MDedge Pediatrics

It’s likely the United States will see another surge of COVID-19 this winter, warned Christopher Murray, MD, director of the Institute for Health Metrics and Evaluation (IHME) at the University of Washington in Seattle.

Speaking at the national conference of State of Reform on April 8, Dr. Murray cited the seasonality of the SARS-CoV-2 virus, which wanes in the summer and waxes in the winter. The “optimistic forecast” of IHME, which has modeled the course of the pandemic for the past 13 months, is that daily deaths will rise a bit in the next month, then decline from May through August, he said.

“Summer should be fairly quiet in terms of COVID, if vaccinations rise and people don’t stop wearing masks,” Dr. Murray said.

But he added that “a considerable surge will occur over next winter,” because the new variants are more transmissible, and people will likely relax social distancing and mask wearing. The IHME predicts that the percentage of Americans who usually don masks will decline from 73% today to 21% by Aug. 1.

With a rapid decline in mask use and a rise in mobility, there will still be more than 1,000 deaths each day by July 1, Dr. Murray said. In a forecast released the day after Dr. Murray spoke, the IHME predicted that by Aug. 1, there will be a total of 618,523 U.S. deaths from COVID-19. Deaths could be as high as 696,651 if mobility among the vaccinated returns to prepandemic levels, the institute forecasts.

Based on cell phone data, Dr. Murray said, the amount of mobility in the United States has already risen to the level of March 2020, when the pandemic was just getting underway.
 

Decreased infections

If there’s one piece of good news in the latest IHME report, it’s that the estimated number of people infected (including those not tested) will drop from 111,581 today to a projected 17,502 on Aug. 1. But in a worst-case scenario, with sharply higher mobility among vaccinated people, the case count on that date would only fall to 73,842.

The SARS-CoV-2 variants are another factor of concern. Dr. Murray distinguished between variants like the one first identified in the U.K. (B.1.1.7) and other “escape variants.”

B.1.1.7, which is now the dominant strain in the United States, increases transmission but doesn’t necessarily escape the immune system or vaccines, he explained.

In contrast, if someone is infected with a variant such as the South African or the Brazilian mutations, he said, a previous COVID-19 infection might not protect the person, and vaccines are less effective against those variants.

Cross-variant immunity may range from 0% to 60% for escape variants, based on the slim amount of data now available, Dr. Murray said. In his view, these variants will be the long-term driver of the pandemic in the United States, while the United Kingdom variant is the short-term driver.

The latest data, he said, show that the Pfizer/BioNTech and Moderna vaccines are 75% effective against the escape variants, with lower efficacy for other vaccines. But booster shots may still be required to protect people against some variants.
 

Human factors

Human behavior will also help determine the course of the pandemic, he noted. Vaccine hesitancy, for example, is still high in the United States.

By the end of May, he predicted, about 180 million people will have received about two doses of vaccine. After that, he said, “vaccination will flatline due to lack of demand.” The two unknowns are how much campaigns to promote vaccination will increase vaccine confidence, and when children will be vaccinated.

In the United States, he said, 69% of adults have been vaccinated or want to get a shot. But that percentage has dropped 5 points since February, and vaccine confidence varies by state.

Dr. Murray emphasized that the winter surge he predicts can be blocked if people change their behaviors. These include a rise in vaccine confidence to 80% and continued mask wearing by most people.

However, if vaccine confidence and mask wearing decline, state governments continue to drop social distancing rules, and the uptake of boosters is low, the winter surge could be more serious, he said.
 

Double surge

Murray also raised the possibility of a double surge of COVID-19 and influenza this winter. Widely expected last winter, this double surge never materialized here or elsewhere, partly because of mask wearing. But Dr. Murray said it could happen this year: History shows that the flu tends to be stronger in years after weak outbreaks.

He advised hospitals to prepare now for whatever might come later this year. Public health authorities, he said, should speed up vaccination, monitor variants closely with additional sequencing, and try to modify behavior in high-risk groups.

Asked to explain the recent surge of COVID-19 cases in Michigan, Dr. Murray attributed it partly to the spread of the B.1.1.7 (U.K.) variant. But he noted that the U.K. variant has expanded even more widely in some other states that haven’t had an explosive surge like Michigan’s.

Moreover, he noted, Michigan doesn’t have low mask use or high mobility. So the upward spiral of COVID-19 infections there is very concerning, he said.

In regard to the role of children as reservoirs of the virus, Dr. Murray pointed out that views on this have changed around the world. For a while, people thought kids didn’t spread COVID-19 very much. That view shifted when U.K. data showed that child transmission of the B.1.1.7 variant increased by half to 9% of contacts in comparison with the original virus strain.

Dutch data, similarly, showed schools contributing to the latest outbreaks, and some European nations have closed schools. In the United States, the trend is to open them.

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

It’s likely the United States will see another surge of COVID-19 this winter, warned Christopher Murray, MD, director of the Institute for Health Metrics and Evaluation (IHME) at the University of Washington in Seattle.

Speaking at the national conference of State of Reform on April 8, Dr. Murray cited the seasonality of the SARS-CoV-2 virus, which wanes in the summer and waxes in the winter. The “optimistic forecast” of IHME, which has modeled the course of the pandemic for the past 13 months, is that daily deaths will rise a bit in the next month, then decline from May through August, he said.

“Summer should be fairly quiet in terms of COVID, if vaccinations rise and people don’t stop wearing masks,” Dr. Murray said.

But he added that “a considerable surge will occur over next winter,” because the new variants are more transmissible, and people will likely relax social distancing and mask wearing. The IHME predicts that the percentage of Americans who usually don masks will decline from 73% today to 21% by Aug. 1.

With a rapid decline in mask use and a rise in mobility, there will still be more than 1,000 deaths each day by July 1, Dr. Murray said. In a forecast released the day after Dr. Murray spoke, the IHME predicted that by Aug. 1, there will be a total of 618,523 U.S. deaths from COVID-19. Deaths could be as high as 696,651 if mobility among the vaccinated returns to prepandemic levels, the institute forecasts.

Based on cell phone data, Dr. Murray said, the amount of mobility in the United States has already risen to the level of March 2020, when the pandemic was just getting underway.
 

Decreased infections

If there’s one piece of good news in the latest IHME report, it’s that the estimated number of people infected (including those not tested) will drop from 111,581 today to a projected 17,502 on Aug. 1. But in a worst-case scenario, with sharply higher mobility among vaccinated people, the case count on that date would only fall to 73,842.

The SARS-CoV-2 variants are another factor of concern. Dr. Murray distinguished between variants like the one first identified in the U.K. (B.1.1.7) and other “escape variants.”

B.1.1.7, which is now the dominant strain in the United States, increases transmission but doesn’t necessarily escape the immune system or vaccines, he explained.

In contrast, if someone is infected with a variant such as the South African or the Brazilian mutations, he said, a previous COVID-19 infection might not protect the person, and vaccines are less effective against those variants.

Cross-variant immunity may range from 0% to 60% for escape variants, based on the slim amount of data now available, Dr. Murray said. In his view, these variants will be the long-term driver of the pandemic in the United States, while the United Kingdom variant is the short-term driver.

The latest data, he said, show that the Pfizer/BioNTech and Moderna vaccines are 75% effective against the escape variants, with lower efficacy for other vaccines. But booster shots may still be required to protect people against some variants.
 

Human factors

Human behavior will also help determine the course of the pandemic, he noted. Vaccine hesitancy, for example, is still high in the United States.

By the end of May, he predicted, about 180 million people will have received about two doses of vaccine. After that, he said, “vaccination will flatline due to lack of demand.” The two unknowns are how much campaigns to promote vaccination will increase vaccine confidence, and when children will be vaccinated.

In the United States, he said, 69% of adults have been vaccinated or want to get a shot. But that percentage has dropped 5 points since February, and vaccine confidence varies by state.

Dr. Murray emphasized that the winter surge he predicts can be blocked if people change their behaviors. These include a rise in vaccine confidence to 80% and continued mask wearing by most people.

However, if vaccine confidence and mask wearing decline, state governments continue to drop social distancing rules, and the uptake of boosters is low, the winter surge could be more serious, he said.
 

Double surge

Murray also raised the possibility of a double surge of COVID-19 and influenza this winter. Widely expected last winter, this double surge never materialized here or elsewhere, partly because of mask wearing. But Dr. Murray said it could happen this year: History shows that the flu tends to be stronger in years after weak outbreaks.

He advised hospitals to prepare now for whatever might come later this year. Public health authorities, he said, should speed up vaccination, monitor variants closely with additional sequencing, and try to modify behavior in high-risk groups.

Asked to explain the recent surge of COVID-19 cases in Michigan, Dr. Murray attributed it partly to the spread of the B.1.1.7 (U.K.) variant. But he noted that the U.K. variant has expanded even more widely in some other states that haven’t had an explosive surge like Michigan’s.

Moreover, he noted, Michigan doesn’t have low mask use or high mobility. So the upward spiral of COVID-19 infections there is very concerning, he said.

In regard to the role of children as reservoirs of the virus, Dr. Murray pointed out that views on this have changed around the world. For a while, people thought kids didn’t spread COVID-19 very much. That view shifted when U.K. data showed that child transmission of the B.1.1.7 variant increased by half to 9% of contacts in comparison with the original virus strain.

Dutch data, similarly, showed schools contributing to the latest outbreaks, and some European nations have closed schools. In the United States, the trend is to open them.

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

It’s likely the United States will see another surge of COVID-19 this winter, warned Christopher Murray, MD, director of the Institute for Health Metrics and Evaluation (IHME) at the University of Washington in Seattle.

Speaking at the national conference of State of Reform on April 8, Dr. Murray cited the seasonality of the SARS-CoV-2 virus, which wanes in the summer and waxes in the winter. The “optimistic forecast” of IHME, which has modeled the course of the pandemic for the past 13 months, is that daily deaths will rise a bit in the next month, then decline from May through August, he said.

“Summer should be fairly quiet in terms of COVID, if vaccinations rise and people don’t stop wearing masks,” Dr. Murray said.

But he added that “a considerable surge will occur over next winter,” because the new variants are more transmissible, and people will likely relax social distancing and mask wearing. The IHME predicts that the percentage of Americans who usually don masks will decline from 73% today to 21% by Aug. 1.

With a rapid decline in mask use and a rise in mobility, there will still be more than 1,000 deaths each day by July 1, Dr. Murray said. In a forecast released the day after Dr. Murray spoke, the IHME predicted that by Aug. 1, there will be a total of 618,523 U.S. deaths from COVID-19. Deaths could be as high as 696,651 if mobility among the vaccinated returns to prepandemic levels, the institute forecasts.

Based on cell phone data, Dr. Murray said, the amount of mobility in the United States has already risen to the level of March 2020, when the pandemic was just getting underway.
 

Decreased infections

If there’s one piece of good news in the latest IHME report, it’s that the estimated number of people infected (including those not tested) will drop from 111,581 today to a projected 17,502 on Aug. 1. But in a worst-case scenario, with sharply higher mobility among vaccinated people, the case count on that date would only fall to 73,842.

The SARS-CoV-2 variants are another factor of concern. Dr. Murray distinguished between variants like the one first identified in the U.K. (B.1.1.7) and other “escape variants.”

B.1.1.7, which is now the dominant strain in the United States, increases transmission but doesn’t necessarily escape the immune system or vaccines, he explained.

In contrast, if someone is infected with a variant such as the South African or the Brazilian mutations, he said, a previous COVID-19 infection might not protect the person, and vaccines are less effective against those variants.

Cross-variant immunity may range from 0% to 60% for escape variants, based on the slim amount of data now available, Dr. Murray said. In his view, these variants will be the long-term driver of the pandemic in the United States, while the United Kingdom variant is the short-term driver.

The latest data, he said, show that the Pfizer/BioNTech and Moderna vaccines are 75% effective against the escape variants, with lower efficacy for other vaccines. But booster shots may still be required to protect people against some variants.
 

Human factors

Human behavior will also help determine the course of the pandemic, he noted. Vaccine hesitancy, for example, is still high in the United States.

By the end of May, he predicted, about 180 million people will have received about two doses of vaccine. After that, he said, “vaccination will flatline due to lack of demand.” The two unknowns are how much campaigns to promote vaccination will increase vaccine confidence, and when children will be vaccinated.

In the United States, he said, 69% of adults have been vaccinated or want to get a shot. But that percentage has dropped 5 points since February, and vaccine confidence varies by state.

Dr. Murray emphasized that the winter surge he predicts can be blocked if people change their behaviors. These include a rise in vaccine confidence to 80% and continued mask wearing by most people.

However, if vaccine confidence and mask wearing decline, state governments continue to drop social distancing rules, and the uptake of boosters is low, the winter surge could be more serious, he said.
 

Double surge

Murray also raised the possibility of a double surge of COVID-19 and influenza this winter. Widely expected last winter, this double surge never materialized here or elsewhere, partly because of mask wearing. But Dr. Murray said it could happen this year: History shows that the flu tends to be stronger in years after weak outbreaks.

He advised hospitals to prepare now for whatever might come later this year. Public health authorities, he said, should speed up vaccination, monitor variants closely with additional sequencing, and try to modify behavior in high-risk groups.

Asked to explain the recent surge of COVID-19 cases in Michigan, Dr. Murray attributed it partly to the spread of the B.1.1.7 (U.K.) variant. But he noted that the U.K. variant has expanded even more widely in some other states that haven’t had an explosive surge like Michigan’s.

Moreover, he noted, Michigan doesn’t have low mask use or high mobility. So the upward spiral of COVID-19 infections there is very concerning, he said.

In regard to the role of children as reservoirs of the virus, Dr. Murray pointed out that views on this have changed around the world. For a while, people thought kids didn’t spread COVID-19 very much. That view shifted when U.K. data showed that child transmission of the B.1.1.7 variant increased by half to 9% of contacts in comparison with the original virus strain.

Dutch data, similarly, showed schools contributing to the latest outbreaks, and some European nations have closed schools. In the United States, the trend is to open them.

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

Dietary intervention that involves the target manipulation of microbiota components may improve the growth rate in children with moderate acute malnutrition, according to new research.

Moderate acute malnutrition affects more than 30 million children worldwide, according to the Food and Nutrition Bulletin. The World Health Organization defines the condition by a weight-for-height measurement that is 2 or 3 standard deviations below the international standard.

A 2014 study published in Nature has shown that malnourishment is associated with defects in children’s gut microbiota, including having microbial communities that are immature and younger than those of their healthy counterparts. Microbiota immaturity also correlates with stunted growth.

The authors of new study, which was published in the New England Journal of Medicine on April 7, 2021, wrote that nutritional interventions and treatments, such as therapeutic calorie-dense foods, have limited effectiveness because they don’t restore growth or fully address repairing the gut microbiome.

“This work supports the notion that healthy growth of children is linked to healthy development of their gut microbiota,” study author Jeffrey Gordon, MD, director of the Edison Family Center for Genome Sciences & Systems Biology at Washington University, St. Louis, said in an interview. “This, in turn, indicates that we need to have a more encompassing view of human developmental biology – one that considers both our ‘human’ and ‘microbial’ parts.”

The study establishes the impact of microbiota repair on a child’s growth rate, which may have implications on policies related to complementary feeding practices, Dr. Gorden noted.
 

Better outcomes seen with microbiota-directed complementary food prototype

For the research, 123 children with moderate acute malnutrition aged between 12 and 18 months were randomly assigned to receive a microbiota-directed complementary food prototype (MDCF-2) or ready-to-use supplementary food (RUSF). The supplementation was given to the kids twice daily for 3 months, followed by 1 month of monitoring. They looked at the weekly rate of change in the weight-for-length z score, weight-for-age z score, mid-upper-arm circumference, length-for-age z score, medical complication, gut microbiota, and blood samples in the group to determine the effectiveness of each food intervention therapy.

They found that, of the 118 children who completed the study, those in the MDCF-2 group had better outcomes than those in the RUSF group based on greater weekly growth in z scores, indicating faster growth rates. For those in the MDCF-2 group, the mean weekly change in weight-for-length z score was 0.021, compared to the RUSF group’s 0.010. When it came to weight-for-age z score, the mean weekly change was 0.017 in the MDCF-2 group and 0.010 in the RUSF group. The mean weekly changes in the mid-upper-arm circumference and length-for-age z scores were similar in both groups.

When examining blood samples of the cohort, researchers noted that 714 proteins were significantly altered after 3-month MDCF-2 supplementation, compared with 82 proteins having shown significant alterations in the RUSF group.

Overall, the findings show that repairing gut microbiota was accompanied by improved weight gain and marked changes in circulating levels of protein biomarkers and mediators of numerous aspects of healthy growth.
 

Results need to be verified on a larger scale

Tim Joos, MD, who was not part of the study, said it is surprising that MDCF-2 was better at promoting growth than existing nutritional supplements.

“The study suggests that remedying malnutrition requires more than just ensuring adequate calorie and nutrient intake,” Dr. Joos, a pediatrician at NeighborCare Health in Seattle, noted in an interview. “It is a small study and needs to be verified on a larger scale and in more diverse locations and pediatric ages (outside of the 12- to 18-month-old cohort studied).”

Wendy S. Garrett, MD, PhD, who also didn’t participate in the study, wrote in an accompanying editorial that overarching questions remain concerning the long-lasting effects of the intervention on children’s growth trajectory and cognitive development. She also said that the study “provides an abundance of fascinating microbiome profile data, plasma protein correlates, and metadata to sift through.”

Dr. Gordon and colleagues said the findings underscore the broad effects gut microbiota has on human biology and they hope this will open the door to better definitions of wellness for infants/children.

Dr. Garrett is the Irene Heinz Given Professor of Immunology and Infectious Diseases in the departments of immunology and infectious diseases and of molecular metabolism at the Harvard School of Public Health, Boston, and she has no disclosures. Dr. Gordon is the recipient of a Thought Leader award from Agilent Technologies. Dr. Joos disclosed no relevant financial relationships.

Dietary intervention that involves the target manipulation of microbiota components may improve the growth rate in children with moderate acute malnutrition, according to new research.

Moderate acute malnutrition affects more than 30 million children worldwide, according to the Food and Nutrition Bulletin. The World Health Organization defines the condition by a weight-for-height measurement that is 2 or 3 standard deviations below the international standard.

A 2014 study published in Nature has shown that malnourishment is associated with defects in children’s gut microbiota, including having microbial communities that are immature and younger than those of their healthy counterparts. Microbiota immaturity also correlates with stunted growth.

The authors of new study, which was published in the New England Journal of Medicine on April 7, 2021, wrote that nutritional interventions and treatments, such as therapeutic calorie-dense foods, have limited effectiveness because they don’t restore growth or fully address repairing the gut microbiome.

“This work supports the notion that healthy growth of children is linked to healthy development of their gut microbiota,” study author Jeffrey Gordon, MD, director of the Edison Family Center for Genome Sciences & Systems Biology at Washington University, St. Louis, said in an interview. “This, in turn, indicates that we need to have a more encompassing view of human developmental biology – one that considers both our ‘human’ and ‘microbial’ parts.”

The study establishes the impact of microbiota repair on a child’s growth rate, which may have implications on policies related to complementary feeding practices, Dr. Gorden noted.
 

Better outcomes seen with microbiota-directed complementary food prototype

For the research, 123 children with moderate acute malnutrition aged between 12 and 18 months were randomly assigned to receive a microbiota-directed complementary food prototype (MDCF-2) or ready-to-use supplementary food (RUSF). The supplementation was given to the kids twice daily for 3 months, followed by 1 month of monitoring. They looked at the weekly rate of change in the weight-for-length z score, weight-for-age z score, mid-upper-arm circumference, length-for-age z score, medical complication, gut microbiota, and blood samples in the group to determine the effectiveness of each food intervention therapy.

They found that, of the 118 children who completed the study, those in the MDCF-2 group had better outcomes than those in the RUSF group based on greater weekly growth in z scores, indicating faster growth rates. For those in the MDCF-2 group, the mean weekly change in weight-for-length z score was 0.021, compared to the RUSF group’s 0.010. When it came to weight-for-age z score, the mean weekly change was 0.017 in the MDCF-2 group and 0.010 in the RUSF group. The mean weekly changes in the mid-upper-arm circumference and length-for-age z scores were similar in both groups.

When examining blood samples of the cohort, researchers noted that 714 proteins were significantly altered after 3-month MDCF-2 supplementation, compared with 82 proteins having shown significant alterations in the RUSF group.

Overall, the findings show that repairing gut microbiota was accompanied by improved weight gain and marked changes in circulating levels of protein biomarkers and mediators of numerous aspects of healthy growth.
 

Results need to be verified on a larger scale

Tim Joos, MD, who was not part of the study, said it is surprising that MDCF-2 was better at promoting growth than existing nutritional supplements.

“The study suggests that remedying malnutrition requires more than just ensuring adequate calorie and nutrient intake,” Dr. Joos, a pediatrician at NeighborCare Health in Seattle, noted in an interview. “It is a small study and needs to be verified on a larger scale and in more diverse locations and pediatric ages (outside of the 12- to 18-month-old cohort studied).”

Wendy S. Garrett, MD, PhD, who also didn’t participate in the study, wrote in an accompanying editorial that overarching questions remain concerning the long-lasting effects of the intervention on children’s growth trajectory and cognitive development. She also said that the study “provides an abundance of fascinating microbiome profile data, plasma protein correlates, and metadata to sift through.”

Dr. Gordon and colleagues said the findings underscore the broad effects gut microbiota has on human biology and they hope this will open the door to better definitions of wellness for infants/children.

Dr. Garrett is the Irene Heinz Given Professor of Immunology and Infectious Diseases in the departments of immunology and infectious diseases and of molecular metabolism at the Harvard School of Public Health, Boston, and she has no disclosures. Dr. Gordon is the recipient of a Thought Leader award from Agilent Technologies. Dr. Joos disclosed no relevant financial relationships.

Dietary intervention that involves the target manipulation of microbiota components may improve the growth rate in children with moderate acute malnutrition, according to new research.

Moderate acute malnutrition affects more than 30 million children worldwide, according to the Food and Nutrition Bulletin. The World Health Organization defines the condition by a weight-for-height measurement that is 2 or 3 standard deviations below the international standard.

A 2014 study published in Nature has shown that malnourishment is associated with defects in children’s gut microbiota, including having microbial communities that are immature and younger than those of their healthy counterparts. Microbiota immaturity also correlates with stunted growth.

The authors of new study, which was published in the New England Journal of Medicine on April 7, 2021, wrote that nutritional interventions and treatments, such as therapeutic calorie-dense foods, have limited effectiveness because they don’t restore growth or fully address repairing the gut microbiome.

“This work supports the notion that healthy growth of children is linked to healthy development of their gut microbiota,” study author Jeffrey Gordon, MD, director of the Edison Family Center for Genome Sciences & Systems Biology at Washington University, St. Louis, said in an interview. “This, in turn, indicates that we need to have a more encompassing view of human developmental biology – one that considers both our ‘human’ and ‘microbial’ parts.”

The study establishes the impact of microbiota repair on a child’s growth rate, which may have implications on policies related to complementary feeding practices, Dr. Gorden noted.
 

Better outcomes seen with microbiota-directed complementary food prototype

For the research, 123 children with moderate acute malnutrition aged between 12 and 18 months were randomly assigned to receive a microbiota-directed complementary food prototype (MDCF-2) or ready-to-use supplementary food (RUSF). The supplementation was given to the kids twice daily for 3 months, followed by 1 month of monitoring. They looked at the weekly rate of change in the weight-for-length z score, weight-for-age z score, mid-upper-arm circumference, length-for-age z score, medical complication, gut microbiota, and blood samples in the group to determine the effectiveness of each food intervention therapy.

They found that, of the 118 children who completed the study, those in the MDCF-2 group had better outcomes than those in the RUSF group based on greater weekly growth in z scores, indicating faster growth rates. For those in the MDCF-2 group, the mean weekly change in weight-for-length z score was 0.021, compared to the RUSF group’s 0.010. When it came to weight-for-age z score, the mean weekly change was 0.017 in the MDCF-2 group and 0.010 in the RUSF group. The mean weekly changes in the mid-upper-arm circumference and length-for-age z scores were similar in both groups.

When examining blood samples of the cohort, researchers noted that 714 proteins were significantly altered after 3-month MDCF-2 supplementation, compared with 82 proteins having shown significant alterations in the RUSF group.

Overall, the findings show that repairing gut microbiota was accompanied by improved weight gain and marked changes in circulating levels of protein biomarkers and mediators of numerous aspects of healthy growth.
 

Results need to be verified on a larger scale

Tim Joos, MD, who was not part of the study, said it is surprising that MDCF-2 was better at promoting growth than existing nutritional supplements.

“The study suggests that remedying malnutrition requires more than just ensuring adequate calorie and nutrient intake,” Dr. Joos, a pediatrician at NeighborCare Health in Seattle, noted in an interview. “It is a small study and needs to be verified on a larger scale and in more diverse locations and pediatric ages (outside of the 12- to 18-month-old cohort studied).”

Wendy S. Garrett, MD, PhD, who also didn’t participate in the study, wrote in an accompanying editorial that overarching questions remain concerning the long-lasting effects of the intervention on children’s growth trajectory and cognitive development. She also said that the study “provides an abundance of fascinating microbiome profile data, plasma protein correlates, and metadata to sift through.”

Dr. Gordon and colleagues said the findings underscore the broad effects gut microbiota has on human biology and they hope this will open the door to better definitions of wellness for infants/children.

Dr. Garrett is the Irene Heinz Given Professor of Immunology and Infectious Diseases in the departments of immunology and infectious diseases and of molecular metabolism at the Harvard School of Public Health, Boston, and she has no disclosures. Dr. Gordon is the recipient of a Thought Leader award from Agilent Technologies. Dr. Joos disclosed no relevant financial relationships.

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

This article was updated 4/13/21.

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

This article was updated 4/13/21.

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

This article was updated 4/13/21.

Secukinumab proved highly effective at improving skin symptoms and quality of life in 6- to 17-year-old patients with moderate to severe plaque psoriasis at 24 weeks of follow-up in an ongoing 4-year phase 2 clinical trial, Adam Reich, MD, PhD, reported at Innovations in Dermatology: Virtual Spring Conference 2021.

Secukinumab (Cosentyx), a fully human monoclonal antibody that inhibits interleukin-17A, is widely approved for treatment of psoriasis in adults. In August 2020, the biologic received an expanded indication in Europe for treatment of 6- to 17-year-olds. Two phase 3 clinical trials are underway in an effort to gain a similar broadened indication in the United States to help address the high unmet need for new treatments for psoriasis in the pediatric population, said Dr. Reich, professor and head of the department of dermatology at the University of Rzeszow (Poland).

He reported on 84 pediatric patients participating in the open-label, phase 2, international study. They were randomized to one of two weight-based dosing regimens. Those in the low-dose arm received secukinumab dosed at 75 mg if they weighed less than 50 kg and 150 mg if they weighed more. In the high-dose arm, patients got secukinumab 75 mg if they weighed less than 25 kg, 150 mg if they weighed 25-50 kg, and 300 mg if they tipped the scales in excess of 50 kg.

The primary endpoint in the study was the week-12 rate of at least a 75% improvement from baseline in the Psoriasis Area and Severity Index score, or PASI 75. The rates were similar: 92.9% of patients in the high-dose arm achieved this endpoint, as did 90.5% in the low-dose arm. The PASI 90 rates were 83.3% and 78%, the PASI 100 rates were 61.9% and 54.8%, and clear or almost clear skin, as measured by the Investigator Global Assessment, was achieved in 88.7% of the high- and 85.7% of the low-dose groups. In addition,61.9% of those in the high-dose secukinumab group and 50% in the low-dose group had a score of 0 or 1 on the Children’s Dermatology Life Quality Index – indicating psoriasis has no impact on daily quality of life, he said at the conference sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

At week 24, roughly 95% of patients in both the low- and high-dose secukinumab groups had achieved PASI 75s, 88% reached a PASI 90 response, and 67% were at PASI 100. Nearly 60% of the low-dose and 70% of the high-dose groups had a score of 0 or 1 on the Children’s Dermatology Life Quality Index.

Treatment-emergent adverse event rates were similar in the two study arms. Of note, there was one case of new-onset inflammatory bowel disease in the high-dose group, and one case of vulvovaginal candidiasis as well.

Discussant Bruce E. Strober, MD, PhD, said that, if secukinumab gets a pediatric indication from the Food and Drug Administration, as seems likely, it won’t alter his biologic treatment hierarchy.

“I treat a lot of kids with psoriasis. We have three approved drugs now in etanercept [Enbrel], ustekinumab [Stelara], and ixekizumab [Taltz]. My bias is still towards ustekinumab because it’s infrequently dosed and that’s a huge issue for children. You want to expose them to as few injections as possible, for obvious reasons: It’s easier for parents and other caregivers,” explained Dr. Strober, a dermatologist at Yale University, New Haven, Conn., and Central Connecticut Dermatology, Cromwell, Conn.

“The other issue is in IL-17 inhibition there has been a slight signal of inflammatory bowel disease popping up in children getting these drugs, and therefore you need to screen patients in this age group very carefully – not only the patients themselves, but their family – for IBD risk. If there is any sign of that I would move the IL-17 inhibitors to the back of the line, compared to ustekinumab and etanercept. Ustekinumab is still clearly the one that I think has to be used first line,” he said.

Dr. Strober offered a final word of advice for his colleagues: “You can’t be afraid to treat children with biologic therapies. In fact, preferentially I would use a biologic therapy over methotrexate or light therapy, which is really difficult for children.”

Dr. Reich and Dr. Strober reported receiving research grants from and serving as a consultant to numerous pharmaceutical companies, including Novartis, which markets secukinumab and funded the study.

MedscapeLIVE! and this news organization are owned by the same parent company.

Secukinumab proved highly effective at improving skin symptoms and quality of life in 6- to 17-year-old patients with moderate to severe plaque psoriasis at 24 weeks of follow-up in an ongoing 4-year phase 2 clinical trial, Adam Reich, MD, PhD, reported at Innovations in Dermatology: Virtual Spring Conference 2021.

Secukinumab (Cosentyx), a fully human monoclonal antibody that inhibits interleukin-17A, is widely approved for treatment of psoriasis in adults. In August 2020, the biologic received an expanded indication in Europe for treatment of 6- to 17-year-olds. Two phase 3 clinical trials are underway in an effort to gain a similar broadened indication in the United States to help address the high unmet need for new treatments for psoriasis in the pediatric population, said Dr. Reich, professor and head of the department of dermatology at the University of Rzeszow (Poland).

He reported on 84 pediatric patients participating in the open-label, phase 2, international study. They were randomized to one of two weight-based dosing regimens. Those in the low-dose arm received secukinumab dosed at 75 mg if they weighed less than 50 kg and 150 mg if they weighed more. In the high-dose arm, patients got secukinumab 75 mg if they weighed less than 25 kg, 150 mg if they weighed 25-50 kg, and 300 mg if they tipped the scales in excess of 50 kg.

The primary endpoint in the study was the week-12 rate of at least a 75% improvement from baseline in the Psoriasis Area and Severity Index score, or PASI 75. The rates were similar: 92.9% of patients in the high-dose arm achieved this endpoint, as did 90.5% in the low-dose arm. The PASI 90 rates were 83.3% and 78%, the PASI 100 rates were 61.9% and 54.8%, and clear or almost clear skin, as measured by the Investigator Global Assessment, was achieved in 88.7% of the high- and 85.7% of the low-dose groups. In addition,61.9% of those in the high-dose secukinumab group and 50% in the low-dose group had a score of 0 or 1 on the Children’s Dermatology Life Quality Index – indicating psoriasis has no impact on daily quality of life, he said at the conference sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

At week 24, roughly 95% of patients in both the low- and high-dose secukinumab groups had achieved PASI 75s, 88% reached a PASI 90 response, and 67% were at PASI 100. Nearly 60% of the low-dose and 70% of the high-dose groups had a score of 0 or 1 on the Children’s Dermatology Life Quality Index.

Treatment-emergent adverse event rates were similar in the two study arms. Of note, there was one case of new-onset inflammatory bowel disease in the high-dose group, and one case of vulvovaginal candidiasis as well.

Discussant Bruce E. Strober, MD, PhD, said that, if secukinumab gets a pediatric indication from the Food and Drug Administration, as seems likely, it won’t alter his biologic treatment hierarchy.

“I treat a lot of kids with psoriasis. We have three approved drugs now in etanercept [Enbrel], ustekinumab [Stelara], and ixekizumab [Taltz]. My bias is still towards ustekinumab because it’s infrequently dosed and that’s a huge issue for children. You want to expose them to as few injections as possible, for obvious reasons: It’s easier for parents and other caregivers,” explained Dr. Strober, a dermatologist at Yale University, New Haven, Conn., and Central Connecticut Dermatology, Cromwell, Conn.

“The other issue is in IL-17 inhibition there has been a slight signal of inflammatory bowel disease popping up in children getting these drugs, and therefore you need to screen patients in this age group very carefully – not only the patients themselves, but their family – for IBD risk. If there is any sign of that I would move the IL-17 inhibitors to the back of the line, compared to ustekinumab and etanercept. Ustekinumab is still clearly the one that I think has to be used first line,” he said.

Dr. Strober offered a final word of advice for his colleagues: “You can’t be afraid to treat children with biologic therapies. In fact, preferentially I would use a biologic therapy over methotrexate or light therapy, which is really difficult for children.”

Dr. Reich and Dr. Strober reported receiving research grants from and serving as a consultant to numerous pharmaceutical companies, including Novartis, which markets secukinumab and funded the study.

MedscapeLIVE! and this news organization are owned by the same parent company.

Secukinumab proved highly effective at improving skin symptoms and quality of life in 6- to 17-year-old patients with moderate to severe plaque psoriasis at 24 weeks of follow-up in an ongoing 4-year phase 2 clinical trial, Adam Reich, MD, PhD, reported at Innovations in Dermatology: Virtual Spring Conference 2021.

Secukinumab (Cosentyx), a fully human monoclonal antibody that inhibits interleukin-17A, is widely approved for treatment of psoriasis in adults. In August 2020, the biologic received an expanded indication in Europe for treatment of 6- to 17-year-olds. Two phase 3 clinical trials are underway in an effort to gain a similar broadened indication in the United States to help address the high unmet need for new treatments for psoriasis in the pediatric population, said Dr. Reich, professor and head of the department of dermatology at the University of Rzeszow (Poland).

He reported on 84 pediatric patients participating in the open-label, phase 2, international study. They were randomized to one of two weight-based dosing regimens. Those in the low-dose arm received secukinumab dosed at 75 mg if they weighed less than 50 kg and 150 mg if they weighed more. In the high-dose arm, patients got secukinumab 75 mg if they weighed less than 25 kg, 150 mg if they weighed 25-50 kg, and 300 mg if they tipped the scales in excess of 50 kg.

The primary endpoint in the study was the week-12 rate of at least a 75% improvement from baseline in the Psoriasis Area and Severity Index score, or PASI 75. The rates were similar: 92.9% of patients in the high-dose arm achieved this endpoint, as did 90.5% in the low-dose arm. The PASI 90 rates were 83.3% and 78%, the PASI 100 rates were 61.9% and 54.8%, and clear or almost clear skin, as measured by the Investigator Global Assessment, was achieved in 88.7% of the high- and 85.7% of the low-dose groups. In addition,61.9% of those in the high-dose secukinumab group and 50% in the low-dose group had a score of 0 or 1 on the Children’s Dermatology Life Quality Index – indicating psoriasis has no impact on daily quality of life, he said at the conference sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.

At week 24, roughly 95% of patients in both the low- and high-dose secukinumab groups had achieved PASI 75s, 88% reached a PASI 90 response, and 67% were at PASI 100. Nearly 60% of the low-dose and 70% of the high-dose groups had a score of 0 or 1 on the Children’s Dermatology Life Quality Index.

Treatment-emergent adverse event rates were similar in the two study arms. Of note, there was one case of new-onset inflammatory bowel disease in the high-dose group, and one case of vulvovaginal candidiasis as well.

Discussant Bruce E. Strober, MD, PhD, said that, if secukinumab gets a pediatric indication from the Food and Drug Administration, as seems likely, it won’t alter his biologic treatment hierarchy.

“I treat a lot of kids with psoriasis. We have three approved drugs now in etanercept [Enbrel], ustekinumab [Stelara], and ixekizumab [Taltz]. My bias is still towards ustekinumab because it’s infrequently dosed and that’s a huge issue for children. You want to expose them to as few injections as possible, for obvious reasons: It’s easier for parents and other caregivers,” explained Dr. Strober, a dermatologist at Yale University, New Haven, Conn., and Central Connecticut Dermatology, Cromwell, Conn.

“The other issue is in IL-17 inhibition there has been a slight signal of inflammatory bowel disease popping up in children getting these drugs, and therefore you need to screen patients in this age group very carefully – not only the patients themselves, but their family – for IBD risk. If there is any sign of that I would move the IL-17 inhibitors to the back of the line, compared to ustekinumab and etanercept. Ustekinumab is still clearly the one that I think has to be used first line,” he said.

Dr. Strober offered a final word of advice for his colleagues: “You can’t be afraid to treat children with biologic therapies. In fact, preferentially I would use a biologic therapy over methotrexate or light therapy, which is really difficult for children.”

Dr. Reich and Dr. Strober reported receiving research grants from and serving as a consultant to numerous pharmaceutical companies, including Novartis, which markets secukinumab and funded the study.

MedscapeLIVE! and this news organization are owned by the same parent company.

An experimental immunotherapy that contains a genetically altered version of herpes simplex virus type 1 (HSV-1) was associated with a doubling in median overall survival for children and adolescents with recurrent or progressive high-grade gliomas.

This is a rapidly fatal form of brain cancer. Among historical control patients, the median overall survival was only 5.3 months.

The new results show a median overall survival of 12.2 months.

They come from a phase 1 trial conducted in 12 patients aged 7-18 years who had high-grade gliomas. All of the patients received the experimental therapy, dubbed G207, which was infused directly into the brain tumors.

“In our secondary objectives, we saw promising overall survival data ... [and] we saw that G207 turned immunologically ‘cold’ tumors to ‘hot,’ ” said lead investigator Gregory K. Friedman, MD, from the University of Alabama at Birmingham.

Dr. Friedman presented the new data at the American Association for Cancer Research Annual Meeting 2021: Week 1 (Abstract CT018). The study was also published simultaneously online in the New England Journal of Medicine.

Although the number of patients in the study was small, the data from this early trial look promising, commented Howard Kaufman, MD, director of the Oncolytic Virus Research Laboratory at Massachusetts General Hospital, Boston, who was not involved in the study.

“This is just a horrendous disease that hasn’t really responded to anything, so seeing some signs of benefit as well as a pretty tolerable safety profile is a very important observation that I think merits further investigation,” he said in an interview.
 

Engineered virus

G207 is an oncolytic form of HSV-1 created through genetic engineering in which a neurovirulence gene was deleted and viral nucleotide reductase was disabled. The engineered mutations prevent HSV-1 from infecting normal cells while allowing the virus to replicate in tumor cells.

The oncolytic virus product can be inoculated directly into tumors to circumvent the blood-brain barrier, and it preferentially infects neural tissue, making it ideal for treating brain tumors, the investigators explain.

One example of this type of product is already on the market. Talimogene laherparepvec is an oncolytic HSV-1 therapy that was approved in 2015 by the Food and Drug Administration for local treatment (i.e., injection directly into the skin lesion) of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma that recurs after initial surgery.

In their article, Dr. Friedman and colleagues summarized some of the data with G207 that “provided a strong rationale for conducting a trial involving children and adolescents.

“In addition to infecting and lysing tumor cells directly, G207 can reverse tumor immune evasion, increase cross-presentation of tumor antigens, and promote an antitumor immune response even in the absence of virus permissivity,” they wrote. “A single radiation dose enhances G207 efficacy in animal models by increasing viral replication and spread.”

In preclinical studies using tumor xenografts, pediatric brain tumors were 11-fold more sensitive to G207, compared with glioblastomas in adults.

The researchers hypothesized that intratumoral G207 would increase the amount of tumor-infiltrating lymphocytes and thereby convert immunologically “cold” pediatric brain tumors to “hot” and “inflamed” tumors.
 

Phase 1 trial

The phase 1 trial included four dose cohorts of children and adolescents with a pathologically proven malignant supratentorial brain tumor of at least 1 cm in diameter that had progressed after surgery, radiotherapy, or chemotherapy.

There were three patients in each dose cohort. One cohort received 107 plaque-forming units, the second received 108 PFU, the third received 107 PFU with 5 Gy of radiation, and the fourth received 108 PFU with 5 Gy radiation.

The patients first underwent stereotactic placement of up to four intratumoral catheters. The next day, they underwent infusion of the assigned PFU doses by controlled-rate infusion over 6 hours.

For the patients who received radiation, 5 Gy were administered to the gross tumor volume within 24 hours following G207 administration.

Among the 12 patients, tumors included 10 glioblastomas, one anaplastic astrocytoma, and one high-grade glioma not otherwise specified.

Responses (radiographic, neuropathologic, or clinical) occurred in 11 of the 12 patients.

Four patients were still alive 18 months after treatment, “which exceeds the life expectancy for newly diagnosed patients,” Dr. Friedman noted. Most patients die within 1 year of being diagnosed with pediatric glioma.

The investigators also found evidence to suggest that survival may be improved for patients who experience seroconversion after exposure to HSV-1 in comparison to patients with HSV-1 antibodies from prior HSV-1 infection. The median overall survival was 18.3 months for patients who experienced seroconversion, compared with 5.1 months for three patients who, at baseline, had IgG antibodies to HSV-1.

No dose-limiting toxicities or serious adverse events attributable to G207 occurred. There were 20 grade 1 adverse events that were potentially related to G207.

There was no evidence of peripheral G207 shedding or viremia, the investigators reported.
 

Radiation effect?

Commenting on the results in an interview, Dr. Kaufman noted that the sample size (12 patients) in this study was too small to determine whether the radiation received by patients in two of the four cohorts had any additive effect.

“Whether to move forward with virus alone or to add the radiation remains an open question that I don’t think was adequately answered,” he said.

Regarding the evidence suggesting that survival was better among patients who did not have antibodies to HSV-1 at baseline, Dr. Kaufman said, “We’ve looked at that in the melanoma population but haven’t seen any correlation there, so that’s interesting.”

The finding could be related to the fact that this was a pediatric population, or it could be related to the location of the tumors in the brain.

“It’s an interesting finding, and it suggests that, in future studies, they might want to select patients who are HSV seronegative up front,” he said.

Dr. Friedman and colleagues are currently planning a phase 2 trial of G207 with 5 Gy of radiation for children and adolescents with recurrent or progressive high-grade gliomas.

The study was supported by grants from the FDA, the National Institutes of Health, Cannonball Kids’ Cancer Foundation, the Rally Foundation for Childhood Cancer Research, Hyundai Hope on Wheels, St. Baldrick’s Foundation, the Department of Defense, the Andrew McDonough B+ Foundation, and the Kaul Pediatric Research Institute; by NIH/National Cancer Institute Cancer Center support grants to the University of Alabama at Birmingham and to the Memorial Sloan Kettering Cancer Center; and by Kelsie’s Crew, Eli’s Block Party Childhood Cancer Foundation, the Eli Jackson Foundation, Jaxon’s FROG Foundation, Battle for a Cure Foundation, and Sandcastle Kids. Dr. Friedman has received grants/support from the organizations listed above, as well as from Eli Lilly and Pfizer. Dr. Kaufman disclosed no relevant financial relationships.

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

An experimental immunotherapy that contains a genetically altered version of herpes simplex virus type 1 (HSV-1) was associated with a doubling in median overall survival for children and adolescents with recurrent or progressive high-grade gliomas.

This is a rapidly fatal form of brain cancer. Among historical control patients, the median overall survival was only 5.3 months.

The new results show a median overall survival of 12.2 months.

They come from a phase 1 trial conducted in 12 patients aged 7-18 years who had high-grade gliomas. All of the patients received the experimental therapy, dubbed G207, which was infused directly into the brain tumors.

“In our secondary objectives, we saw promising overall survival data ... [and] we saw that G207 turned immunologically ‘cold’ tumors to ‘hot,’ ” said lead investigator Gregory K. Friedman, MD, from the University of Alabama at Birmingham.

Dr. Friedman presented the new data at the American Association for Cancer Research Annual Meeting 2021: Week 1 (Abstract CT018). The study was also published simultaneously online in the New England Journal of Medicine.

Although the number of patients in the study was small, the data from this early trial look promising, commented Howard Kaufman, MD, director of the Oncolytic Virus Research Laboratory at Massachusetts General Hospital, Boston, who was not involved in the study.

“This is just a horrendous disease that hasn’t really responded to anything, so seeing some signs of benefit as well as a pretty tolerable safety profile is a very important observation that I think merits further investigation,” he said in an interview.
 

Engineered virus

G207 is an oncolytic form of HSV-1 created through genetic engineering in which a neurovirulence gene was deleted and viral nucleotide reductase was disabled. The engineered mutations prevent HSV-1 from infecting normal cells while allowing the virus to replicate in tumor cells.

The oncolytic virus product can be inoculated directly into tumors to circumvent the blood-brain barrier, and it preferentially infects neural tissue, making it ideal for treating brain tumors, the investigators explain.

One example of this type of product is already on the market. Talimogene laherparepvec is an oncolytic HSV-1 therapy that was approved in 2015 by the Food and Drug Administration for local treatment (i.e., injection directly into the skin lesion) of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma that recurs after initial surgery.

In their article, Dr. Friedman and colleagues summarized some of the data with G207 that “provided a strong rationale for conducting a trial involving children and adolescents.

“In addition to infecting and lysing tumor cells directly, G207 can reverse tumor immune evasion, increase cross-presentation of tumor antigens, and promote an antitumor immune response even in the absence of virus permissivity,” they wrote. “A single radiation dose enhances G207 efficacy in animal models by increasing viral replication and spread.”

In preclinical studies using tumor xenografts, pediatric brain tumors were 11-fold more sensitive to G207, compared with glioblastomas in adults.

The researchers hypothesized that intratumoral G207 would increase the amount of tumor-infiltrating lymphocytes and thereby convert immunologically “cold” pediatric brain tumors to “hot” and “inflamed” tumors.
 

Phase 1 trial

The phase 1 trial included four dose cohorts of children and adolescents with a pathologically proven malignant supratentorial brain tumor of at least 1 cm in diameter that had progressed after surgery, radiotherapy, or chemotherapy.

There were three patients in each dose cohort. One cohort received 107 plaque-forming units, the second received 108 PFU, the third received 107 PFU with 5 Gy of radiation, and the fourth received 108 PFU with 5 Gy radiation.

The patients first underwent stereotactic placement of up to four intratumoral catheters. The next day, they underwent infusion of the assigned PFU doses by controlled-rate infusion over 6 hours.

For the patients who received radiation, 5 Gy were administered to the gross tumor volume within 24 hours following G207 administration.

Among the 12 patients, tumors included 10 glioblastomas, one anaplastic astrocytoma, and one high-grade glioma not otherwise specified.

Responses (radiographic, neuropathologic, or clinical) occurred in 11 of the 12 patients.

Four patients were still alive 18 months after treatment, “which exceeds the life expectancy for newly diagnosed patients,” Dr. Friedman noted. Most patients die within 1 year of being diagnosed with pediatric glioma.

The investigators also found evidence to suggest that survival may be improved for patients who experience seroconversion after exposure to HSV-1 in comparison to patients with HSV-1 antibodies from prior HSV-1 infection. The median overall survival was 18.3 months for patients who experienced seroconversion, compared with 5.1 months for three patients who, at baseline, had IgG antibodies to HSV-1.

No dose-limiting toxicities or serious adverse events attributable to G207 occurred. There were 20 grade 1 adverse events that were potentially related to G207.

There was no evidence of peripheral G207 shedding or viremia, the investigators reported.
 

Radiation effect?

Commenting on the results in an interview, Dr. Kaufman noted that the sample size (12 patients) in this study was too small to determine whether the radiation received by patients in two of the four cohorts had any additive effect.

“Whether to move forward with virus alone or to add the radiation remains an open question that I don’t think was adequately answered,” he said.

Regarding the evidence suggesting that survival was better among patients who did not have antibodies to HSV-1 at baseline, Dr. Kaufman said, “We’ve looked at that in the melanoma population but haven’t seen any correlation there, so that’s interesting.”

The finding could be related to the fact that this was a pediatric population, or it could be related to the location of the tumors in the brain.

“It’s an interesting finding, and it suggests that, in future studies, they might want to select patients who are HSV seronegative up front,” he said.

Dr. Friedman and colleagues are currently planning a phase 2 trial of G207 with 5 Gy of radiation for children and adolescents with recurrent or progressive high-grade gliomas.

The study was supported by grants from the FDA, the National Institutes of Health, Cannonball Kids’ Cancer Foundation, the Rally Foundation for Childhood Cancer Research, Hyundai Hope on Wheels, St. Baldrick’s Foundation, the Department of Defense, the Andrew McDonough B+ Foundation, and the Kaul Pediatric Research Institute; by NIH/National Cancer Institute Cancer Center support grants to the University of Alabama at Birmingham and to the Memorial Sloan Kettering Cancer Center; and by Kelsie’s Crew, Eli’s Block Party Childhood Cancer Foundation, the Eli Jackson Foundation, Jaxon’s FROG Foundation, Battle for a Cure Foundation, and Sandcastle Kids. Dr. Friedman has received grants/support from the organizations listed above, as well as from Eli Lilly and Pfizer. Dr. Kaufman disclosed no relevant financial relationships.

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

An experimental immunotherapy that contains a genetically altered version of herpes simplex virus type 1 (HSV-1) was associated with a doubling in median overall survival for children and adolescents with recurrent or progressive high-grade gliomas.

This is a rapidly fatal form of brain cancer. Among historical control patients, the median overall survival was only 5.3 months.

The new results show a median overall survival of 12.2 months.

They come from a phase 1 trial conducted in 12 patients aged 7-18 years who had high-grade gliomas. All of the patients received the experimental therapy, dubbed G207, which was infused directly into the brain tumors.

“In our secondary objectives, we saw promising overall survival data ... [and] we saw that G207 turned immunologically ‘cold’ tumors to ‘hot,’ ” said lead investigator Gregory K. Friedman, MD, from the University of Alabama at Birmingham.

Dr. Friedman presented the new data at the American Association for Cancer Research Annual Meeting 2021: Week 1 (Abstract CT018). The study was also published simultaneously online in the New England Journal of Medicine.

Although the number of patients in the study was small, the data from this early trial look promising, commented Howard Kaufman, MD, director of the Oncolytic Virus Research Laboratory at Massachusetts General Hospital, Boston, who was not involved in the study.

“This is just a horrendous disease that hasn’t really responded to anything, so seeing some signs of benefit as well as a pretty tolerable safety profile is a very important observation that I think merits further investigation,” he said in an interview.
 

Engineered virus

G207 is an oncolytic form of HSV-1 created through genetic engineering in which a neurovirulence gene was deleted and viral nucleotide reductase was disabled. The engineered mutations prevent HSV-1 from infecting normal cells while allowing the virus to replicate in tumor cells.

The oncolytic virus product can be inoculated directly into tumors to circumvent the blood-brain barrier, and it preferentially infects neural tissue, making it ideal for treating brain tumors, the investigators explain.

One example of this type of product is already on the market. Talimogene laherparepvec is an oncolytic HSV-1 therapy that was approved in 2015 by the Food and Drug Administration for local treatment (i.e., injection directly into the skin lesion) of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma that recurs after initial surgery.

In their article, Dr. Friedman and colleagues summarized some of the data with G207 that “provided a strong rationale for conducting a trial involving children and adolescents.

“In addition to infecting and lysing tumor cells directly, G207 can reverse tumor immune evasion, increase cross-presentation of tumor antigens, and promote an antitumor immune response even in the absence of virus permissivity,” they wrote. “A single radiation dose enhances G207 efficacy in animal models by increasing viral replication and spread.”

In preclinical studies using tumor xenografts, pediatric brain tumors were 11-fold more sensitive to G207, compared with glioblastomas in adults.

The researchers hypothesized that intratumoral G207 would increase the amount of tumor-infiltrating lymphocytes and thereby convert immunologically “cold” pediatric brain tumors to “hot” and “inflamed” tumors.
 

Phase 1 trial

The phase 1 trial included four dose cohorts of children and adolescents with a pathologically proven malignant supratentorial brain tumor of at least 1 cm in diameter that had progressed after surgery, radiotherapy, or chemotherapy.

There were three patients in each dose cohort. One cohort received 107 plaque-forming units, the second received 108 PFU, the third received 107 PFU with 5 Gy of radiation, and the fourth received 108 PFU with 5 Gy radiation.

The patients first underwent stereotactic placement of up to four intratumoral catheters. The next day, they underwent infusion of the assigned PFU doses by controlled-rate infusion over 6 hours.

For the patients who received radiation, 5 Gy were administered to the gross tumor volume within 24 hours following G207 administration.

Among the 12 patients, tumors included 10 glioblastomas, one anaplastic astrocytoma, and one high-grade glioma not otherwise specified.

Responses (radiographic, neuropathologic, or clinical) occurred in 11 of the 12 patients.

Four patients were still alive 18 months after treatment, “which exceeds the life expectancy for newly diagnosed patients,” Dr. Friedman noted. Most patients die within 1 year of being diagnosed with pediatric glioma.

The investigators also found evidence to suggest that survival may be improved for patients who experience seroconversion after exposure to HSV-1 in comparison to patients with HSV-1 antibodies from prior HSV-1 infection. The median overall survival was 18.3 months for patients who experienced seroconversion, compared with 5.1 months for three patients who, at baseline, had IgG antibodies to HSV-1.

No dose-limiting toxicities or serious adverse events attributable to G207 occurred. There were 20 grade 1 adverse events that were potentially related to G207.

There was no evidence of peripheral G207 shedding or viremia, the investigators reported.
 

Radiation effect?

Commenting on the results in an interview, Dr. Kaufman noted that the sample size (12 patients) in this study was too small to determine whether the radiation received by patients in two of the four cohorts had any additive effect.

“Whether to move forward with virus alone or to add the radiation remains an open question that I don’t think was adequately answered,” he said.

Regarding the evidence suggesting that survival was better among patients who did not have antibodies to HSV-1 at baseline, Dr. Kaufman said, “We’ve looked at that in the melanoma population but haven’t seen any correlation there, so that’s interesting.”

The finding could be related to the fact that this was a pediatric population, or it could be related to the location of the tumors in the brain.

“It’s an interesting finding, and it suggests that, in future studies, they might want to select patients who are HSV seronegative up front,” he said.

Dr. Friedman and colleagues are currently planning a phase 2 trial of G207 with 5 Gy of radiation for children and adolescents with recurrent or progressive high-grade gliomas.

The study was supported by grants from the FDA, the National Institutes of Health, Cannonball Kids’ Cancer Foundation, the Rally Foundation for Childhood Cancer Research, Hyundai Hope on Wheels, St. Baldrick’s Foundation, the Department of Defense, the Andrew McDonough B+ Foundation, and the Kaul Pediatric Research Institute; by NIH/National Cancer Institute Cancer Center support grants to the University of Alabama at Birmingham and to the Memorial Sloan Kettering Cancer Center; and by Kelsie’s Crew, Eli’s Block Party Childhood Cancer Foundation, the Eli Jackson Foundation, Jaxon’s FROG Foundation, Battle for a Cure Foundation, and Sandcastle Kids. Dr. Friedman has received grants/support from the organizations listed above, as well as from Eli Lilly and Pfizer. Dr. Kaufman disclosed no relevant financial relationships.

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

Loss of smell, loss of taste, dyspnea, and fatigue are the four most common symptoms that health care professionals in Sweden report 8 months after mild COVID-19 illness, new evidence reveals.

Approximately 1 in 10 health care workers experience one or more moderate to severe symptoms that negatively affect their quality of life, according to the study.

Nenad Cavoski/Getty Images

“We see that a substantial portion of health care workers suffer from long-term symptoms after mild COVID-19,” senior author Charlotte Thålin, MD, PhD, said in an interview. She added that loss of smell and taste “may seem trivial, but have a negative impact on work, social, and home life in the long run.”

The study is noteworthy not only for tracking the COVID-19-related experiences of health care workers over time, but also for what it did not find. There was no increased prevalence of cognitive issues – including memory or concentration – that others have linked to what’s often called long-haul COVID-19.

The research letter was published online April 7, 2021, in JAMA.

“Even if you are young and previously healthy, a mild COVID-19 infection may result in long-term consequences,” said Dr. Thålin, from the department of clinical sciences at Danderyd Hospital, Karolinska Institute, Stockholm.

The researchers did not observe an increased risk for long-term symptoms after asymptomatic COVID-19.
 

Adding to existing evidence

This research letter “adds to the growing body of literature showing that people recovering from COVID have reported a diverse array of symptoms lasting for months after initial infection,” Lekshmi Santhosh, MD, said in an interview. She is physician faculty lead at the University of California, San Francisco Post-COVID OPTIMAL Clinic.

Previous research revealed severe long-term symptoms, including heart palpitations and neurologic impairments, among people hospitalized with COVID-19. However, “there is limited data on the long-term effects after mild COVID-19, and these studies are often hampered by selection bias and without proper control groups,” Dr. Thålin said.

The absence of these more severe symptoms after mild COVID-19 is “reassuring,” she added.

The current findings are part of the ongoing COMMUNITY (COVID-19 Biomarker and Immunity) study looking at long-term immunity. Health care professionals enrolled in the research between April 15 and May 8, 2020, and have initial blood tests repeated every 4 months.

Dr. Thålin, lead author Sebastian Havervall, MD, and their colleagues compared symptom reporting between 323 hospital employees who had mild COVID-19 at least 8 months earlier with 1,072 employees who did not have COVID-19 throughout the study.

The results show that 26% of those who had COVID-19 previously had at least one moderate to severe symptom that lasted more than 2 months, compared with 9% in the control group.

The group with a history of mild COVID-19 was a median 43 years old and 83% were women. The controls were a median 47 years old and 86% were women.

“These data mirror what we have seen across long-term cohorts of patients with COVID-19 infection. Notably, mild illness among previously healthy individuals may be associated with long-term persistent symptoms,” Sarah Jolley, MD, a pulmonologist specializing in critical care at the University of Colorado Hospital in Aurora and director of the Post-COVID Clinic, said in an interview.

“In this cohort, similar to others, this seems to be more pronounced in women,” Dr. Jolley added.
 

Key findings on functioning

At 8 months, using a smartphone app, participants reported presence, duration, and severity of 23 predefined symptoms. Researchers used the Sheehan Disability Scale to gauge functional impairment.

A total of 11% participants reported at least one symptom that negatively affected work or social or home life at 8 months versus only 2% of the control group.

Seropositive participants were almost two times more likely to report that their long-term symptoms moderately to markedly disrupted their work life, 8% versus 4% of seronegative healthcare workers (relative risk, 1.8; 95%; confidence interval, 1.2-2.9).

Disruptions to a social life from long-term symptoms were 2.5 times more likely in the seropositive group. A total 15% of this cohort reported moderate to marked effects, compared with 6% of the seronegative group (RR, 2.5; 95% CI, 1.8-3.6).

The researchers also inquired about home life disruptions, which were reported by 12% of the seropositive health care workers and 5% of the seronegative participants (RR, 2.3; 95% CI, 1.6-3.4).

The study’s findings “tracks with a lot of the other work we’re seeing,” David Putrino, PT, PhD, director of rehabilitation innovation at Mount Sinai Health System in New York, said in an interview. He and his colleagues are responsible for managing the rehabilitation of patients with long COVID.

Interestingly, the proportion of people with persistent symptoms might be underestimated in this research, Dr. Putrino said. “Antibodies are not an entirely reliable biomarker. So what the researchers are using here is the most conservative measure of who may have had the virus.”

Potential recall bias and the subjective rating of symptoms were possible limitations of the study.

When asked to speculate why researchers did not find higher levels of cognitive dysfunction, Dr. Putrino said that self-reports are generally less reliable than measures like the Montreal Cognitive Assessment for detecting cognitive impairment.

Furthermore, unlike many of the people with long-haul COVID-19 whom he treats clinically – ones who are “really struggling” – the health care workers studied in Sweden are functioning well enough to perform their duties at the hospital, so the study population may not represent the population at large.
 

More research required

“More research needs to be conducted to investigate the mechanisms underlying these persistent symptoms, and several centers, including UCSF, are conducting research into why this might be,” Dr. Santhosh said.

Dr. Thålin and colleagues plan to continue following participants. “The primary aim of the COMMUNITY study is to investigate long-term immunity after COVID-19, but we will also look into possible underlying pathophysiological mechanisms behind COVID-19–related long-term symptoms,” she said.

“I hope to see that taste and smell will return,” Dr. Thålin added.

“We’re really just starting to understand the long-term effects of COVID-19,” Putrino said. “This is something we’re going to see a lot of moving forward.”

Dr. Thålin, Dr. Santhosh, Dr. Jolley, and Dr. Putrino disclosed no relevant financial relationships. The research was funded by grants from the Knut and Alice Wallenberg Foundation, Jonas and Christina af Jochnick Foundation, Leif Lundblad Family Foundation, Region Stockholm, and Erling-Persson Family Foundation.

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

Loss of smell, loss of taste, dyspnea, and fatigue are the four most common symptoms that health care professionals in Sweden report 8 months after mild COVID-19 illness, new evidence reveals.

Approximately 1 in 10 health care workers experience one or more moderate to severe symptoms that negatively affect their quality of life, according to the study.

Nenad Cavoski/Getty Images

“We see that a substantial portion of health care workers suffer from long-term symptoms after mild COVID-19,” senior author Charlotte Thålin, MD, PhD, said in an interview. She added that loss of smell and taste “may seem trivial, but have a negative impact on work, social, and home life in the long run.”

The study is noteworthy not only for tracking the COVID-19-related experiences of health care workers over time, but also for what it did not find. There was no increased prevalence of cognitive issues – including memory or concentration – that others have linked to what’s often called long-haul COVID-19.

The research letter was published online April 7, 2021, in JAMA.

“Even if you are young and previously healthy, a mild COVID-19 infection may result in long-term consequences,” said Dr. Thålin, from the department of clinical sciences at Danderyd Hospital, Karolinska Institute, Stockholm.

The researchers did not observe an increased risk for long-term symptoms after asymptomatic COVID-19.
 

Adding to existing evidence

This research letter “adds to the growing body of literature showing that people recovering from COVID have reported a diverse array of symptoms lasting for months after initial infection,” Lekshmi Santhosh, MD, said in an interview. She is physician faculty lead at the University of California, San Francisco Post-COVID OPTIMAL Clinic.

Previous research revealed severe long-term symptoms, including heart palpitations and neurologic impairments, among people hospitalized with COVID-19. However, “there is limited data on the long-term effects after mild COVID-19, and these studies are often hampered by selection bias and without proper control groups,” Dr. Thålin said.

The absence of these more severe symptoms after mild COVID-19 is “reassuring,” she added.

The current findings are part of the ongoing COMMUNITY (COVID-19 Biomarker and Immunity) study looking at long-term immunity. Health care professionals enrolled in the research between April 15 and May 8, 2020, and have initial blood tests repeated every 4 months.

Dr. Thålin, lead author Sebastian Havervall, MD, and their colleagues compared symptom reporting between 323 hospital employees who had mild COVID-19 at least 8 months earlier with 1,072 employees who did not have COVID-19 throughout the study.

The results show that 26% of those who had COVID-19 previously had at least one moderate to severe symptom that lasted more than 2 months, compared with 9% in the control group.

The group with a history of mild COVID-19 was a median 43 years old and 83% were women. The controls were a median 47 years old and 86% were women.

“These data mirror what we have seen across long-term cohorts of patients with COVID-19 infection. Notably, mild illness among previously healthy individuals may be associated with long-term persistent symptoms,” Sarah Jolley, MD, a pulmonologist specializing in critical care at the University of Colorado Hospital in Aurora and director of the Post-COVID Clinic, said in an interview.

“In this cohort, similar to others, this seems to be more pronounced in women,” Dr. Jolley added.
 

Key findings on functioning

At 8 months, using a smartphone app, participants reported presence, duration, and severity of 23 predefined symptoms. Researchers used the Sheehan Disability Scale to gauge functional impairment.

A total of 11% participants reported at least one symptom that negatively affected work or social or home life at 8 months versus only 2% of the control group.

Seropositive participants were almost two times more likely to report that their long-term symptoms moderately to markedly disrupted their work life, 8% versus 4% of seronegative healthcare workers (relative risk, 1.8; 95%; confidence interval, 1.2-2.9).

Disruptions to a social life from long-term symptoms were 2.5 times more likely in the seropositive group. A total 15% of this cohort reported moderate to marked effects, compared with 6% of the seronegative group (RR, 2.5; 95% CI, 1.8-3.6).

The researchers also inquired about home life disruptions, which were reported by 12% of the seropositive health care workers and 5% of the seronegative participants (RR, 2.3; 95% CI, 1.6-3.4).

The study’s findings “tracks with a lot of the other work we’re seeing,” David Putrino, PT, PhD, director of rehabilitation innovation at Mount Sinai Health System in New York, said in an interview. He and his colleagues are responsible for managing the rehabilitation of patients with long COVID.

Interestingly, the proportion of people with persistent symptoms might be underestimated in this research, Dr. Putrino said. “Antibodies are not an entirely reliable biomarker. So what the researchers are using here is the most conservative measure of who may have had the virus.”

Potential recall bias and the subjective rating of symptoms were possible limitations of the study.

When asked to speculate why researchers did not find higher levels of cognitive dysfunction, Dr. Putrino said that self-reports are generally less reliable than measures like the Montreal Cognitive Assessment for detecting cognitive impairment.

Furthermore, unlike many of the people with long-haul COVID-19 whom he treats clinically – ones who are “really struggling” – the health care workers studied in Sweden are functioning well enough to perform their duties at the hospital, so the study population may not represent the population at large.
 

More research required

“More research needs to be conducted to investigate the mechanisms underlying these persistent symptoms, and several centers, including UCSF, are conducting research into why this might be,” Dr. Santhosh said.

Dr. Thålin and colleagues plan to continue following participants. “The primary aim of the COMMUNITY study is to investigate long-term immunity after COVID-19, but we will also look into possible underlying pathophysiological mechanisms behind COVID-19–related long-term symptoms,” she said.

“I hope to see that taste and smell will return,” Dr. Thålin added.

“We’re really just starting to understand the long-term effects of COVID-19,” Putrino said. “This is something we’re going to see a lot of moving forward.”

Dr. Thålin, Dr. Santhosh, Dr. Jolley, and Dr. Putrino disclosed no relevant financial relationships. The research was funded by grants from the Knut and Alice Wallenberg Foundation, Jonas and Christina af Jochnick Foundation, Leif Lundblad Family Foundation, Region Stockholm, and Erling-Persson Family Foundation.

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

Loss of smell, loss of taste, dyspnea, and fatigue are the four most common symptoms that health care professionals in Sweden report 8 months after mild COVID-19 illness, new evidence reveals.

Approximately 1 in 10 health care workers experience one or more moderate to severe symptoms that negatively affect their quality of life, according to the study.

Nenad Cavoski/Getty Images

“We see that a substantial portion of health care workers suffer from long-term symptoms after mild COVID-19,” senior author Charlotte Thålin, MD, PhD, said in an interview. She added that loss of smell and taste “may seem trivial, but have a negative impact on work, social, and home life in the long run.”

The study is noteworthy not only for tracking the COVID-19-related experiences of health care workers over time, but also for what it did not find. There was no increased prevalence of cognitive issues – including memory or concentration – that others have linked to what’s often called long-haul COVID-19.

The research letter was published online April 7, 2021, in JAMA.

“Even if you are young and previously healthy, a mild COVID-19 infection may result in long-term consequences,” said Dr. Thålin, from the department of clinical sciences at Danderyd Hospital, Karolinska Institute, Stockholm.

The researchers did not observe an increased risk for long-term symptoms after asymptomatic COVID-19.
 

Adding to existing evidence

This research letter “adds to the growing body of literature showing that people recovering from COVID have reported a diverse array of symptoms lasting for months after initial infection,” Lekshmi Santhosh, MD, said in an interview. She is physician faculty lead at the University of California, San Francisco Post-COVID OPTIMAL Clinic.

Previous research revealed severe long-term symptoms, including heart palpitations and neurologic impairments, among people hospitalized with COVID-19. However, “there is limited data on the long-term effects after mild COVID-19, and these studies are often hampered by selection bias and without proper control groups,” Dr. Thålin said.

The absence of these more severe symptoms after mild COVID-19 is “reassuring,” she added.

The current findings are part of the ongoing COMMUNITY (COVID-19 Biomarker and Immunity) study looking at long-term immunity. Health care professionals enrolled in the research between April 15 and May 8, 2020, and have initial blood tests repeated every 4 months.

Dr. Thålin, lead author Sebastian Havervall, MD, and their colleagues compared symptom reporting between 323 hospital employees who had mild COVID-19 at least 8 months earlier with 1,072 employees who did not have COVID-19 throughout the study.

The results show that 26% of those who had COVID-19 previously had at least one moderate to severe symptom that lasted more than 2 months, compared with 9% in the control group.

The group with a history of mild COVID-19 was a median 43 years old and 83% were women. The controls were a median 47 years old and 86% were women.

“These data mirror what we have seen across long-term cohorts of patients with COVID-19 infection. Notably, mild illness among previously healthy individuals may be associated with long-term persistent symptoms,” Sarah Jolley, MD, a pulmonologist specializing in critical care at the University of Colorado Hospital in Aurora and director of the Post-COVID Clinic, said in an interview.

“In this cohort, similar to others, this seems to be more pronounced in women,” Dr. Jolley added.
 

Key findings on functioning

At 8 months, using a smartphone app, participants reported presence, duration, and severity of 23 predefined symptoms. Researchers used the Sheehan Disability Scale to gauge functional impairment.

A total of 11% participants reported at least one symptom that negatively affected work or social or home life at 8 months versus only 2% of the control group.

Seropositive participants were almost two times more likely to report that their long-term symptoms moderately to markedly disrupted their work life, 8% versus 4% of seronegative healthcare workers (relative risk, 1.8; 95%; confidence interval, 1.2-2.9).

Disruptions to a social life from long-term symptoms were 2.5 times more likely in the seropositive group. A total 15% of this cohort reported moderate to marked effects, compared with 6% of the seronegative group (RR, 2.5; 95% CI, 1.8-3.6).

The researchers also inquired about home life disruptions, which were reported by 12% of the seropositive health care workers and 5% of the seronegative participants (RR, 2.3; 95% CI, 1.6-3.4).

The study’s findings “tracks with a lot of the other work we’re seeing,” David Putrino, PT, PhD, director of rehabilitation innovation at Mount Sinai Health System in New York, said in an interview. He and his colleagues are responsible for managing the rehabilitation of patients with long COVID.

Interestingly, the proportion of people with persistent symptoms might be underestimated in this research, Dr. Putrino said. “Antibodies are not an entirely reliable biomarker. So what the researchers are using here is the most conservative measure of who may have had the virus.”

Potential recall bias and the subjective rating of symptoms were possible limitations of the study.

When asked to speculate why researchers did not find higher levels of cognitive dysfunction, Dr. Putrino said that self-reports are generally less reliable than measures like the Montreal Cognitive Assessment for detecting cognitive impairment.

Furthermore, unlike many of the people with long-haul COVID-19 whom he treats clinically – ones who are “really struggling” – the health care workers studied in Sweden are functioning well enough to perform their duties at the hospital, so the study population may not represent the population at large.
 

More research required

“More research needs to be conducted to investigate the mechanisms underlying these persistent symptoms, and several centers, including UCSF, are conducting research into why this might be,” Dr. Santhosh said.

Dr. Thålin and colleagues plan to continue following participants. “The primary aim of the COMMUNITY study is to investigate long-term immunity after COVID-19, but we will also look into possible underlying pathophysiological mechanisms behind COVID-19–related long-term symptoms,” she said.

“I hope to see that taste and smell will return,” Dr. Thålin added.

“We’re really just starting to understand the long-term effects of COVID-19,” Putrino said. “This is something we’re going to see a lot of moving forward.”

Dr. Thålin, Dr. Santhosh, Dr. Jolley, and Dr. Putrino disclosed no relevant financial relationships. The research was funded by grants from the Knut and Alice Wallenberg Foundation, Jonas and Christina af Jochnick Foundation, Leif Lundblad Family Foundation, Region Stockholm, and Erling-Persson Family Foundation.

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

For as many disorders of cornification and types of ichthyosis that have been shown to benefit from retinoids, a seemingly equal number have no data or show no improvement.

According to a consensus statement published in the February issue of Pediatric Dermatology, adequate data exist in the medical literature to demonstrate an improvement in use of systemic retinoids for select genotypes of congenital ichthyosiform erythroderma, epidermolytic ichthyosis, erythrokeratodermia variabilis, harlequin ichthyosis, IFAP syndrome (ichthyosis with confetti, ichthyosis follicularis, atrichia, and photophobia), KID syndrome (keratitis-ichthyosis-deafness), KLICK syndrome (keratosis linearis with ichthyosis congenita and sclerosing keratoderma), lamellar ichthyosis, loricrin keratoderma, neutral lipid storage disease with ichthyosis, recessive X-linked ichthyosis, and Sjögren-Larsson syndrome.

At the same time, limited or no data exist to support the use of systemic retinoids for CHILD syndrome (congenital hemidysplasia with ichthyosiform erythroderma and limb defects), CHIME syndrome (colobomas, heart defects, ichthyosiform dermatosis, intellectual disability, and either ear defects or epilepsy), Conradi-Hunermann-Happle syndrome, ichthyosis-hypotrichosis, ichthyosis-hypotrichosis-sclerosis cholangitis, ichthyosis prematurity syndrome, MEDNIK syndrome (mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, and keratoderma), peeling skin disease, Refsum syndrome, and trichothiodystrophy, according to the statement.

“In particular, we did note that, with any disorder that was associated with atopy, the retinoids were often counterproductive,” one of the consensus statement cochairs, Andrea L. Zaenglein, MD, said during the Society for Pediatric Dermatology pre-AAD meeting. “In Netherton syndrome, for example, retinoids seemed to make the skin fragility a lot worse, so typically, they would be avoided in those patients.”

The statement, which she assembled with cochair pediatric dermatologist Moise L. Levy, MD, professor of pediatrics, University of Texas at Austin, and 21 other multidisciplinary experts, recommends considering use of topical retinoids to help decrease scaling of the skin,“but [they] are particularly helpful for more localized complications of ichthyosis, such as digital contractures and ectropion,” said Dr. Zaenglein, professor of dermatology and pediatrics at Penn State University, Hershey. “A lot of it has to do with the size and the volume of the tubes and getting enough [product] to be able to apply it over larger areas. We do tend to use them more focally.”

While systemic absorption can occur with widespread use, no specific lab monitoring is required. Dr. Zaenglein and her colleagues also recommend avoiding the use of tazarotene during pregnancy, since it is contraindicated in pregnancy (category X), but monthly pregnancy tests are not recommended.

During an overview of the document at the meeting, she noted that the recommended dosing for both isotretinoin and acitretin is 0.5-1.0 mg/kg per day and the side effects tend to be dose dependent, “except teratogenicity, which can occur with even low doses of systemic retinoid exposure and early on in pregnancy.” The authors also advise patients to consider drug holidays or lower doses “especially during warmer, more humid months, where you might not need the higher doses to achieve cutaneous effects,” she said.

They emphasized the importance of avoiding pregnancy for 3 years after completion of treatment with acitretin. “While the half-life of acitretin is 49 hours, it’s easily converted with any alcohol exposure to etretinate,” Dr. Zaenglein noted. “Then, the half-life is 120 days.”

The statement, which was sponsored by the Pediatric Dermatology Research Alliance (PEDRA), also addresses the clinical considerations and consequences of long-term systemic retinoid use on bone health, such as premature epiphyseal closure in preadolescent children. “In general, this risk is greater with higher doses of therapies – above 1 mg/kg per day – and over prolonged periods of time, typically 4-6 years,” she said. Other potential effects on bone health include calcifications of tendons and ligaments, osteophytes or “bone spurs,” DISH (diffuse idiopathic skeletal hyperostosis), and potential alterations in bone density and growth.

“We also have to worry about concomitant effects of contraception, particularly if you’re using progestin-only formulations that carry a black box warning for osteoporosis,” Dr. Zaenglein said. “It is recommended that you limit their use to 3 years.” Other factors to consider include genetic risk and modifiable factors that affect bone health, such as diet and physical activity, which may impact susceptibility to systemic retinoid bone toxicity and should be discussed with the patient.

Recommended bone monitoring in children starts with a comprehensive family and personal medical history for skeletal toxicity risk factors, followed by an annual growth assessment (height, weight, body mass index, and growth curve), asking regularly about musculoskeletal symptoms, and following up with appropriate imaging. “Inquiring about their diet is recommended as well, so making sure they’re getting sufficient amounts of calcium and vitamin D, and no additional vitamin A sources that may compound the side effects from systemic retinoids,” Dr. Zaenglein said.

The document also advises that a baseline skeletal radiographic survey be performed in patients aged 16-18 years. This may include imaging of the lateral cervical and thoracic spine, lateral view of the calcanei to include Achilles tendon, hips and symptomatic areas, and bone density evaluation.

The statement addressed the psychiatric considerations and consequences of long-term systemic retinoid use. One cross-sectional study of children with ichthyosis found that 30% screened positive for depression and 38% screened positive for anxiety, “but the role of retinoids is unclear,” Dr. Zaenglein said. “It’s a complicated matter, but patients with a personal history of depression, anxiety, and other affective disorders prior to initiation of systemic retinoid treatment should be monitored carefully for exacerbation of symptoms. Comanagement with a mental health provider should be considered.”

As for contraception considerations with long-term systemic retinoid therapy use, the authors recommend that two forms of contraception be used. “Consider long-acting reversible contraception, especially in sexually active adolescents who have a history of noncompliance, or to remove the risk of teratogenicity for them,” she said. “We’re not sure what additive effects progestin/lower estrogen have on long-term cardiovascular health, including lipids and bone density.”

The authors noted that iPLEDGE is not designed for long-term use. “It’s really designed for the on-label use of systemic retinoids in severe acne, where you’re using it for 5-6 months, not for 5-6 years,” Dr. Zaenglein said. “iPLEDGE does impose significant and financial barriers for our patients. More advocacy is needed to adapt that program for our patients.”

She and her coauthors acknowledged practice gaps and unmet needs in patients with disorders of cornification/types of ichthyosis, including the optimal formulation of retinoids based on ichthyosis subtype, whether there is a benefit to intermittent therapy with respect to risk of toxicity and maintenance of efficacy, and how to minimize the bone-related changes that can occur with treatment. “These are some of the things that we can look further into,” she said. “For now, though, retinoids can improve function and quality of life in patients with ichthyosis and disorders of cornification. Many questions still exist, and more data and research are needed.”

Sun Pharmaceuticals and the Foundation for Ichthyosis and Related Skin Types (FIRST) provided an unrestricted grant for development of the recommendations.

Dr. Zaenglein disclosed that she is a consultant for Pfizer. She is also an advisory board member for Dermata, Sol-Gel, Regeneron, Verrica, and Cassiopea, and has conducted contracted research for AbbVie, Incyte, Arcutis, and Pfizer. The other authors disclosed serving as investigators, advisers, consultants, and/or had other relationships with various pharmaceutical companies.

[email protected]

For as many disorders of cornification and types of ichthyosis that have been shown to benefit from retinoids, a seemingly equal number have no data or show no improvement.

According to a consensus statement published in the February issue of Pediatric Dermatology, adequate data exist in the medical literature to demonstrate an improvement in use of systemic retinoids for select genotypes of congenital ichthyosiform erythroderma, epidermolytic ichthyosis, erythrokeratodermia variabilis, harlequin ichthyosis, IFAP syndrome (ichthyosis with confetti, ichthyosis follicularis, atrichia, and photophobia), KID syndrome (keratitis-ichthyosis-deafness), KLICK syndrome (keratosis linearis with ichthyosis congenita and sclerosing keratoderma), lamellar ichthyosis, loricrin keratoderma, neutral lipid storage disease with ichthyosis, recessive X-linked ichthyosis, and Sjögren-Larsson syndrome.

At the same time, limited or no data exist to support the use of systemic retinoids for CHILD syndrome (congenital hemidysplasia with ichthyosiform erythroderma and limb defects), CHIME syndrome (colobomas, heart defects, ichthyosiform dermatosis, intellectual disability, and either ear defects or epilepsy), Conradi-Hunermann-Happle syndrome, ichthyosis-hypotrichosis, ichthyosis-hypotrichosis-sclerosis cholangitis, ichthyosis prematurity syndrome, MEDNIK syndrome (mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, and keratoderma), peeling skin disease, Refsum syndrome, and trichothiodystrophy, according to the statement.

“In particular, we did note that, with any disorder that was associated with atopy, the retinoids were often counterproductive,” one of the consensus statement cochairs, Andrea L. Zaenglein, MD, said during the Society for Pediatric Dermatology pre-AAD meeting. “In Netherton syndrome, for example, retinoids seemed to make the skin fragility a lot worse, so typically, they would be avoided in those patients.”

The statement, which she assembled with cochair pediatric dermatologist Moise L. Levy, MD, professor of pediatrics, University of Texas at Austin, and 21 other multidisciplinary experts, recommends considering use of topical retinoids to help decrease scaling of the skin,“but [they] are particularly helpful for more localized complications of ichthyosis, such as digital contractures and ectropion,” said Dr. Zaenglein, professor of dermatology and pediatrics at Penn State University, Hershey. “A lot of it has to do with the size and the volume of the tubes and getting enough [product] to be able to apply it over larger areas. We do tend to use them more focally.”

While systemic absorption can occur with widespread use, no specific lab monitoring is required. Dr. Zaenglein and her colleagues also recommend avoiding the use of tazarotene during pregnancy, since it is contraindicated in pregnancy (category X), but monthly pregnancy tests are not recommended.

During an overview of the document at the meeting, she noted that the recommended dosing for both isotretinoin and acitretin is 0.5-1.0 mg/kg per day and the side effects tend to be dose dependent, “except teratogenicity, which can occur with even low doses of systemic retinoid exposure and early on in pregnancy.” The authors also advise patients to consider drug holidays or lower doses “especially during warmer, more humid months, where you might not need the higher doses to achieve cutaneous effects,” she said.

They emphasized the importance of avoiding pregnancy for 3 years after completion of treatment with acitretin. “While the half-life of acitretin is 49 hours, it’s easily converted with any alcohol exposure to etretinate,” Dr. Zaenglein noted. “Then, the half-life is 120 days.”

The statement, which was sponsored by the Pediatric Dermatology Research Alliance (PEDRA), also addresses the clinical considerations and consequences of long-term systemic retinoid use on bone health, such as premature epiphyseal closure in preadolescent children. “In general, this risk is greater with higher doses of therapies – above 1 mg/kg per day – and over prolonged periods of time, typically 4-6 years,” she said. Other potential effects on bone health include calcifications of tendons and ligaments, osteophytes or “bone spurs,” DISH (diffuse idiopathic skeletal hyperostosis), and potential alterations in bone density and growth.

“We also have to worry about concomitant effects of contraception, particularly if you’re using progestin-only formulations that carry a black box warning for osteoporosis,” Dr. Zaenglein said. “It is recommended that you limit their use to 3 years.” Other factors to consider include genetic risk and modifiable factors that affect bone health, such as diet and physical activity, which may impact susceptibility to systemic retinoid bone toxicity and should be discussed with the patient.

Recommended bone monitoring in children starts with a comprehensive family and personal medical history for skeletal toxicity risk factors, followed by an annual growth assessment (height, weight, body mass index, and growth curve), asking regularly about musculoskeletal symptoms, and following up with appropriate imaging. “Inquiring about their diet is recommended as well, so making sure they’re getting sufficient amounts of calcium and vitamin D, and no additional vitamin A sources that may compound the side effects from systemic retinoids,” Dr. Zaenglein said.

The document also advises that a baseline skeletal radiographic survey be performed in patients aged 16-18 years. This may include imaging of the lateral cervical and thoracic spine, lateral view of the calcanei to include Achilles tendon, hips and symptomatic areas, and bone density evaluation.

The statement addressed the psychiatric considerations and consequences of long-term systemic retinoid use. One cross-sectional study of children with ichthyosis found that 30% screened positive for depression and 38% screened positive for anxiety, “but the role of retinoids is unclear,” Dr. Zaenglein said. “It’s a complicated matter, but patients with a personal history of depression, anxiety, and other affective disorders prior to initiation of systemic retinoid treatment should be monitored carefully for exacerbation of symptoms. Comanagement with a mental health provider should be considered.”

As for contraception considerations with long-term systemic retinoid therapy use, the authors recommend that two forms of contraception be used. “Consider long-acting reversible contraception, especially in sexually active adolescents who have a history of noncompliance, or to remove the risk of teratogenicity for them,” she said. “We’re not sure what additive effects progestin/lower estrogen have on long-term cardiovascular health, including lipids and bone density.”

The authors noted that iPLEDGE is not designed for long-term use. “It’s really designed for the on-label use of systemic retinoids in severe acne, where you’re using it for 5-6 months, not for 5-6 years,” Dr. Zaenglein said. “iPLEDGE does impose significant and financial barriers for our patients. More advocacy is needed to adapt that program for our patients.”

She and her coauthors acknowledged practice gaps and unmet needs in patients with disorders of cornification/types of ichthyosis, including the optimal formulation of retinoids based on ichthyosis subtype, whether there is a benefit to intermittent therapy with respect to risk of toxicity and maintenance of efficacy, and how to minimize the bone-related changes that can occur with treatment. “These are some of the things that we can look further into,” she said. “For now, though, retinoids can improve function and quality of life in patients with ichthyosis and disorders of cornification. Many questions still exist, and more data and research are needed.”

Sun Pharmaceuticals and the Foundation for Ichthyosis and Related Skin Types (FIRST) provided an unrestricted grant for development of the recommendations.

Dr. Zaenglein disclosed that she is a consultant for Pfizer. She is also an advisory board member for Dermata, Sol-Gel, Regeneron, Verrica, and Cassiopea, and has conducted contracted research for AbbVie, Incyte, Arcutis, and Pfizer. The other authors disclosed serving as investigators, advisers, consultants, and/or had other relationships with various pharmaceutical companies.

[email protected]

For as many disorders of cornification and types of ichthyosis that have been shown to benefit from retinoids, a seemingly equal number have no data or show no improvement.

According to a consensus statement published in the February issue of Pediatric Dermatology, adequate data exist in the medical literature to demonstrate an improvement in use of systemic retinoids for select genotypes of congenital ichthyosiform erythroderma, epidermolytic ichthyosis, erythrokeratodermia variabilis, harlequin ichthyosis, IFAP syndrome (ichthyosis with confetti, ichthyosis follicularis, atrichia, and photophobia), KID syndrome (keratitis-ichthyosis-deafness), KLICK syndrome (keratosis linearis with ichthyosis congenita and sclerosing keratoderma), lamellar ichthyosis, loricrin keratoderma, neutral lipid storage disease with ichthyosis, recessive X-linked ichthyosis, and Sjögren-Larsson syndrome.

At the same time, limited or no data exist to support the use of systemic retinoids for CHILD syndrome (congenital hemidysplasia with ichthyosiform erythroderma and limb defects), CHIME syndrome (colobomas, heart defects, ichthyosiform dermatosis, intellectual disability, and either ear defects or epilepsy), Conradi-Hunermann-Happle syndrome, ichthyosis-hypotrichosis, ichthyosis-hypotrichosis-sclerosis cholangitis, ichthyosis prematurity syndrome, MEDNIK syndrome (mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, and keratoderma), peeling skin disease, Refsum syndrome, and trichothiodystrophy, according to the statement.

“In particular, we did note that, with any disorder that was associated with atopy, the retinoids were often counterproductive,” one of the consensus statement cochairs, Andrea L. Zaenglein, MD, said during the Society for Pediatric Dermatology pre-AAD meeting. “In Netherton syndrome, for example, retinoids seemed to make the skin fragility a lot worse, so typically, they would be avoided in those patients.”

The statement, which she assembled with cochair pediatric dermatologist Moise L. Levy, MD, professor of pediatrics, University of Texas at Austin, and 21 other multidisciplinary experts, recommends considering use of topical retinoids to help decrease scaling of the skin,“but [they] are particularly helpful for more localized complications of ichthyosis, such as digital contractures and ectropion,” said Dr. Zaenglein, professor of dermatology and pediatrics at Penn State University, Hershey. “A lot of it has to do with the size and the volume of the tubes and getting enough [product] to be able to apply it over larger areas. We do tend to use them more focally.”

While systemic absorption can occur with widespread use, no specific lab monitoring is required. Dr. Zaenglein and her colleagues also recommend avoiding the use of tazarotene during pregnancy, since it is contraindicated in pregnancy (category X), but monthly pregnancy tests are not recommended.

During an overview of the document at the meeting, she noted that the recommended dosing for both isotretinoin and acitretin is 0.5-1.0 mg/kg per day and the side effects tend to be dose dependent, “except teratogenicity, which can occur with even low doses of systemic retinoid exposure and early on in pregnancy.” The authors also advise patients to consider drug holidays or lower doses “especially during warmer, more humid months, where you might not need the higher doses to achieve cutaneous effects,” she said.

They emphasized the importance of avoiding pregnancy for 3 years after completion of treatment with acitretin. “While the half-life of acitretin is 49 hours, it’s easily converted with any alcohol exposure to etretinate,” Dr. Zaenglein noted. “Then, the half-life is 120 days.”

The statement, which was sponsored by the Pediatric Dermatology Research Alliance (PEDRA), also addresses the clinical considerations and consequences of long-term systemic retinoid use on bone health, such as premature epiphyseal closure in preadolescent children. “In general, this risk is greater with higher doses of therapies – above 1 mg/kg per day – and over prolonged periods of time, typically 4-6 years,” she said. Other potential effects on bone health include calcifications of tendons and ligaments, osteophytes or “bone spurs,” DISH (diffuse idiopathic skeletal hyperostosis), and potential alterations in bone density and growth.

“We also have to worry about concomitant effects of contraception, particularly if you’re using progestin-only formulations that carry a black box warning for osteoporosis,” Dr. Zaenglein said. “It is recommended that you limit their use to 3 years.” Other factors to consider include genetic risk and modifiable factors that affect bone health, such as diet and physical activity, which may impact susceptibility to systemic retinoid bone toxicity and should be discussed with the patient.

Recommended bone monitoring in children starts with a comprehensive family and personal medical history for skeletal toxicity risk factors, followed by an annual growth assessment (height, weight, body mass index, and growth curve), asking regularly about musculoskeletal symptoms, and following up with appropriate imaging. “Inquiring about their diet is recommended as well, so making sure they’re getting sufficient amounts of calcium and vitamin D, and no additional vitamin A sources that may compound the side effects from systemic retinoids,” Dr. Zaenglein said.

The document also advises that a baseline skeletal radiographic survey be performed in patients aged 16-18 years. This may include imaging of the lateral cervical and thoracic spine, lateral view of the calcanei to include Achilles tendon, hips and symptomatic areas, and bone density evaluation.

The statement addressed the psychiatric considerations and consequences of long-term systemic retinoid use. One cross-sectional study of children with ichthyosis found that 30% screened positive for depression and 38% screened positive for anxiety, “but the role of retinoids is unclear,” Dr. Zaenglein said. “It’s a complicated matter, but patients with a personal history of depression, anxiety, and other affective disorders prior to initiation of systemic retinoid treatment should be monitored carefully for exacerbation of symptoms. Comanagement with a mental health provider should be considered.”

As for contraception considerations with long-term systemic retinoid therapy use, the authors recommend that two forms of contraception be used. “Consider long-acting reversible contraception, especially in sexually active adolescents who have a history of noncompliance, or to remove the risk of teratogenicity for them,” she said. “We’re not sure what additive effects progestin/lower estrogen have on long-term cardiovascular health, including lipids and bone density.”

The authors noted that iPLEDGE is not designed for long-term use. “It’s really designed for the on-label use of systemic retinoids in severe acne, where you’re using it for 5-6 months, not for 5-6 years,” Dr. Zaenglein said. “iPLEDGE does impose significant and financial barriers for our patients. More advocacy is needed to adapt that program for our patients.”

She and her coauthors acknowledged practice gaps and unmet needs in patients with disorders of cornification/types of ichthyosis, including the optimal formulation of retinoids based on ichthyosis subtype, whether there is a benefit to intermittent therapy with respect to risk of toxicity and maintenance of efficacy, and how to minimize the bone-related changes that can occur with treatment. “These are some of the things that we can look further into,” she said. “For now, though, retinoids can improve function and quality of life in patients with ichthyosis and disorders of cornification. Many questions still exist, and more data and research are needed.”

Sun Pharmaceuticals and the Foundation for Ichthyosis and Related Skin Types (FIRST) provided an unrestricted grant for development of the recommendations.

Dr. Zaenglein disclosed that she is a consultant for Pfizer. She is also an advisory board member for Dermata, Sol-Gel, Regeneron, Verrica, and Cassiopea, and has conducted contracted research for AbbVie, Incyte, Arcutis, and Pfizer. The other authors disclosed serving as investigators, advisers, consultants, and/or had other relationships with various pharmaceutical companies.

[email protected]

People who identify as transgender experience many health disparities, in addition to lack of access to quality care. The most commonly cited barrier is the lack of providers who are knowledgeable about transgender health care, according to past surveys.

Even those who do seek care often have unpleasant experiences. A 2015 survey conducted by the National Center for Transgender Equality found that 33% of those who saw a health care provider reported at least one  unfavorable experience related to being transgender, such as being verbally harassed or refused treatment because of their gender identity. In fact, 23% of those surveyed say they did not seek health care they needed in the past year because of fear of being mistreated as a transgender person.

To find out how physicians can provide more compassionate, effective care for this group, this news organization spoke with K. Ashley Brandt, DO, gender-affirming surgeon and obstetrician/gynecologist in West Reading, Penn. This interview has been edited for length and clarity.

Question: Surveys have shown that many people who identify as transgender will seek only transition care, not primary or preventive care. Why is that?

Dr. Brandt: My answer is multifactorial. Transgender patients do seek primary care – just not as readily. There’s a lot of misconceptions about health care needs for the LGBT community in general. For example, lesbian or bisexual women may be not as well informed about the need for Pap smears compared with their heterosexual counterparts. These misconceptions are further exacerbated in the transgender community.

The fact that a lot of patients seek only transition-related care, but not preventive services, such as primary care and gynecologic care, is also related to fears of discrimination and lack of education of providers. These patients are afraid when they walk into an office that they will be misgendered or their physician won’t be familiar with their health care needs.

What can clinics and clinicians do to create a safe and welcoming environment?

Dr. Brandt: It starts with educating office staff about terminology and gender identities.

A key feature of our EHR is the sexual orientation and gender identity platform, which asks questions about a patient’s gender identity, sexual orientation, sex assigned at birth, and organ inventory. These data are then found in the patient information tab and are just as relevant as their insurance status, age, and date of birth.

There are many ways a doctor’s office can signal to patients that they are inclusive. They can hang LGBTQ-friendly flags or symbols or a sign saying, “We have an anti-discrimination policy” in the waiting room.  A welcoming environment can also be achieved by revising patient questionnaires or forms so that they aren’t gender-specific or binary.

Given that the patient may have limited contact with a primary care clinician, how do you prioritize what you address during the visit?

Dr. Brandt: Similar to cisgender patients, it depends initially on the age of the patient and the reason for the visit. The priorities of an otherwise healthy transgender patient in their 20s are going to be largely the same as for a cisgender patient of the same age. As patients age in the primary care world, you’re addressing more issues, such as colorectal screening, lipid disorders, and mammograms, and that doesn’t change. For the most part, the problems that you address should be specific for that age group.

It becomes more complicated when you add in factors such as hormone therapy and whether patients have had any type of gender-affirming surgery. Those things can change the usual recommendations for screening or risk assessment. We try to figure out what routine health maintenance and cancer screening a patient needs based on age and risk factors, in addition to hormone status and surgical state.

Do you think that many physicians are educated about the care of underserved populations such as transgender patients?

Dr. Brandt: Yes and no. We are definitely getting better at it. For example, the American College of Obstetricians and Gynecologists published a committee opinion highlighting transgender care. So organizations are starting to prioritize these populations and recognize that they are, in fact, underserved and they have special health care needs.

However, the knowledge gaps are still pretty big. I get calls daily from providers asking questions about how to manage patients on hormones, or how to examine a patient who has undergone a vaginoplasty. I hear a lot of horror stories from transgender patients who had their hormones stopped for absurd and medically misinformed reasons.

But I definitely think it’s getting better and it’s being addressed at all levels – the medical school level, the residency level, and the attending level. It just takes time to inform people and for people to get used to the health care needs of these patients.

What should physicians keep in mind when treating patients who identify as transgender?

Dr. Brandt: First and foremost, understanding the terminology and the difference between gender identity, sex, and sexual orientation. Being familiar with that language and being able to speak that language very comfortably and not being awkward about it is a really important thing for primary care physicians and indeed any physician who treats transgender patients.

Physicians should also be aware that any underserved population has higher rates of mental health issues, such as depression and anxiety. Obviously, that goes along with being underserved and the stigma and the disparities that exist for these patients. Having providers educate themselves about what those disparities are and how they impact a patient’s daily life and health is paramount to knowing how to treat patients.

What are your top health concerns for these patients and how do you address them?

Dr. Brandt: I think mental health and safety is probably the number one for me. About 41% of transgender adults have attempted suicide. That number is roughly 51% in transgender youth. That is an astonishing number. These patients have much higher rates of domestic violence, intimate partner violence, and sexual assault, especially trans women and trans women of color. So understanding those statistics is huge.

Obesity, smoking, and substance abuse are my next three. Again, those are things that should be addressed at any visit, regardless of the gender identity or sexual orientation of the patient, but those rates are particularly high in this population.

Fertility and long-term care for patients should be addressed. Many patients who identify as transgender are told they can’t have a family. As a primary care physician, you may see a patient before they are seen by an ob.gyn. or surgeon. Talking about what a patient’s long-term life goals are with fertility and family planning, and what that looks like for them, is a big thing for me. Other providers may not feel that’s a concern, but I believe it should be discussed before initiation of hormone therapy, which can significantly impact fertility in some patients.

Are there nuances to the physical examination that primary care physicians should be aware of when dealing with transmasculine patients vs. transfeminine patients?

Dr. Brandt: Absolutely. And this interview can’t cover the scope of those nuances. An example that comes to mind is the genital exam. For transgender women who have undergone a vaginoplasty, the pelvic exam can be very affirming. Whereas for transgender men, a gynecologic exam can significantly exacerbate dysphoria and there are ways to conduct the exam to limit this discomfort and avoid creating a traumatic experience for the patient. It’s important to be aware that the genital exam, or any type of genitourinary exam, can be either affirming or not affirming.

Sexually transmitted infections are up in the general population, and the trans population is at even higher risk. What should physicians think about when they assess this risk?

Dr. Brandt: It’s really important for primary care clinicians and for gynecologists to learn to be comfortable talking about sexual practices, because what people do behind closed doors is really a key to how to counsel patients about safe sex.

People are well aware of the need to have safe sex. However, depending on the type of sex that you’re having, what body parts go where, what is truly safe can vary and people may not know, for example, to wear a condom when sex toys are involved or that a transgender male on testosterone can become pregnant during penile-vaginal intercourse. Providers really should be very educated on the array of sexual practices that people have and how to counsel them about those. They should know how to ask patients the gender identity of their sexual partners, the sexual orientation of their partners, and what parts go where during sex.

Providers should also talk to patients about PrEP [pre-exposure prophylaxis], whether they identify as cisgender or transgender. My trans patients tend to be a lot more educated about PrEP than other patients. It’s something that many of the residents, even in a standard gynecologic clinic, for example, don’t talk to cisgender patients about because of the stigma surrounding HIV. Many providers still think that the only people who are at risk for HIV are men who have sex with men. And while those rates are higher in some populations, depending on sexual practices, those aren’t the only patients who qualify for PrEP.

Overall, in order to counsel patients about STIs and safe sexual practices, providers should learn to be comfortable talking about sex.

Do you have any strategies on how to make the appointment more successful in addressing those issues?

Dr. Brandt: Bedside manner is a hard thing to teach, and comfort in talking about sex, gender identity, and sexual orientation can vary – but there are a lot of continuing medical education courses that physicians can utilize through the World Professional Association for Transgender Health.

If providers start to notice an influx of patients who identify as transgender or if they want to start seeing transgender patients, it’s really important for them to have that training before they start interacting with patients. In all of medicine, we sort of learn as we go, but this patient population has been subjected to discrimination, violence, error, and misgendering. They have dealt with providers who didn’t understand their health care needs. While this field is evolving, knowing how to appropriately address a patient (using their correct name, pronouns, etc.) is an absolute must.

That needs to be part of a provider’s routine vernacular and not something that they sort of stumble through. You can scare a patient away as soon as they walk into the office with an uneducated front desk staff and things that are seen in the office. Seeking out those educational tools, being aware of your own deficits as a provider and the educational needs of your office, and addressing those needs is really key.

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

People who identify as transgender experience many health disparities, in addition to lack of access to quality care. The most commonly cited barrier is the lack of providers who are knowledgeable about transgender health care, according to past surveys.

Even those who do seek care often have unpleasant experiences. A 2015 survey conducted by the National Center for Transgender Equality found that 33% of those who saw a health care provider reported at least one  unfavorable experience related to being transgender, such as being verbally harassed or refused treatment because of their gender identity. In fact, 23% of those surveyed say they did not seek health care they needed in the past year because of fear of being mistreated as a transgender person.

To find out how physicians can provide more compassionate, effective care for this group, this news organization spoke with K. Ashley Brandt, DO, gender-affirming surgeon and obstetrician/gynecologist in West Reading, Penn. This interview has been edited for length and clarity.

Question: Surveys have shown that many people who identify as transgender will seek only transition care, not primary or preventive care. Why is that?

Dr. Brandt: My answer is multifactorial. Transgender patients do seek primary care – just not as readily. There’s a lot of misconceptions about health care needs for the LGBT community in general. For example, lesbian or bisexual women may be not as well informed about the need for Pap smears compared with their heterosexual counterparts. These misconceptions are further exacerbated in the transgender community.

The fact that a lot of patients seek only transition-related care, but not preventive services, such as primary care and gynecologic care, is also related to fears of discrimination and lack of education of providers. These patients are afraid when they walk into an office that they will be misgendered or their physician won’t be familiar with their health care needs.

What can clinics and clinicians do to create a safe and welcoming environment?

Dr. Brandt: It starts with educating office staff about terminology and gender identities.

A key feature of our EHR is the sexual orientation and gender identity platform, which asks questions about a patient’s gender identity, sexual orientation, sex assigned at birth, and organ inventory. These data are then found in the patient information tab and are just as relevant as their insurance status, age, and date of birth.

There are many ways a doctor’s office can signal to patients that they are inclusive. They can hang LGBTQ-friendly flags or symbols or a sign saying, “We have an anti-discrimination policy” in the waiting room.  A welcoming environment can also be achieved by revising patient questionnaires or forms so that they aren’t gender-specific or binary.

Given that the patient may have limited contact with a primary care clinician, how do you prioritize what you address during the visit?

Dr. Brandt: Similar to cisgender patients, it depends initially on the age of the patient and the reason for the visit. The priorities of an otherwise healthy transgender patient in their 20s are going to be largely the same as for a cisgender patient of the same age. As patients age in the primary care world, you’re addressing more issues, such as colorectal screening, lipid disorders, and mammograms, and that doesn’t change. For the most part, the problems that you address should be specific for that age group.

It becomes more complicated when you add in factors such as hormone therapy and whether patients have had any type of gender-affirming surgery. Those things can change the usual recommendations for screening or risk assessment. We try to figure out what routine health maintenance and cancer screening a patient needs based on age and risk factors, in addition to hormone status and surgical state.

Do you think that many physicians are educated about the care of underserved populations such as transgender patients?

Dr. Brandt: Yes and no. We are definitely getting better at it. For example, the American College of Obstetricians and Gynecologists published a committee opinion highlighting transgender care. So organizations are starting to prioritize these populations and recognize that they are, in fact, underserved and they have special health care needs.

However, the knowledge gaps are still pretty big. I get calls daily from providers asking questions about how to manage patients on hormones, or how to examine a patient who has undergone a vaginoplasty. I hear a lot of horror stories from transgender patients who had their hormones stopped for absurd and medically misinformed reasons.

But I definitely think it’s getting better and it’s being addressed at all levels – the medical school level, the residency level, and the attending level. It just takes time to inform people and for people to get used to the health care needs of these patients.

What should physicians keep in mind when treating patients who identify as transgender?

Dr. Brandt: First and foremost, understanding the terminology and the difference between gender identity, sex, and sexual orientation. Being familiar with that language and being able to speak that language very comfortably and not being awkward about it is a really important thing for primary care physicians and indeed any physician who treats transgender patients.

Physicians should also be aware that any underserved population has higher rates of mental health issues, such as depression and anxiety. Obviously, that goes along with being underserved and the stigma and the disparities that exist for these patients. Having providers educate themselves about what those disparities are and how they impact a patient’s daily life and health is paramount to knowing how to treat patients.

What are your top health concerns for these patients and how do you address them?

Dr. Brandt: I think mental health and safety is probably the number one for me. About 41% of transgender adults have attempted suicide. That number is roughly 51% in transgender youth. That is an astonishing number. These patients have much higher rates of domestic violence, intimate partner violence, and sexual assault, especially trans women and trans women of color. So understanding those statistics is huge.

Obesity, smoking, and substance abuse are my next three. Again, those are things that should be addressed at any visit, regardless of the gender identity or sexual orientation of the patient, but those rates are particularly high in this population.

Fertility and long-term care for patients should be addressed. Many patients who identify as transgender are told they can’t have a family. As a primary care physician, you may see a patient before they are seen by an ob.gyn. or surgeon. Talking about what a patient’s long-term life goals are with fertility and family planning, and what that looks like for them, is a big thing for me. Other providers may not feel that’s a concern, but I believe it should be discussed before initiation of hormone therapy, which can significantly impact fertility in some patients.

Are there nuances to the physical examination that primary care physicians should be aware of when dealing with transmasculine patients vs. transfeminine patients?

Dr. Brandt: Absolutely. And this interview can’t cover the scope of those nuances. An example that comes to mind is the genital exam. For transgender women who have undergone a vaginoplasty, the pelvic exam can be very affirming. Whereas for transgender men, a gynecologic exam can significantly exacerbate dysphoria and there are ways to conduct the exam to limit this discomfort and avoid creating a traumatic experience for the patient. It’s important to be aware that the genital exam, or any type of genitourinary exam, can be either affirming or not affirming.

Sexually transmitted infections are up in the general population, and the trans population is at even higher risk. What should physicians think about when they assess this risk?

Dr. Brandt: It’s really important for primary care clinicians and for gynecologists to learn to be comfortable talking about sexual practices, because what people do behind closed doors is really a key to how to counsel patients about safe sex.

People are well aware of the need to have safe sex. However, depending on the type of sex that you’re having, what body parts go where, what is truly safe can vary and people may not know, for example, to wear a condom when sex toys are involved or that a transgender male on testosterone can become pregnant during penile-vaginal intercourse. Providers really should be very educated on the array of sexual practices that people have and how to counsel them about those. They should know how to ask patients the gender identity of their sexual partners, the sexual orientation of their partners, and what parts go where during sex.

Providers should also talk to patients about PrEP [pre-exposure prophylaxis], whether they identify as cisgender or transgender. My trans patients tend to be a lot more educated about PrEP than other patients. It’s something that many of the residents, even in a standard gynecologic clinic, for example, don’t talk to cisgender patients about because of the stigma surrounding HIV. Many providers still think that the only people who are at risk for HIV are men who have sex with men. And while those rates are higher in some populations, depending on sexual practices, those aren’t the only patients who qualify for PrEP.

Overall, in order to counsel patients about STIs and safe sexual practices, providers should learn to be comfortable talking about sex.

Do you have any strategies on how to make the appointment more successful in addressing those issues?

Dr. Brandt: Bedside manner is a hard thing to teach, and comfort in talking about sex, gender identity, and sexual orientation can vary – but there are a lot of continuing medical education courses that physicians can utilize through the World Professional Association for Transgender Health.

If providers start to notice an influx of patients who identify as transgender or if they want to start seeing transgender patients, it’s really important for them to have that training before they start interacting with patients. In all of medicine, we sort of learn as we go, but this patient population has been subjected to discrimination, violence, error, and misgendering. They have dealt with providers who didn’t understand their health care needs. While this field is evolving, knowing how to appropriately address a patient (using their correct name, pronouns, etc.) is an absolute must.

That needs to be part of a provider’s routine vernacular and not something that they sort of stumble through. You can scare a patient away as soon as they walk into the office with an uneducated front desk staff and things that are seen in the office. Seeking out those educational tools, being aware of your own deficits as a provider and the educational needs of your office, and addressing those needs is really key.

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

People who identify as transgender experience many health disparities, in addition to lack of access to quality care. The most commonly cited barrier is the lack of providers who are knowledgeable about transgender health care, according to past surveys.

Even those who do seek care often have unpleasant experiences. A 2015 survey conducted by the National Center for Transgender Equality found that 33% of those who saw a health care provider reported at least one  unfavorable experience related to being transgender, such as being verbally harassed or refused treatment because of their gender identity. In fact, 23% of those surveyed say they did not seek health care they needed in the past year because of fear of being mistreated as a transgender person.

To find out how physicians can provide more compassionate, effective care for this group, this news organization spoke with K. Ashley Brandt, DO, gender-affirming surgeon and obstetrician/gynecologist in West Reading, Penn. This interview has been edited for length and clarity.

Question: Surveys have shown that many people who identify as transgender will seek only transition care, not primary or preventive care. Why is that?

Dr. Brandt: My answer is multifactorial. Transgender patients do seek primary care – just not as readily. There’s a lot of misconceptions about health care needs for the LGBT community in general. For example, lesbian or bisexual women may be not as well informed about the need for Pap smears compared with their heterosexual counterparts. These misconceptions are further exacerbated in the transgender community.

The fact that a lot of patients seek only transition-related care, but not preventive services, such as primary care and gynecologic care, is also related to fears of discrimination and lack of education of providers. These patients are afraid when they walk into an office that they will be misgendered or their physician won’t be familiar with their health care needs.

What can clinics and clinicians do to create a safe and welcoming environment?

Dr. Brandt: It starts with educating office staff about terminology and gender identities.

A key feature of our EHR is the sexual orientation and gender identity platform, which asks questions about a patient’s gender identity, sexual orientation, sex assigned at birth, and organ inventory. These data are then found in the patient information tab and are just as relevant as their insurance status, age, and date of birth.

There are many ways a doctor’s office can signal to patients that they are inclusive. They can hang LGBTQ-friendly flags or symbols or a sign saying, “We have an anti-discrimination policy” in the waiting room.  A welcoming environment can also be achieved by revising patient questionnaires or forms so that they aren’t gender-specific or binary.

Given that the patient may have limited contact with a primary care clinician, how do you prioritize what you address during the visit?

Dr. Brandt: Similar to cisgender patients, it depends initially on the age of the patient and the reason for the visit. The priorities of an otherwise healthy transgender patient in their 20s are going to be largely the same as for a cisgender patient of the same age. As patients age in the primary care world, you’re addressing more issues, such as colorectal screening, lipid disorders, and mammograms, and that doesn’t change. For the most part, the problems that you address should be specific for that age group.

It becomes more complicated when you add in factors such as hormone therapy and whether patients have had any type of gender-affirming surgery. Those things can change the usual recommendations for screening or risk assessment. We try to figure out what routine health maintenance and cancer screening a patient needs based on age and risk factors, in addition to hormone status and surgical state.

Do you think that many physicians are educated about the care of underserved populations such as transgender patients?

Dr. Brandt: Yes and no. We are definitely getting better at it. For example, the American College of Obstetricians and Gynecologists published a committee opinion highlighting transgender care. So organizations are starting to prioritize these populations and recognize that they are, in fact, underserved and they have special health care needs.

However, the knowledge gaps are still pretty big. I get calls daily from providers asking questions about how to manage patients on hormones, or how to examine a patient who has undergone a vaginoplasty. I hear a lot of horror stories from transgender patients who had their hormones stopped for absurd and medically misinformed reasons.

But I definitely think it’s getting better and it’s being addressed at all levels – the medical school level, the residency level, and the attending level. It just takes time to inform people and for people to get used to the health care needs of these patients.

What should physicians keep in mind when treating patients who identify as transgender?

Dr. Brandt: First and foremost, understanding the terminology and the difference between gender identity, sex, and sexual orientation. Being familiar with that language and being able to speak that language very comfortably and not being awkward about it is a really important thing for primary care physicians and indeed any physician who treats transgender patients.

Physicians should also be aware that any underserved population has higher rates of mental health issues, such as depression and anxiety. Obviously, that goes along with being underserved and the stigma and the disparities that exist for these patients. Having providers educate themselves about what those disparities are and how they impact a patient’s daily life and health is paramount to knowing how to treat patients.

What are your top health concerns for these patients and how do you address them?

Dr. Brandt: I think mental health and safety is probably the number one for me. About 41% of transgender adults have attempted suicide. That number is roughly 51% in transgender youth. That is an astonishing number. These patients have much higher rates of domestic violence, intimate partner violence, and sexual assault, especially trans women and trans women of color. So understanding those statistics is huge.

Obesity, smoking, and substance abuse are my next three. Again, those are things that should be addressed at any visit, regardless of the gender identity or sexual orientation of the patient, but those rates are particularly high in this population.

Fertility and long-term care for patients should be addressed. Many patients who identify as transgender are told they can’t have a family. As a primary care physician, you may see a patient before they are seen by an ob.gyn. or surgeon. Talking about what a patient’s long-term life goals are with fertility and family planning, and what that looks like for them, is a big thing for me. Other providers may not feel that’s a concern, but I believe it should be discussed before initiation of hormone therapy, which can significantly impact fertility in some patients.

Are there nuances to the physical examination that primary care physicians should be aware of when dealing with transmasculine patients vs. transfeminine patients?

Dr. Brandt: Absolutely. And this interview can’t cover the scope of those nuances. An example that comes to mind is the genital exam. For transgender women who have undergone a vaginoplasty, the pelvic exam can be very affirming. Whereas for transgender men, a gynecologic exam can significantly exacerbate dysphoria and there are ways to conduct the exam to limit this discomfort and avoid creating a traumatic experience for the patient. It’s important to be aware that the genital exam, or any type of genitourinary exam, can be either affirming or not affirming.

Sexually transmitted infections are up in the general population, and the trans population is at even higher risk. What should physicians think about when they assess this risk?

Dr. Brandt: It’s really important for primary care clinicians and for gynecologists to learn to be comfortable talking about sexual practices, because what people do behind closed doors is really a key to how to counsel patients about safe sex.

People are well aware of the need to have safe sex. However, depending on the type of sex that you’re having, what body parts go where, what is truly safe can vary and people may not know, for example, to wear a condom when sex toys are involved or that a transgender male on testosterone can become pregnant during penile-vaginal intercourse. Providers really should be very educated on the array of sexual practices that people have and how to counsel them about those. They should know how to ask patients the gender identity of their sexual partners, the sexual orientation of their partners, and what parts go where during sex.

Providers should also talk to patients about PrEP [pre-exposure prophylaxis], whether they identify as cisgender or transgender. My trans patients tend to be a lot more educated about PrEP than other patients. It’s something that many of the residents, even in a standard gynecologic clinic, for example, don’t talk to cisgender patients about because of the stigma surrounding HIV. Many providers still think that the only people who are at risk for HIV are men who have sex with men. And while those rates are higher in some populations, depending on sexual practices, those aren’t the only patients who qualify for PrEP.

Overall, in order to counsel patients about STIs and safe sexual practices, providers should learn to be comfortable talking about sex.

Do you have any strategies on how to make the appointment more successful in addressing those issues?

Dr. Brandt: Bedside manner is a hard thing to teach, and comfort in talking about sex, gender identity, and sexual orientation can vary – but there are a lot of continuing medical education courses that physicians can utilize through the World Professional Association for Transgender Health.

If providers start to notice an influx of patients who identify as transgender or if they want to start seeing transgender patients, it’s really important for them to have that training before they start interacting with patients. In all of medicine, we sort of learn as we go, but this patient population has been subjected to discrimination, violence, error, and misgendering. They have dealt with providers who didn’t understand their health care needs. While this field is evolving, knowing how to appropriately address a patient (using their correct name, pronouns, etc.) is an absolute must.

That needs to be part of a provider’s routine vernacular and not something that they sort of stumble through. You can scare a patient away as soon as they walk into the office with an uneducated front desk staff and things that are seen in the office. Seeking out those educational tools, being aware of your own deficits as a provider and the educational needs of your office, and addressing those needs is really key.

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

Each afternoon, Cyrus Shahpar, MD, the data guru for the White House COVID-19 Response Team, sends an email to staffers with the daily count of COVID-19 vaccinations delivered in the United States.

The numbers, collected from states ahead of the final figures being posted on the Centers for Disease Control and Prevention website, act as a report card of sorts on the team’s efforts.

On Saturday, April 3, it was a new record: 4.1 million vaccinations delivered in a single day, more than the total population of some states.

While the United States has a long way to go before it is done with COVID-19, there’s finally some good news in the nation’s long and blundering slog through the pandemic.

After a rocky start in December 2020 and January 2021, vaccination is happening faster than nearly anyone thought possible. As more people see their friends and family roll up their sleeves, hesitancy is dropping, too.

In settings where large numbers of people are vaccinated, such as nursing homes, COVID-19 cases and deaths have plunged.

Those gains, however, haven’t been shared equally. According to CDC data, 69% of people who are fully vaccinated are White, while just 8% are Black and about 9% are Hispanic, a group that now represents most new COVID-19 cases. 

Officials say that’s partly because the vaccines were rolled out to the elderly first. The average life expectancy for Black people in the United States is now age 72, which means there were fewer people of color represented in the first groups to become eligible. Experts are hopeful that underrepresented groups will start to catch up as more states open up vaccinations to younger people.

Based on overall numbers of daily vaccine doses, the United States ranks third, behind China and India. America ranks fourth – behind Israel, the United Kingdom, and Chile – in the total share of the population that’s been vaccinated, according to the website Our World in Data.
 

A positive development

It’s a stunning turnaround for a country that failed for months to develop effective tests, and still struggles in some quarters to investigate new cases and quarantine their contacts.

The 7-day rolling average of vaccines administered in the United States is currently more than 3 million a day.

“We knew that we needed to get to 3 million a day at some point, if we were going to get most people vaccinated this year, but I don’t think that most people expected it to happen this early,” said Eric Toner, MD, a senior scholar with the Johns Hopkins Center for Health Security in Baltimore.

Before taking office, President Joe Biden pledged to get 100 million shots in arms within his first 100 days in office. After hitting that goal in late March, he doubled it, to 200 million vaccinations by April 30. After first saying all adults should be eligible to get in line for the vaccine by May 1, on April 6, he bumped up that date to April 19. 

Some media reports have seen this repeated moving of the goalposts as calculated – an unstated strategy of underpromising and overdelivering with the aim of rebuilding public trust.

But others pointed out that, even if that’s true, the goals being set aren’t easy, and hitting them has never been a given.

“I think the Biden administration really gets a lot of credit for pushing the companies to get more vaccine out faster than they had planned to,” Dr. Toner said. “And the states have really responded as well as the federal government in terms of getting vaccination sites going. So we’re not only getting the vaccines, we’re getting it into people’s arms faster than expected.”

Others agree.

“We’re doing an amazing job, and I think the U.S. is really beginning to bend the curve,” said Carlos del Rio, MD, an infectious disease specialist and distinguished professor of medicine at Emory University, Atlanta.

“I think overall it’s just that everybody’s putting in a ton of work to get it done,” he said.

On April 3, the day the United States hit its vaccination record, he was volunteering to give vaccinations.

“I mean, of all the bad things we do to people as clinicians, this is one thing that people are very happy about, right?” Dr. del Rio said.

He said he vaccinated a young woman who asked if she could video chat with her mom, who was feeling nervous about getting the shot. He answered her mom’s questions, and later that day, she came down to be vaccinated herself.
 

‘We view it as a war’

The White House COVID-19 Response Team has worked hard to better coordinate the work of so many people at both the federal and state levels, Andy Slavitt, senior adviser for the team, said in an interview.

“We view it as a war, and in a war, you do everything: You bring experienced personnel; you bring all the resources to bear; you create multiple routes,” Mr. Slavitt said. “You don’t leave anything to chance.”

Among the levers the administration has pulled, using the Defense Production Act has helped vaccine manufacturers get needed supplies, Mr. Slavitt said.

The administration has set up an array of Federal Emergency Management Agency–run community vaccination centers and mobile vaccination sites to complement state-led efforts, and it’s activated a federal health law called the Public Readiness and Emergency Preparedness Act, which provides immunity from liability for retired doctors and nurses, among others, who sign up to help give vaccinations. That’s helped get more people into the field giving shots. 

The administration also canceled a plan to allocate vaccines to states based on their pace of administration, which would have punished underperforming states. Instead, doses are allocated based on population. 

In a media call on April 7, when asked whether the administration would send additional vaccines to Michigan, a state that’s seeing a surge of COVID-19 cases with more transmissible variants, Mr. Slavitt said they weren’t managing vaccine supply “according to some formula.”

He said they were distributing based on population “because that’s fundamental,” but were also locating vaccines “surgically in places that have had the greatest disease and where people have the greatest exposure.”

He said sites like community health centers and retail pharmacies have the power to order vaccines directly from the federal government, which helps get more supply to harder-hit areas.

Mr. Slavitt said hitting 4.1 million daily vaccinations on April 3 was gratifying.

“I’ve seen photographs ... of people breaking down in tears when they get their vaccine, people who are giving standing ovations to active military for taking care of them,” he said, “and I think about people who have gone for a long time without hope, or who have been very scared.

“It’s incredibly encouraging to think about maybe a few million people taking a step back to normal life again,” he said.

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

Each afternoon, Cyrus Shahpar, MD, the data guru for the White House COVID-19 Response Team, sends an email to staffers with the daily count of COVID-19 vaccinations delivered in the United States.

The numbers, collected from states ahead of the final figures being posted on the Centers for Disease Control and Prevention website, act as a report card of sorts on the team’s efforts.

On Saturday, April 3, it was a new record: 4.1 million vaccinations delivered in a single day, more than the total population of some states.

While the United States has a long way to go before it is done with COVID-19, there’s finally some good news in the nation’s long and blundering slog through the pandemic.

After a rocky start in December 2020 and January 2021, vaccination is happening faster than nearly anyone thought possible. As more people see their friends and family roll up their sleeves, hesitancy is dropping, too.

In settings where large numbers of people are vaccinated, such as nursing homes, COVID-19 cases and deaths have plunged.

Those gains, however, haven’t been shared equally. According to CDC data, 69% of people who are fully vaccinated are White, while just 8% are Black and about 9% are Hispanic, a group that now represents most new COVID-19 cases. 

Officials say that’s partly because the vaccines were rolled out to the elderly first. The average life expectancy for Black people in the United States is now age 72, which means there were fewer people of color represented in the first groups to become eligible. Experts are hopeful that underrepresented groups will start to catch up as more states open up vaccinations to younger people.

Based on overall numbers of daily vaccine doses, the United States ranks third, behind China and India. America ranks fourth – behind Israel, the United Kingdom, and Chile – in the total share of the population that’s been vaccinated, according to the website Our World in Data.
 

A positive development

It’s a stunning turnaround for a country that failed for months to develop effective tests, and still struggles in some quarters to investigate new cases and quarantine their contacts.

The 7-day rolling average of vaccines administered in the United States is currently more than 3 million a day.

“We knew that we needed to get to 3 million a day at some point, if we were going to get most people vaccinated this year, but I don’t think that most people expected it to happen this early,” said Eric Toner, MD, a senior scholar with the Johns Hopkins Center for Health Security in Baltimore.

Before taking office, President Joe Biden pledged to get 100 million shots in arms within his first 100 days in office. After hitting that goal in late March, he doubled it, to 200 million vaccinations by April 30. After first saying all adults should be eligible to get in line for the vaccine by May 1, on April 6, he bumped up that date to April 19. 

Some media reports have seen this repeated moving of the goalposts as calculated – an unstated strategy of underpromising and overdelivering with the aim of rebuilding public trust.

But others pointed out that, even if that’s true, the goals being set aren’t easy, and hitting them has never been a given.

“I think the Biden administration really gets a lot of credit for pushing the companies to get more vaccine out faster than they had planned to,” Dr. Toner said. “And the states have really responded as well as the federal government in terms of getting vaccination sites going. So we’re not only getting the vaccines, we’re getting it into people’s arms faster than expected.”

Others agree.

“We’re doing an amazing job, and I think the U.S. is really beginning to bend the curve,” said Carlos del Rio, MD, an infectious disease specialist and distinguished professor of medicine at Emory University, Atlanta.

“I think overall it’s just that everybody’s putting in a ton of work to get it done,” he said.

On April 3, the day the United States hit its vaccination record, he was volunteering to give vaccinations.

“I mean, of all the bad things we do to people as clinicians, this is one thing that people are very happy about, right?” Dr. del Rio said.

He said he vaccinated a young woman who asked if she could video chat with her mom, who was feeling nervous about getting the shot. He answered her mom’s questions, and later that day, she came down to be vaccinated herself.
 

‘We view it as a war’

The White House COVID-19 Response Team has worked hard to better coordinate the work of so many people at both the federal and state levels, Andy Slavitt, senior adviser for the team, said in an interview.

“We view it as a war, and in a war, you do everything: You bring experienced personnel; you bring all the resources to bear; you create multiple routes,” Mr. Slavitt said. “You don’t leave anything to chance.”

Among the levers the administration has pulled, using the Defense Production Act has helped vaccine manufacturers get needed supplies, Mr. Slavitt said.

The administration has set up an array of Federal Emergency Management Agency–run community vaccination centers and mobile vaccination sites to complement state-led efforts, and it’s activated a federal health law called the Public Readiness and Emergency Preparedness Act, which provides immunity from liability for retired doctors and nurses, among others, who sign up to help give vaccinations. That’s helped get more people into the field giving shots. 

The administration also canceled a plan to allocate vaccines to states based on their pace of administration, which would have punished underperforming states. Instead, doses are allocated based on population. 

In a media call on April 7, when asked whether the administration would send additional vaccines to Michigan, a state that’s seeing a surge of COVID-19 cases with more transmissible variants, Mr. Slavitt said they weren’t managing vaccine supply “according to some formula.”

He said they were distributing based on population “because that’s fundamental,” but were also locating vaccines “surgically in places that have had the greatest disease and where people have the greatest exposure.”

He said sites like community health centers and retail pharmacies have the power to order vaccines directly from the federal government, which helps get more supply to harder-hit areas.

Mr. Slavitt said hitting 4.1 million daily vaccinations on April 3 was gratifying.

“I’ve seen photographs ... of people breaking down in tears when they get their vaccine, people who are giving standing ovations to active military for taking care of them,” he said, “and I think about people who have gone for a long time without hope, or who have been very scared.

“It’s incredibly encouraging to think about maybe a few million people taking a step back to normal life again,” he said.

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

Each afternoon, Cyrus Shahpar, MD, the data guru for the White House COVID-19 Response Team, sends an email to staffers with the daily count of COVID-19 vaccinations delivered in the United States.

The numbers, collected from states ahead of the final figures being posted on the Centers for Disease Control and Prevention website, act as a report card of sorts on the team’s efforts.

On Saturday, April 3, it was a new record: 4.1 million vaccinations delivered in a single day, more than the total population of some states.

While the United States has a long way to go before it is done with COVID-19, there’s finally some good news in the nation’s long and blundering slog through the pandemic.

After a rocky start in December 2020 and January 2021, vaccination is happening faster than nearly anyone thought possible. As more people see their friends and family roll up their sleeves, hesitancy is dropping, too.

In settings where large numbers of people are vaccinated, such as nursing homes, COVID-19 cases and deaths have plunged.

Those gains, however, haven’t been shared equally. According to CDC data, 69% of people who are fully vaccinated are White, while just 8% are Black and about 9% are Hispanic, a group that now represents most new COVID-19 cases. 

Officials say that’s partly because the vaccines were rolled out to the elderly first. The average life expectancy for Black people in the United States is now age 72, which means there were fewer people of color represented in the first groups to become eligible. Experts are hopeful that underrepresented groups will start to catch up as more states open up vaccinations to younger people.

Based on overall numbers of daily vaccine doses, the United States ranks third, behind China and India. America ranks fourth – behind Israel, the United Kingdom, and Chile – in the total share of the population that’s been vaccinated, according to the website Our World in Data.
 

A positive development

It’s a stunning turnaround for a country that failed for months to develop effective tests, and still struggles in some quarters to investigate new cases and quarantine their contacts.

The 7-day rolling average of vaccines administered in the United States is currently more than 3 million a day.

“We knew that we needed to get to 3 million a day at some point, if we were going to get most people vaccinated this year, but I don’t think that most people expected it to happen this early,” said Eric Toner, MD, a senior scholar with the Johns Hopkins Center for Health Security in Baltimore.

Before taking office, President Joe Biden pledged to get 100 million shots in arms within his first 100 days in office. After hitting that goal in late March, he doubled it, to 200 million vaccinations by April 30. After first saying all adults should be eligible to get in line for the vaccine by May 1, on April 6, he bumped up that date to April 19. 

Some media reports have seen this repeated moving of the goalposts as calculated – an unstated strategy of underpromising and overdelivering with the aim of rebuilding public trust.

But others pointed out that, even if that’s true, the goals being set aren’t easy, and hitting them has never been a given.

“I think the Biden administration really gets a lot of credit for pushing the companies to get more vaccine out faster than they had planned to,” Dr. Toner said. “And the states have really responded as well as the federal government in terms of getting vaccination sites going. So we’re not only getting the vaccines, we’re getting it into people’s arms faster than expected.”

Others agree.

“We’re doing an amazing job, and I think the U.S. is really beginning to bend the curve,” said Carlos del Rio, MD, an infectious disease specialist and distinguished professor of medicine at Emory University, Atlanta.

“I think overall it’s just that everybody’s putting in a ton of work to get it done,” he said.

On April 3, the day the United States hit its vaccination record, he was volunteering to give vaccinations.

“I mean, of all the bad things we do to people as clinicians, this is one thing that people are very happy about, right?” Dr. del Rio said.

He said he vaccinated a young woman who asked if she could video chat with her mom, who was feeling nervous about getting the shot. He answered her mom’s questions, and later that day, she came down to be vaccinated herself.
 

‘We view it as a war’

The White House COVID-19 Response Team has worked hard to better coordinate the work of so many people at both the federal and state levels, Andy Slavitt, senior adviser for the team, said in an interview.

“We view it as a war, and in a war, you do everything: You bring experienced personnel; you bring all the resources to bear; you create multiple routes,” Mr. Slavitt said. “You don’t leave anything to chance.”

Among the levers the administration has pulled, using the Defense Production Act has helped vaccine manufacturers get needed supplies, Mr. Slavitt said.

The administration has set up an array of Federal Emergency Management Agency–run community vaccination centers and mobile vaccination sites to complement state-led efforts, and it’s activated a federal health law called the Public Readiness and Emergency Preparedness Act, which provides immunity from liability for retired doctors and nurses, among others, who sign up to help give vaccinations. That’s helped get more people into the field giving shots. 

The administration also canceled a plan to allocate vaccines to states based on their pace of administration, which would have punished underperforming states. Instead, doses are allocated based on population. 

In a media call on April 7, when asked whether the administration would send additional vaccines to Michigan, a state that’s seeing a surge of COVID-19 cases with more transmissible variants, Mr. Slavitt said they weren’t managing vaccine supply “according to some formula.”

He said they were distributing based on population “because that’s fundamental,” but were also locating vaccines “surgically in places that have had the greatest disease and where people have the greatest exposure.”

He said sites like community health centers and retail pharmacies have the power to order vaccines directly from the federal government, which helps get more supply to harder-hit areas.

Mr. Slavitt said hitting 4.1 million daily vaccinations on April 3 was gratifying.

“I’ve seen photographs ... of people breaking down in tears when they get their vaccine, people who are giving standing ovations to active military for taking care of them,” he said, “and I think about people who have gone for a long time without hope, or who have been very scared.

“It’s incredibly encouraging to think about maybe a few million people taking a step back to normal life again,” he said.

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

Arkansas has become the first state to pass a law prohibiting doctors from giving gender-affirming medical treatments to transgender youths, CNN reported.

Gov. Asa Hutchinson had vetoed the bill on April 5, calling it a “product of the cultural war in America.” But on April 6, the state House and Senate voted to override the veto, making it state law, CNN reported.

At least 17 other states are considering similar legislation, but the Arkansas bill was the first to reach the governor’s desk, the Washington Post reported.

The bill bans doctors from prescribing puberty blockers, hormone therapies, or genital-altering surgeries for anybody under 18. Ever referring a youth for such treatment from another doctor is prohibited.

“It is of grave concern to the General Assembly that the medical community is allowing individuals who experience distress at identifying with their biological sex to be subjects of irreversible and drastic nongenital gender reassignment surgery and irreversible, permanently sterilizing genital gender reassignment surgery, despite the lack of studies showing that the benefits of such extreme interventions outweigh the risks,” the text of the bill said.

Gov. Hutchinson, a Republican, had called the measure a “vast government overreach” in announcing his veto.

“The bill is overbroad, extreme, and does not grandfather those young people who are currently under hormone treatment,” Gov. Hutchinson said. “The young people who are currently under a doctor’s care will be without treatment when this law goes into effect. That means they will be looking to the black market or go out of state ... to find the treatment that they want and need. This is not the right path to put them on.”

Many medical groups have come out against this kind of legislation. The American Academy of Child and Adolescent Psychiatry says it “strongly opposes any efforts – legal, legislative, and otherwise – to block access to these recognized interventions.”

Chase Strangio, the deputy director for transgender justice with the American Civil Liberty Union’s LGBTQ & HIV Project, complimented Gov. Hutchinson for his veto. On April 6, he said the ACLU is preparing to challenge the bill in court, CNN said.

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

Arkansas has become the first state to pass a law prohibiting doctors from giving gender-affirming medical treatments to transgender youths, CNN reported.

Gov. Asa Hutchinson had vetoed the bill on April 5, calling it a “product of the cultural war in America.” But on April 6, the state House and Senate voted to override the veto, making it state law, CNN reported.

At least 17 other states are considering similar legislation, but the Arkansas bill was the first to reach the governor’s desk, the Washington Post reported.

The bill bans doctors from prescribing puberty blockers, hormone therapies, or genital-altering surgeries for anybody under 18. Ever referring a youth for such treatment from another doctor is prohibited.

“It is of grave concern to the General Assembly that the medical community is allowing individuals who experience distress at identifying with their biological sex to be subjects of irreversible and drastic nongenital gender reassignment surgery and irreversible, permanently sterilizing genital gender reassignment surgery, despite the lack of studies showing that the benefits of such extreme interventions outweigh the risks,” the text of the bill said.

Gov. Hutchinson, a Republican, had called the measure a “vast government overreach” in announcing his veto.

“The bill is overbroad, extreme, and does not grandfather those young people who are currently under hormone treatment,” Gov. Hutchinson said. “The young people who are currently under a doctor’s care will be without treatment when this law goes into effect. That means they will be looking to the black market or go out of state ... to find the treatment that they want and need. This is not the right path to put them on.”

Many medical groups have come out against this kind of legislation. The American Academy of Child and Adolescent Psychiatry says it “strongly opposes any efforts – legal, legislative, and otherwise – to block access to these recognized interventions.”

Chase Strangio, the deputy director for transgender justice with the American Civil Liberty Union’s LGBTQ & HIV Project, complimented Gov. Hutchinson for his veto. On April 6, he said the ACLU is preparing to challenge the bill in court, CNN said.

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

Arkansas has become the first state to pass a law prohibiting doctors from giving gender-affirming medical treatments to transgender youths, CNN reported.

Gov. Asa Hutchinson had vetoed the bill on April 5, calling it a “product of the cultural war in America.” But on April 6, the state House and Senate voted to override the veto, making it state law, CNN reported.

At least 17 other states are considering similar legislation, but the Arkansas bill was the first to reach the governor’s desk, the Washington Post reported.

The bill bans doctors from prescribing puberty blockers, hormone therapies, or genital-altering surgeries for anybody under 18. Ever referring a youth for such treatment from another doctor is prohibited.

“It is of grave concern to the General Assembly that the medical community is allowing individuals who experience distress at identifying with their biological sex to be subjects of irreversible and drastic nongenital gender reassignment surgery and irreversible, permanently sterilizing genital gender reassignment surgery, despite the lack of studies showing that the benefits of such extreme interventions outweigh the risks,” the text of the bill said.

Gov. Hutchinson, a Republican, had called the measure a “vast government overreach” in announcing his veto.

“The bill is overbroad, extreme, and does not grandfather those young people who are currently under hormone treatment,” Gov. Hutchinson said. “The young people who are currently under a doctor’s care will be without treatment when this law goes into effect. That means they will be looking to the black market or go out of state ... to find the treatment that they want and need. This is not the right path to put them on.”

Many medical groups have come out against this kind of legislation. The American Academy of Child and Adolescent Psychiatry says it “strongly opposes any efforts – legal, legislative, and otherwise – to block access to these recognized interventions.”

Chase Strangio, the deputy director for transgender justice with the American Civil Liberty Union’s LGBTQ & HIV Project, complimented Gov. Hutchinson for his veto. On April 6, he said the ACLU is preparing to challenge the bill in court, CNN said.

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