders.
 

These disorders include anorexia nervosa, bulimia nervosa, binge eating disorder, and eating disorder–not otherwise specified. The prevalence of these disorders in young people has markedly increased globally over the past 50 years. Eating disorders are among the most life-threatening mental disorders; they were responsible for 318 deaths worldwide in 2019.

Because some individuals with eating disorders conceal core symptoms and avoid or delay seeking specialist care because of feelings of embarrassment, stigma, or ambivalence toward treatment, most cases of eating disorders remain undetected and untreated.

Brazilian researchers conducted studies to assess risky behaviors and predisposing factors among young people. The researchers observed that the probability of experiencing eating disorders was higher among young people who had an intense fear of gaining weight, who experienced thin-ideal internalization, who were excessively concerned about food, who experienced compulsive eating episodes, or who used laxatives. As previously reported, most participants in these studies had never sought professional help.

A study conducted in 2020 concluded that the media greatly influences the construction of one’s body image and the creation of aesthetic standards, particularly for adolescents. Adolescents then change their eating patterns and become more vulnerable to mental disorders related to eating.

A group of researchers from several countries, including Brazilians connected to the State University of Londrina, conducted the Global Proportion of Disordered Eating in Children and Adolescents – A Systematic Review and Meta-analysis. The study was coordinated by José Francisco López-Gil, PhD, of the University of Castilla–La Mancha (Spain). The investigators determined the rate of disordered eating among children and adolescents using the SCOFF (Sick, Control, One, Fat, Food) questionnaire, which is the most widely used screening measure for eating disorders.
 

Methods and results

Four databases were systematically searched (PubMed, Scopus, Web of Science, and the Cochrane Library); date limits were from January 1999 to November 2022. Studies were required to meet the following criteria: participants – studies of community samples of children and adolescents aged 6-18 years – and outcome – disordered eating assessed by the SCOFF questionnaire. The exclusion criteria were studies conducted with young people who had been diagnosed with physical or mental disorders; studies that were published before 1999, because the SCOFF questionnaire was designed in that year; studies in which data were collected during the COVID-19 pandemic, because of the possibility of selection bias; studies that employed data from the same surveys/studies, to avoid duplication; and systematic reviews and/or meta-analyses and qualitative and case studies.

In all, 32 studies, which involved a total of 63,181 participants from 16 countries, were included in the systematic review and meta-analysis, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The overall proportion of children and adolescents with disordered eating was 22.36% (95% confidence interval, 18.84%-26.09%; P < .001; n = 63,181). According to the researchers, girls were significantly more likely to report disordered eating (30.03%; 95% CI, 25.61%-34.65%; n = 27,548) than boys (16.98%; 95% CI, 13.46%-20.81%; n = 26,170; P < .001). It was also observed that disordered eating became more elevated with increasing age (B, 0.03; 95% CI, 0-0.06; P = .049) and BMI (B, 0.03; 95% CI, 0.01-0.05; P < .001).
 

Translation of outcomes

According to the authors, this was the first meta-analysis that comprehensively examined the overall proportion of children and adolescents with disordered eating in terms of gender, mean age, and BMI. They identified 14,856 (22.36%) children and adolescents with disordered eating in the population analyzed (n = 63,181). A relevant consideration made by the researchers is that, in general, disordered eating and eating disorders are not similar. “Not all children and adolescents who reported disordered eating behaviors (for example, selective eating) will necessarily be diagnosed with an eating disorder.” However, disordered eating in childhood or adolescence may predict outcomes associated with eating disorders in early adulthood. “For this reason, this high proportion found is worrisome and calls for urgent action to try to address this situation.”

The study also found that the proportion of children and adolescents with disordered eating was higher among girls than boys. The reasons for the difference in the prevalence with respect to the sex of the participants are not well understood. Boys are presumed to underreport the problem because of the societal perception that these disorders mostly affect girls and because disordered eating has usually been thought by the general population to be exclusive to girls and women. In addition, it has been noted that the current diagnostic criteria for eating disorders fail to detect disordered eating behaviors more commonly observed in boys than girls, such as intensely engaging in muscle mass gain and weight gain with the goal of improving body image satisfaction. On the other hand, the proportion of young people with disordered eating increased with increasing age and BMI. This finding is in line with the scientific literature worldwide.

The study has certain limitations. First, only studies that analyzed disordered eating using the SCOFF questionnaire were included. Second, because of the cross-sectional nature of most of the included studies, a causal relationship cannot be established. Third, owing to the inclusion of binge eating disorder and other eating disorders specified in the DSM-5, there is not enough evidence to support the use of SCOFF in primary care and community-based settings for screening for the range of eating disorders. Fourth, the meta-analysis included studies in which self-report questionnaires were used to assess disordered eating, and consequently, social desirability and recall bias could have influenced the findings.
 

Quick measures required

Identifying the magnitude of disordered eating and its distribution in at-risk populations is crucial for planning and executing actions aimed at preventing, detecting, and treating them. Eating disorders are a global public health problem that health care professionals, families, and other community members involved in caring for children and adolescents must not ignore, the researchers said. In addition to diagnosed eating disorders, parents, guardians, and health care professionals should be aware of symptoms of disordered eating, which include behaviors such as weight-loss dieting, binge eating, self-induced vomiting, excessive exercise, and the use of laxatives or diuretics without medical prescription.

This article was translated from the Medscape Portuguese Edition. A version of this article appeared on Medscape.com.

A multicenter study published in JAMA Pediatrics indicates that an elevated proportion of children and adolescents around the world, particularly girls or those with high body mass index (BMI), experience disordered eating. The high figures are concerning from a public health perspective and highlight the need to implement strategies for preventing eating disorders.
 

These disorders include anorexia nervosa, bulimia nervosa, binge eating disorder, and eating disorder–not otherwise specified. The prevalence of these disorders in young people has markedly increased globally over the past 50 years. Eating disorders are among the most life-threatening mental disorders; they were responsible for 318 deaths worldwide in 2019.

Because some individuals with eating disorders conceal core symptoms and avoid or delay seeking specialist care because of feelings of embarrassment, stigma, or ambivalence toward treatment, most cases of eating disorders remain undetected and untreated.

Brazilian researchers conducted studies to assess risky behaviors and predisposing factors among young people. The researchers observed that the probability of experiencing eating disorders was higher among young people who had an intense fear of gaining weight, who experienced thin-ideal internalization, who were excessively concerned about food, who experienced compulsive eating episodes, or who used laxatives. As previously reported, most participants in these studies had never sought professional help.

A study conducted in 2020 concluded that the media greatly influences the construction of one’s body image and the creation of aesthetic standards, particularly for adolescents. Adolescents then change their eating patterns and become more vulnerable to mental disorders related to eating.

A group of researchers from several countries, including Brazilians connected to the State University of Londrina, conducted the Global Proportion of Disordered Eating in Children and Adolescents – A Systematic Review and Meta-analysis. The study was coordinated by José Francisco López-Gil, PhD, of the University of Castilla–La Mancha (Spain). The investigators determined the rate of disordered eating among children and adolescents using the SCOFF (Sick, Control, One, Fat, Food) questionnaire, which is the most widely used screening measure for eating disorders.
 

Methods and results

Four databases were systematically searched (PubMed, Scopus, Web of Science, and the Cochrane Library); date limits were from January 1999 to November 2022. Studies were required to meet the following criteria: participants – studies of community samples of children and adolescents aged 6-18 years – and outcome – disordered eating assessed by the SCOFF questionnaire. The exclusion criteria were studies conducted with young people who had been diagnosed with physical or mental disorders; studies that were published before 1999, because the SCOFF questionnaire was designed in that year; studies in which data were collected during the COVID-19 pandemic, because of the possibility of selection bias; studies that employed data from the same surveys/studies, to avoid duplication; and systematic reviews and/or meta-analyses and qualitative and case studies.

In all, 32 studies, which involved a total of 63,181 participants from 16 countries, were included in the systematic review and meta-analysis, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The overall proportion of children and adolescents with disordered eating was 22.36% (95% confidence interval, 18.84%-26.09%; P < .001; n = 63,181). According to the researchers, girls were significantly more likely to report disordered eating (30.03%; 95% CI, 25.61%-34.65%; n = 27,548) than boys (16.98%; 95% CI, 13.46%-20.81%; n = 26,170; P < .001). It was also observed that disordered eating became more elevated with increasing age (B, 0.03; 95% CI, 0-0.06; P = .049) and BMI (B, 0.03; 95% CI, 0.01-0.05; P < .001).
 

Translation of outcomes

According to the authors, this was the first meta-analysis that comprehensively examined the overall proportion of children and adolescents with disordered eating in terms of gender, mean age, and BMI. They identified 14,856 (22.36%) children and adolescents with disordered eating in the population analyzed (n = 63,181). A relevant consideration made by the researchers is that, in general, disordered eating and eating disorders are not similar. “Not all children and adolescents who reported disordered eating behaviors (for example, selective eating) will necessarily be diagnosed with an eating disorder.” However, disordered eating in childhood or adolescence may predict outcomes associated with eating disorders in early adulthood. “For this reason, this high proportion found is worrisome and calls for urgent action to try to address this situation.”

The study also found that the proportion of children and adolescents with disordered eating was higher among girls than boys. The reasons for the difference in the prevalence with respect to the sex of the participants are not well understood. Boys are presumed to underreport the problem because of the societal perception that these disorders mostly affect girls and because disordered eating has usually been thought by the general population to be exclusive to girls and women. In addition, it has been noted that the current diagnostic criteria for eating disorders fail to detect disordered eating behaviors more commonly observed in boys than girls, such as intensely engaging in muscle mass gain and weight gain with the goal of improving body image satisfaction. On the other hand, the proportion of young people with disordered eating increased with increasing age and BMI. This finding is in line with the scientific literature worldwide.

The study has certain limitations. First, only studies that analyzed disordered eating using the SCOFF questionnaire were included. Second, because of the cross-sectional nature of most of the included studies, a causal relationship cannot be established. Third, owing to the inclusion of binge eating disorder and other eating disorders specified in the DSM-5, there is not enough evidence to support the use of SCOFF in primary care and community-based settings for screening for the range of eating disorders. Fourth, the meta-analysis included studies in which self-report questionnaires were used to assess disordered eating, and consequently, social desirability and recall bias could have influenced the findings.
 

Quick measures required

Identifying the magnitude of disordered eating and its distribution in at-risk populations is crucial for planning and executing actions aimed at preventing, detecting, and treating them. Eating disorders are a global public health problem that health care professionals, families, and other community members involved in caring for children and adolescents must not ignore, the researchers said. In addition to diagnosed eating disorders, parents, guardians, and health care professionals should be aware of symptoms of disordered eating, which include behaviors such as weight-loss dieting, binge eating, self-induced vomiting, excessive exercise, and the use of laxatives or diuretics without medical prescription.

This article was translated from the Medscape Portuguese Edition. A version of this article appeared on Medscape.com.

A multicenter study published in JAMA Pediatrics indicates that an elevated proportion of children and adolescents around the world, particularly girls or those with high body mass index (BMI), experience disordered eating. The high figures are concerning from a public health perspective and highlight the need to implement strategies for preventing eating disorders.
 

These disorders include anorexia nervosa, bulimia nervosa, binge eating disorder, and eating disorder–not otherwise specified. The prevalence of these disorders in young people has markedly increased globally over the past 50 years. Eating disorders are among the most life-threatening mental disorders; they were responsible for 318 deaths worldwide in 2019.

Because some individuals with eating disorders conceal core symptoms and avoid or delay seeking specialist care because of feelings of embarrassment, stigma, or ambivalence toward treatment, most cases of eating disorders remain undetected and untreated.

Brazilian researchers conducted studies to assess risky behaviors and predisposing factors among young people. The researchers observed that the probability of experiencing eating disorders was higher among young people who had an intense fear of gaining weight, who experienced thin-ideal internalization, who were excessively concerned about food, who experienced compulsive eating episodes, or who used laxatives. As previously reported, most participants in these studies had never sought professional help.

A study conducted in 2020 concluded that the media greatly influences the construction of one’s body image and the creation of aesthetic standards, particularly for adolescents. Adolescents then change their eating patterns and become more vulnerable to mental disorders related to eating.

A group of researchers from several countries, including Brazilians connected to the State University of Londrina, conducted the Global Proportion of Disordered Eating in Children and Adolescents – A Systematic Review and Meta-analysis. The study was coordinated by José Francisco López-Gil, PhD, of the University of Castilla–La Mancha (Spain). The investigators determined the rate of disordered eating among children and adolescents using the SCOFF (Sick, Control, One, Fat, Food) questionnaire, which is the most widely used screening measure for eating disorders.
 

Methods and results

Four databases were systematically searched (PubMed, Scopus, Web of Science, and the Cochrane Library); date limits were from January 1999 to November 2022. Studies were required to meet the following criteria: participants – studies of community samples of children and adolescents aged 6-18 years – and outcome – disordered eating assessed by the SCOFF questionnaire. The exclusion criteria were studies conducted with young people who had been diagnosed with physical or mental disorders; studies that were published before 1999, because the SCOFF questionnaire was designed in that year; studies in which data were collected during the COVID-19 pandemic, because of the possibility of selection bias; studies that employed data from the same surveys/studies, to avoid duplication; and systematic reviews and/or meta-analyses and qualitative and case studies.

In all, 32 studies, which involved a total of 63,181 participants from 16 countries, were included in the systematic review and meta-analysis, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The overall proportion of children and adolescents with disordered eating was 22.36% (95% confidence interval, 18.84%-26.09%; P < .001; n = 63,181). According to the researchers, girls were significantly more likely to report disordered eating (30.03%; 95% CI, 25.61%-34.65%; n = 27,548) than boys (16.98%; 95% CI, 13.46%-20.81%; n = 26,170; P < .001). It was also observed that disordered eating became more elevated with increasing age (B, 0.03; 95% CI, 0-0.06; P = .049) and BMI (B, 0.03; 95% CI, 0.01-0.05; P < .001).
 

Translation of outcomes

According to the authors, this was the first meta-analysis that comprehensively examined the overall proportion of children and adolescents with disordered eating in terms of gender, mean age, and BMI. They identified 14,856 (22.36%) children and adolescents with disordered eating in the population analyzed (n = 63,181). A relevant consideration made by the researchers is that, in general, disordered eating and eating disorders are not similar. “Not all children and adolescents who reported disordered eating behaviors (for example, selective eating) will necessarily be diagnosed with an eating disorder.” However, disordered eating in childhood or adolescence may predict outcomes associated with eating disorders in early adulthood. “For this reason, this high proportion found is worrisome and calls for urgent action to try to address this situation.”

The study also found that the proportion of children and adolescents with disordered eating was higher among girls than boys. The reasons for the difference in the prevalence with respect to the sex of the participants are not well understood. Boys are presumed to underreport the problem because of the societal perception that these disorders mostly affect girls and because disordered eating has usually been thought by the general population to be exclusive to girls and women. In addition, it has been noted that the current diagnostic criteria for eating disorders fail to detect disordered eating behaviors more commonly observed in boys than girls, such as intensely engaging in muscle mass gain and weight gain with the goal of improving body image satisfaction. On the other hand, the proportion of young people with disordered eating increased with increasing age and BMI. This finding is in line with the scientific literature worldwide.

The study has certain limitations. First, only studies that analyzed disordered eating using the SCOFF questionnaire were included. Second, because of the cross-sectional nature of most of the included studies, a causal relationship cannot be established. Third, owing to the inclusion of binge eating disorder and other eating disorders specified in the DSM-5, there is not enough evidence to support the use of SCOFF in primary care and community-based settings for screening for the range of eating disorders. Fourth, the meta-analysis included studies in which self-report questionnaires were used to assess disordered eating, and consequently, social desirability and recall bias could have influenced the findings.
 

Quick measures required

Identifying the magnitude of disordered eating and its distribution in at-risk populations is crucial for planning and executing actions aimed at preventing, detecting, and treating them. Eating disorders are a global public health problem that health care professionals, families, and other community members involved in caring for children and adolescents must not ignore, the researchers said. In addition to diagnosed eating disorders, parents, guardians, and health care professionals should be aware of symptoms of disordered eating, which include behaviors such as weight-loss dieting, binge eating, self-induced vomiting, excessive exercise, and the use of laxatives or diuretics without medical prescription.

This article was translated from the Medscape Portuguese Edition. A version of this article appeared on Medscape.com.

WASHINGTON – Atopic dermatitis (AD) in childhood presents most commonly by age 1 and typically begins on the face, and while it can make infants “miserable,” caregiver and provider concerns about treatment on the face and at such a young age mean it is often “woefully undertreated,” Robert Sidbury, MD, MPH, said at the annual Revolutionizing Atopic Dermatitis conference.

Identifying and mitigating triggers – such as irritation, contact allergy, and infection – is a cornerstone of treatment in infants, but tailored therapy with topical corticosteroids, topical calcineurin inhibitors (TCIs), and topical phosphodiesterase 4 (PDE4) inhibitors also have roles to play, said Dr. Sidbury, chief of dermatology at Seattle Children’s Hospital and professor in the department of pediatrics at the University of Washington, Seattle.

Views on the use of dupilumab as a systemic agent for severe infantile AD, meanwhile, have shifted significantly in the past year with the Food and Drug Administration approval of the biologic for children aged 6 months to 5 years and with extended experience with the biologic in all ages, including children, Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, said at the meeting.

The pediatric dermatologists spoke during a session devoted to AD in infants, during which the diagnosis of AD and the role – and risks – of food allergy testing were also discussed. Diagnosis, said Elaine C. Siegfried, MD, who also spoke during the session, requires careful consideration of mimicking conditions and a broader list of differential diagnoses in those infants with poor growth or frequent infections.

Here are some of the experts’ pearls for practice.
 

Diagnosing AD in infants

Among infants who are growing well and otherwise healthy, the infantile eczema phenotype encompasses AD, seborrheic dermatitis, contact dermatitis, psoriasis – and overlap of more than one of these conditions. “Overlap is common,” said Dr. Siegfried, professor of pediatrics and dermatology at Saint Louis University, and director of the division of pediatric dermatology at Cardinal Glennon Children’s Hospital.

(Initial topical treatment for all these conditions is similar, but optimal treatment may differ for young children with moderate to severe disease that requires systemic treatment, she said in an interview after the meeting.)

Sparing of the diaper area that reflects skin barrier integrity is a classic feature of AD in infants and can be a useful diagnostic sign. In addition, “hypopigmentation is more characteristic of psoriasis” than AD, whereas AD tends to be hyperpigmented, which is most obvious in skin-of-color patients, Dr. Siegfried said.

Disease-specific pigment changes may be related to microbial colonization – such as Malassezia-associated hypopigmentation – or cell turnover, which is faster in psoriasis and slower in AD – with corresponding differences in pigment retention, and may be more obvious in children than adults, she said.

A less common scenario is dermatitis in infants who are not growing well. For these patients, she noted, the differential diagnosis includes metabolic or immune deficiency dermatitis as well as a variety of genodermatoses.

Generalized redness and scaling present on the first day of life is suggestive of non-atopic dermatitis. “If you’re born with red scaly skin, that’s very different than if you develop red skin in the first month or two of life,” Dr. Siegfried said.

When there is diaper area involvement with AD, contact dermatitis, impetigo, and Candida may be complicating factors. And in infants with other morbidities – especially those who are not growing well – diaper area involvement suggests a broader differential diagnosis. “I implore you, if you see children, make sure you weigh and measure them at every appointment,” she said.

Dr. Siegfried has seen infants with Netherton syndrome, and those with cystic fibrosis with zinc deficiency, for instance, presenting with “an eczematous-like picture,” diaper-area involvement, and other morbidities.

For infants with AD, she maintains a high index of suspicion for secondary infections such as molluscum, herpes simplex virus (HSV) with or without streptococci, scabies, tinea, and group A streptococci. “Secondary infections ... may be incognito,” she said. “Look for subtle signs. Even molluscum can be very subtle.”

Secondary allergic contact dermatitis is also common although it’s “technically difficult to confirm the diagnosis,” she said. Patch testing in infants is technically challenging, sensitivity is low, and monosensitization is uncommon. “So I do initial empiric topical allergen avoidance,” she said, keeping in mind ubiquitous and avoidable topical allergens such as Kathon, cocamidopropyl betaine, propylene glycol, disperse blue, and adhesives.
 

Treating AD in infancy

Irritation “is probably one of the biggest triggers” of AD in infants, and the often “pristine” diaper area compared with inflamed eczema elsewhere can demonstrate the importance of moisturization for healthy skin in atopic infants, Dr. Sidbury said.

Among treatments that “punch above their weight” for AD in infants is an ointment-based barrier applied around the mouth, chin, and chest – where the wet/dry impact of drooling is maximal – before and after meals, he said.

Another is hydrocortisone 2.5% mixed 1:1 with mupirocin for those infants who have secondary infections and “that exudative, weepy-looking appearance on the face,” he said. The topical antibiotic in the combination cream “lessens the potency of the steroid and oftentimes by synergy, makes it more effective” by simultaneously treating inflammation, he said. He cautions against products containing neomycin, which can be an allergen.

A combination antibiotic-steroid-emollient cream (the Aron Regimen) can also “sometimes punch above its weight,” Dr. Sidbury said.

Infections typically involve Staphylococcus aureus, but in up to 16% of cases Streptococcus is involved. And notably, lurking underneath the honey-colored crusting of S. aureus infections may be the grouped vesicles that characterize eczema herpeticum, Dr. Sidbury said.

“Counsel [parents] preemptively to treat cold sores immediately [in order to] decrease HSV shedding and minimize risk to their baby,” Dr. Sidbury said.

For treating AD-associated inflammation in skin not affected by secondary infections, over-the-counter 1% hydrocortisone cream is often sufficient, and “for very young babies and preemies in particular, I generally don’t use anything stronger because their skin barrier isn’t fully complete yet, so they absorb more than an older child does,” he said, referring to ages 2 months corrected as a marker for considering a stronger formulation if needed.

Many parents are “very concerned” about topical corticosteroid (TCS) use and pediatricians are also “often concerned,” Dr. Sidbury said. Addressing this concern, he tries to provide context and promote adherence by pointing out that infants have an easily visible vein at the temple area where the skin is naturally thin. If parents were to see this appearance for the first time in other areas while using topical steroids, he tells them, it may be the first sign of skin thinning, but “it’s entirely reversible at that stage.”

He also stressed the cost of not treating. It’s unknown whether “treating aggressively early on prevents any future development or manifestation of eczema, or future comorbidities, but we don’t know that it doesn’t,” Dr. Sidbury said. “And we certainly know how miserable that baby with eczema can be in the short term. So we need to use these medicines.”

Dr. Sidbury utilizes tacrolimus 0.03% ointment, a topical calcineurin inhibitor (TCI), only if he is worried about overuse of steroids, and uses a regimen that alternates the TCI (used in infants off-label because it is approved for ages 2 years and older) with TCS in periods of similar duration (for example, treatment with TCS for 1 week and TCI for 1 week, or rotations of 2 weeks each or 3 days each). “And these rotations may be dynamic depending on severity of the flare at any given time,” he said after the meeting.

Preapproval data from the pivotal trials of tacrolimus are reassuring and can be shared with parents. “Two-year-olds had 90% of BSA [body surface area] treated for 12 weeks” with no signs of systemic risks, Dr. Sidbury said at the meeting.

Crisaborole, a topical phosphodiesterase 4 (PDE4) inhibitor approved for AD down to age 3 months, does not, like tacrolimus, have a boxed warning about a possible risk for cancer, and may also be alternated with TCSs. It will cause stinging in some children, but TCSs and TCIs can also sting in some children, he said, noting that samples can be helpful to predict what will or won’t sting each infant.
 

Systemic treatment in infants

The Liberty AD PRESCHOOL phase 3 trial that supported the FDA’s approval of dupilumab down to 6 months of age, published in 2022 in The Lancet, covered ages 6 months to 5 years but included only six children under the age of 2, “leaving us with a very limited dataset in this age group,” Dr. Eichenfield said at the meeting.

University of California, San Diego

Other data and analyses that have provided reassurance, such as a laboratory safety analysis published online in 2022 showing no meaningful changes in laboratory safety parameters in children as young as 6 months, and pediatric data (not including infants) presented at a RAD meeting in 2022 showing that dupilumab, an interleukin-4 receptor alpha antagonist, may have positive effects on bone mineral density.

Data from the Liberty AD PRESCHOOL open-label extension study presented at the American Academy of Dermatology meeting in 2023, meanwhile, show that “the adverse event profile is not looking much different than what we see in older children,” Dr. Eichenfield said. “There are low rates of severe adverse events and a very low rate of discontinuations.”

At Rady Children’s Hospital, where Dr. Eichenfield is chief of pediatric and adolescent dermatology, dupilumab has become a first-line systemic agent for severe infantile AD, supplanting prior traditional but little used systemic agents such as oral corticosteroids, cyclosporine, methotrexate, azathioprine, or mycophenolate, he said after the meeting.

The decision to use systemics in the first 2 years of life is “a comprehensive one,” requiring knowledge of the child’s history, disease course, and assessment of response to prior therapies, comorbidities and severity, he said.
 

Food allergy in infants with AD

Food allergy is common in children with moderate to severe AD, but true food-triggered AD, with AD being the only symptom of food allergy, is rare, said Anne Marie Singh, MD, associate professor in the division of allergy and immunology and rheumatology at the University of Wisconsin, Madison, who focuses on pediatrics.

Over the years, studies of double-blind placebo-controlled food challenge tests in children with AD have tended to conflate immediate IgE hypersensitivity (and skin symptoms like urticaria) with AD, said Dr. Singh, who directs the university’s Food Allergy Research and Education Center of Excellence. In a recently published study she led involving 374 children with AD referred to allergy and/or dermatology subspecialty clinics at the University of Wisconsin, Madison, 55% had a food allergy but only 2% had food-triggered AD “where eczema is the only symptom and removal of the food cleared up the eczema and its return brought it back,” Dr. Singh said at the meeting. Another 4% had combined IgE-mediated food allergy and food-triggered AD. Almost half of the children with food-triggered AD were under 1 year of age, and egg was the most common trigger, she noted.

Food should be implicated largely by history, Dr. Singh emphasized.

Food allergy testing in the context of AD can be done but is challenging, with the clinical relevance of skin prick testing and food-specific immunoglobulin E (sIgE) difficult to predict. Predictive values of sIgE levels are established for immediate IgE mediated food allergy, but “cut-offs” for food-triggered AD are not established, she explained, noting that “cut-offs are likely higher for our children with AD.”

Elimination diets, moreover, pose significant risks of future oral tolerance and risks of nutritional deficiencies and poor growth, Dr. Singh said. New and immediate reactions to foods that are reintroduced after an elimination diet are common, and research has shown that 20% or more of such reactions involve anaphylaxis. “If an elimination diet is undertaken, you need emergency action plans, injectable epinephrine, and nutrition counseling,” she said.

A recent systematic review and meta-analysis conditionally recommended against elimination diets for the treatment of AD, Dr. Singh noted.

Asked by Dr. Sidbury whether there “is a sweet spot where you can eliminate [foods] without going all the way,” Dr. Singh said she will sometimes do a “diagnostic elimination trial” with food elimination for 2-4 weeks only – a time period after which “I’ll feel really comfortable reintroducing the food.”

Dr. Singh urged dermatologists to “know your allergist” because “patients respond best with a consistent message.”

Dr. Sidbury reported ties with Regeneron, UCB, Pfizer, Leo Pharma, Lilly, and Beiersdorf. Dr. Siegfried reported ties with Pfizer, Regeneron, Sanofi Genzyme, Pfizer, UCB, Novan and Leo Pharma. Dr. Singh reported ties with Incyte and Siolta Therapeutics. Dr. Eichenfield reported ties with Pfizer, Regeneron, Sanofi Genzyme, Incyte, and Pfizer.

WASHINGTON – Atopic dermatitis (AD) in childhood presents most commonly by age 1 and typically begins on the face, and while it can make infants “miserable,” caregiver and provider concerns about treatment on the face and at such a young age mean it is often “woefully undertreated,” Robert Sidbury, MD, MPH, said at the annual Revolutionizing Atopic Dermatitis conference.

Identifying and mitigating triggers – such as irritation, contact allergy, and infection – is a cornerstone of treatment in infants, but tailored therapy with topical corticosteroids, topical calcineurin inhibitors (TCIs), and topical phosphodiesterase 4 (PDE4) inhibitors also have roles to play, said Dr. Sidbury, chief of dermatology at Seattle Children’s Hospital and professor in the department of pediatrics at the University of Washington, Seattle.

Views on the use of dupilumab as a systemic agent for severe infantile AD, meanwhile, have shifted significantly in the past year with the Food and Drug Administration approval of the biologic for children aged 6 months to 5 years and with extended experience with the biologic in all ages, including children, Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, said at the meeting.

The pediatric dermatologists spoke during a session devoted to AD in infants, during which the diagnosis of AD and the role – and risks – of food allergy testing were also discussed. Diagnosis, said Elaine C. Siegfried, MD, who also spoke during the session, requires careful consideration of mimicking conditions and a broader list of differential diagnoses in those infants with poor growth or frequent infections.

Here are some of the experts’ pearls for practice.
 

Diagnosing AD in infants

Among infants who are growing well and otherwise healthy, the infantile eczema phenotype encompasses AD, seborrheic dermatitis, contact dermatitis, psoriasis – and overlap of more than one of these conditions. “Overlap is common,” said Dr. Siegfried, professor of pediatrics and dermatology at Saint Louis University, and director of the division of pediatric dermatology at Cardinal Glennon Children’s Hospital.

(Initial topical treatment for all these conditions is similar, but optimal treatment may differ for young children with moderate to severe disease that requires systemic treatment, she said in an interview after the meeting.)

Sparing of the diaper area that reflects skin barrier integrity is a classic feature of AD in infants and can be a useful diagnostic sign. In addition, “hypopigmentation is more characteristic of psoriasis” than AD, whereas AD tends to be hyperpigmented, which is most obvious in skin-of-color patients, Dr. Siegfried said.

Disease-specific pigment changes may be related to microbial colonization – such as Malassezia-associated hypopigmentation – or cell turnover, which is faster in psoriasis and slower in AD – with corresponding differences in pigment retention, and may be more obvious in children than adults, she said.

A less common scenario is dermatitis in infants who are not growing well. For these patients, she noted, the differential diagnosis includes metabolic or immune deficiency dermatitis as well as a variety of genodermatoses.

Generalized redness and scaling present on the first day of life is suggestive of non-atopic dermatitis. “If you’re born with red scaly skin, that’s very different than if you develop red skin in the first month or two of life,” Dr. Siegfried said.

When there is diaper area involvement with AD, contact dermatitis, impetigo, and Candida may be complicating factors. And in infants with other morbidities – especially those who are not growing well – diaper area involvement suggests a broader differential diagnosis. “I implore you, if you see children, make sure you weigh and measure them at every appointment,” she said.

Dr. Siegfried has seen infants with Netherton syndrome, and those with cystic fibrosis with zinc deficiency, for instance, presenting with “an eczematous-like picture,” diaper-area involvement, and other morbidities.

For infants with AD, she maintains a high index of suspicion for secondary infections such as molluscum, herpes simplex virus (HSV) with or without streptococci, scabies, tinea, and group A streptococci. “Secondary infections ... may be incognito,” she said. “Look for subtle signs. Even molluscum can be very subtle.”

Secondary allergic contact dermatitis is also common although it’s “technically difficult to confirm the diagnosis,” she said. Patch testing in infants is technically challenging, sensitivity is low, and monosensitization is uncommon. “So I do initial empiric topical allergen avoidance,” she said, keeping in mind ubiquitous and avoidable topical allergens such as Kathon, cocamidopropyl betaine, propylene glycol, disperse blue, and adhesives.
 

Treating AD in infancy

Irritation “is probably one of the biggest triggers” of AD in infants, and the often “pristine” diaper area compared with inflamed eczema elsewhere can demonstrate the importance of moisturization for healthy skin in atopic infants, Dr. Sidbury said.

Among treatments that “punch above their weight” for AD in infants is an ointment-based barrier applied around the mouth, chin, and chest – where the wet/dry impact of drooling is maximal – before and after meals, he said.

Another is hydrocortisone 2.5% mixed 1:1 with mupirocin for those infants who have secondary infections and “that exudative, weepy-looking appearance on the face,” he said. The topical antibiotic in the combination cream “lessens the potency of the steroid and oftentimes by synergy, makes it more effective” by simultaneously treating inflammation, he said. He cautions against products containing neomycin, which can be an allergen.

A combination antibiotic-steroid-emollient cream (the Aron Regimen) can also “sometimes punch above its weight,” Dr. Sidbury said.

Infections typically involve Staphylococcus aureus, but in up to 16% of cases Streptococcus is involved. And notably, lurking underneath the honey-colored crusting of S. aureus infections may be the grouped vesicles that characterize eczema herpeticum, Dr. Sidbury said.

“Counsel [parents] preemptively to treat cold sores immediately [in order to] decrease HSV shedding and minimize risk to their baby,” Dr. Sidbury said.

For treating AD-associated inflammation in skin not affected by secondary infections, over-the-counter 1% hydrocortisone cream is often sufficient, and “for very young babies and preemies in particular, I generally don’t use anything stronger because their skin barrier isn’t fully complete yet, so they absorb more than an older child does,” he said, referring to ages 2 months corrected as a marker for considering a stronger formulation if needed.

Many parents are “very concerned” about topical corticosteroid (TCS) use and pediatricians are also “often concerned,” Dr. Sidbury said. Addressing this concern, he tries to provide context and promote adherence by pointing out that infants have an easily visible vein at the temple area where the skin is naturally thin. If parents were to see this appearance for the first time in other areas while using topical steroids, he tells them, it may be the first sign of skin thinning, but “it’s entirely reversible at that stage.”

He also stressed the cost of not treating. It’s unknown whether “treating aggressively early on prevents any future development or manifestation of eczema, or future comorbidities, but we don’t know that it doesn’t,” Dr. Sidbury said. “And we certainly know how miserable that baby with eczema can be in the short term. So we need to use these medicines.”

Dr. Sidbury utilizes tacrolimus 0.03% ointment, a topical calcineurin inhibitor (TCI), only if he is worried about overuse of steroids, and uses a regimen that alternates the TCI (used in infants off-label because it is approved for ages 2 years and older) with TCS in periods of similar duration (for example, treatment with TCS for 1 week and TCI for 1 week, or rotations of 2 weeks each or 3 days each). “And these rotations may be dynamic depending on severity of the flare at any given time,” he said after the meeting.

Preapproval data from the pivotal trials of tacrolimus are reassuring and can be shared with parents. “Two-year-olds had 90% of BSA [body surface area] treated for 12 weeks” with no signs of systemic risks, Dr. Sidbury said at the meeting.

Crisaborole, a topical phosphodiesterase 4 (PDE4) inhibitor approved for AD down to age 3 months, does not, like tacrolimus, have a boxed warning about a possible risk for cancer, and may also be alternated with TCSs. It will cause stinging in some children, but TCSs and TCIs can also sting in some children, he said, noting that samples can be helpful to predict what will or won’t sting each infant.
 

Systemic treatment in infants

The Liberty AD PRESCHOOL phase 3 trial that supported the FDA’s approval of dupilumab down to 6 months of age, published in 2022 in The Lancet, covered ages 6 months to 5 years but included only six children under the age of 2, “leaving us with a very limited dataset in this age group,” Dr. Eichenfield said at the meeting.

University of California, San Diego

Other data and analyses that have provided reassurance, such as a laboratory safety analysis published online in 2022 showing no meaningful changes in laboratory safety parameters in children as young as 6 months, and pediatric data (not including infants) presented at a RAD meeting in 2022 showing that dupilumab, an interleukin-4 receptor alpha antagonist, may have positive effects on bone mineral density.

Data from the Liberty AD PRESCHOOL open-label extension study presented at the American Academy of Dermatology meeting in 2023, meanwhile, show that “the adverse event profile is not looking much different than what we see in older children,” Dr. Eichenfield said. “There are low rates of severe adverse events and a very low rate of discontinuations.”

At Rady Children’s Hospital, where Dr. Eichenfield is chief of pediatric and adolescent dermatology, dupilumab has become a first-line systemic agent for severe infantile AD, supplanting prior traditional but little used systemic agents such as oral corticosteroids, cyclosporine, methotrexate, azathioprine, or mycophenolate, he said after the meeting.

The decision to use systemics in the first 2 years of life is “a comprehensive one,” requiring knowledge of the child’s history, disease course, and assessment of response to prior therapies, comorbidities and severity, he said.
 

Food allergy in infants with AD

Food allergy is common in children with moderate to severe AD, but true food-triggered AD, with AD being the only symptom of food allergy, is rare, said Anne Marie Singh, MD, associate professor in the division of allergy and immunology and rheumatology at the University of Wisconsin, Madison, who focuses on pediatrics.

Over the years, studies of double-blind placebo-controlled food challenge tests in children with AD have tended to conflate immediate IgE hypersensitivity (and skin symptoms like urticaria) with AD, said Dr. Singh, who directs the university’s Food Allergy Research and Education Center of Excellence. In a recently published study she led involving 374 children with AD referred to allergy and/or dermatology subspecialty clinics at the University of Wisconsin, Madison, 55% had a food allergy but only 2% had food-triggered AD “where eczema is the only symptom and removal of the food cleared up the eczema and its return brought it back,” Dr. Singh said at the meeting. Another 4% had combined IgE-mediated food allergy and food-triggered AD. Almost half of the children with food-triggered AD were under 1 year of age, and egg was the most common trigger, she noted.

Food should be implicated largely by history, Dr. Singh emphasized.

Food allergy testing in the context of AD can be done but is challenging, with the clinical relevance of skin prick testing and food-specific immunoglobulin E (sIgE) difficult to predict. Predictive values of sIgE levels are established for immediate IgE mediated food allergy, but “cut-offs” for food-triggered AD are not established, she explained, noting that “cut-offs are likely higher for our children with AD.”

Elimination diets, moreover, pose significant risks of future oral tolerance and risks of nutritional deficiencies and poor growth, Dr. Singh said. New and immediate reactions to foods that are reintroduced after an elimination diet are common, and research has shown that 20% or more of such reactions involve anaphylaxis. “If an elimination diet is undertaken, you need emergency action plans, injectable epinephrine, and nutrition counseling,” she said.

A recent systematic review and meta-analysis conditionally recommended against elimination diets for the treatment of AD, Dr. Singh noted.

Asked by Dr. Sidbury whether there “is a sweet spot where you can eliminate [foods] without going all the way,” Dr. Singh said she will sometimes do a “diagnostic elimination trial” with food elimination for 2-4 weeks only – a time period after which “I’ll feel really comfortable reintroducing the food.”

Dr. Singh urged dermatologists to “know your allergist” because “patients respond best with a consistent message.”

Dr. Sidbury reported ties with Regeneron, UCB, Pfizer, Leo Pharma, Lilly, and Beiersdorf. Dr. Siegfried reported ties with Pfizer, Regeneron, Sanofi Genzyme, Pfizer, UCB, Novan and Leo Pharma. Dr. Singh reported ties with Incyte and Siolta Therapeutics. Dr. Eichenfield reported ties with Pfizer, Regeneron, Sanofi Genzyme, Incyte, and Pfizer.

WASHINGTON – Atopic dermatitis (AD) in childhood presents most commonly by age 1 and typically begins on the face, and while it can make infants “miserable,” caregiver and provider concerns about treatment on the face and at such a young age mean it is often “woefully undertreated,” Robert Sidbury, MD, MPH, said at the annual Revolutionizing Atopic Dermatitis conference.

Identifying and mitigating triggers – such as irritation, contact allergy, and infection – is a cornerstone of treatment in infants, but tailored therapy with topical corticosteroids, topical calcineurin inhibitors (TCIs), and topical phosphodiesterase 4 (PDE4) inhibitors also have roles to play, said Dr. Sidbury, chief of dermatology at Seattle Children’s Hospital and professor in the department of pediatrics at the University of Washington, Seattle.

Views on the use of dupilumab as a systemic agent for severe infantile AD, meanwhile, have shifted significantly in the past year with the Food and Drug Administration approval of the biologic for children aged 6 months to 5 years and with extended experience with the biologic in all ages, including children, Lawrence F. Eichenfield, MD, professor of dermatology and pediatrics at the University of California, San Diego, said at the meeting.

The pediatric dermatologists spoke during a session devoted to AD in infants, during which the diagnosis of AD and the role – and risks – of food allergy testing were also discussed. Diagnosis, said Elaine C. Siegfried, MD, who also spoke during the session, requires careful consideration of mimicking conditions and a broader list of differential diagnoses in those infants with poor growth or frequent infections.

Here are some of the experts’ pearls for practice.
 

Diagnosing AD in infants

Among infants who are growing well and otherwise healthy, the infantile eczema phenotype encompasses AD, seborrheic dermatitis, contact dermatitis, psoriasis – and overlap of more than one of these conditions. “Overlap is common,” said Dr. Siegfried, professor of pediatrics and dermatology at Saint Louis University, and director of the division of pediatric dermatology at Cardinal Glennon Children’s Hospital.

(Initial topical treatment for all these conditions is similar, but optimal treatment may differ for young children with moderate to severe disease that requires systemic treatment, she said in an interview after the meeting.)

Sparing of the diaper area that reflects skin barrier integrity is a classic feature of AD in infants and can be a useful diagnostic sign. In addition, “hypopigmentation is more characteristic of psoriasis” than AD, whereas AD tends to be hyperpigmented, which is most obvious in skin-of-color patients, Dr. Siegfried said.

Disease-specific pigment changes may be related to microbial colonization – such as Malassezia-associated hypopigmentation – or cell turnover, which is faster in psoriasis and slower in AD – with corresponding differences in pigment retention, and may be more obvious in children than adults, she said.

A less common scenario is dermatitis in infants who are not growing well. For these patients, she noted, the differential diagnosis includes metabolic or immune deficiency dermatitis as well as a variety of genodermatoses.

Generalized redness and scaling present on the first day of life is suggestive of non-atopic dermatitis. “If you’re born with red scaly skin, that’s very different than if you develop red skin in the first month or two of life,” Dr. Siegfried said.

When there is diaper area involvement with AD, contact dermatitis, impetigo, and Candida may be complicating factors. And in infants with other morbidities – especially those who are not growing well – diaper area involvement suggests a broader differential diagnosis. “I implore you, if you see children, make sure you weigh and measure them at every appointment,” she said.

Dr. Siegfried has seen infants with Netherton syndrome, and those with cystic fibrosis with zinc deficiency, for instance, presenting with “an eczematous-like picture,” diaper-area involvement, and other morbidities.

For infants with AD, she maintains a high index of suspicion for secondary infections such as molluscum, herpes simplex virus (HSV) with or without streptococci, scabies, tinea, and group A streptococci. “Secondary infections ... may be incognito,” she said. “Look for subtle signs. Even molluscum can be very subtle.”

Secondary allergic contact dermatitis is also common although it’s “technically difficult to confirm the diagnosis,” she said. Patch testing in infants is technically challenging, sensitivity is low, and monosensitization is uncommon. “So I do initial empiric topical allergen avoidance,” she said, keeping in mind ubiquitous and avoidable topical allergens such as Kathon, cocamidopropyl betaine, propylene glycol, disperse blue, and adhesives.
 

Treating AD in infancy

Irritation “is probably one of the biggest triggers” of AD in infants, and the often “pristine” diaper area compared with inflamed eczema elsewhere can demonstrate the importance of moisturization for healthy skin in atopic infants, Dr. Sidbury said.

Among treatments that “punch above their weight” for AD in infants is an ointment-based barrier applied around the mouth, chin, and chest – where the wet/dry impact of drooling is maximal – before and after meals, he said.

Another is hydrocortisone 2.5% mixed 1:1 with mupirocin for those infants who have secondary infections and “that exudative, weepy-looking appearance on the face,” he said. The topical antibiotic in the combination cream “lessens the potency of the steroid and oftentimes by synergy, makes it more effective” by simultaneously treating inflammation, he said. He cautions against products containing neomycin, which can be an allergen.

A combination antibiotic-steroid-emollient cream (the Aron Regimen) can also “sometimes punch above its weight,” Dr. Sidbury said.

Infections typically involve Staphylococcus aureus, but in up to 16% of cases Streptococcus is involved. And notably, lurking underneath the honey-colored crusting of S. aureus infections may be the grouped vesicles that characterize eczema herpeticum, Dr. Sidbury said.

“Counsel [parents] preemptively to treat cold sores immediately [in order to] decrease HSV shedding and minimize risk to their baby,” Dr. Sidbury said.

For treating AD-associated inflammation in skin not affected by secondary infections, over-the-counter 1% hydrocortisone cream is often sufficient, and “for very young babies and preemies in particular, I generally don’t use anything stronger because their skin barrier isn’t fully complete yet, so they absorb more than an older child does,” he said, referring to ages 2 months corrected as a marker for considering a stronger formulation if needed.

Many parents are “very concerned” about topical corticosteroid (TCS) use and pediatricians are also “often concerned,” Dr. Sidbury said. Addressing this concern, he tries to provide context and promote adherence by pointing out that infants have an easily visible vein at the temple area where the skin is naturally thin. If parents were to see this appearance for the first time in other areas while using topical steroids, he tells them, it may be the first sign of skin thinning, but “it’s entirely reversible at that stage.”

He also stressed the cost of not treating. It’s unknown whether “treating aggressively early on prevents any future development or manifestation of eczema, or future comorbidities, but we don’t know that it doesn’t,” Dr. Sidbury said. “And we certainly know how miserable that baby with eczema can be in the short term. So we need to use these medicines.”

Dr. Sidbury utilizes tacrolimus 0.03% ointment, a topical calcineurin inhibitor (TCI), only if he is worried about overuse of steroids, and uses a regimen that alternates the TCI (used in infants off-label because it is approved for ages 2 years and older) with TCS in periods of similar duration (for example, treatment with TCS for 1 week and TCI for 1 week, or rotations of 2 weeks each or 3 days each). “And these rotations may be dynamic depending on severity of the flare at any given time,” he said after the meeting.

Preapproval data from the pivotal trials of tacrolimus are reassuring and can be shared with parents. “Two-year-olds had 90% of BSA [body surface area] treated for 12 weeks” with no signs of systemic risks, Dr. Sidbury said at the meeting.

Crisaborole, a topical phosphodiesterase 4 (PDE4) inhibitor approved for AD down to age 3 months, does not, like tacrolimus, have a boxed warning about a possible risk for cancer, and may also be alternated with TCSs. It will cause stinging in some children, but TCSs and TCIs can also sting in some children, he said, noting that samples can be helpful to predict what will or won’t sting each infant.
 

Systemic treatment in infants

The Liberty AD PRESCHOOL phase 3 trial that supported the FDA’s approval of dupilumab down to 6 months of age, published in 2022 in The Lancet, covered ages 6 months to 5 years but included only six children under the age of 2, “leaving us with a very limited dataset in this age group,” Dr. Eichenfield said at the meeting.

University of California, San Diego

Other data and analyses that have provided reassurance, such as a laboratory safety analysis published online in 2022 showing no meaningful changes in laboratory safety parameters in children as young as 6 months, and pediatric data (not including infants) presented at a RAD meeting in 2022 showing that dupilumab, an interleukin-4 receptor alpha antagonist, may have positive effects on bone mineral density.

Data from the Liberty AD PRESCHOOL open-label extension study presented at the American Academy of Dermatology meeting in 2023, meanwhile, show that “the adverse event profile is not looking much different than what we see in older children,” Dr. Eichenfield said. “There are low rates of severe adverse events and a very low rate of discontinuations.”

At Rady Children’s Hospital, where Dr. Eichenfield is chief of pediatric and adolescent dermatology, dupilumab has become a first-line systemic agent for severe infantile AD, supplanting prior traditional but little used systemic agents such as oral corticosteroids, cyclosporine, methotrexate, azathioprine, or mycophenolate, he said after the meeting.

The decision to use systemics in the first 2 years of life is “a comprehensive one,” requiring knowledge of the child’s history, disease course, and assessment of response to prior therapies, comorbidities and severity, he said.
 

Food allergy in infants with AD

Food allergy is common in children with moderate to severe AD, but true food-triggered AD, with AD being the only symptom of food allergy, is rare, said Anne Marie Singh, MD, associate professor in the division of allergy and immunology and rheumatology at the University of Wisconsin, Madison, who focuses on pediatrics.

Over the years, studies of double-blind placebo-controlled food challenge tests in children with AD have tended to conflate immediate IgE hypersensitivity (and skin symptoms like urticaria) with AD, said Dr. Singh, who directs the university’s Food Allergy Research and Education Center of Excellence. In a recently published study she led involving 374 children with AD referred to allergy and/or dermatology subspecialty clinics at the University of Wisconsin, Madison, 55% had a food allergy but only 2% had food-triggered AD “where eczema is the only symptom and removal of the food cleared up the eczema and its return brought it back,” Dr. Singh said at the meeting. Another 4% had combined IgE-mediated food allergy and food-triggered AD. Almost half of the children with food-triggered AD were under 1 year of age, and egg was the most common trigger, she noted.

Food should be implicated largely by history, Dr. Singh emphasized.

Food allergy testing in the context of AD can be done but is challenging, with the clinical relevance of skin prick testing and food-specific immunoglobulin E (sIgE) difficult to predict. Predictive values of sIgE levels are established for immediate IgE mediated food allergy, but “cut-offs” for food-triggered AD are not established, she explained, noting that “cut-offs are likely higher for our children with AD.”

Elimination diets, moreover, pose significant risks of future oral tolerance and risks of nutritional deficiencies and poor growth, Dr. Singh said. New and immediate reactions to foods that are reintroduced after an elimination diet are common, and research has shown that 20% or more of such reactions involve anaphylaxis. “If an elimination diet is undertaken, you need emergency action plans, injectable epinephrine, and nutrition counseling,” she said.

A recent systematic review and meta-analysis conditionally recommended against elimination diets for the treatment of AD, Dr. Singh noted.

Asked by Dr. Sidbury whether there “is a sweet spot where you can eliminate [foods] without going all the way,” Dr. Singh said she will sometimes do a “diagnostic elimination trial” with food elimination for 2-4 weeks only – a time period after which “I’ll feel really comfortable reintroducing the food.”

Dr. Singh urged dermatologists to “know your allergist” because “patients respond best with a consistent message.”

Dr. Sidbury reported ties with Regeneron, UCB, Pfizer, Leo Pharma, Lilly, and Beiersdorf. Dr. Siegfried reported ties with Pfizer, Regeneron, Sanofi Genzyme, Pfizer, UCB, Novan and Leo Pharma. Dr. Singh reported ties with Incyte and Siolta Therapeutics. Dr. Eichenfield reported ties with Pfizer, Regeneron, Sanofi Genzyme, Incyte, and Pfizer.

BALTIMORE – Less than half of the pregnant patients who met the criteria for thyroid screening were actually screened by their clinician, according to a retrospective cohort study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists in Baltimore. Those who met criteria and did receive screening had higher live birth rates and lower miscarriage rates than those who met the criteria but did not undergo screening, the study found.

“These results suggest that improving thyroid screening adherence may lead to improved pregnancy outcomes,” lead author Allan Dong, MD, of Advocate Lutheran General Hospital in Des Plaines, Ill., told attendees. “However, following targeted screening guidelines can be difficult for clinicians. In practice, universal screening for diabetes and pregnancy may provide more comprehensive screening coverage and potentially lead to improved outcomes.”

Instead of universal screening for thyroid disease, ACOG and the American Thyroid Association recommend targeted screening of high-risk patients, though ATA’s criteria are substantially broader than ACOG’s. But, Dr. Dong told attendees, “guidelines are only beneficial if they are followed appropriately,” and Ob.Gyns. have limited time to screen for risk factors in the midst of other clinical priorities. So he aimed to learn whether Ob.Gyns. were following the guidelines of either organization in screening people at higher risk for thyroid disease.

Dr. Dong and his coauthor, Melisa Lott, DO, reviewed the charts of all 1,025 patients who presented at their institution for new obstetrical visits in 2020 to determine which ones had risk factors that would qualify them for screening under ATA or ACOG guidelines. ACOG’s screening criteria included having a personal or family history of thyroid disease or type 1 diabetes, or there being clinical suspicion for thyroid disease. ATA’s screening criteria included the following:

• Personal or family history of thyroid disease.
• History of head or neck radiation.
• History of a prior thyroid surgery.
• Over age 30.
• Any autoimmune disease.
• A body mass index greater than 40 kg/m².
• History of pregnancy loss, preterm delivery, or infertility.
• Recently used amiodarone lithium or iodine-based contrast.
• Lived in an area of known iodine deficiency.
• Clinical suspicion of thyroid disease.

ATA screening criteria identified four times as many patients requiring screening than did ACOG criteria, Dr. Dong noted. Of the 198 patients who met ACOG’s criteria, 43.9% were screened with thyroid function testing. Meanwhile, 826 patients – including all those who met ACOG’s criteria – met ATA’s criteria for screening, but only 13.1% of them underwent thyroid function testing.

Live birth rates were significantly higher among patients who met ATA criteria and were screened (92.6%) than among patients who met ATA criteria but were not screened (83.3%, P = .006). Similarly, the miscarriage rate was 4.6% in patients who met ATA criteria and were screened, compared to 12.4% in patients who met the criteria but did not undergo thyroid function testing (P = .009).

“A similar difference, although not statistically significant, was noted when comparing patients who were screened appropriately per ACOG criteria with those who met criteria for screening but were not screened,” Dr. Dong told attendees. “However, our study was underpowered to detect this difference due to the lower number of patients who meet criteria for screening under ACOG guidelines.”

The researchers did not find any significant difference in preterm delivery rates.

Anna Whelan, MD, of Women & Infants Hospital of Brown University, Providence, R.I., was not involved in the study but viewed the poster and pointed out that many of the patients, if seen by a primary care provider prior to pregnancy, would likely have been screened by their PCP. The rate of underscreening therefore suggests that patients “are not getting good, consistent primary care because there’s a lack of primary care physicians,” Dr. Whelan said in an interview.

In addition, she added, “maybe not all obstetricians and those providing care, such as midwives and other providers, are aware of the [ATA] guidelines on who should be screened.” She added that additional education about thyroid screening guidelines might be helpful for providers.

Dr. Dong reported being a stock shareholder in 3M, AbbVie, General Electric, Johnson & Johnson, Medtronic, Pfizer, and Viking Therapeutics. Dr. Whelan had no disclosures.
 

BALTIMORE – Less than half of the pregnant patients who met the criteria for thyroid screening were actually screened by their clinician, according to a retrospective cohort study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists in Baltimore. Those who met criteria and did receive screening had higher live birth rates and lower miscarriage rates than those who met the criteria but did not undergo screening, the study found.

“These results suggest that improving thyroid screening adherence may lead to improved pregnancy outcomes,” lead author Allan Dong, MD, of Advocate Lutheran General Hospital in Des Plaines, Ill., told attendees. “However, following targeted screening guidelines can be difficult for clinicians. In practice, universal screening for diabetes and pregnancy may provide more comprehensive screening coverage and potentially lead to improved outcomes.”

Instead of universal screening for thyroid disease, ACOG and the American Thyroid Association recommend targeted screening of high-risk patients, though ATA’s criteria are substantially broader than ACOG’s. But, Dr. Dong told attendees, “guidelines are only beneficial if they are followed appropriately,” and Ob.Gyns. have limited time to screen for risk factors in the midst of other clinical priorities. So he aimed to learn whether Ob.Gyns. were following the guidelines of either organization in screening people at higher risk for thyroid disease.

Dr. Dong and his coauthor, Melisa Lott, DO, reviewed the charts of all 1,025 patients who presented at their institution for new obstetrical visits in 2020 to determine which ones had risk factors that would qualify them for screening under ATA or ACOG guidelines. ACOG’s screening criteria included having a personal or family history of thyroid disease or type 1 diabetes, or there being clinical suspicion for thyroid disease. ATA’s screening criteria included the following:

• Personal or family history of thyroid disease.
• History of head or neck radiation.
• History of a prior thyroid surgery.
• Over age 30.
• Any autoimmune disease.
• A body mass index greater than 40 kg/m².
• History of pregnancy loss, preterm delivery, or infertility.
• Recently used amiodarone lithium or iodine-based contrast.
• Lived in an area of known iodine deficiency.
• Clinical suspicion of thyroid disease.

ATA screening criteria identified four times as many patients requiring screening than did ACOG criteria, Dr. Dong noted. Of the 198 patients who met ACOG’s criteria, 43.9% were screened with thyroid function testing. Meanwhile, 826 patients – including all those who met ACOG’s criteria – met ATA’s criteria for screening, but only 13.1% of them underwent thyroid function testing.

Live birth rates were significantly higher among patients who met ATA criteria and were screened (92.6%) than among patients who met ATA criteria but were not screened (83.3%, P = .006). Similarly, the miscarriage rate was 4.6% in patients who met ATA criteria and were screened, compared to 12.4% in patients who met the criteria but did not undergo thyroid function testing (P = .009).

“A similar difference, although not statistically significant, was noted when comparing patients who were screened appropriately per ACOG criteria with those who met criteria for screening but were not screened,” Dr. Dong told attendees. “However, our study was underpowered to detect this difference due to the lower number of patients who meet criteria for screening under ACOG guidelines.”

The researchers did not find any significant difference in preterm delivery rates.

Anna Whelan, MD, of Women & Infants Hospital of Brown University, Providence, R.I., was not involved in the study but viewed the poster and pointed out that many of the patients, if seen by a primary care provider prior to pregnancy, would likely have been screened by their PCP. The rate of underscreening therefore suggests that patients “are not getting good, consistent primary care because there’s a lack of primary care physicians,” Dr. Whelan said in an interview.

In addition, she added, “maybe not all obstetricians and those providing care, such as midwives and other providers, are aware of the [ATA] guidelines on who should be screened.” She added that additional education about thyroid screening guidelines might be helpful for providers.

Dr. Dong reported being a stock shareholder in 3M, AbbVie, General Electric, Johnson & Johnson, Medtronic, Pfizer, and Viking Therapeutics. Dr. Whelan had no disclosures.
 

BALTIMORE – Less than half of the pregnant patients who met the criteria for thyroid screening were actually screened by their clinician, according to a retrospective cohort study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists in Baltimore. Those who met criteria and did receive screening had higher live birth rates and lower miscarriage rates than those who met the criteria but did not undergo screening, the study found.

“These results suggest that improving thyroid screening adherence may lead to improved pregnancy outcomes,” lead author Allan Dong, MD, of Advocate Lutheran General Hospital in Des Plaines, Ill., told attendees. “However, following targeted screening guidelines can be difficult for clinicians. In practice, universal screening for diabetes and pregnancy may provide more comprehensive screening coverage and potentially lead to improved outcomes.”

Instead of universal screening for thyroid disease, ACOG and the American Thyroid Association recommend targeted screening of high-risk patients, though ATA’s criteria are substantially broader than ACOG’s. But, Dr. Dong told attendees, “guidelines are only beneficial if they are followed appropriately,” and Ob.Gyns. have limited time to screen for risk factors in the midst of other clinical priorities. So he aimed to learn whether Ob.Gyns. were following the guidelines of either organization in screening people at higher risk for thyroid disease.

Dr. Dong and his coauthor, Melisa Lott, DO, reviewed the charts of all 1,025 patients who presented at their institution for new obstetrical visits in 2020 to determine which ones had risk factors that would qualify them for screening under ATA or ACOG guidelines. ACOG’s screening criteria included having a personal or family history of thyroid disease or type 1 diabetes, or there being clinical suspicion for thyroid disease. ATA’s screening criteria included the following:

• Personal or family history of thyroid disease.
• History of head or neck radiation.
• History of a prior thyroid surgery.
• Over age 30.
• Any autoimmune disease.
• A body mass index greater than 40 kg/m².
• History of pregnancy loss, preterm delivery, or infertility.
• Recently used amiodarone lithium or iodine-based contrast.
• Lived in an area of known iodine deficiency.
• Clinical suspicion of thyroid disease.

ATA screening criteria identified four times as many patients requiring screening than did ACOG criteria, Dr. Dong noted. Of the 198 patients who met ACOG’s criteria, 43.9% were screened with thyroid function testing. Meanwhile, 826 patients – including all those who met ACOG’s criteria – met ATA’s criteria for screening, but only 13.1% of them underwent thyroid function testing.

Live birth rates were significantly higher among patients who met ATA criteria and were screened (92.6%) than among patients who met ATA criteria but were not screened (83.3%, P = .006). Similarly, the miscarriage rate was 4.6% in patients who met ATA criteria and were screened, compared to 12.4% in patients who met the criteria but did not undergo thyroid function testing (P = .009).

“A similar difference, although not statistically significant, was noted when comparing patients who were screened appropriately per ACOG criteria with those who met criteria for screening but were not screened,” Dr. Dong told attendees. “However, our study was underpowered to detect this difference due to the lower number of patients who meet criteria for screening under ACOG guidelines.”

The researchers did not find any significant difference in preterm delivery rates.

Anna Whelan, MD, of Women & Infants Hospital of Brown University, Providence, R.I., was not involved in the study but viewed the poster and pointed out that many of the patients, if seen by a primary care provider prior to pregnancy, would likely have been screened by their PCP. The rate of underscreening therefore suggests that patients “are not getting good, consistent primary care because there’s a lack of primary care physicians,” Dr. Whelan said in an interview.

In addition, she added, “maybe not all obstetricians and those providing care, such as midwives and other providers, are aware of the [ATA] guidelines on who should be screened.” She added that additional education about thyroid screening guidelines might be helpful for providers.

Dr. Dong reported being a stock shareholder in 3M, AbbVie, General Electric, Johnson & Johnson, Medtronic, Pfizer, and Viking Therapeutics. Dr. Whelan had no disclosures.
 

In a sign of the power of combination therapy for high-risk chronic lymphocytic leukemia (CLL), a small new study showed that patients were more likely to reach undetectable measurable residual disease (U-MRD) when they added venetoclax to their drug regimen after a year or more of taking ibrutinib.

Of 45 patients, 57% reached U-MRD at 12 months, and 55% reached complete remission, according to the study, published in Leukemia.

By adding venetoclax, “you can get very deep remissions in high-risk patients with ibrutinib,” lead author Philip A. Thompson, MBBS, a hematologist-oncologist with the University of Melbourne and Peter MacCallum Cancer Center, also in Melbourne, said in an interview. “This is a significant advance for really high-risk patients.”

According to Dr. Thompson, Bruton’s tyrosine kinase inhibitors like ibrutinib have revolutionized the treatment of high-risk CLL by forcing the disease into remission for several years and allowing patients to avoid stem cell transplants. “But the drug doesn’t eradicate the disease,” he said, “so eventually these patients develop progression.”

The current hope, he said, is to use a combination therapy like ibrutinib and venetoclax to send CLL into remission with lower chance of drug resistance and then allow patients to stop taking the medications.

Previous research has supported the combination of ibrutinib and venetoclax in CLL in the frontline setting, and the European Commission approved it in 2022 for that use. But “ours is the first [study] that looked at patients who’ve been on ibrutinib for a long time and added venetoclax,” Dr. Thompson said. In some cases, he said, patients in the study had been on ibrutinib for several years.

For the new study, researchers at the University of Texas MD Anderson Cancer Center in Houston – where Dr. Thompson used to work – tracked 45 patients (average age, 68.5 years; 51-80 years) with CLL or small lymphocytic lymphoma who had MRD but no clinical disease progression. They all had at least 1 high-risk feature such as a mutated TP53. They’d been on ibrutinib for a median of 32 months (12-73 months), and two were in complete remission but with MRD.

An intention-to-treat analysis found that 71% reached U-MRD when they finished taking venetoclax. “We were actually pleasantly surprised by the high rate of undetectable MRD,” Dr. Thompson said.

At a median 41-month follow-up, 11% of patients had progressed, but none had died of CLL or Richter transformation, a deadly complication of CLL. “The main side effects were neutropenia and diarrhea, which we were manageable,” Dr. Thompson said.

It’s not clear why the drug combination is especially effective, he said, but it may be because the medications are synergistic. According to the National Cancer Institute, synergy in medicine refers to “the interaction of two or more drugs when their combined effect is greater than the sum of the effects seen when each drug is given alone.”

The findings suggest that “you can get deep remissions in high-risk patients with ibrutinib and venetoclax with very with good tolerability and very low risk of on-treatment progression,” Dr. Thompson said. “We don’t yet have enough progression events to talk about retreatment data, but we do feel that retreatment with Bruton’s tyrosine kinase inhibitors – plus or minus venetoclax – will be successful in the vast majority of patients.”

The combination can be given off label in the United States, Dr. Thompson added. As for expense, adding venetoclax will double the cost of ibrutinib. The two drugs are some of the most expensive medications in the world. But patients will save money if they can stop therapy when they reach remission.

In an interview, hematologist-oncologist Kerry A. Rogers, MD, of Ohio State University, Columbus, who is not involved with the study, praised the research: “While small, this study does say quite a bit about this as a strategy to help people discontinue ibrutinib prior to resistance developing.”

She noted that Bruton’s tyrosine kinase inhibitors “are generally given as a continuous monotherapy, and venetoclax is usually given for a fixed duration in combination with an anti-CD20 antibody.”

Going forward, she said, “the fact that the study was in high-risk patients who have the most to gain from such a combination suggests that similar or better rates of undetectable minimal residual disease might be seen in non–high-risk groups. Additional follow-up should be reported as well as use of this strategy in a larger group of patients before this should be considered a standard approach.”

AbbVie funding the study and provided study drugs. MD Anderson Cancer Center conducted the study and discloses funding from the National Cancer Institute. Dr. Thompson reported ties with AbbVie, Pharmacyclics, Lilly, Adaptive Biotechnologies, Janssen, BeiGene, and Genentech. The other study authors reported multiple disclosures. Dr. Rogers disclosed relationships with Genentech, AbbVie, Novartis, Janssen, Pharmacyclics, BeiGene, Lilly, and AstraZeneca.

In a sign of the power of combination therapy for high-risk chronic lymphocytic leukemia (CLL), a small new study showed that patients were more likely to reach undetectable measurable residual disease (U-MRD) when they added venetoclax to their drug regimen after a year or more of taking ibrutinib.

Of 45 patients, 57% reached U-MRD at 12 months, and 55% reached complete remission, according to the study, published in Leukemia.

By adding venetoclax, “you can get very deep remissions in high-risk patients with ibrutinib,” lead author Philip A. Thompson, MBBS, a hematologist-oncologist with the University of Melbourne and Peter MacCallum Cancer Center, also in Melbourne, said in an interview. “This is a significant advance for really high-risk patients.”

According to Dr. Thompson, Bruton’s tyrosine kinase inhibitors like ibrutinib have revolutionized the treatment of high-risk CLL by forcing the disease into remission for several years and allowing patients to avoid stem cell transplants. “But the drug doesn’t eradicate the disease,” he said, “so eventually these patients develop progression.”

The current hope, he said, is to use a combination therapy like ibrutinib and venetoclax to send CLL into remission with lower chance of drug resistance and then allow patients to stop taking the medications.

Previous research has supported the combination of ibrutinib and venetoclax in CLL in the frontline setting, and the European Commission approved it in 2022 for that use. But “ours is the first [study] that looked at patients who’ve been on ibrutinib for a long time and added venetoclax,” Dr. Thompson said. In some cases, he said, patients in the study had been on ibrutinib for several years.

For the new study, researchers at the University of Texas MD Anderson Cancer Center in Houston – where Dr. Thompson used to work – tracked 45 patients (average age, 68.5 years; 51-80 years) with CLL or small lymphocytic lymphoma who had MRD but no clinical disease progression. They all had at least 1 high-risk feature such as a mutated TP53. They’d been on ibrutinib for a median of 32 months (12-73 months), and two were in complete remission but with MRD.

An intention-to-treat analysis found that 71% reached U-MRD when they finished taking venetoclax. “We were actually pleasantly surprised by the high rate of undetectable MRD,” Dr. Thompson said.

At a median 41-month follow-up, 11% of patients had progressed, but none had died of CLL or Richter transformation, a deadly complication of CLL. “The main side effects were neutropenia and diarrhea, which we were manageable,” Dr. Thompson said.

It’s not clear why the drug combination is especially effective, he said, but it may be because the medications are synergistic. According to the National Cancer Institute, synergy in medicine refers to “the interaction of two or more drugs when their combined effect is greater than the sum of the effects seen when each drug is given alone.”

The findings suggest that “you can get deep remissions in high-risk patients with ibrutinib and venetoclax with very with good tolerability and very low risk of on-treatment progression,” Dr. Thompson said. “We don’t yet have enough progression events to talk about retreatment data, but we do feel that retreatment with Bruton’s tyrosine kinase inhibitors – plus or minus venetoclax – will be successful in the vast majority of patients.”

The combination can be given off label in the United States, Dr. Thompson added. As for expense, adding venetoclax will double the cost of ibrutinib. The two drugs are some of the most expensive medications in the world. But patients will save money if they can stop therapy when they reach remission.

In an interview, hematologist-oncologist Kerry A. Rogers, MD, of Ohio State University, Columbus, who is not involved with the study, praised the research: “While small, this study does say quite a bit about this as a strategy to help people discontinue ibrutinib prior to resistance developing.”

She noted that Bruton’s tyrosine kinase inhibitors “are generally given as a continuous monotherapy, and venetoclax is usually given for a fixed duration in combination with an anti-CD20 antibody.”

Going forward, she said, “the fact that the study was in high-risk patients who have the most to gain from such a combination suggests that similar or better rates of undetectable minimal residual disease might be seen in non–high-risk groups. Additional follow-up should be reported as well as use of this strategy in a larger group of patients before this should be considered a standard approach.”

AbbVie funding the study and provided study drugs. MD Anderson Cancer Center conducted the study and discloses funding from the National Cancer Institute. Dr. Thompson reported ties with AbbVie, Pharmacyclics, Lilly, Adaptive Biotechnologies, Janssen, BeiGene, and Genentech. The other study authors reported multiple disclosures. Dr. Rogers disclosed relationships with Genentech, AbbVie, Novartis, Janssen, Pharmacyclics, BeiGene, Lilly, and AstraZeneca.

In a sign of the power of combination therapy for high-risk chronic lymphocytic leukemia (CLL), a small new study showed that patients were more likely to reach undetectable measurable residual disease (U-MRD) when they added venetoclax to their drug regimen after a year or more of taking ibrutinib.

Of 45 patients, 57% reached U-MRD at 12 months, and 55% reached complete remission, according to the study, published in Leukemia.

By adding venetoclax, “you can get very deep remissions in high-risk patients with ibrutinib,” lead author Philip A. Thompson, MBBS, a hematologist-oncologist with the University of Melbourne and Peter MacCallum Cancer Center, also in Melbourne, said in an interview. “This is a significant advance for really high-risk patients.”

According to Dr. Thompson, Bruton’s tyrosine kinase inhibitors like ibrutinib have revolutionized the treatment of high-risk CLL by forcing the disease into remission for several years and allowing patients to avoid stem cell transplants. “But the drug doesn’t eradicate the disease,” he said, “so eventually these patients develop progression.”

The current hope, he said, is to use a combination therapy like ibrutinib and venetoclax to send CLL into remission with lower chance of drug resistance and then allow patients to stop taking the medications.

Previous research has supported the combination of ibrutinib and venetoclax in CLL in the frontline setting, and the European Commission approved it in 2022 for that use. But “ours is the first [study] that looked at patients who’ve been on ibrutinib for a long time and added venetoclax,” Dr. Thompson said. In some cases, he said, patients in the study had been on ibrutinib for several years.

For the new study, researchers at the University of Texas MD Anderson Cancer Center in Houston – where Dr. Thompson used to work – tracked 45 patients (average age, 68.5 years; 51-80 years) with CLL or small lymphocytic lymphoma who had MRD but no clinical disease progression. They all had at least 1 high-risk feature such as a mutated TP53. They’d been on ibrutinib for a median of 32 months (12-73 months), and two were in complete remission but with MRD.

An intention-to-treat analysis found that 71% reached U-MRD when they finished taking venetoclax. “We were actually pleasantly surprised by the high rate of undetectable MRD,” Dr. Thompson said.

At a median 41-month follow-up, 11% of patients had progressed, but none had died of CLL or Richter transformation, a deadly complication of CLL. “The main side effects were neutropenia and diarrhea, which we were manageable,” Dr. Thompson said.

It’s not clear why the drug combination is especially effective, he said, but it may be because the medications are synergistic. According to the National Cancer Institute, synergy in medicine refers to “the interaction of two or more drugs when their combined effect is greater than the sum of the effects seen when each drug is given alone.”

The findings suggest that “you can get deep remissions in high-risk patients with ibrutinib and venetoclax with very with good tolerability and very low risk of on-treatment progression,” Dr. Thompson said. “We don’t yet have enough progression events to talk about retreatment data, but we do feel that retreatment with Bruton’s tyrosine kinase inhibitors – plus or minus venetoclax – will be successful in the vast majority of patients.”

The combination can be given off label in the United States, Dr. Thompson added. As for expense, adding venetoclax will double the cost of ibrutinib. The two drugs are some of the most expensive medications in the world. But patients will save money if they can stop therapy when they reach remission.

In an interview, hematologist-oncologist Kerry A. Rogers, MD, of Ohio State University, Columbus, who is not involved with the study, praised the research: “While small, this study does say quite a bit about this as a strategy to help people discontinue ibrutinib prior to resistance developing.”

She noted that Bruton’s tyrosine kinase inhibitors “are generally given as a continuous monotherapy, and venetoclax is usually given for a fixed duration in combination with an anti-CD20 antibody.”

Going forward, she said, “the fact that the study was in high-risk patients who have the most to gain from such a combination suggests that similar or better rates of undetectable minimal residual disease might be seen in non–high-risk groups. Additional follow-up should be reported as well as use of this strategy in a larger group of patients before this should be considered a standard approach.”

AbbVie funding the study and provided study drugs. MD Anderson Cancer Center conducted the study and discloses funding from the National Cancer Institute. Dr. Thompson reported ties with AbbVie, Pharmacyclics, Lilly, Adaptive Biotechnologies, Janssen, BeiGene, and Genentech. The other study authors reported multiple disclosures. Dr. Rogers disclosed relationships with Genentech, AbbVie, Novartis, Janssen, Pharmacyclics, BeiGene, Lilly, and AstraZeneca.