Federal Practitioner

 Patients who have had a myocardial infarction experience faster cognitive decline over time than immediately after the event, new research suggests.

Although cognition in the acute phase after MI was not different than those without an MI in large observational cohorts, cognitive decline became significantly different over a median 6.5 years of follow-up.

The results reinforce the idea that heart health is closely tied to brain health, lead study author Michelle C. Johansen, MD, PhD, assistant professor of neurology cerebrovascular division, Johns Hopkins University, Baltimore, said in an interview. “From a clinical standpoint, heart health affects brain health and there may be effective interventions to prevent heart attack from happening that could reduce the rate of cognitive decline.”

The study was presented during the International Stroke Conference sponsored by the American Heart Association.

Researchers are increasingly recognizing the vascular contribution to cognitive impairment, said Dr. Johansen. This could involve “silent” or subclinical strokes that go unrecognized until seen on imaging.

The study included 31,377 adults free of MI and dementia from six large, well-known cohort studies: the Atherosclerosis Risk in Communities Study, the Coronary Artery Risk Development in Young Adults Study, the Cardiovascular Health Study, the Framingham Offspring Study, the Multi-Ethnic Study of Atherosclerosis, and the Northern Manhattan Study

About 56% of study participants were women, 23% were Black, 8% were Hispanic, and 69% were White.

They were followed from 1971 to 2017 with investigators repeatedly measuring vascular risk factors. The median study follow-up was 6.5 years, but some were followed for up to 20 years. During that time, there were 1,047 incident MIs.

The researchers performed a pooled analysis from these studies “using some fancy statistical techniques,” said Dr. Johansen. “The unique thing about this study was we were able to harmonize the cognitive measures.”

This allowed the researchers to determine if incident MI affected cognitive decline soon after the event and then long-term after the event. The primary outcome was change in global cognition. Additional outcomes were memory and executive function.

The median time between the first MI and the cognitive assessment was about 1.8 years but ranged from about 6 months to 4 years, said Dr. Johansen. Participants were a median age of 60 years at the time of the first cognitive assessment.

The researchers adjusted results for demographic factors, heart disease risk factors, and cognitive test results prior to the MI. Participants who had a stroke during the follow-up period were excluded from the analysis as stroke can affect cognition.

The study showed incident MI was associated with significant decline in global cognition (–0.71; 95% confidence interval, –1.02 to 0.42; P < .0001) and executive function (–0.68; 95% CI, –0.97 to 0.39; P < .004), but not memory, after the MI.

As cognition naturally declines with age, the researchers took that into consideration. “We anticipated cognition over time was going to go down, which it did, but the question we asked was: ‘How did the slope, which we knew was going to decline over time, compare in people who did not have a MI versus those that did?’ ” said Dr. Johansen.

After adjusting the model accordingly, the effect estimates indicating declines in global cognition and executive function were not significant.

However, another model that looked at the effect of incident MI on decline in cognitive function over the years following the event found significant differences.

Compared with participants without MI, those with incident MI had significantly faster declines in global cognition (–0.15 points/year faster, 95% CI, –0.21 to –0.10; P < .002), memory (–0.13 points/year faster, 95% CI, –0.23 to –0.04; P = .004), and executive function (–0.14 points/year faster, 95% CI, –0.20 to –0.08; P < .0001).

Dr. Johansen surmised that MI may result in subclinical infarcts or inflammation, or that MI and cognitive decline have shared vascular risk factors.

She said she can only speculate about why there was not more of a cognitive decline surrounding the MI. “It may be that right after the event, subjects are kind of sick from other things so it’s hard to see exactly what’s going on. Sometimes people can have other problems just from being in the hospital and having a heart attack may make cognition difficult to assess.”

The researchers also looked at those who had a second MI. “We asked whether the decline we saw after the first heart attack among those who had two heart attacks was explained by the fact they had more than one heart attack, and the answer to that question is no,” Dr. Johansen said.

The next research steps for Dr. Johansen and associates are to look at differences in race and sex.

Karen L. Furie, MD, chair, department of neurology, Brown University, and chief of neurology at Rhode Island Hospital, the Miriam Hospital, and the Bradley Hospital, all in Providence, provided a comment on the research.

MI and cognitive decline have a number of common risk factors, including hypertension, diabetes, high cholesterol, smoking, physical inactivity, and poor diet that can lead to obesity, said Dr. Furie.

“It’s critically important to identify these risk factors as early as possible,” she said. “People in early and middle life may not be receiving optimal medical management or engaging in ideal lifestyle choices and these contribute to the development and progression of atherosclerotic disease over the subsequent decades.”

In theory, she said, if these risk factors were eliminated or adequately treated earlier in life, “both the heart and brain could age naturally and in a healthy manner, enabling a higher functioning and better quality of life.”

The study was funded by the National Institute of Neurological Disorders and Stroke and the National Institute of Aging of the National Institutes of Health. Dr. Johansen receives research funding from NINDS.

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

 Patients who have had a myocardial infarction experience faster cognitive decline over time than immediately after the event, new research suggests.

Although cognition in the acute phase after MI was not different than those without an MI in large observational cohorts, cognitive decline became significantly different over a median 6.5 years of follow-up.

The results reinforce the idea that heart health is closely tied to brain health, lead study author Michelle C. Johansen, MD, PhD, assistant professor of neurology cerebrovascular division, Johns Hopkins University, Baltimore, said in an interview. “From a clinical standpoint, heart health affects brain health and there may be effective interventions to prevent heart attack from happening that could reduce the rate of cognitive decline.”

The study was presented during the International Stroke Conference sponsored by the American Heart Association.

Researchers are increasingly recognizing the vascular contribution to cognitive impairment, said Dr. Johansen. This could involve “silent” or subclinical strokes that go unrecognized until seen on imaging.

The study included 31,377 adults free of MI and dementia from six large, well-known cohort studies: the Atherosclerosis Risk in Communities Study, the Coronary Artery Risk Development in Young Adults Study, the Cardiovascular Health Study, the Framingham Offspring Study, the Multi-Ethnic Study of Atherosclerosis, and the Northern Manhattan Study

About 56% of study participants were women, 23% were Black, 8% were Hispanic, and 69% were White.

They were followed from 1971 to 2017 with investigators repeatedly measuring vascular risk factors. The median study follow-up was 6.5 years, but some were followed for up to 20 years. During that time, there were 1,047 incident MIs.

The researchers performed a pooled analysis from these studies “using some fancy statistical techniques,” said Dr. Johansen. “The unique thing about this study was we were able to harmonize the cognitive measures.”

This allowed the researchers to determine if incident MI affected cognitive decline soon after the event and then long-term after the event. The primary outcome was change in global cognition. Additional outcomes were memory and executive function.

The median time between the first MI and the cognitive assessment was about 1.8 years but ranged from about 6 months to 4 years, said Dr. Johansen. Participants were a median age of 60 years at the time of the first cognitive assessment.

The researchers adjusted results for demographic factors, heart disease risk factors, and cognitive test results prior to the MI. Participants who had a stroke during the follow-up period were excluded from the analysis as stroke can affect cognition.

The study showed incident MI was associated with significant decline in global cognition (–0.71; 95% confidence interval, –1.02 to 0.42; P < .0001) and executive function (–0.68; 95% CI, –0.97 to 0.39; P < .004), but not memory, after the MI.

As cognition naturally declines with age, the researchers took that into consideration. “We anticipated cognition over time was going to go down, which it did, but the question we asked was: ‘How did the slope, which we knew was going to decline over time, compare in people who did not have a MI versus those that did?’ ” said Dr. Johansen.

After adjusting the model accordingly, the effect estimates indicating declines in global cognition and executive function were not significant.

However, another model that looked at the effect of incident MI on decline in cognitive function over the years following the event found significant differences.

Compared with participants without MI, those with incident MI had significantly faster declines in global cognition (–0.15 points/year faster, 95% CI, –0.21 to –0.10; P < .002), memory (–0.13 points/year faster, 95% CI, –0.23 to –0.04; P = .004), and executive function (–0.14 points/year faster, 95% CI, –0.20 to –0.08; P < .0001).

Dr. Johansen surmised that MI may result in subclinical infarcts or inflammation, or that MI and cognitive decline have shared vascular risk factors.

She said she can only speculate about why there was not more of a cognitive decline surrounding the MI. “It may be that right after the event, subjects are kind of sick from other things so it’s hard to see exactly what’s going on. Sometimes people can have other problems just from being in the hospital and having a heart attack may make cognition difficult to assess.”

The researchers also looked at those who had a second MI. “We asked whether the decline we saw after the first heart attack among those who had two heart attacks was explained by the fact they had more than one heart attack, and the answer to that question is no,” Dr. Johansen said.

The next research steps for Dr. Johansen and associates are to look at differences in race and sex.

Karen L. Furie, MD, chair, department of neurology, Brown University, and chief of neurology at Rhode Island Hospital, the Miriam Hospital, and the Bradley Hospital, all in Providence, provided a comment on the research.

MI and cognitive decline have a number of common risk factors, including hypertension, diabetes, high cholesterol, smoking, physical inactivity, and poor diet that can lead to obesity, said Dr. Furie.

“It’s critically important to identify these risk factors as early as possible,” she said. “People in early and middle life may not be receiving optimal medical management or engaging in ideal lifestyle choices and these contribute to the development and progression of atherosclerotic disease over the subsequent decades.”

In theory, she said, if these risk factors were eliminated or adequately treated earlier in life, “both the heart and brain could age naturally and in a healthy manner, enabling a higher functioning and better quality of life.”

The study was funded by the National Institute of Neurological Disorders and Stroke and the National Institute of Aging of the National Institutes of Health. Dr. Johansen receives research funding from NINDS.

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

 Patients who have had a myocardial infarction experience faster cognitive decline over time than immediately after the event, new research suggests.

Although cognition in the acute phase after MI was not different than those without an MI in large observational cohorts, cognitive decline became significantly different over a median 6.5 years of follow-up.

The results reinforce the idea that heart health is closely tied to brain health, lead study author Michelle C. Johansen, MD, PhD, assistant professor of neurology cerebrovascular division, Johns Hopkins University, Baltimore, said in an interview. “From a clinical standpoint, heart health affects brain health and there may be effective interventions to prevent heart attack from happening that could reduce the rate of cognitive decline.”

The study was presented during the International Stroke Conference sponsored by the American Heart Association.

Researchers are increasingly recognizing the vascular contribution to cognitive impairment, said Dr. Johansen. This could involve “silent” or subclinical strokes that go unrecognized until seen on imaging.

The study included 31,377 adults free of MI and dementia from six large, well-known cohort studies: the Atherosclerosis Risk in Communities Study, the Coronary Artery Risk Development in Young Adults Study, the Cardiovascular Health Study, the Framingham Offspring Study, the Multi-Ethnic Study of Atherosclerosis, and the Northern Manhattan Study

About 56% of study participants were women, 23% were Black, 8% were Hispanic, and 69% were White.

They were followed from 1971 to 2017 with investigators repeatedly measuring vascular risk factors. The median study follow-up was 6.5 years, but some were followed for up to 20 years. During that time, there were 1,047 incident MIs.

The researchers performed a pooled analysis from these studies “using some fancy statistical techniques,” said Dr. Johansen. “The unique thing about this study was we were able to harmonize the cognitive measures.”

This allowed the researchers to determine if incident MI affected cognitive decline soon after the event and then long-term after the event. The primary outcome was change in global cognition. Additional outcomes were memory and executive function.

The median time between the first MI and the cognitive assessment was about 1.8 years but ranged from about 6 months to 4 years, said Dr. Johansen. Participants were a median age of 60 years at the time of the first cognitive assessment.

The researchers adjusted results for demographic factors, heart disease risk factors, and cognitive test results prior to the MI. Participants who had a stroke during the follow-up period were excluded from the analysis as stroke can affect cognition.

The study showed incident MI was associated with significant decline in global cognition (–0.71; 95% confidence interval, –1.02 to 0.42; P < .0001) and executive function (–0.68; 95% CI, –0.97 to 0.39; P < .004), but not memory, after the MI.

As cognition naturally declines with age, the researchers took that into consideration. “We anticipated cognition over time was going to go down, which it did, but the question we asked was: ‘How did the slope, which we knew was going to decline over time, compare in people who did not have a MI versus those that did?’ ” said Dr. Johansen.

After adjusting the model accordingly, the effect estimates indicating declines in global cognition and executive function were not significant.

However, another model that looked at the effect of incident MI on decline in cognitive function over the years following the event found significant differences.

Compared with participants without MI, those with incident MI had significantly faster declines in global cognition (–0.15 points/year faster, 95% CI, –0.21 to –0.10; P < .002), memory (–0.13 points/year faster, 95% CI, –0.23 to –0.04; P = .004), and executive function (–0.14 points/year faster, 95% CI, –0.20 to –0.08; P < .0001).

Dr. Johansen surmised that MI may result in subclinical infarcts or inflammation, or that MI and cognitive decline have shared vascular risk factors.

She said she can only speculate about why there was not more of a cognitive decline surrounding the MI. “It may be that right after the event, subjects are kind of sick from other things so it’s hard to see exactly what’s going on. Sometimes people can have other problems just from being in the hospital and having a heart attack may make cognition difficult to assess.”

The researchers also looked at those who had a second MI. “We asked whether the decline we saw after the first heart attack among those who had two heart attacks was explained by the fact they had more than one heart attack, and the answer to that question is no,” Dr. Johansen said.

The next research steps for Dr. Johansen and associates are to look at differences in race and sex.

Karen L. Furie, MD, chair, department of neurology, Brown University, and chief of neurology at Rhode Island Hospital, the Miriam Hospital, and the Bradley Hospital, all in Providence, provided a comment on the research.

MI and cognitive decline have a number of common risk factors, including hypertension, diabetes, high cholesterol, smoking, physical inactivity, and poor diet that can lead to obesity, said Dr. Furie.

“It’s critically important to identify these risk factors as early as possible,” she said. “People in early and middle life may not be receiving optimal medical management or engaging in ideal lifestyle choices and these contribute to the development and progression of atherosclerotic disease over the subsequent decades.”

In theory, she said, if these risk factors were eliminated or adequately treated earlier in life, “both the heart and brain could age naturally and in a healthy manner, enabling a higher functioning and better quality of life.”

The study was funded by the National Institute of Neurological Disorders and Stroke and the National Institute of Aging of the National Institutes of Health. Dr. Johansen receives research funding from NINDS.

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

Updated guidance for health care providers on multisystem inflammatory syndrome in children (MIS-C) recognizes the evolving nature of the disease and offers strategies for pediatric rheumatologists, who also may be asked to recommend treatment for hyperinflammation in children with acute COVID-19.

Guidance is needed for many reasons, including the variable case definitions for MIS-C, the presence of MIS-C features in other infections and childhood rheumatic diseases, the extrapolation of treatment strategies from other conditions with similar presentations, and the issue of myocardial dysfunction, wrote Lauren A. Henderson, MD, MMSC, of Boston Children’s Hospital, and members of the American College of Rheumatology MIS-C and COVID-19–Related Hyperinflammation Task Force.

However, “modifications to treatment plans, particularly in patients with complex conditions, are highly disease, patient, geography, and time specific, and therefore must be individualized as part of a shared decision-making process,” the authors said. The updated guidance was published in Arthritis & Rheumatology.
 

Update needed in wake of Omicron

“We continue to see cases of MIS-C across the United States due to the spike in SARS-CoV-2 infections from the Omicron variant,” and therefore updated guidance is important at this time, Dr. Henderson told this news organization.

“MIS-C remains a serious complication of COVID-19 in children and the ACR wanted to continue to provide pediatricians with up-to-date recommendations for the management of MIS-C,” she said.

“Children began to present with MIS-C in April 2020. At that time, little was known about this entity. Most of the recommendations in the first version of the MIS-C guidance were based on expert opinion,” she explained. However, “over the last 2 years, pediatricians have worked very hard to conduct high-quality research studies to better understand MIS-C, so we now have more scientific evidence to guide our recommendations.

“In version three of the MIS-C guidance, there are new recommendations on treatment. Previously, it was unclear what medications should be used for first-line treatment in patients with MIS-C. Some children were given intravenous immunoglobulin while others were given IVIg and steroids together. Several new studies show that children with MIS-C who are treated with a combination of IVIg and steroids have better outcomes. Accordingly, the MIS-C guidance now recommends dual therapy with IVIg and steroids in children with MIS-C.”

Diagnostic evaluation

The guidance calls for maintaining a broad differential diagnosis of MIS-C, given that the condition remains rare, and that most children with COVID-19 present with mild symptoms and have excellent outcomes, the authors noted. The range of clinical features associated with MIS-C include fever, mucocutaneous findings, myocardial dysfunction, cardiac conduction abnormalities, shock, gastrointestinal symptoms, and lymphadenopathy.

Some patients also experience neurologic involvement in the form of severe headache, altered mental status, seizures, cranial nerve palsies, meningismus, cerebral edema, and ischemic or hemorrhagic stroke. Given the nonspecific nature of these symptoms, “it is imperative that a diagnostic evaluation for MIS-C include investigation for other possible causes, as deemed appropriate by the treating provider,” the authors emphasized. Other diagnostic considerations include the prevalence and chronology of COVID-19 in the community, which may change over time.
 

MIS-C and Kawasaki disease phenotypes

Earlier in the pandemic, when MIS-C first emerged, it was compared with Kawasaki disease (KD). “However, a closer examination of the literature shows that only about one-quarter to half of patients with a reported diagnosis of MIS-C meet the full diagnostic criteria for KD,” the authors wrote. Key features that separate MIS-C from KD include the greater incidence of KD among children in Japan and East Asia versus the higher incidence of MIS-C among non-Hispanic Black children. In addition, children with MIS-C have shown a wider age range, more prominent gastrointestinal and neurologic symptoms, and more frequent cardiac dysfunction, compared with those with KD.

Cardiac management

Close follow-up with cardiology is essential for children with MIS-C, according to the authors. The recommendations call for repeat echocardiograms for all children with MIS-C at a minimum of 7-14 days, then again at 4-6 weeks after the initial presentation. The authors also recommended additional echocardiograms for children with left ventricular dysfunction and cardiac aortic aneurysms. 

MIS-C treatment

Current treatment recommendations emphasize that patients under investigation for MIS-C with life-threatening manifestations may need immunomodulatory therapy before a full diagnostic evaluation is complete, the authors said. However, patients without life-threatening manifestations should be evaluated before starting immunomodulatory treatment to avoid potentially harmful therapies for pediatric patients who don’t need them.

When MIS-C is refractory to initial immunomodulatory treatment, a second dose of IVIg is not recommended, but intensification therapy is advised with either high-dose (10-30 mg/kg per day) glucocorticoids, anakinra, or infliximab. However, there is little evidence available for selecting a specific agent for intensification therapy.

The task force also advises giving low-dose aspirin (3-5 mg/kg per day, up to 81 mg once daily) to all MIS-C patients without active bleeding or significant bleeding risk until normalization of the platelet count and confirmed normal coronary arteries at least 4 weeks after diagnosis.
 

COVID-19 and hyperinflammation

The task force also noted a distinction between MIS-C and severe COVID-19 in children. Although many children with MIS-C are previously healthy, most children who develop severe COVID-19 during an initial infection have complex conditions or comorbidities such as developmental delay or genetic anomaly, or chronic conditions such as congenital heart disease, type 1 diabetes, or asthma, the authors said. They recommend that “hospitalized children with COVID-19 requiring supplemental oxygen or respiratory support should be considered for immunomodulatory therapy in addition to supportive care and antiviral medications.”

The authors acknowledged the limitations and evolving nature of the recommendations, which will continue to change and do not replace clinical judgment for the management of individual patients. In the meantime, the ACR will support the task force in reviewing new evidence and providing revised versions of the current document.

Many questions about MIS-C remain, Dr. Henderson said in an interview. “It can be very hard to diagnose children with MIS-C because many of the symptoms are similar to those seen in other febrile illness of childhood. We need to identify better biomarkers to help us make the diagnosis of MIS-C. In addition, we need studies to provide information about what treatments should be used if children fail to respond to IVIg and steroids. Finally, it appears that vaccination [against SARS-CoV-2] protects against severe forms of MIS-C, and studies are needed to see how vaccination protects children from MIS-C.”

The development of the guidance was supported by the American College of Rheumatology. Dr. Henderson disclosed relationships with companies including Sobi, Pfizer, and Adaptive Biotechnologies (less than $10,000) and research support from the Childhood Arthritis and Rheumatology Research Alliance and research grant support from Bristol-Myers Squibb.

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

Updated guidance for health care providers on multisystem inflammatory syndrome in children (MIS-C) recognizes the evolving nature of the disease and offers strategies for pediatric rheumatologists, who also may be asked to recommend treatment for hyperinflammation in children with acute COVID-19.

Guidance is needed for many reasons, including the variable case definitions for MIS-C, the presence of MIS-C features in other infections and childhood rheumatic diseases, the extrapolation of treatment strategies from other conditions with similar presentations, and the issue of myocardial dysfunction, wrote Lauren A. Henderson, MD, MMSC, of Boston Children’s Hospital, and members of the American College of Rheumatology MIS-C and COVID-19–Related Hyperinflammation Task Force.

However, “modifications to treatment plans, particularly in patients with complex conditions, are highly disease, patient, geography, and time specific, and therefore must be individualized as part of a shared decision-making process,” the authors said. The updated guidance was published in Arthritis & Rheumatology.
 

Update needed in wake of Omicron

“We continue to see cases of MIS-C across the United States due to the spike in SARS-CoV-2 infections from the Omicron variant,” and therefore updated guidance is important at this time, Dr. Henderson told this news organization.

“MIS-C remains a serious complication of COVID-19 in children and the ACR wanted to continue to provide pediatricians with up-to-date recommendations for the management of MIS-C,” she said.

“Children began to present with MIS-C in April 2020. At that time, little was known about this entity. Most of the recommendations in the first version of the MIS-C guidance were based on expert opinion,” she explained. However, “over the last 2 years, pediatricians have worked very hard to conduct high-quality research studies to better understand MIS-C, so we now have more scientific evidence to guide our recommendations.

“In version three of the MIS-C guidance, there are new recommendations on treatment. Previously, it was unclear what medications should be used for first-line treatment in patients with MIS-C. Some children were given intravenous immunoglobulin while others were given IVIg and steroids together. Several new studies show that children with MIS-C who are treated with a combination of IVIg and steroids have better outcomes. Accordingly, the MIS-C guidance now recommends dual therapy with IVIg and steroids in children with MIS-C.”

Diagnostic evaluation

The guidance calls for maintaining a broad differential diagnosis of MIS-C, given that the condition remains rare, and that most children with COVID-19 present with mild symptoms and have excellent outcomes, the authors noted. The range of clinical features associated with MIS-C include fever, mucocutaneous findings, myocardial dysfunction, cardiac conduction abnormalities, shock, gastrointestinal symptoms, and lymphadenopathy.

Some patients also experience neurologic involvement in the form of severe headache, altered mental status, seizures, cranial nerve palsies, meningismus, cerebral edema, and ischemic or hemorrhagic stroke. Given the nonspecific nature of these symptoms, “it is imperative that a diagnostic evaluation for MIS-C include investigation for other possible causes, as deemed appropriate by the treating provider,” the authors emphasized. Other diagnostic considerations include the prevalence and chronology of COVID-19 in the community, which may change over time.
 

MIS-C and Kawasaki disease phenotypes

Earlier in the pandemic, when MIS-C first emerged, it was compared with Kawasaki disease (KD). “However, a closer examination of the literature shows that only about one-quarter to half of patients with a reported diagnosis of MIS-C meet the full diagnostic criteria for KD,” the authors wrote. Key features that separate MIS-C from KD include the greater incidence of KD among children in Japan and East Asia versus the higher incidence of MIS-C among non-Hispanic Black children. In addition, children with MIS-C have shown a wider age range, more prominent gastrointestinal and neurologic symptoms, and more frequent cardiac dysfunction, compared with those with KD.

Cardiac management

Close follow-up with cardiology is essential for children with MIS-C, according to the authors. The recommendations call for repeat echocardiograms for all children with MIS-C at a minimum of 7-14 days, then again at 4-6 weeks after the initial presentation. The authors also recommended additional echocardiograms for children with left ventricular dysfunction and cardiac aortic aneurysms. 

MIS-C treatment

Current treatment recommendations emphasize that patients under investigation for MIS-C with life-threatening manifestations may need immunomodulatory therapy before a full diagnostic evaluation is complete, the authors said. However, patients without life-threatening manifestations should be evaluated before starting immunomodulatory treatment to avoid potentially harmful therapies for pediatric patients who don’t need them.

When MIS-C is refractory to initial immunomodulatory treatment, a second dose of IVIg is not recommended, but intensification therapy is advised with either high-dose (10-30 mg/kg per day) glucocorticoids, anakinra, or infliximab. However, there is little evidence available for selecting a specific agent for intensification therapy.

The task force also advises giving low-dose aspirin (3-5 mg/kg per day, up to 81 mg once daily) to all MIS-C patients without active bleeding or significant bleeding risk until normalization of the platelet count and confirmed normal coronary arteries at least 4 weeks after diagnosis.
 

COVID-19 and hyperinflammation

The task force also noted a distinction between MIS-C and severe COVID-19 in children. Although many children with MIS-C are previously healthy, most children who develop severe COVID-19 during an initial infection have complex conditions or comorbidities such as developmental delay or genetic anomaly, or chronic conditions such as congenital heart disease, type 1 diabetes, or asthma, the authors said. They recommend that “hospitalized children with COVID-19 requiring supplemental oxygen or respiratory support should be considered for immunomodulatory therapy in addition to supportive care and antiviral medications.”

The authors acknowledged the limitations and evolving nature of the recommendations, which will continue to change and do not replace clinical judgment for the management of individual patients. In the meantime, the ACR will support the task force in reviewing new evidence and providing revised versions of the current document.

Many questions about MIS-C remain, Dr. Henderson said in an interview. “It can be very hard to diagnose children with MIS-C because many of the symptoms are similar to those seen in other febrile illness of childhood. We need to identify better biomarkers to help us make the diagnosis of MIS-C. In addition, we need studies to provide information about what treatments should be used if children fail to respond to IVIg and steroids. Finally, it appears that vaccination [against SARS-CoV-2] protects against severe forms of MIS-C, and studies are needed to see how vaccination protects children from MIS-C.”

The development of the guidance was supported by the American College of Rheumatology. Dr. Henderson disclosed relationships with companies including Sobi, Pfizer, and Adaptive Biotechnologies (less than $10,000) and research support from the Childhood Arthritis and Rheumatology Research Alliance and research grant support from Bristol-Myers Squibb.

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

Updated guidance for health care providers on multisystem inflammatory syndrome in children (MIS-C) recognizes the evolving nature of the disease and offers strategies for pediatric rheumatologists, who also may be asked to recommend treatment for hyperinflammation in children with acute COVID-19.

Guidance is needed for many reasons, including the variable case definitions for MIS-C, the presence of MIS-C features in other infections and childhood rheumatic diseases, the extrapolation of treatment strategies from other conditions with similar presentations, and the issue of myocardial dysfunction, wrote Lauren A. Henderson, MD, MMSC, of Boston Children’s Hospital, and members of the American College of Rheumatology MIS-C and COVID-19–Related Hyperinflammation Task Force.

However, “modifications to treatment plans, particularly in patients with complex conditions, are highly disease, patient, geography, and time specific, and therefore must be individualized as part of a shared decision-making process,” the authors said. The updated guidance was published in Arthritis & Rheumatology.
 

Update needed in wake of Omicron

“We continue to see cases of MIS-C across the United States due to the spike in SARS-CoV-2 infections from the Omicron variant,” and therefore updated guidance is important at this time, Dr. Henderson told this news organization.

“MIS-C remains a serious complication of COVID-19 in children and the ACR wanted to continue to provide pediatricians with up-to-date recommendations for the management of MIS-C,” she said.

“Children began to present with MIS-C in April 2020. At that time, little was known about this entity. Most of the recommendations in the first version of the MIS-C guidance were based on expert opinion,” she explained. However, “over the last 2 years, pediatricians have worked very hard to conduct high-quality research studies to better understand MIS-C, so we now have more scientific evidence to guide our recommendations.

“In version three of the MIS-C guidance, there are new recommendations on treatment. Previously, it was unclear what medications should be used for first-line treatment in patients with MIS-C. Some children were given intravenous immunoglobulin while others were given IVIg and steroids together. Several new studies show that children with MIS-C who are treated with a combination of IVIg and steroids have better outcomes. Accordingly, the MIS-C guidance now recommends dual therapy with IVIg and steroids in children with MIS-C.”

Diagnostic evaluation

The guidance calls for maintaining a broad differential diagnosis of MIS-C, given that the condition remains rare, and that most children with COVID-19 present with mild symptoms and have excellent outcomes, the authors noted. The range of clinical features associated with MIS-C include fever, mucocutaneous findings, myocardial dysfunction, cardiac conduction abnormalities, shock, gastrointestinal symptoms, and lymphadenopathy.

Some patients also experience neurologic involvement in the form of severe headache, altered mental status, seizures, cranial nerve palsies, meningismus, cerebral edema, and ischemic or hemorrhagic stroke. Given the nonspecific nature of these symptoms, “it is imperative that a diagnostic evaluation for MIS-C include investigation for other possible causes, as deemed appropriate by the treating provider,” the authors emphasized. Other diagnostic considerations include the prevalence and chronology of COVID-19 in the community, which may change over time.
 

MIS-C and Kawasaki disease phenotypes

Earlier in the pandemic, when MIS-C first emerged, it was compared with Kawasaki disease (KD). “However, a closer examination of the literature shows that only about one-quarter to half of patients with a reported diagnosis of MIS-C meet the full diagnostic criteria for KD,” the authors wrote. Key features that separate MIS-C from KD include the greater incidence of KD among children in Japan and East Asia versus the higher incidence of MIS-C among non-Hispanic Black children. In addition, children with MIS-C have shown a wider age range, more prominent gastrointestinal and neurologic symptoms, and more frequent cardiac dysfunction, compared with those with KD.

Cardiac management

Close follow-up with cardiology is essential for children with MIS-C, according to the authors. The recommendations call for repeat echocardiograms for all children with MIS-C at a minimum of 7-14 days, then again at 4-6 weeks after the initial presentation. The authors also recommended additional echocardiograms for children with left ventricular dysfunction and cardiac aortic aneurysms. 

MIS-C treatment

Current treatment recommendations emphasize that patients under investigation for MIS-C with life-threatening manifestations may need immunomodulatory therapy before a full diagnostic evaluation is complete, the authors said. However, patients without life-threatening manifestations should be evaluated before starting immunomodulatory treatment to avoid potentially harmful therapies for pediatric patients who don’t need them.

When MIS-C is refractory to initial immunomodulatory treatment, a second dose of IVIg is not recommended, but intensification therapy is advised with either high-dose (10-30 mg/kg per day) glucocorticoids, anakinra, or infliximab. However, there is little evidence available for selecting a specific agent for intensification therapy.

The task force also advises giving low-dose aspirin (3-5 mg/kg per day, up to 81 mg once daily) to all MIS-C patients without active bleeding or significant bleeding risk until normalization of the platelet count and confirmed normal coronary arteries at least 4 weeks after diagnosis.
 

COVID-19 and hyperinflammation

The task force also noted a distinction between MIS-C and severe COVID-19 in children. Although many children with MIS-C are previously healthy, most children who develop severe COVID-19 during an initial infection have complex conditions or comorbidities such as developmental delay or genetic anomaly, or chronic conditions such as congenital heart disease, type 1 diabetes, or asthma, the authors said. They recommend that “hospitalized children with COVID-19 requiring supplemental oxygen or respiratory support should be considered for immunomodulatory therapy in addition to supportive care and antiviral medications.”

The authors acknowledged the limitations and evolving nature of the recommendations, which will continue to change and do not replace clinical judgment for the management of individual patients. In the meantime, the ACR will support the task force in reviewing new evidence and providing revised versions of the current document.

Many questions about MIS-C remain, Dr. Henderson said in an interview. “It can be very hard to diagnose children with MIS-C because many of the symptoms are similar to those seen in other febrile illness of childhood. We need to identify better biomarkers to help us make the diagnosis of MIS-C. In addition, we need studies to provide information about what treatments should be used if children fail to respond to IVIg and steroids. Finally, it appears that vaccination [against SARS-CoV-2] protects against severe forms of MIS-C, and studies are needed to see how vaccination protects children from MIS-C.”

The development of the guidance was supported by the American College of Rheumatology. Dr. Henderson disclosed relationships with companies including Sobi, Pfizer, and Adaptive Biotechnologies (less than $10,000) and research support from the Childhood Arthritis and Rheumatology Research Alliance and research grant support from Bristol-Myers Squibb.

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

The Omicron subvariant, BA.2, is not only more transmissible than the original Omicron strain, BA.1, but may cause more severe disease, a lab study from Japan says.

“Our multiscale investigations suggest that the risk of BA.2 for global health is potentially higher than that of BA.1,” the researchers said in the study published on the preprint server bioRxiv. The study has not been peer-reviewed.

The researchers infected hamsters with BA.1 and BA.2. The hamsters infected with BA.2 got sicker, with more lung damage and loss of body weight. Results were similar when mice were infected with BA.1 and BA.2.

“Infection experiments using hamsters show that BA.2 is more pathogenic than BA.1,” the study said.

BA.1 and BA.2 both appear to evade immunity created by COVID-19 vaccines, the study said. But a booster shot makes illness after infection 74% less likely, CNN said.

What’s more, therapeutic monoclonal antibodies used to treat people infected with COVID didn’t have much effect on BA.2. 

BA.2 was “almost completely resistant” to casirivimab and imdevimab and was 35 times more resistant to sotrovimab, compared to the original B.1.1 virus, the researchers wrote. 

“In summary, our data suggest the possibility that BA.2 would be the most concerned variant to global health,” the researchers wrote. “Currently, both BA.2 and BA.1 are recognised together as Omicron and these are almost undistinguishable. Based on our findings, we propose that BA.2 should be recognised as a unique variant of concern, and this SARS-CoV-2 variant should be monitored in depth.”

If the World Health Organization recognized BA.2 as a “unique variant of concern,” it would be given its own Greek letter.

But some scientists noted that findings in the lab don’t always reflect what’s happening in the real world of people.

“I think it’s always hard to translate differences in animal and cell culture models to what’s going on with regards to human disease,” Jeremy Kamil, PhD, an associate professor of microbiology and immunology at Louisiana State University Health Shreveport, told Newsweek. “That said, the differences do look real.”

“It might be, from a human’s perspective, a worse virus than BA.1 and might be able to transmit better and cause worse disease,” Daniel Rhoads, MD, section head of microbiology at the Cleveland Clinic in Ohio, told CNN. He reviewed the Japanese study but was not involved in it.

Another scientist who reviewed the study but was not involved in the research noted that human immune systems are evolving along with the COVID variants. 

“One of the caveats that we have to think about, as we get new variants that might seem more dangerous, is the fact that there’s two sides to the story,” Deborah Fuller, PhD, a virologist at the University of Washington School of Medicine, told CNN. “Our immune system is evolving as well. And so that’s pushing back on things.”

Scientists have already established that BA.2 is more transmissible than BA.1. The Omicron subvariant has been detected in 74 countries and 47 U.S. states, according to CNN. About 4% of Americans with COVID were infected with BA.2, the outlet reported, citing the CDC, but it’s now the dominant strain in other nations.

It’s not clear yet if BA.2 causes more severe illness in people. While BA.2 spreads faster than BA.1, there’s no evidence the subvariant makes people any sicker, an official with the World Health Organization said, according to CNBC.

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

The Omicron subvariant, BA.2, is not only more transmissible than the original Omicron strain, BA.1, but may cause more severe disease, a lab study from Japan says.

“Our multiscale investigations suggest that the risk of BA.2 for global health is potentially higher than that of BA.1,” the researchers said in the study published on the preprint server bioRxiv. The study has not been peer-reviewed.

The researchers infected hamsters with BA.1 and BA.2. The hamsters infected with BA.2 got sicker, with more lung damage and loss of body weight. Results were similar when mice were infected with BA.1 and BA.2.

“Infection experiments using hamsters show that BA.2 is more pathogenic than BA.1,” the study said.

BA.1 and BA.2 both appear to evade immunity created by COVID-19 vaccines, the study said. But a booster shot makes illness after infection 74% less likely, CNN said.

What’s more, therapeutic monoclonal antibodies used to treat people infected with COVID didn’t have much effect on BA.2. 

BA.2 was “almost completely resistant” to casirivimab and imdevimab and was 35 times more resistant to sotrovimab, compared to the original B.1.1 virus, the researchers wrote. 

“In summary, our data suggest the possibility that BA.2 would be the most concerned variant to global health,” the researchers wrote. “Currently, both BA.2 and BA.1 are recognised together as Omicron and these are almost undistinguishable. Based on our findings, we propose that BA.2 should be recognised as a unique variant of concern, and this SARS-CoV-2 variant should be monitored in depth.”

If the World Health Organization recognized BA.2 as a “unique variant of concern,” it would be given its own Greek letter.

But some scientists noted that findings in the lab don’t always reflect what’s happening in the real world of people.

“I think it’s always hard to translate differences in animal and cell culture models to what’s going on with regards to human disease,” Jeremy Kamil, PhD, an associate professor of microbiology and immunology at Louisiana State University Health Shreveport, told Newsweek. “That said, the differences do look real.”

“It might be, from a human’s perspective, a worse virus than BA.1 and might be able to transmit better and cause worse disease,” Daniel Rhoads, MD, section head of microbiology at the Cleveland Clinic in Ohio, told CNN. He reviewed the Japanese study but was not involved in it.

Another scientist who reviewed the study but was not involved in the research noted that human immune systems are evolving along with the COVID variants. 

“One of the caveats that we have to think about, as we get new variants that might seem more dangerous, is the fact that there’s two sides to the story,” Deborah Fuller, PhD, a virologist at the University of Washington School of Medicine, told CNN. “Our immune system is evolving as well. And so that’s pushing back on things.”

Scientists have already established that BA.2 is more transmissible than BA.1. The Omicron subvariant has been detected in 74 countries and 47 U.S. states, according to CNN. About 4% of Americans with COVID were infected with BA.2, the outlet reported, citing the CDC, but it’s now the dominant strain in other nations.

It’s not clear yet if BA.2 causes more severe illness in people. While BA.2 spreads faster than BA.1, there’s no evidence the subvariant makes people any sicker, an official with the World Health Organization said, according to CNBC.

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

The Omicron subvariant, BA.2, is not only more transmissible than the original Omicron strain, BA.1, but may cause more severe disease, a lab study from Japan says.

“Our multiscale investigations suggest that the risk of BA.2 for global health is potentially higher than that of BA.1,” the researchers said in the study published on the preprint server bioRxiv. The study has not been peer-reviewed.

The researchers infected hamsters with BA.1 and BA.2. The hamsters infected with BA.2 got sicker, with more lung damage and loss of body weight. Results were similar when mice were infected with BA.1 and BA.2.

“Infection experiments using hamsters show that BA.2 is more pathogenic than BA.1,” the study said.

BA.1 and BA.2 both appear to evade immunity created by COVID-19 vaccines, the study said. But a booster shot makes illness after infection 74% less likely, CNN said.

What’s more, therapeutic monoclonal antibodies used to treat people infected with COVID didn’t have much effect on BA.2. 

BA.2 was “almost completely resistant” to casirivimab and imdevimab and was 35 times more resistant to sotrovimab, compared to the original B.1.1 virus, the researchers wrote. 

“In summary, our data suggest the possibility that BA.2 would be the most concerned variant to global health,” the researchers wrote. “Currently, both BA.2 and BA.1 are recognised together as Omicron and these are almost undistinguishable. Based on our findings, we propose that BA.2 should be recognised as a unique variant of concern, and this SARS-CoV-2 variant should be monitored in depth.”

If the World Health Organization recognized BA.2 as a “unique variant of concern,” it would be given its own Greek letter.

But some scientists noted that findings in the lab don’t always reflect what’s happening in the real world of people.

“I think it’s always hard to translate differences in animal and cell culture models to what’s going on with regards to human disease,” Jeremy Kamil, PhD, an associate professor of microbiology and immunology at Louisiana State University Health Shreveport, told Newsweek. “That said, the differences do look real.”

“It might be, from a human’s perspective, a worse virus than BA.1 and might be able to transmit better and cause worse disease,” Daniel Rhoads, MD, section head of microbiology at the Cleveland Clinic in Ohio, told CNN. He reviewed the Japanese study but was not involved in it.

Another scientist who reviewed the study but was not involved in the research noted that human immune systems are evolving along with the COVID variants. 

“One of the caveats that we have to think about, as we get new variants that might seem more dangerous, is the fact that there’s two sides to the story,” Deborah Fuller, PhD, a virologist at the University of Washington School of Medicine, told CNN. “Our immune system is evolving as well. And so that’s pushing back on things.”

Scientists have already established that BA.2 is more transmissible than BA.1. The Omicron subvariant has been detected in 74 countries and 47 U.S. states, according to CNN. About 4% of Americans with COVID were infected with BA.2, the outlet reported, citing the CDC, but it’s now the dominant strain in other nations.

It’s not clear yet if BA.2 causes more severe illness in people. While BA.2 spreads faster than BA.1, there’s no evidence the subvariant makes people any sicker, an official with the World Health Organization said, according to CNBC.

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

Two features are significantly associated with a higher risk for developing long COVID symptoms among people with inflammatory bowel disease (IBD), according to a large Danish population study.

People with Crohn’s disease (CD) who experienced adverse acute COVID-19, defined as requiring hospitalization, were nearly three times more likely to report persistent symptoms 12 weeks after acute infection.

“Long-term, persisting symptoms following COVID-19 is a frequently occurring problem, which is probably underappreciated. IBD specialists should therefore be aware of any of these symptoms and actively ask patients whether they have these problems,” lead author Mohamed Attauabi, MD, PhD, said in an interview.

Dr. Attauabi and colleagues also found that people with ulcerative colitis (UC) who discontinued immunosuppressive agents because of COVID-19 were 1.5 times more likely to experience long COVID symptoms, a result that surprised the researchers.

“This has not been shown before and remains to be confirmed,” said Dr. Attauabi, a fellow in the department of gastroenterology at Herlev Hospital at the University of Copenhagen.

Attauabi presented the results as a digital oral presentation at the 17th congress of the European Crohn’s and Colitis Organisation.
 

A closer look at IBD and COVID-19

Large, hospital-based studies of symptoms consistent with long COVID reveal a high prevalence of fatigue, sleep difficulties, and anxiety at 12 weeks or more post acute infection. However, these were not specific to people with CD or UC, Dr. Attauabi said.

“In patients with IBD, the risk of long-term sequelae of COVID-19 remains to be investigated,” he said.

Dr. Attauabi and colleagues studied 197 people with CD and 319 with UC, all of whom had polymerase chain reaction–confirmed COVID-19. Participants were prospectively enrolled in the population-based Danish IBD-COVID registry from January 28, 2020 to April 1, 2021. At a median of 5.1 months, a subset of 85 people with CD and 137 with UC agreed to report any post-COVID symptoms.

Older age, smoking, IBD disease activity, and presence of comorbidities were not associated with a significantly elevated risk of long COVID.

In a multivariate analysis, hospitalization for COVID-19 among people with CD was significantly associated with long COVID (odds ratio, 2.76; 95% confidence interval, 1.05-3.90; P = .04).

Furthermore, people with UC who stopped taking immunosuppressive agents also had a significantly higher risk (OR, 1.50; 95% CI, 1.07-10.22; P = .01).

“However, IBD medications such as systemic steroids were not associated with this outcome,” Dr. Attauabi said.
 

Fatigue most common long COVID symptom

Fatigue was the most common long COVID symptom, reported by 37% of patients with CD and 36% with UC.

Anosmia and ageusia were also common, reported by 29% and 28% of patients with CD, and 27% and 19% of those with UC, respectively.

“In our cohort of patients with UC or CD who developed COVID-19, the long-term health effects of COVID-19 did not appear to differ among patients with UC or CD nor according to IBD medications,” Dr. Attauabi said.

That is a “great study,” said session cochair Torsten Kucharzik, MD, PhD, head of internal medicine and gastroenterology at Lueneburg (Germany) Hospital.

When Dr. Kucharzik asked about smoking, Dr. Attauabi responded that they collected information on current and previous smoking, but they chose not to include the data because it was not statistically significant.

Dr. Attauabi has reported no relevant financial relationships. Dr. Kucharzik has reported receiving grants from Takeda and personal fees from companies including MSD/Essex, AbbVie, Falk Foundation, Biogen, Bristol-Myers Squibb, Arena, Celgene, Celltrion, Ferring, Janssen, Galapagos, Olympus, Mundipharma, Takeda, Amgen, Pfizer, Roche, and Vifor Pharma.

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

Two features are significantly associated with a higher risk for developing long COVID symptoms among people with inflammatory bowel disease (IBD), according to a large Danish population study.

People with Crohn’s disease (CD) who experienced adverse acute COVID-19, defined as requiring hospitalization, were nearly three times more likely to report persistent symptoms 12 weeks after acute infection.

“Long-term, persisting symptoms following COVID-19 is a frequently occurring problem, which is probably underappreciated. IBD specialists should therefore be aware of any of these symptoms and actively ask patients whether they have these problems,” lead author Mohamed Attauabi, MD, PhD, said in an interview.

Dr. Attauabi and colleagues also found that people with ulcerative colitis (UC) who discontinued immunosuppressive agents because of COVID-19 were 1.5 times more likely to experience long COVID symptoms, a result that surprised the researchers.

“This has not been shown before and remains to be confirmed,” said Dr. Attauabi, a fellow in the department of gastroenterology at Herlev Hospital at the University of Copenhagen.

Attauabi presented the results as a digital oral presentation at the 17th congress of the European Crohn’s and Colitis Organisation.
 

A closer look at IBD and COVID-19

Large, hospital-based studies of symptoms consistent with long COVID reveal a high prevalence of fatigue, sleep difficulties, and anxiety at 12 weeks or more post acute infection. However, these were not specific to people with CD or UC, Dr. Attauabi said.

“In patients with IBD, the risk of long-term sequelae of COVID-19 remains to be investigated,” he said.

Dr. Attauabi and colleagues studied 197 people with CD and 319 with UC, all of whom had polymerase chain reaction–confirmed COVID-19. Participants were prospectively enrolled in the population-based Danish IBD-COVID registry from January 28, 2020 to April 1, 2021. At a median of 5.1 months, a subset of 85 people with CD and 137 with UC agreed to report any post-COVID symptoms.

Older age, smoking, IBD disease activity, and presence of comorbidities were not associated with a significantly elevated risk of long COVID.

In a multivariate analysis, hospitalization for COVID-19 among people with CD was significantly associated with long COVID (odds ratio, 2.76; 95% confidence interval, 1.05-3.90; P = .04).

Furthermore, people with UC who stopped taking immunosuppressive agents also had a significantly higher risk (OR, 1.50; 95% CI, 1.07-10.22; P = .01).

“However, IBD medications such as systemic steroids were not associated with this outcome,” Dr. Attauabi said.
 

Fatigue most common long COVID symptom

Fatigue was the most common long COVID symptom, reported by 37% of patients with CD and 36% with UC.

Anosmia and ageusia were also common, reported by 29% and 28% of patients with CD, and 27% and 19% of those with UC, respectively.

“In our cohort of patients with UC or CD who developed COVID-19, the long-term health effects of COVID-19 did not appear to differ among patients with UC or CD nor according to IBD medications,” Dr. Attauabi said.

That is a “great study,” said session cochair Torsten Kucharzik, MD, PhD, head of internal medicine and gastroenterology at Lueneburg (Germany) Hospital.

When Dr. Kucharzik asked about smoking, Dr. Attauabi responded that they collected information on current and previous smoking, but they chose not to include the data because it was not statistically significant.

Dr. Attauabi has reported no relevant financial relationships. Dr. Kucharzik has reported receiving grants from Takeda and personal fees from companies including MSD/Essex, AbbVie, Falk Foundation, Biogen, Bristol-Myers Squibb, Arena, Celgene, Celltrion, Ferring, Janssen, Galapagos, Olympus, Mundipharma, Takeda, Amgen, Pfizer, Roche, and Vifor Pharma.

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

Two features are significantly associated with a higher risk for developing long COVID symptoms among people with inflammatory bowel disease (IBD), according to a large Danish population study.

People with Crohn’s disease (CD) who experienced adverse acute COVID-19, defined as requiring hospitalization, were nearly three times more likely to report persistent symptoms 12 weeks after acute infection.

“Long-term, persisting symptoms following COVID-19 is a frequently occurring problem, which is probably underappreciated. IBD specialists should therefore be aware of any of these symptoms and actively ask patients whether they have these problems,” lead author Mohamed Attauabi, MD, PhD, said in an interview.

Dr. Attauabi and colleagues also found that people with ulcerative colitis (UC) who discontinued immunosuppressive agents because of COVID-19 were 1.5 times more likely to experience long COVID symptoms, a result that surprised the researchers.

“This has not been shown before and remains to be confirmed,” said Dr. Attauabi, a fellow in the department of gastroenterology at Herlev Hospital at the University of Copenhagen.

Attauabi presented the results as a digital oral presentation at the 17th congress of the European Crohn’s and Colitis Organisation.
 

A closer look at IBD and COVID-19

Large, hospital-based studies of symptoms consistent with long COVID reveal a high prevalence of fatigue, sleep difficulties, and anxiety at 12 weeks or more post acute infection. However, these were not specific to people with CD or UC, Dr. Attauabi said.

“In patients with IBD, the risk of long-term sequelae of COVID-19 remains to be investigated,” he said.

Dr. Attauabi and colleagues studied 197 people with CD and 319 with UC, all of whom had polymerase chain reaction–confirmed COVID-19. Participants were prospectively enrolled in the population-based Danish IBD-COVID registry from January 28, 2020 to April 1, 2021. At a median of 5.1 months, a subset of 85 people with CD and 137 with UC agreed to report any post-COVID symptoms.

Older age, smoking, IBD disease activity, and presence of comorbidities were not associated with a significantly elevated risk of long COVID.

In a multivariate analysis, hospitalization for COVID-19 among people with CD was significantly associated with long COVID (odds ratio, 2.76; 95% confidence interval, 1.05-3.90; P = .04).

Furthermore, people with UC who stopped taking immunosuppressive agents also had a significantly higher risk (OR, 1.50; 95% CI, 1.07-10.22; P = .01).

“However, IBD medications such as systemic steroids were not associated with this outcome,” Dr. Attauabi said.
 

Fatigue most common long COVID symptom

Fatigue was the most common long COVID symptom, reported by 37% of patients with CD and 36% with UC.

Anosmia and ageusia were also common, reported by 29% and 28% of patients with CD, and 27% and 19% of those with UC, respectively.

“In our cohort of patients with UC or CD who developed COVID-19, the long-term health effects of COVID-19 did not appear to differ among patients with UC or CD nor according to IBD medications,” Dr. Attauabi said.

That is a “great study,” said session cochair Torsten Kucharzik, MD, PhD, head of internal medicine and gastroenterology at Lueneburg (Germany) Hospital.

When Dr. Kucharzik asked about smoking, Dr. Attauabi responded that they collected information on current and previous smoking, but they chose not to include the data because it was not statistically significant.

Dr. Attauabi has reported no relevant financial relationships. Dr. Kucharzik has reported receiving grants from Takeda and personal fees from companies including MSD/Essex, AbbVie, Falk Foundation, Biogen, Bristol-Myers Squibb, Arena, Celgene, Celltrion, Ferring, Janssen, Galapagos, Olympus, Mundipharma, Takeda, Amgen, Pfizer, Roche, and Vifor Pharma.

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

Ivermectin treatment given to high-risk patients with mild-to-moderate COVID-19 during the first week of illness did not prevent progression to severe disease, according to results from a randomized clinical trial.

“The study findings do not support the use of ivermectin for patients with COVID-19,” researchers conclude in the paper published online in JAMA Internal Medicine.

The open-label trial was conducted at 20 public hospitals and a COVID-19 quarantine center in Malaysia between May 31 and Oct. 25, 2021. It was led by Steven Chee Loon Lim, MRCP, department of medicine, Raja Permaisuri Bainun Hospital, Perak, Malaysia.

Among 490 patients in the primary analysis, 52 of 241 patients (21.6%) in the ivermectin group and 43 of 249 patients (17.3%) in the control group progressed to severe disease (relative risk, 1.25; 95% confidence interval, 0.87-1.80; P = .25). All major ethnic groups in Malaysia were well represented, the researchers write.

Participants (average age 62.5 and 54.5% women) were randomly assigned 1:1 to receive either a 5-day course of oral ivermectin (0.4 mg/kg body weight daily for 5 days) plus standard of care (n = 241) or standard of care alone (n = 249). Standard of care included symptomatic therapy and monitoring for early deterioration based on clinical findings, laboratory tests, and chest imaging.
 

Secondary outcomes

Secondary outcomes included rates of mechanical ventilation, intensive care unit (ICU) admission, 28-day in-hospital mortality, and side effects.

In all the secondary outcomes, there were no significant differences between groups.

Mechanical ventilation occurred in four patients on the ivermectin protocol (1.7%) versus 10 patients in the control group (4.0%) (RR, 0.41; 95% CI, 0.13-1.30; P = .17); ICU admission occurred in six (2.4%) versus eight (3.2%) (RR, 0.78; 95% CI, 0.27-2.20; P = .79); and 28-day in-hospital death occurred in three (1.2%) versus 10 (4.0%) (RR, 0.31; 95% CI, 0.09-1.11; P = .09).

The most common adverse event was diarrhea, reported by 5.8% in the ivermectin group and 1.6% in the control group.
 

No difference by vaccine status

The researchers conducted a subgroup analysis to evaluate any differences in whether participants were vaccinated. They said that analysis was “unremarkable.”

Just more than half of participants (51.8%) were fully vaccinated, with two doses of COVID-19 vaccines. Among the fully vaccinated patients, 17.7% in the ivermectin group and 9.2% in the control group developed severe disease (RR, 1.92; 95% CI, 0.99-3.71; P = .06).

Ivermectin, an inexpensive and widely available antiparasitic drug, is prescribed to treat COVID-19 but has not been approved by the U.S. Food and Drug Administration for that purpose. Evidence-based data for or against use has been sparse.

The authors write that “although some early clinical studies suggested the potential efficacy of ivermectin in the treatment and prevention of COVID-19, these studies had methodologic weaknesses.”

Dr. Lim and colleagues point out that their findings are consistent with those of the IVERCOR-COVID19 trial, which found ivermectin ineffective in reducing hospitalization risk.

Previous randomized trials of ivermectin for COVID-19 patients that have included at least 400 patients have focused on outpatients.

In the current study, the authors note, patients were hospitalized, which allowed investigators to observe administration of ivermectin with a high adherence rate. Additionally, the researchers used clearly defined criteria for determining progression to severe disease.

Limitations of the current study include that the open-label design might lead to under-reporting of adverse events in the control group while overestimating the drug effects of ivermectin. The study was also not designed to assess the effects of ivermectin on mortality from COVID-19.

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

Ivermectin treatment given to high-risk patients with mild-to-moderate COVID-19 during the first week of illness did not prevent progression to severe disease, according to results from a randomized clinical trial.

“The study findings do not support the use of ivermectin for patients with COVID-19,” researchers conclude in the paper published online in JAMA Internal Medicine.

The open-label trial was conducted at 20 public hospitals and a COVID-19 quarantine center in Malaysia between May 31 and Oct. 25, 2021. It was led by Steven Chee Loon Lim, MRCP, department of medicine, Raja Permaisuri Bainun Hospital, Perak, Malaysia.

Among 490 patients in the primary analysis, 52 of 241 patients (21.6%) in the ivermectin group and 43 of 249 patients (17.3%) in the control group progressed to severe disease (relative risk, 1.25; 95% confidence interval, 0.87-1.80; P = .25). All major ethnic groups in Malaysia were well represented, the researchers write.

Participants (average age 62.5 and 54.5% women) were randomly assigned 1:1 to receive either a 5-day course of oral ivermectin (0.4 mg/kg body weight daily for 5 days) plus standard of care (n = 241) or standard of care alone (n = 249). Standard of care included symptomatic therapy and monitoring for early deterioration based on clinical findings, laboratory tests, and chest imaging.
 

Secondary outcomes

Secondary outcomes included rates of mechanical ventilation, intensive care unit (ICU) admission, 28-day in-hospital mortality, and side effects.

In all the secondary outcomes, there were no significant differences between groups.

Mechanical ventilation occurred in four patients on the ivermectin protocol (1.7%) versus 10 patients in the control group (4.0%) (RR, 0.41; 95% CI, 0.13-1.30; P = .17); ICU admission occurred in six (2.4%) versus eight (3.2%) (RR, 0.78; 95% CI, 0.27-2.20; P = .79); and 28-day in-hospital death occurred in three (1.2%) versus 10 (4.0%) (RR, 0.31; 95% CI, 0.09-1.11; P = .09).

The most common adverse event was diarrhea, reported by 5.8% in the ivermectin group and 1.6% in the control group.
 

No difference by vaccine status

The researchers conducted a subgroup analysis to evaluate any differences in whether participants were vaccinated. They said that analysis was “unremarkable.”

Just more than half of participants (51.8%) were fully vaccinated, with two doses of COVID-19 vaccines. Among the fully vaccinated patients, 17.7% in the ivermectin group and 9.2% in the control group developed severe disease (RR, 1.92; 95% CI, 0.99-3.71; P = .06).

Ivermectin, an inexpensive and widely available antiparasitic drug, is prescribed to treat COVID-19 but has not been approved by the U.S. Food and Drug Administration for that purpose. Evidence-based data for or against use has been sparse.

The authors write that “although some early clinical studies suggested the potential efficacy of ivermectin in the treatment and prevention of COVID-19, these studies had methodologic weaknesses.”

Dr. Lim and colleagues point out that their findings are consistent with those of the IVERCOR-COVID19 trial, which found ivermectin ineffective in reducing hospitalization risk.

Previous randomized trials of ivermectin for COVID-19 patients that have included at least 400 patients have focused on outpatients.

In the current study, the authors note, patients were hospitalized, which allowed investigators to observe administration of ivermectin with a high adherence rate. Additionally, the researchers used clearly defined criteria for determining progression to severe disease.

Limitations of the current study include that the open-label design might lead to under-reporting of adverse events in the control group while overestimating the drug effects of ivermectin. The study was also not designed to assess the effects of ivermectin on mortality from COVID-19.

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

Ivermectin treatment given to high-risk patients with mild-to-moderate COVID-19 during the first week of illness did not prevent progression to severe disease, according to results from a randomized clinical trial.

“The study findings do not support the use of ivermectin for patients with COVID-19,” researchers conclude in the paper published online in JAMA Internal Medicine.

The open-label trial was conducted at 20 public hospitals and a COVID-19 quarantine center in Malaysia between May 31 and Oct. 25, 2021. It was led by Steven Chee Loon Lim, MRCP, department of medicine, Raja Permaisuri Bainun Hospital, Perak, Malaysia.

Among 490 patients in the primary analysis, 52 of 241 patients (21.6%) in the ivermectin group and 43 of 249 patients (17.3%) in the control group progressed to severe disease (relative risk, 1.25; 95% confidence interval, 0.87-1.80; P = .25). All major ethnic groups in Malaysia were well represented, the researchers write.

Participants (average age 62.5 and 54.5% women) were randomly assigned 1:1 to receive either a 5-day course of oral ivermectin (0.4 mg/kg body weight daily for 5 days) plus standard of care (n = 241) or standard of care alone (n = 249). Standard of care included symptomatic therapy and monitoring for early deterioration based on clinical findings, laboratory tests, and chest imaging.
 

Secondary outcomes

Secondary outcomes included rates of mechanical ventilation, intensive care unit (ICU) admission, 28-day in-hospital mortality, and side effects.

In all the secondary outcomes, there were no significant differences between groups.

Mechanical ventilation occurred in four patients on the ivermectin protocol (1.7%) versus 10 patients in the control group (4.0%) (RR, 0.41; 95% CI, 0.13-1.30; P = .17); ICU admission occurred in six (2.4%) versus eight (3.2%) (RR, 0.78; 95% CI, 0.27-2.20; P = .79); and 28-day in-hospital death occurred in three (1.2%) versus 10 (4.0%) (RR, 0.31; 95% CI, 0.09-1.11; P = .09).

The most common adverse event was diarrhea, reported by 5.8% in the ivermectin group and 1.6% in the control group.
 

No difference by vaccine status

The researchers conducted a subgroup analysis to evaluate any differences in whether participants were vaccinated. They said that analysis was “unremarkable.”

Just more than half of participants (51.8%) were fully vaccinated, with two doses of COVID-19 vaccines. Among the fully vaccinated patients, 17.7% in the ivermectin group and 9.2% in the control group developed severe disease (RR, 1.92; 95% CI, 0.99-3.71; P = .06).

Ivermectin, an inexpensive and widely available antiparasitic drug, is prescribed to treat COVID-19 but has not been approved by the U.S. Food and Drug Administration for that purpose. Evidence-based data for or against use has been sparse.

The authors write that “although some early clinical studies suggested the potential efficacy of ivermectin in the treatment and prevention of COVID-19, these studies had methodologic weaknesses.”

Dr. Lim and colleagues point out that their findings are consistent with those of the IVERCOR-COVID19 trial, which found ivermectin ineffective in reducing hospitalization risk.

Previous randomized trials of ivermectin for COVID-19 patients that have included at least 400 patients have focused on outpatients.

In the current study, the authors note, patients were hospitalized, which allowed investigators to observe administration of ivermectin with a high adherence rate. Additionally, the researchers used clearly defined criteria for determining progression to severe disease.

Limitations of the current study include that the open-label design might lead to under-reporting of adverse events in the control group while overestimating the drug effects of ivermectin. The study was also not designed to assess the effects of ivermectin on mortality from COVID-19.

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

Researchers point the finger squarely at starting salaries for physicians as the reason women earn less than their male peers in academic medicine, according to a new study. Worse still, the earning potential of women in most specialties is $214,440 (or 10%) less than their male colleagues over the course of the first 10 years of their careers in academic medicine.

Among the vast majority of subspecialties, women’s starting salaries and their salaries 10 years into their careers were lower than their male colleagues in academic medicine, per the study in JAMA Network Open.

Eva Catenaccio, MD, an epilepsy fellow at Children’s Hospital of Philadelphia and the lead author of the study, told this news organization that the gender disparities in earning potential are “pervasive in academic medicine.” These earnings disparities, which occur in nearly all subspecialties and can reach hundreds of thousands of dollars in the first 10 years of an academic physician’s career, “are largely the result of gender differences in annual salary that start immediately after training,” she said.

Changing the timing of academic promotion and equalizing starting salary and salary growth can help close the salary gap, said Dr. Catenaccio.

The study also reveals that women could face a 1-year delay in promotion from assistant to associate professor, compared with men. This delay could reduce female physicians’ earning potential by a 10-year median of $26,042 (or 2%), whereas failure to be promoted at all could decrease the 10-year earning potential by a median of $218,724 (or 13%).

Across medicine more broadly, male physicians continue to earn 35% more than their female colleagues, according to the 2021 Medscape Physician Compensation Report. The biggest differences in take-home pay exist between male and female specialists, per the report. On average, male physicians earn $376,000, while women’s take-home pay is $283,000.
 

Medical schools and hospital leaders have a role to play

The earning potential during the first 10 years of post-training employment by gender was the most dramatic in neurosurgery, orthopedic surgery, and cardiology, per the study. Three subspecialties where women and men have similar earning potential include pediatric nephrology, pediatric neurology, and pediatric rheumatology.

The coauthors note that it’s commonly understood that women don’t negotiate as often or as successfully as their male colleagues. A 2019 study in JAMA Surgery of 606 male and female surgery residents revealed that while residents of both genders shared similar career goals, women had lower future salary expectations and a significantly more negative view of the salary negotiation process.

Dr. Catenaccio and her coauthors acknowledge that negotiation skills and financial literacy should be taught during medical school and postgraduate training. “However, the onus for ensuring salary equity should not fall on the individual candidate alone; rather, departmental and hospital leadership should take responsibility to ensure uniform starting salaries and prevent gender-based inequalities,” they wrote in the study.

“We hope that this study encourages academic medical institutions to increase transparency and equity around compensation, particularly for junior faculty,” Dr. Catenaccio said in an interview. “This will require both ensuring equal starting salaries and providing periodic adjustments throughout individuals’ careers to prevent divergence in earning potential by gender or any other individual characteristics.”

Harold Simon, MD, MBA, vice chair for faculty for the department of pediatrics and professor of pediatrics and emergency medicine at Emory University, Atlanta, told this news organization that “[i]ncreased transparency around compensation can enable women to advocate for equitable pay. However, the burden for ensuring equity should not fall on individuals but instead must be the primary responsibility of academic institutions.”

Specifically, Dr. Simon advocates for hospital leaders to “ensure equity among providers including compensation [as] a crucial part of maintaining a diverse workforce and, ultimately, providing balanced access to health care for patients.”

In addition, the authors call for periodic compensation evaluations and adjustments to help prevent gender-based salary differences among female and male physicians in academia. “This is absolutely necessary, both to develop future compensation plans and to address any pre-existing gender-based salary inequities for those women currently well into their careers,” they wrote in the study.

Data analysis was conducted from March to May 2021. Researchers used models to estimate the impacts of promotion timing and potential interventions, which include equalizing starting salaries and annual salary rates.

The study included compensation data for 24,593 female and 29,886 male academic physicians across 45 subspecialties. It relied on publicly available data from the Association of American Medical Colleges’ annual Medical School Faculty Salary Survey report.

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

Researchers point the finger squarely at starting salaries for physicians as the reason women earn less than their male peers in academic medicine, according to a new study. Worse still, the earning potential of women in most specialties is $214,440 (or 10%) less than their male colleagues over the course of the first 10 years of their careers in academic medicine.

Among the vast majority of subspecialties, women’s starting salaries and their salaries 10 years into their careers were lower than their male colleagues in academic medicine, per the study in JAMA Network Open.

Eva Catenaccio, MD, an epilepsy fellow at Children’s Hospital of Philadelphia and the lead author of the study, told this news organization that the gender disparities in earning potential are “pervasive in academic medicine.” These earnings disparities, which occur in nearly all subspecialties and can reach hundreds of thousands of dollars in the first 10 years of an academic physician’s career, “are largely the result of gender differences in annual salary that start immediately after training,” she said.

Changing the timing of academic promotion and equalizing starting salary and salary growth can help close the salary gap, said Dr. Catenaccio.

The study also reveals that women could face a 1-year delay in promotion from assistant to associate professor, compared with men. This delay could reduce female physicians’ earning potential by a 10-year median of $26,042 (or 2%), whereas failure to be promoted at all could decrease the 10-year earning potential by a median of $218,724 (or 13%).

Across medicine more broadly, male physicians continue to earn 35% more than their female colleagues, according to the 2021 Medscape Physician Compensation Report. The biggest differences in take-home pay exist between male and female specialists, per the report. On average, male physicians earn $376,000, while women’s take-home pay is $283,000.
 

Medical schools and hospital leaders have a role to play

The earning potential during the first 10 years of post-training employment by gender was the most dramatic in neurosurgery, orthopedic surgery, and cardiology, per the study. Three subspecialties where women and men have similar earning potential include pediatric nephrology, pediatric neurology, and pediatric rheumatology.

The coauthors note that it’s commonly understood that women don’t negotiate as often or as successfully as their male colleagues. A 2019 study in JAMA Surgery of 606 male and female surgery residents revealed that while residents of both genders shared similar career goals, women had lower future salary expectations and a significantly more negative view of the salary negotiation process.

Dr. Catenaccio and her coauthors acknowledge that negotiation skills and financial literacy should be taught during medical school and postgraduate training. “However, the onus for ensuring salary equity should not fall on the individual candidate alone; rather, departmental and hospital leadership should take responsibility to ensure uniform starting salaries and prevent gender-based inequalities,” they wrote in the study.

“We hope that this study encourages academic medical institutions to increase transparency and equity around compensation, particularly for junior faculty,” Dr. Catenaccio said in an interview. “This will require both ensuring equal starting salaries and providing periodic adjustments throughout individuals’ careers to prevent divergence in earning potential by gender or any other individual characteristics.”

Harold Simon, MD, MBA, vice chair for faculty for the department of pediatrics and professor of pediatrics and emergency medicine at Emory University, Atlanta, told this news organization that “[i]ncreased transparency around compensation can enable women to advocate for equitable pay. However, the burden for ensuring equity should not fall on individuals but instead must be the primary responsibility of academic institutions.”

Specifically, Dr. Simon advocates for hospital leaders to “ensure equity among providers including compensation [as] a crucial part of maintaining a diverse workforce and, ultimately, providing balanced access to health care for patients.”

In addition, the authors call for periodic compensation evaluations and adjustments to help prevent gender-based salary differences among female and male physicians in academia. “This is absolutely necessary, both to develop future compensation plans and to address any pre-existing gender-based salary inequities for those women currently well into their careers,” they wrote in the study.

Data analysis was conducted from March to May 2021. Researchers used models to estimate the impacts of promotion timing and potential interventions, which include equalizing starting salaries and annual salary rates.

The study included compensation data for 24,593 female and 29,886 male academic physicians across 45 subspecialties. It relied on publicly available data from the Association of American Medical Colleges’ annual Medical School Faculty Salary Survey report.

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

Researchers point the finger squarely at starting salaries for physicians as the reason women earn less than their male peers in academic medicine, according to a new study. Worse still, the earning potential of women in most specialties is $214,440 (or 10%) less than their male colleagues over the course of the first 10 years of their careers in academic medicine.

Among the vast majority of subspecialties, women’s starting salaries and their salaries 10 years into their careers were lower than their male colleagues in academic medicine, per the study in JAMA Network Open.

Eva Catenaccio, MD, an epilepsy fellow at Children’s Hospital of Philadelphia and the lead author of the study, told this news organization that the gender disparities in earning potential are “pervasive in academic medicine.” These earnings disparities, which occur in nearly all subspecialties and can reach hundreds of thousands of dollars in the first 10 years of an academic physician’s career, “are largely the result of gender differences in annual salary that start immediately after training,” she said.

Changing the timing of academic promotion and equalizing starting salary and salary growth can help close the salary gap, said Dr. Catenaccio.

The study also reveals that women could face a 1-year delay in promotion from assistant to associate professor, compared with men. This delay could reduce female physicians’ earning potential by a 10-year median of $26,042 (or 2%), whereas failure to be promoted at all could decrease the 10-year earning potential by a median of $218,724 (or 13%).

Across medicine more broadly, male physicians continue to earn 35% more than their female colleagues, according to the 2021 Medscape Physician Compensation Report. The biggest differences in take-home pay exist between male and female specialists, per the report. On average, male physicians earn $376,000, while women’s take-home pay is $283,000.
 

Medical schools and hospital leaders have a role to play

The earning potential during the first 10 years of post-training employment by gender was the most dramatic in neurosurgery, orthopedic surgery, and cardiology, per the study. Three subspecialties where women and men have similar earning potential include pediatric nephrology, pediatric neurology, and pediatric rheumatology.

The coauthors note that it’s commonly understood that women don’t negotiate as often or as successfully as their male colleagues. A 2019 study in JAMA Surgery of 606 male and female surgery residents revealed that while residents of both genders shared similar career goals, women had lower future salary expectations and a significantly more negative view of the salary negotiation process.

Dr. Catenaccio and her coauthors acknowledge that negotiation skills and financial literacy should be taught during medical school and postgraduate training. “However, the onus for ensuring salary equity should not fall on the individual candidate alone; rather, departmental and hospital leadership should take responsibility to ensure uniform starting salaries and prevent gender-based inequalities,” they wrote in the study.

“We hope that this study encourages academic medical institutions to increase transparency and equity around compensation, particularly for junior faculty,” Dr. Catenaccio said in an interview. “This will require both ensuring equal starting salaries and providing periodic adjustments throughout individuals’ careers to prevent divergence in earning potential by gender or any other individual characteristics.”

Harold Simon, MD, MBA, vice chair for faculty for the department of pediatrics and professor of pediatrics and emergency medicine at Emory University, Atlanta, told this news organization that “[i]ncreased transparency around compensation can enable women to advocate for equitable pay. However, the burden for ensuring equity should not fall on individuals but instead must be the primary responsibility of academic institutions.”

Specifically, Dr. Simon advocates for hospital leaders to “ensure equity among providers including compensation [as] a crucial part of maintaining a diverse workforce and, ultimately, providing balanced access to health care for patients.”

In addition, the authors call for periodic compensation evaluations and adjustments to help prevent gender-based salary differences among female and male physicians in academia. “This is absolutely necessary, both to develop future compensation plans and to address any pre-existing gender-based salary inequities for those women currently well into their careers,” they wrote in the study.

Data analysis was conducted from March to May 2021. Researchers used models to estimate the impacts of promotion timing and potential interventions, which include equalizing starting salaries and annual salary rates.

The study included compensation data for 24,593 female and 29,886 male academic physicians across 45 subspecialties. It relied on publicly available data from the Association of American Medical Colleges’ annual Medical School Faculty Salary Survey report.

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

LAS VEGAS – In the opinion of Christoph U. Correll, MD, tardive dyskinesia (TD) “has been somewhat forgotten” by psychiatrists because the risk of patients developing the condition is considered to be significantly lower with second-generation antipsychotics compared with first-generation antipsychotics.

“But this does not seem to always be the case, because there is still a risk of TD, and we need to monitor for it,” Dr. Correll, professor of psychiatry and molecular medicine at The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “It is important to minimize the risk of TD by educating patients and caregivers about the risks of and alternatives to antipsychotic medication and early signs of TD.”

First described in 1957, TD is characterized by involuntary repetitive but irregular movements, mostly in the oral, lingual, and buccal regions – such as tongue protruding, puckering, chewing, and grimacing. Less often, there are movements in the hands, legs, feet, and torso. Symptoms can include mannerisms, stereotypies, tics, myoclonus, dystonias, tremor, and akathisia. “TD can be severe, persistent, and have medical and psychosocial consequences,” Dr. Correll said. “It can occur in untreated patients, but treatment with dopamine blocking agents – antipsychotics and metoclopramide – increases risk for TD.”

Differential diagnoses to consider include morbus Huntington, benign familial Chorea, and Sydenham’s Chorea. Less frequent causes of TD include metabolic conditions such as uremia, hyponatremia, hypernatremia, hypoparathyroidism, and hyperparathyroidism. “Those would need to be ruled out during the physical exam,” he said. There can also be inflammatory causes of TD such as herpes simplex virus, varicella, measles, mumps, and rubella.

A standard measure for TD diagnosis is the Abnormal Involuntary Movement Scale (AIMS), an observer-rated 12-item anchored scale that takes 5-10 minutes to administer. However, the AIMS on its own does not diagnose TD. In 1982, researchers developed three diagnostic criteria for TD: At least 3 months of cumulative antipsychotic drug exposure; presence of at least moderate abnormal involuntary movements in one or more body area(s) or mild movements in two or more body areas, and absence of other conditions that might produce involuntary movements (Arch Gen Psychiatry 1982;39:486-7).

The impact of TD on everyday functioning depends on anatomic location as well as severity, Dr. Correll continued. The condition can cause impairments to speech, verbal communication, dentition, temporomandibular joint pain/myalgia, swallowing difficulties, and fine motor skills including instrumental activities of daily living and written communication. Truncal and lower extremity TD can affect gait, posture and postural stability, strength, power flexibility, physical capacity, and one’s ability to exercise. “There are also psychological impairments,” he said. “Patients can develop different awareness so they become self-conscious; there can be cognitive abnormalities, and they can become more anxious or [have an] increased sense of paranoia, isolation, stigma, social and/or educational/vocational impairment.”

According to research by Dr. Correll and colleagues, unmodifiable patient-related risk factors for TD include older age, female sex, and being of white or African descent (J Neurol Sci 2018 June 15; 389:21-7). Unmodifiable illness-related risk factors include longer duration of illness, intellectual disability and brain damage, negative symptoms in schizophrenia, mood disorders, cognitive symptoms in mood disorders, and gene polymorphisms involving antipsychotic metabolism and dopamine functioning. Modifiable comorbidity-related factors include diabetes, smoking, and alcohol/substance abuse, while modifiable treatment-related factors include dopamine receptor blockers, higher cumulative and current antipsychotic dose or plasma levels, early parkinsonian side effects, treatment-emergent akathisia, and anticholinergic co-treatment. In a meta-analysis of 41 studies that aimed to determine the prevalence of TD, the mean age of the 11,493 patients was 43, 66% were male, and 77% had schizophrenia spectrum disorders (J Clin Psychiatry. 2017 Mar;78[3]:e264-78). The global mean TD prevalence was 25%, but the rates were lower with patients on current treatment with second-generation antipsychotics compared with those on first-generation antipsychotics (21% vs. 30%, respectively).

According to Dr. Correll, strategies for preventing TD include confirming and documenting the indication for dopamine antagonist antipsychotic medications, using conservative maintenance doses, and considering the use of SGAs, especially in those at high risk for EPS (extrapyramidal symptoms). “Don’t go too high [with the dose],” he said. “Stay below the EPS threshold. Inform patients and caregivers of the risk of TD and assess for incipient signs regularly using the AIMS.”

Treatment options include discontinuing antipsychotics, adjusting their dose, or switching patients from a first-generation antipsychotic to a second-generation antipsychotic. Supplementation with antioxidants/radical scavengers such as vitamin E, vitamin B₆, ginkgo biloba, and fish oil “can be tried, but have limited evidence, as is the case for melatonin.” Other options include clonazepam, amantadine, donepezil, and tetrabenazine, a reversible and specific inhibitor of vesicular monoamine transporter-2 (VMAT-2), a transporter that packages neurotransmitters (preferentially dopamine) into vesicles for release into the synapse and was approved in 2008 as an orphan drug for the treatment of choreiform movements associated with Huntington’s disease. “Neurologists have using tetrabenazine off-label for TD, but in schizophrenia and other psychiatric care, we rarely use it because it has to be given three times a day and it has a black box warning for depression and suicidality,” he said.

Dr. Correll noted that the Food and Drug Administration approval of two more recent VMAT-2 inhibitors – deutetrabenazine (Austedo) and valbenazine (Ingrezza) – provides an evidence-based care option for the effective management of TD. Deutetrabenazine requires titration over several weeks and twice-daily dosing, while valbenazine can reach the maximum dose by the beginning of week 2 and is dosed once daily. Deutetrabenazine should be taken with food, which is not required valbenazine.

“Both VMAT-2 inhibitors are generally well tolerated and have a positive benefit-risk ratio,” he said. “Both are recommended by the APA guidelines as the preferred and only evidence-based treatment for TD.”

Dr. Correll reported that he has received honoraria from and has been an advisory board member for numerous pharmaceutical companies. He has also received grant support from Janssen, the National Institute of Mental Health, the Patient Centered Outcomes Research Institute, Takeda, and the Thrasher Foundation.

LAS VEGAS – In the opinion of Christoph U. Correll, MD, tardive dyskinesia (TD) “has been somewhat forgotten” by psychiatrists because the risk of patients developing the condition is considered to be significantly lower with second-generation antipsychotics compared with first-generation antipsychotics.

“But this does not seem to always be the case, because there is still a risk of TD, and we need to monitor for it,” Dr. Correll, professor of psychiatry and molecular medicine at The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “It is important to minimize the risk of TD by educating patients and caregivers about the risks of and alternatives to antipsychotic medication and early signs of TD.”

First described in 1957, TD is characterized by involuntary repetitive but irregular movements, mostly in the oral, lingual, and buccal regions – such as tongue protruding, puckering, chewing, and grimacing. Less often, there are movements in the hands, legs, feet, and torso. Symptoms can include mannerisms, stereotypies, tics, myoclonus, dystonias, tremor, and akathisia. “TD can be severe, persistent, and have medical and psychosocial consequences,” Dr. Correll said. “It can occur in untreated patients, but treatment with dopamine blocking agents – antipsychotics and metoclopramide – increases risk for TD.”

Differential diagnoses to consider include morbus Huntington, benign familial Chorea, and Sydenham’s Chorea. Less frequent causes of TD include metabolic conditions such as uremia, hyponatremia, hypernatremia, hypoparathyroidism, and hyperparathyroidism. “Those would need to be ruled out during the physical exam,” he said. There can also be inflammatory causes of TD such as herpes simplex virus, varicella, measles, mumps, and rubella.

A standard measure for TD diagnosis is the Abnormal Involuntary Movement Scale (AIMS), an observer-rated 12-item anchored scale that takes 5-10 minutes to administer. However, the AIMS on its own does not diagnose TD. In 1982, researchers developed three diagnostic criteria for TD: At least 3 months of cumulative antipsychotic drug exposure; presence of at least moderate abnormal involuntary movements in one or more body area(s) or mild movements in two or more body areas, and absence of other conditions that might produce involuntary movements (Arch Gen Psychiatry 1982;39:486-7).

The impact of TD on everyday functioning depends on anatomic location as well as severity, Dr. Correll continued. The condition can cause impairments to speech, verbal communication, dentition, temporomandibular joint pain/myalgia, swallowing difficulties, and fine motor skills including instrumental activities of daily living and written communication. Truncal and lower extremity TD can affect gait, posture and postural stability, strength, power flexibility, physical capacity, and one’s ability to exercise. “There are also psychological impairments,” he said. “Patients can develop different awareness so they become self-conscious; there can be cognitive abnormalities, and they can become more anxious or [have an] increased sense of paranoia, isolation, stigma, social and/or educational/vocational impairment.”

According to research by Dr. Correll and colleagues, unmodifiable patient-related risk factors for TD include older age, female sex, and being of white or African descent (J Neurol Sci 2018 June 15; 389:21-7). Unmodifiable illness-related risk factors include longer duration of illness, intellectual disability and brain damage, negative symptoms in schizophrenia, mood disorders, cognitive symptoms in mood disorders, and gene polymorphisms involving antipsychotic metabolism and dopamine functioning. Modifiable comorbidity-related factors include diabetes, smoking, and alcohol/substance abuse, while modifiable treatment-related factors include dopamine receptor blockers, higher cumulative and current antipsychotic dose or plasma levels, early parkinsonian side effects, treatment-emergent akathisia, and anticholinergic co-treatment. In a meta-analysis of 41 studies that aimed to determine the prevalence of TD, the mean age of the 11,493 patients was 43, 66% were male, and 77% had schizophrenia spectrum disorders (J Clin Psychiatry. 2017 Mar;78[3]:e264-78). The global mean TD prevalence was 25%, but the rates were lower with patients on current treatment with second-generation antipsychotics compared with those on first-generation antipsychotics (21% vs. 30%, respectively).

According to Dr. Correll, strategies for preventing TD include confirming and documenting the indication for dopamine antagonist antipsychotic medications, using conservative maintenance doses, and considering the use of SGAs, especially in those at high risk for EPS (extrapyramidal symptoms). “Don’t go too high [with the dose],” he said. “Stay below the EPS threshold. Inform patients and caregivers of the risk of TD and assess for incipient signs regularly using the AIMS.”

Treatment options include discontinuing antipsychotics, adjusting their dose, or switching patients from a first-generation antipsychotic to a second-generation antipsychotic. Supplementation with antioxidants/radical scavengers such as vitamin E, vitamin B₆, ginkgo biloba, and fish oil “can be tried, but have limited evidence, as is the case for melatonin.” Other options include clonazepam, amantadine, donepezil, and tetrabenazine, a reversible and specific inhibitor of vesicular monoamine transporter-2 (VMAT-2), a transporter that packages neurotransmitters (preferentially dopamine) into vesicles for release into the synapse and was approved in 2008 as an orphan drug for the treatment of choreiform movements associated with Huntington’s disease. “Neurologists have using tetrabenazine off-label for TD, but in schizophrenia and other psychiatric care, we rarely use it because it has to be given three times a day and it has a black box warning for depression and suicidality,” he said.

Dr. Correll noted that the Food and Drug Administration approval of two more recent VMAT-2 inhibitors – deutetrabenazine (Austedo) and valbenazine (Ingrezza) – provides an evidence-based care option for the effective management of TD. Deutetrabenazine requires titration over several weeks and twice-daily dosing, while valbenazine can reach the maximum dose by the beginning of week 2 and is dosed once daily. Deutetrabenazine should be taken with food, which is not required valbenazine.

“Both VMAT-2 inhibitors are generally well tolerated and have a positive benefit-risk ratio,” he said. “Both are recommended by the APA guidelines as the preferred and only evidence-based treatment for TD.”

Dr. Correll reported that he has received honoraria from and has been an advisory board member for numerous pharmaceutical companies. He has also received grant support from Janssen, the National Institute of Mental Health, the Patient Centered Outcomes Research Institute, Takeda, and the Thrasher Foundation.

LAS VEGAS – In the opinion of Christoph U. Correll, MD, tardive dyskinesia (TD) “has been somewhat forgotten” by psychiatrists because the risk of patients developing the condition is considered to be significantly lower with second-generation antipsychotics compared with first-generation antipsychotics.

“But this does not seem to always be the case, because there is still a risk of TD, and we need to monitor for it,” Dr. Correll, professor of psychiatry and molecular medicine at The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “It is important to minimize the risk of TD by educating patients and caregivers about the risks of and alternatives to antipsychotic medication and early signs of TD.”

First described in 1957, TD is characterized by involuntary repetitive but irregular movements, mostly in the oral, lingual, and buccal regions – such as tongue protruding, puckering, chewing, and grimacing. Less often, there are movements in the hands, legs, feet, and torso. Symptoms can include mannerisms, stereotypies, tics, myoclonus, dystonias, tremor, and akathisia. “TD can be severe, persistent, and have medical and psychosocial consequences,” Dr. Correll said. “It can occur in untreated patients, but treatment with dopamine blocking agents – antipsychotics and metoclopramide – increases risk for TD.”

Differential diagnoses to consider include morbus Huntington, benign familial Chorea, and Sydenham’s Chorea. Less frequent causes of TD include metabolic conditions such as uremia, hyponatremia, hypernatremia, hypoparathyroidism, and hyperparathyroidism. “Those would need to be ruled out during the physical exam,” he said. There can also be inflammatory causes of TD such as herpes simplex virus, varicella, measles, mumps, and rubella.

A standard measure for TD diagnosis is the Abnormal Involuntary Movement Scale (AIMS), an observer-rated 12-item anchored scale that takes 5-10 minutes to administer. However, the AIMS on its own does not diagnose TD. In 1982, researchers developed three diagnostic criteria for TD: At least 3 months of cumulative antipsychotic drug exposure; presence of at least moderate abnormal involuntary movements in one or more body area(s) or mild movements in two or more body areas, and absence of other conditions that might produce involuntary movements (Arch Gen Psychiatry 1982;39:486-7).

The impact of TD on everyday functioning depends on anatomic location as well as severity, Dr. Correll continued. The condition can cause impairments to speech, verbal communication, dentition, temporomandibular joint pain/myalgia, swallowing difficulties, and fine motor skills including instrumental activities of daily living and written communication. Truncal and lower extremity TD can affect gait, posture and postural stability, strength, power flexibility, physical capacity, and one’s ability to exercise. “There are also psychological impairments,” he said. “Patients can develop different awareness so they become self-conscious; there can be cognitive abnormalities, and they can become more anxious or [have an] increased sense of paranoia, isolation, stigma, social and/or educational/vocational impairment.”

According to research by Dr. Correll and colleagues, unmodifiable patient-related risk factors for TD include older age, female sex, and being of white or African descent (J Neurol Sci 2018 June 15; 389:21-7). Unmodifiable illness-related risk factors include longer duration of illness, intellectual disability and brain damage, negative symptoms in schizophrenia, mood disorders, cognitive symptoms in mood disorders, and gene polymorphisms involving antipsychotic metabolism and dopamine functioning. Modifiable comorbidity-related factors include diabetes, smoking, and alcohol/substance abuse, while modifiable treatment-related factors include dopamine receptor blockers, higher cumulative and current antipsychotic dose or plasma levels, early parkinsonian side effects, treatment-emergent akathisia, and anticholinergic co-treatment. In a meta-analysis of 41 studies that aimed to determine the prevalence of TD, the mean age of the 11,493 patients was 43, 66% were male, and 77% had schizophrenia spectrum disorders (J Clin Psychiatry. 2017 Mar;78[3]:e264-78). The global mean TD prevalence was 25%, but the rates were lower with patients on current treatment with second-generation antipsychotics compared with those on first-generation antipsychotics (21% vs. 30%, respectively).

According to Dr. Correll, strategies for preventing TD include confirming and documenting the indication for dopamine antagonist antipsychotic medications, using conservative maintenance doses, and considering the use of SGAs, especially in those at high risk for EPS (extrapyramidal symptoms). “Don’t go too high [with the dose],” he said. “Stay below the EPS threshold. Inform patients and caregivers of the risk of TD and assess for incipient signs regularly using the AIMS.”

Treatment options include discontinuing antipsychotics, adjusting their dose, or switching patients from a first-generation antipsychotic to a second-generation antipsychotic. Supplementation with antioxidants/radical scavengers such as vitamin E, vitamin B₆, ginkgo biloba, and fish oil “can be tried, but have limited evidence, as is the case for melatonin.” Other options include clonazepam, amantadine, donepezil, and tetrabenazine, a reversible and specific inhibitor of vesicular monoamine transporter-2 (VMAT-2), a transporter that packages neurotransmitters (preferentially dopamine) into vesicles for release into the synapse and was approved in 2008 as an orphan drug for the treatment of choreiform movements associated with Huntington’s disease. “Neurologists have using tetrabenazine off-label for TD, but in schizophrenia and other psychiatric care, we rarely use it because it has to be given three times a day and it has a black box warning for depression and suicidality,” he said.

Dr. Correll noted that the Food and Drug Administration approval of two more recent VMAT-2 inhibitors – deutetrabenazine (Austedo) and valbenazine (Ingrezza) – provides an evidence-based care option for the effective management of TD. Deutetrabenazine requires titration over several weeks and twice-daily dosing, while valbenazine can reach the maximum dose by the beginning of week 2 and is dosed once daily. Deutetrabenazine should be taken with food, which is not required valbenazine.

“Both VMAT-2 inhibitors are generally well tolerated and have a positive benefit-risk ratio,” he said. “Both are recommended by the APA guidelines as the preferred and only evidence-based treatment for TD.”

Dr. Correll reported that he has received honoraria from and has been an advisory board member for numerous pharmaceutical companies. He has also received grant support from Janssen, the National Institute of Mental Health, the Patient Centered Outcomes Research Institute, Takeda, and the Thrasher Foundation.

Reports based on a press release in October 2021 suggested it, but now the full data tell the story: Early monitoring and treatment of anal high-grade squamous intraepithelial lesions (HSIL) cut risk for anal cancer by 57% in people living with HIV.

“We now show, for the first time, that treatment of anal HSIL is effective in reducing the incidence of anal cancer,” said Joel Palefsky, MD, lead investigator of the Anal Cancer/HSIL Outcomes Research (ANCHOR) study and founder/director of the Anal Neoplasia Clinic at the University of California, San Francisco. “These data should be included in an overall assessment for inclusion of screening for and treating HSIL as standard of care in people living with HIV.”

Dr. Palefsky presented the full results in a special session at the Conference on Retroviruses and Opportunistic Infections, which drew excitement, gratitude, and relief from both researchers and clinicians, who flocked to the session.

But it’s not just people with HIV who will benefit from this research. Dr. Palefsky suggested that the findings should also be considered as guides for other people at high-risk for anal cancer, such as people who are immunocompromised for other reasons, including those with lupus, ulcerative colitis, Crohn’s disease, or cisgender women who have had vulvar or cervical cancer or precancer.

“If we can show efficacy in the most challenging group of all, which are people living with HIV, we think the results can be as good, if not even better, in the other groups at high risk of anal cancer,” Dr. Palefsky said.

But to serve anyone – whether living with HIV or not – infrastructure, algorithms, and workforce training are going be needed to meet the currently unserved people through use of high-resolution anoscopy (HRA) and other screening technology, he said.

Dr. Palefsy and colleagues screened 10,723 people living with HIV being served at 15 clinics nationwide. More than half, 52.2%, had anal HSIL – 53.3% of the cisgender men living with HIV in the trial, 45.8% of the cis women living with HIV, and a full 62.5% of transgender participants.

Those 4,446 participants were split evenly between the treatment arm and the control arm. Those in the treatment arm received treatment for HSIL on their first study visit via one of five options: hyfrecation, office-based electrocautery ablation, infrared coagulation, topical 5-fluorouracil cream, or topical imiquimod. Then, every 6 months after that, they came in for HRA, blood tests, anal Pap smears, and biopsies to check for any lingering or new HSIL. If clinicians found such cells, they received treatment again. If biopsies still showed HSIL and clinician and participant were worried about cancer, they could come in as frequently as every 3 months and receive treatment each time.

The active-monitoring control group still received an anal Pap smear, blood tests, biopsy, and HRA every 6 months – a level of care that is currently not mandated anywhere for people living with HIV, Dr. Palefsky said in an interview. They were also able to come in for more frequent monitoring (every 3 months) if clinicians were worried about cancer.

“Those in both arms would have been getting more attention than if they had not participated in the study,” he said.

In addition, during screening, researchers found that cancer was already present in 17 other people, who skipped the study to go right to treatment.

Participants reflected the demographics of the HIV epidemic in the United States. They were older (median age, 51 years), mostly gay (78%), and cisgender male (80%). Close to half, 42%, were Black, and 16% were Latinx. In addition, cisgender women made up 16% of the participants and transgender people, and nonbinary individuals accounted for more than 3% of the participants. In addition, one in three smoked.

The vast majority of participants had well-controlled HIV and healthy immune systems, though half in each arm had a history of AIDS, defined as lowest-ever CD4 immune cell counts below 200. Today, more than 80% of participants had undetectable viral loads, defined as a viral load less than 50 copies/mL, and another 7% had HIV viral loads below 200. In total, 9.3% in the treatment arm and 10.9% in the control arm had HIV viral loads higher than that. At time of enrollment, CD4 counts were above 600 in each group, indicating healthy immune systems.

Although all participants were there because they had anal HSIL, more than 1 in 10 – 13% – had abnormal cells so extensive that they covered more than half of the anal canal or the perianal region.

Once everyone was enrolled, researchers began monitoring and treatment, looking specifically for 31 cases of cancer – a number the team had determined that they’d need in order to draw any conclusions. Dr. Palefsky didn’t have to wait long. They were still trying to enroll the last 1,000 participants to have the power necessary to reach that number when the cancer diagnoses came in.

Dr. Palefsky told this news organization that the reason for that is unclear. It could be that some of those cases would have resolved on their own, and so the swiftness with which they reached the required number of cancer cases belies their seriousness. It could also be that the particular people who enrolled in this trial were engaging in behaviors that put them at even higher risk for anal cancer than the population of people living with HIV in the United States.

Or it could be that symptom-based screening is missing a lot of cancers that currently go untreated.

“So perhaps we will be seeing an increase in anal cancer reported in the future compared to the currently reported rates,” he said. “We don’t really know.”

Regardless of the reason for the speed to cases of cancer, the results were definitive: Nine participants were diagnosed with invasive anal cancer in the treatment arm, while 21 were diagnosed with invasive anal cancer in the control arm. That’s a 57% reduction in cancer occurrence between the arms. Or, to put it another way, the rate of anal cancer among people in the treatment arm was 173 per 100,000 people-years. In the active monitoring arm, it was 402 per 100,000 person-years. For context, the overall rate of anal cancer among people living with HIV is 50 per 100,000 person-years. The rate in the general U.S. population is 8 per 100,000 people-years.

The experimental treatment was such a definitive success that the investigators stopped the trial and shifted all participants in the control arm to treatment.
 

‘We have to build’

Before Dr. Palefsky was even done presenting the data, clinicians, people living with HIV, and experts at the session were already brainstorming as to how to get these results into practice.

“These data are what we have long needed to fuel some action on this important problem, including medical cost reimbursement through insurance and increasing the number of persons trained and capable in anal cancer screening,” John Brooks, MD, head of the epidemiology research team at the Centers for Disease Control and Prevention’s division of HIV/AIDS prevention, wrote in the virtual chat.

Jeff Taylor, a member of the ANCHOR advisory board and a person living with HIV who participated in one of the first azidothymidine trials in the late 1980s, responded quickly.

“What kind of advocacy from researchers, HIV clinicians and [people living with HIV] is needed to get this on treatment guidelines, HRA providers trained and certified, and payors to cover this so [people living with HIV] actually have access to lifesaving screening and [treatment]?” Mr. Taylor asked.

It’s a serious challenge. David Malebranche, MD, an Atlanta-based internal medicine physician who specializes in sexual health and HIV, commented in an interview. When he saw the initial press release last year on the ANCHOR findings, his first reaction was: “Thank god. We finally have some data to show what we’ve been trying to get people to do” all along.

But then he wondered, who is going to perform these tests? It’s a fair question. Currently, the wait for an HRA is 6-12 months in many parts of the country. And Dr. Malebranche can’t imagine this being added to his already full plate as a primary care provider.

“If you tell a primary care provider now that they have to do a rectal Pap smear, that’s going to be a problem while you’re also asking them to screen each patient for depression, anxiety, domestic abuse, intimate partner violence, all the healthcare maintenance and all the other screening tests – and then you deal with not only the urgent complaint but then all the complex medical issues on top of that – in a 15-minute or 10-minute visit,” he said.

Now that we have these data, he said, “we have to build.”

Dr. Palefsky agreed. Very few centers have enough people skilled at performing HRAs to meet the current demand, and it’s not realistic to expect clinicians to perform an HRA every 6 months like the study team did. There need to be algorithms put in place to help practitioners figure out who among their patients living with HIV could benefit from this increased screening, as well as biomarkers to identify HSIL progression and regression without the use of HRA, Dr. Palefsky told attendees. And more clinicians need to be recruited and trained to read HRAs, which can be difficult for the untrained eye to decipher.

Dr. Malebranche added another, more fundamental thing that needs to be built. Dr. Malebranche has worked in HIV clinics where the majority of his patients qualify for insurance under the Ryan White Program and get their medications through the AIDS Drug Assistance Program. While Ryan White programs can provide critical wraparound care, Dr. Malebranche has had to refer out for something like an HRA or cancer treatment. But the people who only access care through such programs may not have coverage with the clinics that perform HRA or that treat cancer. And that’s if they can even find someone to see them.

“If I live in a state like Georgia, which doesn’t have Medicaid expansion and we have people who are uninsured, where do you send them?” Dr. Malebranche asked. “This isn’t theoretical. I ran into this problem when I was working at the AIDS Healthcare Foundation last year. ... This is a call for infrastructure.”

The study was funded by the National Cancer Institute. Dr. Brooks reported no relevant financial relationships. Dr. Palefsky has received consultant fees from Merck, Vir Biotechnology, Virion Therapeutics, and Antiva Bioscience, as well as speaker fees from Merck. Dr. Malebranche has received consulting and advising fees from ViiV Healthcare.

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

Reports based on a press release in October 2021 suggested it, but now the full data tell the story: Early monitoring and treatment of anal high-grade squamous intraepithelial lesions (HSIL) cut risk for anal cancer by 57% in people living with HIV.

“We now show, for the first time, that treatment of anal HSIL is effective in reducing the incidence of anal cancer,” said Joel Palefsky, MD, lead investigator of the Anal Cancer/HSIL Outcomes Research (ANCHOR) study and founder/director of the Anal Neoplasia Clinic at the University of California, San Francisco. “These data should be included in an overall assessment for inclusion of screening for and treating HSIL as standard of care in people living with HIV.”

Dr. Palefsky presented the full results in a special session at the Conference on Retroviruses and Opportunistic Infections, which drew excitement, gratitude, and relief from both researchers and clinicians, who flocked to the session.

But it’s not just people with HIV who will benefit from this research. Dr. Palefsky suggested that the findings should also be considered as guides for other people at high-risk for anal cancer, such as people who are immunocompromised for other reasons, including those with lupus, ulcerative colitis, Crohn’s disease, or cisgender women who have had vulvar or cervical cancer or precancer.

“If we can show efficacy in the most challenging group of all, which are people living with HIV, we think the results can be as good, if not even better, in the other groups at high risk of anal cancer,” Dr. Palefsky said.

But to serve anyone – whether living with HIV or not – infrastructure, algorithms, and workforce training are going be needed to meet the currently unserved people through use of high-resolution anoscopy (HRA) and other screening technology, he said.

Dr. Palefsy and colleagues screened 10,723 people living with HIV being served at 15 clinics nationwide. More than half, 52.2%, had anal HSIL – 53.3% of the cisgender men living with HIV in the trial, 45.8% of the cis women living with HIV, and a full 62.5% of transgender participants.

Those 4,446 participants were split evenly between the treatment arm and the control arm. Those in the treatment arm received treatment for HSIL on their first study visit via one of five options: hyfrecation, office-based electrocautery ablation, infrared coagulation, topical 5-fluorouracil cream, or topical imiquimod. Then, every 6 months after that, they came in for HRA, blood tests, anal Pap smears, and biopsies to check for any lingering or new HSIL. If clinicians found such cells, they received treatment again. If biopsies still showed HSIL and clinician and participant were worried about cancer, they could come in as frequently as every 3 months and receive treatment each time.

The active-monitoring control group still received an anal Pap smear, blood tests, biopsy, and HRA every 6 months – a level of care that is currently not mandated anywhere for people living with HIV, Dr. Palefsky said in an interview. They were also able to come in for more frequent monitoring (every 3 months) if clinicians were worried about cancer.

“Those in both arms would have been getting more attention than if they had not participated in the study,” he said.

In addition, during screening, researchers found that cancer was already present in 17 other people, who skipped the study to go right to treatment.

Participants reflected the demographics of the HIV epidemic in the United States. They were older (median age, 51 years), mostly gay (78%), and cisgender male (80%). Close to half, 42%, were Black, and 16% were Latinx. In addition, cisgender women made up 16% of the participants and transgender people, and nonbinary individuals accounted for more than 3% of the participants. In addition, one in three smoked.

The vast majority of participants had well-controlled HIV and healthy immune systems, though half in each arm had a history of AIDS, defined as lowest-ever CD4 immune cell counts below 200. Today, more than 80% of participants had undetectable viral loads, defined as a viral load less than 50 copies/mL, and another 7% had HIV viral loads below 200. In total, 9.3% in the treatment arm and 10.9% in the control arm had HIV viral loads higher than that. At time of enrollment, CD4 counts were above 600 in each group, indicating healthy immune systems.

Although all participants were there because they had anal HSIL, more than 1 in 10 – 13% – had abnormal cells so extensive that they covered more than half of the anal canal or the perianal region.

Once everyone was enrolled, researchers began monitoring and treatment, looking specifically for 31 cases of cancer – a number the team had determined that they’d need in order to draw any conclusions. Dr. Palefsky didn’t have to wait long. They were still trying to enroll the last 1,000 participants to have the power necessary to reach that number when the cancer diagnoses came in.

Dr. Palefsky told this news organization that the reason for that is unclear. It could be that some of those cases would have resolved on their own, and so the swiftness with which they reached the required number of cancer cases belies their seriousness. It could also be that the particular people who enrolled in this trial were engaging in behaviors that put them at even higher risk for anal cancer than the population of people living with HIV in the United States.

Or it could be that symptom-based screening is missing a lot of cancers that currently go untreated.

“So perhaps we will be seeing an increase in anal cancer reported in the future compared to the currently reported rates,” he said. “We don’t really know.”

Regardless of the reason for the speed to cases of cancer, the results were definitive: Nine participants were diagnosed with invasive anal cancer in the treatment arm, while 21 were diagnosed with invasive anal cancer in the control arm. That’s a 57% reduction in cancer occurrence between the arms. Or, to put it another way, the rate of anal cancer among people in the treatment arm was 173 per 100,000 people-years. In the active monitoring arm, it was 402 per 100,000 person-years. For context, the overall rate of anal cancer among people living with HIV is 50 per 100,000 person-years. The rate in the general U.S. population is 8 per 100,000 people-years.

The experimental treatment was such a definitive success that the investigators stopped the trial and shifted all participants in the control arm to treatment.
 

‘We have to build’

Before Dr. Palefsky was even done presenting the data, clinicians, people living with HIV, and experts at the session were already brainstorming as to how to get these results into practice.

“These data are what we have long needed to fuel some action on this important problem, including medical cost reimbursement through insurance and increasing the number of persons trained and capable in anal cancer screening,” John Brooks, MD, head of the epidemiology research team at the Centers for Disease Control and Prevention’s division of HIV/AIDS prevention, wrote in the virtual chat.

Jeff Taylor, a member of the ANCHOR advisory board and a person living with HIV who participated in one of the first azidothymidine trials in the late 1980s, responded quickly.

“What kind of advocacy from researchers, HIV clinicians and [people living with HIV] is needed to get this on treatment guidelines, HRA providers trained and certified, and payors to cover this so [people living with HIV] actually have access to lifesaving screening and [treatment]?” Mr. Taylor asked.

It’s a serious challenge. David Malebranche, MD, an Atlanta-based internal medicine physician who specializes in sexual health and HIV, commented in an interview. When he saw the initial press release last year on the ANCHOR findings, his first reaction was: “Thank god. We finally have some data to show what we’ve been trying to get people to do” all along.

But then he wondered, who is going to perform these tests? It’s a fair question. Currently, the wait for an HRA is 6-12 months in many parts of the country. And Dr. Malebranche can’t imagine this being added to his already full plate as a primary care provider.

“If you tell a primary care provider now that they have to do a rectal Pap smear, that’s going to be a problem while you’re also asking them to screen each patient for depression, anxiety, domestic abuse, intimate partner violence, all the healthcare maintenance and all the other screening tests – and then you deal with not only the urgent complaint but then all the complex medical issues on top of that – in a 15-minute or 10-minute visit,” he said.

Now that we have these data, he said, “we have to build.”

Dr. Palefsky agreed. Very few centers have enough people skilled at performing HRAs to meet the current demand, and it’s not realistic to expect clinicians to perform an HRA every 6 months like the study team did. There need to be algorithms put in place to help practitioners figure out who among their patients living with HIV could benefit from this increased screening, as well as biomarkers to identify HSIL progression and regression without the use of HRA, Dr. Palefsky told attendees. And more clinicians need to be recruited and trained to read HRAs, which can be difficult for the untrained eye to decipher.

Dr. Malebranche added another, more fundamental thing that needs to be built. Dr. Malebranche has worked in HIV clinics where the majority of his patients qualify for insurance under the Ryan White Program and get their medications through the AIDS Drug Assistance Program. While Ryan White programs can provide critical wraparound care, Dr. Malebranche has had to refer out for something like an HRA or cancer treatment. But the people who only access care through such programs may not have coverage with the clinics that perform HRA or that treat cancer. And that’s if they can even find someone to see them.

“If I live in a state like Georgia, which doesn’t have Medicaid expansion and we have people who are uninsured, where do you send them?” Dr. Malebranche asked. “This isn’t theoretical. I ran into this problem when I was working at the AIDS Healthcare Foundation last year. ... This is a call for infrastructure.”

The study was funded by the National Cancer Institute. Dr. Brooks reported no relevant financial relationships. Dr. Palefsky has received consultant fees from Merck, Vir Biotechnology, Virion Therapeutics, and Antiva Bioscience, as well as speaker fees from Merck. Dr. Malebranche has received consulting and advising fees from ViiV Healthcare.

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

Reports based on a press release in October 2021 suggested it, but now the full data tell the story: Early monitoring and treatment of anal high-grade squamous intraepithelial lesions (HSIL) cut risk for anal cancer by 57% in people living with HIV.

“We now show, for the first time, that treatment of anal HSIL is effective in reducing the incidence of anal cancer,” said Joel Palefsky, MD, lead investigator of the Anal Cancer/HSIL Outcomes Research (ANCHOR) study and founder/director of the Anal Neoplasia Clinic at the University of California, San Francisco. “These data should be included in an overall assessment for inclusion of screening for and treating HSIL as standard of care in people living with HIV.”

Dr. Palefsky presented the full results in a special session at the Conference on Retroviruses and Opportunistic Infections, which drew excitement, gratitude, and relief from both researchers and clinicians, who flocked to the session.

But it’s not just people with HIV who will benefit from this research. Dr. Palefsky suggested that the findings should also be considered as guides for other people at high-risk for anal cancer, such as people who are immunocompromised for other reasons, including those with lupus, ulcerative colitis, Crohn’s disease, or cisgender women who have had vulvar or cervical cancer or precancer.

“If we can show efficacy in the most challenging group of all, which are people living with HIV, we think the results can be as good, if not even better, in the other groups at high risk of anal cancer,” Dr. Palefsky said.

But to serve anyone – whether living with HIV or not – infrastructure, algorithms, and workforce training are going be needed to meet the currently unserved people through use of high-resolution anoscopy (HRA) and other screening technology, he said.

Dr. Palefsy and colleagues screened 10,723 people living with HIV being served at 15 clinics nationwide. More than half, 52.2%, had anal HSIL – 53.3% of the cisgender men living with HIV in the trial, 45.8% of the cis women living with HIV, and a full 62.5% of transgender participants.

Those 4,446 participants were split evenly between the treatment arm and the control arm. Those in the treatment arm received treatment for HSIL on their first study visit via one of five options: hyfrecation, office-based electrocautery ablation, infrared coagulation, topical 5-fluorouracil cream, or topical imiquimod. Then, every 6 months after that, they came in for HRA, blood tests, anal Pap smears, and biopsies to check for any lingering or new HSIL. If clinicians found such cells, they received treatment again. If biopsies still showed HSIL and clinician and participant were worried about cancer, they could come in as frequently as every 3 months and receive treatment each time.

The active-monitoring control group still received an anal Pap smear, blood tests, biopsy, and HRA every 6 months – a level of care that is currently not mandated anywhere for people living with HIV, Dr. Palefsky said in an interview. They were also able to come in for more frequent monitoring (every 3 months) if clinicians were worried about cancer.

“Those in both arms would have been getting more attention than if they had not participated in the study,” he said.

In addition, during screening, researchers found that cancer was already present in 17 other people, who skipped the study to go right to treatment.

Participants reflected the demographics of the HIV epidemic in the United States. They were older (median age, 51 years), mostly gay (78%), and cisgender male (80%). Close to half, 42%, were Black, and 16% were Latinx. In addition, cisgender women made up 16% of the participants and transgender people, and nonbinary individuals accounted for more than 3% of the participants. In addition, one in three smoked.

The vast majority of participants had well-controlled HIV and healthy immune systems, though half in each arm had a history of AIDS, defined as lowest-ever CD4 immune cell counts below 200. Today, more than 80% of participants had undetectable viral loads, defined as a viral load less than 50 copies/mL, and another 7% had HIV viral loads below 200. In total, 9.3% in the treatment arm and 10.9% in the control arm had HIV viral loads higher than that. At time of enrollment, CD4 counts were above 600 in each group, indicating healthy immune systems.

Although all participants were there because they had anal HSIL, more than 1 in 10 – 13% – had abnormal cells so extensive that they covered more than half of the anal canal or the perianal region.

Once everyone was enrolled, researchers began monitoring and treatment, looking specifically for 31 cases of cancer – a number the team had determined that they’d need in order to draw any conclusions. Dr. Palefsky didn’t have to wait long. They were still trying to enroll the last 1,000 participants to have the power necessary to reach that number when the cancer diagnoses came in.

Dr. Palefsky told this news organization that the reason for that is unclear. It could be that some of those cases would have resolved on their own, and so the swiftness with which they reached the required number of cancer cases belies their seriousness. It could also be that the particular people who enrolled in this trial were engaging in behaviors that put them at even higher risk for anal cancer than the population of people living with HIV in the United States.

Or it could be that symptom-based screening is missing a lot of cancers that currently go untreated.

“So perhaps we will be seeing an increase in anal cancer reported in the future compared to the currently reported rates,” he said. “We don’t really know.”

Regardless of the reason for the speed to cases of cancer, the results were definitive: Nine participants were diagnosed with invasive anal cancer in the treatment arm, while 21 were diagnosed with invasive anal cancer in the control arm. That’s a 57% reduction in cancer occurrence between the arms. Or, to put it another way, the rate of anal cancer among people in the treatment arm was 173 per 100,000 people-years. In the active monitoring arm, it was 402 per 100,000 person-years. For context, the overall rate of anal cancer among people living with HIV is 50 per 100,000 person-years. The rate in the general U.S. population is 8 per 100,000 people-years.

The experimental treatment was such a definitive success that the investigators stopped the trial and shifted all participants in the control arm to treatment.
 

‘We have to build’

Before Dr. Palefsky was even done presenting the data, clinicians, people living with HIV, and experts at the session were already brainstorming as to how to get these results into practice.

“These data are what we have long needed to fuel some action on this important problem, including medical cost reimbursement through insurance and increasing the number of persons trained and capable in anal cancer screening,” John Brooks, MD, head of the epidemiology research team at the Centers for Disease Control and Prevention’s division of HIV/AIDS prevention, wrote in the virtual chat.

Jeff Taylor, a member of the ANCHOR advisory board and a person living with HIV who participated in one of the first azidothymidine trials in the late 1980s, responded quickly.

“What kind of advocacy from researchers, HIV clinicians and [people living with HIV] is needed to get this on treatment guidelines, HRA providers trained and certified, and payors to cover this so [people living with HIV] actually have access to lifesaving screening and [treatment]?” Mr. Taylor asked.

It’s a serious challenge. David Malebranche, MD, an Atlanta-based internal medicine physician who specializes in sexual health and HIV, commented in an interview. When he saw the initial press release last year on the ANCHOR findings, his first reaction was: “Thank god. We finally have some data to show what we’ve been trying to get people to do” all along.

But then he wondered, who is going to perform these tests? It’s a fair question. Currently, the wait for an HRA is 6-12 months in many parts of the country. And Dr. Malebranche can’t imagine this being added to his already full plate as a primary care provider.

“If you tell a primary care provider now that they have to do a rectal Pap smear, that’s going to be a problem while you’re also asking them to screen each patient for depression, anxiety, domestic abuse, intimate partner violence, all the healthcare maintenance and all the other screening tests – and then you deal with not only the urgent complaint but then all the complex medical issues on top of that – in a 15-minute or 10-minute visit,” he said.

Now that we have these data, he said, “we have to build.”

Dr. Palefsky agreed. Very few centers have enough people skilled at performing HRAs to meet the current demand, and it’s not realistic to expect clinicians to perform an HRA every 6 months like the study team did. There need to be algorithms put in place to help practitioners figure out who among their patients living with HIV could benefit from this increased screening, as well as biomarkers to identify HSIL progression and regression without the use of HRA, Dr. Palefsky told attendees. And more clinicians need to be recruited and trained to read HRAs, which can be difficult for the untrained eye to decipher.

Dr. Malebranche added another, more fundamental thing that needs to be built. Dr. Malebranche has worked in HIV clinics where the majority of his patients qualify for insurance under the Ryan White Program and get their medications through the AIDS Drug Assistance Program. While Ryan White programs can provide critical wraparound care, Dr. Malebranche has had to refer out for something like an HRA or cancer treatment. But the people who only access care through such programs may not have coverage with the clinics that perform HRA or that treat cancer. And that’s if they can even find someone to see them.

“If I live in a state like Georgia, which doesn’t have Medicaid expansion and we have people who are uninsured, where do you send them?” Dr. Malebranche asked. “This isn’t theoretical. I ran into this problem when I was working at the AIDS Healthcare Foundation last year. ... This is a call for infrastructure.”

The study was funded by the National Cancer Institute. Dr. Brooks reported no relevant financial relationships. Dr. Palefsky has received consultant fees from Merck, Vir Biotechnology, Virion Therapeutics, and Antiva Bioscience, as well as speaker fees from Merck. Dr. Malebranche has received consulting and advising fees from ViiV Healthcare.

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

Use of direct oral anticoagulant drugs (DOACs) appears to be just as effective as warfarin in preventing future thrombotic events in patients with cerebral venous thrombosis (CVT) stroke and are less likely to result in major bleeding, a retrospective study suggests.

The ACTION CVT study was presented at the International Stroke Conference (ISC) 2022 by Ekaterina Bakradze, MD, assistant professor of neurology at the University of Alabama at Birmingham.

It was also simultaneously published online in Stroke.

“This real-world data supports use of direct oral anticoagulant drugs as a reasonable alternative to warfarin in patients with cerebral venous thrombosis,” Dr. Bakradze concluded.

But she added that because this study was based on retrospective observational data, the findings should be interpreted with caution and require confirmation by larger prospective studies.

Two such studies are now underway: the Direct Oral Anticoagulants in the Treatment of Cerebral Venous Thrombosis (DOAC-CVT) study and the randomized Study of Rivaroxaban for Cerebral Venous Thrombosis (SECRET) trial.

Dr. Bakradze explained that cerebral venous thrombosis is a less common cause of stroke and occurs more often in women and younger patients, with a median age of 37 years. Current recommended treatment consists of heparin followed by oral anticoagulation.

She noted that although randomized trials and current guidelines indicate that DOACs are a preferred alternative to warfarin for the treatment of patients with venous thromboembolism, there are limited data on their use in patients with CVT.

A small, randomized trial (RESPECT-CVT) showed no significant difference in efficacy and safety outcomes between dabigatran and warfarin in patients with cerebral venous thrombosis, but with only 120 patients, this trial was too small for definite answers to this question.

A better understanding of this issue is important, because the mechanisms underlying cerebral venous thrombosis and other thromboembolism and their subsequent risks may differ, Dr. Bakradze said.

As randomized trials in patients with cerebral venous thrombosis are difficult to perform because the condition has a low incidence and low event rates, the researchers decided to look at this question with a large retrospective multicenter study.

The ACTION-CVT study involved 845 consecutive patients with cerebral venous thrombosis over 6 years (from January 2015 and December 2020) from 27 centers in Italy, New Zealand, Switzerland, and the United States. Patients were identified from medical records with diagnostic codes and confirmed with imaging.

The primary predictor in the study was oral anticoagulant type (DOAC vs. warfarin). Study outcomes were abstracted by individual sites through review of all available medical records.

The primary outcome was recurrent venous thrombosis (venous thromboembolism or cerebral venous thrombosis) during follow-up. Imaging outcomes based on recanalization status on last venous imaging study abstracted from radiology reports were also reported.

The safety outcome was major hemorrhage, defined as new or worsening intracranial hemorrhage (ICH), or major extracranial hemorrhage. Results were adjusted for age, sex, and relevant medical conditions.

The mean age of the patients included was 44.8 years, 64.7% were women, 33% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times.

Results showed that during a median follow-up of 345 days, there were 5.68 recurrent venous thrombosis events, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years.

Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization.

When compared with warfarin, DOAC treatment was associated with similar risk for recurrent venous thrombosis (adjusted hazard ratio, 0.94; 95% confidence interval, 0.51-1.73; P = .84), death (aHR, 0.71, 95% CI, 0.24-2.08; P = .53), and rate of partial/complete recanalization (aHR, 0.92, 95% CI, 0.48-1.73; P = .79).

But patients who received a DOAC had a significantly lower rate of major hemorrhage (aHR, 0.35; 95% CI, 0.15-0.81; P = .02).

When examined separately, the occurrence of ICH per 100 patient-years was much lower among the patients prescribed DOACs than those who were prescribed warfarin (1.52 vs. 3.51), whereas the occurrence of major bleeding outside the brain was similar (0.91 vs. 1.15).