Dermatology News

An estimated 50% of children with atopic dermatitis (AD) struggle with sleep problems, with complaints that vary from sleep fragmentation to restlessness and limb movements, according to Stephen H. Sheldon, DO.

“They wake up frequently,” Dr. Sheldon, professor of pediatrics and neurology at Northwestern University, Chicago, said during the Revolutionizing Atopic Dermatitis symposium. “They may not stay up for long periods of time, but they move about often. There’s a loss of about 50 minutes of sleep per night in children with AD. This loss can result in significant sleep debt the following day. They have difficulty settling at night. Once they get into bed, they have difficulty falling asleep, and many of them have difficulty staying asleep.”

At the sleep medicine center at Lurie Children’s Hospital of Chicago, he and his colleagues have observed that some children with AD complain of difficulty with limb movements. “Part of the issue has been that they have been diagnosed with different sleep-related disorders, such as period limb movement disorder, restless leg syndrome, and growing pain,” Dr. Sheldon said. “Often, they do not know how to describe the manifestations of their leg discomfort in restless leg syndrome and period limb movement disorder and limb movements of sleep.”

Children who complain of growing pains say that their legs hurt, he continued. Sometimes they’ll say that they feel like spiders are crawling on their legs, or that their legs itch, but they often say they have pain in their legs that wakes them up and keeps them from keeping their legs still.

According to the American Academy of Sleep Medicine, periodic limb movement disorder of sleep is characterized by frequent limb movements that last at least 0.5 seconds and are separated by no more than 90 seconds. “They’re four movements in a row that are at least 5 seconds apart,” Dr. Sheldon said.

Interestingly, he added, children who have limb movement disorder have symptoms during the day, similar to adults. “But we see many children with periodic limb movements of sleep whose arms and legs are moving all night, and they don’t have many symptoms during the day.” These children may have difficulty falling or staying asleep, but do not fulfill all of the American Academy of Sleep Medicine criteria for diagnosis of periodic limb movement disorder, he added.

In 2018, Lourdes M. DelRosso, MD, EdD, of Seattle Children’s Hospital, and colleagues described a new sleep problem they termed restless sleep disorder: those who do not fit the criteria for any other sleep disorder but have daytime impairment.

“On video they have very frequent movements – more than five movements an hour of major body activity,” Dr. Sheldon explained. “They’ll move their trunk, their legs, and reposition themselves. We have found that there are many children who presented to the sleep disorder center with restless sleep, limb movement disorder, periodic limb movements of sleep, and daytime symptoms that would fulfill the criteria of periodic limb movement disorder but also have atopic dermatitis.”

Recently, Dr. Sheldon and his colleagues used polysomnographic variables to study children who presented to Lurie Children’s Hospital with AD and symptoms such as difficulty maintaining sleep and snoring with allergic rhinitis. They found that there were increased periods of being awake after the onset of sleep, “meaning the children fell asleep fairly easily in the beginning of the night but they had significant wake after they fell asleep,” he said. “They would wake up in the middle of the night and stay awake for long periods of time – either one long session or multiple shorter sessions throughout the night. They had increased total limb movements per hour of sleep. This means that their limb movements were greater than five events per hour of sleep and it resulted in restless sleep and limb movements that would fulfill the criteria of periodic limb movement disorder.”

Most of these children had mild to moderate AD, he continued. “We feel that the sensory afferent loop in these youngsters doesn’t really turn off completely when they’re asleep. This is ripe for further study, but it makes intuitive sense that if the sensory afferent loop continues during sleep, it may affect the arousal system significantly.”

Dr. Sheldon recommended that any child who presents with a diagnosis of periodic limb movement disorder, periodic limb movements of sleep, or restless sleep disorder should be evaluated for AD. “The treatment then, would first require differentiation between periodic limb movement disorder of sleep and AD. Both should be addressed at the same time in order to solve the child’s daytime AD problem as well as the sleep-related issues that occur with an AD diagnosis.”

He reported having no financial disclosures.

An estimated 50% of children with atopic dermatitis (AD) struggle with sleep problems, with complaints that vary from sleep fragmentation to restlessness and limb movements, according to Stephen H. Sheldon, DO.

“They wake up frequently,” Dr. Sheldon, professor of pediatrics and neurology at Northwestern University, Chicago, said during the Revolutionizing Atopic Dermatitis symposium. “They may not stay up for long periods of time, but they move about often. There’s a loss of about 50 minutes of sleep per night in children with AD. This loss can result in significant sleep debt the following day. They have difficulty settling at night. Once they get into bed, they have difficulty falling asleep, and many of them have difficulty staying asleep.”

At the sleep medicine center at Lurie Children’s Hospital of Chicago, he and his colleagues have observed that some children with AD complain of difficulty with limb movements. “Part of the issue has been that they have been diagnosed with different sleep-related disorders, such as period limb movement disorder, restless leg syndrome, and growing pain,” Dr. Sheldon said. “Often, they do not know how to describe the manifestations of their leg discomfort in restless leg syndrome and period limb movement disorder and limb movements of sleep.”

Children who complain of growing pains say that their legs hurt, he continued. Sometimes they’ll say that they feel like spiders are crawling on their legs, or that their legs itch, but they often say they have pain in their legs that wakes them up and keeps them from keeping their legs still.

According to the American Academy of Sleep Medicine, periodic limb movement disorder of sleep is characterized by frequent limb movements that last at least 0.5 seconds and are separated by no more than 90 seconds. “They’re four movements in a row that are at least 5 seconds apart,” Dr. Sheldon said.

Interestingly, he added, children who have limb movement disorder have symptoms during the day, similar to adults. “But we see many children with periodic limb movements of sleep whose arms and legs are moving all night, and they don’t have many symptoms during the day.” These children may have difficulty falling or staying asleep, but do not fulfill all of the American Academy of Sleep Medicine criteria for diagnosis of periodic limb movement disorder, he added.

In 2018, Lourdes M. DelRosso, MD, EdD, of Seattle Children’s Hospital, and colleagues described a new sleep problem they termed restless sleep disorder: those who do not fit the criteria for any other sleep disorder but have daytime impairment.

“On video they have very frequent movements – more than five movements an hour of major body activity,” Dr. Sheldon explained. “They’ll move their trunk, their legs, and reposition themselves. We have found that there are many children who presented to the sleep disorder center with restless sleep, limb movement disorder, periodic limb movements of sleep, and daytime symptoms that would fulfill the criteria of periodic limb movement disorder but also have atopic dermatitis.”

Recently, Dr. Sheldon and his colleagues used polysomnographic variables to study children who presented to Lurie Children’s Hospital with AD and symptoms such as difficulty maintaining sleep and snoring with allergic rhinitis. They found that there were increased periods of being awake after the onset of sleep, “meaning the children fell asleep fairly easily in the beginning of the night but they had significant wake after they fell asleep,” he said. “They would wake up in the middle of the night and stay awake for long periods of time – either one long session or multiple shorter sessions throughout the night. They had increased total limb movements per hour of sleep. This means that their limb movements were greater than five events per hour of sleep and it resulted in restless sleep and limb movements that would fulfill the criteria of periodic limb movement disorder.”

Most of these children had mild to moderate AD, he continued. “We feel that the sensory afferent loop in these youngsters doesn’t really turn off completely when they’re asleep. This is ripe for further study, but it makes intuitive sense that if the sensory afferent loop continues during sleep, it may affect the arousal system significantly.”

Dr. Sheldon recommended that any child who presents with a diagnosis of periodic limb movement disorder, periodic limb movements of sleep, or restless sleep disorder should be evaluated for AD. “The treatment then, would first require differentiation between periodic limb movement disorder of sleep and AD. Both should be addressed at the same time in order to solve the child’s daytime AD problem as well as the sleep-related issues that occur with an AD diagnosis.”

He reported having no financial disclosures.

An estimated 50% of children with atopic dermatitis (AD) struggle with sleep problems, with complaints that vary from sleep fragmentation to restlessness and limb movements, according to Stephen H. Sheldon, DO.

“They wake up frequently,” Dr. Sheldon, professor of pediatrics and neurology at Northwestern University, Chicago, said during the Revolutionizing Atopic Dermatitis symposium. “They may not stay up for long periods of time, but they move about often. There’s a loss of about 50 minutes of sleep per night in children with AD. This loss can result in significant sleep debt the following day. They have difficulty settling at night. Once they get into bed, they have difficulty falling asleep, and many of them have difficulty staying asleep.”

At the sleep medicine center at Lurie Children’s Hospital of Chicago, he and his colleagues have observed that some children with AD complain of difficulty with limb movements. “Part of the issue has been that they have been diagnosed with different sleep-related disorders, such as period limb movement disorder, restless leg syndrome, and growing pain,” Dr. Sheldon said. “Often, they do not know how to describe the manifestations of their leg discomfort in restless leg syndrome and period limb movement disorder and limb movements of sleep.”

Children who complain of growing pains say that their legs hurt, he continued. Sometimes they’ll say that they feel like spiders are crawling on their legs, or that their legs itch, but they often say they have pain in their legs that wakes them up and keeps them from keeping their legs still.

According to the American Academy of Sleep Medicine, periodic limb movement disorder of sleep is characterized by frequent limb movements that last at least 0.5 seconds and are separated by no more than 90 seconds. “They’re four movements in a row that are at least 5 seconds apart,” Dr. Sheldon said.

Interestingly, he added, children who have limb movement disorder have symptoms during the day, similar to adults. “But we see many children with periodic limb movements of sleep whose arms and legs are moving all night, and they don’t have many symptoms during the day.” These children may have difficulty falling or staying asleep, but do not fulfill all of the American Academy of Sleep Medicine criteria for diagnosis of periodic limb movement disorder, he added.

In 2018, Lourdes M. DelRosso, MD, EdD, of Seattle Children’s Hospital, and colleagues described a new sleep problem they termed restless sleep disorder: those who do not fit the criteria for any other sleep disorder but have daytime impairment.

“On video they have very frequent movements – more than five movements an hour of major body activity,” Dr. Sheldon explained. “They’ll move their trunk, their legs, and reposition themselves. We have found that there are many children who presented to the sleep disorder center with restless sleep, limb movement disorder, periodic limb movements of sleep, and daytime symptoms that would fulfill the criteria of periodic limb movement disorder but also have atopic dermatitis.”

Recently, Dr. Sheldon and his colleagues used polysomnographic variables to study children who presented to Lurie Children’s Hospital with AD and symptoms such as difficulty maintaining sleep and snoring with allergic rhinitis. They found that there were increased periods of being awake after the onset of sleep, “meaning the children fell asleep fairly easily in the beginning of the night but they had significant wake after they fell asleep,” he said. “They would wake up in the middle of the night and stay awake for long periods of time – either one long session or multiple shorter sessions throughout the night. They had increased total limb movements per hour of sleep. This means that their limb movements were greater than five events per hour of sleep and it resulted in restless sleep and limb movements that would fulfill the criteria of periodic limb movement disorder.”

Most of these children had mild to moderate AD, he continued. “We feel that the sensory afferent loop in these youngsters doesn’t really turn off completely when they’re asleep. This is ripe for further study, but it makes intuitive sense that if the sensory afferent loop continues during sleep, it may affect the arousal system significantly.”

Dr. Sheldon recommended that any child who presents with a diagnosis of periodic limb movement disorder, periodic limb movements of sleep, or restless sleep disorder should be evaluated for AD. “The treatment then, would first require differentiation between periodic limb movement disorder of sleep and AD. Both should be addressed at the same time in order to solve the child’s daytime AD problem as well as the sleep-related issues that occur with an AD diagnosis.”

He reported having no financial disclosures.

The United States reported 1.35 million new COVID-19 cases on Jan. 10, logging the highest daily total for any country in the world during the pandemic.

The United States set the previous record of 1 million cases on Jan. 3. (A large number of cases are reported on Mondays, since many states don’t provide updates over the weekend, according to Reuters.)

Still, the 7-day average for new cases has surpassed 700,000, tripling in 2 weeks as the contagious Omicron variant continues to spread across the country.

The daily record of new cases came a day after the United States crossed the grim milestone of 60 million COVID-19 cases during the pandemic, according to the latest data from Johns Hopkins University. More than 11 million new cases were reported in the past 28 days, with 5 million reported since Jan. 2.

Globally, more than 310 million cases have been reported, resulting in nearly 5.5 million COVID-19 deaths. Almost 40 million cases have been confirmed worldwide during the past month, with the United States accounting for 28% of those.

Texas became the second state to report more than 5 million cases since the pandemic began, behind California’s total of 6 million cases. Florida has reported more than 4.6 million, while New York has reported more than 4.1 million.

The United States has also hit an all-time high for hospitalizations, with nearly 146,000 COVID-19 patients in hospitals across the country, according to the latest data from the U.S. Department of Health and Human Services. The previous record was 142,000 hospitalizations in January 2021.

Jan. 11’s hospitalizations are more than twice as many as 2 weeks ago, according to CNN. About 78% of inpatient beds are in use nationwide, and 21% are being used for COVID-19 patients.

Deaths are averaging about 1,700 per day, Reuters reported, which is up from 1,400 in recent days but not much higher than earlier this winter. The peak average was 3,400 daily deaths in mid-January 2021.

The surging numbers of cases and hospitalizations across the country are straining hospitals. On Jan. 10, Virginia Gov. Ralph Northam declared a state of emergency after the number of intensive care unit hospitalizations more than doubled since Dec. 1, CNN reported. The order allows hospitals to expand bed capacity, use telehealth options, and be more flexible with staffing.

Texas is hiring at least 2,700 medical staff to help with the surge, CNN reported, and Kentucky has mobilized the National Guard to provide support.

“Omicron continues to burn through the commonwealth, growing at levels we have never seen before. Omicron is significantly more contagious than even the Delta variant,” Kentucky Gov. Andy Beshear said during a news briefing Jan. 10.

Kentucky reported its highest weekly total of cases last week and has its highest rate of positive tests, at 26%. Mr. Beshear said the state is down to 134 available adult ICU beds.

“If it spreads at the rate we are seeing, it is certainly going to fill up our hospitals,” he said.

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

The United States reported 1.35 million new COVID-19 cases on Jan. 10, logging the highest daily total for any country in the world during the pandemic.

The United States set the previous record of 1 million cases on Jan. 3. (A large number of cases are reported on Mondays, since many states don’t provide updates over the weekend, according to Reuters.)

Still, the 7-day average for new cases has surpassed 700,000, tripling in 2 weeks as the contagious Omicron variant continues to spread across the country.

The daily record of new cases came a day after the United States crossed the grim milestone of 60 million COVID-19 cases during the pandemic, according to the latest data from Johns Hopkins University. More than 11 million new cases were reported in the past 28 days, with 5 million reported since Jan. 2.

Globally, more than 310 million cases have been reported, resulting in nearly 5.5 million COVID-19 deaths. Almost 40 million cases have been confirmed worldwide during the past month, with the United States accounting for 28% of those.

Texas became the second state to report more than 5 million cases since the pandemic began, behind California’s total of 6 million cases. Florida has reported more than 4.6 million, while New York has reported more than 4.1 million.

The United States has also hit an all-time high for hospitalizations, with nearly 146,000 COVID-19 patients in hospitals across the country, according to the latest data from the U.S. Department of Health and Human Services. The previous record was 142,000 hospitalizations in January 2021.

Jan. 11’s hospitalizations are more than twice as many as 2 weeks ago, according to CNN. About 78% of inpatient beds are in use nationwide, and 21% are being used for COVID-19 patients.

Deaths are averaging about 1,700 per day, Reuters reported, which is up from 1,400 in recent days but not much higher than earlier this winter. The peak average was 3,400 daily deaths in mid-January 2021.

The surging numbers of cases and hospitalizations across the country are straining hospitals. On Jan. 10, Virginia Gov. Ralph Northam declared a state of emergency after the number of intensive care unit hospitalizations more than doubled since Dec. 1, CNN reported. The order allows hospitals to expand bed capacity, use telehealth options, and be more flexible with staffing.

Texas is hiring at least 2,700 medical staff to help with the surge, CNN reported, and Kentucky has mobilized the National Guard to provide support.

“Omicron continues to burn through the commonwealth, growing at levels we have never seen before. Omicron is significantly more contagious than even the Delta variant,” Kentucky Gov. Andy Beshear said during a news briefing Jan. 10.

Kentucky reported its highest weekly total of cases last week and has its highest rate of positive tests, at 26%. Mr. Beshear said the state is down to 134 available adult ICU beds.

“If it spreads at the rate we are seeing, it is certainly going to fill up our hospitals,” he said.

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

The United States reported 1.35 million new COVID-19 cases on Jan. 10, logging the highest daily total for any country in the world during the pandemic.

The United States set the previous record of 1 million cases on Jan. 3. (A large number of cases are reported on Mondays, since many states don’t provide updates over the weekend, according to Reuters.)

Still, the 7-day average for new cases has surpassed 700,000, tripling in 2 weeks as the contagious Omicron variant continues to spread across the country.

The daily record of new cases came a day after the United States crossed the grim milestone of 60 million COVID-19 cases during the pandemic, according to the latest data from Johns Hopkins University. More than 11 million new cases were reported in the past 28 days, with 5 million reported since Jan. 2.

Globally, more than 310 million cases have been reported, resulting in nearly 5.5 million COVID-19 deaths. Almost 40 million cases have been confirmed worldwide during the past month, with the United States accounting for 28% of those.

Texas became the second state to report more than 5 million cases since the pandemic began, behind California’s total of 6 million cases. Florida has reported more than 4.6 million, while New York has reported more than 4.1 million.

The United States has also hit an all-time high for hospitalizations, with nearly 146,000 COVID-19 patients in hospitals across the country, according to the latest data from the U.S. Department of Health and Human Services. The previous record was 142,000 hospitalizations in January 2021.

Jan. 11’s hospitalizations are more than twice as many as 2 weeks ago, according to CNN. About 78% of inpatient beds are in use nationwide, and 21% are being used for COVID-19 patients.

Deaths are averaging about 1,700 per day, Reuters reported, which is up from 1,400 in recent days but not much higher than earlier this winter. The peak average was 3,400 daily deaths in mid-January 2021.

The surging numbers of cases and hospitalizations across the country are straining hospitals. On Jan. 10, Virginia Gov. Ralph Northam declared a state of emergency after the number of intensive care unit hospitalizations more than doubled since Dec. 1, CNN reported. The order allows hospitals to expand bed capacity, use telehealth options, and be more flexible with staffing.

Texas is hiring at least 2,700 medical staff to help with the surge, CNN reported, and Kentucky has mobilized the National Guard to provide support.

“Omicron continues to burn through the commonwealth, growing at levels we have never seen before. Omicron is significantly more contagious than even the Delta variant,” Kentucky Gov. Andy Beshear said during a news briefing Jan. 10.

Kentucky reported its highest weekly total of cases last week and has its highest rate of positive tests, at 26%. Mr. Beshear said the state is down to 134 available adult ICU beds.

“If it spreads at the rate we are seeing, it is certainly going to fill up our hospitals,” he said.

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

A new study has found that proactive therapeutic drug monitoring (TDM) with maintenance infliximab is more effective than standard therapy in sustaining control of immune-mediated inflammatory diseases.

The findings from the Norwegian Drug Monitoring B (NOR-DRUM B) trial, published Dec. 21, 2021, in JAMA, provide greater support to the usefulness of TDM in proactively monitoring serum drug levels and antidrug antibodies to infliximab, which has been previously shown to have benefit in patients with inflammatory bowel disease, but leave the benefits of proactive versus reactive monitoring and the cost-effectiveness of the approach in individual immune-mediated inflammatory diseases still open to questioning.

Alexander Raths/ThinkStock

TDM is ‘not the holy grail,’ and that’s OK

“This is an important milestone in the field of TDM with biologics for immunoinflammatory diseases,” Niels Vande Casteele, PharmD, PhD, of the University of California, San Diego, told this news organization. He was not involved in the study.

“When you read through the study, you can see the authors used the TAXIT trial results to inform their study design and the sample size,” he added, referencing his 2015 study on infliximab guide dosing for patients with inflammatory bowel disease, “the first-ever randomized, controlled trial of proactive TDM with any biologic.”

For the TAXIT study’s primary outcome of clinical and biochemical remission at 1 year, “continued concentration-based dosing was not superior to clinically based dosing for achieving remission.” But in regard to their secondary outcome of sustained remission, their results were quite similar to the results of NOR-DRUM B.

“If anything, we already showed a benefit of proactive TDM in 2015,” he said, “but I’m very glad that the authors looked at the trial design and teased out where TDM could be the most important and have the biggest impact, which is to maintain that sustained disease remission over a prolonged period.”

As for next steps, Dr. Vande Casteele noted that TDM isn’t a one-size-fits-all upgrade for drug treatments. But that doesn’t mean it won’t be very useful in many patients.

“What the paper is saying, and what we’ve been finding all along, is that TDM is not the holy grail,” he said. “But it is a tool in the physicians’ toolbox to optimize treatments and maximize efficacy, and there are some patients who truly benefit from it.”
 

Study details

To determine if proactive TDM with infliximab led to more sustained disease control than standard therapy, first author Silje Watterdal Syversen, MD, PhD, of Diakonhjemmet Hospital in Oslo, and coauthors conducted a 52-week, randomized, parallel-group, open-label trial. From 20 Norwegian hospitals, they recruited 458 patients with rheumatoid arthritis (n = 80), spondyloarthritis (n = 138), psoriatic arthritis (n = 54), ulcerative colitis (n = 81), Crohn’s disease (n = 68), or psoriasis (n = 37) who were undergoing maintenance therapy with the biologic.

The 454 patients who received at least one randomly allocated dose of infliximab were treated with one of two strategies: TDM (n = 227) or standard therapy (n = 227). The TDM group received dose and interval adjustments based on an algorithm that factored in serum drug levels and antidrug antibodies. The standard therapy group was treated on the basis of clinical judgment and physician discretion. The average age across groups was roughly 45 years, and just under 50% were women.

Overall, sustained disease control without worsening was achieved in 167 patients (73.6%) in the TDM group and 127 patients (55.9%) in the standard therapy group, with an estimated adjusted difference of 17.6% (95% confidence interval, 9.0%-26.2%; P < .001). The estimated hazard ratio of disease worsening was 2.1 (95% CI, 1.5-2.9) for standard therapy, compared with TDM. A total of 27 patients (15%) in the standard therapy group and 21 patients (9.2%) in the TDM group developed significant levels of antidrug antibodies, defined here as 50 mcg/L or more.

A total of 34 patients discontinued infliximab in each group; in the TDM group, most discontinued because of antidrug antibody formation, while the main reason for discontinuing in the standard therapy group was disease worsening. Adverse events were reported in 137 patients (60%) in the TDM group and 142 patients (63%) in the standard therapy group.

Removing barriers to TDM

It’s not clear that proactive TDM will benefit treatment with all biologic disease-modifying antirheumatic drugs (bDMARDs), but the findings from Dr. Syversen and colleagues state the clear value of using drug monitoring to guide maintenance therapy with infliximab, Zachary S. Wallace, MD, and Jeffrey A. Sparks, MD, wrote in an accompanying editorial.

“The relatively large sample size and rigorous study design ... helped to overcome some limitations of previous observational studies and small clinical trials that yielded conflicting results regarding TDM,” they added, noting that these findings contrasted somewhat with the NOR-DRUM A trial in which TDM did not improve remission induction in patients initiating infliximab therapy.

Along those lines, they recognized that TDM appears to have a greater effect in patients on maintenance infliximab, compared with those just starting the drug, surmising – among several explanations – that achieving remission in someone beginning treatment is a more difficult outcome to achieve than controlling disease in a patient already in remission.

For now, more clinical trials assessing specific diseases and involving other bDMARDs are needed; Dr. Wallace and Dr. Sparks stated that it’s time to remove barriers to implementing TDM – including the need for medical insurance preauthorization before increasing drug doses – and potentially “introduce a new era in treatment approach to maintenance therapy for patients with immune-mediated inflammatory diseases.”

The authors acknowledged their study’s limitations, including disease worsening being measured in part by patient-physician consensus and thus potentially subject to bias. In addition, they did not have the statistical ability to test TDM effectiveness in each of the six disease groups, noting that “these diseases have inherent differences, and findings may not be completely generalizable across groups.”

The study was funded by grants from the Norwegian Regional Health Authorities and the South-Eastern Norway Regional Health Authorities. The authors reported numerous potential conflicts of interest, including receiving personal fees and grants from various pharmaceutical companies. Dr. Wallace and Dr. Sparks also reported receiving research support and fees from pharmaceutical companies. Dr. Vande Casteele reported receiving research grants and personal fees from multiple pharmaceutical companies, all outside of the reviewed work.

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

A new study has found that proactive therapeutic drug monitoring (TDM) with maintenance infliximab is more effective than standard therapy in sustaining control of immune-mediated inflammatory diseases.

The findings from the Norwegian Drug Monitoring B (NOR-DRUM B) trial, published Dec. 21, 2021, in JAMA, provide greater support to the usefulness of TDM in proactively monitoring serum drug levels and antidrug antibodies to infliximab, which has been previously shown to have benefit in patients with inflammatory bowel disease, but leave the benefits of proactive versus reactive monitoring and the cost-effectiveness of the approach in individual immune-mediated inflammatory diseases still open to questioning.

Alexander Raths/ThinkStock

TDM is ‘not the holy grail,’ and that’s OK

“This is an important milestone in the field of TDM with biologics for immunoinflammatory diseases,” Niels Vande Casteele, PharmD, PhD, of the University of California, San Diego, told this news organization. He was not involved in the study.

“When you read through the study, you can see the authors used the TAXIT trial results to inform their study design and the sample size,” he added, referencing his 2015 study on infliximab guide dosing for patients with inflammatory bowel disease, “the first-ever randomized, controlled trial of proactive TDM with any biologic.”

For the TAXIT study’s primary outcome of clinical and biochemical remission at 1 year, “continued concentration-based dosing was not superior to clinically based dosing for achieving remission.” But in regard to their secondary outcome of sustained remission, their results were quite similar to the results of NOR-DRUM B.

“If anything, we already showed a benefit of proactive TDM in 2015,” he said, “but I’m very glad that the authors looked at the trial design and teased out where TDM could be the most important and have the biggest impact, which is to maintain that sustained disease remission over a prolonged period.”

As for next steps, Dr. Vande Casteele noted that TDM isn’t a one-size-fits-all upgrade for drug treatments. But that doesn’t mean it won’t be very useful in many patients.

“What the paper is saying, and what we’ve been finding all along, is that TDM is not the holy grail,” he said. “But it is a tool in the physicians’ toolbox to optimize treatments and maximize efficacy, and there are some patients who truly benefit from it.”
 

Study details

To determine if proactive TDM with infliximab led to more sustained disease control than standard therapy, first author Silje Watterdal Syversen, MD, PhD, of Diakonhjemmet Hospital in Oslo, and coauthors conducted a 52-week, randomized, parallel-group, open-label trial. From 20 Norwegian hospitals, they recruited 458 patients with rheumatoid arthritis (n = 80), spondyloarthritis (n = 138), psoriatic arthritis (n = 54), ulcerative colitis (n = 81), Crohn’s disease (n = 68), or psoriasis (n = 37) who were undergoing maintenance therapy with the biologic.

The 454 patients who received at least one randomly allocated dose of infliximab were treated with one of two strategies: TDM (n = 227) or standard therapy (n = 227). The TDM group received dose and interval adjustments based on an algorithm that factored in serum drug levels and antidrug antibodies. The standard therapy group was treated on the basis of clinical judgment and physician discretion. The average age across groups was roughly 45 years, and just under 50% were women.

Overall, sustained disease control without worsening was achieved in 167 patients (73.6%) in the TDM group and 127 patients (55.9%) in the standard therapy group, with an estimated adjusted difference of 17.6% (95% confidence interval, 9.0%-26.2%; P < .001). The estimated hazard ratio of disease worsening was 2.1 (95% CI, 1.5-2.9) for standard therapy, compared with TDM. A total of 27 patients (15%) in the standard therapy group and 21 patients (9.2%) in the TDM group developed significant levels of antidrug antibodies, defined here as 50 mcg/L or more.

A total of 34 patients discontinued infliximab in each group; in the TDM group, most discontinued because of antidrug antibody formation, while the main reason for discontinuing in the standard therapy group was disease worsening. Adverse events were reported in 137 patients (60%) in the TDM group and 142 patients (63%) in the standard therapy group.

Removing barriers to TDM

It’s not clear that proactive TDM will benefit treatment with all biologic disease-modifying antirheumatic drugs (bDMARDs), but the findings from Dr. Syversen and colleagues state the clear value of using drug monitoring to guide maintenance therapy with infliximab, Zachary S. Wallace, MD, and Jeffrey A. Sparks, MD, wrote in an accompanying editorial.

“The relatively large sample size and rigorous study design ... helped to overcome some limitations of previous observational studies and small clinical trials that yielded conflicting results regarding TDM,” they added, noting that these findings contrasted somewhat with the NOR-DRUM A trial in which TDM did not improve remission induction in patients initiating infliximab therapy.

Along those lines, they recognized that TDM appears to have a greater effect in patients on maintenance infliximab, compared with those just starting the drug, surmising – among several explanations – that achieving remission in someone beginning treatment is a more difficult outcome to achieve than controlling disease in a patient already in remission.

For now, more clinical trials assessing specific diseases and involving other bDMARDs are needed; Dr. Wallace and Dr. Sparks stated that it’s time to remove barriers to implementing TDM – including the need for medical insurance preauthorization before increasing drug doses – and potentially “introduce a new era in treatment approach to maintenance therapy for patients with immune-mediated inflammatory diseases.”

The authors acknowledged their study’s limitations, including disease worsening being measured in part by patient-physician consensus and thus potentially subject to bias. In addition, they did not have the statistical ability to test TDM effectiveness in each of the six disease groups, noting that “these diseases have inherent differences, and findings may not be completely generalizable across groups.”

The study was funded by grants from the Norwegian Regional Health Authorities and the South-Eastern Norway Regional Health Authorities. The authors reported numerous potential conflicts of interest, including receiving personal fees and grants from various pharmaceutical companies. Dr. Wallace and Dr. Sparks also reported receiving research support and fees from pharmaceutical companies. Dr. Vande Casteele reported receiving research grants and personal fees from multiple pharmaceutical companies, all outside of the reviewed work.

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

A new study has found that proactive therapeutic drug monitoring (TDM) with maintenance infliximab is more effective than standard therapy in sustaining control of immune-mediated inflammatory diseases.

The findings from the Norwegian Drug Monitoring B (NOR-DRUM B) trial, published Dec. 21, 2021, in JAMA, provide greater support to the usefulness of TDM in proactively monitoring serum drug levels and antidrug antibodies to infliximab, which has been previously shown to have benefit in patients with inflammatory bowel disease, but leave the benefits of proactive versus reactive monitoring and the cost-effectiveness of the approach in individual immune-mediated inflammatory diseases still open to questioning.

Alexander Raths/ThinkStock

TDM is ‘not the holy grail,’ and that’s OK

“This is an important milestone in the field of TDM with biologics for immunoinflammatory diseases,” Niels Vande Casteele, PharmD, PhD, of the University of California, San Diego, told this news organization. He was not involved in the study.

“When you read through the study, you can see the authors used the TAXIT trial results to inform their study design and the sample size,” he added, referencing his 2015 study on infliximab guide dosing for patients with inflammatory bowel disease, “the first-ever randomized, controlled trial of proactive TDM with any biologic.”

For the TAXIT study’s primary outcome of clinical and biochemical remission at 1 year, “continued concentration-based dosing was not superior to clinically based dosing for achieving remission.” But in regard to their secondary outcome of sustained remission, their results were quite similar to the results of NOR-DRUM B.

“If anything, we already showed a benefit of proactive TDM in 2015,” he said, “but I’m very glad that the authors looked at the trial design and teased out where TDM could be the most important and have the biggest impact, which is to maintain that sustained disease remission over a prolonged period.”

As for next steps, Dr. Vande Casteele noted that TDM isn’t a one-size-fits-all upgrade for drug treatments. But that doesn’t mean it won’t be very useful in many patients.

“What the paper is saying, and what we’ve been finding all along, is that TDM is not the holy grail,” he said. “But it is a tool in the physicians’ toolbox to optimize treatments and maximize efficacy, and there are some patients who truly benefit from it.”
 

Study details

To determine if proactive TDM with infliximab led to more sustained disease control than standard therapy, first author Silje Watterdal Syversen, MD, PhD, of Diakonhjemmet Hospital in Oslo, and coauthors conducted a 52-week, randomized, parallel-group, open-label trial. From 20 Norwegian hospitals, they recruited 458 patients with rheumatoid arthritis (n = 80), spondyloarthritis (n = 138), psoriatic arthritis (n = 54), ulcerative colitis (n = 81), Crohn’s disease (n = 68), or psoriasis (n = 37) who were undergoing maintenance therapy with the biologic.

The 454 patients who received at least one randomly allocated dose of infliximab were treated with one of two strategies: TDM (n = 227) or standard therapy (n = 227). The TDM group received dose and interval adjustments based on an algorithm that factored in serum drug levels and antidrug antibodies. The standard therapy group was treated on the basis of clinical judgment and physician discretion. The average age across groups was roughly 45 years, and just under 50% were women.

Overall, sustained disease control without worsening was achieved in 167 patients (73.6%) in the TDM group and 127 patients (55.9%) in the standard therapy group, with an estimated adjusted difference of 17.6% (95% confidence interval, 9.0%-26.2%; P < .001). The estimated hazard ratio of disease worsening was 2.1 (95% CI, 1.5-2.9) for standard therapy, compared with TDM. A total of 27 patients (15%) in the standard therapy group and 21 patients (9.2%) in the TDM group developed significant levels of antidrug antibodies, defined here as 50 mcg/L or more.

A total of 34 patients discontinued infliximab in each group; in the TDM group, most discontinued because of antidrug antibody formation, while the main reason for discontinuing in the standard therapy group was disease worsening. Adverse events were reported in 137 patients (60%) in the TDM group and 142 patients (63%) in the standard therapy group.

Removing barriers to TDM

It’s not clear that proactive TDM will benefit treatment with all biologic disease-modifying antirheumatic drugs (bDMARDs), but the findings from Dr. Syversen and colleagues state the clear value of using drug monitoring to guide maintenance therapy with infliximab, Zachary S. Wallace, MD, and Jeffrey A. Sparks, MD, wrote in an accompanying editorial.

“The relatively large sample size and rigorous study design ... helped to overcome some limitations of previous observational studies and small clinical trials that yielded conflicting results regarding TDM,” they added, noting that these findings contrasted somewhat with the NOR-DRUM A trial in which TDM did not improve remission induction in patients initiating infliximab therapy.

Along those lines, they recognized that TDM appears to have a greater effect in patients on maintenance infliximab, compared with those just starting the drug, surmising – among several explanations – that achieving remission in someone beginning treatment is a more difficult outcome to achieve than controlling disease in a patient already in remission.

For now, more clinical trials assessing specific diseases and involving other bDMARDs are needed; Dr. Wallace and Dr. Sparks stated that it’s time to remove barriers to implementing TDM – including the need for medical insurance preauthorization before increasing drug doses – and potentially “introduce a new era in treatment approach to maintenance therapy for patients with immune-mediated inflammatory diseases.”

The authors acknowledged their study’s limitations, including disease worsening being measured in part by patient-physician consensus and thus potentially subject to bias. In addition, they did not have the statistical ability to test TDM effectiveness in each of the six disease groups, noting that “these diseases have inherent differences, and findings may not be completely generalizable across groups.”

The study was funded by grants from the Norwegian Regional Health Authorities and the South-Eastern Norway Regional Health Authorities. The authors reported numerous potential conflicts of interest, including receiving personal fees and grants from various pharmaceutical companies. Dr. Wallace and Dr. Sparks also reported receiving research support and fees from pharmaceutical companies. Dr. Vande Casteele reported receiving research grants and personal fees from multiple pharmaceutical companies, all outside of the reviewed work.

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

The risk of myocarditis after immunization with mRNA-based vaccines against SARS-CoV-2 raised concerns when it came to light in early 2021. But as report after report showed such cases to be rare and usually mild and self-limited, focus has turned to the “how and why.”  

The mechanism linking the BNT162b2 (Pfizer-BioNTech) and especially mRNA-1273 (Moderna) vaccines to the occurrence of myocarditis is unclear for now, but one potential driver may be tied to a peculiarity that became apparent early: It occurs overwhelmingly in younger males, from 16 to perhaps 40 or 50 years of age. Excess risk has not been consistently seen among women, girls, and older men.

peterschreiber_media/iStock/Getty Images

That observation has led to speculation that higher testosterone levels in adolescent boys and young men may somehow promote the adverse vaccine effect, whereas greater levels of estrogen among girls and women in the same age range may be cardioprotective.
 

Unlikely, brief, and ‘benign’

“Most of the myocarditis is benign, by which I mean that maybe the patients are admitted due to chest pain, but without reduction in ventricular function,” Enrico Ammirati, MD, PhD, a myocarditis expert at De Gasperis Cardio Center and Transplant Center, Niguarda Hospital, Milan, said in an interview.

In a Nov. 14 address on this topic at the annual scientific sessions of the American Heart Association, Dror Mevorach, MD, described the typical case presentation as “mild” and one that clears in fairly short order based on resolution of “clinical symptoms, inflammatory markers and troponin decline, EKG normalization, echo normalization, and a relatively short length of hospital stay.”

Dr. Mevorach, of Hadassah Hebrew University Medical Center, Jerusalem, subsequently published the findings in a report in the New England Journal of Medicine that described 136 confirmed myocarditis cases among more than 5 million people in Israel immunized with the Pfizer-BioNTech vaccine. Myocarditis was considered “mild” in 129 cases, or 95%.

And the risk is tiny, compared with myocarditis from infection by SARS-CoV-2, not to mention the possibility of nasty clinical COVID-19 complications such as pneumonia and pulmonary embolism, Dr. Mevorach observed.

Many other reports agree that the incidence is minimal, especially given the rewards of vaccination. In a separate NEJM publication in September 2021 – from Noam Barda, MD, Clalit (Israel) Research Institute, and colleagues on 1.7 million people in that country, about half unvaccinated and half given the Pfizer-BioNTech vaccine – there were an estimated 2.7 cases of  myocarditis per 100,000 vaccinated persons. There were also 11 cases of myocarditis per 100,000 persons who were positive for SARS-CoV-2 infection.

And in a recent case series of vaccinated people aged 16 or older, the myocarditis rate after a first or second Pfizer-BioNTech or Moderna injection was estimated at 1 or fewer per 100,000. The corresponding estimate was 4 such cases per 100,000 after a positive SARS-CoV-2 test among the same population, notes a report published Dec.14, 2021, in Nature Medicine.

In general, “the risk of any kind of cardiac injury is vastly lower with a vaccine than it is with the actual viral infection,” Leslie T. Cooper Jr., MD, a myocarditis expert and clinical trialist at the Mayo Clinic, Jacksonville, Fla., said in an interview. With the mRNA-based vaccines, “we do not have any conceivable danger signal that would outweigh the benefit of vaccination.”
 

Males of a certain age

Evidence that such myocarditis predominates in young adult men and adolescent boys, especially following a second vaccine dose, is remarkably consistent.

The risk was elevated only among mRNA-based vaccine recipients who were younger than 40 in the recent Nature Medicine analysis. Among that group, estimates after a second dose numbered fewer than 1 case per 100,000 for Pfizer-BioNTech and 1.5 per 100,000 for Moderna.

In a third analysis from Israel – also in NEJM, from Guy Witberg, MD, Rabin Medical Center, Petah Tikva, and colleagues, based on 2.5 million people aged 16 and older with at least one Pfizer-BioNTech injection – 2.1 cases per 100,000 were estimated overall, but the number rose to 10.7 per 100,000 among those aged 16-29 years.

In Dr. Mevorach’s NEJM report, estimates after a second Pfizer-BioNTech vaccine dose were 1 per 26,000 males versus 1 in 218,000 females, compared with 1 myocarditis case in 10,857 persons among “the general unvaccinated population.”

Most recipients of a first vaccine dose were younger than 50, and 16- to 29-year-olds accounted for most who completed two doses, noted Dr. Mevorach. Younger males bore the brunt of any myocarditis: the estimated prevalence after a second dose among males aged 16-19 was 1 per 6,637, compared with 1 per 99,853 females in the same age range, the group reported.

In the BMJ report, based on about 5 million people 12 years of age or older in Denmark, the estimated rates of myocarditis or pericarditis associated with Moderna immunization were 2 per 100,000 among women but 6.3 per 100,000 for men. The incidence and sex difference was much lower among those getting the Pfizer-BioNTech vaccine: 1.3 per 100,000 and 1.5 per 100,000 in women and men, respectively.
 

Sex hormones may be key

The predominance of vaccine-associated myocarditis among adolescent and young adult males is probably more about the myocarditis itself than the vaccines, observed Biykem Bozkurt, MD, PhD, who has been studying COVID-related myocarditis at Baylor College of Medicine, Houston.

Male sex historically is associated in both epidemiologic studies and experimental models with a greater propensity for most any form of myocarditis, Dr. Bozkurt said in an interview. Given that males aged 16-19 or so appear to be at highest risk of myocarditis as a complication of SARS-CoV-2 vaccination, the mechanism may well be related to sex hormones.  

“Therefore, testosterone is implicated as a player in their higher risk of inflammation and injury and lack of adaptive response in terms of healing, and in terms of prevention of injury,” Dr. Bozkurt said. For its part, estrogen inhibits proinflammatory processes and, in particular, “blunts cell-mediated immune responses.”

“We don’t know the mechanism, but a theory that attributes a protective role to estrogen, or a risk associated with testosterone, is reasonable. It makes sense, at least based on epidemiological data,” Dr. Ammirati agreed. Still, “we do not have any direct evidence in human beings.”

Sex-associated differences in experimental myocarditis have been reported in the journals for at least 70 years, but “the testosterone literature and the estrogen literature have not been evaluated in detail in vaccine-associated myocarditis,” Dr. Cooper said.

Most myocarditis in the laboratory is viral, Dr. Cooper observed, and “the links between testosterone, viruses, and inflammation have been pretty well worked out, I would say, if you’re a mouse. If you’re a human, I think it’s still a bit uncertain.”

Were it to apply in humans, greater testosterone levels might independently promote myocarditis, “and if estrogen is cardioprotective, it would be another mechanism,” Dr. Cooper said. “That would translate to slight male predominance in most kinds of myocarditis.”

In males, compared with females, “the heart can be more vulnerable to events such as arrhythmias or to immune-mediated phenomena. So, probably there is also higher vulnerability to myocarditis in men,” Dr. Ammirati noted.

Male predominance in vaccine-related myocarditis is provocative, so it’s worth considering whether testosterone is part of the mechanism as well as the possibility of estrogen cardioprotection, Dr. Ammirati said. But given limitations of the animal models, “we don’t really have robust data to support any part of that.”

Although myocarditis is in some way immune mediated, “and hormones can modulate the response,” the mechanism has to be more than just sex hormones, he said. “They probably cannot explain the specificity for the heart. It’s not a systemic response, it’s an organ-specific response.”
 

Modulation of immune responses

Details about the immune processes underlying mRNA-vaccine myocarditis, hormone modulated or not, have been elusive. The complication doesn’t resemble serum sickness, nor does it seem to be a reaction to infection by other cardiotropic viruses, such as coxsackie virus B, a cause of viral myocarditis, Dr. Bozkurt said. The latter had been a compelling possibility because such hypersensitivity to smallpox vaccination is well recognized.

“We don’t know the mechanism, that’s the short answer. But there are many hypotheses,” she said. One candidate widely proposed in the literature: autoantibodies driven by molecular mimicry between the SARS-CoV-2 spike protein targeted by the mRNA vaccines and a structurally similar myocardial protein, possibly alpha-myosin, noted Dr. Bozkurt and colleagues in a recent publication.

But elevations in specific “antiheart antibodies” have not been documented in recipients of the two mRNA-based vaccines, said Dr. Cooper. “So, I would say that – although molecular mimicry is a well-established mechanism of, for example, rheumatic carditis after a streptococcal A infection – that has not been demonstrated yet for COVID-19 mRNA vaccination–related myocarditis.”

“We probably won’t know, ever, with a huge level of certainty, the exact mechanisms,” Dr. Cooper added. There is no animal model for vaccine-induced myocarditis, and “We’re still talking very, very small numbers of patients. The vast majority of them recover,” and so don’t generally provide mechanistic clues.  
 

Prospects for younger children

Vaccination against SARS-CoV-2 has now been authorized by the Centers for Disease Control and Prevention for kids as young as 5-11 years, using the Pfizer-BioNTech vaccine. Experience so far suggests the immunization is safe in that age group with negligible risk of myocarditis or other complications. But with prospects of possible authorization in children younger than 5, should myocarditis be a concern for them?

Probably not, if the complication is driven primarily by sex hormones, Dr. Cooper proposed. “One would predict that before puberty you would have a lower – much, much lower – rate of myocarditis in males than you would in the 16- to 19-year-old range, and that it would be roughly equal to females.” Dr. Ammirati and Dr. Bozkurt largely agreed.

It remains to be seen whether the vaccine-related myocarditis risk applies to children younger than 12, “but I doubt it. I think it’s going to be puberty-related,” Dr. Bozkurt said. Still, “I don’t want to hypothesize without data.”

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

The risk of myocarditis after immunization with mRNA-based vaccines against SARS-CoV-2 raised concerns when it came to light in early 2021. But as report after report showed such cases to be rare and usually mild and self-limited, focus has turned to the “how and why.”  

The mechanism linking the BNT162b2 (Pfizer-BioNTech) and especially mRNA-1273 (Moderna) vaccines to the occurrence of myocarditis is unclear for now, but one potential driver may be tied to a peculiarity that became apparent early: It occurs overwhelmingly in younger males, from 16 to perhaps 40 or 50 years of age. Excess risk has not been consistently seen among women, girls, and older men.

peterschreiber_media/iStock/Getty Images

That observation has led to speculation that higher testosterone levels in adolescent boys and young men may somehow promote the adverse vaccine effect, whereas greater levels of estrogen among girls and women in the same age range may be cardioprotective.
 

Unlikely, brief, and ‘benign’

“Most of the myocarditis is benign, by which I mean that maybe the patients are admitted due to chest pain, but without reduction in ventricular function,” Enrico Ammirati, MD, PhD, a myocarditis expert at De Gasperis Cardio Center and Transplant Center, Niguarda Hospital, Milan, said in an interview.

In a Nov. 14 address on this topic at the annual scientific sessions of the American Heart Association, Dror Mevorach, MD, described the typical case presentation as “mild” and one that clears in fairly short order based on resolution of “clinical symptoms, inflammatory markers and troponin decline, EKG normalization, echo normalization, and a relatively short length of hospital stay.”

Dr. Mevorach, of Hadassah Hebrew University Medical Center, Jerusalem, subsequently published the findings in a report in the New England Journal of Medicine that described 136 confirmed myocarditis cases among more than 5 million people in Israel immunized with the Pfizer-BioNTech vaccine. Myocarditis was considered “mild” in 129 cases, or 95%.

And the risk is tiny, compared with myocarditis from infection by SARS-CoV-2, not to mention the possibility of nasty clinical COVID-19 complications such as pneumonia and pulmonary embolism, Dr. Mevorach observed.

Many other reports agree that the incidence is minimal, especially given the rewards of vaccination. In a separate NEJM publication in September 2021 – from Noam Barda, MD, Clalit (Israel) Research Institute, and colleagues on 1.7 million people in that country, about half unvaccinated and half given the Pfizer-BioNTech vaccine – there were an estimated 2.7 cases of  myocarditis per 100,000 vaccinated persons. There were also 11 cases of myocarditis per 100,000 persons who were positive for SARS-CoV-2 infection.

And in a recent case series of vaccinated people aged 16 or older, the myocarditis rate after a first or second Pfizer-BioNTech or Moderna injection was estimated at 1 or fewer per 100,000. The corresponding estimate was 4 such cases per 100,000 after a positive SARS-CoV-2 test among the same population, notes a report published Dec.14, 2021, in Nature Medicine.

In general, “the risk of any kind of cardiac injury is vastly lower with a vaccine than it is with the actual viral infection,” Leslie T. Cooper Jr., MD, a myocarditis expert and clinical trialist at the Mayo Clinic, Jacksonville, Fla., said in an interview. With the mRNA-based vaccines, “we do not have any conceivable danger signal that would outweigh the benefit of vaccination.”
 

Males of a certain age

Evidence that such myocarditis predominates in young adult men and adolescent boys, especially following a second vaccine dose, is remarkably consistent.

The risk was elevated only among mRNA-based vaccine recipients who were younger than 40 in the recent Nature Medicine analysis. Among that group, estimates after a second dose numbered fewer than 1 case per 100,000 for Pfizer-BioNTech and 1.5 per 100,000 for Moderna.

In a third analysis from Israel – also in NEJM, from Guy Witberg, MD, Rabin Medical Center, Petah Tikva, and colleagues, based on 2.5 million people aged 16 and older with at least one Pfizer-BioNTech injection – 2.1 cases per 100,000 were estimated overall, but the number rose to 10.7 per 100,000 among those aged 16-29 years.

In Dr. Mevorach’s NEJM report, estimates after a second Pfizer-BioNTech vaccine dose were 1 per 26,000 males versus 1 in 218,000 females, compared with 1 myocarditis case in 10,857 persons among “the general unvaccinated population.”

Most recipients of a first vaccine dose were younger than 50, and 16- to 29-year-olds accounted for most who completed two doses, noted Dr. Mevorach. Younger males bore the brunt of any myocarditis: the estimated prevalence after a second dose among males aged 16-19 was 1 per 6,637, compared with 1 per 99,853 females in the same age range, the group reported.

In the BMJ report, based on about 5 million people 12 years of age or older in Denmark, the estimated rates of myocarditis or pericarditis associated with Moderna immunization were 2 per 100,000 among women but 6.3 per 100,000 for men. The incidence and sex difference was much lower among those getting the Pfizer-BioNTech vaccine: 1.3 per 100,000 and 1.5 per 100,000 in women and men, respectively.
 

Sex hormones may be key

The predominance of vaccine-associated myocarditis among adolescent and young adult males is probably more about the myocarditis itself than the vaccines, observed Biykem Bozkurt, MD, PhD, who has been studying COVID-related myocarditis at Baylor College of Medicine, Houston.

Male sex historically is associated in both epidemiologic studies and experimental models with a greater propensity for most any form of myocarditis, Dr. Bozkurt said in an interview. Given that males aged 16-19 or so appear to be at highest risk of myocarditis as a complication of SARS-CoV-2 vaccination, the mechanism may well be related to sex hormones.  

“Therefore, testosterone is implicated as a player in their higher risk of inflammation and injury and lack of adaptive response in terms of healing, and in terms of prevention of injury,” Dr. Bozkurt said. For its part, estrogen inhibits proinflammatory processes and, in particular, “blunts cell-mediated immune responses.”

“We don’t know the mechanism, but a theory that attributes a protective role to estrogen, or a risk associated with testosterone, is reasonable. It makes sense, at least based on epidemiological data,” Dr. Ammirati agreed. Still, “we do not have any direct evidence in human beings.”

Sex-associated differences in experimental myocarditis have been reported in the journals for at least 70 years, but “the testosterone literature and the estrogen literature have not been evaluated in detail in vaccine-associated myocarditis,” Dr. Cooper said.

Most myocarditis in the laboratory is viral, Dr. Cooper observed, and “the links between testosterone, viruses, and inflammation have been pretty well worked out, I would say, if you’re a mouse. If you’re a human, I think it’s still a bit uncertain.”

Were it to apply in humans, greater testosterone levels might independently promote myocarditis, “and if estrogen is cardioprotective, it would be another mechanism,” Dr. Cooper said. “That would translate to slight male predominance in most kinds of myocarditis.”

In males, compared with females, “the heart can be more vulnerable to events such as arrhythmias or to immune-mediated phenomena. So, probably there is also higher vulnerability to myocarditis in men,” Dr. Ammirati noted.

Male predominance in vaccine-related myocarditis is provocative, so it’s worth considering whether testosterone is part of the mechanism as well as the possibility of estrogen cardioprotection, Dr. Ammirati said. But given limitations of the animal models, “we don’t really have robust data to support any part of that.”

Although myocarditis is in some way immune mediated, “and hormones can modulate the response,” the mechanism has to be more than just sex hormones, he said. “They probably cannot explain the specificity for the heart. It’s not a systemic response, it’s an organ-specific response.”
 

Modulation of immune responses

Details about the immune processes underlying mRNA-vaccine myocarditis, hormone modulated or not, have been elusive. The complication doesn’t resemble serum sickness, nor does it seem to be a reaction to infection by other cardiotropic viruses, such as coxsackie virus B, a cause of viral myocarditis, Dr. Bozkurt said. The latter had been a compelling possibility because such hypersensitivity to smallpox vaccination is well recognized.

“We don’t know the mechanism, that’s the short answer. But there are many hypotheses,” she said. One candidate widely proposed in the literature: autoantibodies driven by molecular mimicry between the SARS-CoV-2 spike protein targeted by the mRNA vaccines and a structurally similar myocardial protein, possibly alpha-myosin, noted Dr. Bozkurt and colleagues in a recent publication.

But elevations in specific “antiheart antibodies” have not been documented in recipients of the two mRNA-based vaccines, said Dr. Cooper. “So, I would say that – although molecular mimicry is a well-established mechanism of, for example, rheumatic carditis after a streptococcal A infection – that has not been demonstrated yet for COVID-19 mRNA vaccination–related myocarditis.”

“We probably won’t know, ever, with a huge level of certainty, the exact mechanisms,” Dr. Cooper added. There is no animal model for vaccine-induced myocarditis, and “We’re still talking very, very small numbers of patients. The vast majority of them recover,” and so don’t generally provide mechanistic clues.  
 

Prospects for younger children

Vaccination against SARS-CoV-2 has now been authorized by the Centers for Disease Control and Prevention for kids as young as 5-11 years, using the Pfizer-BioNTech vaccine. Experience so far suggests the immunization is safe in that age group with negligible risk of myocarditis or other complications. But with prospects of possible authorization in children younger than 5, should myocarditis be a concern for them?

Probably not, if the complication is driven primarily by sex hormones, Dr. Cooper proposed. “One would predict that before puberty you would have a lower – much, much lower – rate of myocarditis in males than you would in the 16- to 19-year-old range, and that it would be roughly equal to females.” Dr. Ammirati and Dr. Bozkurt largely agreed.

It remains to be seen whether the vaccine-related myocarditis risk applies to children younger than 12, “but I doubt it. I think it’s going to be puberty-related,” Dr. Bozkurt said. Still, “I don’t want to hypothesize without data.”

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

The risk of myocarditis after immunization with mRNA-based vaccines against SARS-CoV-2 raised concerns when it came to light in early 2021. But as report after report showed such cases to be rare and usually mild and self-limited, focus has turned to the “how and why.”  

The mechanism linking the BNT162b2 (Pfizer-BioNTech) and especially mRNA-1273 (Moderna) vaccines to the occurrence of myocarditis is unclear for now, but one potential driver may be tied to a peculiarity that became apparent early: It occurs overwhelmingly in younger males, from 16 to perhaps 40 or 50 years of age. Excess risk has not been consistently seen among women, girls, and older men.

peterschreiber_media/iStock/Getty Images

That observation has led to speculation that higher testosterone levels in adolescent boys and young men may somehow promote the adverse vaccine effect, whereas greater levels of estrogen among girls and women in the same age range may be cardioprotective.
 

Unlikely, brief, and ‘benign’

“Most of the myocarditis is benign, by which I mean that maybe the patients are admitted due to chest pain, but without reduction in ventricular function,” Enrico Ammirati, MD, PhD, a myocarditis expert at De Gasperis Cardio Center and Transplant Center, Niguarda Hospital, Milan, said in an interview.

In a Nov. 14 address on this topic at the annual scientific sessions of the American Heart Association, Dror Mevorach, MD, described the typical case presentation as “mild” and one that clears in fairly short order based on resolution of “clinical symptoms, inflammatory markers and troponin decline, EKG normalization, echo normalization, and a relatively short length of hospital stay.”

Dr. Mevorach, of Hadassah Hebrew University Medical Center, Jerusalem, subsequently published the findings in a report in the New England Journal of Medicine that described 136 confirmed myocarditis cases among more than 5 million people in Israel immunized with the Pfizer-BioNTech vaccine. Myocarditis was considered “mild” in 129 cases, or 95%.

And the risk is tiny, compared with myocarditis from infection by SARS-CoV-2, not to mention the possibility of nasty clinical COVID-19 complications such as pneumonia and pulmonary embolism, Dr. Mevorach observed.

Many other reports agree that the incidence is minimal, especially given the rewards of vaccination. In a separate NEJM publication in September 2021 – from Noam Barda, MD, Clalit (Israel) Research Institute, and colleagues on 1.7 million people in that country, about half unvaccinated and half given the Pfizer-BioNTech vaccine – there were an estimated 2.7 cases of  myocarditis per 100,000 vaccinated persons. There were also 11 cases of myocarditis per 100,000 persons who were positive for SARS-CoV-2 infection.

And in a recent case series of vaccinated people aged 16 or older, the myocarditis rate after a first or second Pfizer-BioNTech or Moderna injection was estimated at 1 or fewer per 100,000. The corresponding estimate was 4 such cases per 100,000 after a positive SARS-CoV-2 test among the same population, notes a report published Dec.14, 2021, in Nature Medicine.

In general, “the risk of any kind of cardiac injury is vastly lower with a vaccine than it is with the actual viral infection,” Leslie T. Cooper Jr., MD, a myocarditis expert and clinical trialist at the Mayo Clinic, Jacksonville, Fla., said in an interview. With the mRNA-based vaccines, “we do not have any conceivable danger signal that would outweigh the benefit of vaccination.”
 

Males of a certain age

Evidence that such myocarditis predominates in young adult men and adolescent boys, especially following a second vaccine dose, is remarkably consistent.

The risk was elevated only among mRNA-based vaccine recipients who were younger than 40 in the recent Nature Medicine analysis. Among that group, estimates after a second dose numbered fewer than 1 case per 100,000 for Pfizer-BioNTech and 1.5 per 100,000 for Moderna.

In a third analysis from Israel – also in NEJM, from Guy Witberg, MD, Rabin Medical Center, Petah Tikva, and colleagues, based on 2.5 million people aged 16 and older with at least one Pfizer-BioNTech injection – 2.1 cases per 100,000 were estimated overall, but the number rose to 10.7 per 100,000 among those aged 16-29 years.

In Dr. Mevorach’s NEJM report, estimates after a second Pfizer-BioNTech vaccine dose were 1 per 26,000 males versus 1 in 218,000 females, compared with 1 myocarditis case in 10,857 persons among “the general unvaccinated population.”

Most recipients of a first vaccine dose were younger than 50, and 16- to 29-year-olds accounted for most who completed two doses, noted Dr. Mevorach. Younger males bore the brunt of any myocarditis: the estimated prevalence after a second dose among males aged 16-19 was 1 per 6,637, compared with 1 per 99,853 females in the same age range, the group reported.

In the BMJ report, based on about 5 million people 12 years of age or older in Denmark, the estimated rates of myocarditis or pericarditis associated with Moderna immunization were 2 per 100,000 among women but 6.3 per 100,000 for men. The incidence and sex difference was much lower among those getting the Pfizer-BioNTech vaccine: 1.3 per 100,000 and 1.5 per 100,000 in women and men, respectively.
 

Sex hormones may be key

The predominance of vaccine-associated myocarditis among adolescent and young adult males is probably more about the myocarditis itself than the vaccines, observed Biykem Bozkurt, MD, PhD, who has been studying COVID-related myocarditis at Baylor College of Medicine, Houston.

Male sex historically is associated in both epidemiologic studies and experimental models with a greater propensity for most any form of myocarditis, Dr. Bozkurt said in an interview. Given that males aged 16-19 or so appear to be at highest risk of myocarditis as a complication of SARS-CoV-2 vaccination, the mechanism may well be related to sex hormones.  

“Therefore, testosterone is implicated as a player in their higher risk of inflammation and injury and lack of adaptive response in terms of healing, and in terms of prevention of injury,” Dr. Bozkurt said. For its part, estrogen inhibits proinflammatory processes and, in particular, “blunts cell-mediated immune responses.”

“We don’t know the mechanism, but a theory that attributes a protective role to estrogen, or a risk associated with testosterone, is reasonable. It makes sense, at least based on epidemiological data,” Dr. Ammirati agreed. Still, “we do not have any direct evidence in human beings.”

Sex-associated differences in experimental myocarditis have been reported in the journals for at least 70 years, but “the testosterone literature and the estrogen literature have not been evaluated in detail in vaccine-associated myocarditis,” Dr. Cooper said.

Most myocarditis in the laboratory is viral, Dr. Cooper observed, and “the links between testosterone, viruses, and inflammation have been pretty well worked out, I would say, if you’re a mouse. If you’re a human, I think it’s still a bit uncertain.”

Were it to apply in humans, greater testosterone levels might independently promote myocarditis, “and if estrogen is cardioprotective, it would be another mechanism,” Dr. Cooper said. “That would translate to slight male predominance in most kinds of myocarditis.”

In males, compared with females, “the heart can be more vulnerable to events such as arrhythmias or to immune-mediated phenomena. So, probably there is also higher vulnerability to myocarditis in men,” Dr. Ammirati noted.

Male predominance in vaccine-related myocarditis is provocative, so it’s worth considering whether testosterone is part of the mechanism as well as the possibility of estrogen cardioprotection, Dr. Ammirati said. But given limitations of the animal models, “we don’t really have robust data to support any part of that.”

Although myocarditis is in some way immune mediated, “and hormones can modulate the response,” the mechanism has to be more than just sex hormones, he said. “They probably cannot explain the specificity for the heart. It’s not a systemic response, it’s an organ-specific response.”
 

Modulation of immune responses

Details about the immune processes underlying mRNA-vaccine myocarditis, hormone modulated or not, have been elusive. The complication doesn’t resemble serum sickness, nor does it seem to be a reaction to infection by other cardiotropic viruses, such as coxsackie virus B, a cause of viral myocarditis, Dr. Bozkurt said. The latter had been a compelling possibility because such hypersensitivity to smallpox vaccination is well recognized.

“We don’t know the mechanism, that’s the short answer. But there are many hypotheses,” she said. One candidate widely proposed in the literature: autoantibodies driven by molecular mimicry between the SARS-CoV-2 spike protein targeted by the mRNA vaccines and a structurally similar myocardial protein, possibly alpha-myosin, noted Dr. Bozkurt and colleagues in a recent publication.

But elevations in specific “antiheart antibodies” have not been documented in recipients of the two mRNA-based vaccines, said Dr. Cooper. “So, I would say that – although molecular mimicry is a well-established mechanism of, for example, rheumatic carditis after a streptococcal A infection – that has not been demonstrated yet for COVID-19 mRNA vaccination–related myocarditis.”

“We probably won’t know, ever, with a huge level of certainty, the exact mechanisms,” Dr. Cooper added. There is no animal model for vaccine-induced myocarditis, and “We’re still talking very, very small numbers of patients. The vast majority of them recover,” and so don’t generally provide mechanistic clues.  
 

Prospects for younger children

Vaccination against SARS-CoV-2 has now been authorized by the Centers for Disease Control and Prevention for kids as young as 5-11 years, using the Pfizer-BioNTech vaccine. Experience so far suggests the immunization is safe in that age group with negligible risk of myocarditis or other complications. But with prospects of possible authorization in children younger than 5, should myocarditis be a concern for them?

Probably not, if the complication is driven primarily by sex hormones, Dr. Cooper proposed. “One would predict that before puberty you would have a lower – much, much lower – rate of myocarditis in males than you would in the 16- to 19-year-old range, and that it would be roughly equal to females.” Dr. Ammirati and Dr. Bozkurt largely agreed.

It remains to be seen whether the vaccine-related myocarditis risk applies to children younger than 12, “but I doubt it. I think it’s going to be puberty-related,” Dr. Bozkurt said. Still, “I don’t want to hypothesize without data.”

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

Physician assistants (PAs) are angry with me, and with good reason. I had the audacity to lump them together with nurse practitioners (NPs) in my book “Patients at Risk,” an act which one highly placed PA leader called “distasteful” in a private conversation with me.

I will admit that PAs have reason to be upset. With competitive acceptance rates including a requirement for extensive health care experience before PA school, standardized training, and at least 2,000 hours of clinical experience before graduation, the profession is a stark contrast to the haphazard training and 500 clinical hours required of NPs today. Further, unlike NPs, who have sought independent practice since the 1980s, PAs have traditionally been close allies with physicians, generally working in a 1:1 supervision model.

The truth is that it hurt to include PAs with NPs in my book. I’ve had my own close relationships with PAs over the years and found the PAs I worked with to be outstanding clinicians. Unfortunately, the profession has given me no choice. Following a model set by the NP profession, PA leaders have elected to forgo the traditional physician relationship model, instead seeking the right to practice independently without physician involvement.

Their efforts began with a change in terminology. “Optimal team practice” (OTP) was supposed to give PAs more flexibility, allowing them to work for hospitals or physician groups rather than under the responsibility of one physician. Not surprisingly, corporations and even academic centers have been quick to take advantage, hiring PAs and placing them in positions without adequate physician support. OTP paved the way for independent practice, as PAs sought and gained independence from any physician supervision in North Dakota, the first state to grant them that right.

Most recently, PAs have determined to change their name entirely, calling themselves physician associates. This move by the American Academy of Physician Assistants is the culmination of a years-long marketing study on how to increase the relevance and improve patient perception of the PA profession. The AAPA decision is expected to galvanize state and local PA organizations to lobby legislators for legal and regulatory changes that allow the use of the “physician associate” title, which is not currently a legal representation of PA licensure.

PAs’ latest attempt at title and branding reform follows years of advocacy to not be referred to as physician extenders or midlevel providers. For example, to gain more public acceptance of the PA model, the profession launched the public relations campaign “Your PA Can,” closely mirroring the “We Choose NPs” media blitz. PAs have also followed other dangerous precedents set by NPs, including 100% online training and a new “Doctor of Medical Science” degree, allowing PAs, as well as NPs, to now be called “doctors.”

I can understand PA reasoning even if I don’t agree with it. PAs are frustrated to be treated as second-class citizens compared with NPs, who have been granted independent practice in half the states in the union despite having a fraction of PA training. Frankly, it’s unfair that NPs are being hired preferentially over PAs simply because of looser legal requirements for physician oversight. The bottom line is that NPs have been more successful at persuading legislators to allow them independence – but that doesn’t make it right for either group.

While PAs have more clinical training upon graduation than NPs, they still have far less than physicians. PAs generally attend a 2-year master’s degree program after college which includes 2,000 hours of hands-on clinical work. By comparison, the average medical student spends 4 years and receives 5,000-6,000 hours of supervised clinical training upon graduation. But this isn’t considered enough for a graduate medical student to practice medicine independently.

Physicians must complete at least 3 years of postgraduate residency training in most states to receive a medical license, and by the time a physician is permitted to practice medicine unsupervised, they will have attained no fewer than 15,000-20,000 hours of supervised clinical practice, with years of specialty-specific training.

Patients want and deserve access to truly physician-led care, but in many parts of the country, physicians are being replaced by nonphysician practitioners to boost corporate profits. In many cases, patients are kept in the dark about the differences in training between the medical professionals now in charge of their care. The American Medical Association and other critics have expressed concern that the proposed title of “physician associate” is likely to further obscure the training and roles of medical professionals, already a source of confusion to patients.

One specific criticism is that a physician associate has historically referred to a physician (MD or DO) in a private practice group who has not yet achieved the status of partner. These physician associates are fully licensed medical doctors who have completed medical school and residency training and are in the process of completing a partnership track with their group to participate fully in financial and administrative processes. This nomenclature is similar to that of attorneys on a partnership track. Thus, the use of the term “physician associate” for someone other than a medical doctor is seen as misleading, particularly to patients who cannot be expected to have familiarity with the differences in training.

Efforts to separate the PA profession from a close-working relationship with a physician are bad not only for patients but for PAs as well. Many PAs who desire physician involvement may find themselves hung out to dry, hired by companies and expected to perform outside of their comfort level. The profession also risks ostracizing physician allies, many of whom have preferentially sought to work with PAs.

My sincere hope is that the PA profession will return to its traditional roots of a physician-PA relationship, a model that has been demonstrated to result in high-quality patient care. When that day comes, I will happily re-title my book. But as long as the AAPA continues to work to remove physicians from the equation, patients are indeed at risk.
 

Rebekah Bernard, MD, is a family physician in Fort Myers, Florida, and president of Physicians for Patient Protection. She is the coauthor of Patients at Risk: The Rise of the Nurse Practitioner and Physician Assistant in Healthcare (Irvine, Calif.: Universal Publishers, 2020). She had no relevant financial disclosures. A version of this article first appeared on Medscape.com.

Physician assistants (PAs) are angry with me, and with good reason. I had the audacity to lump them together with nurse practitioners (NPs) in my book “Patients at Risk,” an act which one highly placed PA leader called “distasteful” in a private conversation with me.

I will admit that PAs have reason to be upset. With competitive acceptance rates including a requirement for extensive health care experience before PA school, standardized training, and at least 2,000 hours of clinical experience before graduation, the profession is a stark contrast to the haphazard training and 500 clinical hours required of NPs today. Further, unlike NPs, who have sought independent practice since the 1980s, PAs have traditionally been close allies with physicians, generally working in a 1:1 supervision model.

The truth is that it hurt to include PAs with NPs in my book. I’ve had my own close relationships with PAs over the years and found the PAs I worked with to be outstanding clinicians. Unfortunately, the profession has given me no choice. Following a model set by the NP profession, PA leaders have elected to forgo the traditional physician relationship model, instead seeking the right to practice independently without physician involvement.

Their efforts began with a change in terminology. “Optimal team practice” (OTP) was supposed to give PAs more flexibility, allowing them to work for hospitals or physician groups rather than under the responsibility of one physician. Not surprisingly, corporations and even academic centers have been quick to take advantage, hiring PAs and placing them in positions without adequate physician support. OTP paved the way for independent practice, as PAs sought and gained independence from any physician supervision in North Dakota, the first state to grant them that right.

Most recently, PAs have determined to change their name entirely, calling themselves physician associates. This move by the American Academy of Physician Assistants is the culmination of a years-long marketing study on how to increase the relevance and improve patient perception of the PA profession. The AAPA decision is expected to galvanize state and local PA organizations to lobby legislators for legal and regulatory changes that allow the use of the “physician associate” title, which is not currently a legal representation of PA licensure.

PAs’ latest attempt at title and branding reform follows years of advocacy to not be referred to as physician extenders or midlevel providers. For example, to gain more public acceptance of the PA model, the profession launched the public relations campaign “Your PA Can,” closely mirroring the “We Choose NPs” media blitz. PAs have also followed other dangerous precedents set by NPs, including 100% online training and a new “Doctor of Medical Science” degree, allowing PAs, as well as NPs, to now be called “doctors.”

I can understand PA reasoning even if I don’t agree with it. PAs are frustrated to be treated as second-class citizens compared with NPs, who have been granted independent practice in half the states in the union despite having a fraction of PA training. Frankly, it’s unfair that NPs are being hired preferentially over PAs simply because of looser legal requirements for physician oversight. The bottom line is that NPs have been more successful at persuading legislators to allow them independence – but that doesn’t make it right for either group.

While PAs have more clinical training upon graduation than NPs, they still have far less than physicians. PAs generally attend a 2-year master’s degree program after college which includes 2,000 hours of hands-on clinical work. By comparison, the average medical student spends 4 years and receives 5,000-6,000 hours of supervised clinical training upon graduation. But this isn’t considered enough for a graduate medical student to practice medicine independently.

Physicians must complete at least 3 years of postgraduate residency training in most states to receive a medical license, and by the time a physician is permitted to practice medicine unsupervised, they will have attained no fewer than 15,000-20,000 hours of supervised clinical practice, with years of specialty-specific training.

Patients want and deserve access to truly physician-led care, but in many parts of the country, physicians are being replaced by nonphysician practitioners to boost corporate profits. In many cases, patients are kept in the dark about the differences in training between the medical professionals now in charge of their care. The American Medical Association and other critics have expressed concern that the proposed title of “physician associate” is likely to further obscure the training and roles of medical professionals, already a source of confusion to patients.

One specific criticism is that a physician associate has historically referred to a physician (MD or DO) in a private practice group who has not yet achieved the status of partner. These physician associates are fully licensed medical doctors who have completed medical school and residency training and are in the process of completing a partnership track with their group to participate fully in financial and administrative processes. This nomenclature is similar to that of attorneys on a partnership track. Thus, the use of the term “physician associate” for someone other than a medical doctor is seen as misleading, particularly to patients who cannot be expected to have familiarity with the differences in training.

Efforts to separate the PA profession from a close-working relationship with a physician are bad not only for patients but for PAs as well. Many PAs who desire physician involvement may find themselves hung out to dry, hired by companies and expected to perform outside of their comfort level. The profession also risks ostracizing physician allies, many of whom have preferentially sought to work with PAs.

My sincere hope is that the PA profession will return to its traditional roots of a physician-PA relationship, a model that has been demonstrated to result in high-quality patient care. When that day comes, I will happily re-title my book. But as long as the AAPA continues to work to remove physicians from the equation, patients are indeed at risk.
 

Rebekah Bernard, MD, is a family physician in Fort Myers, Florida, and president of Physicians for Patient Protection. She is the coauthor of Patients at Risk: The Rise of the Nurse Practitioner and Physician Assistant in Healthcare (Irvine, Calif.: Universal Publishers, 2020). She had no relevant financial disclosures. A version of this article first appeared on Medscape.com.

Physician assistants (PAs) are angry with me, and with good reason. I had the audacity to lump them together with nurse practitioners (NPs) in my book “Patients at Risk,” an act which one highly placed PA leader called “distasteful” in a private conversation with me.

I will admit that PAs have reason to be upset. With competitive acceptance rates including a requirement for extensive health care experience before PA school, standardized training, and at least 2,000 hours of clinical experience before graduation, the profession is a stark contrast to the haphazard training and 500 clinical hours required of NPs today. Further, unlike NPs, who have sought independent practice since the 1980s, PAs have traditionally been close allies with physicians, generally working in a 1:1 supervision model.

The truth is that it hurt to include PAs with NPs in my book. I’ve had my own close relationships with PAs over the years and found the PAs I worked with to be outstanding clinicians. Unfortunately, the profession has given me no choice. Following a model set by the NP profession, PA leaders have elected to forgo the traditional physician relationship model, instead seeking the right to practice independently without physician involvement.

Their efforts began with a change in terminology. “Optimal team practice” (OTP) was supposed to give PAs more flexibility, allowing them to work for hospitals or physician groups rather than under the responsibility of one physician. Not surprisingly, corporations and even academic centers have been quick to take advantage, hiring PAs and placing them in positions without adequate physician support. OTP paved the way for independent practice, as PAs sought and gained independence from any physician supervision in North Dakota, the first state to grant them that right.

Most recently, PAs have determined to change their name entirely, calling themselves physician associates. This move by the American Academy of Physician Assistants is the culmination of a years-long marketing study on how to increase the relevance and improve patient perception of the PA profession. The AAPA decision is expected to galvanize state and local PA organizations to lobby legislators for legal and regulatory changes that allow the use of the “physician associate” title, which is not currently a legal representation of PA licensure.

PAs’ latest attempt at title and branding reform follows years of advocacy to not be referred to as physician extenders or midlevel providers. For example, to gain more public acceptance of the PA model, the profession launched the public relations campaign “Your PA Can,” closely mirroring the “We Choose NPs” media blitz. PAs have also followed other dangerous precedents set by NPs, including 100% online training and a new “Doctor of Medical Science” degree, allowing PAs, as well as NPs, to now be called “doctors.”

I can understand PA reasoning even if I don’t agree with it. PAs are frustrated to be treated as second-class citizens compared with NPs, who have been granted independent practice in half the states in the union despite having a fraction of PA training. Frankly, it’s unfair that NPs are being hired preferentially over PAs simply because of looser legal requirements for physician oversight. The bottom line is that NPs have been more successful at persuading legislators to allow them independence – but that doesn’t make it right for either group.

While PAs have more clinical training upon graduation than NPs, they still have far less than physicians. PAs generally attend a 2-year master’s degree program after college which includes 2,000 hours of hands-on clinical work. By comparison, the average medical student spends 4 years and receives 5,000-6,000 hours of supervised clinical training upon graduation. But this isn’t considered enough for a graduate medical student to practice medicine independently.

Physicians must complete at least 3 years of postgraduate residency training in most states to receive a medical license, and by the time a physician is permitted to practice medicine unsupervised, they will have attained no fewer than 15,000-20,000 hours of supervised clinical practice, with years of specialty-specific training.

Patients want and deserve access to truly physician-led care, but in many parts of the country, physicians are being replaced by nonphysician practitioners to boost corporate profits. In many cases, patients are kept in the dark about the differences in training between the medical professionals now in charge of their care. The American Medical Association and other critics have expressed concern that the proposed title of “physician associate” is likely to further obscure the training and roles of medical professionals, already a source of confusion to patients.

One specific criticism is that a physician associate has historically referred to a physician (MD or DO) in a private practice group who has not yet achieved the status of partner. These physician associates are fully licensed medical doctors who have completed medical school and residency training and are in the process of completing a partnership track with their group to participate fully in financial and administrative processes. This nomenclature is similar to that of attorneys on a partnership track. Thus, the use of the term “physician associate” for someone other than a medical doctor is seen as misleading, particularly to patients who cannot be expected to have familiarity with the differences in training.

Efforts to separate the PA profession from a close-working relationship with a physician are bad not only for patients but for PAs as well. Many PAs who desire physician involvement may find themselves hung out to dry, hired by companies and expected to perform outside of their comfort level. The profession also risks ostracizing physician allies, many of whom have preferentially sought to work with PAs.

My sincere hope is that the PA profession will return to its traditional roots of a physician-PA relationship, a model that has been demonstrated to result in high-quality patient care. When that day comes, I will happily re-title my book. But as long as the AAPA continues to work to remove physicians from the equation, patients are indeed at risk.
 

Rebekah Bernard, MD, is a family physician in Fort Myers, Florida, and president of Physicians for Patient Protection. She is the coauthor of Patients at Risk: The Rise of the Nurse Practitioner and Physician Assistant in Healthcare (Irvine, Calif.: Universal Publishers, 2020). She had no relevant financial disclosures. A version of this article first appeared on Medscape.com.

Some Americans with a weakened immune system who face high risks for severe COVID-19 become eligible this week to receive a fourth dose of a coronavirus vaccine.

The Centers for Disease Control and Prevention endorsed a third dose of the Pfizer or Moderna vaccines  for moderately and severely immunocompromised people on Aug. 13, which is considered part of their first immunization series rather than a booster shot.

In October, the CDC said moderately and severely immunocompromised people could receive a booster shot, or a fourth dose of the vaccine , 6 months after their third dose.

But the CDC last week shortened the timeline to 5 months for a booster shot of the Pfizer or Moderna vaccines. That means immunocompromised people could begin signing up for a fourth shot later this week, the New York Times reported.

About 2.7% of U.S. adults, or about 7 million adults, are considered immunocompromised, according to the CDC. They’re more likely to contract severe COVID-19, have a higher risk for long COVID, have lower antibody levels after vaccination, and develop serious breakthrough infections. About 40% of hospitalized breakthrough cases are among immunocompromised people.

According to  CDC guidance, people are considered to be “moderately or severely immunocompromised” if they have:

• Active cancer treatment for tumors or cancers of the blood
• Had an organ transplant and are taking medicine to suppress the immune system
• Had a stem cell transplant in the last 2 years and are taking medicine to suppress the immune system
• Advanced or untreated HIV infection
• Moderate or severe primary immunodeficiency, such as DiGeorge syndrome or Wiskott-Aldrich syndrome
• Active treatment with high-dose corticosteroids or other drugs that suppress the immune response

So far, only moderately and severely immunocompromised Americans are eligible for a fourth shot. Israel has begun offering fourth doses to high-risk groups, including older adults, but the Biden administration hasn’t yet said whether the United States will follow, the Times reported.

Overall, the focus remains on getting third shots to Americans who are eligible for boosters, Rochelle Walensky, MD, the CDC director, told reporters Jan. 7. U.S. officials will remain in touch with Israel to follow their data on fourth shots.

“We will be following our own data carefully as well, to see how these boosters are working in terms of waning effectiveness, not just for infection but, importantly, for severe disease,” she said.

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

Some Americans with a weakened immune system who face high risks for severe COVID-19 become eligible this week to receive a fourth dose of a coronavirus vaccine.

The Centers for Disease Control and Prevention endorsed a third dose of the Pfizer or Moderna vaccines  for moderately and severely immunocompromised people on Aug. 13, which is considered part of their first immunization series rather than a booster shot.

In October, the CDC said moderately and severely immunocompromised people could receive a booster shot, or a fourth dose of the vaccine , 6 months after their third dose.

But the CDC last week shortened the timeline to 5 months for a booster shot of the Pfizer or Moderna vaccines. That means immunocompromised people could begin signing up for a fourth shot later this week, the New York Times reported.

About 2.7% of U.S. adults, or about 7 million adults, are considered immunocompromised, according to the CDC. They’re more likely to contract severe COVID-19, have a higher risk for long COVID, have lower antibody levels after vaccination, and develop serious breakthrough infections. About 40% of hospitalized breakthrough cases are among immunocompromised people.

According to  CDC guidance, people are considered to be “moderately or severely immunocompromised” if they have:

• Active cancer treatment for tumors or cancers of the blood
• Had an organ transplant and are taking medicine to suppress the immune system
• Had a stem cell transplant in the last 2 years and are taking medicine to suppress the immune system
• Advanced or untreated HIV infection
• Moderate or severe primary immunodeficiency, such as DiGeorge syndrome or Wiskott-Aldrich syndrome
• Active treatment with high-dose corticosteroids or other drugs that suppress the immune response

So far, only moderately and severely immunocompromised Americans are eligible for a fourth shot. Israel has begun offering fourth doses to high-risk groups, including older adults, but the Biden administration hasn’t yet said whether the United States will follow, the Times reported.

Overall, the focus remains on getting third shots to Americans who are eligible for boosters, Rochelle Walensky, MD, the CDC director, told reporters Jan. 7. U.S. officials will remain in touch with Israel to follow their data on fourth shots.

“We will be following our own data carefully as well, to see how these boosters are working in terms of waning effectiveness, not just for infection but, importantly, for severe disease,” she said.

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

Some Americans with a weakened immune system who face high risks for severe COVID-19 become eligible this week to receive a fourth dose of a coronavirus vaccine.

The Centers for Disease Control and Prevention endorsed a third dose of the Pfizer or Moderna vaccines  for moderately and severely immunocompromised people on Aug. 13, which is considered part of their first immunization series rather than a booster shot.

In October, the CDC said moderately and severely immunocompromised people could receive a booster shot, or a fourth dose of the vaccine , 6 months after their third dose.

But the CDC last week shortened the timeline to 5 months for a booster shot of the Pfizer or Moderna vaccines. That means immunocompromised people could begin signing up for a fourth shot later this week, the New York Times reported.

About 2.7% of U.S. adults, or about 7 million adults, are considered immunocompromised, according to the CDC. They’re more likely to contract severe COVID-19, have a higher risk for long COVID, have lower antibody levels after vaccination, and develop serious breakthrough infections. About 40% of hospitalized breakthrough cases are among immunocompromised people.

According to  CDC guidance, people are considered to be “moderately or severely immunocompromised” if they have:

• Active cancer treatment for tumors or cancers of the blood
• Had an organ transplant and are taking medicine to suppress the immune system
• Had a stem cell transplant in the last 2 years and are taking medicine to suppress the immune system
• Advanced or untreated HIV infection
• Moderate or severe primary immunodeficiency, such as DiGeorge syndrome or Wiskott-Aldrich syndrome
• Active treatment with high-dose corticosteroids or other drugs that suppress the immune response

So far, only moderately and severely immunocompromised Americans are eligible for a fourth shot. Israel has begun offering fourth doses to high-risk groups, including older adults, but the Biden administration hasn’t yet said whether the United States will follow, the Times reported.

Overall, the focus remains on getting third shots to Americans who are eligible for boosters, Rochelle Walensky, MD, the CDC director, told reporters Jan. 7. U.S. officials will remain in touch with Israel to follow their data on fourth shots.

“We will be following our own data carefully as well, to see how these boosters are working in terms of waning effectiveness, not just for infection but, importantly, for severe disease,” she said.

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

SARS-CoV-2 infection was associated with an increased risk for diabetes among youth, whereas other acute respiratory infections were not, new data from the U.S. Centers for Disease Control and Prevention indicate.

The results from two large U.S. health claims databases were published in an early release in the CDC’s Morbidity and Mortality Weekly Report by Catherine E. Barrett, PhD, and colleagues of the CDC’s COVID-19 Emergency Response Team and Division of Diabetes Translation.

Clinicians should monitor individuals younger than 18 years in the months following a SARS-CoV-2 infection for new diabetes onset, they advise.

The findings, which are supported by independent studies in adults, “underscore the importance of COVID-19 prevention among all age groups, including vaccination for all eligible children and adolescents, and chronic disease prevention and treatment,” Dr. Barrett and colleagues say.

Diabetes type couldn’t be reliably distinguished from the databases, which is noted as an important study limitation.

“SARS-CoV-2 infection might lead to type 1 or type 2 diabetes through complex and differing mechanisms,” they say.

Emerging evidence began to suggest, in mid-2020, that COVID-19 may trigger the onset of diabetes in healthy people. A new global registry was subsequently established to collect data on patients with COVID-19–related diabetes, called the CoviDiab registry.
 

Not clear if diabetes after COVID-19 is transient or permanent

From one of the databases used in the new study, known as IQVIA, 80,893 individuals aged younger than 18 years diagnosed with COVID-19 during March 2020 to February 26, 2021, were compared with age- and sex-matched people during that period who did not have COVID-19 and to prepandemic groups with and without a diagnosis of acute respiratory illness during March 1, 2017, to February 26, 2018.

From the second database, HealthVerity, 439,439 youth diagnosed with COVID-19 during March 1, 2020, to June 28, 2021, were compared with age- and sex-matched youth without COVID-19. Here, there was no prepandemic comparison group.

Diabetes diagnoses were coded in 0.08% with COVID-19 vs. 0.03% without COVID-19 in IQVIA and in 0.25% vs. 0.19% in HealthVerity.

Thus, new diabetes diagnoses were 166% and 31% more likely to occur in those with COVID-19 in IQVIA and HealthVerity, respectively. And in IQVIA, those with COVID-19 were 116% more likely to develop diabetes than were those with prepandemic acute respiratory illnesses. Those differences were all significant, whereas non–SARS-CoV-2 respiratory infections were not associated with diabetes, Dr. Barrett and colleagues say.

In both databases, diabetic ketoacidosis (DKA) was more common at diabetes onset among those with, vs. without, COVID-19: 48.5% vs. 13.6% in IQVIA and 40.2% vs. 29.7% in HealthVerity. In IQVIA, 22.0% with prepandemic acute respiratory illness presented with DKA.

Dr. Barrett and colleagues offer several potential explanations for the observed association between COVID-19 and diabetes, including a direct attack on pancreatic beta cells expressing angiotensin-converting enzyme 2 receptors, or via stress hyperglycemia resulting from cytokine storm and alterations in glucose metabolism.

Another possibility is the precipitation to diabetes from prediabetes; the latter is a condition present in one in five U.S. adolescents.

Steroid treatment during hospitalization might have led to transient hyperglycemia, but only 1.5% to 2.2% of diabetes codes were for drug- or chemical-induced diabetes. The majority were for type 1 or 2.

Alternatively, pandemic-associated weight gain might have also contributed to risks for both severe COVID-19 and type 2 diabetes.

“Although this study can provide information on the risk for diabetes following SARS-CoV-2 infection, additional data are needed to understand underlying pathogenic mechanisms, either those caused by SARS-CoV-2 infection itself or resulting from treatments, and whether a COVID-19–associated diabetes diagnosis is transient or leads to a chronic condition,” Dr. Barrett and colleagues conclude.

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

SARS-CoV-2 infection was associated with an increased risk for diabetes among youth, whereas other acute respiratory infections were not, new data from the U.S. Centers for Disease Control and Prevention indicate.

The results from two large U.S. health claims databases were published in an early release in the CDC’s Morbidity and Mortality Weekly Report by Catherine E. Barrett, PhD, and colleagues of the CDC’s COVID-19 Emergency Response Team and Division of Diabetes Translation.

Clinicians should monitor individuals younger than 18 years in the months following a SARS-CoV-2 infection for new diabetes onset, they advise.

The findings, which are supported by independent studies in adults, “underscore the importance of COVID-19 prevention among all age groups, including vaccination for all eligible children and adolescents, and chronic disease prevention and treatment,” Dr. Barrett and colleagues say.

Diabetes type couldn’t be reliably distinguished from the databases, which is noted as an important study limitation.

“SARS-CoV-2 infection might lead to type 1 or type 2 diabetes through complex and differing mechanisms,” they say.

Emerging evidence began to suggest, in mid-2020, that COVID-19 may trigger the onset of diabetes in healthy people. A new global registry was subsequently established to collect data on patients with COVID-19–related diabetes, called the CoviDiab registry.
 

Not clear if diabetes after COVID-19 is transient or permanent

From one of the databases used in the new study, known as IQVIA, 80,893 individuals aged younger than 18 years diagnosed with COVID-19 during March 2020 to February 26, 2021, were compared with age- and sex-matched people during that period who did not have COVID-19 and to prepandemic groups with and without a diagnosis of acute respiratory illness during March 1, 2017, to February 26, 2018.

From the second database, HealthVerity, 439,439 youth diagnosed with COVID-19 during March 1, 2020, to June 28, 2021, were compared with age- and sex-matched youth without COVID-19. Here, there was no prepandemic comparison group.

Diabetes diagnoses were coded in 0.08% with COVID-19 vs. 0.03% without COVID-19 in IQVIA and in 0.25% vs. 0.19% in HealthVerity.

Thus, new diabetes diagnoses were 166% and 31% more likely to occur in those with COVID-19 in IQVIA and HealthVerity, respectively. And in IQVIA, those with COVID-19 were 116% more likely to develop diabetes than were those with prepandemic acute respiratory illnesses. Those differences were all significant, whereas non–SARS-CoV-2 respiratory infections were not associated with diabetes, Dr. Barrett and colleagues say.

In both databases, diabetic ketoacidosis (DKA) was more common at diabetes onset among those with, vs. without, COVID-19: 48.5% vs. 13.6% in IQVIA and 40.2% vs. 29.7% in HealthVerity. In IQVIA, 22.0% with prepandemic acute respiratory illness presented with DKA.

Dr. Barrett and colleagues offer several potential explanations for the observed association between COVID-19 and diabetes, including a direct attack on pancreatic beta cells expressing angiotensin-converting enzyme 2 receptors, or via stress hyperglycemia resulting from cytokine storm and alterations in glucose metabolism.

Another possibility is the precipitation to diabetes from prediabetes; the latter is a condition present in one in five U.S. adolescents.

Steroid treatment during hospitalization might have led to transient hyperglycemia, but only 1.5% to 2.2% of diabetes codes were for drug- or chemical-induced diabetes. The majority were for type 1 or 2.

Alternatively, pandemic-associated weight gain might have also contributed to risks for both severe COVID-19 and type 2 diabetes.

“Although this study can provide information on the risk for diabetes following SARS-CoV-2 infection, additional data are needed to understand underlying pathogenic mechanisms, either those caused by SARS-CoV-2 infection itself or resulting from treatments, and whether a COVID-19–associated diabetes diagnosis is transient or leads to a chronic condition,” Dr. Barrett and colleagues conclude.

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

SARS-CoV-2 infection was associated with an increased risk for diabetes among youth, whereas other acute respiratory infections were not, new data from the U.S. Centers for Disease Control and Prevention indicate.

The results from two large U.S. health claims databases were published in an early release in the CDC’s Morbidity and Mortality Weekly Report by Catherine E. Barrett, PhD, and colleagues of the CDC’s COVID-19 Emergency Response Team and Division of Diabetes Translation.

Clinicians should monitor individuals younger than 18 years in the months following a SARS-CoV-2 infection for new diabetes onset, they advise.

The findings, which are supported by independent studies in adults, “underscore the importance of COVID-19 prevention among all age groups, including vaccination for all eligible children and adolescents, and chronic disease prevention and treatment,” Dr. Barrett and colleagues say.

Diabetes type couldn’t be reliably distinguished from the databases, which is noted as an important study limitation.

“SARS-CoV-2 infection might lead to type 1 or type 2 diabetes through complex and differing mechanisms,” they say.

Emerging evidence began to suggest, in mid-2020, that COVID-19 may trigger the onset of diabetes in healthy people. A new global registry was subsequently established to collect data on patients with COVID-19–related diabetes, called the CoviDiab registry.
 

Not clear if diabetes after COVID-19 is transient or permanent

From one of the databases used in the new study, known as IQVIA, 80,893 individuals aged younger than 18 years diagnosed with COVID-19 during March 2020 to February 26, 2021, were compared with age- and sex-matched people during that period who did not have COVID-19 and to prepandemic groups with and without a diagnosis of acute respiratory illness during March 1, 2017, to February 26, 2018.

From the second database, HealthVerity, 439,439 youth diagnosed with COVID-19 during March 1, 2020, to June 28, 2021, were compared with age- and sex-matched youth without COVID-19. Here, there was no prepandemic comparison group.

Diabetes diagnoses were coded in 0.08% with COVID-19 vs. 0.03% without COVID-19 in IQVIA and in 0.25% vs. 0.19% in HealthVerity.

Thus, new diabetes diagnoses were 166% and 31% more likely to occur in those with COVID-19 in IQVIA and HealthVerity, respectively. And in IQVIA, those with COVID-19 were 116% more likely to develop diabetes than were those with prepandemic acute respiratory illnesses. Those differences were all significant, whereas non–SARS-CoV-2 respiratory infections were not associated with diabetes, Dr. Barrett and colleagues say.

In both databases, diabetic ketoacidosis (DKA) was more common at diabetes onset among those with, vs. without, COVID-19: 48.5% vs. 13.6% in IQVIA and 40.2% vs. 29.7% in HealthVerity. In IQVIA, 22.0% with prepandemic acute respiratory illness presented with DKA.

Dr. Barrett and colleagues offer several potential explanations for the observed association between COVID-19 and diabetes, including a direct attack on pancreatic beta cells expressing angiotensin-converting enzyme 2 receptors, or via stress hyperglycemia resulting from cytokine storm and alterations in glucose metabolism.

Another possibility is the precipitation to diabetes from prediabetes; the latter is a condition present in one in five U.S. adolescents.

Steroid treatment during hospitalization might have led to transient hyperglycemia, but only 1.5% to 2.2% of diabetes codes were for drug- or chemical-induced diabetes. The majority were for type 1 or 2.

Alternatively, pandemic-associated weight gain might have also contributed to risks for both severe COVID-19 and type 2 diabetes.

“Although this study can provide information on the risk for diabetes following SARS-CoV-2 infection, additional data are needed to understand underlying pathogenic mechanisms, either those caused by SARS-CoV-2 infection itself or resulting from treatments, and whether a COVID-19–associated diabetes diagnosis is transient or leads to a chronic condition,” Dr. Barrett and colleagues conclude.

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

Many states have restored restrictions on telehealth use that they suspended earlier in the COVID-19 pandemic, according to a new report jointly prepared by the Reason Institute, the Pioneer Institute, and the Cicero Institute.

Among the most important restrictions that have been reinstated in some states are those barring requirements for insurers to cover telehealth and regulations that prohibit telehealth visits across state lines, unless the physician is licensed in both states.

“Only three states – Arizona, Florida, and Indiana – allow all health care providers to easily practice telehealth across state lines,” says a news release on the think tanks’ report. “Forty-seven others have arbitrary barriers in place that limit patients’ access to specialists and available appointments based purely on residency.”

“Once the [state-based] public health emergency declarations started to end or executive orders were withdrawn, many of the new flexibilities for providers, insurers, and patients were lost overnight,” Vittorio Nastasi, a policy analyst at Reason Foundation and a co-author of the report, says in the news release. “States need to adopt a number of telehealth reforms to provide their residents better access to this safe and effective virtual care.”

On a positive note, the report says, most states have removed the requirement that a patient must first see a provider in person before they can use telehealth services. The exceptions are Tennessee, Alaska, and West Virginia, which require an in-person visit before certain telehealth services can be provided.

In addition, 20 states allow nurse practitioners to conduct telehealth visits without being under the supervision of a physician. Prior to the pandemic, some states allowed only doctors to use telehealth, the report says, but, during the COVID crisis, “the acute shortage of providers in many counties adds to the need for more kinds of providers to be able to use it.”

A number of states place restrictions on the telehealth modalities that can be utilized. Under the definition by the American Telemedicine Association, telehealth includes audio-video visits, remote patient monitoring, and “store and forward” telemedicine, which entails collecting clinical information and sending it to another site for evaluation. The latter method is particularly useful for consultations with specialists, the report notes.
 

Coverage mandates and payment parity

The report also examines other parameters of telehealth regulations in each state, including whether they have telehealth coverage mandates and whether they require physicians to be paid the same amount for similar types of in-person and telehealth visits.

The report views insurance mandates as beneficial, but not if they require coverage of all virtual services. While telehealth can be a game changer for post-stroke care and for other “treatment-intensive conditions,” the report says, the evidence of better outcomes for other conditions treated through telehealth is far less certain. Therefore, it advises states to “protect flexibility so that new innovative models can emerge.”

Ateev Mehrotra, MD, a professor at Harvard Medical School who studies telehealth, agrees that it offers more value in some clinical situations than in others. “High value is improving quality or outcomes at a reasonable cost,” he told this news organization. “If a telemedicine visit for stroke can save a person’s life and prevent disability, let’s pay for it. A telemedicine visit for a cold may not be necessary. Mom’s chicken soup is fine.”

A little over half of the states still require payment parity, according to the report. While these regulations are intended to promote the use of telehealth, the authors note, they can increase the growth of health care costs. Moreover, they argue, it’s hard to defend equal payments for virtual visits when the overhead required to deliver them – such as office rental, utility, and labor costs – is much lower than that for in-person visits. Also, it makes no sense for health systems to charge facility fees for telehealth visits when these visits can be initiated from anywhere, they say.

Dr. Mehrotra concurs with this view. “If you see someone in your office, your fee includes all the overhead for your office, and it’s a substantial cost,” he says. “For many procedures, it’s more than half of the cost. If you have a telemedicine visit and you’re at home, why would you pay the same amount? The visit may take the same amount of time, but all the money that goes for overhead is not accounted for.”
 

Telemedicine across state lines

The report’s contention about the difficulty of conducting telehealth encounters across most state lines seems to be at odds with the growth in the Interstate Medical Licensure Compact, which makes it easier for physicians in one compact member state to get licensed in others. Currently, 35 states belong to the compact, Joe Knickrehm, vice president of communications for the Federation of State Medical Boards, told this news organization.

In addition, he says, “12 state boards issue a special purpose license, telemedicine license or certificate, or license to practice medicine across state lines to allow for the practice of telemedicine.”

The catch, Dr. Mehrotra says, is that, despite the streamlining of license applications in compact member states, the fees charged by the state boards are still very high – a point that the report also makes. “If I want to have broad scope of practice, I’d have to pay thousands of dollars to many states. The license fees start to add up. Also, I have to keep track of each state’s CME requirements, which are all different. Keeping up with all of that is an administration burden, and it’s a pain.”

Mr. Knickrehm contends that obtaining multiple licenses via the compact “is generally less expensive for physicians than the cost of requesting transcripts, fingerprints, and other necessary paperwork each time they apply for licensure in a new state. Physicians are seeing the benefits of an expedited process that allows them to begin practicing more quickly [in other states].”

Dr. Mehrotra says he has seen the same retrenchment in state telehealth regulations that the report references. However, he says, “CMS [the Centers for Medicare & Medicaid Services] has signaled that at least through 2022 and maybe into 2023, they’ll continue their extensions of telemedicine [pandemic regulations].” After that, Congress would have to decide whether to make the changes permanent.

“Right now, it’s hard for me to see how a payer is going to pull back on telehealth, unless there’s ample evidence of overuse of telehealth,” he argues. “With the public and providers liking telehealth, it’s hard to say on theoretical grounds that we should stop using it. That’s why Medicare and others have extended it and why Congress will too.”

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

Many states have restored restrictions on telehealth use that they suspended earlier in the COVID-19 pandemic, according to a new report jointly prepared by the Reason Institute, the Pioneer Institute, and the Cicero Institute.

Among the most important restrictions that have been reinstated in some states are those barring requirements for insurers to cover telehealth and regulations that prohibit telehealth visits across state lines, unless the physician is licensed in both states.

“Only three states – Arizona, Florida, and Indiana – allow all health care providers to easily practice telehealth across state lines,” says a news release on the think tanks’ report. “Forty-seven others have arbitrary barriers in place that limit patients’ access to specialists and available appointments based purely on residency.”

“Once the [state-based] public health emergency declarations started to end or executive orders were withdrawn, many of the new flexibilities for providers, insurers, and patients were lost overnight,” Vittorio Nastasi, a policy analyst at Reason Foundation and a co-author of the report, says in the news release. “States need to adopt a number of telehealth reforms to provide their residents better access to this safe and effective virtual care.”

On a positive note, the report says, most states have removed the requirement that a patient must first see a provider in person before they can use telehealth services. The exceptions are Tennessee, Alaska, and West Virginia, which require an in-person visit before certain telehealth services can be provided.

In addition, 20 states allow nurse practitioners to conduct telehealth visits without being under the supervision of a physician. Prior to the pandemic, some states allowed only doctors to use telehealth, the report says, but, during the COVID crisis, “the acute shortage of providers in many counties adds to the need for more kinds of providers to be able to use it.”

A number of states place restrictions on the telehealth modalities that can be utilized. Under the definition by the American Telemedicine Association, telehealth includes audio-video visits, remote patient monitoring, and “store and forward” telemedicine, which entails collecting clinical information and sending it to another site for evaluation. The latter method is particularly useful for consultations with specialists, the report notes.
 

Coverage mandates and payment parity

The report also examines other parameters of telehealth regulations in each state, including whether they have telehealth coverage mandates and whether they require physicians to be paid the same amount for similar types of in-person and telehealth visits.

The report views insurance mandates as beneficial, but not if they require coverage of all virtual services. While telehealth can be a game changer for post-stroke care and for other “treatment-intensive conditions,” the report says, the evidence of better outcomes for other conditions treated through telehealth is far less certain. Therefore, it advises states to “protect flexibility so that new innovative models can emerge.”

Ateev Mehrotra, MD, a professor at Harvard Medical School who studies telehealth, agrees that it offers more value in some clinical situations than in others. “High value is improving quality or outcomes at a reasonable cost,” he told this news organization. “If a telemedicine visit for stroke can save a person’s life and prevent disability, let’s pay for it. A telemedicine visit for a cold may not be necessary. Mom’s chicken soup is fine.”

A little over half of the states still require payment parity, according to the report. While these regulations are intended to promote the use of telehealth, the authors note, they can increase the growth of health care costs. Moreover, they argue, it’s hard to defend equal payments for virtual visits when the overhead required to deliver them – such as office rental, utility, and labor costs – is much lower than that for in-person visits. Also, it makes no sense for health systems to charge facility fees for telehealth visits when these visits can be initiated from anywhere, they say.

Dr. Mehrotra concurs with this view. “If you see someone in your office, your fee includes all the overhead for your office, and it’s a substantial cost,” he says. “For many procedures, it’s more than half of the cost. If you have a telemedicine visit and you’re at home, why would you pay the same amount? The visit may take the same amount of time, but all the money that goes for overhead is not accounted for.”
 

Telemedicine across state lines

The report’s contention about the difficulty of conducting telehealth encounters across most state lines seems to be at odds with the growth in the Interstate Medical Licensure Compact, which makes it easier for physicians in one compact member state to get licensed in others. Currently, 35 states belong to the compact, Joe Knickrehm, vice president of communications for the Federation of State Medical Boards, told this news organization.

In addition, he says, “12 state boards issue a special purpose license, telemedicine license or certificate, or license to practice medicine across state lines to allow for the practice of telemedicine.”

The catch, Dr. Mehrotra says, is that, despite the streamlining of license applications in compact member states, the fees charged by the state boards are still very high – a point that the report also makes. “If I want to have broad scope of practice, I’d have to pay thousands of dollars to many states. The license fees start to add up. Also, I have to keep track of each state’s CME requirements, which are all different. Keeping up with all of that is an administration burden, and it’s a pain.”

Mr. Knickrehm contends that obtaining multiple licenses via the compact “is generally less expensive for physicians than the cost of requesting transcripts, fingerprints, and other necessary paperwork each time they apply for licensure in a new state. Physicians are seeing the benefits of an expedited process that allows them to begin practicing more quickly [in other states].”

Dr. Mehrotra says he has seen the same retrenchment in state telehealth regulations that the report references. However, he says, “CMS [the Centers for Medicare & Medicaid Services] has signaled that at least through 2022 and maybe into 2023, they’ll continue their extensions of telemedicine [pandemic regulations].” After that, Congress would have to decide whether to make the changes permanent.

“Right now, it’s hard for me to see how a payer is going to pull back on telehealth, unless there’s ample evidence of overuse of telehealth,” he argues. “With the public and providers liking telehealth, it’s hard to say on theoretical grounds that we should stop using it. That’s why Medicare and others have extended it and why Congress will too.”

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

Many states have restored restrictions on telehealth use that they suspended earlier in the COVID-19 pandemic, according to a new report jointly prepared by the Reason Institute, the Pioneer Institute, and the Cicero Institute.

Among the most important restrictions that have been reinstated in some states are those barring requirements for insurers to cover telehealth and regulations that prohibit telehealth visits across state lines, unless the physician is licensed in both states.

“Only three states – Arizona, Florida, and Indiana – allow all health care providers to easily practice telehealth across state lines,” says a news release on the think tanks’ report. “Forty-seven others have arbitrary barriers in place that limit patients’ access to specialists and available appointments based purely on residency.”

“Once the [state-based] public health emergency declarations started to end or executive orders were withdrawn, many of the new flexibilities for providers, insurers, and patients were lost overnight,” Vittorio Nastasi, a policy analyst at Reason Foundation and a co-author of the report, says in the news release. “States need to adopt a number of telehealth reforms to provide their residents better access to this safe and effective virtual care.”

On a positive note, the report says, most states have removed the requirement that a patient must first see a provider in person before they can use telehealth services. The exceptions are Tennessee, Alaska, and West Virginia, which require an in-person visit before certain telehealth services can be provided.

In addition, 20 states allow nurse practitioners to conduct telehealth visits without being under the supervision of a physician. Prior to the pandemic, some states allowed only doctors to use telehealth, the report says, but, during the COVID crisis, “the acute shortage of providers in many counties adds to the need for more kinds of providers to be able to use it.”

A number of states place restrictions on the telehealth modalities that can be utilized. Under the definition by the American Telemedicine Association, telehealth includes audio-video visits, remote patient monitoring, and “store and forward” telemedicine, which entails collecting clinical information and sending it to another site for evaluation. The latter method is particularly useful for consultations with specialists, the report notes.
 

Coverage mandates and payment parity

The report also examines other parameters of telehealth regulations in each state, including whether they have telehealth coverage mandates and whether they require physicians to be paid the same amount for similar types of in-person and telehealth visits.

The report views insurance mandates as beneficial, but not if they require coverage of all virtual services. While telehealth can be a game changer for post-stroke care and for other “treatment-intensive conditions,” the report says, the evidence of better outcomes for other conditions treated through telehealth is far less certain. Therefore, it advises states to “protect flexibility so that new innovative models can emerge.”

Ateev Mehrotra, MD, a professor at Harvard Medical School who studies telehealth, agrees that it offers more value in some clinical situations than in others. “High value is improving quality or outcomes at a reasonable cost,” he told this news organization. “If a telemedicine visit for stroke can save a person’s life and prevent disability, let’s pay for it. A telemedicine visit for a cold may not be necessary. Mom’s chicken soup is fine.”

A little over half of the states still require payment parity, according to the report. While these regulations are intended to promote the use of telehealth, the authors note, they can increase the growth of health care costs. Moreover, they argue, it’s hard to defend equal payments for virtual visits when the overhead required to deliver them – such as office rental, utility, and labor costs – is much lower than that for in-person visits. Also, it makes no sense for health systems to charge facility fees for telehealth visits when these visits can be initiated from anywhere, they say.

Dr. Mehrotra concurs with this view. “If you see someone in your office, your fee includes all the overhead for your office, and it’s a substantial cost,” he says. “For many procedures, it’s more than half of the cost. If you have a telemedicine visit and you’re at home, why would you pay the same amount? The visit may take the same amount of time, but all the money that goes for overhead is not accounted for.”
 

Telemedicine across state lines

The report’s contention about the difficulty of conducting telehealth encounters across most state lines seems to be at odds with the growth in the Interstate Medical Licensure Compact, which makes it easier for physicians in one compact member state to get licensed in others. Currently, 35 states belong to the compact, Joe Knickrehm, vice president of communications for the Federation of State Medical Boards, told this news organization.

In addition, he says, “12 state boards issue a special purpose license, telemedicine license or certificate, or license to practice medicine across state lines to allow for the practice of telemedicine.”

The catch, Dr. Mehrotra says, is that, despite the streamlining of license applications in compact member states, the fees charged by the state boards are still very high – a point that the report also makes. “If I want to have broad scope of practice, I’d have to pay thousands of dollars to many states. The license fees start to add up. Also, I have to keep track of each state’s CME requirements, which are all different. Keeping up with all of that is an administration burden, and it’s a pain.”

Mr. Knickrehm contends that obtaining multiple licenses via the compact “is generally less expensive for physicians than the cost of requesting transcripts, fingerprints, and other necessary paperwork each time they apply for licensure in a new state. Physicians are seeing the benefits of an expedited process that allows them to begin practicing more quickly [in other states].”

Dr. Mehrotra says he has seen the same retrenchment in state telehealth regulations that the report references. However, he says, “CMS [the Centers for Medicare & Medicaid Services] has signaled that at least through 2022 and maybe into 2023, they’ll continue their extensions of telemedicine [pandemic regulations].” After that, Congress would have to decide whether to make the changes permanent.

“Right now, it’s hard for me to see how a payer is going to pull back on telehealth, unless there’s ample evidence of overuse of telehealth,” he argues. “With the public and providers liking telehealth, it’s hard to say on theoretical grounds that we should stop using it. That’s why Medicare and others have extended it and why Congress will too.”

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

If you don’t think it’s important to assess for sleep disorders in your patients with atopic dermatitis (AD), think again.

According to Sabra M. Abbott, MD, PhD, professor of neurology at Northwestern University, Chicago, AD is associated with difficulty falling asleep, nighttime awakenings, early morning awakenings, increased daytime sleepiness, decreased sleep efficiency, increased arousals, awakenings, and sleep fragmentation, as well as increased night kicks and nocturnal leg cramps, and a more than twofold increased risk for insomnia.

During the Revolutionizing Atopic Dermatitis symposium, she offered key questions to ask AD patients who present with sleep complaints:

When do you go to bed? “This does not refer to when you get into bed, but when do you actually go to bed with an intention to go to sleep, outside of watching television or answering emails?” Dr. Abbott said.

How long does it take for you to fall asleep?

Do you wake up in the middle of the night, and for how long? What do you do if you wake up?

When do you wake up in the morning? Is it on your own, or with an alarm clock?

Does this schedule change on nonworkdays?

Do you have daytime impairment? Meaning, do your sleep complaints impact how you function during the daytime?

Do you snore? Meaning, is there concern for sleep apnea?

Do you have uncomfortable sensations in your legs? Are they worse in the evening and improve with movement? These are signs of possible restless legs syndrome.

The Epworth Sleepiness Scale is one self-administered questionnaire to consider using for AD patients with sleep complaints. “This provides patients with several examples of typical scenarios they might encounter during the day and queries whether or not they feel that they could deal with any of those scenarios,” Dr. Abbott said. “A score of greater than 10 indicates that they are sleepy; it’s not just an overall sense of fatigue and decreased energy.”

Other brief self-assessment tools she recommended are the Insomnia Severity Index and the STOP-Bang questionnaire.

Dr. Abbott reported having no financial disclosures.

[email protected]

If you don’t think it’s important to assess for sleep disorders in your patients with atopic dermatitis (AD), think again.

According to Sabra M. Abbott, MD, PhD, professor of neurology at Northwestern University, Chicago, AD is associated with difficulty falling asleep, nighttime awakenings, early morning awakenings, increased daytime sleepiness, decreased sleep efficiency, increased arousals, awakenings, and sleep fragmentation, as well as increased night kicks and nocturnal leg cramps, and a more than twofold increased risk for insomnia.

During the Revolutionizing Atopic Dermatitis symposium, she offered key questions to ask AD patients who present with sleep complaints:

When do you go to bed? “This does not refer to when you get into bed, but when do you actually go to bed with an intention to go to sleep, outside of watching television or answering emails?” Dr. Abbott said.

How long does it take for you to fall asleep?

Do you wake up in the middle of the night, and for how long? What do you do if you wake up?

When do you wake up in the morning? Is it on your own, or with an alarm clock?

Does this schedule change on nonworkdays?

Do you have daytime impairment? Meaning, do your sleep complaints impact how you function during the daytime?

Do you snore? Meaning, is there concern for sleep apnea?

Do you have uncomfortable sensations in your legs? Are they worse in the evening and improve with movement? These are signs of possible restless legs syndrome.

The Epworth Sleepiness Scale is one self-administered questionnaire to consider using for AD patients with sleep complaints. “This provides patients with several examples of typical scenarios they might encounter during the day and queries whether or not they feel that they could deal with any of those scenarios,” Dr. Abbott said. “A score of greater than 10 indicates that they are sleepy; it’s not just an overall sense of fatigue and decreased energy.”

Other brief self-assessment tools she recommended are the Insomnia Severity Index and the STOP-Bang questionnaire.

Dr. Abbott reported having no financial disclosures.

[email protected]

If you don’t think it’s important to assess for sleep disorders in your patients with atopic dermatitis (AD), think again.

According to Sabra M. Abbott, MD, PhD, professor of neurology at Northwestern University, Chicago, AD is associated with difficulty falling asleep, nighttime awakenings, early morning awakenings, increased daytime sleepiness, decreased sleep efficiency, increased arousals, awakenings, and sleep fragmentation, as well as increased night kicks and nocturnal leg cramps, and a more than twofold increased risk for insomnia.

During the Revolutionizing Atopic Dermatitis symposium, she offered key questions to ask AD patients who present with sleep complaints:

When do you go to bed? “This does not refer to when you get into bed, but when do you actually go to bed with an intention to go to sleep, outside of watching television or answering emails?” Dr. Abbott said.

How long does it take for you to fall asleep?

Do you wake up in the middle of the night, and for how long? What do you do if you wake up?

When do you wake up in the morning? Is it on your own, or with an alarm clock?

Does this schedule change on nonworkdays?

Do you have daytime impairment? Meaning, do your sleep complaints impact how you function during the daytime?

Do you snore? Meaning, is there concern for sleep apnea?

Do you have uncomfortable sensations in your legs? Are they worse in the evening and improve with movement? These are signs of possible restless legs syndrome.

The Epworth Sleepiness Scale is one self-administered questionnaire to consider using for AD patients with sleep complaints. “This provides patients with several examples of typical scenarios they might encounter during the day and queries whether or not they feel that they could deal with any of those scenarios,” Dr. Abbott said. “A score of greater than 10 indicates that they are sleepy; it’s not just an overall sense of fatigue and decreased energy.”

Other brief self-assessment tools she recommended are the Insomnia Severity Index and the STOP-Bang questionnaire.

Dr. Abbott reported having no financial disclosures.

[email protected]

The Mayo Clinic fired 700 employees this week who didn’t comply with its COVID-19 vaccine mandate.

The medical center, which is Minnesota’s largest employer, has major campuses in Arizona, Florida, and Minnesota and operates hospitals in Iowa and Wisconsin.

Employees had until Jan. 3 to get vaccinated or receive approval for an exemption. On Jan. 4, the hospital fired those who didn’t meet the requirement, according to Action News Jax, a CBS affiliate in Florida.

The 700 employees make up about 1% of Mayo Clinic’s 73,000-person workforce. So far, none of the employees at the campus in Jacksonville, Fla., have been affected, the news outlet reported.

“Florida staff who are not in compliance with our vaccination program remain employed pending the outcome of litigation related to the Centers for Medicare & Medicaid Services requirements,” a Mayo Clinic spokesperson told Action News Jax.

The federal government and Florida remain at odds over vaccine mandates, and several lawsuits are winding through the court system. Florida Gov. Ron DeSantis signed legislation in November that bans private Florida employers from requiring all employees to get vaccinated and calls for various exemption options, according to The Florida Times-Union. The state law clashes with a federal rule that requires vaccinations for all health care workers at hospitals that receive Medicare and Medicaid funding.

The Mayo Clinic mandate required employees to receive at least one COVID-19 vaccine dose and not be “overdue” for a second dose, according to the statement. Only medical and religious exemptions were allowed, and most medical and religious exemptions were approved.

“While Mayo Clinic is saddened to lose valuable employees, we need to take all steps necessary to keep our patients, workforce, visitors, and communities safe,” Mayo Clinic wrote in its statement. “If individuals released from employment choose to get vaccinated at a later date, the opportunity exists for them to apply and return to Mayo Clinic for future job openings.”

With the latest surge in COVID-19 cases from the Omicron variant, the Mayo Clinic also encouraged unvaccinated people to get a shot and those who are eligible for a booster to get one “as soon as possible.”

“Based on science and data, it’s clear that vaccination keeps people out of the hospital and saves lives,” according to the statement. “That’s true for everyone in our communities – and it’s especially true for the many patients with serious or complex diseases who seek care at Mayo Clinic each day.”

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

The Mayo Clinic fired 700 employees this week who didn’t comply with its COVID-19 vaccine mandate.

The medical center, which is Minnesota’s largest employer, has major campuses in Arizona, Florida, and Minnesota and operates hospitals in Iowa and Wisconsin.

Employees had until Jan. 3 to get vaccinated or receive approval for an exemption. On Jan. 4, the hospital fired those who didn’t meet the requirement, according to Action News Jax, a CBS affiliate in Florida.

The 700 employees make up about 1% of Mayo Clinic’s 73,000-person workforce. So far, none of the employees at the campus in Jacksonville, Fla., have been affected, the news outlet reported.

“Florida staff who are not in compliance with our vaccination program remain employed pending the outcome of litigation related to the Centers for Medicare & Medicaid Services requirements,” a Mayo Clinic spokesperson told Action News Jax.

The federal government and Florida remain at odds over vaccine mandates, and several lawsuits are winding through the court system. Florida Gov. Ron DeSantis signed legislation in November that bans private Florida employers from requiring all employees to get vaccinated and calls for various exemption options, according to The Florida Times-Union. The state law clashes with a federal rule that requires vaccinations for all health care workers at hospitals that receive Medicare and Medicaid funding.

The Mayo Clinic mandate required employees to receive at least one COVID-19 vaccine dose and not be “overdue” for a second dose, according to the statement. Only medical and religious exemptions were allowed, and most medical and religious exemptions were approved.

“While Mayo Clinic is saddened to lose valuable employees, we need to take all steps necessary to keep our patients, workforce, visitors, and communities safe,” Mayo Clinic wrote in its statement. “If individuals released from employment choose to get vaccinated at a later date, the opportunity exists for them to apply and return to Mayo Clinic for future job openings.”

With the latest surge in COVID-19 cases from the Omicron variant, the Mayo Clinic also encouraged unvaccinated people to get a shot and those who are eligible for a booster to get one “as soon as possible.”

“Based on science and data, it’s clear that vaccination keeps people out of the hospital and saves lives,” according to the statement. “That’s true for everyone in our communities – and it’s especially true for the many patients with serious or complex diseases who seek care at Mayo Clinic each day.”

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

The Mayo Clinic fired 700 employees this week who didn’t comply with its COVID-19 vaccine mandate.

The medical center, which is Minnesota’s largest employer, has major campuses in Arizona, Florida, and Minnesota and operates hospitals in Iowa and Wisconsin.

Employees had until Jan. 3 to get vaccinated or receive approval for an exemption. On Jan. 4, the hospital fired those who didn’t meet the requirement, according to Action News Jax, a CBS affiliate in Florida.

The 700 employees make up about 1% of Mayo Clinic’s 73,000-person workforce. So far, none of the employees at the campus in Jacksonville, Fla., have been affected, the news outlet reported.

“Florida staff who are not in compliance with our vaccination program remain employed pending the outcome of litigation related to the Centers for Medicare & Medicaid Services requirements,” a Mayo Clinic spokesperson told Action News Jax.

The federal government and Florida remain at odds over vaccine mandates, and several lawsuits are winding through the court system. Florida Gov. Ron DeSantis signed legislation in November that bans private Florida employers from requiring all employees to get vaccinated and calls for various exemption options, according to The Florida Times-Union. The state law clashes with a federal rule that requires vaccinations for all health care workers at hospitals that receive Medicare and Medicaid funding.

The Mayo Clinic mandate required employees to receive at least one COVID-19 vaccine dose and not be “overdue” for a second dose, according to the statement. Only medical and religious exemptions were allowed, and most medical and religious exemptions were approved.

“While Mayo Clinic is saddened to lose valuable employees, we need to take all steps necessary to keep our patients, workforce, visitors, and communities safe,” Mayo Clinic wrote in its statement. “If individuals released from employment choose to get vaccinated at a later date, the opportunity exists for them to apply and return to Mayo Clinic for future job openings.”

With the latest surge in COVID-19 cases from the Omicron variant, the Mayo Clinic also encouraged unvaccinated people to get a shot and those who are eligible for a booster to get one “as soon as possible.”

“Based on science and data, it’s clear that vaccination keeps people out of the hospital and saves lives,” according to the statement. “That’s true for everyone in our communities – and it’s especially true for the many patients with serious or complex diseases who seek care at Mayo Clinic each day.”

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