Physicians with difficult patient scenarios regularly bring their questions to the AGA Community to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. The upgraded networking platform now features a newsfeed for difficult patient scenarios and regularly scheduled Roundtable discussions with experts in the field.

In case you missed it, here are some clinical discussions and Roundtables in the newsfeed this month:

Which of the following patients needs a liver biopsy and why? (https://community.gastro.org/posts/23108)

Next steps for a Crohn’s patient (https://community.gastro.org/posts/23000)

Fecal calprotectin versus histology (https://community.gastro.org/posts/22969)

Collecting and sending specimen for disaccharidase assay (https://community.gastro.org/posts/23092)

Roundtables (https://community.gastro.org/discussions)
Q&A with CRC task force: Endoscopic Recognition and Management Strategies for Malignant Colorectal Polyps

View all upcoming Roundtables in the community at https://community.gastro.org/discussions.

Physicians with difficult patient scenarios regularly bring their questions to the AGA Community to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. The upgraded networking platform now features a newsfeed for difficult patient scenarios and regularly scheduled Roundtable discussions with experts in the field.

In case you missed it, here are some clinical discussions and Roundtables in the newsfeed this month:

Which of the following patients needs a liver biopsy and why? (https://community.gastro.org/posts/23108)

Next steps for a Crohn’s patient (https://community.gastro.org/posts/23000)

Fecal calprotectin versus histology (https://community.gastro.org/posts/22969)

Collecting and sending specimen for disaccharidase assay (https://community.gastro.org/posts/23092)

Roundtables (https://community.gastro.org/discussions)
Q&A with CRC task force: Endoscopic Recognition and Management Strategies for Malignant Colorectal Polyps

View all upcoming Roundtables in the community at https://community.gastro.org/discussions.

Physicians with difficult patient scenarios regularly bring their questions to the AGA Community to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. The upgraded networking platform now features a newsfeed for difficult patient scenarios and regularly scheduled Roundtable discussions with experts in the field.

In case you missed it, here are some clinical discussions and Roundtables in the newsfeed this month:

Which of the following patients needs a liver biopsy and why? (https://community.gastro.org/posts/23108)

Next steps for a Crohn’s patient (https://community.gastro.org/posts/23000)

Fecal calprotectin versus histology (https://community.gastro.org/posts/22969)

Collecting and sending specimen for disaccharidase assay (https://community.gastro.org/posts/23092)

Roundtables (https://community.gastro.org/discussions)
Q&A with CRC task force: Endoscopic Recognition and Management Strategies for Malignant Colorectal Polyps

View all upcoming Roundtables in the community at https://community.gastro.org/discussions.

With the publication or presentation of studies in 2020, there has been a significant expansion of treatment options for children with atopic dermatitis (AD) or psoriasis, Lawrence F. Eichenfield, MD, said at the annual Coastal Dermatology Symposium, held virtually.

Dr. Eichenfield, professor of dermatology and pediatrics, at the University of California, San Diego, presented a list of studies, some of which resulted in approvals of pediatric indications in 2020, that he believes deserve attention.
 

Crisaborole

Crisaborole ointment, 2% is now approved for topical treatment of children aged as young as 3 months, based on the results of the CrisADe CARE1 phase 4 study. In this open-label study of infants aged from 3 months to under 2 years with mild to moderate AD, treated with crisaborole twice a day for 28 days, the mean reduction from baseline in the Eczema Area and Severity Index (EASI) score was 49.6% on day 15 and 57.5% on day 29. The most common side effects were erythema and application-site pain, but neither occurred in more than 4% of patients. The discontinuation rate was less than 3%.

When the indication for treatment of young children down to age 3 months (from 24 months) was granted by the Food and Drug Administration in March 2020, crisaborole, a phosphodiesterase-4 inhibitor, became the only nonsteroidal approved for treatment of AD in children aged younger than 2 years, Dr. Eichenfield pointed out.
 

Tacrolimus

The topical calcineurin inhibitor tacrolimus (Protopic) poses no detectable risk of cancer in children treated for AD, according to a prospective, multinational study that followed nearly 8,000 children with AD who used topical tacrolimus for at least 6 weeks over 10 years. With 44,469 person-years of follow-up in a population with at least 6 weeks of exposure to tacrolimus, there were six confirmed cancers, a rate not different than background rates, and no lymphomas.

“I have always tried to educate my patients about the potential use of the topical calcineurin inhibitors while reassuring them that the data did not support significant risk,” Dr. Eichenfield said. However, a large set of data reconfirming a low risk of cancer, although not definitive, “are really nice to have.”
 

Ruxolitinib

For treatment of AD in children aged as young as 12 years, a cream formulation of ruxolitinib, a Janus kinase 1/JAK2 inhibitor, met its primary outcomes in the phase 3 TRuE AD1 and TRuE AD2 trials. (These data are not yet published but were presented at the Revolutionizing Atopic Dermatitis virtual symposium in April 2020.) The primary endpoint of 75% EASI clearance (EASI-75) was achieved in approximately 62% of patients treated with the 1.5% dose of ruxolitinib twice daily. This was a highly significant advantage over vehicle in both studies (P < .0001).

The EASI-75 rates at 8 weeks for the 0.75% formulation, at 56% and 51.5% for the TRuE AD1 and TRuE AD2 trials, respectively, were lower but also superior (P < .0001) to the 24.6% and 14.4% response rates on vehicle, respectively.

Emphasizing a consistent benefit on multiple secondary endpoints, including the “really early itch decrease,” Dr. Eichenfield described the phase 3 data as “really excellent results.” The data have not yet led to FDA approval of ruxolitinib for AD, but approval seems likely. Dr. Eichenfield noted that other drugs in the same class, such as abrocitinib and upadacitinib, have also demonstrated promising efficacy in children aged 12 years or older.
 

Dupilumab

Dupilumab, an interleukin-4 receptor alpha antagonist, was approved in May, 2020, for the treatment of AD in children ages 6-11 years, on the basis of a recently published phase 3, randomized, placebo-controlled trial that enrolled children aged between 6 and 11 years, comparing dupilumab and topical corticosteroids and placebo plus topical corticosteroids. Severe involvement was an entry criterion.

At 16 weeks, an EASI-75 response was achieved by 67% of the group randomized to 200 mg of dupilumab administered every 2 weeks and 70% of the group randomized to 300 mg every 4 weeks versus 27% of those randomized to placebo. More patients in the dupilumab arms developed conjunctivitis (10.8% vs. 4.7%) and had injection-site reactions (8.5% vs. 3.5%), but the monoclonal antibody was otherwise well tolerated and safe.

These data suggest that younger patients with severe disease “do, if anything, better than adults,” Dr. Eichenfield said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education. He cautioned that avoiding live vaccines, which is recommended in patients on dupilumab, “is likely more of an issue in children.”

Ixekizumab

Ixekizumab has been approved for pediatric patients aged as young as 6 years who are eligible for systemic therapy on the basis of a phase 3 trial. For the primary endpoint of 75% clearance on the Psoriasis Area and Severity Index, the response rates were 89% for the IL-17 inhibitor administered every 4 weeks and 25% for placebo. The study also associated ixekizumab with a significant improvement in quality of life.

The availability of more targeted therapies for children are likely. In Europe, secukinumab, another IL-17 inhibitor, was approved for treatment in pediatric patients this past summer, Dr. Eichenfield noted. These data are not yet published, but he expects targeted therapies to join a growing list of biologics already approved in children.

For drugs with established efficacy and safety, he advised, “look at your pediatric psoriasis patients and don’t be wimpy.” In children with poorly controlled psoriasis, he concluded these drugs have been associated with improved quality of life.

In November 2019, the American Academy of Dermatology and National Psoriasis Foundation published psoriasis management guidelines for children. Not all of the most recently approved therapies are included in these guidelines, which are the first to provide specific recommendations for children, but Dr. Eichenfield also included this publication among his top picks for important contributions to the pediatric dermatology literature in 2020.

Dr. Eichenfield reported financial relationships with 20 pharmaceutical companies that manufacture dermatologic products, including those for the diseases he discussed.

This publication and Global Academy for Medical Education are owned by the same parent company.

With the publication or presentation of studies in 2020, there has been a significant expansion of treatment options for children with atopic dermatitis (AD) or psoriasis, Lawrence F. Eichenfield, MD, said at the annual Coastal Dermatology Symposium, held virtually.

Dr. Eichenfield, professor of dermatology and pediatrics, at the University of California, San Diego, presented a list of studies, some of which resulted in approvals of pediatric indications in 2020, that he believes deserve attention.
 

Crisaborole

Crisaborole ointment, 2% is now approved for topical treatment of children aged as young as 3 months, based on the results of the CrisADe CARE1 phase 4 study. In this open-label study of infants aged from 3 months to under 2 years with mild to moderate AD, treated with crisaborole twice a day for 28 days, the mean reduction from baseline in the Eczema Area and Severity Index (EASI) score was 49.6% on day 15 and 57.5% on day 29. The most common side effects were erythema and application-site pain, but neither occurred in more than 4% of patients. The discontinuation rate was less than 3%.

When the indication for treatment of young children down to age 3 months (from 24 months) was granted by the Food and Drug Administration in March 2020, crisaborole, a phosphodiesterase-4 inhibitor, became the only nonsteroidal approved for treatment of AD in children aged younger than 2 years, Dr. Eichenfield pointed out.
 

Tacrolimus

The topical calcineurin inhibitor tacrolimus (Protopic) poses no detectable risk of cancer in children treated for AD, according to a prospective, multinational study that followed nearly 8,000 children with AD who used topical tacrolimus for at least 6 weeks over 10 years. With 44,469 person-years of follow-up in a population with at least 6 weeks of exposure to tacrolimus, there were six confirmed cancers, a rate not different than background rates, and no lymphomas.

“I have always tried to educate my patients about the potential use of the topical calcineurin inhibitors while reassuring them that the data did not support significant risk,” Dr. Eichenfield said. However, a large set of data reconfirming a low risk of cancer, although not definitive, “are really nice to have.”
 

Ruxolitinib

For treatment of AD in children aged as young as 12 years, a cream formulation of ruxolitinib, a Janus kinase 1/JAK2 inhibitor, met its primary outcomes in the phase 3 TRuE AD1 and TRuE AD2 trials. (These data are not yet published but were presented at the Revolutionizing Atopic Dermatitis virtual symposium in April 2020.) The primary endpoint of 75% EASI clearance (EASI-75) was achieved in approximately 62% of patients treated with the 1.5% dose of ruxolitinib twice daily. This was a highly significant advantage over vehicle in both studies (P < .0001).

The EASI-75 rates at 8 weeks for the 0.75% formulation, at 56% and 51.5% for the TRuE AD1 and TRuE AD2 trials, respectively, were lower but also superior (P < .0001) to the 24.6% and 14.4% response rates on vehicle, respectively.

Emphasizing a consistent benefit on multiple secondary endpoints, including the “really early itch decrease,” Dr. Eichenfield described the phase 3 data as “really excellent results.” The data have not yet led to FDA approval of ruxolitinib for AD, but approval seems likely. Dr. Eichenfield noted that other drugs in the same class, such as abrocitinib and upadacitinib, have also demonstrated promising efficacy in children aged 12 years or older.
 

Dupilumab

Dupilumab, an interleukin-4 receptor alpha antagonist, was approved in May, 2020, for the treatment of AD in children ages 6-11 years, on the basis of a recently published phase 3, randomized, placebo-controlled trial that enrolled children aged between 6 and 11 years, comparing dupilumab and topical corticosteroids and placebo plus topical corticosteroids. Severe involvement was an entry criterion.

At 16 weeks, an EASI-75 response was achieved by 67% of the group randomized to 200 mg of dupilumab administered every 2 weeks and 70% of the group randomized to 300 mg every 4 weeks versus 27% of those randomized to placebo. More patients in the dupilumab arms developed conjunctivitis (10.8% vs. 4.7%) and had injection-site reactions (8.5% vs. 3.5%), but the monoclonal antibody was otherwise well tolerated and safe.

These data suggest that younger patients with severe disease “do, if anything, better than adults,” Dr. Eichenfield said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education. He cautioned that avoiding live vaccines, which is recommended in patients on dupilumab, “is likely more of an issue in children.”

Ixekizumab

Ixekizumab has been approved for pediatric patients aged as young as 6 years who are eligible for systemic therapy on the basis of a phase 3 trial. For the primary endpoint of 75% clearance on the Psoriasis Area and Severity Index, the response rates were 89% for the IL-17 inhibitor administered every 4 weeks and 25% for placebo. The study also associated ixekizumab with a significant improvement in quality of life.

The availability of more targeted therapies for children are likely. In Europe, secukinumab, another IL-17 inhibitor, was approved for treatment in pediatric patients this past summer, Dr. Eichenfield noted. These data are not yet published, but he expects targeted therapies to join a growing list of biologics already approved in children.

For drugs with established efficacy and safety, he advised, “look at your pediatric psoriasis patients and don’t be wimpy.” In children with poorly controlled psoriasis, he concluded these drugs have been associated with improved quality of life.

In November 2019, the American Academy of Dermatology and National Psoriasis Foundation published psoriasis management guidelines for children. Not all of the most recently approved therapies are included in these guidelines, which are the first to provide specific recommendations for children, but Dr. Eichenfield also included this publication among his top picks for important contributions to the pediatric dermatology literature in 2020.

Dr. Eichenfield reported financial relationships with 20 pharmaceutical companies that manufacture dermatologic products, including those for the diseases he discussed.

This publication and Global Academy for Medical Education are owned by the same parent company.

With the publication or presentation of studies in 2020, there has been a significant expansion of treatment options for children with atopic dermatitis (AD) or psoriasis, Lawrence F. Eichenfield, MD, said at the annual Coastal Dermatology Symposium, held virtually.

Dr. Eichenfield, professor of dermatology and pediatrics, at the University of California, San Diego, presented a list of studies, some of which resulted in approvals of pediatric indications in 2020, that he believes deserve attention.
 

Crisaborole

Crisaborole ointment, 2% is now approved for topical treatment of children aged as young as 3 months, based on the results of the CrisADe CARE1 phase 4 study. In this open-label study of infants aged from 3 months to under 2 years with mild to moderate AD, treated with crisaborole twice a day for 28 days, the mean reduction from baseline in the Eczema Area and Severity Index (EASI) score was 49.6% on day 15 and 57.5% on day 29. The most common side effects were erythema and application-site pain, but neither occurred in more than 4% of patients. The discontinuation rate was less than 3%.

When the indication for treatment of young children down to age 3 months (from 24 months) was granted by the Food and Drug Administration in March 2020, crisaborole, a phosphodiesterase-4 inhibitor, became the only nonsteroidal approved for treatment of AD in children aged younger than 2 years, Dr. Eichenfield pointed out.
 

Tacrolimus

The topical calcineurin inhibitor tacrolimus (Protopic) poses no detectable risk of cancer in children treated for AD, according to a prospective, multinational study that followed nearly 8,000 children with AD who used topical tacrolimus for at least 6 weeks over 10 years. With 44,469 person-years of follow-up in a population with at least 6 weeks of exposure to tacrolimus, there were six confirmed cancers, a rate not different than background rates, and no lymphomas.

“I have always tried to educate my patients about the potential use of the topical calcineurin inhibitors while reassuring them that the data did not support significant risk,” Dr. Eichenfield said. However, a large set of data reconfirming a low risk of cancer, although not definitive, “are really nice to have.”
 

Ruxolitinib

For treatment of AD in children aged as young as 12 years, a cream formulation of ruxolitinib, a Janus kinase 1/JAK2 inhibitor, met its primary outcomes in the phase 3 TRuE AD1 and TRuE AD2 trials. (These data are not yet published but were presented at the Revolutionizing Atopic Dermatitis virtual symposium in April 2020.) The primary endpoint of 75% EASI clearance (EASI-75) was achieved in approximately 62% of patients treated with the 1.5% dose of ruxolitinib twice daily. This was a highly significant advantage over vehicle in both studies (P < .0001).

The EASI-75 rates at 8 weeks for the 0.75% formulation, at 56% and 51.5% for the TRuE AD1 and TRuE AD2 trials, respectively, were lower but also superior (P < .0001) to the 24.6% and 14.4% response rates on vehicle, respectively.

Emphasizing a consistent benefit on multiple secondary endpoints, including the “really early itch decrease,” Dr. Eichenfield described the phase 3 data as “really excellent results.” The data have not yet led to FDA approval of ruxolitinib for AD, but approval seems likely. Dr. Eichenfield noted that other drugs in the same class, such as abrocitinib and upadacitinib, have also demonstrated promising efficacy in children aged 12 years or older.
 

Dupilumab

Dupilumab, an interleukin-4 receptor alpha antagonist, was approved in May, 2020, for the treatment of AD in children ages 6-11 years, on the basis of a recently published phase 3, randomized, placebo-controlled trial that enrolled children aged between 6 and 11 years, comparing dupilumab and topical corticosteroids and placebo plus topical corticosteroids. Severe involvement was an entry criterion.

At 16 weeks, an EASI-75 response was achieved by 67% of the group randomized to 200 mg of dupilumab administered every 2 weeks and 70% of the group randomized to 300 mg every 4 weeks versus 27% of those randomized to placebo. More patients in the dupilumab arms developed conjunctivitis (10.8% vs. 4.7%) and had injection-site reactions (8.5% vs. 3.5%), but the monoclonal antibody was otherwise well tolerated and safe.

These data suggest that younger patients with severe disease “do, if anything, better than adults,” Dr. Eichenfield said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education. He cautioned that avoiding live vaccines, which is recommended in patients on dupilumab, “is likely more of an issue in children.”

Ixekizumab

Ixekizumab has been approved for pediatric patients aged as young as 6 years who are eligible for systemic therapy on the basis of a phase 3 trial. For the primary endpoint of 75% clearance on the Psoriasis Area and Severity Index, the response rates were 89% for the IL-17 inhibitor administered every 4 weeks and 25% for placebo. The study also associated ixekizumab with a significant improvement in quality of life.

The availability of more targeted therapies for children are likely. In Europe, secukinumab, another IL-17 inhibitor, was approved for treatment in pediatric patients this past summer, Dr. Eichenfield noted. These data are not yet published, but he expects targeted therapies to join a growing list of biologics already approved in children.

For drugs with established efficacy and safety, he advised, “look at your pediatric psoriasis patients and don’t be wimpy.” In children with poorly controlled psoriasis, he concluded these drugs have been associated with improved quality of life.

In November 2019, the American Academy of Dermatology and National Psoriasis Foundation published psoriasis management guidelines for children. Not all of the most recently approved therapies are included in these guidelines, which are the first to provide specific recommendations for children, but Dr. Eichenfield also included this publication among his top picks for important contributions to the pediatric dermatology literature in 2020.

Dr. Eichenfield reported financial relationships with 20 pharmaceutical companies that manufacture dermatologic products, including those for the diseases he discussed.

This publication and Global Academy for Medical Education are owned by the same parent company.

Respiratory syncytial virus vaccine development has progressed rapidly in recent years, and there is hope that an efficacious vaccine soon may be approved.

Dr. Craig Lyerla/CDC

Louis Bont, MD, PhD, provided an overview of the most recent developments in the complex respiratory syncytial virus (RSV) vaccine landscape at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year.

RSV imposes significant burden worldwide, with 33 million patients, 3 million hospitalizations, and at least 120,000 deaths, reported Dr. Bont of the Wilhelmina Children’s Hospital, University Medical Centre, Utrecht, the Netherlands. Of those deaths, more than 50% are in infants younger than 5 months, and “about 99% of the children dying from RSV live in low- and middle-income countries.”

“There are high-risk populations, such as children with prematurity, congenital heart disease, lung disease, and Down syndrome, but about 73% of all children who are hospitalized for RSV infection were previously healthy children,” Dr. Bont explained. “So, we need to find a solution for all children to prevent RSV infection.”

As observed by Nienke Scheltema in a Lancet Global Health article, population distributions of RSV infection mortality show that, regardless of whether children have comorbidities or they are previously healthy, most children die at a very young age, Dr. Bont explained. These data suggest “that a maternal vaccine or an antibody prophylaxis approach from birth onwards or during the first RSV season is the solution for the problem.”

The path to developing an RSV vaccine has now narrowed its focus onto a structural element of RSV, the prefusion F protein. This shift started with the discovery by Jason McLellan (Science, 2013 [two papers]) that there are two variants of the RSV F-fusion protein: the very stable postfusion conformation and the prefusion active conformation, a metastable protein that exists for a “fraction of a second,” Dr. Bont said.

“The interesting thing is that epitopes that are visible at the prefusion, metastable state … induce highly neutralizing antibodies, whereas epitopes at the postfusion conformation do not,” Dr. Bont explained. “So, by stabilizing the prefusion state, we start inducing neutralizing antibodies that will protect against severe RSV infection, and this is the basic concept of all the vaccine developments currently ongoing.”

These RSV vaccine developments fall into five approach types: live-attenuated or chimeric vaccines, vector-based vaccines, monoclonal antibodies, particle-based vaccines, and subunit or protein-based vaccines.

One breakthrough, which was presented at last year’s ESPID meeting, is the monoclonal antibody nirsevimab. In addition to being nine times more potent than the broadly used antibody palivizumab, it is also more stable; whereas many antibodies have a half-life of 3 weeks, nirsevimab has a half-life of 100 days. “The idea is that a single injection at the start of the RSV season protects children in the first RSV season of their life, a dangerous episode for them.” Dr. Bont explained. The originators, AstraZeneca and Sanofi Pasteur, have “the vision that every child on this planet should receive a single injection with this antibody in the first season,” he explained.

Studies of nanoparticle-based maternal vaccines have also revealed interesting results: Although a phase 3 trial investigating such vaccines didn’t achieve its primary endpoint, “interestingly, 15% of all RSV infections were mild, and only 2% were very severe and leading to hypoxemia,” Dr. Bont noted. “But if we look at vaccine efficacy, we see the opposite – the vaccine was not very efficacious to prevent mild disease, but very efficacious to prevent severe hypoxemia; actually, this is exactly what you would like to see in a vaccine.”

Investigations into live-attenuated and vector-based vaccines have been promising as well, Dr. Bont shared. Studies of live-attenuated vaccines suggest they have a future and that we can move onto their next phase of clinical development, and a study investigating adenoviral vector-based vaccines has demonstrated safety, efficacy, and immunogenicity, though it has also shown that we should anticipate some side effects when using them.

Simple subunit vaccines for RSV are also being explored – a study of DS-Cav1, a stabilized prefusion F subunit protein candidate vaccine, has shown that it has a superior functional profile, compared with previous pre-F subunit vaccines. However, it seemed to be more efficacious against strains of RSV A than strains of RSV B, the dominant strain.

Dr. Bont also discussed exciting work by Sesterhenn et al., in which they used a computer-based program to develop their own vaccine. Using their in-depth knowledge of the RSV prefusion F protein and a computer program, Sesterhenn et al. developed a trivalent vaccine, produced it, and showed – both in vitro and in monkeys – that such vaccines can work up to the level of preclinical in vivo experiments.

“We can now make vaccines behind our computer,” Dr. Bont declared. “And the system doesn’t only work for RSV vaccines, but also for other pathogens – as long as you have an in-depth molecular knowledge of the target epitope,” he added.

Joanne Wildenbeest, MD, PhD, at the Utrecht University, the Netherlands commented: “Lower respiratory tract infections due to RSV are among the leading causes of death worldwide in children under the age of 5, especially young infants. The recent advances in the development of a vaccine and passive immunization are important steps towards the goal to reduce childhood mortality due to RSV worldwide. Since RSV-related mortality is mainly seen in developing countries it is important that, once a vaccine has been approved, it will also be made easily available to these countries.”

Dr. Bont reported the following disclosures: ReSViNET (a nonprofit foundation); investigator-initiated studies with the Bill & Melinda Gates Foundation, AbbVie, MedImmune, and MeMed; participation with Pfizer, Regeneron, and Janssen; and consultancy with GlaxoSmithKline, Ablynx, Novavax, and Janssen.

Respiratory syncytial virus vaccine development has progressed rapidly in recent years, and there is hope that an efficacious vaccine soon may be approved.

Dr. Craig Lyerla/CDC

Louis Bont, MD, PhD, provided an overview of the most recent developments in the complex respiratory syncytial virus (RSV) vaccine landscape at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year.

RSV imposes significant burden worldwide, with 33 million patients, 3 million hospitalizations, and at least 120,000 deaths, reported Dr. Bont of the Wilhelmina Children’s Hospital, University Medical Centre, Utrecht, the Netherlands. Of those deaths, more than 50% are in infants younger than 5 months, and “about 99% of the children dying from RSV live in low- and middle-income countries.”

“There are high-risk populations, such as children with prematurity, congenital heart disease, lung disease, and Down syndrome, but about 73% of all children who are hospitalized for RSV infection were previously healthy children,” Dr. Bont explained. “So, we need to find a solution for all children to prevent RSV infection.”

As observed by Nienke Scheltema in a Lancet Global Health article, population distributions of RSV infection mortality show that, regardless of whether children have comorbidities or they are previously healthy, most children die at a very young age, Dr. Bont explained. These data suggest “that a maternal vaccine or an antibody prophylaxis approach from birth onwards or during the first RSV season is the solution for the problem.”

The path to developing an RSV vaccine has now narrowed its focus onto a structural element of RSV, the prefusion F protein. This shift started with the discovery by Jason McLellan (Science, 2013 [two papers]) that there are two variants of the RSV F-fusion protein: the very stable postfusion conformation and the prefusion active conformation, a metastable protein that exists for a “fraction of a second,” Dr. Bont said.

“The interesting thing is that epitopes that are visible at the prefusion, metastable state … induce highly neutralizing antibodies, whereas epitopes at the postfusion conformation do not,” Dr. Bont explained. “So, by stabilizing the prefusion state, we start inducing neutralizing antibodies that will protect against severe RSV infection, and this is the basic concept of all the vaccine developments currently ongoing.”

These RSV vaccine developments fall into five approach types: live-attenuated or chimeric vaccines, vector-based vaccines, monoclonal antibodies, particle-based vaccines, and subunit or protein-based vaccines.

One breakthrough, which was presented at last year’s ESPID meeting, is the monoclonal antibody nirsevimab. In addition to being nine times more potent than the broadly used antibody palivizumab, it is also more stable; whereas many antibodies have a half-life of 3 weeks, nirsevimab has a half-life of 100 days. “The idea is that a single injection at the start of the RSV season protects children in the first RSV season of their life, a dangerous episode for them.” Dr. Bont explained. The originators, AstraZeneca and Sanofi Pasteur, have “the vision that every child on this planet should receive a single injection with this antibody in the first season,” he explained.

Studies of nanoparticle-based maternal vaccines have also revealed interesting results: Although a phase 3 trial investigating such vaccines didn’t achieve its primary endpoint, “interestingly, 15% of all RSV infections were mild, and only 2% were very severe and leading to hypoxemia,” Dr. Bont noted. “But if we look at vaccine efficacy, we see the opposite – the vaccine was not very efficacious to prevent mild disease, but very efficacious to prevent severe hypoxemia; actually, this is exactly what you would like to see in a vaccine.”

Investigations into live-attenuated and vector-based vaccines have been promising as well, Dr. Bont shared. Studies of live-attenuated vaccines suggest they have a future and that we can move onto their next phase of clinical development, and a study investigating adenoviral vector-based vaccines has demonstrated safety, efficacy, and immunogenicity, though it has also shown that we should anticipate some side effects when using them.

Simple subunit vaccines for RSV are also being explored – a study of DS-Cav1, a stabilized prefusion F subunit protein candidate vaccine, has shown that it has a superior functional profile, compared with previous pre-F subunit vaccines. However, it seemed to be more efficacious against strains of RSV A than strains of RSV B, the dominant strain.

Dr. Bont also discussed exciting work by Sesterhenn et al., in which they used a computer-based program to develop their own vaccine. Using their in-depth knowledge of the RSV prefusion F protein and a computer program, Sesterhenn et al. developed a trivalent vaccine, produced it, and showed – both in vitro and in monkeys – that such vaccines can work up to the level of preclinical in vivo experiments.

“We can now make vaccines behind our computer,” Dr. Bont declared. “And the system doesn’t only work for RSV vaccines, but also for other pathogens – as long as you have an in-depth molecular knowledge of the target epitope,” he added.

Joanne Wildenbeest, MD, PhD, at the Utrecht University, the Netherlands commented: “Lower respiratory tract infections due to RSV are among the leading causes of death worldwide in children under the age of 5, especially young infants. The recent advances in the development of a vaccine and passive immunization are important steps towards the goal to reduce childhood mortality due to RSV worldwide. Since RSV-related mortality is mainly seen in developing countries it is important that, once a vaccine has been approved, it will also be made easily available to these countries.”

Dr. Bont reported the following disclosures: ReSViNET (a nonprofit foundation); investigator-initiated studies with the Bill & Melinda Gates Foundation, AbbVie, MedImmune, and MeMed; participation with Pfizer, Regeneron, and Janssen; and consultancy with GlaxoSmithKline, Ablynx, Novavax, and Janssen.

Respiratory syncytial virus vaccine development has progressed rapidly in recent years, and there is hope that an efficacious vaccine soon may be approved.

Dr. Craig Lyerla/CDC

Louis Bont, MD, PhD, provided an overview of the most recent developments in the complex respiratory syncytial virus (RSV) vaccine landscape at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year.

RSV imposes significant burden worldwide, with 33 million patients, 3 million hospitalizations, and at least 120,000 deaths, reported Dr. Bont of the Wilhelmina Children’s Hospital, University Medical Centre, Utrecht, the Netherlands. Of those deaths, more than 50% are in infants younger than 5 months, and “about 99% of the children dying from RSV live in low- and middle-income countries.”

“There are high-risk populations, such as children with prematurity, congenital heart disease, lung disease, and Down syndrome, but about 73% of all children who are hospitalized for RSV infection were previously healthy children,” Dr. Bont explained. “So, we need to find a solution for all children to prevent RSV infection.”

As observed by Nienke Scheltema in a Lancet Global Health article, population distributions of RSV infection mortality show that, regardless of whether children have comorbidities or they are previously healthy, most children die at a very young age, Dr. Bont explained. These data suggest “that a maternal vaccine or an antibody prophylaxis approach from birth onwards or during the first RSV season is the solution for the problem.”

The path to developing an RSV vaccine has now narrowed its focus onto a structural element of RSV, the prefusion F protein. This shift started with the discovery by Jason McLellan (Science, 2013 [two papers]) that there are two variants of the RSV F-fusion protein: the very stable postfusion conformation and the prefusion active conformation, a metastable protein that exists for a “fraction of a second,” Dr. Bont said.

“The interesting thing is that epitopes that are visible at the prefusion, metastable state … induce highly neutralizing antibodies, whereas epitopes at the postfusion conformation do not,” Dr. Bont explained. “So, by stabilizing the prefusion state, we start inducing neutralizing antibodies that will protect against severe RSV infection, and this is the basic concept of all the vaccine developments currently ongoing.”

These RSV vaccine developments fall into five approach types: live-attenuated or chimeric vaccines, vector-based vaccines, monoclonal antibodies, particle-based vaccines, and subunit or protein-based vaccines.

One breakthrough, which was presented at last year’s ESPID meeting, is the monoclonal antibody nirsevimab. In addition to being nine times more potent than the broadly used antibody palivizumab, it is also more stable; whereas many antibodies have a half-life of 3 weeks, nirsevimab has a half-life of 100 days. “The idea is that a single injection at the start of the RSV season protects children in the first RSV season of their life, a dangerous episode for them.” Dr. Bont explained. The originators, AstraZeneca and Sanofi Pasteur, have “the vision that every child on this planet should receive a single injection with this antibody in the first season,” he explained.

Studies of nanoparticle-based maternal vaccines have also revealed interesting results: Although a phase 3 trial investigating such vaccines didn’t achieve its primary endpoint, “interestingly, 15% of all RSV infections were mild, and only 2% were very severe and leading to hypoxemia,” Dr. Bont noted. “But if we look at vaccine efficacy, we see the opposite – the vaccine was not very efficacious to prevent mild disease, but very efficacious to prevent severe hypoxemia; actually, this is exactly what you would like to see in a vaccine.”

Investigations into live-attenuated and vector-based vaccines have been promising as well, Dr. Bont shared. Studies of live-attenuated vaccines suggest they have a future and that we can move onto their next phase of clinical development, and a study investigating adenoviral vector-based vaccines has demonstrated safety, efficacy, and immunogenicity, though it has also shown that we should anticipate some side effects when using them.

Simple subunit vaccines for RSV are also being explored – a study of DS-Cav1, a stabilized prefusion F subunit protein candidate vaccine, has shown that it has a superior functional profile, compared with previous pre-F subunit vaccines. However, it seemed to be more efficacious against strains of RSV A than strains of RSV B, the dominant strain.

Dr. Bont also discussed exciting work by Sesterhenn et al., in which they used a computer-based program to develop their own vaccine. Using their in-depth knowledge of the RSV prefusion F protein and a computer program, Sesterhenn et al. developed a trivalent vaccine, produced it, and showed – both in vitro and in monkeys – that such vaccines can work up to the level of preclinical in vivo experiments.

“We can now make vaccines behind our computer,” Dr. Bont declared. “And the system doesn’t only work for RSV vaccines, but also for other pathogens – as long as you have an in-depth molecular knowledge of the target epitope,” he added.

Joanne Wildenbeest, MD, PhD, at the Utrecht University, the Netherlands commented: “Lower respiratory tract infections due to RSV are among the leading causes of death worldwide in children under the age of 5, especially young infants. The recent advances in the development of a vaccine and passive immunization are important steps towards the goal to reduce childhood mortality due to RSV worldwide. Since RSV-related mortality is mainly seen in developing countries it is important that, once a vaccine has been approved, it will also be made easily available to these countries.”

Dr. Bont reported the following disclosures: ReSViNET (a nonprofit foundation); investigator-initiated studies with the Bill & Melinda Gates Foundation, AbbVie, MedImmune, and MeMed; participation with Pfizer, Regeneron, and Janssen; and consultancy with GlaxoSmithKline, Ablynx, Novavax, and Janssen.

The European PET-Boost trial finds that both of two strategies for delivering a radiation boost to locally advanced non–small cell lung cancer (NSCLC) tumors improve local control relative to that seen historically. Results were reported at the European Society for Radiology and Oncology 2020 Online Congress. 

“From previous studies, we know that local recurrences have an important negative impact on survival,” said presenting author Saskia A. Cooke, an MD, PhD candidate in the department of Radiation Oncology Research, the Netherlands Cancer Institute, Amsterdam.

In addition, research shows that, despite advances in drug therapy, the most common site of progression in this population is intrathoracic.

“These results further underline the need to develop treatment strategies which effectively prevent intrathoracic and local recurrences,” Ms. Cooke said.

PET-Boost is a multicenter, randomized trial that enrolled patients with inoperable stage II or III NSCLC and a primary tumor measuring 4 cm or greater.

“The study was a phase 2 ‘pick the winner’ trial, which, by design, does not compare the two arms to one another but to a historic rate of outcome,” Ms. Cooke explained.

The patients were randomized evenly to receive the standard 66 Gy of radiotherapy given in 24 fractions of 2.75 Gy with one of two dose-escalation strategies: a boost to the whole primary tumor or a boost to only the tumor area having high metabolic activity, with a maximum standard uptake value (SUVmax) of at least 50% on the pretreatment FDG-PET scan.

For each patient, both plans were created before randomization, with the dose escalated as high as possible up to an organ-at-risk constraint, Ms. Cooke noted.

“A key element is that the two plans were made isotoxic by equaling the mean lung dose, and in both arms, the dose was delivered integrated into the 24 fractions, so without prolongation of the overall treatment time,” she said.

The trial’s goal was to improve the 1-year rate of freedom from local failure from the 70% seen historically with conventional chemoradiotherapy to 85%.

The trial was stopped early because of slow accrual, after enrollment of 107 patients, Ms. Cooke reported. The large majority received concurrent or sequential chemotherapy with their radiotherapy.

With a median follow-up of 12.6 months for the endpoint, the 1-year rate of freedom from local failure as determined on centrally reviewed CT scans was 97% with the whole-tumor boost and 91% with the PET-directed boost. The 2-year rates were 89% and 82%, respectively.

With a median follow-up of 61 months for the endpoint, the 1-year rate of overall survival was 77% with the whole-tumor boost and 62% with the PET-directed boost. The 2-year rates were 46% and 43%, respectively.

The two boost strategies increased acute and late toxicity over that seen historically, but not to unacceptable levels, as reported previously (Radiother Oncol. 2019;131:166-73).

“In this PET-Boost trial, using hypofractionated personalized dose escalation led to a very good local control rate, which, in both arms, was more than 90% at 1 year,” Ms. Cooke summarized.

In fact, values compare favorably with those seen in the phase 3 RTOG 0617 trial using conventional chemoradiotherapy and dose escalation, even though patients in that trial had smaller tumors.

“Survival, especially in the group treated with the homogeneous boost, was actually similar to the RTOG 0617 high-dose arm and also quite similar to the 1-year survival in the placebo arm of the PACIFIC trial,” she added. The somewhat poorer survival at 2 years in PET-Boost was likely related, in part, to the large tumor volumes and the mediastinal radiation dose, she speculated.

The investigators are now evaluating specific sites of failure and extrathoracic recurrences, as well as assessing associations of toxicity with organ-at-risk doses and quality of life.

“While further results of the trial are awaited, so far, we do believe that in selected patients with locally advanced NSCLC, hypofractionated dose escalation to the tumor is a very important subject for future research,” Ms. Cooke said.

The investigators plan to carry the whole-tumor boost strategy forward because it yields similar efficacy but is easier to plan.

Not ready for prime time

“Overall, this study conceptually is well designed as it is forward thinking and uses imaging to personalize radiation treatment, going to higher doses to active areas of disease based on FDG-PET imaging,” Arya Amini, MD, assistant clinical professor in the department of radiation oncology, City of Hope Comprehensive Cancer Center, Duarte, Calif., said in an interview.

SOURCE: Lalezari F et al. ESTRO 2020. Abstract OC-0609.

The European PET-Boost trial finds that both of two strategies for delivering a radiation boost to locally advanced non–small cell lung cancer (NSCLC) tumors improve local control relative to that seen historically. Results were reported at the European Society for Radiology and Oncology 2020 Online Congress. 

“From previous studies, we know that local recurrences have an important negative impact on survival,” said presenting author Saskia A. Cooke, an MD, PhD candidate in the department of Radiation Oncology Research, the Netherlands Cancer Institute, Amsterdam.

In addition, research shows that, despite advances in drug therapy, the most common site of progression in this population is intrathoracic.

“These results further underline the need to develop treatment strategies which effectively prevent intrathoracic and local recurrences,” Ms. Cooke said.

PET-Boost is a multicenter, randomized trial that enrolled patients with inoperable stage II or III NSCLC and a primary tumor measuring 4 cm or greater.

“The study was a phase 2 ‘pick the winner’ trial, which, by design, does not compare the two arms to one another but to a historic rate of outcome,” Ms. Cooke explained.

The patients were randomized evenly to receive the standard 66 Gy of radiotherapy given in 24 fractions of 2.75 Gy with one of two dose-escalation strategies: a boost to the whole primary tumor or a boost to only the tumor area having high metabolic activity, with a maximum standard uptake value (SUVmax) of at least 50% on the pretreatment FDG-PET scan.

For each patient, both plans were created before randomization, with the dose escalated as high as possible up to an organ-at-risk constraint, Ms. Cooke noted.

“A key element is that the two plans were made isotoxic by equaling the mean lung dose, and in both arms, the dose was delivered integrated into the 24 fractions, so without prolongation of the overall treatment time,” she said.

The trial’s goal was to improve the 1-year rate of freedom from local failure from the 70% seen historically with conventional chemoradiotherapy to 85%.

The trial was stopped early because of slow accrual, after enrollment of 107 patients, Ms. Cooke reported. The large majority received concurrent or sequential chemotherapy with their radiotherapy.

With a median follow-up of 12.6 months for the endpoint, the 1-year rate of freedom from local failure as determined on centrally reviewed CT scans was 97% with the whole-tumor boost and 91% with the PET-directed boost. The 2-year rates were 89% and 82%, respectively.

With a median follow-up of 61 months for the endpoint, the 1-year rate of overall survival was 77% with the whole-tumor boost and 62% with the PET-directed boost. The 2-year rates were 46% and 43%, respectively.

The two boost strategies increased acute and late toxicity over that seen historically, but not to unacceptable levels, as reported previously (Radiother Oncol. 2019;131:166-73).

“In this PET-Boost trial, using hypofractionated personalized dose escalation led to a very good local control rate, which, in both arms, was more than 90% at 1 year,” Ms. Cooke summarized.

In fact, values compare favorably with those seen in the phase 3 RTOG 0617 trial using conventional chemoradiotherapy and dose escalation, even though patients in that trial had smaller tumors.

“Survival, especially in the group treated with the homogeneous boost, was actually similar to the RTOG 0617 high-dose arm and also quite similar to the 1-year survival in the placebo arm of the PACIFIC trial,” she added. The somewhat poorer survival at 2 years in PET-Boost was likely related, in part, to the large tumor volumes and the mediastinal radiation dose, she speculated.

The investigators are now evaluating specific sites of failure and extrathoracic recurrences, as well as assessing associations of toxicity with organ-at-risk doses and quality of life.

“While further results of the trial are awaited, so far, we do believe that in selected patients with locally advanced NSCLC, hypofractionated dose escalation to the tumor is a very important subject for future research,” Ms. Cooke said.

The investigators plan to carry the whole-tumor boost strategy forward because it yields similar efficacy but is easier to plan.

Not ready for prime time

“Overall, this study conceptually is well designed as it is forward thinking and uses imaging to personalize radiation treatment, going to higher doses to active areas of disease based on FDG-PET imaging,” Arya Amini, MD, assistant clinical professor in the department of radiation oncology, City of Hope Comprehensive Cancer Center, Duarte, Calif., said in an interview.

SOURCE: Lalezari F et al. ESTRO 2020. Abstract OC-0609.

The European PET-Boost trial finds that both of two strategies for delivering a radiation boost to locally advanced non–small cell lung cancer (NSCLC) tumors improve local control relative to that seen historically. Results were reported at the European Society for Radiology and Oncology 2020 Online Congress. 

“From previous studies, we know that local recurrences have an important negative impact on survival,” said presenting author Saskia A. Cooke, an MD, PhD candidate in the department of Radiation Oncology Research, the Netherlands Cancer Institute, Amsterdam.

In addition, research shows that, despite advances in drug therapy, the most common site of progression in this population is intrathoracic.

“These results further underline the need to develop treatment strategies which effectively prevent intrathoracic and local recurrences,” Ms. Cooke said.

PET-Boost is a multicenter, randomized trial that enrolled patients with inoperable stage II or III NSCLC and a primary tumor measuring 4 cm or greater.

“The study was a phase 2 ‘pick the winner’ trial, which, by design, does not compare the two arms to one another but to a historic rate of outcome,” Ms. Cooke explained.

The patients were randomized evenly to receive the standard 66 Gy of radiotherapy given in 24 fractions of 2.75 Gy with one of two dose-escalation strategies: a boost to the whole primary tumor or a boost to only the tumor area having high metabolic activity, with a maximum standard uptake value (SUVmax) of at least 50% on the pretreatment FDG-PET scan.

For each patient, both plans were created before randomization, with the dose escalated as high as possible up to an organ-at-risk constraint, Ms. Cooke noted.

“A key element is that the two plans were made isotoxic by equaling the mean lung dose, and in both arms, the dose was delivered integrated into the 24 fractions, so without prolongation of the overall treatment time,” she said.

The trial’s goal was to improve the 1-year rate of freedom from local failure from the 70% seen historically with conventional chemoradiotherapy to 85%.

The trial was stopped early because of slow accrual, after enrollment of 107 patients, Ms. Cooke reported. The large majority received concurrent or sequential chemotherapy with their radiotherapy.

With a median follow-up of 12.6 months for the endpoint, the 1-year rate of freedom from local failure as determined on centrally reviewed CT scans was 97% with the whole-tumor boost and 91% with the PET-directed boost. The 2-year rates were 89% and 82%, respectively.

With a median follow-up of 61 months for the endpoint, the 1-year rate of overall survival was 77% with the whole-tumor boost and 62% with the PET-directed boost. The 2-year rates were 46% and 43%, respectively.

The two boost strategies increased acute and late toxicity over that seen historically, but not to unacceptable levels, as reported previously (Radiother Oncol. 2019;131:166-73).

“In this PET-Boost trial, using hypofractionated personalized dose escalation led to a very good local control rate, which, in both arms, was more than 90% at 1 year,” Ms. Cooke summarized.

In fact, values compare favorably with those seen in the phase 3 RTOG 0617 trial using conventional chemoradiotherapy and dose escalation, even though patients in that trial had smaller tumors.

“Survival, especially in the group treated with the homogeneous boost, was actually similar to the RTOG 0617 high-dose arm and also quite similar to the 1-year survival in the placebo arm of the PACIFIC trial,” she added. The somewhat poorer survival at 2 years in PET-Boost was likely related, in part, to the large tumor volumes and the mediastinal radiation dose, she speculated.

The investigators are now evaluating specific sites of failure and extrathoracic recurrences, as well as assessing associations of toxicity with organ-at-risk doses and quality of life.

“While further results of the trial are awaited, so far, we do believe that in selected patients with locally advanced NSCLC, hypofractionated dose escalation to the tumor is a very important subject for future research,” Ms. Cooke said.

The investigators plan to carry the whole-tumor boost strategy forward because it yields similar efficacy but is easier to plan.

Not ready for prime time

“Overall, this study conceptually is well designed as it is forward thinking and uses imaging to personalize radiation treatment, going to higher doses to active areas of disease based on FDG-PET imaging,” Arya Amini, MD, assistant clinical professor in the department of radiation oncology, City of Hope Comprehensive Cancer Center, Duarte, Calif., said in an interview.

SOURCE: Lalezari F et al. ESTRO 2020. Abstract OC-0609.

Medicare officials stuck with their plan to increase payments for office visits for primary care and several other specialties that focus on helping patients manage complex conditions such as diabetes. In doing so, Medicare also finalized cuts for other fields, triggering a new wave of protests. While gastroenterology is estimated to experience a 4% cut, other fields are expecting cuts up to 10%.

The final version of the 2021 Medicare physician fee schedule was unveiled on the night of Dec. 1. The Centers for Medicare & Medicaid Services posted an unofficial copy of the rule, which will later be published in the Federal Register.

CMS said it completed work on this massive annual review of payments for clinicians later than it usually does because of the demands of the federal response to the COVID-19 pandemic. The 2021 physician fee rule takes effect on Jan. 1, 2021, within a 30-day period instead of the usual 60-day time frame.

The rule, which runs to more than 2,100 pages, makes myriad changes in Medicare policies, including rules on telehealth, and expands the roles of nurse practitioners and physician assistants.

The most contentious item proposed for 2021 was a reshuffling of payments among specialties as part of an overhaul of Medicare’s approach to valuing evaluation and management (E/M) services. There was broader support for other aspects of the E/M overhaul, which are intended to cut some of the administrative hassle clinicians face.

“This finalized policy marks the most significant updates to E/M codes in 30 years, reducing burden on doctors imposed by the coding system and rewarding time spent evaluating and managing their patients’ care,” CMS Administrator Seema Verma said in a statement. “In the past, the system has rewarded interventions and procedures over time spent with patients – time taken preventing disease and managing chronic illnesses.”

In the final rule, CMS summarized these results of the E/M changes in Table 106. CMS largely stuck with the approach outlined in a draft rule released in August, with minor changes in the amounts of cuts and increases.

Specialties in line for increases under the 2021 final physician fee schedule include allergy/immunology (9%), endocrinology (16%), family practice (13%), general practice (7%), geriatrics (3%), hematology/oncology (14%), internal medicine (4%), nephrology (6%), physician assistants (8%), psychiatry (7%), rheumatology (15%), and urology (8%).

In line for cuts would be anesthesiology (–8%), cardiac surgery (–8%), emergency medicine (–6%), general surgery (–6%), infectious disease (–4%), neurosurgery (–6%), physical/occupational therapy (–9%), plastic surgery (–7%), radiology (–10%), and thoracic surgery (–8%). The changes also would lead to an expected 4% decrease for gastroenterology. The GI societies are among the groups pressing Congress to intercede.

“Long overdue”

But there also are champions for the approach CMS took in the E/M overhaul. The influential Medicare Payment Advisory Commission (MedPAC) has argued strongly for keeping the budget-neutral approach to the E/M overhaul.

In an Oct. 2 comment to CMS about the draft 2021 physician fee schedule, MedPAC Chairman Michael E. Chernew, PhD, said this approach would “help rebalance the fee schedule from services that have become overvalued to services that have become undervalued.”

This budget-neutral approach also “will go further in reducing the large gap in compensation between primary care physicians (who had a median income of $243,000 in 2018) and specialists such as surgeons (whose median income was $426,000 in 2018),” Dr. Chernew wrote.

In a tweet, Robert B. Doherty, senior vice president of governmental affairs and public policy for the American College of Physicians, said CMS had “finalized long overdue payment increases for primary and comprehensive care including an add-in for more complex visits.”

The American Academy of Family Physicians joined ACP in a Nov. 30 letter to congressional leaders, urging them to allow Medicare “to increase investment in primary care, benefiting millions of Medicare patients and the program itself, and reject last-minute efforts to prevent these essential and long-overdue changes from going fully into effect on January 1, 2021.”

In the letter, AAFP and ACP and their cosigners argued for a need to address “underinvestment” in primary care by finalizing the E/M overhaul.

“Given that six in ten American adults have a chronic disease and four in ten have two or more chronic conditions, why would we, as a country, accept such an inadequate investment in the very care model that stands to provide maximum value to these patients?” they wrote. “Since we know that individuals with a longitudinal relationship with a primary care physician have better health outcomes and use fewer health care resources, why would we continue to direct money to higher-cost, marginal value services?”

Based on reporting from Medscape.com.

Medicare officials stuck with their plan to increase payments for office visits for primary care and several other specialties that focus on helping patients manage complex conditions such as diabetes. In doing so, Medicare also finalized cuts for other fields, triggering a new wave of protests. While gastroenterology is estimated to experience a 4% cut, other fields are expecting cuts up to 10%.

The final version of the 2021 Medicare physician fee schedule was unveiled on the night of Dec. 1. The Centers for Medicare & Medicaid Services posted an unofficial copy of the rule, which will later be published in the Federal Register.

CMS said it completed work on this massive annual review of payments for clinicians later than it usually does because of the demands of the federal response to the COVID-19 pandemic. The 2021 physician fee rule takes effect on Jan. 1, 2021, within a 30-day period instead of the usual 60-day time frame.

The rule, which runs to more than 2,100 pages, makes myriad changes in Medicare policies, including rules on telehealth, and expands the roles of nurse practitioners and physician assistants.

The most contentious item proposed for 2021 was a reshuffling of payments among specialties as part of an overhaul of Medicare’s approach to valuing evaluation and management (E/M) services. There was broader support for other aspects of the E/M overhaul, which are intended to cut some of the administrative hassle clinicians face.

“This finalized policy marks the most significant updates to E/M codes in 30 years, reducing burden on doctors imposed by the coding system and rewarding time spent evaluating and managing their patients’ care,” CMS Administrator Seema Verma said in a statement. “In the past, the system has rewarded interventions and procedures over time spent with patients – time taken preventing disease and managing chronic illnesses.”

In the final rule, CMS summarized these results of the E/M changes in Table 106. CMS largely stuck with the approach outlined in a draft rule released in August, with minor changes in the amounts of cuts and increases.

Specialties in line for increases under the 2021 final physician fee schedule include allergy/immunology (9%), endocrinology (16%), family practice (13%), general practice (7%), geriatrics (3%), hematology/oncology (14%), internal medicine (4%), nephrology (6%), physician assistants (8%), psychiatry (7%), rheumatology (15%), and urology (8%).

In line for cuts would be anesthesiology (–8%), cardiac surgery (–8%), emergency medicine (–6%), general surgery (–6%), infectious disease (–4%), neurosurgery (–6%), physical/occupational therapy (–9%), plastic surgery (–7%), radiology (–10%), and thoracic surgery (–8%). The changes also would lead to an expected 4% decrease for gastroenterology. The GI societies are among the groups pressing Congress to intercede.

“Long overdue”

But there also are champions for the approach CMS took in the E/M overhaul. The influential Medicare Payment Advisory Commission (MedPAC) has argued strongly for keeping the budget-neutral approach to the E/M overhaul.

In an Oct. 2 comment to CMS about the draft 2021 physician fee schedule, MedPAC Chairman Michael E. Chernew, PhD, said this approach would “help rebalance the fee schedule from services that have become overvalued to services that have become undervalued.”

This budget-neutral approach also “will go further in reducing the large gap in compensation between primary care physicians (who had a median income of $243,000 in 2018) and specialists such as surgeons (whose median income was $426,000 in 2018),” Dr. Chernew wrote.

In a tweet, Robert B. Doherty, senior vice president of governmental affairs and public policy for the American College of Physicians, said CMS had “finalized long overdue payment increases for primary and comprehensive care including an add-in for more complex visits.”

The American Academy of Family Physicians joined ACP in a Nov. 30 letter to congressional leaders, urging them to allow Medicare “to increase investment in primary care, benefiting millions of Medicare patients and the program itself, and reject last-minute efforts to prevent these essential and long-overdue changes from going fully into effect on January 1, 2021.”

In the letter, AAFP and ACP and their cosigners argued for a need to address “underinvestment” in primary care by finalizing the E/M overhaul.

“Given that six in ten American adults have a chronic disease and four in ten have two or more chronic conditions, why would we, as a country, accept such an inadequate investment in the very care model that stands to provide maximum value to these patients?” they wrote. “Since we know that individuals with a longitudinal relationship with a primary care physician have better health outcomes and use fewer health care resources, why would we continue to direct money to higher-cost, marginal value services?”

Based on reporting from Medscape.com.

Medicare officials stuck with their plan to increase payments for office visits for primary care and several other specialties that focus on helping patients manage complex conditions such as diabetes. In doing so, Medicare also finalized cuts for other fields, triggering a new wave of protests. While gastroenterology is estimated to experience a 4% cut, other fields are expecting cuts up to 10%.

The final version of the 2021 Medicare physician fee schedule was unveiled on the night of Dec. 1. The Centers for Medicare & Medicaid Services posted an unofficial copy of the rule, which will later be published in the Federal Register.

CMS said it completed work on this massive annual review of payments for clinicians later than it usually does because of the demands of the federal response to the COVID-19 pandemic. The 2021 physician fee rule takes effect on Jan. 1, 2021, within a 30-day period instead of the usual 60-day time frame.

The rule, which runs to more than 2,100 pages, makes myriad changes in Medicare policies, including rules on telehealth, and expands the roles of nurse practitioners and physician assistants.

The most contentious item proposed for 2021 was a reshuffling of payments among specialties as part of an overhaul of Medicare’s approach to valuing evaluation and management (E/M) services. There was broader support for other aspects of the E/M overhaul, which are intended to cut some of the administrative hassle clinicians face.

“This finalized policy marks the most significant updates to E/M codes in 30 years, reducing burden on doctors imposed by the coding system and rewarding time spent evaluating and managing their patients’ care,” CMS Administrator Seema Verma said in a statement. “In the past, the system has rewarded interventions and procedures over time spent with patients – time taken preventing disease and managing chronic illnesses.”

In the final rule, CMS summarized these results of the E/M changes in Table 106. CMS largely stuck with the approach outlined in a draft rule released in August, with minor changes in the amounts of cuts and increases.

Specialties in line for increases under the 2021 final physician fee schedule include allergy/immunology (9%), endocrinology (16%), family practice (13%), general practice (7%), geriatrics (3%), hematology/oncology (14%), internal medicine (4%), nephrology (6%), physician assistants (8%), psychiatry (7%), rheumatology (15%), and urology (8%).

In line for cuts would be anesthesiology (–8%), cardiac surgery (–8%), emergency medicine (–6%), general surgery (–6%), infectious disease (–4%), neurosurgery (–6%), physical/occupational therapy (–9%), plastic surgery (–7%), radiology (–10%), and thoracic surgery (–8%). The changes also would lead to an expected 4% decrease for gastroenterology. The GI societies are among the groups pressing Congress to intercede.

“Long overdue”

But there also are champions for the approach CMS took in the E/M overhaul. The influential Medicare Payment Advisory Commission (MedPAC) has argued strongly for keeping the budget-neutral approach to the E/M overhaul.

In an Oct. 2 comment to CMS about the draft 2021 physician fee schedule, MedPAC Chairman Michael E. Chernew, PhD, said this approach would “help rebalance the fee schedule from services that have become overvalued to services that have become undervalued.”

This budget-neutral approach also “will go further in reducing the large gap in compensation between primary care physicians (who had a median income of $243,000 in 2018) and specialists such as surgeons (whose median income was $426,000 in 2018),” Dr. Chernew wrote.

In a tweet, Robert B. Doherty, senior vice president of governmental affairs and public policy for the American College of Physicians, said CMS had “finalized long overdue payment increases for primary and comprehensive care including an add-in for more complex visits.”

The American Academy of Family Physicians joined ACP in a Nov. 30 letter to congressional leaders, urging them to allow Medicare “to increase investment in primary care, benefiting millions of Medicare patients and the program itself, and reject last-minute efforts to prevent these essential and long-overdue changes from going fully into effect on January 1, 2021.”

In the letter, AAFP and ACP and their cosigners argued for a need to address “underinvestment” in primary care by finalizing the E/M overhaul.

“Given that six in ten American adults have a chronic disease and four in ten have two or more chronic conditions, why would we, as a country, accept such an inadequate investment in the very care model that stands to provide maximum value to these patients?” they wrote. “Since we know that individuals with a longitudinal relationship with a primary care physician have better health outcomes and use fewer health care resources, why would we continue to direct money to higher-cost, marginal value services?”

Based on reporting from Medscape.com.

A diagnosis of atopic dermatitis in individuals ages 15 years or older, compared with controls without atopic dermatitis, was nearly twice as likely to be associated with autoimmune disease, in a case control study derived from Swedish national health care registry data.

Atopic dermatitis (AD) is known to be associated with other atopic conditions, and there is increasing evidence it is associated with some nonatopic conditions, including some cancers, cardiovascular disease, and neuropsychiatric disorders, according to Lina U. Ivert, MD, of the dermatology and venereology unit at the Karolinska Institutet, Stockholm, and coauthors. There are also some data indicating that autoimmune diseases, particularly those involving the skin and gastrointestinal tract, are more common in people with AD.

The aim of their study, published in the British Journal of Dermatology, was to investigate a wide spectrum of autoimmune diseases for associations with AD in a large-scale, population-based study using Swedish registers. Findings could lead to better monitoring of comorbidities and deeper understanding of disease burden and AD pathophysiology, they noted.
 

Large-scale study

With data from the Swedish Board of Health and Welfare’s National Patient Register on inpatient diagnoses since 1964 and specialist outpatient visits since 2001, the investigators included all patients aged 15 years and older with AD diagnoses (104,832) and matched them with controls from the general population (1,022,435). The authors noted that the large number of people included in the analysis allowed for robust estimates, and underscored that 80% of the AD patients included had received their diagnosis in a dermatology department, which reduces the risk of misclassification.

Association with autoimmune disease

The investigators found an association between AD and autoimmune disease, with an adjusted odds ratio) of 1.97 (95% confidence interval, 1.93-2.01). The association was present with several organ systems, particularly the skin and gastrointestinal tract, and with connective tissue diseases. The strongest associations with autoimmune skin diseases were found for dermatitis herpetiformis (aOR, 9.76; 95% CI, 8.10-11.8), alopecia areata (aOR, 5.11; 95% CI, 4.75-5.49), and chronic urticaria (aOR, 4.82; 95% CI, 4.48-5.19).

AD was associated with gastrointestinal diseases, including celiac disease (aOR, 1.96; 95% CI, 1.84-2.09), Crohn disease (aOR 1.83; CI, 1.71-1.96), and ulcerative colitis (aOR 1.58; 95% CI, 1.49-1.68).

Connective tissue diseases significantly associated with AD included systemic lupus erythematosus (aOR, 1.65; 95% CI, 1.42-1.90), ankylosing spondylitis (aOR, 1.46; 95% CI, 1.29-1.66), and RA (aOR, 1.44; 95% CI,1.34-1.54]). Hematologic or hepatic autoimmune disease associations with AD were not observed.
 

Stronger association with multiple diseases

The association between AD and two or more autoimmune diseases was significantly stronger than the association between AD and having one autoimmune disease. For example, the OR for AD among people with three to five autoimmune diseases was 3.33 (95% CI, 2.86-3.87), and was stronger in men (OR, 3.96; 95% CI, 2.92-5.37) than in women (OR, 3.14; 95% CI, 2.63-3.74).
 

Sex differences

In the study overall, the association with AD and autoimmune diseases was stronger in men (aOR, 2.18; 95% CI, 2.10-2.25), compared with women (aOR, 1.89; 95% CI, 1.85-1.93), but this “sex difference was only statistically significant between AD and RA and between AD and Celiac disease,” they noted.

Associations between AD and dermatomyositis, systemic scleroderma, systemic lupus erythematosus, Hashimoto’s disease, Graves disease, multiple sclerosis, and polymyalgia rheumatica were found only in women. Dr. Ivert and coauthors observed that “women are in general more likely to develop autoimmune diseases, and 80% of patients with autoimmune diseases are women.”
 

Provocative questions

Commenting on the findings, Jonathan Silverberg, MD, PhD, MPH, associate professor of dermatology, George Washington University, Washington, said, “At a high level, it is important for clinicians to recognize that atopic dermatitis is a systemic immune-mediated disease. AD is associated with higher rates of comorbid autoimmune disease, similar to psoriasis and other chronic inflammatory skin diseases.”

“At this point, there is nothing immediately actionable about these results,” noted Dr. Silverberg, who was not an author of this study. “That said, in my mind, they raise some provocative questions: What is the difference between AD in adults who do versus those who do not get comorbid autoimmune disease? Does AD then present differently? Does it respond to the same therapies? These will have to be the subject of future research.”

The study was funded by the Swedish Asthma and Allergy Association Research Foundation, Hudfonden (the Welander-Finsen Foundation), and the Swedish Society for Dermatology and Venereology. The authors disclosed no conflicts of interest.

SOURCE: Ivert LU et al. Br J Dermatol. 2020 Oct 22. doi: 10.1111/bjd.19624.

A diagnosis of atopic dermatitis in individuals ages 15 years or older, compared with controls without atopic dermatitis, was nearly twice as likely to be associated with autoimmune disease, in a case control study derived from Swedish national health care registry data.

Atopic dermatitis (AD) is known to be associated with other atopic conditions, and there is increasing evidence it is associated with some nonatopic conditions, including some cancers, cardiovascular disease, and neuropsychiatric disorders, according to Lina U. Ivert, MD, of the dermatology and venereology unit at the Karolinska Institutet, Stockholm, and coauthors. There are also some data indicating that autoimmune diseases, particularly those involving the skin and gastrointestinal tract, are more common in people with AD.

The aim of their study, published in the British Journal of Dermatology, was to investigate a wide spectrum of autoimmune diseases for associations with AD in a large-scale, population-based study using Swedish registers. Findings could lead to better monitoring of comorbidities and deeper understanding of disease burden and AD pathophysiology, they noted.
 

Large-scale study

With data from the Swedish Board of Health and Welfare’s National Patient Register on inpatient diagnoses since 1964 and specialist outpatient visits since 2001, the investigators included all patients aged 15 years and older with AD diagnoses (104,832) and matched them with controls from the general population (1,022,435). The authors noted that the large number of people included in the analysis allowed for robust estimates, and underscored that 80% of the AD patients included had received their diagnosis in a dermatology department, which reduces the risk of misclassification.

Association with autoimmune disease

The investigators found an association between AD and autoimmune disease, with an adjusted odds ratio) of 1.97 (95% confidence interval, 1.93-2.01). The association was present with several organ systems, particularly the skin and gastrointestinal tract, and with connective tissue diseases. The strongest associations with autoimmune skin diseases were found for dermatitis herpetiformis (aOR, 9.76; 95% CI, 8.10-11.8), alopecia areata (aOR, 5.11; 95% CI, 4.75-5.49), and chronic urticaria (aOR, 4.82; 95% CI, 4.48-5.19).

AD was associated with gastrointestinal diseases, including celiac disease (aOR, 1.96; 95% CI, 1.84-2.09), Crohn disease (aOR 1.83; CI, 1.71-1.96), and ulcerative colitis (aOR 1.58; 95% CI, 1.49-1.68).

Connective tissue diseases significantly associated with AD included systemic lupus erythematosus (aOR, 1.65; 95% CI, 1.42-1.90), ankylosing spondylitis (aOR, 1.46; 95% CI, 1.29-1.66), and RA (aOR, 1.44; 95% CI,1.34-1.54]). Hematologic or hepatic autoimmune disease associations with AD were not observed.
 

Stronger association with multiple diseases

The association between AD and two or more autoimmune diseases was significantly stronger than the association between AD and having one autoimmune disease. For example, the OR for AD among people with three to five autoimmune diseases was 3.33 (95% CI, 2.86-3.87), and was stronger in men (OR, 3.96; 95% CI, 2.92-5.37) than in women (OR, 3.14; 95% CI, 2.63-3.74).
 

Sex differences

In the study overall, the association with AD and autoimmune diseases was stronger in men (aOR, 2.18; 95% CI, 2.10-2.25), compared with women (aOR, 1.89; 95% CI, 1.85-1.93), but this “sex difference was only statistically significant between AD and RA and between AD and Celiac disease,” they noted.

Associations between AD and dermatomyositis, systemic scleroderma, systemic lupus erythematosus, Hashimoto’s disease, Graves disease, multiple sclerosis, and polymyalgia rheumatica were found only in women. Dr. Ivert and coauthors observed that “women are in general more likely to develop autoimmune diseases, and 80% of patients with autoimmune diseases are women.”
 

Provocative questions

Commenting on the findings, Jonathan Silverberg, MD, PhD, MPH, associate professor of dermatology, George Washington University, Washington, said, “At a high level, it is important for clinicians to recognize that atopic dermatitis is a systemic immune-mediated disease. AD is associated with higher rates of comorbid autoimmune disease, similar to psoriasis and other chronic inflammatory skin diseases.”

“At this point, there is nothing immediately actionable about these results,” noted Dr. Silverberg, who was not an author of this study. “That said, in my mind, they raise some provocative questions: What is the difference between AD in adults who do versus those who do not get comorbid autoimmune disease? Does AD then present differently? Does it respond to the same therapies? These will have to be the subject of future research.”

The study was funded by the Swedish Asthma and Allergy Association Research Foundation, Hudfonden (the Welander-Finsen Foundation), and the Swedish Society for Dermatology and Venereology. The authors disclosed no conflicts of interest.

SOURCE: Ivert LU et al. Br J Dermatol. 2020 Oct 22. doi: 10.1111/bjd.19624.

A diagnosis of atopic dermatitis in individuals ages 15 years or older, compared with controls without atopic dermatitis, was nearly twice as likely to be associated with autoimmune disease, in a case control study derived from Swedish national health care registry data.

Atopic dermatitis (AD) is known to be associated with other atopic conditions, and there is increasing evidence it is associated with some nonatopic conditions, including some cancers, cardiovascular disease, and neuropsychiatric disorders, according to Lina U. Ivert, MD, of the dermatology and venereology unit at the Karolinska Institutet, Stockholm, and coauthors. There are also some data indicating that autoimmune diseases, particularly those involving the skin and gastrointestinal tract, are more common in people with AD.

The aim of their study, published in the British Journal of Dermatology, was to investigate a wide spectrum of autoimmune diseases for associations with AD in a large-scale, population-based study using Swedish registers. Findings could lead to better monitoring of comorbidities and deeper understanding of disease burden and AD pathophysiology, they noted.
 

Large-scale study

With data from the Swedish Board of Health and Welfare’s National Patient Register on inpatient diagnoses since 1964 and specialist outpatient visits since 2001, the investigators included all patients aged 15 years and older with AD diagnoses (104,832) and matched them with controls from the general population (1,022,435). The authors noted that the large number of people included in the analysis allowed for robust estimates, and underscored that 80% of the AD patients included had received their diagnosis in a dermatology department, which reduces the risk of misclassification.

Association with autoimmune disease

The investigators found an association between AD and autoimmune disease, with an adjusted odds ratio) of 1.97 (95% confidence interval, 1.93-2.01). The association was present with several organ systems, particularly the skin and gastrointestinal tract, and with connective tissue diseases. The strongest associations with autoimmune skin diseases were found for dermatitis herpetiformis (aOR, 9.76; 95% CI, 8.10-11.8), alopecia areata (aOR, 5.11; 95% CI, 4.75-5.49), and chronic urticaria (aOR, 4.82; 95% CI, 4.48-5.19).

AD was associated with gastrointestinal diseases, including celiac disease (aOR, 1.96; 95% CI, 1.84-2.09), Crohn disease (aOR 1.83; CI, 1.71-1.96), and ulcerative colitis (aOR 1.58; 95% CI, 1.49-1.68).

Connective tissue diseases significantly associated with AD included systemic lupus erythematosus (aOR, 1.65; 95% CI, 1.42-1.90), ankylosing spondylitis (aOR, 1.46; 95% CI, 1.29-1.66), and RA (aOR, 1.44; 95% CI,1.34-1.54]). Hematologic or hepatic autoimmune disease associations with AD were not observed.
 

Stronger association with multiple diseases

The association between AD and two or more autoimmune diseases was significantly stronger than the association between AD and having one autoimmune disease. For example, the OR for AD among people with three to five autoimmune diseases was 3.33 (95% CI, 2.86-3.87), and was stronger in men (OR, 3.96; 95% CI, 2.92-5.37) than in women (OR, 3.14; 95% CI, 2.63-3.74).
 

Sex differences

In the study overall, the association with AD and autoimmune diseases was stronger in men (aOR, 2.18; 95% CI, 2.10-2.25), compared with women (aOR, 1.89; 95% CI, 1.85-1.93), but this “sex difference was only statistically significant between AD and RA and between AD and Celiac disease,” they noted.

Associations between AD and dermatomyositis, systemic scleroderma, systemic lupus erythematosus, Hashimoto’s disease, Graves disease, multiple sclerosis, and polymyalgia rheumatica were found only in women. Dr. Ivert and coauthors observed that “women are in general more likely to develop autoimmune diseases, and 80% of patients with autoimmune diseases are women.”
 

Provocative questions

Commenting on the findings, Jonathan Silverberg, MD, PhD, MPH, associate professor of dermatology, George Washington University, Washington, said, “At a high level, it is important for clinicians to recognize that atopic dermatitis is a systemic immune-mediated disease. AD is associated with higher rates of comorbid autoimmune disease, similar to psoriasis and other chronic inflammatory skin diseases.”

“At this point, there is nothing immediately actionable about these results,” noted Dr. Silverberg, who was not an author of this study. “That said, in my mind, they raise some provocative questions: What is the difference between AD in adults who do versus those who do not get comorbid autoimmune disease? Does AD then present differently? Does it respond to the same therapies? These will have to be the subject of future research.”

The study was funded by the Swedish Asthma and Allergy Association Research Foundation, Hudfonden (the Welander-Finsen Foundation), and the Swedish Society for Dermatology and Venereology. The authors disclosed no conflicts of interest.

SOURCE: Ivert LU et al. Br J Dermatol. 2020 Oct 22. doi: 10.1111/bjd.19624.

Wound cultures from patients with the rare disease epidermolysis bullosa (EB) were most frequently positive for Staphylococcus aureus (SA), Pseudomonas aeruginosa (PA), and Streptococcus pyogenes (GAS) – and antibiotic resistance was common – in a retrospective analysis of over 700 wound cultures from 158 patients across the United States and Canada.

The findings from the EB Clinical Characterization and Outcomes Database speak to the value of surveillance cultures with routine testing for microbial resistance – including mupirocin resistance – and to the importance of antibiotic stewardship not only for oral antibiotics but for topicals as well, according to Laura E. Levin, MD, and Kimberly D. Morel, MD, of the departments of dermatology and pediatrics, Columbia University Irving Medical Center, New York, the lead and senior authors, respectively, of the paper recently published in Pediatric Dermatology.

Almost all of the 158 patients with at least one wound culture recorded in the database from the period of 2001-2018 had one or more positive culture results. Of 152 patients with positive cultures, 131 (86%) were positive for SA and 56 (37%) and 34 (22%) were positive for PA and GAS, respectively. Other bacteria isolated included Corynebacterium spp and Proteus spp. Nearly half (47%) of patients with SA-positive cultures had methicillin-resistant SA, and 68% had methicillin-susceptible SA. (Some patients grew both MSSA and MRSA at different points in time.)

Mupirocin-susceptibility testing was performed at only some of the 13 participating centers. Of 15 patients whose cultures had recorded SA mupirocin-susceptibility testing, 11 had cultures positive for mupirocin-susceptible SA and 6 (40%) had mupirocin-resistant SA isolates (2 patients grew both). Of these six patients, half had isolates that were also methicillin-resistant.

Mupirocin, a topical antibiotic, has been a cornerstone of decolonization regimens for MSSA and MRSA, but resistance has been demonstrated in other research as well and is not specific to EB, wrote Dr. Levin, Dr. Morel, and coauthors.

“Pediatric dermatologists often rely on topical antimicrobials in the treatment of patients’ open wounds to both prevent and treat infection, depending on the clinical scenario,” and surveillance cultures with routine testing for mupirocin resistance can help guide antibiotic choice and management strategies, Dr. Levin said in an interview.

More broadly, she added, “it’s helpful to know what bacteria are routinely colonizing wounds, not causing infection, versus those that are more likely to be associated with infection, chronic wounds, or the risk of developing skin cancer ... [to know] which wounds need to be treated more aggressively.”

A subset of patients with EB have been known to be at risk for squamous cell carcinoma, and research is implicating certain bacteria “as contributing to wound inflammation,” Dr. Morel said in an interview.

SCC was reported in 23 out of 717 patients in the database – but fewer than half of the patients with SCC had recorded wound cultures. The small numbers precluded the identification of microbes that may confer significant risk.

Correlating particular microbes with clinical features also will take more research. About half (57%) of the patients with recorded wound cultures had wounds with purulent exudate or other features of clinical infection. However, the presence or absence of clinical signs of infection was not temporally correlated with culture results in the database.

The 158 patients with recorded wound cultures had a mean age of 12.8 years and represented a range of EB subtypes.

PA was present in the wounds of patients as young as 1 month old, the authors noted. Investigators are “looking to further study PA and characterize clinical features ... to understand more about this microbe and its impact on patients with EB,” Dr. Morel said.

In the meantime, the analysis reaffirms the importance of antibiotic stewardship. Mupirocin is labeled to be used three times a day for a short period of time, but “tends to be prescribed and used less judiciously than intended,” Dr. Morel said. “It’s important [not to overuse it]. We have seen that patients’ culture results become sensitive to mupirocin again in the future when they avoid it for a period of time.”

The work was supported by the EB Research Partnership and EB Medical Research Foundation, as well as an NIH/NCATS grant. No investigator disclosures were listed.

SOURCE: Pediatr Dermatol. 2020 Nov 28. doi: 10.1111/pde.14444.

Wound cultures from patients with the rare disease epidermolysis bullosa (EB) were most frequently positive for Staphylococcus aureus (SA), Pseudomonas aeruginosa (PA), and Streptococcus pyogenes (GAS) – and antibiotic resistance was common – in a retrospective analysis of over 700 wound cultures from 158 patients across the United States and Canada.

The findings from the EB Clinical Characterization and Outcomes Database speak to the value of surveillance cultures with routine testing for microbial resistance – including mupirocin resistance – and to the importance of antibiotic stewardship not only for oral antibiotics but for topicals as well, according to Laura E. Levin, MD, and Kimberly D. Morel, MD, of the departments of dermatology and pediatrics, Columbia University Irving Medical Center, New York, the lead and senior authors, respectively, of the paper recently published in Pediatric Dermatology.

Almost all of the 158 patients with at least one wound culture recorded in the database from the period of 2001-2018 had one or more positive culture results. Of 152 patients with positive cultures, 131 (86%) were positive for SA and 56 (37%) and 34 (22%) were positive for PA and GAS, respectively. Other bacteria isolated included Corynebacterium spp and Proteus spp. Nearly half (47%) of patients with SA-positive cultures had methicillin-resistant SA, and 68% had methicillin-susceptible SA. (Some patients grew both MSSA and MRSA at different points in time.)

Mupirocin-susceptibility testing was performed at only some of the 13 participating centers. Of 15 patients whose cultures had recorded SA mupirocin-susceptibility testing, 11 had cultures positive for mupirocin-susceptible SA and 6 (40%) had mupirocin-resistant SA isolates (2 patients grew both). Of these six patients, half had isolates that were also methicillin-resistant.

Mupirocin, a topical antibiotic, has been a cornerstone of decolonization regimens for MSSA and MRSA, but resistance has been demonstrated in other research as well and is not specific to EB, wrote Dr. Levin, Dr. Morel, and coauthors.

“Pediatric dermatologists often rely on topical antimicrobials in the treatment of patients’ open wounds to both prevent and treat infection, depending on the clinical scenario,” and surveillance cultures with routine testing for mupirocin resistance can help guide antibiotic choice and management strategies, Dr. Levin said in an interview.

More broadly, she added, “it’s helpful to know what bacteria are routinely colonizing wounds, not causing infection, versus those that are more likely to be associated with infection, chronic wounds, or the risk of developing skin cancer ... [to know] which wounds need to be treated more aggressively.”

A subset of patients with EB have been known to be at risk for squamous cell carcinoma, and research is implicating certain bacteria “as contributing to wound inflammation,” Dr. Morel said in an interview.

SCC was reported in 23 out of 717 patients in the database – but fewer than half of the patients with SCC had recorded wound cultures. The small numbers precluded the identification of microbes that may confer significant risk.

Correlating particular microbes with clinical features also will take more research. About half (57%) of the patients with recorded wound cultures had wounds with purulent exudate or other features of clinical infection. However, the presence or absence of clinical signs of infection was not temporally correlated with culture results in the database.

The 158 patients with recorded wound cultures had a mean age of 12.8 years and represented a range of EB subtypes.

PA was present in the wounds of patients as young as 1 month old, the authors noted. Investigators are “looking to further study PA and characterize clinical features ... to understand more about this microbe and its impact on patients with EB,” Dr. Morel said.

In the meantime, the analysis reaffirms the importance of antibiotic stewardship. Mupirocin is labeled to be used three times a day for a short period of time, but “tends to be prescribed and used less judiciously than intended,” Dr. Morel said. “It’s important [not to overuse it]. We have seen that patients’ culture results become sensitive to mupirocin again in the future when they avoid it for a period of time.”

The work was supported by the EB Research Partnership and EB Medical Research Foundation, as well as an NIH/NCATS grant. No investigator disclosures were listed.

SOURCE: Pediatr Dermatol. 2020 Nov 28. doi: 10.1111/pde.14444.

Wound cultures from patients with the rare disease epidermolysis bullosa (EB) were most frequently positive for Staphylococcus aureus (SA), Pseudomonas aeruginosa (PA), and Streptococcus pyogenes (GAS) – and antibiotic resistance was common – in a retrospective analysis of over 700 wound cultures from 158 patients across the United States and Canada.

The findings from the EB Clinical Characterization and Outcomes Database speak to the value of surveillance cultures with routine testing for microbial resistance – including mupirocin resistance – and to the importance of antibiotic stewardship not only for oral antibiotics but for topicals as well, according to Laura E. Levin, MD, and Kimberly D. Morel, MD, of the departments of dermatology and pediatrics, Columbia University Irving Medical Center, New York, the lead and senior authors, respectively, of the paper recently published in Pediatric Dermatology.

Almost all of the 158 patients with at least one wound culture recorded in the database from the period of 2001-2018 had one or more positive culture results. Of 152 patients with positive cultures, 131 (86%) were positive for SA and 56 (37%) and 34 (22%) were positive for PA and GAS, respectively. Other bacteria isolated included Corynebacterium spp and Proteus spp. Nearly half (47%) of patients with SA-positive cultures had methicillin-resistant SA, and 68% had methicillin-susceptible SA. (Some patients grew both MSSA and MRSA at different points in time.)

Mupirocin-susceptibility testing was performed at only some of the 13 participating centers. Of 15 patients whose cultures had recorded SA mupirocin-susceptibility testing, 11 had cultures positive for mupirocin-susceptible SA and 6 (40%) had mupirocin-resistant SA isolates (2 patients grew both). Of these six patients, half had isolates that were also methicillin-resistant.

Mupirocin, a topical antibiotic, has been a cornerstone of decolonization regimens for MSSA and MRSA, but resistance has been demonstrated in other research as well and is not specific to EB, wrote Dr. Levin, Dr. Morel, and coauthors.

“Pediatric dermatologists often rely on topical antimicrobials in the treatment of patients’ open wounds to both prevent and treat infection, depending on the clinical scenario,” and surveillance cultures with routine testing for mupirocin resistance can help guide antibiotic choice and management strategies, Dr. Levin said in an interview.

More broadly, she added, “it’s helpful to know what bacteria are routinely colonizing wounds, not causing infection, versus those that are more likely to be associated with infection, chronic wounds, or the risk of developing skin cancer ... [to know] which wounds need to be treated more aggressively.”

A subset of patients with EB have been known to be at risk for squamous cell carcinoma, and research is implicating certain bacteria “as contributing to wound inflammation,” Dr. Morel said in an interview.

SCC was reported in 23 out of 717 patients in the database – but fewer than half of the patients with SCC had recorded wound cultures. The small numbers precluded the identification of microbes that may confer significant risk.

Correlating particular microbes with clinical features also will take more research. About half (57%) of the patients with recorded wound cultures had wounds with purulent exudate or other features of clinical infection. However, the presence or absence of clinical signs of infection was not temporally correlated with culture results in the database.

The 158 patients with recorded wound cultures had a mean age of 12.8 years and represented a range of EB subtypes.

PA was present in the wounds of patients as young as 1 month old, the authors noted. Investigators are “looking to further study PA and characterize clinical features ... to understand more about this microbe and its impact on patients with EB,” Dr. Morel said.

In the meantime, the analysis reaffirms the importance of antibiotic stewardship. Mupirocin is labeled to be used three times a day for a short period of time, but “tends to be prescribed and used less judiciously than intended,” Dr. Morel said. “It’s important [not to overuse it]. We have seen that patients’ culture results become sensitive to mupirocin again in the future when they avoid it for a period of time.”

The work was supported by the EB Research Partnership and EB Medical Research Foundation, as well as an NIH/NCATS grant. No investigator disclosures were listed.

SOURCE: Pediatr Dermatol. 2020 Nov 28. doi: 10.1111/pde.14444.

Black and Latinx children are more likely to be evaluated for child abuse and referred to child protective services than their White peers, according to research discussed by Tiffani J. Johnson, MD, an assistant professor of emergency medicine at the University of California, Davis.

Darrin Klimek/Thinkstock

“These disparities in child abuse evaluation and reporting are bidirectional,” she said. “We also recognize that abuse is more likely to be unrecognized in White children.”

Dr. Johnson presented data on the health disparities in child abuse reporting in a session at the annual meeting of the American Academy of Pediatrics, held virtually this year. Health care disparities, as defined by the National Academy of Sciences, refers to differences in the quality of care between minority and nonminority populations that are not caused by clinical appropriateness, access, need, or patient preference, she explained. Instead, they result from discrimination, bias, stereotyping, and uncertainty.
 

Disparities lead to harm in all children

For example, a 2018 systematic review found that Black and other non-White children were significantly more likely than White children to be evaluated with a skeletal survey. In one of the studies included, at a large urban academic center, Black and Latinx children with accidental fractures were 8.75 times more likely to undergo a skeletal survey than White children and 4.3 times more likely to be reported to child protective services.

“And let me emphasize that these are children who were ultimately found to have accidental fractures,” Dr. Johnson said.

Meanwhile, in an analysis of known cases of head trauma, researchers found that abuse was missed in 37% of White children, compared with 19% of non-White children.

“These only represent the tip of the iceberg as a true number of cases of abuse may never really be detected because some cases are still unknown,” Dr. Johnson told attendees. And the harm of these disparities runs in both directions.

“Failing to diagnose abuse in White children clearly puts them at increased risk for return visits and return evaluations for repeated abuse by the perpetrators,” she said. But harm also can result from overreporting and investigation, including psychological trauma and a waste of limited resources. Overinvestigation also can erode family-physician relationships and perpetuate distrust of medical care in communities of color.

Yet at the same time, it’s clear that Black children, adolescents, and young adults are not protected from harm in society more generally, when at home, where they learn, or where they play, Dr. Johnson said, referencing the deaths of Breonna Taylor and Tamir Rice as examples.

KatarzynaBialasiewicz/Thinkstock

“And now we’re seeing increased evidence that children are not protected in the health care center when we think about the many disparities that have been identified in the care and outcomes of children, including the disproportionality in terms of child abuse evaluation and referrals,” Dr. Johnson said.

Racism is a root cause of that harm to Black children, she said, as the systemic structure of opportunities unfairly disadvantages some individuals and communities while unfairly advantaging others, thereby “sapping the strength of the whole society through the waste of human resources.”

Tonya Chaffee, MD, MPH, a clinical professor of health sciences at the University of California, San Francisco, who attended the session, said she particularly appreciated “seeing data on which racial/ethnic populations have child abuse reports made and the disparities that exist that are similar to what we are noticing in our own institution.”
 

Role of individual-level implicit bias and racism

While institutional and structural racism play a substantial role in health care disparities, Dr. Johnson focused primarily on the impact of personal racism when it comes to child abuse evaluations, through overt discrimination, explicit bias, implicit bias, and stigmatization. The most challenging of these to identify and acknowledge is often implicit bias, a tendency to believe, even unconsciously, that some people or ideas are better than others, which results in unfair treatment.

For example, a 2016 study found that half of medical students and residents held at least one biological belief about differences between Black and White individuals that was actually false, such as Black people having more pain tolerance or stronger bones than White people, which then affected treatment recommendations.

“Implicit bias refers to our attitudes that lie below the surface, but they can still influence our behaviors,” Dr. Johnson explained. She encouraged providers to take the implicit bias test online to learn about their own unrecognized implicit biases. These biases have a hand in influencing decisions particularly in fast-paced environments where cognitive load is high – such as EDs, where many child abuse evaluations occur.

For example, in one study Dr. Johnson led, the researchers measured implicit bias in participants before and after an ED shift to assess how cognitive load affected bias. They found that participants who care for more than 10 patients, the average score for implicit bias increased.

Similarly, “when the ED was more overcrowded, there was also increased bias at the end of the shift, compared to the beginning of the shift,” Dr. Johnson said. She asked clinicians to take into consideration that at the start of the shift, they may feel well rested and freshly caffeinated, able to suppress or overcome the biases that they know they have.

“But our biases [are] more likely to come into play with every subsequent decision that we make throughout the day when we’re engaged in clinical encounters,” such as who does and does not receive a skeletal survey or get referred to child protective services, she said.

In another study where she hypothesized that resident physicians would have less bias on the child race implicit bias test than on the adult race one, Dr. Johnson reported that 85% of 91 residents working in an ED had an implicit pro-White/anti-Black bias in the test on adult race, but an even higher bias score – 91% – with child race.

Research has found that even children’s names can conjure implicit bias when it comes to stereotypically “White-sounding” names versus stereotypically “Black-sounding names.”

The implicit bias among clinicians extends beyond care of different children. Research has also identified association between higher implicit bias scores and less interpersonal treatment, less supportive communication, less patient-centered communication, poorer patient ratings of satisfaction, and greater patient-reported difficulty with following recommendations, Dr. Johnson said.

“I want you to think about that because I know that when we’re engaging with parents and making decisions about whether or not we’re going to do a skeletal survey or report someone for it, there is a lot of subjectivity that comes into play with how you’re interacting with families,” Dr. Johnson said. Those verbal and nonverbal cues may be triggering to parents, which then affects your interaction with them. Further, research shows that these biases may impact treatment decisions as well.

Personal-mediated racism also shows up in the use of stigmatizing language, Dr. Johnson said.

“When providers read stigmatizing language in the patient’s medical records, it was associated with them having more negative attitudes about that patient,” which then influenced their clinical decision-making, she said. “So when providers got primed with stigmatizing language, they subsequently had less aggressive pain management for those patients.”
 

Clinical implications for patient care

Dr. Johnson encouraged attendees to be careful about the language and tone they use in communicating with other health care providers and during documentation in medical records. Disparities in child abuse evaluation and reporting tend to be greater in EDs with more subjective conditions, whereas disparities are lower in departments with more established protocols.

She recommended several changes to practice that can reduce the impact of implicit bias. Universal screening for child abuse can increase how many injuries are found, but usually at the cost of increased resources and radiation. Another option is use of validated clinical decision support rules to identify who is at high or low risk for maltreatment, something Dr. Johnson is working on in her research.

But it’s also important for individual providers to confront their personal biases. Evidence-based strategies for reducing bias include perspective taking, focusing on common identities with patients, using counter-stereotypical imaging, seeking increased opportunity for cross-cultural contact, and mindfulness meditation.

“When you interact with people of different backgrounds, it helps to reduce the impact of stereotypes in society about those individuals,” Dr. Johnson told attendees. It’s also important to recognize how diversity in your clinical team can reduce bias.

“We need to work with our institutions to confront racial biases in child abuse reporting and develop quality improvement projects to ensure reporting is done objectively,” Dr. Chaffee said in an interview after attending the session. “This will require training and likely policy changes, including how reports are made to child welfare and/or the police moving forward.”

Black and Latinx children are more likely to be evaluated for child abuse and referred to child protective services than their White peers, according to research discussed by Tiffani J. Johnson, MD, an assistant professor of emergency medicine at the University of California, Davis.

Darrin Klimek/Thinkstock

“These disparities in child abuse evaluation and reporting are bidirectional,” she said. “We also recognize that abuse is more likely to be unrecognized in White children.”

Dr. Johnson presented data on the health disparities in child abuse reporting in a session at the annual meeting of the American Academy of Pediatrics, held virtually this year. Health care disparities, as defined by the National Academy of Sciences, refers to differences in the quality of care between minority and nonminority populations that are not caused by clinical appropriateness, access, need, or patient preference, she explained. Instead, they result from discrimination, bias, stereotyping, and uncertainty.
 

Disparities lead to harm in all children

For example, a 2018 systematic review found that Black and other non-White children were significantly more likely than White children to be evaluated with a skeletal survey. In one of the studies included, at a large urban academic center, Black and Latinx children with accidental fractures were 8.75 times more likely to undergo a skeletal survey than White children and 4.3 times more likely to be reported to child protective services.

“And let me emphasize that these are children who were ultimately found to have accidental fractures,” Dr. Johnson said.

Meanwhile, in an analysis of known cases of head trauma, researchers found that abuse was missed in 37% of White children, compared with 19% of non-White children.

“These only represent the tip of the iceberg as a true number of cases of abuse may never really be detected because some cases are still unknown,” Dr. Johnson told attendees. And the harm of these disparities runs in both directions.

“Failing to diagnose abuse in White children clearly puts them at increased risk for return visits and return evaluations for repeated abuse by the perpetrators,” she said. But harm also can result from overreporting and investigation, including psychological trauma and a waste of limited resources. Overinvestigation also can erode family-physician relationships and perpetuate distrust of medical care in communities of color.

Yet at the same time, it’s clear that Black children, adolescents, and young adults are not protected from harm in society more generally, when at home, where they learn, or where they play, Dr. Johnson said, referencing the deaths of Breonna Taylor and Tamir Rice as examples.

KatarzynaBialasiewicz/Thinkstock

“And now we’re seeing increased evidence that children are not protected in the health care center when we think about the many disparities that have been identified in the care and outcomes of children, including the disproportionality in terms of child abuse evaluation and referrals,” Dr. Johnson said.

Racism is a root cause of that harm to Black children, she said, as the systemic structure of opportunities unfairly disadvantages some individuals and communities while unfairly advantaging others, thereby “sapping the strength of the whole society through the waste of human resources.”

Tonya Chaffee, MD, MPH, a clinical professor of health sciences at the University of California, San Francisco, who attended the session, said she particularly appreciated “seeing data on which racial/ethnic populations have child abuse reports made and the disparities that exist that are similar to what we are noticing in our own institution.”
 

Role of individual-level implicit bias and racism

While institutional and structural racism play a substantial role in health care disparities, Dr. Johnson focused primarily on the impact of personal racism when it comes to child abuse evaluations, through overt discrimination, explicit bias, implicit bias, and stigmatization. The most challenging of these to identify and acknowledge is often implicit bias, a tendency to believe, even unconsciously, that some people or ideas are better than others, which results in unfair treatment.

For example, a 2016 study found that half of medical students and residents held at least one biological belief about differences between Black and White individuals that was actually false, such as Black people having more pain tolerance or stronger bones than White people, which then affected treatment recommendations.

“Implicit bias refers to our attitudes that lie below the surface, but they can still influence our behaviors,” Dr. Johnson explained. She encouraged providers to take the implicit bias test online to learn about their own unrecognized implicit biases. These biases have a hand in influencing decisions particularly in fast-paced environments where cognitive load is high – such as EDs, where many child abuse evaluations occur.

For example, in one study Dr. Johnson led, the researchers measured implicit bias in participants before and after an ED shift to assess how cognitive load affected bias. They found that participants who care for more than 10 patients, the average score for implicit bias increased.

Similarly, “when the ED was more overcrowded, there was also increased bias at the end of the shift, compared to the beginning of the shift,” Dr. Johnson said. She asked clinicians to take into consideration that at the start of the shift, they may feel well rested and freshly caffeinated, able to suppress or overcome the biases that they know they have.

“But our biases [are] more likely to come into play with every subsequent decision that we make throughout the day when we’re engaged in clinical encounters,” such as who does and does not receive a skeletal survey or get referred to child protective services, she said.

In another study where she hypothesized that resident physicians would have less bias on the child race implicit bias test than on the adult race one, Dr. Johnson reported that 85% of 91 residents working in an ED had an implicit pro-White/anti-Black bias in the test on adult race, but an even higher bias score – 91% – with child race.

Research has found that even children’s names can conjure implicit bias when it comes to stereotypically “White-sounding” names versus stereotypically “Black-sounding names.”

The implicit bias among clinicians extends beyond care of different children. Research has also identified association between higher implicit bias scores and less interpersonal treatment, less supportive communication, less patient-centered communication, poorer patient ratings of satisfaction, and greater patient-reported difficulty with following recommendations, Dr. Johnson said.

“I want you to think about that because I know that when we’re engaging with parents and making decisions about whether or not we’re going to do a skeletal survey or report someone for it, there is a lot of subjectivity that comes into play with how you’re interacting with families,” Dr. Johnson said. Those verbal and nonverbal cues may be triggering to parents, which then affects your interaction with them. Further, research shows that these biases may impact treatment decisions as well.

Personal-mediated racism also shows up in the use of stigmatizing language, Dr. Johnson said.

“When providers read stigmatizing language in the patient’s medical records, it was associated with them having more negative attitudes about that patient,” which then influenced their clinical decision-making, she said. “So when providers got primed with stigmatizing language, they subsequently had less aggressive pain management for those patients.”
 

Clinical implications for patient care

Dr. Johnson encouraged attendees to be careful about the language and tone they use in communicating with other health care providers and during documentation in medical records. Disparities in child abuse evaluation and reporting tend to be greater in EDs with more subjective conditions, whereas disparities are lower in departments with more established protocols.

She recommended several changes to practice that can reduce the impact of implicit bias. Universal screening for child abuse can increase how many injuries are found, but usually at the cost of increased resources and radiation. Another option is use of validated clinical decision support rules to identify who is at high or low risk for maltreatment, something Dr. Johnson is working on in her research.

But it’s also important for individual providers to confront their personal biases. Evidence-based strategies for reducing bias include perspective taking, focusing on common identities with patients, using counter-stereotypical imaging, seeking increased opportunity for cross-cultural contact, and mindfulness meditation.

“When you interact with people of different backgrounds, it helps to reduce the impact of stereotypes in society about those individuals,” Dr. Johnson told attendees. It’s also important to recognize how diversity in your clinical team can reduce bias.

“We need to work with our institutions to confront racial biases in child abuse reporting and develop quality improvement projects to ensure reporting is done objectively,” Dr. Chaffee said in an interview after attending the session. “This will require training and likely policy changes, including how reports are made to child welfare and/or the police moving forward.”

Black and Latinx children are more likely to be evaluated for child abuse and referred to child protective services than their White peers, according to research discussed by Tiffani J. Johnson, MD, an assistant professor of emergency medicine at the University of California, Davis.

Darrin Klimek/Thinkstock

“These disparities in child abuse evaluation and reporting are bidirectional,” she said. “We also recognize that abuse is more likely to be unrecognized in White children.”

Dr. Johnson presented data on the health disparities in child abuse reporting in a session at the annual meeting of the American Academy of Pediatrics, held virtually this year. Health care disparities, as defined by the National Academy of Sciences, refers to differences in the quality of care between minority and nonminority populations that are not caused by clinical appropriateness, access, need, or patient preference, she explained. Instead, they result from discrimination, bias, stereotyping, and uncertainty.
 

Disparities lead to harm in all children

For example, a 2018 systematic review found that Black and other non-White children were significantly more likely than White children to be evaluated with a skeletal survey. In one of the studies included, at a large urban academic center, Black and Latinx children with accidental fractures were 8.75 times more likely to undergo a skeletal survey than White children and 4.3 times more likely to be reported to child protective services.

“And let me emphasize that these are children who were ultimately found to have accidental fractures,” Dr. Johnson said.

Meanwhile, in an analysis of known cases of head trauma, researchers found that abuse was missed in 37% of White children, compared with 19% of non-White children.

“These only represent the tip of the iceberg as a true number of cases of abuse may never really be detected because some cases are still unknown,” Dr. Johnson told attendees. And the harm of these disparities runs in both directions.

“Failing to diagnose abuse in White children clearly puts them at increased risk for return visits and return evaluations for repeated abuse by the perpetrators,” she said. But harm also can result from overreporting and investigation, including psychological trauma and a waste of limited resources. Overinvestigation also can erode family-physician relationships and perpetuate distrust of medical care in communities of color.

Yet at the same time, it’s clear that Black children, adolescents, and young adults are not protected from harm in society more generally, when at home, where they learn, or where they play, Dr. Johnson said, referencing the deaths of Breonna Taylor and Tamir Rice as examples.

KatarzynaBialasiewicz/Thinkstock

“And now we’re seeing increased evidence that children are not protected in the health care center when we think about the many disparities that have been identified in the care and outcomes of children, including the disproportionality in terms of child abuse evaluation and referrals,” Dr. Johnson said.

Racism is a root cause of that harm to Black children, she said, as the systemic structure of opportunities unfairly disadvantages some individuals and communities while unfairly advantaging others, thereby “sapping the strength of the whole society through the waste of human resources.”

Tonya Chaffee, MD, MPH, a clinical professor of health sciences at the University of California, San Francisco, who attended the session, said she particularly appreciated “seeing data on which racial/ethnic populations have child abuse reports made and the disparities that exist that are similar to what we are noticing in our own institution.”
 

Role of individual-level implicit bias and racism

While institutional and structural racism play a substantial role in health care disparities, Dr. Johnson focused primarily on the impact of personal racism when it comes to child abuse evaluations, through overt discrimination, explicit bias, implicit bias, and stigmatization. The most challenging of these to identify and acknowledge is often implicit bias, a tendency to believe, even unconsciously, that some people or ideas are better than others, which results in unfair treatment.

For example, a 2016 study found that half of medical students and residents held at least one biological belief about differences between Black and White individuals that was actually false, such as Black people having more pain tolerance or stronger bones than White people, which then affected treatment recommendations.

“Implicit bias refers to our attitudes that lie below the surface, but they can still influence our behaviors,” Dr. Johnson explained. She encouraged providers to take the implicit bias test online to learn about their own unrecognized implicit biases. These biases have a hand in influencing decisions particularly in fast-paced environments where cognitive load is high – such as EDs, where many child abuse evaluations occur.

For example, in one study Dr. Johnson led, the researchers measured implicit bias in participants before and after an ED shift to assess how cognitive load affected bias. They found that participants who care for more than 10 patients, the average score for implicit bias increased.

Similarly, “when the ED was more overcrowded, there was also increased bias at the end of the shift, compared to the beginning of the shift,” Dr. Johnson said. She asked clinicians to take into consideration that at the start of the shift, they may feel well rested and freshly caffeinated, able to suppress or overcome the biases that they know they have.

“But our biases [are] more likely to come into play with every subsequent decision that we make throughout the day when we’re engaged in clinical encounters,” such as who does and does not receive a skeletal survey or get referred to child protective services, she said.

In another study where she hypothesized that resident physicians would have less bias on the child race implicit bias test than on the adult race one, Dr. Johnson reported that 85% of 91 residents working in an ED had an implicit pro-White/anti-Black bias in the test on adult race, but an even higher bias score – 91% – with child race.

Research has found that even children’s names can conjure implicit bias when it comes to stereotypically “White-sounding” names versus stereotypically “Black-sounding names.”

The implicit bias among clinicians extends beyond care of different children. Research has also identified association between higher implicit bias scores and less interpersonal treatment, less supportive communication, less patient-centered communication, poorer patient ratings of satisfaction, and greater patient-reported difficulty with following recommendations, Dr. Johnson said.

“I want you to think about that because I know that when we’re engaging with parents and making decisions about whether or not we’re going to do a skeletal survey or report someone for it, there is a lot of subjectivity that comes into play with how you’re interacting with families,” Dr. Johnson said. Those verbal and nonverbal cues may be triggering to parents, which then affects your interaction with them. Further, research shows that these biases may impact treatment decisions as well.

Personal-mediated racism also shows up in the use of stigmatizing language, Dr. Johnson said.

“When providers read stigmatizing language in the patient’s medical records, it was associated with them having more negative attitudes about that patient,” which then influenced their clinical decision-making, she said. “So when providers got primed with stigmatizing language, they subsequently had less aggressive pain management for those patients.”
 

Clinical implications for patient care

Dr. Johnson encouraged attendees to be careful about the language and tone they use in communicating with other health care providers and during documentation in medical records. Disparities in child abuse evaluation and reporting tend to be greater in EDs with more subjective conditions, whereas disparities are lower in departments with more established protocols.

She recommended several changes to practice that can reduce the impact of implicit bias. Universal screening for child abuse can increase how many injuries are found, but usually at the cost of increased resources and radiation. Another option is use of validated clinical decision support rules to identify who is at high or low risk for maltreatment, something Dr. Johnson is working on in her research.

But it’s also important for individual providers to confront their personal biases. Evidence-based strategies for reducing bias include perspective taking, focusing on common identities with patients, using counter-stereotypical imaging, seeking increased opportunity for cross-cultural contact, and mindfulness meditation.

“When you interact with people of different backgrounds, it helps to reduce the impact of stereotypes in society about those individuals,” Dr. Johnson told attendees. It’s also important to recognize how diversity in your clinical team can reduce bias.

“We need to work with our institutions to confront racial biases in child abuse reporting and develop quality improvement projects to ensure reporting is done objectively,” Dr. Chaffee said in an interview after attending the session. “This will require training and likely policy changes, including how reports are made to child welfare and/or the police moving forward.”

Pediatric Hospital Medicine (PHM) only recently became a recognized pediatric subspecialty with the first certification exam taking place in 2019. As a new field composed largely of women, it has a unique opportunity to set the example of how to operationalize gender equity in leadership by tracking metrics, creating intentional processes for hiring and promotion, and implementing policies in a transparent way.

In this issue of the Journal of Hospital Medicine, Allan et al¹ report that women, who comprise 70% of the field, appear proportionally represented in associate/assistant but not senior leadership roles when compared to the PHM field at large. Eighty-one percent of associate division directors but only 55% of division directors were women, and 82% of assistant fellowship directors but only 66% of fellowship directors were women. These downward trends in the proportion of women in leadership roles as the roles become more senior is not an unfamiliar pattern. This echoes academic pediatric positions more broadly: women’s representation slides from 63% of active physicians to approximately 57% active faculty and then to 26% as department chairs.² The same story holds true for deans’ offices in US medical schools, where 34% of associate deans are women and yet only 18% of deans are women. The number of women deans has only increased by about one each year, on average, since 2009.³ C-suite leadership roles in healthcare mimic this same downward trajectory.⁴ Burden et al found that while there was equal gender representation of hospitalists and general internists who worked in university hospitals, women led only a minority of (adult) hospital medicine (16%) or general internal medicine (35%) sections or divisions at university hospitals.⁵ Women with intersectionality, such as Black women and other women of color, are even more grossly underrepresented in leadership roles.

How can we change this pattern to ensure that leadership in PHM, and in medicine in general, represents diverse voices and reflects the community it serves? Allan et al have established an important baseline for tracking gender equity in PHM. Institutions, organizations, and societies must now prioritize, value and promote a culture of diversity, inclusivity, sponsorship, and allyship. For example, institutions can create and enforce policies in which compensation and promotion are tied to a leader’s achievement of transparent gender equity and diversity targets to ensure accountability. Institutions should commit dedicated and substantive funding to diversity, equity, and inclusion efforts and provide a regular diversity report that tracks gender distribution, hiring and attrition, and representation in leadership. Institutions should implement “best search practices” for all leadership positions. Additionally, all faculty should receive regular and ongoing professional development planning to enhance academic productivity and professional satisfaction and improve retention.

Women in medicine disproportionately experience many issues, including harassment, bias, and childcare and household responsibilities, that adversely affect their career trajectory. PHM is in a unique position to trailblaze a new framework for ensuring gender equity in its field. Let’s not lose this opportunity to set a new course that other specialties can follow.

Pediatric Hospital Medicine (PHM) only recently became a recognized pediatric subspecialty with the first certification exam taking place in 2019. As a new field composed largely of women, it has a unique opportunity to set the example of how to operationalize gender equity in leadership by tracking metrics, creating intentional processes for hiring and promotion, and implementing policies in a transparent way.

In this issue of the Journal of Hospital Medicine, Allan et al¹ report that women, who comprise 70% of the field, appear proportionally represented in associate/assistant but not senior leadership roles when compared to the PHM field at large. Eighty-one percent of associate division directors but only 55% of division directors were women, and 82% of assistant fellowship directors but only 66% of fellowship directors were women. These downward trends in the proportion of women in leadership roles as the roles become more senior is not an unfamiliar pattern. This echoes academic pediatric positions more broadly: women’s representation slides from 63% of active physicians to approximately 57% active faculty and then to 26% as department chairs.² The same story holds true for deans’ offices in US medical schools, where 34% of associate deans are women and yet only 18% of deans are women. The number of women deans has only increased by about one each year, on average, since 2009.³ C-suite leadership roles in healthcare mimic this same downward trajectory.⁴ Burden et al found that while there was equal gender representation of hospitalists and general internists who worked in university hospitals, women led only a minority of (adult) hospital medicine (16%) or general internal medicine (35%) sections or divisions at university hospitals.⁵ Women with intersectionality, such as Black women and other women of color, are even more grossly underrepresented in leadership roles.

How can we change this pattern to ensure that leadership in PHM, and in medicine in general, represents diverse voices and reflects the community it serves? Allan et al have established an important baseline for tracking gender equity in PHM. Institutions, organizations, and societies must now prioritize, value and promote a culture of diversity, inclusivity, sponsorship, and allyship. For example, institutions can create and enforce policies in which compensation and promotion are tied to a leader’s achievement of transparent gender equity and diversity targets to ensure accountability. Institutions should commit dedicated and substantive funding to diversity, equity, and inclusion efforts and provide a regular diversity report that tracks gender distribution, hiring and attrition, and representation in leadership. Institutions should implement “best search practices” for all leadership positions. Additionally, all faculty should receive regular and ongoing professional development planning to enhance academic productivity and professional satisfaction and improve retention.

Women in medicine disproportionately experience many issues, including harassment, bias, and childcare and household responsibilities, that adversely affect their career trajectory. PHM is in a unique position to trailblaze a new framework for ensuring gender equity in its field. Let’s not lose this opportunity to set a new course that other specialties can follow.

Pediatric Hospital Medicine (PHM) only recently became a recognized pediatric subspecialty with the first certification exam taking place in 2019. As a new field composed largely of women, it has a unique opportunity to set the example of how to operationalize gender equity in leadership by tracking metrics, creating intentional processes for hiring and promotion, and implementing policies in a transparent way.

In this issue of the Journal of Hospital Medicine, Allan et al¹ report that women, who comprise 70% of the field, appear proportionally represented in associate/assistant but not senior leadership roles when compared to the PHM field at large. Eighty-one percent of associate division directors but only 55% of division directors were women, and 82% of assistant fellowship directors but only 66% of fellowship directors were women. These downward trends in the proportion of women in leadership roles as the roles become more senior is not an unfamiliar pattern. This echoes academic pediatric positions more broadly: women’s representation slides from 63% of active physicians to approximately 57% active faculty and then to 26% as department chairs.² The same story holds true for deans’ offices in US medical schools, where 34% of associate deans are women and yet only 18% of deans are women. The number of women deans has only increased by about one each year, on average, since 2009.³ C-suite leadership roles in healthcare mimic this same downward trajectory.⁴ Burden et al found that while there was equal gender representation of hospitalists and general internists who worked in university hospitals, women led only a minority of (adult) hospital medicine (16%) or general internal medicine (35%) sections or divisions at university hospitals.⁵ Women with intersectionality, such as Black women and other women of color, are even more grossly underrepresented in leadership roles.

How can we change this pattern to ensure that leadership in PHM, and in medicine in general, represents diverse voices and reflects the community it serves? Allan et al have established an important baseline for tracking gender equity in PHM. Institutions, organizations, and societies must now prioritize, value and promote a culture of diversity, inclusivity, sponsorship, and allyship. For example, institutions can create and enforce policies in which compensation and promotion are tied to a leader’s achievement of transparent gender equity and diversity targets to ensure accountability. Institutions should commit dedicated and substantive funding to diversity, equity, and inclusion efforts and provide a regular diversity report that tracks gender distribution, hiring and attrition, and representation in leadership. Institutions should implement “best search practices” for all leadership positions. Additionally, all faculty should receive regular and ongoing professional development planning to enhance academic productivity and professional satisfaction and improve retention.

Women in medicine disproportionately experience many issues, including harassment, bias, and childcare and household responsibilities, that adversely affect their career trajectory. PHM is in a unique position to trailblaze a new framework for ensuring gender equity in its field. Let’s not lose this opportunity to set a new course that other specialties can follow.

Nearly 30% of healthcare spending may relate to overuse of unnecessary medical interventions.¹ Deimplementation of such practices can reduce negative outcomes and unnecessary costs.² Nonetheless, changing practice is difficult. Why is it so hard to stop doing things that don’t work? A variety of factors influences deimplementation, and research aiming to identify and understand these factors can promote the delivery of more appropriate care.²

In this issue, Wolk et al describe barriers and facilitators in deimplementing non-guideline adherent use of continuous pulse oximetry (CPO) in pediatric patients with bronchiolitis not requiring supplemental oxygen.³ Unnecessary CPO use for these patients is associated with increased hospitalization rates, length of stay, alarm fatigue, and costs, without evidence of improved clinical outcomes. Despite these data, many hospitals participating in the multicenter Eliminating Monitor Overuse study struggled to decrease CPO usage. The authors conducted semistructured interviews with a broad range of stakeholders from 12 hospitals, representing a variety of institutions with low and high CPO utilization rates.

Specific barriers to deimplementation included institutional factors, eg, unclear or missing guidelines, a culture of high utilization, and challenges educating medical staff. Perceived parental discomfort with stopping CPO was also observed. Four key facilitators were noted: strong institutional leadership, evidence-based guidelines, electronic health record order sets or reminders, and clear institutional policy. These results are similar to other deimplementation studies.

A commonality to deimplementation studies is the difficulty of changing practice. Much like implementation, deimplementation requires multipronged approaches that are sensitive to contextual factors. Interventions must account for local conditions, such as resource availability, practice norms, current workflows and processes of care, relationships among clinicians, and leadership, to create feasible and sustainable change.

Deimplementation may be even more challenging than implementation of new practices, however, because of loss aversion—the tendency to prefer avoiding losses to acquiring equivalent gains. “Taking away” something that clinicians are used to, even when proven to not be helpful, can feel uncomfortable, hindering adoption. Rather than simply discontinuing a practice, replacing it with a better option may help to overcome behavioral inertia and motivate change.

Underscoring the importance of local influences, clinicians often respond more to their close colleagues’ practices than to knowledge of national guidelines. Leveraging existing peer networks can facilitate collaboration, learning, and behavior change.⁴ Nudge strategies, in which local contexts are primed to promote desired behaviors, are also increasingly used.⁴ Priming has been effective in deimplementation efforts in medication prescribing and diagnostic testing.⁴

Including patients’ and families’ perspectives in deimplementation research is critical to practice change. Because diagnostic and treatment plans occur in the context of collaborative decision-making with patients, caregivers, and families, these groups are critical to engage in deimplementation efforts.

Hospitalists’ efforts at the front line of improvement require us to become more proficient in not only adopting evidence-based practices, but also in discontinuing ineffective ones. Identifying what we should stop doing is only the first step. Deimplementation is critical to this effort. Wolk et al provide insights into factors that influence deimplementation success. However, more work is needed, particularly regarding adapting approaches to local contexts, minimizing perceived loss, leveraging local conditions to shape behavior, and partnering with patients and families to achieve higher-value care.

Nearly 30% of healthcare spending may relate to overuse of unnecessary medical interventions.¹ Deimplementation of such practices can reduce negative outcomes and unnecessary costs.² Nonetheless, changing practice is difficult. Why is it so hard to stop doing things that don’t work? A variety of factors influences deimplementation, and research aiming to identify and understand these factors can promote the delivery of more appropriate care.²

In this issue, Wolk et al describe barriers and facilitators in deimplementing non-guideline adherent use of continuous pulse oximetry (CPO) in pediatric patients with bronchiolitis not requiring supplemental oxygen.³ Unnecessary CPO use for these patients is associated with increased hospitalization rates, length of stay, alarm fatigue, and costs, without evidence of improved clinical outcomes. Despite these data, many hospitals participating in the multicenter Eliminating Monitor Overuse study struggled to decrease CPO usage. The authors conducted semistructured interviews with a broad range of stakeholders from 12 hospitals, representing a variety of institutions with low and high CPO utilization rates.

Specific barriers to deimplementation included institutional factors, eg, unclear or missing guidelines, a culture of high utilization, and challenges educating medical staff. Perceived parental discomfort with stopping CPO was also observed. Four key facilitators were noted: strong institutional leadership, evidence-based guidelines, electronic health record order sets or reminders, and clear institutional policy. These results are similar to other deimplementation studies.

A commonality to deimplementation studies is the difficulty of changing practice. Much like implementation, deimplementation requires multipronged approaches that are sensitive to contextual factors. Interventions must account for local conditions, such as resource availability, practice norms, current workflows and processes of care, relationships among clinicians, and leadership, to create feasible and sustainable change.

Deimplementation may be even more challenging than implementation of new practices, however, because of loss aversion—the tendency to prefer avoiding losses to acquiring equivalent gains. “Taking away” something that clinicians are used to, even when proven to not be helpful, can feel uncomfortable, hindering adoption. Rather than simply discontinuing a practice, replacing it with a better option may help to overcome behavioral inertia and motivate change.

Underscoring the importance of local influences, clinicians often respond more to their close colleagues’ practices than to knowledge of national guidelines. Leveraging existing peer networks can facilitate collaboration, learning, and behavior change.⁴ Nudge strategies, in which local contexts are primed to promote desired behaviors, are also increasingly used.⁴ Priming has been effective in deimplementation efforts in medication prescribing and diagnostic testing.⁴

Including patients’ and families’ perspectives in deimplementation research is critical to practice change. Because diagnostic and treatment plans occur in the context of collaborative decision-making with patients, caregivers, and families, these groups are critical to engage in deimplementation efforts.

Hospitalists’ efforts at the front line of improvement require us to become more proficient in not only adopting evidence-based practices, but also in discontinuing ineffective ones. Identifying what we should stop doing is only the first step. Deimplementation is critical to this effort. Wolk et al provide insights into factors that influence deimplementation success. However, more work is needed, particularly regarding adapting approaches to local contexts, minimizing perceived loss, leveraging local conditions to shape behavior, and partnering with patients and families to achieve higher-value care.

Nearly 30% of healthcare spending may relate to overuse of unnecessary medical interventions.¹ Deimplementation of such practices can reduce negative outcomes and unnecessary costs.² Nonetheless, changing practice is difficult. Why is it so hard to stop doing things that don’t work? A variety of factors influences deimplementation, and research aiming to identify and understand these factors can promote the delivery of more appropriate care.²

In this issue, Wolk et al describe barriers and facilitators in deimplementing non-guideline adherent use of continuous pulse oximetry (CPO) in pediatric patients with bronchiolitis not requiring supplemental oxygen.³ Unnecessary CPO use for these patients is associated with increased hospitalization rates, length of stay, alarm fatigue, and costs, without evidence of improved clinical outcomes. Despite these data, many hospitals participating in the multicenter Eliminating Monitor Overuse study struggled to decrease CPO usage. The authors conducted semistructured interviews with a broad range of stakeholders from 12 hospitals, representing a variety of institutions with low and high CPO utilization rates.

Specific barriers to deimplementation included institutional factors, eg, unclear or missing guidelines, a culture of high utilization, and challenges educating medical staff. Perceived parental discomfort with stopping CPO was also observed. Four key facilitators were noted: strong institutional leadership, evidence-based guidelines, electronic health record order sets or reminders, and clear institutional policy. These results are similar to other deimplementation studies.

A commonality to deimplementation studies is the difficulty of changing practice. Much like implementation, deimplementation requires multipronged approaches that are sensitive to contextual factors. Interventions must account for local conditions, such as resource availability, practice norms, current workflows and processes of care, relationships among clinicians, and leadership, to create feasible and sustainable change.

Deimplementation may be even more challenging than implementation of new practices, however, because of loss aversion—the tendency to prefer avoiding losses to acquiring equivalent gains. “Taking away” something that clinicians are used to, even when proven to not be helpful, can feel uncomfortable, hindering adoption. Rather than simply discontinuing a practice, replacing it with a better option may help to overcome behavioral inertia and motivate change.

Underscoring the importance of local influences, clinicians often respond more to their close colleagues’ practices than to knowledge of national guidelines. Leveraging existing peer networks can facilitate collaboration, learning, and behavior change.⁴ Nudge strategies, in which local contexts are primed to promote desired behaviors, are also increasingly used.⁴ Priming has been effective in deimplementation efforts in medication prescribing and diagnostic testing.⁴

Including patients’ and families’ perspectives in deimplementation research is critical to practice change. Because diagnostic and treatment plans occur in the context of collaborative decision-making with patients, caregivers, and families, these groups are critical to engage in deimplementation efforts.

Hospitalists’ efforts at the front line of improvement require us to become more proficient in not only adopting evidence-based practices, but also in discontinuing ineffective ones. Identifying what we should stop doing is only the first step. Deimplementation is critical to this effort. Wolk et al provide insights into factors that influence deimplementation success. However, more work is needed, particularly regarding adapting approaches to local contexts, minimizing perceived loss, leveraging local conditions to shape behavior, and partnering with patients and families to achieve higher-value care.