Ustekinumab (Stelara, Janssen) appears superior to vedolizumab (Entyvio, Takeda) on multiple measures of response and remission among patients with Crohn’s disease who failed at least one anti–tumor necrosis factor (TNF) therapy, in a retrospective analysis.

Of patients taking ustekinumab, a higher proportion (51%) met the primary endpoint of corticosteroid-free clinical remission at week 54. In the vedolizumab group, only 41% achieved the same outcome.

“Failure to anti-TNF therapy is a major concern in Crohn’s disease,” Anthony Buisson, MD, PhD, head of the Inflammatory Bowel Disease Unit, University Hospital Estaing, Clermont-Ferrand, France, said during the Digestive Disease Week 2021 virtual meeting.

Dr. Buisson estimated that 15% of patients with Crohn’s disease experience primary failure from an anti-TNF agent. Also, only slightly more than one-third (37%) remain in clinical remission at 1 year.

With that in mind, Dr. Buisson and his colleagues conducted the VENUS study to evaluate outcomes between ustekinumab and vedolizumab. These two biologic agents are indicated for Crohn’s disease and feature different mechanisms of action, compared with anti-TNF agents.

They assessed 312 adults with Crohn’s disease from two patient cohorts in France. All participants failed prior treatment with at least one anti-TNF agent, including approximately 20% who experienced a primary nonresponse.

The retrospective analysis included 224 patients treated with ustekinumab and another 88 with vedolizumab between July 2014 and May 2020. The two groups were comparable based on a propensity analysis. Other medications were allowed at the physician’s discretion.
 

Nonresponders and other outcomes

“Vedolizumab patients were more likely to be primary nonresponders than ustekinumab patients,” Dr. Buisson said. This group included 6% of patients taking ustekinumab versus 14% of those taking vedolizumab.

In contrast, regarding secondary loss of response, “we did not observe any [significant] difference between two groups,” he added.

The investigators defined corticosteroid-free remission as a Crohn’s Disease Activity Index less than 150 at week 54. They also assessed “deep remission” at 14 weeks, which was defined as meeting corticosteroid-free remission and a fecal calprotectin of less than 100 mcg/g.

They found that 26% of patients who received ustekinumab met the deep remission criteria versus 4% of those who received vedolizumab.

Dr. Buisson and colleagues also looked at time to drug escalation. A Kaplan Meier curve revealed that patients taking vedolizumab were more likely to be escalated, compared with those taking ustekinumab (hazard ratio, 1.35).

Furthermore, those treated with vedolizumab also featured a higher risk for drug discontinuation because of therapeutic failure (HR, 1.53).

“This is an interesting study comparing ustekinumab with vedolizumab in Crohn’s disease patients who have failed prior anti-TNF therapy,” Farah Monzur, MD, who was not affiliated with the study, told this news organization. “Although the researchers assessed corticosteroid-free remission and ‘deep remission,’ ” she said, endoscopic and histologic remission were not studied, “which have become the new targets to achieve.”

“Even so, this study adds to the literature, aiming to position these newer biologics in the treatment algorithm,” added Dr. Monzur, assistant professor of medicine and medical director of ambulatory GI at Stony Brook (N.Y.) Medicine.
 

Superior in subgroup analyses as well

“No subgroups were identified where vedolizumab was more effective than ustekinumab,” Dr. Buisson said. “In contrast, ustekinumab was more effective in five subgroups.”

The subgroups favoring ustekinumab included those patients not taking steroids at baseline, with no prior bowel resection, with a noncomplicated phenotype, with upper gastrointestinal involvement, and older than 35 years of age.

The retrospective analysis design was a limitation. The long follow-up and large sample size were strengths.

The authors concluded that ustekinumab was more effective to achieve early and long-term efficacy than vedolizumab in patients with Crohn’s disease who previously failed to anti-TNF agents.

“However, these data should be confirmed in a head-to-head randomized controlled trial,” Dr. Buisson said.

Dr. Buisson disclosed that he is a consultant for Janssen and Takeda. Dr. Monzur has disclosed no relevant financial relationships.

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

Ustekinumab (Stelara, Janssen) appears superior to vedolizumab (Entyvio, Takeda) on multiple measures of response and remission among patients with Crohn’s disease who failed at least one anti–tumor necrosis factor (TNF) therapy, in a retrospective analysis.

Of patients taking ustekinumab, a higher proportion (51%) met the primary endpoint of corticosteroid-free clinical remission at week 54. In the vedolizumab group, only 41% achieved the same outcome.

“Failure to anti-TNF therapy is a major concern in Crohn’s disease,” Anthony Buisson, MD, PhD, head of the Inflammatory Bowel Disease Unit, University Hospital Estaing, Clermont-Ferrand, France, said during the Digestive Disease Week 2021 virtual meeting.

Dr. Buisson estimated that 15% of patients with Crohn’s disease experience primary failure from an anti-TNF agent. Also, only slightly more than one-third (37%) remain in clinical remission at 1 year.

With that in mind, Dr. Buisson and his colleagues conducted the VENUS study to evaluate outcomes between ustekinumab and vedolizumab. These two biologic agents are indicated for Crohn’s disease and feature different mechanisms of action, compared with anti-TNF agents.

They assessed 312 adults with Crohn’s disease from two patient cohorts in France. All participants failed prior treatment with at least one anti-TNF agent, including approximately 20% who experienced a primary nonresponse.

The retrospective analysis included 224 patients treated with ustekinumab and another 88 with vedolizumab between July 2014 and May 2020. The two groups were comparable based on a propensity analysis. Other medications were allowed at the physician’s discretion.
 

Nonresponders and other outcomes

“Vedolizumab patients were more likely to be primary nonresponders than ustekinumab patients,” Dr. Buisson said. This group included 6% of patients taking ustekinumab versus 14% of those taking vedolizumab.

In contrast, regarding secondary loss of response, “we did not observe any [significant] difference between two groups,” he added.

The investigators defined corticosteroid-free remission as a Crohn’s Disease Activity Index less than 150 at week 54. They also assessed “deep remission” at 14 weeks, which was defined as meeting corticosteroid-free remission and a fecal calprotectin of less than 100 mcg/g.

They found that 26% of patients who received ustekinumab met the deep remission criteria versus 4% of those who received vedolizumab.

Dr. Buisson and colleagues also looked at time to drug escalation. A Kaplan Meier curve revealed that patients taking vedolizumab were more likely to be escalated, compared with those taking ustekinumab (hazard ratio, 1.35).

Furthermore, those treated with vedolizumab also featured a higher risk for drug discontinuation because of therapeutic failure (HR, 1.53).

“This is an interesting study comparing ustekinumab with vedolizumab in Crohn’s disease patients who have failed prior anti-TNF therapy,” Farah Monzur, MD, who was not affiliated with the study, told this news organization. “Although the researchers assessed corticosteroid-free remission and ‘deep remission,’ ” she said, endoscopic and histologic remission were not studied, “which have become the new targets to achieve.”

“Even so, this study adds to the literature, aiming to position these newer biologics in the treatment algorithm,” added Dr. Monzur, assistant professor of medicine and medical director of ambulatory GI at Stony Brook (N.Y.) Medicine.
 

Superior in subgroup analyses as well

“No subgroups were identified where vedolizumab was more effective than ustekinumab,” Dr. Buisson said. “In contrast, ustekinumab was more effective in five subgroups.”

The subgroups favoring ustekinumab included those patients not taking steroids at baseline, with no prior bowel resection, with a noncomplicated phenotype, with upper gastrointestinal involvement, and older than 35 years of age.

The retrospective analysis design was a limitation. The long follow-up and large sample size were strengths.

The authors concluded that ustekinumab was more effective to achieve early and long-term efficacy than vedolizumab in patients with Crohn’s disease who previously failed to anti-TNF agents.

“However, these data should be confirmed in a head-to-head randomized controlled trial,” Dr. Buisson said.

Dr. Buisson disclosed that he is a consultant for Janssen and Takeda. Dr. Monzur has disclosed no relevant financial relationships.

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

Ustekinumab (Stelara, Janssen) appears superior to vedolizumab (Entyvio, Takeda) on multiple measures of response and remission among patients with Crohn’s disease who failed at least one anti–tumor necrosis factor (TNF) therapy, in a retrospective analysis.

Of patients taking ustekinumab, a higher proportion (51%) met the primary endpoint of corticosteroid-free clinical remission at week 54. In the vedolizumab group, only 41% achieved the same outcome.

“Failure to anti-TNF therapy is a major concern in Crohn’s disease,” Anthony Buisson, MD, PhD, head of the Inflammatory Bowel Disease Unit, University Hospital Estaing, Clermont-Ferrand, France, said during the Digestive Disease Week 2021 virtual meeting.

Dr. Buisson estimated that 15% of patients with Crohn’s disease experience primary failure from an anti-TNF agent. Also, only slightly more than one-third (37%) remain in clinical remission at 1 year.

With that in mind, Dr. Buisson and his colleagues conducted the VENUS study to evaluate outcomes between ustekinumab and vedolizumab. These two biologic agents are indicated for Crohn’s disease and feature different mechanisms of action, compared with anti-TNF agents.

They assessed 312 adults with Crohn’s disease from two patient cohorts in France. All participants failed prior treatment with at least one anti-TNF agent, including approximately 20% who experienced a primary nonresponse.

The retrospective analysis included 224 patients treated with ustekinumab and another 88 with vedolizumab between July 2014 and May 2020. The two groups were comparable based on a propensity analysis. Other medications were allowed at the physician’s discretion.
 

Nonresponders and other outcomes

“Vedolizumab patients were more likely to be primary nonresponders than ustekinumab patients,” Dr. Buisson said. This group included 6% of patients taking ustekinumab versus 14% of those taking vedolizumab.

In contrast, regarding secondary loss of response, “we did not observe any [significant] difference between two groups,” he added.

The investigators defined corticosteroid-free remission as a Crohn’s Disease Activity Index less than 150 at week 54. They also assessed “deep remission” at 14 weeks, which was defined as meeting corticosteroid-free remission and a fecal calprotectin of less than 100 mcg/g.

They found that 26% of patients who received ustekinumab met the deep remission criteria versus 4% of those who received vedolizumab.

Dr. Buisson and colleagues also looked at time to drug escalation. A Kaplan Meier curve revealed that patients taking vedolizumab were more likely to be escalated, compared with those taking ustekinumab (hazard ratio, 1.35).

Furthermore, those treated with vedolizumab also featured a higher risk for drug discontinuation because of therapeutic failure (HR, 1.53).

“This is an interesting study comparing ustekinumab with vedolizumab in Crohn’s disease patients who have failed prior anti-TNF therapy,” Farah Monzur, MD, who was not affiliated with the study, told this news organization. “Although the researchers assessed corticosteroid-free remission and ‘deep remission,’ ” she said, endoscopic and histologic remission were not studied, “which have become the new targets to achieve.”

“Even so, this study adds to the literature, aiming to position these newer biologics in the treatment algorithm,” added Dr. Monzur, assistant professor of medicine and medical director of ambulatory GI at Stony Brook (N.Y.) Medicine.
 

Superior in subgroup analyses as well

“No subgroups were identified where vedolizumab was more effective than ustekinumab,” Dr. Buisson said. “In contrast, ustekinumab was more effective in five subgroups.”

The subgroups favoring ustekinumab included those patients not taking steroids at baseline, with no prior bowel resection, with a noncomplicated phenotype, with upper gastrointestinal involvement, and older than 35 years of age.

The retrospective analysis design was a limitation. The long follow-up and large sample size were strengths.

The authors concluded that ustekinumab was more effective to achieve early and long-term efficacy than vedolizumab in patients with Crohn’s disease who previously failed to anti-TNF agents.

“However, these data should be confirmed in a head-to-head randomized controlled trial,” Dr. Buisson said.

Dr. Buisson disclosed that he is a consultant for Janssen and Takeda. Dr. Monzur has disclosed no relevant financial relationships.

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

Researchers have discovered a new dopaminergic neural circuit leading to the hindbrain that is involved in satiety (feeling full and eating cessation) in mice, which may eventually lead to new ways to treat obesity.

Moreover, when mice were given methylphenidate (Ritalin, Concerta) – a stimulant approved to treat attention deficit hyperactivity disorder (ADHD) with a well-known side effect of decreasing appetite – signals in this dopaminergic pathway were enhanced and the mice ate less.

The study by Yong Han, PhD, a postdoctoral associate at Baylor College of Medicine, Houston, and colleagues was published online May 27 in Science Advances.

“We identified a new dopamine neural circuit from the midbrain to the hindbrain (brainstem) that regulates feeding behavior through an enhanced satiation response,” senior author Qi Wu, PhD, assistant professor in pediatrics-nutrition at Baylor College of Medicine, summarized in an interview.

The findings suggest that “people with obesity have a compromised dopaminergic neural pathway, presumably in ways that delay the satiation response, which makes them eat more, have a larger meal,” he explained.
 

Newly identified brain circuit plays a key role in satiety response

The study is about a circuit in the brain that helps precisely regulate the size of food portion consumed, Dr. Wu emphasized in a statement from the university, adding that the satiation response is as important as appetite.

Importantly, the results also provide clues about how methylphenidate can lead to weight loss.  

Regulators have deemed that methylphenidate, a controlled substance with other side effects such as anxiety and a fast heart rate, is safe and effective for ADHD, Dr. Wu noted.

He speculated that, “If researchers want to do clinical trials of methylphenidate for obesity, it ultimately could evolve to be an anti-obesity drug, alone or combined with other drugs, or possibly derivatives of methylphenidate could be tested.”

The brain circuit “we discovered is the first to be fully described to regulate portion size via dopamine signaling,” Dr. Han stressed in the statement.

“Our new study shows that a circuit connecting neurons that produce dopamine, a chemical messenger previously known for the regulation of motivation and pleasure, has a new [critical] role in the control of feeding through dynamically regulating the satiety response,” he explained.
 

Brain signals that control portion size 

Earlier studies that investigated how the dopaminergic system may regulate food intake, appetite, and body weight, have produced conflicting results, Dr. Wu said.

The researchers performed several experiments in mice that included the use of cell-specific circuitry mapping, optogenetics, and real-time recordings of brain activity.

They identified a new dopaminergic neural circuit comprised of dopaminergic neurons in the caudal ventral tegmental area (DA-VTA neurons) in the midbrain that directly innervate dopamine receptor D1-expressing neurons within the lateral parabrachial nucleus (DRD1-LPBN neurons) in the hindbrain.

There were four main findings:

• DA-VTA neurons were activated immediately before the cessation of each feeding bout.
• Actively inhibiting DA-VTA neurons before the end of each feeding bout prolonged the feeding.
• Activating DRD1-LPBN neurons inhibited feeding.
• Mice that lacked the DRD1 gene ate much more and gained weight.

“Our study illuminates a hindbrain dopaminergic circuit that controls feeding through dynamic regulation in satiety response and meal structure,” the researchers reiterate.

The study was supported by grants from the National Institutes of Health, NIH Digestive Diseases Center, Pew Charitable Trust, American Diabetes Association, Baylor Collaborative Faculty Research Investment Program, USDA/CRIS, USDA/ARS, American Heart Association, and NIH Centers of Biomedical Research Excellence, and by Pew and Kavli scholarships. The researchers have reported no relevant financial disclosures. 

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

Researchers have discovered a new dopaminergic neural circuit leading to the hindbrain that is involved in satiety (feeling full and eating cessation) in mice, which may eventually lead to new ways to treat obesity.

Moreover, when mice were given methylphenidate (Ritalin, Concerta) – a stimulant approved to treat attention deficit hyperactivity disorder (ADHD) with a well-known side effect of decreasing appetite – signals in this dopaminergic pathway were enhanced and the mice ate less.

The study by Yong Han, PhD, a postdoctoral associate at Baylor College of Medicine, Houston, and colleagues was published online May 27 in Science Advances.

“We identified a new dopamine neural circuit from the midbrain to the hindbrain (brainstem) that regulates feeding behavior through an enhanced satiation response,” senior author Qi Wu, PhD, assistant professor in pediatrics-nutrition at Baylor College of Medicine, summarized in an interview.

The findings suggest that “people with obesity have a compromised dopaminergic neural pathway, presumably in ways that delay the satiation response, which makes them eat more, have a larger meal,” he explained.
 

Newly identified brain circuit plays a key role in satiety response

The study is about a circuit in the brain that helps precisely regulate the size of food portion consumed, Dr. Wu emphasized in a statement from the university, adding that the satiation response is as important as appetite.

Importantly, the results also provide clues about how methylphenidate can lead to weight loss.  

Regulators have deemed that methylphenidate, a controlled substance with other side effects such as anxiety and a fast heart rate, is safe and effective for ADHD, Dr. Wu noted.

He speculated that, “If researchers want to do clinical trials of methylphenidate for obesity, it ultimately could evolve to be an anti-obesity drug, alone or combined with other drugs, or possibly derivatives of methylphenidate could be tested.”

The brain circuit “we discovered is the first to be fully described to regulate portion size via dopamine signaling,” Dr. Han stressed in the statement.

“Our new study shows that a circuit connecting neurons that produce dopamine, a chemical messenger previously known for the regulation of motivation and pleasure, has a new [critical] role in the control of feeding through dynamically regulating the satiety response,” he explained.
 

Brain signals that control portion size 

Earlier studies that investigated how the dopaminergic system may regulate food intake, appetite, and body weight, have produced conflicting results, Dr. Wu said.

The researchers performed several experiments in mice that included the use of cell-specific circuitry mapping, optogenetics, and real-time recordings of brain activity.

They identified a new dopaminergic neural circuit comprised of dopaminergic neurons in the caudal ventral tegmental area (DA-VTA neurons) in the midbrain that directly innervate dopamine receptor D1-expressing neurons within the lateral parabrachial nucleus (DRD1-LPBN neurons) in the hindbrain.

There were four main findings:

• DA-VTA neurons were activated immediately before the cessation of each feeding bout.
• Actively inhibiting DA-VTA neurons before the end of each feeding bout prolonged the feeding.
• Activating DRD1-LPBN neurons inhibited feeding.
• Mice that lacked the DRD1 gene ate much more and gained weight.

“Our study illuminates a hindbrain dopaminergic circuit that controls feeding through dynamic regulation in satiety response and meal structure,” the researchers reiterate.

The study was supported by grants from the National Institutes of Health, NIH Digestive Diseases Center, Pew Charitable Trust, American Diabetes Association, Baylor Collaborative Faculty Research Investment Program, USDA/CRIS, USDA/ARS, American Heart Association, and NIH Centers of Biomedical Research Excellence, and by Pew and Kavli scholarships. The researchers have reported no relevant financial disclosures. 

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

Researchers have discovered a new dopaminergic neural circuit leading to the hindbrain that is involved in satiety (feeling full and eating cessation) in mice, which may eventually lead to new ways to treat obesity.

Moreover, when mice were given methylphenidate (Ritalin, Concerta) – a stimulant approved to treat attention deficit hyperactivity disorder (ADHD) with a well-known side effect of decreasing appetite – signals in this dopaminergic pathway were enhanced and the mice ate less.

The study by Yong Han, PhD, a postdoctoral associate at Baylor College of Medicine, Houston, and colleagues was published online May 27 in Science Advances.

“We identified a new dopamine neural circuit from the midbrain to the hindbrain (brainstem) that regulates feeding behavior through an enhanced satiation response,” senior author Qi Wu, PhD, assistant professor in pediatrics-nutrition at Baylor College of Medicine, summarized in an interview.

The findings suggest that “people with obesity have a compromised dopaminergic neural pathway, presumably in ways that delay the satiation response, which makes them eat more, have a larger meal,” he explained.
 

Newly identified brain circuit plays a key role in satiety response

The study is about a circuit in the brain that helps precisely regulate the size of food portion consumed, Dr. Wu emphasized in a statement from the university, adding that the satiation response is as important as appetite.

Importantly, the results also provide clues about how methylphenidate can lead to weight loss.  

Regulators have deemed that methylphenidate, a controlled substance with other side effects such as anxiety and a fast heart rate, is safe and effective for ADHD, Dr. Wu noted.

He speculated that, “If researchers want to do clinical trials of methylphenidate for obesity, it ultimately could evolve to be an anti-obesity drug, alone or combined with other drugs, or possibly derivatives of methylphenidate could be tested.”

The brain circuit “we discovered is the first to be fully described to regulate portion size via dopamine signaling,” Dr. Han stressed in the statement.

“Our new study shows that a circuit connecting neurons that produce dopamine, a chemical messenger previously known for the regulation of motivation and pleasure, has a new [critical] role in the control of feeding through dynamically regulating the satiety response,” he explained.
 

Brain signals that control portion size 

Earlier studies that investigated how the dopaminergic system may regulate food intake, appetite, and body weight, have produced conflicting results, Dr. Wu said.

The researchers performed several experiments in mice that included the use of cell-specific circuitry mapping, optogenetics, and real-time recordings of brain activity.

They identified a new dopaminergic neural circuit comprised of dopaminergic neurons in the caudal ventral tegmental area (DA-VTA neurons) in the midbrain that directly innervate dopamine receptor D1-expressing neurons within the lateral parabrachial nucleus (DRD1-LPBN neurons) in the hindbrain.

There were four main findings:

• DA-VTA neurons were activated immediately before the cessation of each feeding bout.
• Actively inhibiting DA-VTA neurons before the end of each feeding bout prolonged the feeding.
• Activating DRD1-LPBN neurons inhibited feeding.
• Mice that lacked the DRD1 gene ate much more and gained weight.

“Our study illuminates a hindbrain dopaminergic circuit that controls feeding through dynamic regulation in satiety response and meal structure,” the researchers reiterate.

The study was supported by grants from the National Institutes of Health, NIH Digestive Diseases Center, Pew Charitable Trust, American Diabetes Association, Baylor Collaborative Faculty Research Investment Program, USDA/CRIS, USDA/ARS, American Heart Association, and NIH Centers of Biomedical Research Excellence, and by Pew and Kavli scholarships. The researchers have reported no relevant financial disclosures. 

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

Converge 2021 session

COVID-19 in Children

Presenter

Philip Zachariah, MD, MPH

Session summary

Children have been less severely affected by COVID-19 than adults (hospitalization rates around 5%). However, once hospitalized, ICU admission rates in children have been similar to adults, around 30%. Mortality has been 1%-2%. Risk factors for more severe acute SARS CoV-2 infections include age extremes, minorities, obesity, medical complexity, immunocompromised pediatric patients, and asthma.

Multisystem-inflammatory-syndrome-in-children (MIS-C) continues to present among persistently febrile children with multisystem findings and the history of acute COVID-19 infection in prior 3-6 weeks. There seems to be a link between the immunological defects in type I and II interferon production, as autoantibodies to type I interferon may predispose to severe disease. Dr. Zachariah of Columbia University Medical Center in New York, discussed the recent study exploring intravenous immunoglobulin (IVIG) alone versus IVIG and steroids as treatment options for MIS-C. So far, the failure rates in IVIG-alone group were higher (51%) versus IVIG and steroids (9%).

Besides MIS-C, many neurological manifestations of COVID-19 have been seen among children including GBS, seizures, encephalitis, cranial neuropathies, and demyelination cases. Diabetic ketoacidosis (DKA), secondary hemophagocytic lymphohistiocytosis (HLH), and pseudo-appendicitis have all been described in the literature, however, larger case control studied are needed.

In children, clinical vascular thrombotic events (VTEs) are rare. Anticoagulant thromboprophylaxis is suggested for hospitalized patients with COVID-19–related illness, whose D-dimer is >5 times upper limit of normal values and who have one or more non–COVID-19 related clinical risk factors for hospital acquired VTEs.

Key takeaways

• Once hospitalized, the ICU admission rates for children have been similar to those in adults, ~30%.
• MIS-C is showing lower failure rates if treated with IVIG and steroids, and most reliable laboratory findings should be elevated C-reactive protein, lymphopenia, and elevated brain natriuretic peptide.
• In hospitalized children with COVID-19, clinical VTEs are rare.

Dr. Giordano is an associate professor of pediatrics at Columbia University Medical Center in New York. She is a pediatric hospitalist with expertise in pediatric surgical comanagement

Converge 2021 session

COVID-19 in Children

Presenter

Philip Zachariah, MD, MPH

Session summary

Children have been less severely affected by COVID-19 than adults (hospitalization rates around 5%). However, once hospitalized, ICU admission rates in children have been similar to adults, around 30%. Mortality has been 1%-2%. Risk factors for more severe acute SARS CoV-2 infections include age extremes, minorities, obesity, medical complexity, immunocompromised pediatric patients, and asthma.

Multisystem-inflammatory-syndrome-in-children (MIS-C) continues to present among persistently febrile children with multisystem findings and the history of acute COVID-19 infection in prior 3-6 weeks. There seems to be a link between the immunological defects in type I and II interferon production, as autoantibodies to type I interferon may predispose to severe disease. Dr. Zachariah of Columbia University Medical Center in New York, discussed the recent study exploring intravenous immunoglobulin (IVIG) alone versus IVIG and steroids as treatment options for MIS-C. So far, the failure rates in IVIG-alone group were higher (51%) versus IVIG and steroids (9%).

Besides MIS-C, many neurological manifestations of COVID-19 have been seen among children including GBS, seizures, encephalitis, cranial neuropathies, and demyelination cases. Diabetic ketoacidosis (DKA), secondary hemophagocytic lymphohistiocytosis (HLH), and pseudo-appendicitis have all been described in the literature, however, larger case control studied are needed.

In children, clinical vascular thrombotic events (VTEs) are rare. Anticoagulant thromboprophylaxis is suggested for hospitalized patients with COVID-19–related illness, whose D-dimer is >5 times upper limit of normal values and who have one or more non–COVID-19 related clinical risk factors for hospital acquired VTEs.

Key takeaways

• Once hospitalized, the ICU admission rates for children have been similar to those in adults, ~30%.
• MIS-C is showing lower failure rates if treated with IVIG and steroids, and most reliable laboratory findings should be elevated C-reactive protein, lymphopenia, and elevated brain natriuretic peptide.
• In hospitalized children with COVID-19, clinical VTEs are rare.

Dr. Giordano is an associate professor of pediatrics at Columbia University Medical Center in New York. She is a pediatric hospitalist with expertise in pediatric surgical comanagement

Converge 2021 session

COVID-19 in Children

Presenter

Philip Zachariah, MD, MPH

Session summary

Children have been less severely affected by COVID-19 than adults (hospitalization rates around 5%). However, once hospitalized, ICU admission rates in children have been similar to adults, around 30%. Mortality has been 1%-2%. Risk factors for more severe acute SARS CoV-2 infections include age extremes, minorities, obesity, medical complexity, immunocompromised pediatric patients, and asthma.

Multisystem-inflammatory-syndrome-in-children (MIS-C) continues to present among persistently febrile children with multisystem findings and the history of acute COVID-19 infection in prior 3-6 weeks. There seems to be a link between the immunological defects in type I and II interferon production, as autoantibodies to type I interferon may predispose to severe disease. Dr. Zachariah of Columbia University Medical Center in New York, discussed the recent study exploring intravenous immunoglobulin (IVIG) alone versus IVIG and steroids as treatment options for MIS-C. So far, the failure rates in IVIG-alone group were higher (51%) versus IVIG and steroids (9%).

Besides MIS-C, many neurological manifestations of COVID-19 have been seen among children including GBS, seizures, encephalitis, cranial neuropathies, and demyelination cases. Diabetic ketoacidosis (DKA), secondary hemophagocytic lymphohistiocytosis (HLH), and pseudo-appendicitis have all been described in the literature, however, larger case control studied are needed.

In children, clinical vascular thrombotic events (VTEs) are rare. Anticoagulant thromboprophylaxis is suggested for hospitalized patients with COVID-19–related illness, whose D-dimer is >5 times upper limit of normal values and who have one or more non–COVID-19 related clinical risk factors for hospital acquired VTEs.

Key takeaways

• Once hospitalized, the ICU admission rates for children have been similar to those in adults, ~30%.
• MIS-C is showing lower failure rates if treated with IVIG and steroids, and most reliable laboratory findings should be elevated C-reactive protein, lymphopenia, and elevated brain natriuretic peptide.
• In hospitalized children with COVID-19, clinical VTEs are rare.

Dr. Giordano is an associate professor of pediatrics at Columbia University Medical Center in New York. She is a pediatric hospitalist with expertise in pediatric surgical comanagement

Treating insulin resistance may improve treatment-resistant bipolar depression, early research suggests.

In a randomized, placebo-controlled trial, treatment with the diabetes drug metformin reversed insulin resistance in 50% of patients, and this reversal was associated with significant improvement of depressive symptoms. One patient randomly assigned to placebo also achieved a reversal of insulin resistance and improved depressive symptoms.

“The study needs replication, but this early clinical trial suggests that the mitigation of insulin resistance by metformin significantly improves depressive symptoms in a significant percentage of treatment resistant bipolar patients,” presenting author Jessica M. Gannon, MD, University of Pittsburgh Medical Center (UPMC), said in an interview.

“It looks like in treatment-resistant bipolar depression, treating insulin resistance is a way to get people well again, to get out of their depression,” principal investigator Cynthia Calkin, MD, Dalhousie University, Halifax, N.S., added.

The findings were presented at the virtual American Society of Clinical Psychopharmacology 2021 Annual Meeting.
 

Chronic inflammation

The study was a joint effort by UPMC and Dalhousie University and was sponsored by the Stanley Medical Research Institute.

Patients with bipolar disorder (BD) who are obese tend to have more serious illness, with a more chronic course, more rapid cycling, and more morbidity. These patients also fail to respond to lithium, Dr. Calkin said.

“Untreated hyperinsulinemia could be contributing to a state of chronic inflammation and be involved in disease progression. So the question for me was, if we treat this insulin resistance, would patients get better?” she said.

Dr. Calkin said investigators used metformin because it is already used by psychiatrists for weight management in patients on antipsychotics.

“I wanted to test the drug that would work to reverse insulin resistance and that psychiatrists would be comfortable prescribing,” she said.

The 26-week study randomly assigned 20 patients to receive metformin and 25 patients to placebo.

All participants were 18 years and older, had a diagnosis of BD I or II, and had nonremitting BD defined by moderate depressive symptoms as measured on the Montgomery-Asberg Depression Rating Scale (MADRS) score of 15 or greater, despite being on optimal, guideline-compatible treatment.

All patients were stable, were on optimal doses of mood-stabilizing medications for at least 4 weeks prior to study entry, and had insulin resistance as defined by a Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) ≥1.8.

Characteristics were similar between the two groups, including baseline MADRS scores, body mass index, fasting glucose and insulin serum levels.

Patients were titrated up to 2,000 mg of metformin, which was the full dose, over 2 weeks and then maintained on treatment for a further 24 weeks.
 

Highly resistant population

The study’s primary outcome measure was change in MADRS score, with a response defined as a 30% reduction in MADRS from baseline.

By week 14, 10 metformin-treated patients (50%) and one patient in the placebo group (4%) no longer met insulin resistance criteria.

“It was a bit of a surprise to me that 50% of patients converted to being insulin sensitive again. When you use metformin to treat diabetes, people respond to it at more than a 50% rate, so I was expecting more people to respond,” Dr. Calkin said.

Nevertheless, the 11 patients who did respond and reversed insulin resistance achieved greater reduction in MADRS scores compared with nonconverters.

“Those who reversed their insulin resistance showed a remarkable resolution in their depressive symptoms. The reduction in MADRS scores began at week six, and were maintained through to the end of the study, and the Cohen’s d effect size for MADRS depression scores for converters was 0.52 at week 14 and 0.55 at week 26,” Dr. Calkin said.

“They were moderately to severely depressed going in, and at the end of the study, they had mild residual depressive symptoms, or they were completely well. These were very treatment-resistant patients.”

“All had failed, on average, eight or nine trials in their lifetime. When they came to us, nothing else would work. That’s one of the remarkable things about our results, just how well they responded when they had not responded to any other psychotropic medications. This approach may be very helpful for some patients,” Dr. Calkin said.
 

A holistic approach

Commenting on the study, Michael E. Thase, MD, professor of psychiatry, University of Pennsylvania, Philadelphia, said the findings need to be replicated but provide further support for the broader strategy of taking a holistic approach to the care of patients with difficult-to-treat mood disorders.

“Approximately one-half of people with treatment-resistant bipolar depression showed evidence of glucose resistance, and that adjunctive treatment with metformin, a medication that enhances insulin sensitivity, was moderately effective in normalizing glucose metabolism, with about a 50% response rate. Among those who experienced improved glucose regulation, there was a significant reduction in depressive symptoms,” he noted.

The study was funded by the Stanley Medical Research Institute (SMRI). Dr. Calkin and Dr. Thase have disclosed no relevant financial relationships.

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

Treating insulin resistance may improve treatment-resistant bipolar depression, early research suggests.

In a randomized, placebo-controlled trial, treatment with the diabetes drug metformin reversed insulin resistance in 50% of patients, and this reversal was associated with significant improvement of depressive symptoms. One patient randomly assigned to placebo also achieved a reversal of insulin resistance and improved depressive symptoms.

“The study needs replication, but this early clinical trial suggests that the mitigation of insulin resistance by metformin significantly improves depressive symptoms in a significant percentage of treatment resistant bipolar patients,” presenting author Jessica M. Gannon, MD, University of Pittsburgh Medical Center (UPMC), said in an interview.

“It looks like in treatment-resistant bipolar depression, treating insulin resistance is a way to get people well again, to get out of their depression,” principal investigator Cynthia Calkin, MD, Dalhousie University, Halifax, N.S., added.

The findings were presented at the virtual American Society of Clinical Psychopharmacology 2021 Annual Meeting.
 

Chronic inflammation

The study was a joint effort by UPMC and Dalhousie University and was sponsored by the Stanley Medical Research Institute.

Patients with bipolar disorder (BD) who are obese tend to have more serious illness, with a more chronic course, more rapid cycling, and more morbidity. These patients also fail to respond to lithium, Dr. Calkin said.

“Untreated hyperinsulinemia could be contributing to a state of chronic inflammation and be involved in disease progression. So the question for me was, if we treat this insulin resistance, would patients get better?” she said.

Dr. Calkin said investigators used metformin because it is already used by psychiatrists for weight management in patients on antipsychotics.

“I wanted to test the drug that would work to reverse insulin resistance and that psychiatrists would be comfortable prescribing,” she said.

The 26-week study randomly assigned 20 patients to receive metformin and 25 patients to placebo.

All participants were 18 years and older, had a diagnosis of BD I or II, and had nonremitting BD defined by moderate depressive symptoms as measured on the Montgomery-Asberg Depression Rating Scale (MADRS) score of 15 or greater, despite being on optimal, guideline-compatible treatment.

All patients were stable, were on optimal doses of mood-stabilizing medications for at least 4 weeks prior to study entry, and had insulin resistance as defined by a Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) ≥1.8.

Characteristics were similar between the two groups, including baseline MADRS scores, body mass index, fasting glucose and insulin serum levels.

Patients were titrated up to 2,000 mg of metformin, which was the full dose, over 2 weeks and then maintained on treatment for a further 24 weeks.
 

Highly resistant population

The study’s primary outcome measure was change in MADRS score, with a response defined as a 30% reduction in MADRS from baseline.

By week 14, 10 metformin-treated patients (50%) and one patient in the placebo group (4%) no longer met insulin resistance criteria.

“It was a bit of a surprise to me that 50% of patients converted to being insulin sensitive again. When you use metformin to treat diabetes, people respond to it at more than a 50% rate, so I was expecting more people to respond,” Dr. Calkin said.

Nevertheless, the 11 patients who did respond and reversed insulin resistance achieved greater reduction in MADRS scores compared with nonconverters.

“Those who reversed their insulin resistance showed a remarkable resolution in their depressive symptoms. The reduction in MADRS scores began at week six, and were maintained through to the end of the study, and the Cohen’s d effect size for MADRS depression scores for converters was 0.52 at week 14 and 0.55 at week 26,” Dr. Calkin said.

“They were moderately to severely depressed going in, and at the end of the study, they had mild residual depressive symptoms, or they were completely well. These were very treatment-resistant patients.”

“All had failed, on average, eight or nine trials in their lifetime. When they came to us, nothing else would work. That’s one of the remarkable things about our results, just how well they responded when they had not responded to any other psychotropic medications. This approach may be very helpful for some patients,” Dr. Calkin said.
 

A holistic approach

Commenting on the study, Michael E. Thase, MD, professor of psychiatry, University of Pennsylvania, Philadelphia, said the findings need to be replicated but provide further support for the broader strategy of taking a holistic approach to the care of patients with difficult-to-treat mood disorders.

“Approximately one-half of people with treatment-resistant bipolar depression showed evidence of glucose resistance, and that adjunctive treatment with metformin, a medication that enhances insulin sensitivity, was moderately effective in normalizing glucose metabolism, with about a 50% response rate. Among those who experienced improved glucose regulation, there was a significant reduction in depressive symptoms,” he noted.

The study was funded by the Stanley Medical Research Institute (SMRI). Dr. Calkin and Dr. Thase have disclosed no relevant financial relationships.

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

Treating insulin resistance may improve treatment-resistant bipolar depression, early research suggests.

In a randomized, placebo-controlled trial, treatment with the diabetes drug metformin reversed insulin resistance in 50% of patients, and this reversal was associated with significant improvement of depressive symptoms. One patient randomly assigned to placebo also achieved a reversal of insulin resistance and improved depressive symptoms.

“The study needs replication, but this early clinical trial suggests that the mitigation of insulin resistance by metformin significantly improves depressive symptoms in a significant percentage of treatment resistant bipolar patients,” presenting author Jessica M. Gannon, MD, University of Pittsburgh Medical Center (UPMC), said in an interview.

“It looks like in treatment-resistant bipolar depression, treating insulin resistance is a way to get people well again, to get out of their depression,” principal investigator Cynthia Calkin, MD, Dalhousie University, Halifax, N.S., added.

The findings were presented at the virtual American Society of Clinical Psychopharmacology 2021 Annual Meeting.
 

Chronic inflammation

The study was a joint effort by UPMC and Dalhousie University and was sponsored by the Stanley Medical Research Institute.

Patients with bipolar disorder (BD) who are obese tend to have more serious illness, with a more chronic course, more rapid cycling, and more morbidity. These patients also fail to respond to lithium, Dr. Calkin said.

“Untreated hyperinsulinemia could be contributing to a state of chronic inflammation and be involved in disease progression. So the question for me was, if we treat this insulin resistance, would patients get better?” she said.

Dr. Calkin said investigators used metformin because it is already used by psychiatrists for weight management in patients on antipsychotics.

“I wanted to test the drug that would work to reverse insulin resistance and that psychiatrists would be comfortable prescribing,” she said.

The 26-week study randomly assigned 20 patients to receive metformin and 25 patients to placebo.

All participants were 18 years and older, had a diagnosis of BD I or II, and had nonremitting BD defined by moderate depressive symptoms as measured on the Montgomery-Asberg Depression Rating Scale (MADRS) score of 15 or greater, despite being on optimal, guideline-compatible treatment.

All patients were stable, were on optimal doses of mood-stabilizing medications for at least 4 weeks prior to study entry, and had insulin resistance as defined by a Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) ≥1.8.

Characteristics were similar between the two groups, including baseline MADRS scores, body mass index, fasting glucose and insulin serum levels.

Patients were titrated up to 2,000 mg of metformin, which was the full dose, over 2 weeks and then maintained on treatment for a further 24 weeks.
 

Highly resistant population

The study’s primary outcome measure was change in MADRS score, with a response defined as a 30% reduction in MADRS from baseline.

By week 14, 10 metformin-treated patients (50%) and one patient in the placebo group (4%) no longer met insulin resistance criteria.

“It was a bit of a surprise to me that 50% of patients converted to being insulin sensitive again. When you use metformin to treat diabetes, people respond to it at more than a 50% rate, so I was expecting more people to respond,” Dr. Calkin said.

Nevertheless, the 11 patients who did respond and reversed insulin resistance achieved greater reduction in MADRS scores compared with nonconverters.

“Those who reversed their insulin resistance showed a remarkable resolution in their depressive symptoms. The reduction in MADRS scores began at week six, and were maintained through to the end of the study, and the Cohen’s d effect size for MADRS depression scores for converters was 0.52 at week 14 and 0.55 at week 26,” Dr. Calkin said.

“They were moderately to severely depressed going in, and at the end of the study, they had mild residual depressive symptoms, or they were completely well. These were very treatment-resistant patients.”

“All had failed, on average, eight or nine trials in their lifetime. When they came to us, nothing else would work. That’s one of the remarkable things about our results, just how well they responded when they had not responded to any other psychotropic medications. This approach may be very helpful for some patients,” Dr. Calkin said.
 

A holistic approach

Commenting on the study, Michael E. Thase, MD, professor of psychiatry, University of Pennsylvania, Philadelphia, said the findings need to be replicated but provide further support for the broader strategy of taking a holistic approach to the care of patients with difficult-to-treat mood disorders.

“Approximately one-half of people with treatment-resistant bipolar depression showed evidence of glucose resistance, and that adjunctive treatment with metformin, a medication that enhances insulin sensitivity, was moderately effective in normalizing glucose metabolism, with about a 50% response rate. Among those who experienced improved glucose regulation, there was a significant reduction in depressive symptoms,” he noted.

The study was funded by the Stanley Medical Research Institute (SMRI). Dr. Calkin and Dr. Thase have disclosed no relevant financial relationships.

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

A prebiotic therapy in development significantly reduced the number of days per month that people with gastroesophageal reflux disease (GERD) experienced heartburn.

The prebiotic treatment, maltosyl-isomalto-oligosaccharides (MIMO, ISOT-101), under development by ISOThrive, was also associated with reduced symptom severity and improved quality of life, John Selling, MD, chief medical officer at ISOThrive, said during the presentation of his study at the virtual Digestive Disease Week (DDW) 2021.

ISOT-101 is a nondigestible, nonabsorbable prebiotic carbohydrate produced by bacterial fermentation of sucrose and maltose. It was “possibly a staple of the bacterial diet that was present in the human diet during the past 10,000 years,” Dr. Selling said. He is a clinical associate professor of medicine and gastroenterology at Stanford (Calif.) University.

The prebiotic, however, “has been absent in our diet for about 50 to 100 years, driven by changes in agriculture, food production, food preservation, and dietary preferences,” he added.

Acid suppression treatments, such as proton pump inhibitors (PPIs), have long been a staple of treating GERD. However, about 40% of people taking PPIs still have symptoms, Dr. Selling said. He noted that there are concerns about the health risks associated with long-term PPI use.

A prebiotic could work because the distal esophageal microbiome in people with GERD “differs greatly” from that of healthy persons, Dr. Selling said. The prebiotic could help reduce an abnormal increase in gram-negative bacteria in these patients, for example. These bacterial strains express lipopolysaccharides on their outer cell membranes, which, in turn, alter cytokine signaling. This mechanism could lead to the hyperinflammatory state associated with GERD.

Dr. Selling and colleagues hypothesized that this treatment could help resolve GERD symptoms in two ways. The prebiotic could selectively feed the beneficial gram-positive bacteria in the distal esophagus, thereby helping to restore a healthy balance of bacteria. ISOT-101 could also produce bacteriocins that help kill the harmful gram-negative bacteria and control inflammation.

To assess the efficacy and tolerability of ISOT-101, Dr. Selling and colleagues plan to evaluate use of the agent in 110 people with GERD. The data presented at this year’s DDW are based on the first 44 participants to complete the study protocol.

Participants had to have active symptoms four or more days a week. They verbally reported symptoms to investigators and completed a daily ReQuest validated GERD symptom questionnaire.

After a week of baseline screening, participants consumed about a quarter teaspoon of ISOT-101 as the last substance swallowed before bed every night. The investigators asked participants to rate their GI symptoms, general well-being including any sleep disturbances, and quality of life on the Short Form 36 (SF-36) health survey. Participants also recorded use of any other medications during the 4-week study.

“I thought this was a very interesting study, as it proposes an alternative approach to manage patients with GERD,” Richa Shukla, MD, who was not affiliated with the research, said in an interview when asked to comment. “We see many patients with typical GERD symptoms who do not respond to PPI therapy, and perhaps considering an alternative cause and treatment may help with these patients.”

Dr. Shukla shared a couple of caveats. “This is a relatively small study, and it has not yet completed its enrollment target, so it will be helpful to see what the results are with the full study.” Also, it would be useful to know how many participants also took a PPI during the study, she said.

“Essentially, a lot remains unknown, but the study holds promise for patients,” added Dr. Shukla, assistant professor in the section of gastroenterology and hepatology at Baylor College of Medicine, Houston. “I think there is a lot of interest in the microbiome and how modulating it can impact inflammatory conditions.”
 

Key findings

The increase in heartburn-free days translated to more than eight additional days a month in which patients had no complaints of acid or heartburn. The difference from baseline was statistically significant (P < .001).

About two-thirds (66%) of participants were classified as “strong responders” to treatment, meaning they experienced an improvement of >50% in their ReQuest symptom scores over the 4 weeks. Again, the difference compared to baseline was statistically significant (P < .001).

The researchers also reported statistically significant improvements in quality-of-life indicators, such as well-being and sleep (P < .001).

The primary endpoint of the study was tolerability. The prebiotic was defined as tolerable if the ReQuest symptom scores and SF-36 scores remained constant or improved by the fourth week. ReQuest symptom scores improved for 89% of participants.

Two participants experienced nausea. No other adverse events related to ISOT-101 were reported. For five participants, ReQuest GI subscores worsened over time. For four participants, ReQuest total symptom scores worsened over time; that score represents a sum of GI and general well-being scores.
 

Unanswered questions

Inflammation in GERD is likely due to bacterial dysbiosis and acid-induced injury, Dr. Selling said.

If development of the prebiotic continues successfully, it could represent a paradigm shift in this clinical area, he said. “It suggests moving from acid reduction to also reducing dysbiosis as a treatment modality.”

But it remains unclear whether ISOT-101 would be indicated as monotherapy or for use in combination with other therapies for GERD.

Another unanswered question is whether the agent could be used to treat progressive disease. “This type of bacterial dysbiosis remains throughout the disease progression, from GERD to Barrett’s esophagus to esophageal adenocarcinoma,” Dr. Selling said.

The investigators reported that further controlled studies are forthcoming.

Dr. Selling is a co-founder and chief medical officer at ISOThrive. Dr. Shukla has disclosed no relevant financial relationships. David Johnson, MD, one of the authors of the abstract, is an advisor and contributor to Medscape.

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

A prebiotic therapy in development significantly reduced the number of days per month that people with gastroesophageal reflux disease (GERD) experienced heartburn.

The prebiotic treatment, maltosyl-isomalto-oligosaccharides (MIMO, ISOT-101), under development by ISOThrive, was also associated with reduced symptom severity and improved quality of life, John Selling, MD, chief medical officer at ISOThrive, said during the presentation of his study at the virtual Digestive Disease Week (DDW) 2021.

ISOT-101 is a nondigestible, nonabsorbable prebiotic carbohydrate produced by bacterial fermentation of sucrose and maltose. It was “possibly a staple of the bacterial diet that was present in the human diet during the past 10,000 years,” Dr. Selling said. He is a clinical associate professor of medicine and gastroenterology at Stanford (Calif.) University.

The prebiotic, however, “has been absent in our diet for about 50 to 100 years, driven by changes in agriculture, food production, food preservation, and dietary preferences,” he added.

Acid suppression treatments, such as proton pump inhibitors (PPIs), have long been a staple of treating GERD. However, about 40% of people taking PPIs still have symptoms, Dr. Selling said. He noted that there are concerns about the health risks associated with long-term PPI use.

A prebiotic could work because the distal esophageal microbiome in people with GERD “differs greatly” from that of healthy persons, Dr. Selling said. The prebiotic could help reduce an abnormal increase in gram-negative bacteria in these patients, for example. These bacterial strains express lipopolysaccharides on their outer cell membranes, which, in turn, alter cytokine signaling. This mechanism could lead to the hyperinflammatory state associated with GERD.

Dr. Selling and colleagues hypothesized that this treatment could help resolve GERD symptoms in two ways. The prebiotic could selectively feed the beneficial gram-positive bacteria in the distal esophagus, thereby helping to restore a healthy balance of bacteria. ISOT-101 could also produce bacteriocins that help kill the harmful gram-negative bacteria and control inflammation.

To assess the efficacy and tolerability of ISOT-101, Dr. Selling and colleagues plan to evaluate use of the agent in 110 people with GERD. The data presented at this year’s DDW are based on the first 44 participants to complete the study protocol.

Participants had to have active symptoms four or more days a week. They verbally reported symptoms to investigators and completed a daily ReQuest validated GERD symptom questionnaire.

After a week of baseline screening, participants consumed about a quarter teaspoon of ISOT-101 as the last substance swallowed before bed every night. The investigators asked participants to rate their GI symptoms, general well-being including any sleep disturbances, and quality of life on the Short Form 36 (SF-36) health survey. Participants also recorded use of any other medications during the 4-week study.

“I thought this was a very interesting study, as it proposes an alternative approach to manage patients with GERD,” Richa Shukla, MD, who was not affiliated with the research, said in an interview when asked to comment. “We see many patients with typical GERD symptoms who do not respond to PPI therapy, and perhaps considering an alternative cause and treatment may help with these patients.”

Dr. Shukla shared a couple of caveats. “This is a relatively small study, and it has not yet completed its enrollment target, so it will be helpful to see what the results are with the full study.” Also, it would be useful to know how many participants also took a PPI during the study, she said.

“Essentially, a lot remains unknown, but the study holds promise for patients,” added Dr. Shukla, assistant professor in the section of gastroenterology and hepatology at Baylor College of Medicine, Houston. “I think there is a lot of interest in the microbiome and how modulating it can impact inflammatory conditions.”
 

Key findings

The increase in heartburn-free days translated to more than eight additional days a month in which patients had no complaints of acid or heartburn. The difference from baseline was statistically significant (P < .001).

About two-thirds (66%) of participants were classified as “strong responders” to treatment, meaning they experienced an improvement of >50% in their ReQuest symptom scores over the 4 weeks. Again, the difference compared to baseline was statistically significant (P < .001).

The researchers also reported statistically significant improvements in quality-of-life indicators, such as well-being and sleep (P < .001).

The primary endpoint of the study was tolerability. The prebiotic was defined as tolerable if the ReQuest symptom scores and SF-36 scores remained constant or improved by the fourth week. ReQuest symptom scores improved for 89% of participants.

Two participants experienced nausea. No other adverse events related to ISOT-101 were reported. For five participants, ReQuest GI subscores worsened over time. For four participants, ReQuest total symptom scores worsened over time; that score represents a sum of GI and general well-being scores.
 

Unanswered questions

Inflammation in GERD is likely due to bacterial dysbiosis and acid-induced injury, Dr. Selling said.

If development of the prebiotic continues successfully, it could represent a paradigm shift in this clinical area, he said. “It suggests moving from acid reduction to also reducing dysbiosis as a treatment modality.”

But it remains unclear whether ISOT-101 would be indicated as monotherapy or for use in combination with other therapies for GERD.

Another unanswered question is whether the agent could be used to treat progressive disease. “This type of bacterial dysbiosis remains throughout the disease progression, from GERD to Barrett’s esophagus to esophageal adenocarcinoma,” Dr. Selling said.

The investigators reported that further controlled studies are forthcoming.

Dr. Selling is a co-founder and chief medical officer at ISOThrive. Dr. Shukla has disclosed no relevant financial relationships. David Johnson, MD, one of the authors of the abstract, is an advisor and contributor to Medscape.

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

A prebiotic therapy in development significantly reduced the number of days per month that people with gastroesophageal reflux disease (GERD) experienced heartburn.

The prebiotic treatment, maltosyl-isomalto-oligosaccharides (MIMO, ISOT-101), under development by ISOThrive, was also associated with reduced symptom severity and improved quality of life, John Selling, MD, chief medical officer at ISOThrive, said during the presentation of his study at the virtual Digestive Disease Week (DDW) 2021.

ISOT-101 is a nondigestible, nonabsorbable prebiotic carbohydrate produced by bacterial fermentation of sucrose and maltose. It was “possibly a staple of the bacterial diet that was present in the human diet during the past 10,000 years,” Dr. Selling said. He is a clinical associate professor of medicine and gastroenterology at Stanford (Calif.) University.

The prebiotic, however, “has been absent in our diet for about 50 to 100 years, driven by changes in agriculture, food production, food preservation, and dietary preferences,” he added.

Acid suppression treatments, such as proton pump inhibitors (PPIs), have long been a staple of treating GERD. However, about 40% of people taking PPIs still have symptoms, Dr. Selling said. He noted that there are concerns about the health risks associated with long-term PPI use.

A prebiotic could work because the distal esophageal microbiome in people with GERD “differs greatly” from that of healthy persons, Dr. Selling said. The prebiotic could help reduce an abnormal increase in gram-negative bacteria in these patients, for example. These bacterial strains express lipopolysaccharides on their outer cell membranes, which, in turn, alter cytokine signaling. This mechanism could lead to the hyperinflammatory state associated with GERD.

Dr. Selling and colleagues hypothesized that this treatment could help resolve GERD symptoms in two ways. The prebiotic could selectively feed the beneficial gram-positive bacteria in the distal esophagus, thereby helping to restore a healthy balance of bacteria. ISOT-101 could also produce bacteriocins that help kill the harmful gram-negative bacteria and control inflammation.

To assess the efficacy and tolerability of ISOT-101, Dr. Selling and colleagues plan to evaluate use of the agent in 110 people with GERD. The data presented at this year’s DDW are based on the first 44 participants to complete the study protocol.

Participants had to have active symptoms four or more days a week. They verbally reported symptoms to investigators and completed a daily ReQuest validated GERD symptom questionnaire.

After a week of baseline screening, participants consumed about a quarter teaspoon of ISOT-101 as the last substance swallowed before bed every night. The investigators asked participants to rate their GI symptoms, general well-being including any sleep disturbances, and quality of life on the Short Form 36 (SF-36) health survey. Participants also recorded use of any other medications during the 4-week study.

“I thought this was a very interesting study, as it proposes an alternative approach to manage patients with GERD,” Richa Shukla, MD, who was not affiliated with the research, said in an interview when asked to comment. “We see many patients with typical GERD symptoms who do not respond to PPI therapy, and perhaps considering an alternative cause and treatment may help with these patients.”

Dr. Shukla shared a couple of caveats. “This is a relatively small study, and it has not yet completed its enrollment target, so it will be helpful to see what the results are with the full study.” Also, it would be useful to know how many participants also took a PPI during the study, she said.

“Essentially, a lot remains unknown, but the study holds promise for patients,” added Dr. Shukla, assistant professor in the section of gastroenterology and hepatology at Baylor College of Medicine, Houston. “I think there is a lot of interest in the microbiome and how modulating it can impact inflammatory conditions.”
 

Key findings

The increase in heartburn-free days translated to more than eight additional days a month in which patients had no complaints of acid or heartburn. The difference from baseline was statistically significant (P < .001).

About two-thirds (66%) of participants were classified as “strong responders” to treatment, meaning they experienced an improvement of >50% in their ReQuest symptom scores over the 4 weeks. Again, the difference compared to baseline was statistically significant (P < .001).

The researchers also reported statistically significant improvements in quality-of-life indicators, such as well-being and sleep (P < .001).

The primary endpoint of the study was tolerability. The prebiotic was defined as tolerable if the ReQuest symptom scores and SF-36 scores remained constant or improved by the fourth week. ReQuest symptom scores improved for 89% of participants.

Two participants experienced nausea. No other adverse events related to ISOT-101 were reported. For five participants, ReQuest GI subscores worsened over time. For four participants, ReQuest total symptom scores worsened over time; that score represents a sum of GI and general well-being scores.
 

Unanswered questions

Inflammation in GERD is likely due to bacterial dysbiosis and acid-induced injury, Dr. Selling said.

If development of the prebiotic continues successfully, it could represent a paradigm shift in this clinical area, he said. “It suggests moving from acid reduction to also reducing dysbiosis as a treatment modality.”

But it remains unclear whether ISOT-101 would be indicated as monotherapy or for use in combination with other therapies for GERD.

Another unanswered question is whether the agent could be used to treat progressive disease. “This type of bacterial dysbiosis remains throughout the disease progression, from GERD to Barrett’s esophagus to esophageal adenocarcinoma,” Dr. Selling said.

The investigators reported that further controlled studies are forthcoming.

Dr. Selling is a co-founder and chief medical officer at ISOThrive. Dr. Shukla has disclosed no relevant financial relationships. David Johnson, MD, one of the authors of the abstract, is an advisor and contributor to Medscape.

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

A group of 117 people who work at the Houston Methodist Health System has filed a lawsuit against the medical center, objecting to its policy of requiring employees and contractors to be vaccinated against COVID-19 or risk losing their jobs.

Plaintiffs include Jennifer Bridges, RN, a medical-surgical nurse at the hospital who has become the public face and voice of health care workers who object to mandatory vaccination, as well as Bob Nevens, the hospital’s director of corporate risk.

Mr. Nevens said the hospital was requiring him to be vaccinated even though he doesn’t treat patients and has been working from home for most of the past year.

“My civil rights and liberties have been trampled on,” he said in comments posted on an online petition. “My right to protect myself from unknown side effects of these vaccines has been placed below the optics of ‘leading medicine,’ “ he said.

Mr. Nevens says in his comments that he was fired on April 15, although the lawsuit says he is currently employed by the hospital’s corporate office.

The Texas attorney who filed the lawsuit, Jared Woodfill, is known to champion conservative causes. In March 2020, he challenged Harris County’s stay-at-home order, charging that it violated religious liberty. He was chairman of the Harris County Republican Party for more than a decade. His website says he is a frequent guest on the local Fox News affiliate.

The lawsuit hinges on a section of the federal law that authorizes emergency use of medical products – US Code 360bbb-3.

That law says that individuals to whom the product is administered should be informed “of the option to accept or refuse administration of the product, of the consequence, if any, of refusing administration of the product, and of the alternatives to the product that are available and of their benefits and risks.”

Legal experts are split as to what the provision means for vaccination mandates. Courts have not yet weighed in with their interpretations of the law.

The petition also repeats a popular antivaccination argument that likens requiring a vaccine approved for emergency use to the kind of medical experimentation performed by Nazi doctors on Jewish prisoners in concentration camps. It says forcing people to choose between an experimental vaccine and a job is a violation of the Nuremberg Code, which says that people must voluntarily and knowingly consent to participating in research.

The vaccines have already been tested in clinical trials. People who are getting them now are not part of those studies, though vaccine manufacturers, regulators, and safety experts are still watching closely for any sign of problems tied to the new shots.

It is true, however, that the emergency use authorization granted by the U.S. Food and Drug Administraiton sped up the process of getting the vaccines onto market. Vaccine manufacturers are currently completing the process of submitting documentation required for a full biologics license application, the mechanism the FDA uses for full approval.

Houston Methodist sent an email to employees in April notifying them that they had until June 7 to start the vaccination process or apply for a medical or religious exemption. Those who decide not to will be terminated.

Marc Boom, MD, the health care system’s president and CEO, has explained that the policy is in place to protect patients and that it was the first hospital in the United States to require it. Since then, other hospitals, including the University of Pennsylvania Health System, have required COVID vaccines.

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

A group of 117 people who work at the Houston Methodist Health System has filed a lawsuit against the medical center, objecting to its policy of requiring employees and contractors to be vaccinated against COVID-19 or risk losing their jobs.

Plaintiffs include Jennifer Bridges, RN, a medical-surgical nurse at the hospital who has become the public face and voice of health care workers who object to mandatory vaccination, as well as Bob Nevens, the hospital’s director of corporate risk.

Mr. Nevens said the hospital was requiring him to be vaccinated even though he doesn’t treat patients and has been working from home for most of the past year.

“My civil rights and liberties have been trampled on,” he said in comments posted on an online petition. “My right to protect myself from unknown side effects of these vaccines has been placed below the optics of ‘leading medicine,’ “ he said.

Mr. Nevens says in his comments that he was fired on April 15, although the lawsuit says he is currently employed by the hospital’s corporate office.

The Texas attorney who filed the lawsuit, Jared Woodfill, is known to champion conservative causes. In March 2020, he challenged Harris County’s stay-at-home order, charging that it violated religious liberty. He was chairman of the Harris County Republican Party for more than a decade. His website says he is a frequent guest on the local Fox News affiliate.

The lawsuit hinges on a section of the federal law that authorizes emergency use of medical products – US Code 360bbb-3.

That law says that individuals to whom the product is administered should be informed “of the option to accept or refuse administration of the product, of the consequence, if any, of refusing administration of the product, and of the alternatives to the product that are available and of their benefits and risks.”

Legal experts are split as to what the provision means for vaccination mandates. Courts have not yet weighed in with their interpretations of the law.

The petition also repeats a popular antivaccination argument that likens requiring a vaccine approved for emergency use to the kind of medical experimentation performed by Nazi doctors on Jewish prisoners in concentration camps. It says forcing people to choose between an experimental vaccine and a job is a violation of the Nuremberg Code, which says that people must voluntarily and knowingly consent to participating in research.

The vaccines have already been tested in clinical trials. People who are getting them now are not part of those studies, though vaccine manufacturers, regulators, and safety experts are still watching closely for any sign of problems tied to the new shots.

It is true, however, that the emergency use authorization granted by the U.S. Food and Drug Administraiton sped up the process of getting the vaccines onto market. Vaccine manufacturers are currently completing the process of submitting documentation required for a full biologics license application, the mechanism the FDA uses for full approval.

Houston Methodist sent an email to employees in April notifying them that they had until June 7 to start the vaccination process or apply for a medical or religious exemption. Those who decide not to will be terminated.

Marc Boom, MD, the health care system’s president and CEO, has explained that the policy is in place to protect patients and that it was the first hospital in the United States to require it. Since then, other hospitals, including the University of Pennsylvania Health System, have required COVID vaccines.

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

A group of 117 people who work at the Houston Methodist Health System has filed a lawsuit against the medical center, objecting to its policy of requiring employees and contractors to be vaccinated against COVID-19 or risk losing their jobs.

Plaintiffs include Jennifer Bridges, RN, a medical-surgical nurse at the hospital who has become the public face and voice of health care workers who object to mandatory vaccination, as well as Bob Nevens, the hospital’s director of corporate risk.

Mr. Nevens said the hospital was requiring him to be vaccinated even though he doesn’t treat patients and has been working from home for most of the past year.

“My civil rights and liberties have been trampled on,” he said in comments posted on an online petition. “My right to protect myself from unknown side effects of these vaccines has been placed below the optics of ‘leading medicine,’ “ he said.

Mr. Nevens says in his comments that he was fired on April 15, although the lawsuit says he is currently employed by the hospital’s corporate office.

The Texas attorney who filed the lawsuit, Jared Woodfill, is known to champion conservative causes. In March 2020, he challenged Harris County’s stay-at-home order, charging that it violated religious liberty. He was chairman of the Harris County Republican Party for more than a decade. His website says he is a frequent guest on the local Fox News affiliate.

The lawsuit hinges on a section of the federal law that authorizes emergency use of medical products – US Code 360bbb-3.

That law says that individuals to whom the product is administered should be informed “of the option to accept or refuse administration of the product, of the consequence, if any, of refusing administration of the product, and of the alternatives to the product that are available and of their benefits and risks.”

Legal experts are split as to what the provision means for vaccination mandates. Courts have not yet weighed in with their interpretations of the law.

The petition also repeats a popular antivaccination argument that likens requiring a vaccine approved for emergency use to the kind of medical experimentation performed by Nazi doctors on Jewish prisoners in concentration camps. It says forcing people to choose between an experimental vaccine and a job is a violation of the Nuremberg Code, which says that people must voluntarily and knowingly consent to participating in research.

The vaccines have already been tested in clinical trials. People who are getting them now are not part of those studies, though vaccine manufacturers, regulators, and safety experts are still watching closely for any sign of problems tied to the new shots.

It is true, however, that the emergency use authorization granted by the U.S. Food and Drug Administraiton sped up the process of getting the vaccines onto market. Vaccine manufacturers are currently completing the process of submitting documentation required for a full biologics license application, the mechanism the FDA uses for full approval.

Houston Methodist sent an email to employees in April notifying them that they had until June 7 to start the vaccination process or apply for a medical or religious exemption. Those who decide not to will be terminated.

Marc Boom, MD, the health care system’s president and CEO, has explained that the policy is in place to protect patients and that it was the first hospital in the United States to require it. Since then, other hospitals, including the University of Pennsylvania Health System, have required COVID vaccines.

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

The Diagnosis: Favre-Racouchot Syndrome

Favre-Racouchot syndrome, also known as nodular elastosis with cysts and comedones, is seen in approximately 6% of adults aged 40 to 60 years and predominantly is observed in White males.¹ Typically, patients have a history of prolonged recreational or occupational UV exposure and tobacco use. The diagnosis can be made clinically; no biopsy is necessary. If a biopsy is performed, histologic findings typically consist of notable actinic elastosis, epidermal atrophy, and comedones. The differential diagnosis includes acne comedones, colloid milium, milia, chloracne, and trichoepithelioma.² Associated conditions that have been found concurrently include cutis rhomboidalis nuchae, actinic keratosis, erosive pustular dermatosis, actinic granuloma, and basal and squamous cell carcinomas.²

The pathogenesis, while not fully understood, seems to involve a combination of chronic UV radiation exposure and heavy cigarette smoking that eventually leads to cutaneous atrophy and keratinization of the pilosebaceous follicles as well as the formation of comedones.² Radiation therapy also has been implicated as a possible causative agent of Favre-Racouchot syndrome.¹ Clinically, symmetric distribution of large black comedones over the temporal and periorbital areas is seen surrounded by distinct signs of UV-damaged skin, including wrinkles and atrophic skin.³ Although there seems to be a synergistic effect between cigarette smoking and chronic UV exposure, evidence favors smoking as the major cause of this condition,^4,5 which causes striking visual changes but is a benign process. UV protection and smoking cessation are the most important factors for prevention and limiting progression.

Treatment consists of typical comedonal therapies such as tretinoin or comedone extraction. Procedural options in conjunction with medical therapy include dermabrasion or laser therapy. Newer studies have shown promising results for both CO₂ laser treatment and plasma exeresis.⁶ Plasma exeresis is a noninvasive technique that causes ionization of atmospheric gas between the device and tissue, ultimately causing sublimation of the target tissue.⁷ It is important to carefully evaluate and follow up with these patients due to their history of extensive UV exposure. Both short-term and long-term follow-up is recommended due to high rates of reoccurrence within 10 to 12 months and the dangers of chronic UV exposure– related malignancies.⁶

The Diagnosis: Favre-Racouchot Syndrome

Favre-Racouchot syndrome, also known as nodular elastosis with cysts and comedones, is seen in approximately 6% of adults aged 40 to 60 years and predominantly is observed in White males.¹ Typically, patients have a history of prolonged recreational or occupational UV exposure and tobacco use. The diagnosis can be made clinically; no biopsy is necessary. If a biopsy is performed, histologic findings typically consist of notable actinic elastosis, epidermal atrophy, and comedones. The differential diagnosis includes acne comedones, colloid milium, milia, chloracne, and trichoepithelioma.² Associated conditions that have been found concurrently include cutis rhomboidalis nuchae, actinic keratosis, erosive pustular dermatosis, actinic granuloma, and basal and squamous cell carcinomas.²

The pathogenesis, while not fully understood, seems to involve a combination of chronic UV radiation exposure and heavy cigarette smoking that eventually leads to cutaneous atrophy and keratinization of the pilosebaceous follicles as well as the formation of comedones.² Radiation therapy also has been implicated as a possible causative agent of Favre-Racouchot syndrome.¹ Clinically, symmetric distribution of large black comedones over the temporal and periorbital areas is seen surrounded by distinct signs of UV-damaged skin, including wrinkles and atrophic skin.³ Although there seems to be a synergistic effect between cigarette smoking and chronic UV exposure, evidence favors smoking as the major cause of this condition,^4,5 which causes striking visual changes but is a benign process. UV protection and smoking cessation are the most important factors for prevention and limiting progression.

Treatment consists of typical comedonal therapies such as tretinoin or comedone extraction. Procedural options in conjunction with medical therapy include dermabrasion or laser therapy. Newer studies have shown promising results for both CO₂ laser treatment and plasma exeresis.⁶ Plasma exeresis is a noninvasive technique that causes ionization of atmospheric gas between the device and tissue, ultimately causing sublimation of the target tissue.⁷ It is important to carefully evaluate and follow up with these patients due to their history of extensive UV exposure. Both short-term and long-term follow-up is recommended due to high rates of reoccurrence within 10 to 12 months and the dangers of chronic UV exposure– related malignancies.⁶

The Diagnosis: Favre-Racouchot Syndrome

Favre-Racouchot syndrome, also known as nodular elastosis with cysts and comedones, is seen in approximately 6% of adults aged 40 to 60 years and predominantly is observed in White males.¹ Typically, patients have a history of prolonged recreational or occupational UV exposure and tobacco use. The diagnosis can be made clinically; no biopsy is necessary. If a biopsy is performed, histologic findings typically consist of notable actinic elastosis, epidermal atrophy, and comedones. The differential diagnosis includes acne comedones, colloid milium, milia, chloracne, and trichoepithelioma.² Associated conditions that have been found concurrently include cutis rhomboidalis nuchae, actinic keratosis, erosive pustular dermatosis, actinic granuloma, and basal and squamous cell carcinomas.²

The pathogenesis, while not fully understood, seems to involve a combination of chronic UV radiation exposure and heavy cigarette smoking that eventually leads to cutaneous atrophy and keratinization of the pilosebaceous follicles as well as the formation of comedones.² Radiation therapy also has been implicated as a possible causative agent of Favre-Racouchot syndrome.¹ Clinically, symmetric distribution of large black comedones over the temporal and periorbital areas is seen surrounded by distinct signs of UV-damaged skin, including wrinkles and atrophic skin.³ Although there seems to be a synergistic effect between cigarette smoking and chronic UV exposure, evidence favors smoking as the major cause of this condition,^4,5 which causes striking visual changes but is a benign process. UV protection and smoking cessation are the most important factors for prevention and limiting progression.

Treatment consists of typical comedonal therapies such as tretinoin or comedone extraction. Procedural options in conjunction with medical therapy include dermabrasion or laser therapy. Newer studies have shown promising results for both CO₂ laser treatment and plasma exeresis.⁶ Plasma exeresis is a noninvasive technique that causes ionization of atmospheric gas between the device and tissue, ultimately causing sublimation of the target tissue.⁷ It is important to carefully evaluate and follow up with these patients due to their history of extensive UV exposure. Both short-term and long-term follow-up is recommended due to high rates of reoccurrence within 10 to 12 months and the dangers of chronic UV exposure– related malignancies.⁶

Researchers in Spain have shared heartening results from the first randomized controlled trial to assess risk for COVID-19 transmission at an indoor live music concert.
 

The study, published May 27 in The Lancet Infectious Diseases, led by virologist Boris Revollo, MD, from the Germans Trias i Pujol University Hospital in Barcelona, included comprehensive safety measures.

It was conducted on Dec. 12, 2020, at a time when local travel restrictions were in place, indoor meetings were limited to six people, and vaccines were not yet available.

All 465 event attendees got same-day SARS-CoV-2 screening with antigen-detecting rapid diagnostic tests before they entered, wore masks throughout, and followed crowd-control measures in the well-ventilated venue, which can hold up to 900 people.

The control group consisted of 495 participants randomly assigned to go home instead of attending the concert after the screening.

None of the attendees tested positive for SARS-CoV-2 infection by polymerase chain reaction (PCR) test 8 days after the 5-hour event, but two in the control group did.

In fact, the study showed that the risk for infection was no higher among those at the concert than it was for those who lived in the same community and did not attend.

The Bayesian estimate for the incidence between the test and control groups was –0.15% (95% confidence Interval, –0.72 to 0.44).

“Our findings pave the way to reactivate cultural activities halted during COVID-19, which could have important sociocultural and economic implications,” the authors wrote.
 

All wore masks throughout

Among the comprehensive safety measures were that, in addition to testing, all attendees had their temperature checked before gaining access and were given an N95 face mask, which had to be worn at all times inside.

Hand sanitizer was provided in multiple locations, access doors remained open to allow fresh air to circulate, and the coat room was closed to prevent clustering.

There was no mandated distancing, people could sing and dance, and alcohol was available in a bar located in a separate room – and drinks were allowed only in that space.

Rosanna W Peeling, PhD, professor and chair of diagnostic research at the London School of Hygiene and Tropical Medicine in the United Kingdom, and David L. Heymann, MD, of the department of infectious disease epidemiology there, said in an accompanying commentary that there is a great need for studies like this one to help build evidence for a return to normal gatherings.

“So many countries don’t have any policy or any way of doing this because they don’t have the evidence,” Dr. Peeling said in an interview.

The study was well done and a strength was the testing 8 days later, which can be hard to do for similar events when people disperse to locations outside the community where the event or gathering was held, she said.
 

Study prompts additional questions

Dr. Peeling and Dr. Heymann wrote that the work raises questions such as whether triple-layered masks would have been sufficient. Or how does rapid antigen testing at the entrance compare with molecular screening within 72 hours of entering? 

They noted that there are questions around whether existing rapid diagnostic tests are able to detect COVID-19 variants.

Dr. Peeling said that these kinds of results need to be shared and shared more quickly, “if we’re ever going to get out of this pandemic.”

Studies like this are also difficult, she noted, because they may involve non–health sector entities such as city governments and concert organizers working together with researchers.

In addition, the safety measures come at considerable expense and it’s unclear whether those could be employed routinely at such events.

“It’s not really sustainable at sports events with 20,000 people,” Dr. Peeling said.

Infectious disease expert William Schaffner, MD, of Vanderbilt University, Nashville, Tenn., told this news organization that the study results “come a little late to the party.”

If this study had been done in today’s era with authorized vaccines, “it would have been a moot issue,” he said. “The mask is a barrier to transmission, but we now have a much more solid barrier we could put in place, which is vaccination.

“That said, it does reinforce the fact that classical mask wearing does really offer protection even in a crowded venue,” Dr. Schaffner said.

He added that the study was relatively small and he’d like to see it replicated in larger concerts or group gatherings.

Dr. Peeling and Dr. Heymann report no relevant financial relationships. A coauthor is an employee and stockholder of Primavera Sound, sponsor of the study. All other authors declare no relevant financial relationships.
 

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

Researchers in Spain have shared heartening results from the first randomized controlled trial to assess risk for COVID-19 transmission at an indoor live music concert.
 

The study, published May 27 in The Lancet Infectious Diseases, led by virologist Boris Revollo, MD, from the Germans Trias i Pujol University Hospital in Barcelona, included comprehensive safety measures.

It was conducted on Dec. 12, 2020, at a time when local travel restrictions were in place, indoor meetings were limited to six people, and vaccines were not yet available.

All 465 event attendees got same-day SARS-CoV-2 screening with antigen-detecting rapid diagnostic tests before they entered, wore masks throughout, and followed crowd-control measures in the well-ventilated venue, which can hold up to 900 people.

The control group consisted of 495 participants randomly assigned to go home instead of attending the concert after the screening.

None of the attendees tested positive for SARS-CoV-2 infection by polymerase chain reaction (PCR) test 8 days after the 5-hour event, but two in the control group did.

In fact, the study showed that the risk for infection was no higher among those at the concert than it was for those who lived in the same community and did not attend.

The Bayesian estimate for the incidence between the test and control groups was –0.15% (95% confidence Interval, –0.72 to 0.44).

“Our findings pave the way to reactivate cultural activities halted during COVID-19, which could have important sociocultural and economic implications,” the authors wrote.
 

All wore masks throughout

Among the comprehensive safety measures were that, in addition to testing, all attendees had their temperature checked before gaining access and were given an N95 face mask, which had to be worn at all times inside.

Hand sanitizer was provided in multiple locations, access doors remained open to allow fresh air to circulate, and the coat room was closed to prevent clustering.

There was no mandated distancing, people could sing and dance, and alcohol was available in a bar located in a separate room – and drinks were allowed only in that space.

Rosanna W Peeling, PhD, professor and chair of diagnostic research at the London School of Hygiene and Tropical Medicine in the United Kingdom, and David L. Heymann, MD, of the department of infectious disease epidemiology there, said in an accompanying commentary that there is a great need for studies like this one to help build evidence for a return to normal gatherings.

“So many countries don’t have any policy or any way of doing this because they don’t have the evidence,” Dr. Peeling said in an interview.

The study was well done and a strength was the testing 8 days later, which can be hard to do for similar events when people disperse to locations outside the community where the event or gathering was held, she said.
 

Study prompts additional questions

Dr. Peeling and Dr. Heymann wrote that the work raises questions such as whether triple-layered masks would have been sufficient. Or how does rapid antigen testing at the entrance compare with molecular screening within 72 hours of entering? 

They noted that there are questions around whether existing rapid diagnostic tests are able to detect COVID-19 variants.

Dr. Peeling said that these kinds of results need to be shared and shared more quickly, “if we’re ever going to get out of this pandemic.”

Studies like this are also difficult, she noted, because they may involve non–health sector entities such as city governments and concert organizers working together with researchers.

In addition, the safety measures come at considerable expense and it’s unclear whether those could be employed routinely at such events.

“It’s not really sustainable at sports events with 20,000 people,” Dr. Peeling said.

Infectious disease expert William Schaffner, MD, of Vanderbilt University, Nashville, Tenn., told this news organization that the study results “come a little late to the party.”

If this study had been done in today’s era with authorized vaccines, “it would have been a moot issue,” he said. “The mask is a barrier to transmission, but we now have a much more solid barrier we could put in place, which is vaccination.

“That said, it does reinforce the fact that classical mask wearing does really offer protection even in a crowded venue,” Dr. Schaffner said.

He added that the study was relatively small and he’d like to see it replicated in larger concerts or group gatherings.

Dr. Peeling and Dr. Heymann report no relevant financial relationships. A coauthor is an employee and stockholder of Primavera Sound, sponsor of the study. All other authors declare no relevant financial relationships.
 

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

Researchers in Spain have shared heartening results from the first randomized controlled trial to assess risk for COVID-19 transmission at an indoor live music concert.
 

The study, published May 27 in The Lancet Infectious Diseases, led by virologist Boris Revollo, MD, from the Germans Trias i Pujol University Hospital in Barcelona, included comprehensive safety measures.

It was conducted on Dec. 12, 2020, at a time when local travel restrictions were in place, indoor meetings were limited to six people, and vaccines were not yet available.

All 465 event attendees got same-day SARS-CoV-2 screening with antigen-detecting rapid diagnostic tests before they entered, wore masks throughout, and followed crowd-control measures in the well-ventilated venue, which can hold up to 900 people.

The control group consisted of 495 participants randomly assigned to go home instead of attending the concert after the screening.

None of the attendees tested positive for SARS-CoV-2 infection by polymerase chain reaction (PCR) test 8 days after the 5-hour event, but two in the control group did.

In fact, the study showed that the risk for infection was no higher among those at the concert than it was for those who lived in the same community and did not attend.

The Bayesian estimate for the incidence between the test and control groups was –0.15% (95% confidence Interval, –0.72 to 0.44).

“Our findings pave the way to reactivate cultural activities halted during COVID-19, which could have important sociocultural and economic implications,” the authors wrote.
 

All wore masks throughout

Among the comprehensive safety measures were that, in addition to testing, all attendees had their temperature checked before gaining access and were given an N95 face mask, which had to be worn at all times inside.

Hand sanitizer was provided in multiple locations, access doors remained open to allow fresh air to circulate, and the coat room was closed to prevent clustering.

There was no mandated distancing, people could sing and dance, and alcohol was available in a bar located in a separate room – and drinks were allowed only in that space.

Rosanna W Peeling, PhD, professor and chair of diagnostic research at the London School of Hygiene and Tropical Medicine in the United Kingdom, and David L. Heymann, MD, of the department of infectious disease epidemiology there, said in an accompanying commentary that there is a great need for studies like this one to help build evidence for a return to normal gatherings.

“So many countries don’t have any policy or any way of doing this because they don’t have the evidence,” Dr. Peeling said in an interview.

The study was well done and a strength was the testing 8 days later, which can be hard to do for similar events when people disperse to locations outside the community where the event or gathering was held, she said.
 

Study prompts additional questions

Dr. Peeling and Dr. Heymann wrote that the work raises questions such as whether triple-layered masks would have been sufficient. Or how does rapid antigen testing at the entrance compare with molecular screening within 72 hours of entering? 

They noted that there are questions around whether existing rapid diagnostic tests are able to detect COVID-19 variants.

Dr. Peeling said that these kinds of results need to be shared and shared more quickly, “if we’re ever going to get out of this pandemic.”

Studies like this are also difficult, she noted, because they may involve non–health sector entities such as city governments and concert organizers working together with researchers.

In addition, the safety measures come at considerable expense and it’s unclear whether those could be employed routinely at such events.

“It’s not really sustainable at sports events with 20,000 people,” Dr. Peeling said.

Infectious disease expert William Schaffner, MD, of Vanderbilt University, Nashville, Tenn., told this news organization that the study results “come a little late to the party.”

If this study had been done in today’s era with authorized vaccines, “it would have been a moot issue,” he said. “The mask is a barrier to transmission, but we now have a much more solid barrier we could put in place, which is vaccination.

“That said, it does reinforce the fact that classical mask wearing does really offer protection even in a crowded venue,” Dr. Schaffner said.

He added that the study was relatively small and he’d like to see it replicated in larger concerts or group gatherings.

Dr. Peeling and Dr. Heymann report no relevant financial relationships. A coauthor is an employee and stockholder of Primavera Sound, sponsor of the study. All other authors declare no relevant financial relationships.
 

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

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has included more drugs and data and is moving toward a slightly more stepped approach to treating some forms of psoriatic disease in the latest iteration of their recommendations.

“There’s been an explosion over the last few years in terms of the number of medications,” available to treat psoriasis and psoriatic arthritis, Laura C. Coates, MBChB, PhD, said in an interview ahead of presenting the draft recommendations at the annual European Congress of Rheumatology.

“The good thing about having more drugs is you’ve got more choice, but actually it makes these recommendations even more important because it becomes more complicated to choose optimal treatment for individuals,” added Dr. Coates, a senior clinical research fellow at the University of Oxford (England).

“We’ve been waiting for a while now for the new GRAPPA recommendations,” Laure Gossec, MD, PhD, of Sorbonne University and Pitié-Salpêtrière Hospital in Paris, said in a separate interview.

New overarching principle and position statements

The goal of the recommendations hasn’t really changed since the first iteration of the guidelines in 2009, Dr. Coates noted in her presentation. They are intended to provide clinicians with recommendations “based on the best available evidence” for the management of patients with psoriatic disease.

To that end, a through process was followed, starting with the setting of PICO (Patient/population/problem; intervention; comparison; outcome) questions followed by systematic literature searches, data extraction, and review that assess the quality of evidence and then grade it accordingly before using it to inform the recommendation statements.

There is a new overarching principle that says: “These recommendations, which include the most current data concerning the optimal assessment of and therapeutic approached to psoriatic arthritis, present contextual considerations to empower shared decision making.”

The other overarching principles remain the same as in the 2015 version, with “minor wording changes particularly around the comorbidities overarching principle,” Dr. Coates said.

Also new are two position statements. “One of them is specifically around biosimilars, because that’s been a big shift since 2015,” Dr. Coates said. “It has basic rules about what evidence there should be, what we should consider when we’re using them, and patient involvement and decision making.”

The second statement covers “similar advice on tapering or discontinuing therapy – what we do when people are doing really well, how we should stop or taper, and which drugs we should choose to stop along with shared decision making with patients.”

GRAPPA intentionally gives clinicians more freedom

While there may be data to show differences in efficacy and side effects between the various drugs cited in the recommendations, “GRAPPA makes the choice to not prioritize one drug over another,” Dr. Gossec said. This decision gives “a lot of freedom then to the physician to make the decision.”

One important change according to Dr. Gossec is that oral “NSAIDs have clearly been put back as first-line treatment, before going on to disease-modifying drugs for most of the musculoskeletal manifestations. She added that for skin manifestations, topical NSAIDs were recommended, but that NSAIDs were more recommended for IBD and uveitis of course.

“I feel that’s a big step towards more of a step-up approach,” Dr. Gossec said. “The old recommendations were not clear that you would precede an NSAID before moving on to a disease-modifying drug. So, I think that makes it a little bit more similar to the 2019 EULAR recommendations.” The use of csDMARDs such as methotrexate has also been “pushed up a notch” in peripheral arthritis, she said.

What’s next?

There are a few fine tunings still to be made before the final recommendations are published. They also have to be discussed at the meeting of the GRAPPA task force, which consists of rheumatologists, dermatologists, and patient representatives.

Besides the recommendations manuscript, there will be individual papers detailing the evidence underpinning the recommendations in each of the eight domains, Dr. Coates noted. Those “will look at relative efficacy in detail,” she said. “There will be a lot more discussion/evidence summary included” to help with drug selection.

“We also plan to have some case studies to illustrate how the recommendations can be used, similar to that included in the 2015 recommendations,” she added.

Paul Studenic, MD, PhD, of the Karolinska Institute in Stockholm and Medical University of Vienna, tweeted that the GRAPPA recommendations showed treatment “needs to be tailored to the patient” taking “comorbidities as well as the heterogeneity of features of the clinical presentation into account.”

He said in an interview: “The third edition of the GRAPPA is a huge collaborative effort.” The new overarching principle put the recommendations in the context of shared decision making and, he added, they emphasize an “integrated management plan taking not only ‘classical’-related manifestations like uveitis into account but [also] a spectrum of comorbidities and reproductive health.”

GRAPPA is a not-for-profit organization and receives funding from multiple pharmaceutical companies. Currently this includes AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, Pfizer, UCB, and Sun Pharma with Galapagos and Nordic Bioscience as Innovation Partners. Dr. Coates acknowledged receiving research funding, honoraria, speaker fees or all of these from most of the aforementioned companies.

Dr. Gossec has received research funding or other support from numerous pharmaceutical companies and is a member of GRAPPA and the task force that developed the EULAR guidelines on the pharmacological management of psoriatic arthritis.

Dr. Studenic had nothing to disclose.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has included more drugs and data and is moving toward a slightly more stepped approach to treating some forms of psoriatic disease in the latest iteration of their recommendations.

“There’s been an explosion over the last few years in terms of the number of medications,” available to treat psoriasis and psoriatic arthritis, Laura C. Coates, MBChB, PhD, said in an interview ahead of presenting the draft recommendations at the annual European Congress of Rheumatology.

“The good thing about having more drugs is you’ve got more choice, but actually it makes these recommendations even more important because it becomes more complicated to choose optimal treatment for individuals,” added Dr. Coates, a senior clinical research fellow at the University of Oxford (England).

“We’ve been waiting for a while now for the new GRAPPA recommendations,” Laure Gossec, MD, PhD, of Sorbonne University and Pitié-Salpêtrière Hospital in Paris, said in a separate interview.

New overarching principle and position statements

The goal of the recommendations hasn’t really changed since the first iteration of the guidelines in 2009, Dr. Coates noted in her presentation. They are intended to provide clinicians with recommendations “based on the best available evidence” for the management of patients with psoriatic disease.

To that end, a through process was followed, starting with the setting of PICO (Patient/population/problem; intervention; comparison; outcome) questions followed by systematic literature searches, data extraction, and review that assess the quality of evidence and then grade it accordingly before using it to inform the recommendation statements.

There is a new overarching principle that says: “These recommendations, which include the most current data concerning the optimal assessment of and therapeutic approached to psoriatic arthritis, present contextual considerations to empower shared decision making.”

The other overarching principles remain the same as in the 2015 version, with “minor wording changes particularly around the comorbidities overarching principle,” Dr. Coates said.

Also new are two position statements. “One of them is specifically around biosimilars, because that’s been a big shift since 2015,” Dr. Coates said. “It has basic rules about what evidence there should be, what we should consider when we’re using them, and patient involvement and decision making.”

The second statement covers “similar advice on tapering or discontinuing therapy – what we do when people are doing really well, how we should stop or taper, and which drugs we should choose to stop along with shared decision making with patients.”

GRAPPA intentionally gives clinicians more freedom

While there may be data to show differences in efficacy and side effects between the various drugs cited in the recommendations, “GRAPPA makes the choice to not prioritize one drug over another,” Dr. Gossec said. This decision gives “a lot of freedom then to the physician to make the decision.”

One important change according to Dr. Gossec is that oral “NSAIDs have clearly been put back as first-line treatment, before going on to disease-modifying drugs for most of the musculoskeletal manifestations. She added that for skin manifestations, topical NSAIDs were recommended, but that NSAIDs were more recommended for IBD and uveitis of course.

“I feel that’s a big step towards more of a step-up approach,” Dr. Gossec said. “The old recommendations were not clear that you would precede an NSAID before moving on to a disease-modifying drug. So, I think that makes it a little bit more similar to the 2019 EULAR recommendations.” The use of csDMARDs such as methotrexate has also been “pushed up a notch” in peripheral arthritis, she said.

What’s next?

There are a few fine tunings still to be made before the final recommendations are published. They also have to be discussed at the meeting of the GRAPPA task force, which consists of rheumatologists, dermatologists, and patient representatives.

Besides the recommendations manuscript, there will be individual papers detailing the evidence underpinning the recommendations in each of the eight domains, Dr. Coates noted. Those “will look at relative efficacy in detail,” she said. “There will be a lot more discussion/evidence summary included” to help with drug selection.

“We also plan to have some case studies to illustrate how the recommendations can be used, similar to that included in the 2015 recommendations,” she added.

Paul Studenic, MD, PhD, of the Karolinska Institute in Stockholm and Medical University of Vienna, tweeted that the GRAPPA recommendations showed treatment “needs to be tailored to the patient” taking “comorbidities as well as the heterogeneity of features of the clinical presentation into account.”

He said in an interview: “The third edition of the GRAPPA is a huge collaborative effort.” The new overarching principle put the recommendations in the context of shared decision making and, he added, they emphasize an “integrated management plan taking not only ‘classical’-related manifestations like uveitis into account but [also] a spectrum of comorbidities and reproductive health.”

GRAPPA is a not-for-profit organization and receives funding from multiple pharmaceutical companies. Currently this includes AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, Pfizer, UCB, and Sun Pharma with Galapagos and Nordic Bioscience as Innovation Partners. Dr. Coates acknowledged receiving research funding, honoraria, speaker fees or all of these from most of the aforementioned companies.

Dr. Gossec has received research funding or other support from numerous pharmaceutical companies and is a member of GRAPPA and the task force that developed the EULAR guidelines on the pharmacological management of psoriatic arthritis.

Dr. Studenic had nothing to disclose.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has included more drugs and data and is moving toward a slightly more stepped approach to treating some forms of psoriatic disease in the latest iteration of their recommendations.

“There’s been an explosion over the last few years in terms of the number of medications,” available to treat psoriasis and psoriatic arthritis, Laura C. Coates, MBChB, PhD, said in an interview ahead of presenting the draft recommendations at the annual European Congress of Rheumatology.

“The good thing about having more drugs is you’ve got more choice, but actually it makes these recommendations even more important because it becomes more complicated to choose optimal treatment for individuals,” added Dr. Coates, a senior clinical research fellow at the University of Oxford (England).

“We’ve been waiting for a while now for the new GRAPPA recommendations,” Laure Gossec, MD, PhD, of Sorbonne University and Pitié-Salpêtrière Hospital in Paris, said in a separate interview.

New overarching principle and position statements

The goal of the recommendations hasn’t really changed since the first iteration of the guidelines in 2009, Dr. Coates noted in her presentation. They are intended to provide clinicians with recommendations “based on the best available evidence” for the management of patients with psoriatic disease.

To that end, a through process was followed, starting with the setting of PICO (Patient/population/problem; intervention; comparison; outcome) questions followed by systematic literature searches, data extraction, and review that assess the quality of evidence and then grade it accordingly before using it to inform the recommendation statements.

There is a new overarching principle that says: “These recommendations, which include the most current data concerning the optimal assessment of and therapeutic approached to psoriatic arthritis, present contextual considerations to empower shared decision making.”

The other overarching principles remain the same as in the 2015 version, with “minor wording changes particularly around the comorbidities overarching principle,” Dr. Coates said.

Also new are two position statements. “One of them is specifically around biosimilars, because that’s been a big shift since 2015,” Dr. Coates said. “It has basic rules about what evidence there should be, what we should consider when we’re using them, and patient involvement and decision making.”

The second statement covers “similar advice on tapering or discontinuing therapy – what we do when people are doing really well, how we should stop or taper, and which drugs we should choose to stop along with shared decision making with patients.”

GRAPPA intentionally gives clinicians more freedom

While there may be data to show differences in efficacy and side effects between the various drugs cited in the recommendations, “GRAPPA makes the choice to not prioritize one drug over another,” Dr. Gossec said. This decision gives “a lot of freedom then to the physician to make the decision.”

One important change according to Dr. Gossec is that oral “NSAIDs have clearly been put back as first-line treatment, before going on to disease-modifying drugs for most of the musculoskeletal manifestations. She added that for skin manifestations, topical NSAIDs were recommended, but that NSAIDs were more recommended for IBD and uveitis of course.

“I feel that’s a big step towards more of a step-up approach,” Dr. Gossec said. “The old recommendations were not clear that you would precede an NSAID before moving on to a disease-modifying drug. So, I think that makes it a little bit more similar to the 2019 EULAR recommendations.” The use of csDMARDs such as methotrexate has also been “pushed up a notch” in peripheral arthritis, she said.

What’s next?

There are a few fine tunings still to be made before the final recommendations are published. They also have to be discussed at the meeting of the GRAPPA task force, which consists of rheumatologists, dermatologists, and patient representatives.

Besides the recommendations manuscript, there will be individual papers detailing the evidence underpinning the recommendations in each of the eight domains, Dr. Coates noted. Those “will look at relative efficacy in detail,” she said. “There will be a lot more discussion/evidence summary included” to help with drug selection.

“We also plan to have some case studies to illustrate how the recommendations can be used, similar to that included in the 2015 recommendations,” she added.

Paul Studenic, MD, PhD, of the Karolinska Institute in Stockholm and Medical University of Vienna, tweeted that the GRAPPA recommendations showed treatment “needs to be tailored to the patient” taking “comorbidities as well as the heterogeneity of features of the clinical presentation into account.”

He said in an interview: “The third edition of the GRAPPA is a huge collaborative effort.” The new overarching principle put the recommendations in the context of shared decision making and, he added, they emphasize an “integrated management plan taking not only ‘classical’-related manifestations like uveitis into account but [also] a spectrum of comorbidities and reproductive health.”

GRAPPA is a not-for-profit organization and receives funding from multiple pharmaceutical companies. Currently this includes AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, Pfizer, UCB, and Sun Pharma with Galapagos and Nordic Bioscience as Innovation Partners. Dr. Coates acknowledged receiving research funding, honoraria, speaker fees or all of these from most of the aforementioned companies.

Dr. Gossec has received research funding or other support from numerous pharmaceutical companies and is a member of GRAPPA and the task force that developed the EULAR guidelines on the pharmacological management of psoriatic arthritis.

Dr. Studenic had nothing to disclose.

Almost 50% of patients with migraine hesitate to seek appropriate care, new research shows. A survey of nearly 18,000 participants with migraine showed that 46% were reluctant to consult a physician about their condition. Among those who hesitated, 58% ultimately consulted a physician, but 42% did not.

Common reasons for failure to seek treatment included believing that migraine was not severe enough to warrant a consultation, worries about cost and health insurance, and concern that the health care professional would not take the disorder seriously.

This is the first study to query patients with migraine regarding whether and why they have hesitated to seek care, said coinvestigator Robert E. Shapiro, MD, PhD, professor of neurologic sciences and director of the division of headache medicine at the University of Vermont, Burlington. “Previous studies have noted differences in care seeking by demographic or other distinguishing characteristics but have not asked people with migraine whether they actually intended to seek or not seek such care,” he said.

Dr. Shapiro presented the findings at the American Headache Society’s 2021 annual meeting.
 

Delays prevent diagnosis and care

For patients with migraine, hesitating to consult a physician causes delays in, and sometimes prevents, receiving a diagnosis and appropriate care.

To assess the proportion of patients who hesitate to seek a consultation for migraine care, as well as reasons for doing so, the investigators examined data from the Observational Survey of the Epidemiology, Treatment, and Care of Migraine (OVERCOME) study. OVERCOME incorporated a prospective web-based survey that was administered to a representative sample of 41,925 individuals in the United States.

Eligible participants who completed the study’s baseline assessment had had at least one migraine attack in the previous year and either met criteria for migraine on the basis of a validated diagnostic screen or provided a self-report of a migraine diagnosis by a health care practitioner. In all, 39,494 participants reported whether they had hesitated to seek a consultation from a physician for migraine care. Of these, 17,951 were included in the analysis.

Among the 46% who hesitated to seek care, 58% ultimately sought migraine care, and 42% did not.

The investigators also examined sociodemographic characteristics and migraine-related data, including the number of monthly headache days and information regarding nausea, photophobia, and phonophobia.

Patient-reported outcomes included days with migraine-related disability during the past 3 months, treatment optimization, and the degree to which migraine limited regular activities. Investigators also examined participants’ health care use in the previous 12 months and reasons for hesitating to seek migraine care.
 

Reasons for hesitancy

A total of 17,920 participants provided reasons for hesitating to seek a migraine consultation. These included a desire to take care of migraine attacks on one’s own (45%), the belief that migraine would not be taken seriously (35%), the belief that the migraine attacks were not serious or painful enough (29%), inability to afford or unwillingness to spend money on care (29%), lack of or inadequate health insurance (21%), and fear of receiving a serious diagnosis (19%).

Reasons for hesitation differed between participants who ultimately sought a consultation with a physician and those who did not. Those who did not receive a consultation (n = 7,495) were more likely to want to take care of the migraine attacks on their own (48% vs. 43%) and to believe the attacks were not serious or painful enough (36% vs. 25%).

Participants who hesitated but later sought a consultation were more likely to report concerns that migraine would not be taken seriously (38% vs. 31%) and fear of receiving a serious diagnosis (22% vs. 15%).

Among those who did not seek a consultation versus those who did, a significantly higher proportion were women (76% vs. 73%; P < .001).

“This is an interesting finding, since prior studies have indicated that, overall, women with migraine are more likely to have consulted a doctor for it – and also more likely to have been diagnosed with it,” Dr. Shapiro said.

On the other hand, women were 30% more likely to visit emergency departments or urgent care clinics for migraine care than men, he noted.

“These findings suggest some women may be experiencing particular barriers to receiving successful consultation care and that they may persistently hesitate to seek it,” said Dr. Shapiro. He noted that these barriers might be financial or attitudinal.

“Women are reported to be less likely to receive treatment for pain conditions, and furthermore, stigma toward migraine in particular may limit its perceived seriousness,” he said.
 

‘Equitable access’ needed

Those with full-time employment were significantly more likely to seek a migraine consultation than were those who were not employed full time (46% vs. 42%; P < .001). Patients who sought care were more likely to have health insurance (87% vs. 78%; P < .001).

Having health insurance (odds ratio [OR], 1.99), having previously received a migraine diagnosis (OR, 2.71), and degree of disability (severe vs. none: OR, 2.76; moderate vs. none: OR, 2.04) were associated with increased likelihood of seeking a migraine consultation among those who initially hesitated. Other factors included being male (OR, 1.49), having nausea (OR, 1.15), or being employed full time (OR, 1.24).

“Taken together, our findings suggest consultation rates may be limited by financial barriers and pervasive attitudes that migraine is either not serious or is untreatable,” said Dr. Shapiro. Consistent with this hypothesis is the finding that individuals with migraine who had received an appropriate diagnosis and were therefore better informed about the condition were more likely to continue to seek care for it, he noted.

Because most outpatient medical encounters for migraine are with primary care practitioners, it may make sense to ensure that such clinicians are “well trained in diagnosing and treating common presentations of migraine,” Dr. Shapiro said. It is equally important to ensure “equitable access to health insurance to pay for these consultations,” he added.
 

‘Take migraine more seriously’

Commenting on the findings, Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, said the study was well designed.

Potential weaknesses include the fact that patients were required only to have one migraine attack per year and that not all were diagnosed by a headache specialist using ICHD-3 criteria.

Still, “online, validated, patient-reported data is quite acceptable,” said Dr. Rapoport, who was not involved in the research.

He noted that there is a clear message from the findings for all physicians who see patients with headache disorders: “You will increase the chance of patients consulting and continuing to consult when you make an accurate migraine diagnosis, take migraine more seriously, and understand the stigmas attached to it – and when there are reduced institutional barriers and costs of health care.”

The findings suggest that neurologists should strive to provide patients with ongoing care and medication, he added. In addition, there is a need for further education about the stigma associated with migraine and about how others view this disabling disease, Dr. Rapoport concluded.

The study was funded by Eli Lilly. Dr. Shapiro has consulted for Eli Lilly and Lundbeck. Dr. Rapoport has reported no relevant financial relationships.
 

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

Almost 50% of patients with migraine hesitate to seek appropriate care, new research shows. A survey of nearly 18,000 participants with migraine showed that 46% were reluctant to consult a physician about their condition. Among those who hesitated, 58% ultimately consulted a physician, but 42% did not.

Common reasons for failure to seek treatment included believing that migraine was not severe enough to warrant a consultation, worries about cost and health insurance, and concern that the health care professional would not take the disorder seriously.

This is the first study to query patients with migraine regarding whether and why they have hesitated to seek care, said coinvestigator Robert E. Shapiro, MD, PhD, professor of neurologic sciences and director of the division of headache medicine at the University of Vermont, Burlington. “Previous studies have noted differences in care seeking by demographic or other distinguishing characteristics but have not asked people with migraine whether they actually intended to seek or not seek such care,” he said.

Dr. Shapiro presented the findings at the American Headache Society’s 2021 annual meeting.
 

Delays prevent diagnosis and care

For patients with migraine, hesitating to consult a physician causes delays in, and sometimes prevents, receiving a diagnosis and appropriate care.

To assess the proportion of patients who hesitate to seek a consultation for migraine care, as well as reasons for doing so, the investigators examined data from the Observational Survey of the Epidemiology, Treatment, and Care of Migraine (OVERCOME) study. OVERCOME incorporated a prospective web-based survey that was administered to a representative sample of 41,925 individuals in the United States.

Eligible participants who completed the study’s baseline assessment had had at least one migraine attack in the previous year and either met criteria for migraine on the basis of a validated diagnostic screen or provided a self-report of a migraine diagnosis by a health care practitioner. In all, 39,494 participants reported whether they had hesitated to seek a consultation from a physician for migraine care. Of these, 17,951 were included in the analysis.

Among the 46% who hesitated to seek care, 58% ultimately sought migraine care, and 42% did not.

The investigators also examined sociodemographic characteristics and migraine-related data, including the number of monthly headache days and information regarding nausea, photophobia, and phonophobia.

Patient-reported outcomes included days with migraine-related disability during the past 3 months, treatment optimization, and the degree to which migraine limited regular activities. Investigators also examined participants’ health care use in the previous 12 months and reasons for hesitating to seek migraine care.
 

Reasons for hesitancy

A total of 17,920 participants provided reasons for hesitating to seek a migraine consultation. These included a desire to take care of migraine attacks on one’s own (45%), the belief that migraine would not be taken seriously (35%), the belief that the migraine attacks were not serious or painful enough (29%), inability to afford or unwillingness to spend money on care (29%), lack of or inadequate health insurance (21%), and fear of receiving a serious diagnosis (19%).

Reasons for hesitation differed between participants who ultimately sought a consultation with a physician and those who did not. Those who did not receive a consultation (n = 7,495) were more likely to want to take care of the migraine attacks on their own (48% vs. 43%) and to believe the attacks were not serious or painful enough (36% vs. 25%).

Participants who hesitated but later sought a consultation were more likely to report concerns that migraine would not be taken seriously (38% vs. 31%) and fear of receiving a serious diagnosis (22% vs. 15%).

Among those who did not seek a consultation versus those who did, a significantly higher proportion were women (76% vs. 73%; P < .001).

“This is an interesting finding, since prior studies have indicated that, overall, women with migraine are more likely to have consulted a doctor for it – and also more likely to have been diagnosed with it,” Dr. Shapiro said.

On the other hand, women were 30% more likely to visit emergency departments or urgent care clinics for migraine care than men, he noted.

“These findings suggest some women may be experiencing particular barriers to receiving successful consultation care and that they may persistently hesitate to seek it,” said Dr. Shapiro. He noted that these barriers might be financial or attitudinal.

“Women are reported to be less likely to receive treatment for pain conditions, and furthermore, stigma toward migraine in particular may limit its perceived seriousness,” he said.
 

‘Equitable access’ needed

Those with full-time employment were significantly more likely to seek a migraine consultation than were those who were not employed full time (46% vs. 42%; P < .001). Patients who sought care were more likely to have health insurance (87% vs. 78%; P < .001).

Having health insurance (odds ratio [OR], 1.99), having previously received a migraine diagnosis (OR, 2.71), and degree of disability (severe vs. none: OR, 2.76; moderate vs. none: OR, 2.04) were associated with increased likelihood of seeking a migraine consultation among those who initially hesitated. Other factors included being male (OR, 1.49), having nausea (OR, 1.15), or being employed full time (OR, 1.24).

“Taken together, our findings suggest consultation rates may be limited by financial barriers and pervasive attitudes that migraine is either not serious or is untreatable,” said Dr. Shapiro. Consistent with this hypothesis is the finding that individuals with migraine who had received an appropriate diagnosis and were therefore better informed about the condition were more likely to continue to seek care for it, he noted.

Because most outpatient medical encounters for migraine are with primary care practitioners, it may make sense to ensure that such clinicians are “well trained in diagnosing and treating common presentations of migraine,” Dr. Shapiro said. It is equally important to ensure “equitable access to health insurance to pay for these consultations,” he added.
 

‘Take migraine more seriously’

Commenting on the findings, Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, said the study was well designed.

Potential weaknesses include the fact that patients were required only to have one migraine attack per year and that not all were diagnosed by a headache specialist using ICHD-3 criteria.

Still, “online, validated, patient-reported data is quite acceptable,” said Dr. Rapoport, who was not involved in the research.

He noted that there is a clear message from the findings for all physicians who see patients with headache disorders: “You will increase the chance of patients consulting and continuing to consult when you make an accurate migraine diagnosis, take migraine more seriously, and understand the stigmas attached to it – and when there are reduced institutional barriers and costs of health care.”

The findings suggest that neurologists should strive to provide patients with ongoing care and medication, he added. In addition, there is a need for further education about the stigma associated with migraine and about how others view this disabling disease, Dr. Rapoport concluded.

The study was funded by Eli Lilly. Dr. Shapiro has consulted for Eli Lilly and Lundbeck. Dr. Rapoport has reported no relevant financial relationships.
 

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

Almost 50% of patients with migraine hesitate to seek appropriate care, new research shows. A survey of nearly 18,000 participants with migraine showed that 46% were reluctant to consult a physician about their condition. Among those who hesitated, 58% ultimately consulted a physician, but 42% did not.

Common reasons for failure to seek treatment included believing that migraine was not severe enough to warrant a consultation, worries about cost and health insurance, and concern that the health care professional would not take the disorder seriously.

This is the first study to query patients with migraine regarding whether and why they have hesitated to seek care, said coinvestigator Robert E. Shapiro, MD, PhD, professor of neurologic sciences and director of the division of headache medicine at the University of Vermont, Burlington. “Previous studies have noted differences in care seeking by demographic or other distinguishing characteristics but have not asked people with migraine whether they actually intended to seek or not seek such care,” he said.

Dr. Shapiro presented the findings at the American Headache Society’s 2021 annual meeting.
 

Delays prevent diagnosis and care

For patients with migraine, hesitating to consult a physician causes delays in, and sometimes prevents, receiving a diagnosis and appropriate care.

To assess the proportion of patients who hesitate to seek a consultation for migraine care, as well as reasons for doing so, the investigators examined data from the Observational Survey of the Epidemiology, Treatment, and Care of Migraine (OVERCOME) study. OVERCOME incorporated a prospective web-based survey that was administered to a representative sample of 41,925 individuals in the United States.

Eligible participants who completed the study’s baseline assessment had had at least one migraine attack in the previous year and either met criteria for migraine on the basis of a validated diagnostic screen or provided a self-report of a migraine diagnosis by a health care practitioner. In all, 39,494 participants reported whether they had hesitated to seek a consultation from a physician for migraine care. Of these, 17,951 were included in the analysis.

Among the 46% who hesitated to seek care, 58% ultimately sought migraine care, and 42% did not.

The investigators also examined sociodemographic characteristics and migraine-related data, including the number of monthly headache days and information regarding nausea, photophobia, and phonophobia.

Patient-reported outcomes included days with migraine-related disability during the past 3 months, treatment optimization, and the degree to which migraine limited regular activities. Investigators also examined participants’ health care use in the previous 12 months and reasons for hesitating to seek migraine care.
 

Reasons for hesitancy

A total of 17,920 participants provided reasons for hesitating to seek a migraine consultation. These included a desire to take care of migraine attacks on one’s own (45%), the belief that migraine would not be taken seriously (35%), the belief that the migraine attacks were not serious or painful enough (29%), inability to afford or unwillingness to spend money on care (29%), lack of or inadequate health insurance (21%), and fear of receiving a serious diagnosis (19%).

Reasons for hesitation differed between participants who ultimately sought a consultation with a physician and those who did not. Those who did not receive a consultation (n = 7,495) were more likely to want to take care of the migraine attacks on their own (48% vs. 43%) and to believe the attacks were not serious or painful enough (36% vs. 25%).

Participants who hesitated but later sought a consultation were more likely to report concerns that migraine would not be taken seriously (38% vs. 31%) and fear of receiving a serious diagnosis (22% vs. 15%).

Among those who did not seek a consultation versus those who did, a significantly higher proportion were women (76% vs. 73%; P < .001).

“This is an interesting finding, since prior studies have indicated that, overall, women with migraine are more likely to have consulted a doctor for it – and also more likely to have been diagnosed with it,” Dr. Shapiro said.

On the other hand, women were 30% more likely to visit emergency departments or urgent care clinics for migraine care than men, he noted.

“These findings suggest some women may be experiencing particular barriers to receiving successful consultation care and that they may persistently hesitate to seek it,” said Dr. Shapiro. He noted that these barriers might be financial or attitudinal.

“Women are reported to be less likely to receive treatment for pain conditions, and furthermore, stigma toward migraine in particular may limit its perceived seriousness,” he said.
 

‘Equitable access’ needed

Those with full-time employment were significantly more likely to seek a migraine consultation than were those who were not employed full time (46% vs. 42%; P < .001). Patients who sought care were more likely to have health insurance (87% vs. 78%; P < .001).

Having health insurance (odds ratio [OR], 1.99), having previously received a migraine diagnosis (OR, 2.71), and degree of disability (severe vs. none: OR, 2.76; moderate vs. none: OR, 2.04) were associated with increased likelihood of seeking a migraine consultation among those who initially hesitated. Other factors included being male (OR, 1.49), having nausea (OR, 1.15), or being employed full time (OR, 1.24).

“Taken together, our findings suggest consultation rates may be limited by financial barriers and pervasive attitudes that migraine is either not serious or is untreatable,” said Dr. Shapiro. Consistent with this hypothesis is the finding that individuals with migraine who had received an appropriate diagnosis and were therefore better informed about the condition were more likely to continue to seek care for it, he noted.

Because most outpatient medical encounters for migraine are with primary care practitioners, it may make sense to ensure that such clinicians are “well trained in diagnosing and treating common presentations of migraine,” Dr. Shapiro said. It is equally important to ensure “equitable access to health insurance to pay for these consultations,” he added.
 

‘Take migraine more seriously’

Commenting on the findings, Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, said the study was well designed.

Potential weaknesses include the fact that patients were required only to have one migraine attack per year and that not all were diagnosed by a headache specialist using ICHD-3 criteria.

Still, “online, validated, patient-reported data is quite acceptable,” said Dr. Rapoport, who was not involved in the research.

He noted that there is a clear message from the findings for all physicians who see patients with headache disorders: “You will increase the chance of patients consulting and continuing to consult when you make an accurate migraine diagnosis, take migraine more seriously, and understand the stigmas attached to it – and when there are reduced institutional barriers and costs of health care.”

The findings suggest that neurologists should strive to provide patients with ongoing care and medication, he added. In addition, there is a need for further education about the stigma associated with migraine and about how others view this disabling disease, Dr. Rapoport concluded.

The study was funded by Eli Lilly. Dr. Shapiro has consulted for Eli Lilly and Lundbeck. Dr. Rapoport has reported no relevant financial relationships.
 

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