Ted Bosworth

For patients with central centrifugal cicatricial alopecia (CCCA), several therapies showing benefit in case studies might reasonably be considered for those who have failed standard interventions, according to a review of current strategies for this challenging disease, delivered at the virtual Skin of Color Update 2020.

Courtesy Johns Hopkins Medicine

Two case reports of favorable results with topical metformin were published earlier this year. A subsequent case in which metformin provided a major improvement in quality of life has provided further encouragement, according to Crystal Aguh, MD, director of the ethnic skin program at Johns Hopkins University, Baltimore.

In the subsequent case, there was complete scalp coverage, allowing the patient to no longer use a wig, which is “tough to achieve in patients with advanced disease,” Dr. Aguh said.

In the two published cases, 10% metformin compounded in Lipoderm (PCCA) produced notable hair growth within 6 months. Dr. Aguh said that the case studies were prompted by experimental evidence associating metformin with an antifibrotic effect.

This finding is potentially important. Most current treatments for CCCA are based on anti-inflammatory activity, according to Dr. Aguh, but fibrosis is strongly implicated in the pathogenesis of CCCA. Of several lines of evidence, one is the association between CCCA and other fibrosing conditions.

For example, women with CCCA “are several times more likely to have uterine fibroids than women without CCCA,” said Dr. Aguh, citing a study that she published in 2018. She suggested that there is an urgent need for new treatment options because of the “often-disappointing” responses to current standard therapies.

In the CCCA cases treated so far, topical metformin has been well tolerated, which is attributed to the low level of systemic absorption. No nausea or other gastrointestinal side effects common to oral metformin have been so far observed in Dr. Aguh’s cases.

“Some patients experience scalp dryness or irritation,” she said, but added that a light coating of emollient typically relieves this complaint.

Despite the promising results, topical metformin “is not a silver bullet,” Dr. Aguh cautioned. She estimated that only 10%-15% of patients respond, but this treatment can be considered “as an adjunctive option to avoid another round of intralesional steroids.”

Platelet-rich plasma (PRP) is another option that has demonstrated promise in a published case report for which Dr. Aguh served as a coauthor. In this series of two patients, only one had CCCA. The other had lichen planopilaris, but both patients experienced hair regrowth after failing standard therapies.

When treating alopecia with PRP, Dr. Aguh typically offers three or four sessions spaced 4 weeks apart. She does not start other treatments at the same time, but she does not discontinue topical treatments that patients are already taking, including topical minoxidil.

Again, like topical metformin, PRP is reasonably considered in patients who have failed standard therapies, according to Dr. Aguh. She cautioned that responses are not permanent. Patients who respond typically require retreatment a year or more later, but good responses have been seen after retreatment.

Appropriate hair care can help. Dr. Aguh recounted a case in which a patient with presumed CCCA was referred after failing intralesional triamcinolone injections. Ultimately, the patient was diagnosed with acquired trichorrhexis nodosa, but the large clinical improvements gained from better hair care practices, including avoidance of chemical relaxants and thermal styling, are relevant to CCCA, as well as other conditions resulting in hair loss.

In a book written by Dr. Aguh, titled “90 Days to Beautiful Hair,” strategies for better hair care practices include advice to reduce tension on hair follicles.

The role of increased traction is an issue in CCCA, agreed Amy McMichael, MD, chair of the department of dermatology, Wake Forest University, Winston-Salem, N.C. Although she provided data at the meeting suggesting that CCCA is a fibrosing disease linked to genetic susceptibility, she said there is also a “strong association” between the severity of CCCA and extensions, hair weaving, and other tension-associated hairstyles.

While there is an urgent need to develop therapies that address the underlying pathophysiology of CCCA, she concurred that patients with this or other conditions associated with hair loss, such as seborrheic dermatitis or frontal fibrosing alopecia, should not ignore appropriate hair care.

Dr. Aguh has financial relationships with LEO Pharma and UCB Pharma. Dr. McMichael’s disclosures included serving as an investigator and/or consultant for companies that included Allergan, Procter & Gamble, Nutrafol, Johnson & Johnson, and Aclaris.

For patients with central centrifugal cicatricial alopecia (CCCA), several therapies showing benefit in case studies might reasonably be considered for those who have failed standard interventions, according to a review of current strategies for this challenging disease, delivered at the virtual Skin of Color Update 2020.

Courtesy Johns Hopkins Medicine

Two case reports of favorable results with topical metformin were published earlier this year. A subsequent case in which metformin provided a major improvement in quality of life has provided further encouragement, according to Crystal Aguh, MD, director of the ethnic skin program at Johns Hopkins University, Baltimore.

In the subsequent case, there was complete scalp coverage, allowing the patient to no longer use a wig, which is “tough to achieve in patients with advanced disease,” Dr. Aguh said.

In the two published cases, 10% metformin compounded in Lipoderm (PCCA) produced notable hair growth within 6 months. Dr. Aguh said that the case studies were prompted by experimental evidence associating metformin with an antifibrotic effect.

This finding is potentially important. Most current treatments for CCCA are based on anti-inflammatory activity, according to Dr. Aguh, but fibrosis is strongly implicated in the pathogenesis of CCCA. Of several lines of evidence, one is the association between CCCA and other fibrosing conditions.

For example, women with CCCA “are several times more likely to have uterine fibroids than women without CCCA,” said Dr. Aguh, citing a study that she published in 2018. She suggested that there is an urgent need for new treatment options because of the “often-disappointing” responses to current standard therapies.

In the CCCA cases treated so far, topical metformin has been well tolerated, which is attributed to the low level of systemic absorption. No nausea or other gastrointestinal side effects common to oral metformin have been so far observed in Dr. Aguh’s cases.

“Some patients experience scalp dryness or irritation,” she said, but added that a light coating of emollient typically relieves this complaint.

Despite the promising results, topical metformin “is not a silver bullet,” Dr. Aguh cautioned. She estimated that only 10%-15% of patients respond, but this treatment can be considered “as an adjunctive option to avoid another round of intralesional steroids.”

Platelet-rich plasma (PRP) is another option that has demonstrated promise in a published case report for which Dr. Aguh served as a coauthor. In this series of two patients, only one had CCCA. The other had lichen planopilaris, but both patients experienced hair regrowth after failing standard therapies.

When treating alopecia with PRP, Dr. Aguh typically offers three or four sessions spaced 4 weeks apart. She does not start other treatments at the same time, but she does not discontinue topical treatments that patients are already taking, including topical minoxidil.

Again, like topical metformin, PRP is reasonably considered in patients who have failed standard therapies, according to Dr. Aguh. She cautioned that responses are not permanent. Patients who respond typically require retreatment a year or more later, but good responses have been seen after retreatment.

Appropriate hair care can help. Dr. Aguh recounted a case in which a patient with presumed CCCA was referred after failing intralesional triamcinolone injections. Ultimately, the patient was diagnosed with acquired trichorrhexis nodosa, but the large clinical improvements gained from better hair care practices, including avoidance of chemical relaxants and thermal styling, are relevant to CCCA, as well as other conditions resulting in hair loss.

In a book written by Dr. Aguh, titled “90 Days to Beautiful Hair,” strategies for better hair care practices include advice to reduce tension on hair follicles.

The role of increased traction is an issue in CCCA, agreed Amy McMichael, MD, chair of the department of dermatology, Wake Forest University, Winston-Salem, N.C. Although she provided data at the meeting suggesting that CCCA is a fibrosing disease linked to genetic susceptibility, she said there is also a “strong association” between the severity of CCCA and extensions, hair weaving, and other tension-associated hairstyles.

While there is an urgent need to develop therapies that address the underlying pathophysiology of CCCA, she concurred that patients with this or other conditions associated with hair loss, such as seborrheic dermatitis or frontal fibrosing alopecia, should not ignore appropriate hair care.

Dr. Aguh has financial relationships with LEO Pharma and UCB Pharma. Dr. McMichael’s disclosures included serving as an investigator and/or consultant for companies that included Allergan, Procter & Gamble, Nutrafol, Johnson & Johnson, and Aclaris.

For patients with central centrifugal cicatricial alopecia (CCCA), several therapies showing benefit in case studies might reasonably be considered for those who have failed standard interventions, according to a review of current strategies for this challenging disease, delivered at the virtual Skin of Color Update 2020.

Courtesy Johns Hopkins Medicine

Two case reports of favorable results with topical metformin were published earlier this year. A subsequent case in which metformin provided a major improvement in quality of life has provided further encouragement, according to Crystal Aguh, MD, director of the ethnic skin program at Johns Hopkins University, Baltimore.

In the subsequent case, there was complete scalp coverage, allowing the patient to no longer use a wig, which is “tough to achieve in patients with advanced disease,” Dr. Aguh said.

In the two published cases, 10% metformin compounded in Lipoderm (PCCA) produced notable hair growth within 6 months. Dr. Aguh said that the case studies were prompted by experimental evidence associating metformin with an antifibrotic effect.

This finding is potentially important. Most current treatments for CCCA are based on anti-inflammatory activity, according to Dr. Aguh, but fibrosis is strongly implicated in the pathogenesis of CCCA. Of several lines of evidence, one is the association between CCCA and other fibrosing conditions.

For example, women with CCCA “are several times more likely to have uterine fibroids than women without CCCA,” said Dr. Aguh, citing a study that she published in 2018. She suggested that there is an urgent need for new treatment options because of the “often-disappointing” responses to current standard therapies.

In the CCCA cases treated so far, topical metformin has been well tolerated, which is attributed to the low level of systemic absorption. No nausea or other gastrointestinal side effects common to oral metformin have been so far observed in Dr. Aguh’s cases.

“Some patients experience scalp dryness or irritation,” she said, but added that a light coating of emollient typically relieves this complaint.

Despite the promising results, topical metformin “is not a silver bullet,” Dr. Aguh cautioned. She estimated that only 10%-15% of patients respond, but this treatment can be considered “as an adjunctive option to avoid another round of intralesional steroids.”

Platelet-rich plasma (PRP) is another option that has demonstrated promise in a published case report for which Dr. Aguh served as a coauthor. In this series of two patients, only one had CCCA. The other had lichen planopilaris, but both patients experienced hair regrowth after failing standard therapies.

When treating alopecia with PRP, Dr. Aguh typically offers three or four sessions spaced 4 weeks apart. She does not start other treatments at the same time, but she does not discontinue topical treatments that patients are already taking, including topical minoxidil.

Again, like topical metformin, PRP is reasonably considered in patients who have failed standard therapies, according to Dr. Aguh. She cautioned that responses are not permanent. Patients who respond typically require retreatment a year or more later, but good responses have been seen after retreatment.

Appropriate hair care can help. Dr. Aguh recounted a case in which a patient with presumed CCCA was referred after failing intralesional triamcinolone injections. Ultimately, the patient was diagnosed with acquired trichorrhexis nodosa, but the large clinical improvements gained from better hair care practices, including avoidance of chemical relaxants and thermal styling, are relevant to CCCA, as well as other conditions resulting in hair loss.

In a book written by Dr. Aguh, titled “90 Days to Beautiful Hair,” strategies for better hair care practices include advice to reduce tension on hair follicles.

The role of increased traction is an issue in CCCA, agreed Amy McMichael, MD, chair of the department of dermatology, Wake Forest University, Winston-Salem, N.C. Although she provided data at the meeting suggesting that CCCA is a fibrosing disease linked to genetic susceptibility, she said there is also a “strong association” between the severity of CCCA and extensions, hair weaving, and other tension-associated hairstyles.

While there is an urgent need to develop therapies that address the underlying pathophysiology of CCCA, she concurred that patients with this or other conditions associated with hair loss, such as seborrheic dermatitis or frontal fibrosing alopecia, should not ignore appropriate hair care.

Dr. Aguh has financial relationships with LEO Pharma and UCB Pharma. Dr. McMichael’s disclosures included serving as an investigator and/or consultant for companies that included Allergan, Procter & Gamble, Nutrafol, Johnson & Johnson, and Aclaris.

In rural counties, the absence of active labor and delivery (L&D) units is associated with a significant increase in perinatal mortality, according to a retrospective study using county-level data from the Alabama Department of Public Health.

stockce/Thinkstock

Although association does not establish causation, these data raise concern “for the current trend of diminishing L&D units that is occurring in many rural settings,” according to the authors of the study, led by John B. Waits, MD, of Cahaba Medical Care, Centreville, Ala., in Annals of Family Medicine.

When mortality per 1,000 live births was compared over a 15-year period (2003-2017) between 15 counties with and 21 counties without local L&D units, those with the units had lower overall infant mortality (9.23 vs. 7.89; P = .0011), perinatal mortality (8.89 vs. 10.82; P < .001), and neonatal mortality (4.74 vs. 5.67; P = .0034). The percentages of low-birth-weight babies born between 2003 and 2014 were 9.86% versus 10.61% (P < .001) for counties with and without L&D units, respectively.

The relative increased risks (RR) for these adverse outcomes in counties without L&D units were statistically significant and substantial, ranging from about 8% for a pregnancy resulting in a low-birth-weight infant to slightly more than 21% for perinatal mortality.

Over the study period, there were 165,525 live births in the 15 counties with L&D units and 72,177 births in the 21 counties with no such units. In counties without L&D units, the average proportion of White people was higher (73.47% vs. 60.86%), and that of African Americans was lower (22.76% vs. 36.23%). Median income ($40,759 vs. $35,604) and per capita income ($22,474 vs. $20,641) was slightly higher.

Of the 67 counties in Alabama, this study did not include those considered urbanized by the Alabama Office of Management and Budget even if classified rural by other statewide offices, such as the Alabama Rural Health Association. Any county with at least one L&D unit was considered to have a local unit. Three counties with L&D units that closed before the observation period was completed were excluded from the analysis.

The Alabama data appear to identify a major problem in need of an urgent solution, according to John S. Cullen, MD, a family physician in Valdez, Alaska, and chair of the American Academy of Family Physicians Board of Directors.

“Almost 20% of U.S. women of reproductive age live in rural communities,” he said in an interview. The data from this study provides compelling evidence “that the loss of rural maternity care in this country has contributed to the increase in newborn mortality in rural communities.”

There are many limitations for this study, according to the authors. They acknowledged that they could not control for many potentially important variables, such as travel time to hospitals for those in counties with L&D units when compared with those without. They also acknowledged the lack of data regarding availability of prenatal care in places with or without L&D units.

If lack of L&D services in rural areas is a source of adverse outcomes, data suggesting that the ongoing decline in L&D units are worrisome, according to the authors. Of studies they cited, one showed nearly a 10% loss in rural L&D services in a recent 10-year period.

The authors also noted that about half of the 3,143 counties in the United States do not have a practicing obstetrician, and that fewer than 7% of obstetricians-gynecologists practice in rural settings.

In many rural counties, including the county where the lead author practices, family practitioners provide 100% of local obstetric care, but access to these clinicians also appears to be declining, according to the paper. The ratio of primary care physicians to patients is already lower in non-metropolitan than metropolitan areas (39.8 vs. 53.3). The American Board of Family Medicine has reported that fewer than 10% of family physicians now provide maternity care, the authors wrote.

“If a causal relationship does exist [between lack of L&D units and adverse perinatal outcomes], then rural populations would definitively benefit from having local access to a L&D unit,” the authors stated.

The lead author, Dr. Waits, said in an interview that there are two obstacles to an increase in rural L&D units: malpractice premiums and reimbursement for indigent deliveries. The large malpractice premiums required to cover OB care are hurdles for caregivers, such as family physicians, as well as the hospitals where they practice.

Reforms from the legislative or regulatory perspective are needed to permit malpractice insurance to be issued at a reasonable cost, according to Dr. Waits. Such reforms are a “moral imperative” so that the malpractice issue is not allowed to “shipwreck infant and maternal mortality,” he said.

Of the many potential solutions, such as increased use of telemedicine, legislative initiatives to reduce the malpractice burden, or new support and incentives for family physicians to deliver OB care, each is burdened with obstacles to overcome, according to Dr. Waits. This does not mean these solutions should not be pursued alone or together, but he made it clear that the no solution is easy. In the meantime, Dr. Waits indicated a need to consider practical and immediate strategies to fix the problem.

“There should be incentives for rural emergency departments and ambulance systems to train in the [American Academy of Family Physicians’] Basic Life Support in Obstetrics (BLSO) certification courses each year. I am not aware of any specific evidence around this, but it is a known fact that, when L&Ds close, institutional memory of OB emergencies recede, and preparedness suffers,” he said.

Dr. Cullen agreed that if the closing of L&D units explains the higher rate of perinatal mortality in rural areas, both short-term and long-term solutions are needed.

“Every community must have a plan for obstetric and newborn emergencies. The decision to not offer maternity care means that rural providers will still provide maternity care but not be ready for emergencies,” he said, echoing a point made by Dr. Waits.

The study authors disclosed no conflicts. Dr. Cullen reported having no disclosures. 

SOURCE: Waits JB et al. Ann Fam Med. 2020;18:446-51.

In rural counties, the absence of active labor and delivery (L&D) units is associated with a significant increase in perinatal mortality, according to a retrospective study using county-level data from the Alabama Department of Public Health.

stockce/Thinkstock

Although association does not establish causation, these data raise concern “for the current trend of diminishing L&D units that is occurring in many rural settings,” according to the authors of the study, led by John B. Waits, MD, of Cahaba Medical Care, Centreville, Ala., in Annals of Family Medicine.

When mortality per 1,000 live births was compared over a 15-year period (2003-2017) between 15 counties with and 21 counties without local L&D units, those with the units had lower overall infant mortality (9.23 vs. 7.89; P = .0011), perinatal mortality (8.89 vs. 10.82; P < .001), and neonatal mortality (4.74 vs. 5.67; P = .0034). The percentages of low-birth-weight babies born between 2003 and 2014 were 9.86% versus 10.61% (P < .001) for counties with and without L&D units, respectively.

The relative increased risks (RR) for these adverse outcomes in counties without L&D units were statistically significant and substantial, ranging from about 8% for a pregnancy resulting in a low-birth-weight infant to slightly more than 21% for perinatal mortality.

Over the study period, there were 165,525 live births in the 15 counties with L&D units and 72,177 births in the 21 counties with no such units. In counties without L&D units, the average proportion of White people was higher (73.47% vs. 60.86%), and that of African Americans was lower (22.76% vs. 36.23%). Median income ($40,759 vs. $35,604) and per capita income ($22,474 vs. $20,641) was slightly higher.

Of the 67 counties in Alabama, this study did not include those considered urbanized by the Alabama Office of Management and Budget even if classified rural by other statewide offices, such as the Alabama Rural Health Association. Any county with at least one L&D unit was considered to have a local unit. Three counties with L&D units that closed before the observation period was completed were excluded from the analysis.

The Alabama data appear to identify a major problem in need of an urgent solution, according to John S. Cullen, MD, a family physician in Valdez, Alaska, and chair of the American Academy of Family Physicians Board of Directors.

“Almost 20% of U.S. women of reproductive age live in rural communities,” he said in an interview. The data from this study provides compelling evidence “that the loss of rural maternity care in this country has contributed to the increase in newborn mortality in rural communities.”

There are many limitations for this study, according to the authors. They acknowledged that they could not control for many potentially important variables, such as travel time to hospitals for those in counties with L&D units when compared with those without. They also acknowledged the lack of data regarding availability of prenatal care in places with or without L&D units.

If lack of L&D services in rural areas is a source of adverse outcomes, data suggesting that the ongoing decline in L&D units are worrisome, according to the authors. Of studies they cited, one showed nearly a 10% loss in rural L&D services in a recent 10-year period.

The authors also noted that about half of the 3,143 counties in the United States do not have a practicing obstetrician, and that fewer than 7% of obstetricians-gynecologists practice in rural settings.

In many rural counties, including the county where the lead author practices, family practitioners provide 100% of local obstetric care, but access to these clinicians also appears to be declining, according to the paper. The ratio of primary care physicians to patients is already lower in non-metropolitan than metropolitan areas (39.8 vs. 53.3). The American Board of Family Medicine has reported that fewer than 10% of family physicians now provide maternity care, the authors wrote.

“If a causal relationship does exist [between lack of L&D units and adverse perinatal outcomes], then rural populations would definitively benefit from having local access to a L&D unit,” the authors stated.

The lead author, Dr. Waits, said in an interview that there are two obstacles to an increase in rural L&D units: malpractice premiums and reimbursement for indigent deliveries. The large malpractice premiums required to cover OB care are hurdles for caregivers, such as family physicians, as well as the hospitals where they practice.

Reforms from the legislative or regulatory perspective are needed to permit malpractice insurance to be issued at a reasonable cost, according to Dr. Waits. Such reforms are a “moral imperative” so that the malpractice issue is not allowed to “shipwreck infant and maternal mortality,” he said.

Of the many potential solutions, such as increased use of telemedicine, legislative initiatives to reduce the malpractice burden, or new support and incentives for family physicians to deliver OB care, each is burdened with obstacles to overcome, according to Dr. Waits. This does not mean these solutions should not be pursued alone or together, but he made it clear that the no solution is easy. In the meantime, Dr. Waits indicated a need to consider practical and immediate strategies to fix the problem.

“There should be incentives for rural emergency departments and ambulance systems to train in the [American Academy of Family Physicians’] Basic Life Support in Obstetrics (BLSO) certification courses each year. I am not aware of any specific evidence around this, but it is a known fact that, when L&Ds close, institutional memory of OB emergencies recede, and preparedness suffers,” he said.

Dr. Cullen agreed that if the closing of L&D units explains the higher rate of perinatal mortality in rural areas, both short-term and long-term solutions are needed.

“Every community must have a plan for obstetric and newborn emergencies. The decision to not offer maternity care means that rural providers will still provide maternity care but not be ready for emergencies,” he said, echoing a point made by Dr. Waits.

The study authors disclosed no conflicts. Dr. Cullen reported having no disclosures. 

SOURCE: Waits JB et al. Ann Fam Med. 2020;18:446-51.

In rural counties, the absence of active labor and delivery (L&D) units is associated with a significant increase in perinatal mortality, according to a retrospective study using county-level data from the Alabama Department of Public Health.

stockce/Thinkstock

Although association does not establish causation, these data raise concern “for the current trend of diminishing L&D units that is occurring in many rural settings,” according to the authors of the study, led by John B. Waits, MD, of Cahaba Medical Care, Centreville, Ala., in Annals of Family Medicine.

When mortality per 1,000 live births was compared over a 15-year period (2003-2017) between 15 counties with and 21 counties without local L&D units, those with the units had lower overall infant mortality (9.23 vs. 7.89; P = .0011), perinatal mortality (8.89 vs. 10.82; P < .001), and neonatal mortality (4.74 vs. 5.67; P = .0034). The percentages of low-birth-weight babies born between 2003 and 2014 were 9.86% versus 10.61% (P < .001) for counties with and without L&D units, respectively.

The relative increased risks (RR) for these adverse outcomes in counties without L&D units were statistically significant and substantial, ranging from about 8% for a pregnancy resulting in a low-birth-weight infant to slightly more than 21% for perinatal mortality.

Over the study period, there were 165,525 live births in the 15 counties with L&D units and 72,177 births in the 21 counties with no such units. In counties without L&D units, the average proportion of White people was higher (73.47% vs. 60.86%), and that of African Americans was lower (22.76% vs. 36.23%). Median income ($40,759 vs. $35,604) and per capita income ($22,474 vs. $20,641) was slightly higher.

Of the 67 counties in Alabama, this study did not include those considered urbanized by the Alabama Office of Management and Budget even if classified rural by other statewide offices, such as the Alabama Rural Health Association. Any county with at least one L&D unit was considered to have a local unit. Three counties with L&D units that closed before the observation period was completed were excluded from the analysis.

The Alabama data appear to identify a major problem in need of an urgent solution, according to John S. Cullen, MD, a family physician in Valdez, Alaska, and chair of the American Academy of Family Physicians Board of Directors.

“Almost 20% of U.S. women of reproductive age live in rural communities,” he said in an interview. The data from this study provides compelling evidence “that the loss of rural maternity care in this country has contributed to the increase in newborn mortality in rural communities.”

There are many limitations for this study, according to the authors. They acknowledged that they could not control for many potentially important variables, such as travel time to hospitals for those in counties with L&D units when compared with those without. They also acknowledged the lack of data regarding availability of prenatal care in places with or without L&D units.

If lack of L&D services in rural areas is a source of adverse outcomes, data suggesting that the ongoing decline in L&D units are worrisome, according to the authors. Of studies they cited, one showed nearly a 10% loss in rural L&D services in a recent 10-year period.

The authors also noted that about half of the 3,143 counties in the United States do not have a practicing obstetrician, and that fewer than 7% of obstetricians-gynecologists practice in rural settings.

In many rural counties, including the county where the lead author practices, family practitioners provide 100% of local obstetric care, but access to these clinicians also appears to be declining, according to the paper. The ratio of primary care physicians to patients is already lower in non-metropolitan than metropolitan areas (39.8 vs. 53.3). The American Board of Family Medicine has reported that fewer than 10% of family physicians now provide maternity care, the authors wrote.

“If a causal relationship does exist [between lack of L&D units and adverse perinatal outcomes], then rural populations would definitively benefit from having local access to a L&D unit,” the authors stated.

The lead author, Dr. Waits, said in an interview that there are two obstacles to an increase in rural L&D units: malpractice premiums and reimbursement for indigent deliveries. The large malpractice premiums required to cover OB care are hurdles for caregivers, such as family physicians, as well as the hospitals where they practice.

Reforms from the legislative or regulatory perspective are needed to permit malpractice insurance to be issued at a reasonable cost, according to Dr. Waits. Such reforms are a “moral imperative” so that the malpractice issue is not allowed to “shipwreck infant and maternal mortality,” he said.

Of the many potential solutions, such as increased use of telemedicine, legislative initiatives to reduce the malpractice burden, or new support and incentives for family physicians to deliver OB care, each is burdened with obstacles to overcome, according to Dr. Waits. This does not mean these solutions should not be pursued alone or together, but he made it clear that the no solution is easy. In the meantime, Dr. Waits indicated a need to consider practical and immediate strategies to fix the problem.

“There should be incentives for rural emergency departments and ambulance systems to train in the [American Academy of Family Physicians’] Basic Life Support in Obstetrics (BLSO) certification courses each year. I am not aware of any specific evidence around this, but it is a known fact that, when L&Ds close, institutional memory of OB emergencies recede, and preparedness suffers,” he said.

Dr. Cullen agreed that if the closing of L&D units explains the higher rate of perinatal mortality in rural areas, both short-term and long-term solutions are needed.

“Every community must have a plan for obstetric and newborn emergencies. The decision to not offer maternity care means that rural providers will still provide maternity care but not be ready for emergencies,” he said, echoing a point made by Dr. Waits.

The study authors disclosed no conflicts. Dr. Cullen reported having no disclosures. 

SOURCE: Waits JB et al. Ann Fam Med. 2020;18:446-51.

The risk of depression is elevated in patients with cardiovascular diseases, but several specific antihypertensive therapies are associated with a reduced risk, and none appear to increase the risk, according to a population-based study that evaluated 10 years of data in nearly 4 million subjects.

“As the first study on individual antihypertensives and risk of depression, we found a decreased risk of depression with nine drugs,” reported a collaborative group of investigators from multiple institutions in Denmark where the study was undertaken.

In a study period spanning from 2005 to 2015, risk of a diagnosis of depression was evaluated in patients taking any of 41 antihypertensive therapies in four major categories. These were identified as angiotensin agents (ACE inhibitors or angiotensin II receptor blockers), calcium antagonists, beta-blockers, and diuretics.

Within these groups, agents associated with a reduced risk of depression were: two angiotensin agents, enalapril and ramipril; three calcium antagonists, amlodipine, verapamil, and verapamil combinations; and four beta-blockers, propranolol, atenolol, bisoprolol, and carvedilol. The remaining drugs in these classes and diuretics were not associated with a reduced risk of depression. However, no antihypertensive agent was linked to an increased risk of depression.

All people living in Denmark are assigned a unique personal identification number that permits health information to be tracked across multiple registers. In this study, information was linked for several registries, including the Danish Medical Register on Vital Statistics, the Medicinal Product Statistics, and the Danish Psychiatric Central Register.

Data from a total of 3.75 million patients exposed to antihypertensive therapy during the study period were evaluated. Roughly 1 million of them were exposed to angiotensin drugs and slightly more than a million were exposed to diuretics. For calcium antagonists or beta-blockers, the numbers were approximately 835,000 and 775,000, respectively.

After adjustment for such factors as concomitant somatic diagnoses, sex, age, and employment status, the hazard ratios for depression among drugs associated with protection identified a risk reduction of 10%-25% in most cases when those who had been given 6-10 prescriptions or more than 10 prescriptions were compared with those who received 2 or fewer.

At the level of 10 or more prescriptions, for example, the risk reductions were 17% for ramipril (HR, 0.83; 95% CI, 0.78-0.89), 8% for enalapril (HR, 0.92; 95% CI, 0.88-0.96), 18% for amlodipine (HR, 0.82; 95% CI, 0.79-0.86), 15% for verapamil (HR, 0.85; 95% CI, 0.79-0.83), 28% for propranolol (HR, 0.72; 95% CI, 0.67-0.77), 20% for atenolol (HR, 0.80; 95% CI, 0.74-0.86), 25% for bisoprolol (HR, 0.75; 95% CI, 0.67-0.84), and 16% for carvedilol (HR, 0.84; 95% CI, 0.75-0.95).

For verapamil combinations, the risk reduction was 67% (HR, 0.33; 95% CI, 0.17-0.63), but the investigators cautioned that only 130 individuals were exposed to verapamil combinations, limiting the reliability of this analysis.
 

Interpreting the findings

A study hypothesis, the observed protective effect against depression, was expected for angiotensin drugs and calcium-channel blockers, but not for beta-blockers, according to the investigators.

“The renin-angiotensin systems is one of the pathways known to modulate inflammation in the central nervous system and seems involved in the regulation of the stress response. Angiotensin agents may also exert anti-inflammatory effects,” the investigators explained. “Dysregulation of intracellular calcium is evident in depression, including receptor-regulated calcium signaling.”

In contrast, beta-blockers have been associated with increased risk of depression in some but not all studies, according to the investigators. They maintained that some clinicians avoid these agents in patients with a history of mood disorders.

In attempting to account for the variability within drug classes regarding protection and lack of protection against depression, the investigators speculated that differences in pharmacologic properties, such as relative lipophilicity or anti-inflammatory effect, might be important.

Despite the large amount of data, William B. White, MD, professor emeritus at the Calhoun Cardiology Center, University of Connecticut, Farmington, is not convinced.

“In observational studies, even those with very large samples sizes, bias and confounding are hard to extricate with controls and propensity-score matching,” Dr. White said. From his perspective, the protective effects of some but not all drugs within a class “give one the impression that the findings are likely random.”

A member of the editorial board of the journal in which this study appeared, Dr. White said he was not involved in the review of the manuscript. Ultimately, he believed that the results are difficult to interpret.

“For example, there is no plausible rationale for why 2 of the 16 ACE inhibitors or angiotensin II receptor blockers or 4 of the 15 beta-blockers or 3 of the 10 calcium-channel blockers would reduce depression while the others in the class would have no effect,” he said.

Despite the investigators’ conclusion that these data should drive drug choice for patients at risk of depression, “I would say the results of this analysis would not lead me to alter clinical practice,” Dr. White added.

According to the principal investigator of the study, Lars Vedel Kessing, MD, DSc, professor of psychiatry at the University of Copenhagen, many variables affect choice of antihypertensive drug. However, the depression risk is elevated in patients with cardiovascular or cerebrovascular disease and hypertension.

When risk of a mood disorder is a concern, use of one of the nine drugs associated with protection from depression should be considered, “especially in patients at increased risk of developing depression, including patients with prior depression or anxiety and patients with a family history of depression,” he and his coinvestigators concluded.

However, Dr. Kessing said in an interview that the data do not help with individual treatment choices. “We do not compare different antihypertensives against each other due to the risk of confounding by indications, so, no, it is not reasonable to consider relative risk among specific agents.”

The authors reported no potential conflicts of interest involving this topic.

SOURCE: Kessing LV et al. Hypertension. 2020 Aug 24. doi: 10.1161/HYPERTENSIONAHA.120.15605.

The risk of depression is elevated in patients with cardiovascular diseases, but several specific antihypertensive therapies are associated with a reduced risk, and none appear to increase the risk, according to a population-based study that evaluated 10 years of data in nearly 4 million subjects.

“As the first study on individual antihypertensives and risk of depression, we found a decreased risk of depression with nine drugs,” reported a collaborative group of investigators from multiple institutions in Denmark where the study was undertaken.

In a study period spanning from 2005 to 2015, risk of a diagnosis of depression was evaluated in patients taking any of 41 antihypertensive therapies in four major categories. These were identified as angiotensin agents (ACE inhibitors or angiotensin II receptor blockers), calcium antagonists, beta-blockers, and diuretics.

Within these groups, agents associated with a reduced risk of depression were: two angiotensin agents, enalapril and ramipril; three calcium antagonists, amlodipine, verapamil, and verapamil combinations; and four beta-blockers, propranolol, atenolol, bisoprolol, and carvedilol. The remaining drugs in these classes and diuretics were not associated with a reduced risk of depression. However, no antihypertensive agent was linked to an increased risk of depression.

All people living in Denmark are assigned a unique personal identification number that permits health information to be tracked across multiple registers. In this study, information was linked for several registries, including the Danish Medical Register on Vital Statistics, the Medicinal Product Statistics, and the Danish Psychiatric Central Register.

Data from a total of 3.75 million patients exposed to antihypertensive therapy during the study period were evaluated. Roughly 1 million of them were exposed to angiotensin drugs and slightly more than a million were exposed to diuretics. For calcium antagonists or beta-blockers, the numbers were approximately 835,000 and 775,000, respectively.

After adjustment for such factors as concomitant somatic diagnoses, sex, age, and employment status, the hazard ratios for depression among drugs associated with protection identified a risk reduction of 10%-25% in most cases when those who had been given 6-10 prescriptions or more than 10 prescriptions were compared with those who received 2 or fewer.

At the level of 10 or more prescriptions, for example, the risk reductions were 17% for ramipril (HR, 0.83; 95% CI, 0.78-0.89), 8% for enalapril (HR, 0.92; 95% CI, 0.88-0.96), 18% for amlodipine (HR, 0.82; 95% CI, 0.79-0.86), 15% for verapamil (HR, 0.85; 95% CI, 0.79-0.83), 28% for propranolol (HR, 0.72; 95% CI, 0.67-0.77), 20% for atenolol (HR, 0.80; 95% CI, 0.74-0.86), 25% for bisoprolol (HR, 0.75; 95% CI, 0.67-0.84), and 16% for carvedilol (HR, 0.84; 95% CI, 0.75-0.95).

For verapamil combinations, the risk reduction was 67% (HR, 0.33; 95% CI, 0.17-0.63), but the investigators cautioned that only 130 individuals were exposed to verapamil combinations, limiting the reliability of this analysis.
 

Interpreting the findings

A study hypothesis, the observed protective effect against depression, was expected for angiotensin drugs and calcium-channel blockers, but not for beta-blockers, according to the investigators.

“The renin-angiotensin systems is one of the pathways known to modulate inflammation in the central nervous system and seems involved in the regulation of the stress response. Angiotensin agents may also exert anti-inflammatory effects,” the investigators explained. “Dysregulation of intracellular calcium is evident in depression, including receptor-regulated calcium signaling.”

In contrast, beta-blockers have been associated with increased risk of depression in some but not all studies, according to the investigators. They maintained that some clinicians avoid these agents in patients with a history of mood disorders.

In attempting to account for the variability within drug classes regarding protection and lack of protection against depression, the investigators speculated that differences in pharmacologic properties, such as relative lipophilicity or anti-inflammatory effect, might be important.

Despite the large amount of data, William B. White, MD, professor emeritus at the Calhoun Cardiology Center, University of Connecticut, Farmington, is not convinced.

“In observational studies, even those with very large samples sizes, bias and confounding are hard to extricate with controls and propensity-score matching,” Dr. White said. From his perspective, the protective effects of some but not all drugs within a class “give one the impression that the findings are likely random.”

A member of the editorial board of the journal in which this study appeared, Dr. White said he was not involved in the review of the manuscript. Ultimately, he believed that the results are difficult to interpret.

“For example, there is no plausible rationale for why 2 of the 16 ACE inhibitors or angiotensin II receptor blockers or 4 of the 15 beta-blockers or 3 of the 10 calcium-channel blockers would reduce depression while the others in the class would have no effect,” he said.

Despite the investigators’ conclusion that these data should drive drug choice for patients at risk of depression, “I would say the results of this analysis would not lead me to alter clinical practice,” Dr. White added.

According to the principal investigator of the study, Lars Vedel Kessing, MD, DSc, professor of psychiatry at the University of Copenhagen, many variables affect choice of antihypertensive drug. However, the depression risk is elevated in patients with cardiovascular or cerebrovascular disease and hypertension.

When risk of a mood disorder is a concern, use of one of the nine drugs associated with protection from depression should be considered, “especially in patients at increased risk of developing depression, including patients with prior depression or anxiety and patients with a family history of depression,” he and his coinvestigators concluded.

However, Dr. Kessing said in an interview that the data do not help with individual treatment choices. “We do not compare different antihypertensives against each other due to the risk of confounding by indications, so, no, it is not reasonable to consider relative risk among specific agents.”

The authors reported no potential conflicts of interest involving this topic.

SOURCE: Kessing LV et al. Hypertension. 2020 Aug 24. doi: 10.1161/HYPERTENSIONAHA.120.15605.

The risk of depression is elevated in patients with cardiovascular diseases, but several specific antihypertensive therapies are associated with a reduced risk, and none appear to increase the risk, according to a population-based study that evaluated 10 years of data in nearly 4 million subjects.

“As the first study on individual antihypertensives and risk of depression, we found a decreased risk of depression with nine drugs,” reported a collaborative group of investigators from multiple institutions in Denmark where the study was undertaken.

In a study period spanning from 2005 to 2015, risk of a diagnosis of depression was evaluated in patients taking any of 41 antihypertensive therapies in four major categories. These were identified as angiotensin agents (ACE inhibitors or angiotensin II receptor blockers), calcium antagonists, beta-blockers, and diuretics.

Within these groups, agents associated with a reduced risk of depression were: two angiotensin agents, enalapril and ramipril; three calcium antagonists, amlodipine, verapamil, and verapamil combinations; and four beta-blockers, propranolol, atenolol, bisoprolol, and carvedilol. The remaining drugs in these classes and diuretics were not associated with a reduced risk of depression. However, no antihypertensive agent was linked to an increased risk of depression.

All people living in Denmark are assigned a unique personal identification number that permits health information to be tracked across multiple registers. In this study, information was linked for several registries, including the Danish Medical Register on Vital Statistics, the Medicinal Product Statistics, and the Danish Psychiatric Central Register.

Data from a total of 3.75 million patients exposed to antihypertensive therapy during the study period were evaluated. Roughly 1 million of them were exposed to angiotensin drugs and slightly more than a million were exposed to diuretics. For calcium antagonists or beta-blockers, the numbers were approximately 835,000 and 775,000, respectively.

After adjustment for such factors as concomitant somatic diagnoses, sex, age, and employment status, the hazard ratios for depression among drugs associated with protection identified a risk reduction of 10%-25% in most cases when those who had been given 6-10 prescriptions or more than 10 prescriptions were compared with those who received 2 or fewer.

At the level of 10 or more prescriptions, for example, the risk reductions were 17% for ramipril (HR, 0.83; 95% CI, 0.78-0.89), 8% for enalapril (HR, 0.92; 95% CI, 0.88-0.96), 18% for amlodipine (HR, 0.82; 95% CI, 0.79-0.86), 15% for verapamil (HR, 0.85; 95% CI, 0.79-0.83), 28% for propranolol (HR, 0.72; 95% CI, 0.67-0.77), 20% for atenolol (HR, 0.80; 95% CI, 0.74-0.86), 25% for bisoprolol (HR, 0.75; 95% CI, 0.67-0.84), and 16% for carvedilol (HR, 0.84; 95% CI, 0.75-0.95).

For verapamil combinations, the risk reduction was 67% (HR, 0.33; 95% CI, 0.17-0.63), but the investigators cautioned that only 130 individuals were exposed to verapamil combinations, limiting the reliability of this analysis.
 

Interpreting the findings

A study hypothesis, the observed protective effect against depression, was expected for angiotensin drugs and calcium-channel blockers, but not for beta-blockers, according to the investigators.

“The renin-angiotensin systems is one of the pathways known to modulate inflammation in the central nervous system and seems involved in the regulation of the stress response. Angiotensin agents may also exert anti-inflammatory effects,” the investigators explained. “Dysregulation of intracellular calcium is evident in depression, including receptor-regulated calcium signaling.”

In contrast, beta-blockers have been associated with increased risk of depression in some but not all studies, according to the investigators. They maintained that some clinicians avoid these agents in patients with a history of mood disorders.

In attempting to account for the variability within drug classes regarding protection and lack of protection against depression, the investigators speculated that differences in pharmacologic properties, such as relative lipophilicity or anti-inflammatory effect, might be important.

Despite the large amount of data, William B. White, MD, professor emeritus at the Calhoun Cardiology Center, University of Connecticut, Farmington, is not convinced.

“In observational studies, even those with very large samples sizes, bias and confounding are hard to extricate with controls and propensity-score matching,” Dr. White said. From his perspective, the protective effects of some but not all drugs within a class “give one the impression that the findings are likely random.”

A member of the editorial board of the journal in which this study appeared, Dr. White said he was not involved in the review of the manuscript. Ultimately, he believed that the results are difficult to interpret.

“For example, there is no plausible rationale for why 2 of the 16 ACE inhibitors or angiotensin II receptor blockers or 4 of the 15 beta-blockers or 3 of the 10 calcium-channel blockers would reduce depression while the others in the class would have no effect,” he said.

Despite the investigators’ conclusion that these data should drive drug choice for patients at risk of depression, “I would say the results of this analysis would not lead me to alter clinical practice,” Dr. White added.

According to the principal investigator of the study, Lars Vedel Kessing, MD, DSc, professor of psychiatry at the University of Copenhagen, many variables affect choice of antihypertensive drug. However, the depression risk is elevated in patients with cardiovascular or cerebrovascular disease and hypertension.

When risk of a mood disorder is a concern, use of one of the nine drugs associated with protection from depression should be considered, “especially in patients at increased risk of developing depression, including patients with prior depression or anxiety and patients with a family history of depression,” he and his coinvestigators concluded.

However, Dr. Kessing said in an interview that the data do not help with individual treatment choices. “We do not compare different antihypertensives against each other due to the risk of confounding by indications, so, no, it is not reasonable to consider relative risk among specific agents.”

The authors reported no potential conflicts of interest involving this topic.

SOURCE: Kessing LV et al. Hypertension. 2020 Aug 24. doi: 10.1161/HYPERTENSIONAHA.120.15605.

Pulmonary artery denervation (PADN) provides persistent and clinically significant hemodynamic improvements in patients with persistent chronic thromboembolic hypertension (CTEPH) after pulmonary endarterectomy (PEA), according to a randomized, sham-controlled trial.

“PADN in patients with CTEPH after PEA was safe and effective,” according to an investigating team led by Alexander Romanov, MD, PhD.

The mean reduction in pulmonary vascular resistance (PVR) was 258 dyn/sec per cm^–5 for those randomized to PADN versus 149 dyn/sec per cm^–5 (P = .001) for those randomized to the sham procedure, according to the newly published findings.

For the 6-minute walk test (6MWT), the mean distance was 470 m for the experimental group versus 399 m (P = .03) for the controls.

Several secondary endpoints measuring hemodynamics also favored PADN relative to the sham procedure at 12 months. This included the relative increase in tricuspid annular systolic excursion (P = .03) and the increase in the right ventricular fraction area (P < .001).

A total of 50 patients with residual CTEPH for at least 6 months after PEA despite medical therapy were enrolled and randomized. Entry criteria included a mean pulmonary artery pressure (PAP) of 25 mm Hg or greater or PVR greater than 400 dyn/sec per cm^–5 on right heart catheterization. Patients with comorbidities associated with a life expectancy of less than 1 year were excluded.

Those randomized to the sham group were treated with riociguat over the course of follow-up. This therapy was not offered to patients in the PADN group, but all patients were blinded to the procedure and told that riociguat might or might not be administered.

Following the procedure, participating clinicians, who were also blinded to the procedure, were instructed to provide standard therapies for heart failure, such beta-blockers, diuretics, or digoxin, as needed. All patients were placed on an oral anticoagulant.

At 12 months the mean PAP (26 vs. 35 mm Hg; P < .001) and the mean systolic PAP (46 vs. 54 mm Hg; P = .01) were significantly lower in the PADN group versus those who underwent a sham procedure.

About 52% of the PADN group versus 12% of the sham group were classified as responders by the definition of a PVR reduction of at least 150 dyn/sec per cm^–5 and 6MWT improvement of at least 20%, compared with baseline, reported Dr. Romanov, of the E. Meshalkin National Medical Research Center, ministry of health, Novosibirsk, Russia, and coinvestigators.

Of the three deaths caused by heart failure over the course of follow-up, two occurred in the sham group. Of the eight hospitalizations for heart failure, seven (29% of the sham group) occurred among controls versus one in those treated with PADN (4% of this group; P = .049).

There was one groin hematoma at the puncture site in each group. Both resolved without any consequences prior to hospital discharge. There were no other significant procedure-related complications in either group.

Larger multicenter trials are needed to confirm these findings, according to both the trial investigators and Marius M. Hoeper, MD, who is charge of the pulmonary hypertension program at the Hannover (Germany) Medical School.

In an editorial that accompanied publication of these findings, Dr. Hoeper identified the small sample size of this study as one of its limitations, but he said the results are consistent with several other small studies associating pulmonary artery denervation with benefit in pulmonary hypertension.

“It appears as if we are currently witnessing the emergence of a new treatment option for various forms of pulmonary hypertension,” Dr. Hoeper wrote. In his critique of the study, he suggested that it would have been “more informative” if both groups were on background riociguat, but the data from this and other studies so far indicates that ablation to achieve denervation “is safe and feasible.”

The PADN technique used in this study might be relevant to the results. Dr. Hoeper noted that the investigators employed catheter tip–based electroanatomic mapping with a novel remote navigation system with three-dimensional imaging of the right ventricle and central pulmonary arteries.

“Apparently, this approach minimizes radiation exposure and provides precise location of ablation sites,” Dr. Hoeper observed. However, he called for direct comparisons of this tool to the guidance systems used in other studies.

In an interview, Dr. Hoeper acknowledged that it is not yet clear that a large-scale trial of pulmonary artery denervation for the indication evaluated in this study is coming. He noted several strategies in CTEPH are widely used without trials confirming a reduction in clinical events.

“Balloon pulmonary angioplasty for CTEPH has become an established treatment around the world without any randomized, controlled trial and without demonstration of improved outcomes. A couple of well-conducted observational trials might be sufficient to convince physicians to introduce PADN as well,” he said. If such studies associated PADN with “improvements in hemodynamics, exercise capacity, and patient-reported outcomes, it might be sufficient.”

Currently, Dr. Hoeper is most concerned about obtaining further evidence of safety, which he characterized as a “major issue.”

If a multicenter trial is conducted “the primary endpoint should be focused on clinical events,” according to Dr. Romanov, who was asked to comment on the next steps in validating PADN for the treatment of CTEPH-associated pulmonary hypertension persisting after endarterectomy.

“The mortality rate during 1-year long-term follow-up is not so high, but heart failure progression is a problem. So in my view, the primary endpoint should be a composite of death and heart failure hospitalization,” he said. He called for follow-up duration of 2-3 years.

Jonathan Steinberg, MD, director of cardiac clinical trials and education, Summit Medical Group, Montclair, N.J., also called a trial with hard endpoints, such as death, the ideal.

In the meantime, hemodynamic and functional measures “are still quite valuable and move the ball forward for this intervention,” he said in an interview. Senior author of this trial and principle investigator of the recent ERADICATE-AF trial, which evaluated renal denervation in preventing recurrence of atrial fibrillation (JAMA. 2020;323:248-55), Dr. Steinberg predicted, “I do indeed suspect we will see trials that are more accomplishable [than a large-scale, randomized, controlled trial] in the not too distant future.”

Dr. Romanov received funding from Biosense Webster. Dr. Hoeper has received fees for lectures and/or consultations from Acceleron, Actelion, Bayer, Janssen, Merck Sharp & Dohme, and Pfizer.

SOURCE: Romanov A et al. J Am Coll Cardiol. 2020 Aug 17;76:916-26.

Pulmonary artery denervation (PADN) provides persistent and clinically significant hemodynamic improvements in patients with persistent chronic thromboembolic hypertension (CTEPH) after pulmonary endarterectomy (PEA), according to a randomized, sham-controlled trial.

“PADN in patients with CTEPH after PEA was safe and effective,” according to an investigating team led by Alexander Romanov, MD, PhD.

The mean reduction in pulmonary vascular resistance (PVR) was 258 dyn/sec per cm^–5 for those randomized to PADN versus 149 dyn/sec per cm^–5 (P = .001) for those randomized to the sham procedure, according to the newly published findings.

For the 6-minute walk test (6MWT), the mean distance was 470 m for the experimental group versus 399 m (P = .03) for the controls.

Several secondary endpoints measuring hemodynamics also favored PADN relative to the sham procedure at 12 months. This included the relative increase in tricuspid annular systolic excursion (P = .03) and the increase in the right ventricular fraction area (P < .001).

A total of 50 patients with residual CTEPH for at least 6 months after PEA despite medical therapy were enrolled and randomized. Entry criteria included a mean pulmonary artery pressure (PAP) of 25 mm Hg or greater or PVR greater than 400 dyn/sec per cm^–5 on right heart catheterization. Patients with comorbidities associated with a life expectancy of less than 1 year were excluded.

Those randomized to the sham group were treated with riociguat over the course of follow-up. This therapy was not offered to patients in the PADN group, but all patients were blinded to the procedure and told that riociguat might or might not be administered.

Following the procedure, participating clinicians, who were also blinded to the procedure, were instructed to provide standard therapies for heart failure, such beta-blockers, diuretics, or digoxin, as needed. All patients were placed on an oral anticoagulant.

At 12 months the mean PAP (26 vs. 35 mm Hg; P < .001) and the mean systolic PAP (46 vs. 54 mm Hg; P = .01) were significantly lower in the PADN group versus those who underwent a sham procedure.

About 52% of the PADN group versus 12% of the sham group were classified as responders by the definition of a PVR reduction of at least 150 dyn/sec per cm^–5 and 6MWT improvement of at least 20%, compared with baseline, reported Dr. Romanov, of the E. Meshalkin National Medical Research Center, ministry of health, Novosibirsk, Russia, and coinvestigators.

Of the three deaths caused by heart failure over the course of follow-up, two occurred in the sham group. Of the eight hospitalizations for heart failure, seven (29% of the sham group) occurred among controls versus one in those treated with PADN (4% of this group; P = .049).

There was one groin hematoma at the puncture site in each group. Both resolved without any consequences prior to hospital discharge. There were no other significant procedure-related complications in either group.

Larger multicenter trials are needed to confirm these findings, according to both the trial investigators and Marius M. Hoeper, MD, who is charge of the pulmonary hypertension program at the Hannover (Germany) Medical School.

In an editorial that accompanied publication of these findings, Dr. Hoeper identified the small sample size of this study as one of its limitations, but he said the results are consistent with several other small studies associating pulmonary artery denervation with benefit in pulmonary hypertension.

“It appears as if we are currently witnessing the emergence of a new treatment option for various forms of pulmonary hypertension,” Dr. Hoeper wrote. In his critique of the study, he suggested that it would have been “more informative” if both groups were on background riociguat, but the data from this and other studies so far indicates that ablation to achieve denervation “is safe and feasible.”

The PADN technique used in this study might be relevant to the results. Dr. Hoeper noted that the investigators employed catheter tip–based electroanatomic mapping with a novel remote navigation system with three-dimensional imaging of the right ventricle and central pulmonary arteries.

“Apparently, this approach minimizes radiation exposure and provides precise location of ablation sites,” Dr. Hoeper observed. However, he called for direct comparisons of this tool to the guidance systems used in other studies.

In an interview, Dr. Hoeper acknowledged that it is not yet clear that a large-scale trial of pulmonary artery denervation for the indication evaluated in this study is coming. He noted several strategies in CTEPH are widely used without trials confirming a reduction in clinical events.

“Balloon pulmonary angioplasty for CTEPH has become an established treatment around the world without any randomized, controlled trial and without demonstration of improved outcomes. A couple of well-conducted observational trials might be sufficient to convince physicians to introduce PADN as well,” he said. If such studies associated PADN with “improvements in hemodynamics, exercise capacity, and patient-reported outcomes, it might be sufficient.”

Currently, Dr. Hoeper is most concerned about obtaining further evidence of safety, which he characterized as a “major issue.”

If a multicenter trial is conducted “the primary endpoint should be focused on clinical events,” according to Dr. Romanov, who was asked to comment on the next steps in validating PADN for the treatment of CTEPH-associated pulmonary hypertension persisting after endarterectomy.

“The mortality rate during 1-year long-term follow-up is not so high, but heart failure progression is a problem. So in my view, the primary endpoint should be a composite of death and heart failure hospitalization,” he said. He called for follow-up duration of 2-3 years.

Jonathan Steinberg, MD, director of cardiac clinical trials and education, Summit Medical Group, Montclair, N.J., also called a trial with hard endpoints, such as death, the ideal.

In the meantime, hemodynamic and functional measures “are still quite valuable and move the ball forward for this intervention,” he said in an interview. Senior author of this trial and principle investigator of the recent ERADICATE-AF trial, which evaluated renal denervation in preventing recurrence of atrial fibrillation (JAMA. 2020;323:248-55), Dr. Steinberg predicted, “I do indeed suspect we will see trials that are more accomplishable [than a large-scale, randomized, controlled trial] in the not too distant future.”

Dr. Romanov received funding from Biosense Webster. Dr. Hoeper has received fees for lectures and/or consultations from Acceleron, Actelion, Bayer, Janssen, Merck Sharp & Dohme, and Pfizer.

SOURCE: Romanov A et al. J Am Coll Cardiol. 2020 Aug 17;76:916-26.

Pulmonary artery denervation (PADN) provides persistent and clinically significant hemodynamic improvements in patients with persistent chronic thromboembolic hypertension (CTEPH) after pulmonary endarterectomy (PEA), according to a randomized, sham-controlled trial.

“PADN in patients with CTEPH after PEA was safe and effective,” according to an investigating team led by Alexander Romanov, MD, PhD.

The mean reduction in pulmonary vascular resistance (PVR) was 258 dyn/sec per cm^–5 for those randomized to PADN versus 149 dyn/sec per cm^–5 (P = .001) for those randomized to the sham procedure, according to the newly published findings.

For the 6-minute walk test (6MWT), the mean distance was 470 m for the experimental group versus 399 m (P = .03) for the controls.

Several secondary endpoints measuring hemodynamics also favored PADN relative to the sham procedure at 12 months. This included the relative increase in tricuspid annular systolic excursion (P = .03) and the increase in the right ventricular fraction area (P < .001).

A total of 50 patients with residual CTEPH for at least 6 months after PEA despite medical therapy were enrolled and randomized. Entry criteria included a mean pulmonary artery pressure (PAP) of 25 mm Hg or greater or PVR greater than 400 dyn/sec per cm^–5 on right heart catheterization. Patients with comorbidities associated with a life expectancy of less than 1 year were excluded.

Those randomized to the sham group were treated with riociguat over the course of follow-up. This therapy was not offered to patients in the PADN group, but all patients were blinded to the procedure and told that riociguat might or might not be administered.

Following the procedure, participating clinicians, who were also blinded to the procedure, were instructed to provide standard therapies for heart failure, such beta-blockers, diuretics, or digoxin, as needed. All patients were placed on an oral anticoagulant.

At 12 months the mean PAP (26 vs. 35 mm Hg; P < .001) and the mean systolic PAP (46 vs. 54 mm Hg; P = .01) were significantly lower in the PADN group versus those who underwent a sham procedure.

About 52% of the PADN group versus 12% of the sham group were classified as responders by the definition of a PVR reduction of at least 150 dyn/sec per cm^–5 and 6MWT improvement of at least 20%, compared with baseline, reported Dr. Romanov, of the E. Meshalkin National Medical Research Center, ministry of health, Novosibirsk, Russia, and coinvestigators.

Of the three deaths caused by heart failure over the course of follow-up, two occurred in the sham group. Of the eight hospitalizations for heart failure, seven (29% of the sham group) occurred among controls versus one in those treated with PADN (4% of this group; P = .049).

There was one groin hematoma at the puncture site in each group. Both resolved without any consequences prior to hospital discharge. There were no other significant procedure-related complications in either group.

Larger multicenter trials are needed to confirm these findings, according to both the trial investigators and Marius M. Hoeper, MD, who is charge of the pulmonary hypertension program at the Hannover (Germany) Medical School.

In an editorial that accompanied publication of these findings, Dr. Hoeper identified the small sample size of this study as one of its limitations, but he said the results are consistent with several other small studies associating pulmonary artery denervation with benefit in pulmonary hypertension.

“It appears as if we are currently witnessing the emergence of a new treatment option for various forms of pulmonary hypertension,” Dr. Hoeper wrote. In his critique of the study, he suggested that it would have been “more informative” if both groups were on background riociguat, but the data from this and other studies so far indicates that ablation to achieve denervation “is safe and feasible.”

The PADN technique used in this study might be relevant to the results. Dr. Hoeper noted that the investigators employed catheter tip–based electroanatomic mapping with a novel remote navigation system with three-dimensional imaging of the right ventricle and central pulmonary arteries.

“Apparently, this approach minimizes radiation exposure and provides precise location of ablation sites,” Dr. Hoeper observed. However, he called for direct comparisons of this tool to the guidance systems used in other studies.

In an interview, Dr. Hoeper acknowledged that it is not yet clear that a large-scale trial of pulmonary artery denervation for the indication evaluated in this study is coming. He noted several strategies in CTEPH are widely used without trials confirming a reduction in clinical events.

“Balloon pulmonary angioplasty for CTEPH has become an established treatment around the world without any randomized, controlled trial and without demonstration of improved outcomes. A couple of well-conducted observational trials might be sufficient to convince physicians to introduce PADN as well,” he said. If such studies associated PADN with “improvements in hemodynamics, exercise capacity, and patient-reported outcomes, it might be sufficient.”

Currently, Dr. Hoeper is most concerned about obtaining further evidence of safety, which he characterized as a “major issue.”

If a multicenter trial is conducted “the primary endpoint should be focused on clinical events,” according to Dr. Romanov, who was asked to comment on the next steps in validating PADN for the treatment of CTEPH-associated pulmonary hypertension persisting after endarterectomy.

“The mortality rate during 1-year long-term follow-up is not so high, but heart failure progression is a problem. So in my view, the primary endpoint should be a composite of death and heart failure hospitalization,” he said. He called for follow-up duration of 2-3 years.

Jonathan Steinberg, MD, director of cardiac clinical trials and education, Summit Medical Group, Montclair, N.J., also called a trial with hard endpoints, such as death, the ideal.

In the meantime, hemodynamic and functional measures “are still quite valuable and move the ball forward for this intervention,” he said in an interview. Senior author of this trial and principle investigator of the recent ERADICATE-AF trial, which evaluated renal denervation in preventing recurrence of atrial fibrillation (JAMA. 2020;323:248-55), Dr. Steinberg predicted, “I do indeed suspect we will see trials that are more accomplishable [than a large-scale, randomized, controlled trial] in the not too distant future.”

Dr. Romanov received funding from Biosense Webster. Dr. Hoeper has received fees for lectures and/or consultations from Acceleron, Actelion, Bayer, Janssen, Merck Sharp & Dohme, and Pfizer.

SOURCE: Romanov A et al. J Am Coll Cardiol. 2020 Aug 17;76:916-26.

A substantial decrease in hospital admissions for acute MI was accompanied by a rise in mortality, particularly for ST-segment elevation MI (STEMI), following the onset of the COVID-19 pandemic, according to a cross-sectional retrospective study.

Although it can’t be confirmed from these results that the observed increase in in-hospital acute MI (AMI) mortality are related to delays in seeking treatment, this is a reasonable working hypothesis until more is known, commented Harlan Krumholz, MD, who was not involved in the study.

The analysis, derived from data collected at 49 centers in a hospital system spread across six states, supports previous reports that patients with AMI were avoiding hospitalization, according to the investigators, who were led by Tyler J. Gluckman, MD, medical director of the Center for Cardiovascular Analytics, Providence Heart Institute, Portland, Ore.

When compared with a nearly 14-month period that preceded the COVID-19 pandemic, the rate of AMI-associated hospitalization fell by 19 cases per week (95% confidence interval, –29.0 to –9.0 cases) in the early COVID-19 period, which was defined by the investigators as spanning from Feb. 23, 2020 to March 28, 2020.

The case rate per week then increased by 10.5 (95% CI, 4.6-16.5 cases) in a subsequent 8-week period spanning between March 29, 2020, and May 16, 2020. Although a substantial increase from the early COVID-19 period, the case rate remained below the baseline established before COVID-19.

The analysis looked at 15,244 AMI hospitalizations among 14,724 patients treated in the Providence St. Joseph Hospital System, which has facilities in Alaska, California, Montana, Oregon, Texas, and Washington. The 1,915 AMI cases captured from Feb. 23, 2020, represented 13% of the total.
 

Differences in mortality, patients, treatment

In the early period, the ratio of observed-to-expected (O/E) mortality relative to the pre–COVID-19 baseline increased by 27% (odds ratio, 1.27; 95% CI, 1.07-1.48). When STEMI was analyzed separately, the O/E mortality was nearly double that of the baseline period (OR, 1.96; 95% CI, 1.22-2.70). In the latter post–COVID-19 period of observation, the overall increase in AMI-associated mortality on the basis of an O/E ratio was no longer significant relative to the baseline period (OR, 1.23; 95% CI, 0.98-1.47). However, the relative increase in STEMI-associated mortality on an O/E basis was even greater (OR, 2.40; 95% CI, 1.65-3.16) in the second COVID-19 period analyzed. Even after risk adjustment, the OR for STEMI mortality remained significantly elevated relative to baseline (1.52; 95% CI, 1.02-2.26).

The differences in AMI patients treated before the onset of the COVID-19 pandemic and those treated afterwards might be relevant, according to the investigators. Specifically, patients hospitalized after Feb. 23, 2020 were 1-3 years younger (P < .001) depending on type of AMI, and more likely to be Asian (P = .01).

The length of stay was 6 hours shorter in the early COVID-19 period and 7 hours shorter in the latter period relative to baseline, but an analysis of treatment approaches to non-STEMI and STEMI during the COVID-19 pandemic were not found to be significantly different from baseline.

Prior to the COVID-19 pandemic, 79% of STEMI patients and 77% of non-STEMI patients were discharged home, which was significantly lower than in the early COVID-19 period, when 83% (P = .02) of STEMI and 81% (P = .006) of non-STEMI patients were discharged home. In the latter period, discharge to home care was also significantly higher than in the baseline period.
 

More than fear of COVID-19?

One theory to account for the reduction in AMI hospitalizations and the increase in AMI-related mortality is the possibility that patients were slow to seek care at acute care hospitals because of concern about COVID-19 infection, according to Dr. Gluckman and coinvestigators.

“Given the time-sensitive nature of STEMI, any delay by patients, emergency medical services, the emergency department, or cardiac catheterization laboratory may have played a role,” they suggested.

In an interview, Dr. Gluckman said that further effort to identify the reasons for the increased AMI-related mortality is planned. Pulling data from the electronic medical records of the patients included in this retrospective analysis might be a “challenge,” but Dr. Gluckman reported that he and his coinvestigators plan to look at a different set of registry data that might provide information on sources of delay, particularly in the STEMI population.

“This includes looking at a number of time factors, such as symptom onset to first medical contact, first medical contact to device, and door-in-door-out times,” Dr. Gluckman said. The goal is to “better understand if delays [in treatment] occurred during the pandemic and, if so, how they may have contributed to increases in risk adjusted mortality.”

Dr. Krumholz, director of the Yale Center for Outcomes Research and Evaluation, New Haven, Conn., called this study a “useful” confirmation of changes in AMI-related care with the onset of the COVID-19 pandemic. As reported anecdotally, the study “indicates marked decreases in hospitalizations of patients with AMI even in areas that were not experiencing big outbreaks but did have some restrictions to limit spread,” he noted.

More data gathered by other centers might provide information about what it all means.

“There remain so many questions about what happened and what consequences accrued,” Dr. Krumholz observed. “In the meantime, we need to continue to send the message that people with symptoms that suggest a heart attack need to rapidly seek care.”

The investigators reported having no financial conflicts of interest.

SOURCE: Gluckman TJ et al. JAMA Cardiol. 2020 Aug 7. doi: 10.1001/jamacardio.2020.3629.

A substantial decrease in hospital admissions for acute MI was accompanied by a rise in mortality, particularly for ST-segment elevation MI (STEMI), following the onset of the COVID-19 pandemic, according to a cross-sectional retrospective study.

Although it can’t be confirmed from these results that the observed increase in in-hospital acute MI (AMI) mortality are related to delays in seeking treatment, this is a reasonable working hypothesis until more is known, commented Harlan Krumholz, MD, who was not involved in the study.

The analysis, derived from data collected at 49 centers in a hospital system spread across six states, supports previous reports that patients with AMI were avoiding hospitalization, according to the investigators, who were led by Tyler J. Gluckman, MD, medical director of the Center for Cardiovascular Analytics, Providence Heart Institute, Portland, Ore.

When compared with a nearly 14-month period that preceded the COVID-19 pandemic, the rate of AMI-associated hospitalization fell by 19 cases per week (95% confidence interval, –29.0 to –9.0 cases) in the early COVID-19 period, which was defined by the investigators as spanning from Feb. 23, 2020 to March 28, 2020.

The case rate per week then increased by 10.5 (95% CI, 4.6-16.5 cases) in a subsequent 8-week period spanning between March 29, 2020, and May 16, 2020. Although a substantial increase from the early COVID-19 period, the case rate remained below the baseline established before COVID-19.

The analysis looked at 15,244 AMI hospitalizations among 14,724 patients treated in the Providence St. Joseph Hospital System, which has facilities in Alaska, California, Montana, Oregon, Texas, and Washington. The 1,915 AMI cases captured from Feb. 23, 2020, represented 13% of the total.
 

Differences in mortality, patients, treatment

In the early period, the ratio of observed-to-expected (O/E) mortality relative to the pre–COVID-19 baseline increased by 27% (odds ratio, 1.27; 95% CI, 1.07-1.48). When STEMI was analyzed separately, the O/E mortality was nearly double that of the baseline period (OR, 1.96; 95% CI, 1.22-2.70). In the latter post–COVID-19 period of observation, the overall increase in AMI-associated mortality on the basis of an O/E ratio was no longer significant relative to the baseline period (OR, 1.23; 95% CI, 0.98-1.47). However, the relative increase in STEMI-associated mortality on an O/E basis was even greater (OR, 2.40; 95% CI, 1.65-3.16) in the second COVID-19 period analyzed. Even after risk adjustment, the OR for STEMI mortality remained significantly elevated relative to baseline (1.52; 95% CI, 1.02-2.26).

The differences in AMI patients treated before the onset of the COVID-19 pandemic and those treated afterwards might be relevant, according to the investigators. Specifically, patients hospitalized after Feb. 23, 2020 were 1-3 years younger (P < .001) depending on type of AMI, and more likely to be Asian (P = .01).

The length of stay was 6 hours shorter in the early COVID-19 period and 7 hours shorter in the latter period relative to baseline, but an analysis of treatment approaches to non-STEMI and STEMI during the COVID-19 pandemic were not found to be significantly different from baseline.

Prior to the COVID-19 pandemic, 79% of STEMI patients and 77% of non-STEMI patients were discharged home, which was significantly lower than in the early COVID-19 period, when 83% (P = .02) of STEMI and 81% (P = .006) of non-STEMI patients were discharged home. In the latter period, discharge to home care was also significantly higher than in the baseline period.
 

More than fear of COVID-19?

One theory to account for the reduction in AMI hospitalizations and the increase in AMI-related mortality is the possibility that patients were slow to seek care at acute care hospitals because of concern about COVID-19 infection, according to Dr. Gluckman and coinvestigators.

“Given the time-sensitive nature of STEMI, any delay by patients, emergency medical services, the emergency department, or cardiac catheterization laboratory may have played a role,” they suggested.

In an interview, Dr. Gluckman said that further effort to identify the reasons for the increased AMI-related mortality is planned. Pulling data from the electronic medical records of the patients included in this retrospective analysis might be a “challenge,” but Dr. Gluckman reported that he and his coinvestigators plan to look at a different set of registry data that might provide information on sources of delay, particularly in the STEMI population.

“This includes looking at a number of time factors, such as symptom onset to first medical contact, first medical contact to device, and door-in-door-out times,” Dr. Gluckman said. The goal is to “better understand if delays [in treatment] occurred during the pandemic and, if so, how they may have contributed to increases in risk adjusted mortality.”

Dr. Krumholz, director of the Yale Center for Outcomes Research and Evaluation, New Haven, Conn., called this study a “useful” confirmation of changes in AMI-related care with the onset of the COVID-19 pandemic. As reported anecdotally, the study “indicates marked decreases in hospitalizations of patients with AMI even in areas that were not experiencing big outbreaks but did have some restrictions to limit spread,” he noted.

More data gathered by other centers might provide information about what it all means.

“There remain so many questions about what happened and what consequences accrued,” Dr. Krumholz observed. “In the meantime, we need to continue to send the message that people with symptoms that suggest a heart attack need to rapidly seek care.”

The investigators reported having no financial conflicts of interest.

SOURCE: Gluckman TJ et al. JAMA Cardiol. 2020 Aug 7. doi: 10.1001/jamacardio.2020.3629.

A substantial decrease in hospital admissions for acute MI was accompanied by a rise in mortality, particularly for ST-segment elevation MI (STEMI), following the onset of the COVID-19 pandemic, according to a cross-sectional retrospective study.

Although it can’t be confirmed from these results that the observed increase in in-hospital acute MI (AMI) mortality are related to delays in seeking treatment, this is a reasonable working hypothesis until more is known, commented Harlan Krumholz, MD, who was not involved in the study.

The analysis, derived from data collected at 49 centers in a hospital system spread across six states, supports previous reports that patients with AMI were avoiding hospitalization, according to the investigators, who were led by Tyler J. Gluckman, MD, medical director of the Center for Cardiovascular Analytics, Providence Heart Institute, Portland, Ore.

When compared with a nearly 14-month period that preceded the COVID-19 pandemic, the rate of AMI-associated hospitalization fell by 19 cases per week (95% confidence interval, –29.0 to –9.0 cases) in the early COVID-19 period, which was defined by the investigators as spanning from Feb. 23, 2020 to March 28, 2020.

The case rate per week then increased by 10.5 (95% CI, 4.6-16.5 cases) in a subsequent 8-week period spanning between March 29, 2020, and May 16, 2020. Although a substantial increase from the early COVID-19 period, the case rate remained below the baseline established before COVID-19.

The analysis looked at 15,244 AMI hospitalizations among 14,724 patients treated in the Providence St. Joseph Hospital System, which has facilities in Alaska, California, Montana, Oregon, Texas, and Washington. The 1,915 AMI cases captured from Feb. 23, 2020, represented 13% of the total.
 

Differences in mortality, patients, treatment

In the early period, the ratio of observed-to-expected (O/E) mortality relative to the pre–COVID-19 baseline increased by 27% (odds ratio, 1.27; 95% CI, 1.07-1.48). When STEMI was analyzed separately, the O/E mortality was nearly double that of the baseline period (OR, 1.96; 95% CI, 1.22-2.70). In the latter post–COVID-19 period of observation, the overall increase in AMI-associated mortality on the basis of an O/E ratio was no longer significant relative to the baseline period (OR, 1.23; 95% CI, 0.98-1.47). However, the relative increase in STEMI-associated mortality on an O/E basis was even greater (OR, 2.40; 95% CI, 1.65-3.16) in the second COVID-19 period analyzed. Even after risk adjustment, the OR for STEMI mortality remained significantly elevated relative to baseline (1.52; 95% CI, 1.02-2.26).

The differences in AMI patients treated before the onset of the COVID-19 pandemic and those treated afterwards might be relevant, according to the investigators. Specifically, patients hospitalized after Feb. 23, 2020 were 1-3 years younger (P < .001) depending on type of AMI, and more likely to be Asian (P = .01).

The length of stay was 6 hours shorter in the early COVID-19 period and 7 hours shorter in the latter period relative to baseline, but an analysis of treatment approaches to non-STEMI and STEMI during the COVID-19 pandemic were not found to be significantly different from baseline.

Prior to the COVID-19 pandemic, 79% of STEMI patients and 77% of non-STEMI patients were discharged home, which was significantly lower than in the early COVID-19 period, when 83% (P = .02) of STEMI and 81% (P = .006) of non-STEMI patients were discharged home. In the latter period, discharge to home care was also significantly higher than in the baseline period.
 

More than fear of COVID-19?

One theory to account for the reduction in AMI hospitalizations and the increase in AMI-related mortality is the possibility that patients were slow to seek care at acute care hospitals because of concern about COVID-19 infection, according to Dr. Gluckman and coinvestigators.

“Given the time-sensitive nature of STEMI, any delay by patients, emergency medical services, the emergency department, or cardiac catheterization laboratory may have played a role,” they suggested.

In an interview, Dr. Gluckman said that further effort to identify the reasons for the increased AMI-related mortality is planned. Pulling data from the electronic medical records of the patients included in this retrospective analysis might be a “challenge,” but Dr. Gluckman reported that he and his coinvestigators plan to look at a different set of registry data that might provide information on sources of delay, particularly in the STEMI population.

“This includes looking at a number of time factors, such as symptom onset to first medical contact, first medical contact to device, and door-in-door-out times,” Dr. Gluckman said. The goal is to “better understand if delays [in treatment] occurred during the pandemic and, if so, how they may have contributed to increases in risk adjusted mortality.”

Dr. Krumholz, director of the Yale Center for Outcomes Research and Evaluation, New Haven, Conn., called this study a “useful” confirmation of changes in AMI-related care with the onset of the COVID-19 pandemic. As reported anecdotally, the study “indicates marked decreases in hospitalizations of patients with AMI even in areas that were not experiencing big outbreaks but did have some restrictions to limit spread,” he noted.

More data gathered by other centers might provide information about what it all means.

“There remain so many questions about what happened and what consequences accrued,” Dr. Krumholz observed. “In the meantime, we need to continue to send the message that people with symptoms that suggest a heart attack need to rapidly seek care.”

The investigators reported having no financial conflicts of interest.

SOURCE: Gluckman TJ et al. JAMA Cardiol. 2020 Aug 7. doi: 10.1001/jamacardio.2020.3629.

A methodical, constructive, goal-oriented rapid repetition of emergency response simulations has emerged as a dominant strategy for pediatric readiness in the hospital setting, according to a detailed description of one such program at the virtual Pediatric Hospital Medicine.

Rather than a single run-through followed by a lengthy debriefing, which has been a traditional approach, short simulations done rapidly and repeatedly until skills are mastered improve skill development, according to Jeanmarie Schied, MD, of the department of pediatrics, University of Chicago Medicine.

A methodical, constructive, goal-oriented rapid repetition of emergency response simulations has emerged as a dominant strategy for pediatric readiness in the hospital setting, according to a detailed description of one such program at the virtual Pediatric Hospital Medicine.

Rather than a single run-through followed by a lengthy debriefing, which has been a traditional approach, short simulations done rapidly and repeatedly until skills are mastered improve skill development, according to Jeanmarie Schied, MD, of the department of pediatrics, University of Chicago Medicine.

A methodical, constructive, goal-oriented rapid repetition of emergency response simulations has emerged as a dominant strategy for pediatric readiness in the hospital setting, according to a detailed description of one such program at the virtual Pediatric Hospital Medicine.

Rather than a single run-through followed by a lengthy debriefing, which has been a traditional approach, short simulations done rapidly and repeatedly until skills are mastered improve skill development, according to Jeanmarie Schied, MD, of the department of pediatrics, University of Chicago Medicine.

Collecting cells from the skin surface with adhesive tape strips is demonstrating a level of accuracy that is rivaling skin biopsies for atopic dermatitis and psoriasis, promising a minimally invasive approach for monitoring these and potentially other dermatologic diseases, according to the latest advances with this approach.

Courtesy Mount Sinai Health System

“Tape strips are not going to fully replace biopsies, but we think they will have an important role in diagnosing and monitoring response to therapy by avoiding the potential scarring and pain of biopsy,” reported Emma Guttman-Yassky, MD, PhD, professor of dermatology and director of the laboratory inflammatory skin diseases at the Icahn School of Medicine at Mount Sinai Medical Center, New York.

The concept of using adhesive strips to remove surface skin cells for clinical study has been around for more than 20 years, but there has been recent progress. A newly published study, which compared skin from patients with atopic dermatitis (AD) or psoriasis with that of controls, was characterized as “the most comprehensive tape strip molecular profiling in any inflammatory skin disease to date and the first to fully characterize and compare AD to psoriasis,” wrote Dr. Guttman-Yassky, the senior author, and coauthors.

It also appears to be a leap forward. RNA sequencing detected thousands of differentially expressed genes reflecting immune and barrier biomarkers characteristic of the molecular phenotypes of atopic dermatitis and psoriasis. These were not only found to be consistent with biopsy studies but identified additional unique genes and pathways relevant to their pathological signature.

“In the past, the success rate for transcriptome sequencing even for a more limited panel of proteins was approaching 50% when considering both lesional, nonlesional skin, and healthy skin, but we are now approaching 100% for sample recovery and for analysis of RNA and genes,” Dr. Guttman-Yassky said in an interview.

Tissue samples were obtained with tape strips from lesional and nonlesional skin from 20 patients with AD and 20 patients with psoriasis. Compared with 20 tape strips from controls, they were evaluated with RNA sequencing followed by quantitative real-time polymerase chain reaction of immune and barrier biomarkers.

The sample recovery rate was 96% overall and 95% or better regardless of whether the skin was lesional or nonlesional.

With RNA sequencing of more than 20,000 transcripts, including multiple cellular, immune, and barrier biomarkers, an enormous amount of data was generated, but the key finding is that these diseases are readily distinguished with profiling based on tape strips.

Although numerous biomarkers were shared, “tape strips completely discriminate between atopic dermatitis and psoriasis with a degree of reliability that is comparable to skin biopsy,” Dr. Guttman-Yassky said.

One of the biomarkers, expression of nitric oxide synthase 2/inducible nitric oxide synthase, distinguished AD from psoriasis with 100% accuracy. As previously reported in biopsy studies, other biomarkers collectively associated AD with a profile related to a Th2-type inflammatory response and psoriasis with a Th17-type inflammatory response.

Tape strips also confirmed significant pathology in the nonlesional as well as the lesional skin of patients with AD or psoriasis. This included an increase in Th2-type products, such as interleukin-4 and IL-13, in nonlesional skin of atopic dermatitis and Th17-type products, such as IL-17, in nonlesional skin of psoriasis.

Some biomarkers of AD and psoriasis had an even greater differentiation in tape strips than previously reported from biopsy studies, according to Dr. Guttman-Yassky. In this study, tape strips also captured more differentially expressed genes than previously reported with biopsies.

One potential limitation of tape strips is that the RNA isolation process is time consuming, but this might be less of an issue in routine clinical use if there is a more refined number of biomarkers that are targeted or if technological improvements simplify processing, Dr. Guttman-Yassky pointed out.

To develop clinical utility for tape strips beyond AD and psoriasis, more work is needed to standardize the depth of sampling, which is variable with tape strips, she noted. Depth is relevant to the analysis of gene expression and mRNA activity of each dermatologic disease.

“Tape strips remain a research tool for now, but we do think that this technique can be refined and employed for clinical purposes, including diagnosis and monitoring response to treatment,” she said.

Relative to biopsy, the advantages are not difficult to envision. Dr. Guttman-Yassky, who recently published a study of tape strips for evaluating AD in children emphasized that tape strips are generally painless.

“Patients really do not mind tape strips,” she said. Although she believes that tape strips are providing unique insight into the pathology of inflammatory diseases not necessarily available with biopsy, she emphasized the practical value. Not least, “these could really help when the goal is to evaluate response to therapy over time.”

Another investigator who has conducted studies with tape strips, Maja-Lisa Clausen, MD, PhD, also thinks tape strips are likely to become routine clinical tools.

“Once the basis research, validation, and data are out, I think numerous companies will be ready to develop machines for more quick and easy processing, compared to the more labor intensive process that is used today for research,” explained Dr. Clausen, who is in the department of dermatology, Bispebjerb Hospital, University of Copenhagen.

She considers tape strips particularly promising for children, but she thinks the biomarker profiling made possible by these strips might be leading to personalized treatment programs for dermatologic diseases.

“What we need is further validation; which tape to use, how deep, and the importance of storage, which is a big issue in the clinic,” Dr. Clausen said in an interview.

Dr. Guttman-Yassky has financial relationships with multiple pharmaceutical companies, including those with therapies for psoriasis.

SOURCE: Guttman-Yassky E et al. J Allergy Clin Immunol. 2020 Jul 9. doi: 10.1016/j.jaci.2020.05.048.

Collecting cells from the skin surface with adhesive tape strips is demonstrating a level of accuracy that is rivaling skin biopsies for atopic dermatitis and psoriasis, promising a minimally invasive approach for monitoring these and potentially other dermatologic diseases, according to the latest advances with this approach.

Courtesy Mount Sinai Health System

“Tape strips are not going to fully replace biopsies, but we think they will have an important role in diagnosing and monitoring response to therapy by avoiding the potential scarring and pain of biopsy,” reported Emma Guttman-Yassky, MD, PhD, professor of dermatology and director of the laboratory inflammatory skin diseases at the Icahn School of Medicine at Mount Sinai Medical Center, New York.

The concept of using adhesive strips to remove surface skin cells for clinical study has been around for more than 20 years, but there has been recent progress. A newly published study, which compared skin from patients with atopic dermatitis (AD) or psoriasis with that of controls, was characterized as “the most comprehensive tape strip molecular profiling in any inflammatory skin disease to date and the first to fully characterize and compare AD to psoriasis,” wrote Dr. Guttman-Yassky, the senior author, and coauthors.

It also appears to be a leap forward. RNA sequencing detected thousands of differentially expressed genes reflecting immune and barrier biomarkers characteristic of the molecular phenotypes of atopic dermatitis and psoriasis. These were not only found to be consistent with biopsy studies but identified additional unique genes and pathways relevant to their pathological signature.

“In the past, the success rate for transcriptome sequencing even for a more limited panel of proteins was approaching 50% when considering both lesional, nonlesional skin, and healthy skin, but we are now approaching 100% for sample recovery and for analysis of RNA and genes,” Dr. Guttman-Yassky said in an interview.

Tissue samples were obtained with tape strips from lesional and nonlesional skin from 20 patients with AD and 20 patients with psoriasis. Compared with 20 tape strips from controls, they were evaluated with RNA sequencing followed by quantitative real-time polymerase chain reaction of immune and barrier biomarkers.

The sample recovery rate was 96% overall and 95% or better regardless of whether the skin was lesional or nonlesional.

With RNA sequencing of more than 20,000 transcripts, including multiple cellular, immune, and barrier biomarkers, an enormous amount of data was generated, but the key finding is that these diseases are readily distinguished with profiling based on tape strips.

Although numerous biomarkers were shared, “tape strips completely discriminate between atopic dermatitis and psoriasis with a degree of reliability that is comparable to skin biopsy,” Dr. Guttman-Yassky said.

One of the biomarkers, expression of nitric oxide synthase 2/inducible nitric oxide synthase, distinguished AD from psoriasis with 100% accuracy. As previously reported in biopsy studies, other biomarkers collectively associated AD with a profile related to a Th2-type inflammatory response and psoriasis with a Th17-type inflammatory response.

Tape strips also confirmed significant pathology in the nonlesional as well as the lesional skin of patients with AD or psoriasis. This included an increase in Th2-type products, such as interleukin-4 and IL-13, in nonlesional skin of atopic dermatitis and Th17-type products, such as IL-17, in nonlesional skin of psoriasis.

Some biomarkers of AD and psoriasis had an even greater differentiation in tape strips than previously reported from biopsy studies, according to Dr. Guttman-Yassky. In this study, tape strips also captured more differentially expressed genes than previously reported with biopsies.

One potential limitation of tape strips is that the RNA isolation process is time consuming, but this might be less of an issue in routine clinical use if there is a more refined number of biomarkers that are targeted or if technological improvements simplify processing, Dr. Guttman-Yassky pointed out.

To develop clinical utility for tape strips beyond AD and psoriasis, more work is needed to standardize the depth of sampling, which is variable with tape strips, she noted. Depth is relevant to the analysis of gene expression and mRNA activity of each dermatologic disease.

“Tape strips remain a research tool for now, but we do think that this technique can be refined and employed for clinical purposes, including diagnosis and monitoring response to treatment,” she said.

Relative to biopsy, the advantages are not difficult to envision. Dr. Guttman-Yassky, who recently published a study of tape strips for evaluating AD in children emphasized that tape strips are generally painless.

“Patients really do not mind tape strips,” she said. Although she believes that tape strips are providing unique insight into the pathology of inflammatory diseases not necessarily available with biopsy, she emphasized the practical value. Not least, “these could really help when the goal is to evaluate response to therapy over time.”

Another investigator who has conducted studies with tape strips, Maja-Lisa Clausen, MD, PhD, also thinks tape strips are likely to become routine clinical tools.

“Once the basis research, validation, and data are out, I think numerous companies will be ready to develop machines for more quick and easy processing, compared to the more labor intensive process that is used today for research,” explained Dr. Clausen, who is in the department of dermatology, Bispebjerb Hospital, University of Copenhagen.

She considers tape strips particularly promising for children, but she thinks the biomarker profiling made possible by these strips might be leading to personalized treatment programs for dermatologic diseases.

“What we need is further validation; which tape to use, how deep, and the importance of storage, which is a big issue in the clinic,” Dr. Clausen said in an interview.

Dr. Guttman-Yassky has financial relationships with multiple pharmaceutical companies, including those with therapies for psoriasis.

SOURCE: Guttman-Yassky E et al. J Allergy Clin Immunol. 2020 Jul 9. doi: 10.1016/j.jaci.2020.05.048.

Collecting cells from the skin surface with adhesive tape strips is demonstrating a level of accuracy that is rivaling skin biopsies for atopic dermatitis and psoriasis, promising a minimally invasive approach for monitoring these and potentially other dermatologic diseases, according to the latest advances with this approach.

Courtesy Mount Sinai Health System

“Tape strips are not going to fully replace biopsies, but we think they will have an important role in diagnosing and monitoring response to therapy by avoiding the potential scarring and pain of biopsy,” reported Emma Guttman-Yassky, MD, PhD, professor of dermatology and director of the laboratory inflammatory skin diseases at the Icahn School of Medicine at Mount Sinai Medical Center, New York.

The concept of using adhesive strips to remove surface skin cells for clinical study has been around for more than 20 years, but there has been recent progress. A newly published study, which compared skin from patients with atopic dermatitis (AD) or psoriasis with that of controls, was characterized as “the most comprehensive tape strip molecular profiling in any inflammatory skin disease to date and the first to fully characterize and compare AD to psoriasis,” wrote Dr. Guttman-Yassky, the senior author, and coauthors.

It also appears to be a leap forward. RNA sequencing detected thousands of differentially expressed genes reflecting immune and barrier biomarkers characteristic of the molecular phenotypes of atopic dermatitis and psoriasis. These were not only found to be consistent with biopsy studies but identified additional unique genes and pathways relevant to their pathological signature.

“In the past, the success rate for transcriptome sequencing even for a more limited panel of proteins was approaching 50% when considering both lesional, nonlesional skin, and healthy skin, but we are now approaching 100% for sample recovery and for analysis of RNA and genes,” Dr. Guttman-Yassky said in an interview.

Tissue samples were obtained with tape strips from lesional and nonlesional skin from 20 patients with AD and 20 patients with psoriasis. Compared with 20 tape strips from controls, they were evaluated with RNA sequencing followed by quantitative real-time polymerase chain reaction of immune and barrier biomarkers.

The sample recovery rate was 96% overall and 95% or better regardless of whether the skin was lesional or nonlesional.

With RNA sequencing of more than 20,000 transcripts, including multiple cellular, immune, and barrier biomarkers, an enormous amount of data was generated, but the key finding is that these diseases are readily distinguished with profiling based on tape strips.

Although numerous biomarkers were shared, “tape strips completely discriminate between atopic dermatitis and psoriasis with a degree of reliability that is comparable to skin biopsy,” Dr. Guttman-Yassky said.

One of the biomarkers, expression of nitric oxide synthase 2/inducible nitric oxide synthase, distinguished AD from psoriasis with 100% accuracy. As previously reported in biopsy studies, other biomarkers collectively associated AD with a profile related to a Th2-type inflammatory response and psoriasis with a Th17-type inflammatory response.

Tape strips also confirmed significant pathology in the nonlesional as well as the lesional skin of patients with AD or psoriasis. This included an increase in Th2-type products, such as interleukin-4 and IL-13, in nonlesional skin of atopic dermatitis and Th17-type products, such as IL-17, in nonlesional skin of psoriasis.

Some biomarkers of AD and psoriasis had an even greater differentiation in tape strips than previously reported from biopsy studies, according to Dr. Guttman-Yassky. In this study, tape strips also captured more differentially expressed genes than previously reported with biopsies.

One potential limitation of tape strips is that the RNA isolation process is time consuming, but this might be less of an issue in routine clinical use if there is a more refined number of biomarkers that are targeted or if technological improvements simplify processing, Dr. Guttman-Yassky pointed out.

To develop clinical utility for tape strips beyond AD and psoriasis, more work is needed to standardize the depth of sampling, which is variable with tape strips, she noted. Depth is relevant to the analysis of gene expression and mRNA activity of each dermatologic disease.

“Tape strips remain a research tool for now, but we do think that this technique can be refined and employed for clinical purposes, including diagnosis and monitoring response to treatment,” she said.

Relative to biopsy, the advantages are not difficult to envision. Dr. Guttman-Yassky, who recently published a study of tape strips for evaluating AD in children emphasized that tape strips are generally painless.

“Patients really do not mind tape strips,” she said. Although she believes that tape strips are providing unique insight into the pathology of inflammatory diseases not necessarily available with biopsy, she emphasized the practical value. Not least, “these could really help when the goal is to evaluate response to therapy over time.”

Another investigator who has conducted studies with tape strips, Maja-Lisa Clausen, MD, PhD, also thinks tape strips are likely to become routine clinical tools.

“Once the basis research, validation, and data are out, I think numerous companies will be ready to develop machines for more quick and easy processing, compared to the more labor intensive process that is used today for research,” explained Dr. Clausen, who is in the department of dermatology, Bispebjerb Hospital, University of Copenhagen.

She considers tape strips particularly promising for children, but she thinks the biomarker profiling made possible by these strips might be leading to personalized treatment programs for dermatologic diseases.

“What we need is further validation; which tape to use, how deep, and the importance of storage, which is a big issue in the clinic,” Dr. Clausen said in an interview.

Dr. Guttman-Yassky has financial relationships with multiple pharmaceutical companies, including those with therapies for psoriasis.

SOURCE: Guttman-Yassky E et al. J Allergy Clin Immunol. 2020 Jul 9. doi: 10.1016/j.jaci.2020.05.048.

The rapid decline in pediatric hospital visits that came quickly after COVID-19 has emerged as a major public health threat, creating the need for adaptations among those offering hospital-based care, according to an objective look at patient numbers that was presented at the virtual Pediatric Hospital Medicine.

“Pre-COVID, operating margins had already taken a significant decline – and there are lots of different reasons for why this was happening – but a lot of hospitals in the United States were going from seeing about a 5% operating margin to closer to 2% to 3%,” said Magna Dias, MD, medical director, pediatric inpatient services, at Yale New Haven Children’s Hospital, Bridgeport, Conn.

This nearly 50% decline “was already putting pressure on us in the community hospital setting where pediatrics is not necessarily generating a ton of revenue to justify our programs, but post COVID, our operating revenue – and this is a report from May – was down 282%,” Dr. Dias reported.

Dr. Dias said that hundreds of hospitals have furloughed workers in the United States since the pandemic began. Although the job losses are not confined to pediatric care, statistics show that pediatrics is one of the hardest hit specialties.

“Looking specifically at ED [emergency department] visits under age 14, one study showed a 71% to 72% decrease post COVID,” Dr. Dias said. This included a 97% reduction in ED visits for flu and more than an 80% reduction in visits for asthma, otitis media, and nausea or vomiting.

It is not clear when children will return to the hospital in pre-COVID-19 numbers, but it might not be soon if the a second wave of infections follows the first, according to Dr. Dias. She suggested that pediatric hospitalists should be thinking about how to expand their services.

“One thing we are really good at in terms of working in the community hospital is diversification. We are used to working in more than one area and being flexible,” Dr. Dias said. Quoting Charles Darwin, who concluded that adaption to change predicts species survival, Dr. Dias advised pediatric hospitalists to look for new opportunities.

Taking on a broader range of responsibilities will not be a significant leap for many pediatric hospitalists. In a survey conducted several years ago by the American Academy of Pediatrics (AAP), hospital staff pediatricians were associated with activities ranging from work in the neonatal intensive care unit to primary ED coverage, according to Dr. Dias. Now with declining patient volumes on pediatric floors, she foresees an even greater expansion, including the care of young adults.

One organization formed in response to the COVID-19 pandemic, called the Pediatric Overflow Planning Contingency Response Network (POPCoRN) has been taking a lead in guiding the delivery of adult care in a pediatric environment. As a cochair of a community hospital special interest group within POPCoRN, Dr. Dias said she has participated in these discussions.

“At some centers, they have gone from age 18 to 21, some have gone up to age 25, some have gone up to 30 years,” she said.

Many centers are working to leverage telemedicine to reach pediatric patients no longer coming to the hospital, according to Dr. Dias.

“There are a lot of people being very creative in telemedicine,” she said. While it is considered as one way “to keep children at your institution,” Dr. Dias said others are considering how telemedicine might provide new opportunities. For one example, telemedicine might be an opportunity to deliver care in rural hospitals without pediatric services.

In an AAP survey of pediatric hospitalists conducted several years ago, justifying services was listed as the second most important concern right after access to subspecialty support. Due to COVID-19, Dr. Dias expects the order of these concerns to flip. Indeed, she predicted that many pediatric hospitalists are going to need to reassess their programs.

“We have started looking at what are our opportunities for building back revenue as well as how to recession-proof our practices should there be another surge and another decrease in pediatric volume,” Dr. Dias said.

The changes in pediatric care are not confined to the hospital setting. According to Amy H. Porter, MD, assistant professor of pediatrics at the Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, Calif., COVID-19 has “changed the way pediatric medicine is being practiced.”

Although she works in outpatient pediatric care, she said that routine care “is way down” in this setting as well. Like Dr. Dias, she has witnessed a major increase in the use of telemedicine to reach pediatric patients, but she is very concerned about the large proportion of children who are missing routine care, including vaccinations.

“We were already seeing outbreaks of whooping cough and measles pre COVID, so we are quite worried that we will see more,” Dr. Porter said.

A reduction in demand for care does not have the same immediate effect on revenue at a large health maintenance organization like Kaiser Permanente, but growing unemployment in the general population will mean fewer HMO members. In turn, this could have an impact on the entire system.

“When membership goes down, then it will have implications for how we can provide services,” Dr. Porter said.

In the meantime, social workers at Kaiser Permanente “are tirelessly working” to help parents losing benefits to obtain medicines for sick children with chronic diseases, according to Dr. Porter. She echoed the comments of Dr. Dias in predicting major changes in pediatric care if the COVID-19 pandemic and its economic consequences persist.

The conference was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

The rapid decline in pediatric hospital visits that came quickly after COVID-19 has emerged as a major public health threat, creating the need for adaptations among those offering hospital-based care, according to an objective look at patient numbers that was presented at the virtual Pediatric Hospital Medicine.

“Pre-COVID, operating margins had already taken a significant decline – and there are lots of different reasons for why this was happening – but a lot of hospitals in the United States were going from seeing about a 5% operating margin to closer to 2% to 3%,” said Magna Dias, MD, medical director, pediatric inpatient services, at Yale New Haven Children’s Hospital, Bridgeport, Conn.

This nearly 50% decline “was already putting pressure on us in the community hospital setting where pediatrics is not necessarily generating a ton of revenue to justify our programs, but post COVID, our operating revenue – and this is a report from May – was down 282%,” Dr. Dias reported.

Dr. Dias said that hundreds of hospitals have furloughed workers in the United States since the pandemic began. Although the job losses are not confined to pediatric care, statistics show that pediatrics is one of the hardest hit specialties.

“Looking specifically at ED [emergency department] visits under age 14, one study showed a 71% to 72% decrease post COVID,” Dr. Dias said. This included a 97% reduction in ED visits for flu and more than an 80% reduction in visits for asthma, otitis media, and nausea or vomiting.

It is not clear when children will return to the hospital in pre-COVID-19 numbers, but it might not be soon if the a second wave of infections follows the first, according to Dr. Dias. She suggested that pediatric hospitalists should be thinking about how to expand their services.

“One thing we are really good at in terms of working in the community hospital is diversification. We are used to working in more than one area and being flexible,” Dr. Dias said. Quoting Charles Darwin, who concluded that adaption to change predicts species survival, Dr. Dias advised pediatric hospitalists to look for new opportunities.

Taking on a broader range of responsibilities will not be a significant leap for many pediatric hospitalists. In a survey conducted several years ago by the American Academy of Pediatrics (AAP), hospital staff pediatricians were associated with activities ranging from work in the neonatal intensive care unit to primary ED coverage, according to Dr. Dias. Now with declining patient volumes on pediatric floors, she foresees an even greater expansion, including the care of young adults.

One organization formed in response to the COVID-19 pandemic, called the Pediatric Overflow Planning Contingency Response Network (POPCoRN) has been taking a lead in guiding the delivery of adult care in a pediatric environment. As a cochair of a community hospital special interest group within POPCoRN, Dr. Dias said she has participated in these discussions.

“At some centers, they have gone from age 18 to 21, some have gone up to age 25, some have gone up to 30 years,” she said.

Many centers are working to leverage telemedicine to reach pediatric patients no longer coming to the hospital, according to Dr. Dias.

“There are a lot of people being very creative in telemedicine,” she said. While it is considered as one way “to keep children at your institution,” Dr. Dias said others are considering how telemedicine might provide new opportunities. For one example, telemedicine might be an opportunity to deliver care in rural hospitals without pediatric services.

In an AAP survey of pediatric hospitalists conducted several years ago, justifying services was listed as the second most important concern right after access to subspecialty support. Due to COVID-19, Dr. Dias expects the order of these concerns to flip. Indeed, she predicted that many pediatric hospitalists are going to need to reassess their programs.

“We have started looking at what are our opportunities for building back revenue as well as how to recession-proof our practices should there be another surge and another decrease in pediatric volume,” Dr. Dias said.

The changes in pediatric care are not confined to the hospital setting. According to Amy H. Porter, MD, assistant professor of pediatrics at the Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, Calif., COVID-19 has “changed the way pediatric medicine is being practiced.”

Although she works in outpatient pediatric care, she said that routine care “is way down” in this setting as well. Like Dr. Dias, she has witnessed a major increase in the use of telemedicine to reach pediatric patients, but she is very concerned about the large proportion of children who are missing routine care, including vaccinations.

“We were already seeing outbreaks of whooping cough and measles pre COVID, so we are quite worried that we will see more,” Dr. Porter said.

A reduction in demand for care does not have the same immediate effect on revenue at a large health maintenance organization like Kaiser Permanente, but growing unemployment in the general population will mean fewer HMO members. In turn, this could have an impact on the entire system.

“When membership goes down, then it will have implications for how we can provide services,” Dr. Porter said.

In the meantime, social workers at Kaiser Permanente “are tirelessly working” to help parents losing benefits to obtain medicines for sick children with chronic diseases, according to Dr. Porter. She echoed the comments of Dr. Dias in predicting major changes in pediatric care if the COVID-19 pandemic and its economic consequences persist.

The conference was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

The rapid decline in pediatric hospital visits that came quickly after COVID-19 has emerged as a major public health threat, creating the need for adaptations among those offering hospital-based care, according to an objective look at patient numbers that was presented at the virtual Pediatric Hospital Medicine.

“Pre-COVID, operating margins had already taken a significant decline – and there are lots of different reasons for why this was happening – but a lot of hospitals in the United States were going from seeing about a 5% operating margin to closer to 2% to 3%,” said Magna Dias, MD, medical director, pediatric inpatient services, at Yale New Haven Children’s Hospital, Bridgeport, Conn.

This nearly 50% decline “was already putting pressure on us in the community hospital setting where pediatrics is not necessarily generating a ton of revenue to justify our programs, but post COVID, our operating revenue – and this is a report from May – was down 282%,” Dr. Dias reported.

Dr. Dias said that hundreds of hospitals have furloughed workers in the United States since the pandemic began. Although the job losses are not confined to pediatric care, statistics show that pediatrics is one of the hardest hit specialties.

“Looking specifically at ED [emergency department] visits under age 14, one study showed a 71% to 72% decrease post COVID,” Dr. Dias said. This included a 97% reduction in ED visits for flu and more than an 80% reduction in visits for asthma, otitis media, and nausea or vomiting.

It is not clear when children will return to the hospital in pre-COVID-19 numbers, but it might not be soon if the a second wave of infections follows the first, according to Dr. Dias. She suggested that pediatric hospitalists should be thinking about how to expand their services.

“One thing we are really good at in terms of working in the community hospital is diversification. We are used to working in more than one area and being flexible,” Dr. Dias said. Quoting Charles Darwin, who concluded that adaption to change predicts species survival, Dr. Dias advised pediatric hospitalists to look for new opportunities.

Taking on a broader range of responsibilities will not be a significant leap for many pediatric hospitalists. In a survey conducted several years ago by the American Academy of Pediatrics (AAP), hospital staff pediatricians were associated with activities ranging from work in the neonatal intensive care unit to primary ED coverage, according to Dr. Dias. Now with declining patient volumes on pediatric floors, she foresees an even greater expansion, including the care of young adults.

One organization formed in response to the COVID-19 pandemic, called the Pediatric Overflow Planning Contingency Response Network (POPCoRN) has been taking a lead in guiding the delivery of adult care in a pediatric environment. As a cochair of a community hospital special interest group within POPCoRN, Dr. Dias said she has participated in these discussions.

“At some centers, they have gone from age 18 to 21, some have gone up to age 25, some have gone up to 30 years,” she said.

Many centers are working to leverage telemedicine to reach pediatric patients no longer coming to the hospital, according to Dr. Dias.

“There are a lot of people being very creative in telemedicine,” she said. While it is considered as one way “to keep children at your institution,” Dr. Dias said others are considering how telemedicine might provide new opportunities. For one example, telemedicine might be an opportunity to deliver care in rural hospitals without pediatric services.

In an AAP survey of pediatric hospitalists conducted several years ago, justifying services was listed as the second most important concern right after access to subspecialty support. Due to COVID-19, Dr. Dias expects the order of these concerns to flip. Indeed, she predicted that many pediatric hospitalists are going to need to reassess their programs.

“We have started looking at what are our opportunities for building back revenue as well as how to recession-proof our practices should there be another surge and another decrease in pediatric volume,” Dr. Dias said.

The changes in pediatric care are not confined to the hospital setting. According to Amy H. Porter, MD, assistant professor of pediatrics at the Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, Calif., COVID-19 has “changed the way pediatric medicine is being practiced.”

Although she works in outpatient pediatric care, she said that routine care “is way down” in this setting as well. Like Dr. Dias, she has witnessed a major increase in the use of telemedicine to reach pediatric patients, but she is very concerned about the large proportion of children who are missing routine care, including vaccinations.

“We were already seeing outbreaks of whooping cough and measles pre COVID, so we are quite worried that we will see more,” Dr. Porter said.

A reduction in demand for care does not have the same immediate effect on revenue at a large health maintenance organization like Kaiser Permanente, but growing unemployment in the general population will mean fewer HMO members. In turn, this could have an impact on the entire system.

“When membership goes down, then it will have implications for how we can provide services,” Dr. Porter said.

In the meantime, social workers at Kaiser Permanente “are tirelessly working” to help parents losing benefits to obtain medicines for sick children with chronic diseases, according to Dr. Porter. She echoed the comments of Dr. Dias in predicting major changes in pediatric care if the COVID-19 pandemic and its economic consequences persist.

The conference was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

Parents who refuse one indicated neonatal preventive therapy often refuse others even when the reasons are different, according to an update at the virtual Pediatric Hospital Medicine virtual. This finding indicates the value of preparing policies and strategies to guide parents to appropriate medical decisions in advance.

“Elimination of nonmedical exceptions to vaccinations and intramuscular vitamin K made it into two of the AAP [American Academy of Pediatrics] top 10 public health resolutions, most likely because refusal rates are going up,” reported Ha N. Nguyen, MD, of the division of pediatric hospital medicine at Stanford (Calif.) University.

Importantly, state laws differ. For example, erythromycin ointment is mandated in neonates for prevention of gonococcal ophthalmia neonatorum in many states, including New York, where it can be administered without consent, according to Dr. Nguyen. Conversely, California does not mandate this preventive therapy even though the law does not offer medico-legal protection to providers if it is not given.

“There is a glaring gap in the way the [California] law was written,” said Dr. Nguyen, who used this as an example of why protocols and strategies to reduce risk of parental refusal of neonatal therapies should be informed by, and consistent with, state laws.

Because of the low levels of vitamin K in infants, the rate of bleeding within the first few months of life is nearly 2%, according to figures cited by Dr. Nguyen. It falls to less than 0.001% with administration of intramuscular vitamin K.

Families who refuse intramuscular vitamin K often state that they understand the risks, but data from a survey Dr. Nguyen cited found this is not necessarily true. In this survey, about two-thirds knew that bleeding was the risk, but less than 20% understood bleeding risks included intracranial hemorrhage, and less than 10% were aware that there was potential for a fatal outcome.

“This is a huge piece of the puzzle for counseling,” Dr. Nguyen said. “The discussion with parents should explicitly involve the explanation that the risks include brain bleeds and death.”

Although most infant bleeds attributed to low vitamin K stores are mucocutaneous or gastrointestinal, intracranial hemorrhage does occur, and these outcomes can be devastating. Up to 25% of infants who experience an intracranial hemorrhage die, while 60% of those who survive have some degree of neurodevelopmental impairment, according to Dr. Nguyen.

Oral vitamin K, which requires multiple doses, is not an appropriate substitute for the recommended single injection of the intramuscular formulation. The one study that compared intramuscular and oral vitamin K did not prove equivalence, and no oral vitamin K products have been approved by the Food and Drug Administration, Dr. Nguyen reported.

“We do know confidently that oral vitamin K does often result in poor adherence,” she said,

In a recent review article of parental vitamin K refusal, one of the most significant predictors of refusal of any recommended neonatal preventive treatment was refusal of another. According to data in that article, summarized by Dr. Nguyen, 68% of the parents who declined intramuscular vitamin K also declined erythromycin ointment, and more than 90% declined hepatitis B vaccine.

Parents who refuse one indicated neonatal preventive therapy often refuse others even when the reasons are different, according to an update at the virtual Pediatric Hospital Medicine virtual. This finding indicates the value of preparing policies and strategies to guide parents to appropriate medical decisions in advance.

“Elimination of nonmedical exceptions to vaccinations and intramuscular vitamin K made it into two of the AAP [American Academy of Pediatrics] top 10 public health resolutions, most likely because refusal rates are going up,” reported Ha N. Nguyen, MD, of the division of pediatric hospital medicine at Stanford (Calif.) University.

Importantly, state laws differ. For example, erythromycin ointment is mandated in neonates for prevention of gonococcal ophthalmia neonatorum in many states, including New York, where it can be administered without consent, according to Dr. Nguyen. Conversely, California does not mandate this preventive therapy even though the law does not offer medico-legal protection to providers if it is not given.

“There is a glaring gap in the way the [California] law was written,” said Dr. Nguyen, who used this as an example of why protocols and strategies to reduce risk of parental refusal of neonatal therapies should be informed by, and consistent with, state laws.

Because of the low levels of vitamin K in infants, the rate of bleeding within the first few months of life is nearly 2%, according to figures cited by Dr. Nguyen. It falls to less than 0.001% with administration of intramuscular vitamin K.

Families who refuse intramuscular vitamin K often state that they understand the risks, but data from a survey Dr. Nguyen cited found this is not necessarily true. In this survey, about two-thirds knew that bleeding was the risk, but less than 20% understood bleeding risks included intracranial hemorrhage, and less than 10% were aware that there was potential for a fatal outcome.

“This is a huge piece of the puzzle for counseling,” Dr. Nguyen said. “The discussion with parents should explicitly involve the explanation that the risks include brain bleeds and death.”

Although most infant bleeds attributed to low vitamin K stores are mucocutaneous or gastrointestinal, intracranial hemorrhage does occur, and these outcomes can be devastating. Up to 25% of infants who experience an intracranial hemorrhage die, while 60% of those who survive have some degree of neurodevelopmental impairment, according to Dr. Nguyen.

Oral vitamin K, which requires multiple doses, is not an appropriate substitute for the recommended single injection of the intramuscular formulation. The one study that compared intramuscular and oral vitamin K did not prove equivalence, and no oral vitamin K products have been approved by the Food and Drug Administration, Dr. Nguyen reported.

“We do know confidently that oral vitamin K does often result in poor adherence,” she said,

In a recent review article of parental vitamin K refusal, one of the most significant predictors of refusal of any recommended neonatal preventive treatment was refusal of another. According to data in that article, summarized by Dr. Nguyen, 68% of the parents who declined intramuscular vitamin K also declined erythromycin ointment, and more than 90% declined hepatitis B vaccine.

Parents who refuse one indicated neonatal preventive therapy often refuse others even when the reasons are different, according to an update at the virtual Pediatric Hospital Medicine virtual. This finding indicates the value of preparing policies and strategies to guide parents to appropriate medical decisions in advance.

“Elimination of nonmedical exceptions to vaccinations and intramuscular vitamin K made it into two of the AAP [American Academy of Pediatrics] top 10 public health resolutions, most likely because refusal rates are going up,” reported Ha N. Nguyen, MD, of the division of pediatric hospital medicine at Stanford (Calif.) University.

Importantly, state laws differ. For example, erythromycin ointment is mandated in neonates for prevention of gonococcal ophthalmia neonatorum in many states, including New York, where it can be administered without consent, according to Dr. Nguyen. Conversely, California does not mandate this preventive therapy even though the law does not offer medico-legal protection to providers if it is not given.

“There is a glaring gap in the way the [California] law was written,” said Dr. Nguyen, who used this as an example of why protocols and strategies to reduce risk of parental refusal of neonatal therapies should be informed by, and consistent with, state laws.

Because of the low levels of vitamin K in infants, the rate of bleeding within the first few months of life is nearly 2%, according to figures cited by Dr. Nguyen. It falls to less than 0.001% with administration of intramuscular vitamin K.

Families who refuse intramuscular vitamin K often state that they understand the risks, but data from a survey Dr. Nguyen cited found this is not necessarily true. In this survey, about two-thirds knew that bleeding was the risk, but less than 20% understood bleeding risks included intracranial hemorrhage, and less than 10% were aware that there was potential for a fatal outcome.

“This is a huge piece of the puzzle for counseling,” Dr. Nguyen said. “The discussion with parents should explicitly involve the explanation that the risks include brain bleeds and death.”

Although most infant bleeds attributed to low vitamin K stores are mucocutaneous or gastrointestinal, intracranial hemorrhage does occur, and these outcomes can be devastating. Up to 25% of infants who experience an intracranial hemorrhage die, while 60% of those who survive have some degree of neurodevelopmental impairment, according to Dr. Nguyen.

Oral vitamin K, which requires multiple doses, is not an appropriate substitute for the recommended single injection of the intramuscular formulation. The one study that compared intramuscular and oral vitamin K did not prove equivalence, and no oral vitamin K products have been approved by the Food and Drug Administration, Dr. Nguyen reported.

“We do know confidently that oral vitamin K does often result in poor adherence,” she said,

In a recent review article of parental vitamin K refusal, one of the most significant predictors of refusal of any recommended neonatal preventive treatment was refusal of another. According to data in that article, summarized by Dr. Nguyen, 68% of the parents who declined intramuscular vitamin K also declined erythromycin ointment, and more than 90% declined hepatitis B vaccine.

One of the take-away messages from a review of multisystem inflammatory syndrome in children (MIS-C) is that clinicians treating this condition “need to be comfortable with uncertainty,” Melissa Hazen, MD, said at a synthesis of multiple published case series and personal experience summarized at the virtual Pediatric Hospital Medicine meeting.

She emphasized MIS-C patient care “requires flexibility,” and she advised clinicians managing these patients to open the lines of communication with the many specialists who often are required to deal with complications affecting an array of organ systems.

MIS-C might best be understood as the most serious manifestation of an immune-mediated response to COVID-19 infection that ranges from transient mild symptoms to the life-threatening multiple organ involvement that characterizes this newly recognized threat. Although “most children who encounter this pathogen only develop mild disease,” the spectrum of the disease can move in a subset of patients to a “Kawasaki-like illness” without hemodynamic instability and then to MIS-C “with highly elevated systemic inflammatory markers and multiple organ involvement,” explained Dr. Hazen, an attending physician in the rheumatology program at Boston Children’s Hospital.

A reliable profile of MIS-C is only beginning to emerge from the series of published case series, most of which have only recently reached publication, according to Dr. Hazen. In general, the description of the most common symptoms and their course has been relatively consistent.

In 186 cases of MIS-C collected in a study funded by the Centers for Disease Control and Prevention, 148 (80%) were admitted to intensive care, 90 patients (48%) received vasoactive support, 37 (20%) received mechanical ventilation, and 4 (2%) died.¹ The median age was 8 years (range, 3-13 years) in this study. The case definition was fever for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of COVID-19 infection. In this cohort of 186 children, 92% had gastrointestinal, 80% had cardiovascular, 76% had hematologic, and 70% had respiratory system involvement.

In a different series of 95 cases collected in New York State, 79 (80%) were admitted to intensive care, 61 (62%) received vasoactive support, 10 (10%) received mechanical ventilation, 4 (4%) received extracorporeal membrane oxygenation (ECMO), and 2 (2%) died. ² Thirty-one percent patients were aged 0-5 years, 42% were 6-12 years, and 26% were 13-20 years of age. In that series, for which the case definition was elevation of two or more inflammatory markers, virologic evidence of COVID-19 infection, 80% had gastrointestinal system involvement, and 53% had evidence of myocarditis.

In both of these series, as well as others published and unpublished, the peak in MIS-C cases has occurred about 3 to 4 weeks after peak COVID-19 activity, according to Diana Lee, MD, a pediatrician at Icahn School of Medicine at Mount Sinai, New York. This pattern, reported by others, was observed in New York State, where 230 cases of MIS-C were collected from the beginning of May until the end of June, which reflected this 3- to 4-week delay in peak incidence.

“This does seem to be a rare syndrome since this [group of] 230 cases is amongst the entire population of children in New York State. So, yes, we should be keeping this in mind in our differential, but we should not forget all the other reasons that children can have a fever,” she said.

Both Dr. Hazen and Dr. Lee cautioned that MIS-C, despite a general consistency among published studies, remains a moving target in regard to how it is being characterized. In a 2-day period in May, the CDC, the World Health Organization, and New York State all issued descriptions of MIS-C, employing compatible but slightly different terminology and diagnostic criteria. Many questions regarding optimal methods of diagnosis, treatment, and follow-up remain unanswered.

Questions regarding the risk to the cardiovascular system, one of the organs most commonly affected in MIS-C, are among the most urgent. It is not now clear how best to monitor cardiovascular involvement, how to intervene, and how to follow patients in the postinfection period, according to Kevin G. Friedman, MD, a pediatrician at Harvard Medical School, Boston, and an attending physician in the department of cardiology at Boston Children’s Hospital.

“The most frequent complication we have seen is ventricular dysfunction, which occurs in about half of these patients,” he reported. “Usually it is in the mild to moderate range, but occasionally patients have an ejection fraction of less than 40%.”

Coronary abnormalities, typically in the form of dilations or small aneurysms, occur in 10%-20% of children with MIS-C, according to Dr. Friedman. Giant aneurysms have been reported.

“Some of these findings can progress including in both the acute phase and, particularly for the coronary aneurysms, in the subacute phase. We recommend echocardiograms and EKGs at diagnosis and at 1-2 weeks to recheck coronary size or sooner if there are clinical indications,” Dr. Friedman advised.

Protocols like these are constantly under review as more information becomes available. There are as yet no guidelines, and practice differs across institutions, according to the investigators summarizing this information.

None of the speakers had any relevant financial disclosures.

References

1. Feldstein LR et al. Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med. 2020;383:334-46.

2. Dufort EM et al. Multisystem inflammatory syndrome in children in New York State. N Engl J Med 2020;383:347-58.

One of the take-away messages from a review of multisystem inflammatory syndrome in children (MIS-C) is that clinicians treating this condition “need to be comfortable with uncertainty,” Melissa Hazen, MD, said at a synthesis of multiple published case series and personal experience summarized at the virtual Pediatric Hospital Medicine meeting.

She emphasized MIS-C patient care “requires flexibility,” and she advised clinicians managing these patients to open the lines of communication with the many specialists who often are required to deal with complications affecting an array of organ systems.

MIS-C might best be understood as the most serious manifestation of an immune-mediated response to COVID-19 infection that ranges from transient mild symptoms to the life-threatening multiple organ involvement that characterizes this newly recognized threat. Although “most children who encounter this pathogen only develop mild disease,” the spectrum of the disease can move in a subset of patients to a “Kawasaki-like illness” without hemodynamic instability and then to MIS-C “with highly elevated systemic inflammatory markers and multiple organ involvement,” explained Dr. Hazen, an attending physician in the rheumatology program at Boston Children’s Hospital.

A reliable profile of MIS-C is only beginning to emerge from the series of published case series, most of which have only recently reached publication, according to Dr. Hazen. In general, the description of the most common symptoms and their course has been relatively consistent.

In 186 cases of MIS-C collected in a study funded by the Centers for Disease Control and Prevention, 148 (80%) were admitted to intensive care, 90 patients (48%) received vasoactive support, 37 (20%) received mechanical ventilation, and 4 (2%) died.¹ The median age was 8 years (range, 3-13 years) in this study. The case definition was fever for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of COVID-19 infection. In this cohort of 186 children, 92% had gastrointestinal, 80% had cardiovascular, 76% had hematologic, and 70% had respiratory system involvement.

In a different series of 95 cases collected in New York State, 79 (80%) were admitted to intensive care, 61 (62%) received vasoactive support, 10 (10%) received mechanical ventilation, 4 (4%) received extracorporeal membrane oxygenation (ECMO), and 2 (2%) died. ² Thirty-one percent patients were aged 0-5 years, 42% were 6-12 years, and 26% were 13-20 years of age. In that series, for which the case definition was elevation of two or more inflammatory markers, virologic evidence of COVID-19 infection, 80% had gastrointestinal system involvement, and 53% had evidence of myocarditis.

In both of these series, as well as others published and unpublished, the peak in MIS-C cases has occurred about 3 to 4 weeks after peak COVID-19 activity, according to Diana Lee, MD, a pediatrician at Icahn School of Medicine at Mount Sinai, New York. This pattern, reported by others, was observed in New York State, where 230 cases of MIS-C were collected from the beginning of May until the end of June, which reflected this 3- to 4-week delay in peak incidence.

“This does seem to be a rare syndrome since this [group of] 230 cases is amongst the entire population of children in New York State. So, yes, we should be keeping this in mind in our differential, but we should not forget all the other reasons that children can have a fever,” she said.

Both Dr. Hazen and Dr. Lee cautioned that MIS-C, despite a general consistency among published studies, remains a moving target in regard to how it is being characterized. In a 2-day period in May, the CDC, the World Health Organization, and New York State all issued descriptions of MIS-C, employing compatible but slightly different terminology and diagnostic criteria. Many questions regarding optimal methods of diagnosis, treatment, and follow-up remain unanswered.

Questions regarding the risk to the cardiovascular system, one of the organs most commonly affected in MIS-C, are among the most urgent. It is not now clear how best to monitor cardiovascular involvement, how to intervene, and how to follow patients in the postinfection period, according to Kevin G. Friedman, MD, a pediatrician at Harvard Medical School, Boston, and an attending physician in the department of cardiology at Boston Children’s Hospital.

“The most frequent complication we have seen is ventricular dysfunction, which occurs in about half of these patients,” he reported. “Usually it is in the mild to moderate range, but occasionally patients have an ejection fraction of less than 40%.”

Coronary abnormalities, typically in the form of dilations or small aneurysms, occur in 10%-20% of children with MIS-C, according to Dr. Friedman. Giant aneurysms have been reported.

“Some of these findings can progress including in both the acute phase and, particularly for the coronary aneurysms, in the subacute phase. We recommend echocardiograms and EKGs at diagnosis and at 1-2 weeks to recheck coronary size or sooner if there are clinical indications,” Dr. Friedman advised.

Protocols like these are constantly under review as more information becomes available. There are as yet no guidelines, and practice differs across institutions, according to the investigators summarizing this information.

None of the speakers had any relevant financial disclosures.

References

1. Feldstein LR et al. Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med. 2020;383:334-46.

2. Dufort EM et al. Multisystem inflammatory syndrome in children in New York State. N Engl J Med 2020;383:347-58.

One of the take-away messages from a review of multisystem inflammatory syndrome in children (MIS-C) is that clinicians treating this condition “need to be comfortable with uncertainty,” Melissa Hazen, MD, said at a synthesis of multiple published case series and personal experience summarized at the virtual Pediatric Hospital Medicine meeting.

She emphasized MIS-C patient care “requires flexibility,” and she advised clinicians managing these patients to open the lines of communication with the many specialists who often are required to deal with complications affecting an array of organ systems.

MIS-C might best be understood as the most serious manifestation of an immune-mediated response to COVID-19 infection that ranges from transient mild symptoms to the life-threatening multiple organ involvement that characterizes this newly recognized threat. Although “most children who encounter this pathogen only develop mild disease,” the spectrum of the disease can move in a subset of patients to a “Kawasaki-like illness” without hemodynamic instability and then to MIS-C “with highly elevated systemic inflammatory markers and multiple organ involvement,” explained Dr. Hazen, an attending physician in the rheumatology program at Boston Children’s Hospital.

A reliable profile of MIS-C is only beginning to emerge from the series of published case series, most of which have only recently reached publication, according to Dr. Hazen. In general, the description of the most common symptoms and their course has been relatively consistent.

In 186 cases of MIS-C collected in a study funded by the Centers for Disease Control and Prevention, 148 (80%) were admitted to intensive care, 90 patients (48%) received vasoactive support, 37 (20%) received mechanical ventilation, and 4 (2%) died.¹ The median age was 8 years (range, 3-13 years) in this study. The case definition was fever for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of COVID-19 infection. In this cohort of 186 children, 92% had gastrointestinal, 80% had cardiovascular, 76% had hematologic, and 70% had respiratory system involvement.

In a different series of 95 cases collected in New York State, 79 (80%) were admitted to intensive care, 61 (62%) received vasoactive support, 10 (10%) received mechanical ventilation, 4 (4%) received extracorporeal membrane oxygenation (ECMO), and 2 (2%) died. ² Thirty-one percent patients were aged 0-5 years, 42% were 6-12 years, and 26% were 13-20 years of age. In that series, for which the case definition was elevation of two or more inflammatory markers, virologic evidence of COVID-19 infection, 80% had gastrointestinal system involvement, and 53% had evidence of myocarditis.

In both of these series, as well as others published and unpublished, the peak in MIS-C cases has occurred about 3 to 4 weeks after peak COVID-19 activity, according to Diana Lee, MD, a pediatrician at Icahn School of Medicine at Mount Sinai, New York. This pattern, reported by others, was observed in New York State, where 230 cases of MIS-C were collected from the beginning of May until the end of June, which reflected this 3- to 4-week delay in peak incidence.

“This does seem to be a rare syndrome since this [group of] 230 cases is amongst the entire population of children in New York State. So, yes, we should be keeping this in mind in our differential, but we should not forget all the other reasons that children can have a fever,” she said.

Both Dr. Hazen and Dr. Lee cautioned that MIS-C, despite a general consistency among published studies, remains a moving target in regard to how it is being characterized. In a 2-day period in May, the CDC, the World Health Organization, and New York State all issued descriptions of MIS-C, employing compatible but slightly different terminology and diagnostic criteria. Many questions regarding optimal methods of diagnosis, treatment, and follow-up remain unanswered.

Questions regarding the risk to the cardiovascular system, one of the organs most commonly affected in MIS-C, are among the most urgent. It is not now clear how best to monitor cardiovascular involvement, how to intervene, and how to follow patients in the postinfection period, according to Kevin G. Friedman, MD, a pediatrician at Harvard Medical School, Boston, and an attending physician in the department of cardiology at Boston Children’s Hospital.

“The most frequent complication we have seen is ventricular dysfunction, which occurs in about half of these patients,” he reported. “Usually it is in the mild to moderate range, but occasionally patients have an ejection fraction of less than 40%.”

Coronary abnormalities, typically in the form of dilations or small aneurysms, occur in 10%-20% of children with MIS-C, according to Dr. Friedman. Giant aneurysms have been reported.

“Some of these findings can progress including in both the acute phase and, particularly for the coronary aneurysms, in the subacute phase. We recommend echocardiograms and EKGs at diagnosis and at 1-2 weeks to recheck coronary size or sooner if there are clinical indications,” Dr. Friedman advised.

Protocols like these are constantly under review as more information becomes available. There are as yet no guidelines, and practice differs across institutions, according to the investigators summarizing this information.

None of the speakers had any relevant financial disclosures.

References

1. Feldstein LR et al. Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med. 2020;383:334-46.

2. Dufort EM et al. Multisystem inflammatory syndrome in children in New York State. N Engl J Med 2020;383:347-58.