Clinician Reviews

Estimating an individual’s risk of cardiovascular disease (CVD) remains the cornerstone of the 2021 European Society of Cardiology guidelines on CVD prevention in clinical practice. The new guidelines were published online Aug. 30 in the European Heart Journal to coincide with presentation at the European Stroke Congress (ESOC) 2021.   

They were developed by an ESOC task force in collaboration with 12 medical societies and with special contribution of the European Association of Preventive Cardiology.

“A chief goal of the task force was to create a single CVD prevention guideline for everyone – for primary care, for hospital care, for guiding clinical practice – so one guideline for all,” said cochair of the guideline committee Frank Visseren, MD, PhD, University Medical Center Utrecht, Netherlands. “We also wanted to make a more personalized CVD prevention guideline, instead of a one-size-fits-all. In clinical practice, people are very, very different, and we really want to have a more individualized prevention guideline,” said Dr. Visseren, as well as provide “more room for shared decision-making.”
 

Prevention at the individual and population levels

The new guidelines also give more attention to CVD prevention in older persons. “Many of our patients are over 70 years old and we really want to have more detail, more guidance on older persons,” said Dr. Visseren.

The guideline is divided into two sections. One section covers CVD prevention at the individual level in apparently healthy people, in patients with established CVD, and in those with diabetes, familial hypercholesterolemia, or chronic kidney disease.

The other section covers CVD prevention at the population level, including public health policy, interventions, and the environment, including putting in place measures to reduce air pollution, use of fossil fuels, and limiting carbon dioxide emissions.

Targets for blood lipids, blood pressure, and glycemic control in diabetes remain in line with recent ESC guidelines on dyslipidemias, hypertension, or diabetes.

However, the guidelines introduce a new stepwise treatment-intensification approach to achieve these targets, with consideration of CVD risk, treatment benefit of risk factors, risk modifiers, comorbidities, and patient preferences.

The 2021 CVD prevention guidelines also embrace the recently published Systemic Coronary Risk Estimation 2 (SCORE2) and Systemic Coronary Risk Estimation 2-Older Persons (SCORE2-OP) algorithms. “The algorithms we are using are a bit old and we want to have more updated risk prediction, because that’s the starting point of CVD prevention,” Dr. Visseren said.

The guidelines also introduce age-specific risk thresholds for risk factor treatments in apparently healthy people and provide estimation of lifetime CVD risk and treatment benefit. This will allow clinicians to have “an informed discussion with patients on lifetime risk and potential treatment benefits,” Dr. Visseren said.

For the first time, the guidelines recommend smoking cessation regardless of whether it leads to weight gain, as weight gain does not lessen the benefits of cessation.

Regarding exercise, adults of all ages should aim for at least 150-300 minutes a week of moderate, or 75-150 minutes a week of vigorous, aerobic physical activity. The guidelines recommend reducing sedentary time and engaging in at least light activity throughout the day.

Regarding nutrition, the guidelines advise adopting a Mediterranean or similar diet; restricting alcohol intake to a maximum of 100 g per week (a standard drink is 8-14 g); eating fish, preferably fatty fish, at least once a week; and restricting consumption of meat, particularly processed meat.

Also for the first time, the guidelines state that bariatric surgery should be considered for obese individuals at elevated risk of CVD when a healthy diet and exercise fail to lead to weight loss that is maintained.

They note that individuals with mental disorders need additional attention and support to improve adherence to lifestyle changes and drug treatment.

They advise consideration of referring patients with heart disease and significant stress and anxiety to psychotherapeutic stress management to reduce stress symptoms and improve CV outcomes.

Potential cost issues that could be considered when implementing the guidelines are also reviewed.

Dr. Visseren acknowledged and thanked the task force members for continuing their work on the guidelines over the 2 “challenging” years.
 

Setting the bar lower?

Discussant for the guideline presentation, Diederick Grobbee, MD, University Medical Center Utrecht, who was not involved in drafting the guidelines, said he does have one conflict of interest, which is a “passion for prevention.” From that perspective, he said the guideline panel “should be applauded; the once-every-5-year issuing of the prevention guidelines is a major event.”

Dr. Grobbee noted that the working group “really tried to follow their ambitions and goals, in a way making the guidelines simpler, or perhaps setting the bar not initially as high as we used to do, which may, in fact, sometimes scare off physicians and patients alike.”

“We’ve had prevention guidelines for quite some time now, yet looking at what is accomplished in practice is sobering,” said Dr. Grobbee. Introducing a stepwise approach is “really appealing,” he added.

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

Estimating an individual’s risk of cardiovascular disease (CVD) remains the cornerstone of the 2021 European Society of Cardiology guidelines on CVD prevention in clinical practice. The new guidelines were published online Aug. 30 in the European Heart Journal to coincide with presentation at the European Stroke Congress (ESOC) 2021.   

They were developed by an ESOC task force in collaboration with 12 medical societies and with special contribution of the European Association of Preventive Cardiology.

“A chief goal of the task force was to create a single CVD prevention guideline for everyone – for primary care, for hospital care, for guiding clinical practice – so one guideline for all,” said cochair of the guideline committee Frank Visseren, MD, PhD, University Medical Center Utrecht, Netherlands. “We also wanted to make a more personalized CVD prevention guideline, instead of a one-size-fits-all. In clinical practice, people are very, very different, and we really want to have a more individualized prevention guideline,” said Dr. Visseren, as well as provide “more room for shared decision-making.”
 

Prevention at the individual and population levels

The new guidelines also give more attention to CVD prevention in older persons. “Many of our patients are over 70 years old and we really want to have more detail, more guidance on older persons,” said Dr. Visseren.

The guideline is divided into two sections. One section covers CVD prevention at the individual level in apparently healthy people, in patients with established CVD, and in those with diabetes, familial hypercholesterolemia, or chronic kidney disease.

The other section covers CVD prevention at the population level, including public health policy, interventions, and the environment, including putting in place measures to reduce air pollution, use of fossil fuels, and limiting carbon dioxide emissions.

Targets for blood lipids, blood pressure, and glycemic control in diabetes remain in line with recent ESC guidelines on dyslipidemias, hypertension, or diabetes.

However, the guidelines introduce a new stepwise treatment-intensification approach to achieve these targets, with consideration of CVD risk, treatment benefit of risk factors, risk modifiers, comorbidities, and patient preferences.

The 2021 CVD prevention guidelines also embrace the recently published Systemic Coronary Risk Estimation 2 (SCORE2) and Systemic Coronary Risk Estimation 2-Older Persons (SCORE2-OP) algorithms. “The algorithms we are using are a bit old and we want to have more updated risk prediction, because that’s the starting point of CVD prevention,” Dr. Visseren said.

The guidelines also introduce age-specific risk thresholds for risk factor treatments in apparently healthy people and provide estimation of lifetime CVD risk and treatment benefit. This will allow clinicians to have “an informed discussion with patients on lifetime risk and potential treatment benefits,” Dr. Visseren said.

For the first time, the guidelines recommend smoking cessation regardless of whether it leads to weight gain, as weight gain does not lessen the benefits of cessation.

Regarding exercise, adults of all ages should aim for at least 150-300 minutes a week of moderate, or 75-150 minutes a week of vigorous, aerobic physical activity. The guidelines recommend reducing sedentary time and engaging in at least light activity throughout the day.

Regarding nutrition, the guidelines advise adopting a Mediterranean or similar diet; restricting alcohol intake to a maximum of 100 g per week (a standard drink is 8-14 g); eating fish, preferably fatty fish, at least once a week; and restricting consumption of meat, particularly processed meat.

Also for the first time, the guidelines state that bariatric surgery should be considered for obese individuals at elevated risk of CVD when a healthy diet and exercise fail to lead to weight loss that is maintained.

They note that individuals with mental disorders need additional attention and support to improve adherence to lifestyle changes and drug treatment.

They advise consideration of referring patients with heart disease and significant stress and anxiety to psychotherapeutic stress management to reduce stress symptoms and improve CV outcomes.

Potential cost issues that could be considered when implementing the guidelines are also reviewed.

Dr. Visseren acknowledged and thanked the task force members for continuing their work on the guidelines over the 2 “challenging” years.
 

Setting the bar lower?

Discussant for the guideline presentation, Diederick Grobbee, MD, University Medical Center Utrecht, who was not involved in drafting the guidelines, said he does have one conflict of interest, which is a “passion for prevention.” From that perspective, he said the guideline panel “should be applauded; the once-every-5-year issuing of the prevention guidelines is a major event.”

Dr. Grobbee noted that the working group “really tried to follow their ambitions and goals, in a way making the guidelines simpler, or perhaps setting the bar not initially as high as we used to do, which may, in fact, sometimes scare off physicians and patients alike.”

“We’ve had prevention guidelines for quite some time now, yet looking at what is accomplished in practice is sobering,” said Dr. Grobbee. Introducing a stepwise approach is “really appealing,” he added.

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

Estimating an individual’s risk of cardiovascular disease (CVD) remains the cornerstone of the 2021 European Society of Cardiology guidelines on CVD prevention in clinical practice. The new guidelines were published online Aug. 30 in the European Heart Journal to coincide with presentation at the European Stroke Congress (ESOC) 2021.   

They were developed by an ESOC task force in collaboration with 12 medical societies and with special contribution of the European Association of Preventive Cardiology.

“A chief goal of the task force was to create a single CVD prevention guideline for everyone – for primary care, for hospital care, for guiding clinical practice – so one guideline for all,” said cochair of the guideline committee Frank Visseren, MD, PhD, University Medical Center Utrecht, Netherlands. “We also wanted to make a more personalized CVD prevention guideline, instead of a one-size-fits-all. In clinical practice, people are very, very different, and we really want to have a more individualized prevention guideline,” said Dr. Visseren, as well as provide “more room for shared decision-making.”
 

Prevention at the individual and population levels

The new guidelines also give more attention to CVD prevention in older persons. “Many of our patients are over 70 years old and we really want to have more detail, more guidance on older persons,” said Dr. Visseren.

The guideline is divided into two sections. One section covers CVD prevention at the individual level in apparently healthy people, in patients with established CVD, and in those with diabetes, familial hypercholesterolemia, or chronic kidney disease.

The other section covers CVD prevention at the population level, including public health policy, interventions, and the environment, including putting in place measures to reduce air pollution, use of fossil fuels, and limiting carbon dioxide emissions.

Targets for blood lipids, blood pressure, and glycemic control in diabetes remain in line with recent ESC guidelines on dyslipidemias, hypertension, or diabetes.

However, the guidelines introduce a new stepwise treatment-intensification approach to achieve these targets, with consideration of CVD risk, treatment benefit of risk factors, risk modifiers, comorbidities, and patient preferences.

The 2021 CVD prevention guidelines also embrace the recently published Systemic Coronary Risk Estimation 2 (SCORE2) and Systemic Coronary Risk Estimation 2-Older Persons (SCORE2-OP) algorithms. “The algorithms we are using are a bit old and we want to have more updated risk prediction, because that’s the starting point of CVD prevention,” Dr. Visseren said.

The guidelines also introduce age-specific risk thresholds for risk factor treatments in apparently healthy people and provide estimation of lifetime CVD risk and treatment benefit. This will allow clinicians to have “an informed discussion with patients on lifetime risk and potential treatment benefits,” Dr. Visseren said.

For the first time, the guidelines recommend smoking cessation regardless of whether it leads to weight gain, as weight gain does not lessen the benefits of cessation.

Regarding exercise, adults of all ages should aim for at least 150-300 minutes a week of moderate, or 75-150 minutes a week of vigorous, aerobic physical activity. The guidelines recommend reducing sedentary time and engaging in at least light activity throughout the day.

Regarding nutrition, the guidelines advise adopting a Mediterranean or similar diet; restricting alcohol intake to a maximum of 100 g per week (a standard drink is 8-14 g); eating fish, preferably fatty fish, at least once a week; and restricting consumption of meat, particularly processed meat.

Also for the first time, the guidelines state that bariatric surgery should be considered for obese individuals at elevated risk of CVD when a healthy diet and exercise fail to lead to weight loss that is maintained.

They note that individuals with mental disorders need additional attention and support to improve adherence to lifestyle changes and drug treatment.

They advise consideration of referring patients with heart disease and significant stress and anxiety to psychotherapeutic stress management to reduce stress symptoms and improve CV outcomes.

Potential cost issues that could be considered when implementing the guidelines are also reviewed.

Dr. Visseren acknowledged and thanked the task force members for continuing their work on the guidelines over the 2 “challenging” years.
 

Setting the bar lower?

Discussant for the guideline presentation, Diederick Grobbee, MD, University Medical Center Utrecht, who was not involved in drafting the guidelines, said he does have one conflict of interest, which is a “passion for prevention.” From that perspective, he said the guideline panel “should be applauded; the once-every-5-year issuing of the prevention guidelines is a major event.”

Dr. Grobbee noted that the working group “really tried to follow their ambitions and goals, in a way making the guidelines simpler, or perhaps setting the bar not initially as high as we used to do, which may, in fact, sometimes scare off physicians and patients alike.”

“We’ve had prevention guidelines for quite some time now, yet looking at what is accomplished in practice is sobering,” said Dr. Grobbee. Introducing a stepwise approach is “really appealing,” he added.

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

The U.S. Food and Drug Administration has approved lonapegsomatropin (Skytrofa, Ascendis Pharma), the first weekly subcutaneous injectable growth hormone for children with growth hormone deficiency (GHD).

The approval was based on the findings of the 52-week, phase 3 heiGHt trial in 161 treatment-naive pediatric patients with GHD, which was recently published in the Journal of Clinical Endocrinology & Metabolism.

Since 1987, the standard treatment for pediatric GHD, in which the pituitary gland does not produce enough growth hormone, has been a daily injection of somatropin (recombinant DNA human growth hormone).

“I am excited to be able to reduce the number of shots for some children requiring growth hormone therapy” with this new dosing option, Bradley S. Miller, MD, PhD, who was not involved with the research, said in an email.

“I am hopeful that a once-weekly growth hormone option will improve adherence to growth hormone therapy, leading to improved growth and metabolic outcomes,” added Dr. Miller, professor and division director, pediatric endocrinology, at the University of Minnesota Masonic Children’s Hospital, Minneapolis.

Lonapegsomatropin is approved for the treatment of pediatric patients age 1 year and older who weigh at least 11.5 kg (25.4 pounds) and have short stature due to inadequate secretion of endogenous growth hormone, according to the prescribing information.

The drug molecule consists of a prodrug of somatropin that is inactive when it is bound to a proprietary TransCon (transient conjugation) inert carrier using a TransCon linker. The three-part molecule breaks apart after injection, exposing the active somatropin that is slowly released.

The heiGHt trial demonstrated noninferiority of lonapegsomatropin to somatropin daily injections. Children who received weekly lonapegsomatropin grew 11.2 cm (4.4 inches) per year, whereas those who received an equivalent total dose of somatropin daily injections grew 10.3 cm (4.1 inches) per year.

Safety outcomes – the ratio of bone age to chronologic age, adverse events, tolerability, and immunogenicity – were similar in both groups.
 

Anticipated uptake, other drugs on horizon

Lonapegsomatropin is expected to be available shortly in the United States along with a suite of patient support programs, according to a company press release.

“The impact of the approval of lonapegsomatropin on clinical practice will depend upon its availability, coverage by insurance providers, and patient/provider comfort with using a new product,” Dr. Miller said.

For most pediatric endocrinologists, daily growth hormone has been available their entire careers, so he expects it will take some time for the pediatric endocrinology community to be comfortable prescribing long-acting growth hormone (LAGH), the name given to the once-weekly products.

In the meantime, an FDA decision on another once-weekly growth hormone, somatrogon (OPKO Health/Pfizer) for children with GHD is expected very soon, in October 2021.

And a weekly injectable somapacitan (Sogroya, Novo Nordisk), approved by the FDA in September last year for adults with GHD, is also being studied in children, with estimated study completion in 2024.

“Approval of more LAGH molecules, approval of LAGH for more indications, real-world evidence of safety, efficacy, and improved adherence, and personal experience with LAGH will all likely lead to increased LAGH use over time,” Dr. Miller speculated.

“Over the long-term, I expect insurance providers will cover LAGH products,” he surmised, “but that the price will be similar to or slightly higher than daily growth hormone.”

However, if improved adherence with LAGH is demonstrated and associated with better treatment outcomes, the price of LAGH will likely increase and use of daily growth hormone will decrease, he predicts.

Paul Saenger, MD, who was not involved with the research, believes “all three long-acting growth hormone drugs will eventually be approved for GHD in children.”

“The price will be the same or may be at most 10% more than daily growth hormone replacement,” Dr. Saenger, a pediatric endocrinologist and clinical assistant professor at NYU Long Island School of Medicine, New York, said in an email.

However, daily subcutaneous injections will still be warranted for certain children with GHD, Dr. Miller noted.

“Daily growth hormone may be better than LAGH for a small number of children who have severe GHD associated with hypoglycemia,” he said. “The low levels of growth hormone at the end of the weekly interval of LAGH may allow hypoglycemia to occur in this population.”
 

Phase 3 trial in 161 treatment-naive children with GHD

The heiGHt trial randomized treatment-naive prepubertal children with GHD 2:1 to weekly lonapegsomatropin or daily somatropin (Genotropin, Pfizer) at 73 sites in 15 countries.

The children were a mean age of 8.5 years (range, 3.2-13.1 years), 82% were boys, and 94% were White.

There were no reported serious adverse events or discontinuations related to lonapegsomatropin.

The most common adverse reactions in ≥5% of these pediatric patients were viral infection (15%), pyrexia (15%), cough (11%), nausea and vomiting (11%), hemorrhage (7%), diarrhea (6%), abdominal pain (6%), and arthralgia and arthritis (6%).

Both study groups reported low incidences of transient, non-neutralizing anti-hGH binding antibodies and no cases of persistent antibodies.

Trial limitations include the fact the study was not blinded (as patients received a weekly or daily injection) and drug doses were fixed at 0.24 mg human growth hormone/kg/week, although in real-world clinical practice, doses may be titrated.

Lonapegsomatropin has been studied in more than 300 children with GHD in the phase 3 program in the heiGHt trial (treatment-naive patients), fliGHt trial (treatment-experienced patients), and enliGHten trial (an ongoing long-term extension trial that includes some patients who have been taking lonapegsomatropin for more than 4 years).

The study was sponsored by Ascendis Pharma. Some of the phase 3 study authors are company employees.

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

The U.S. Food and Drug Administration has approved lonapegsomatropin (Skytrofa, Ascendis Pharma), the first weekly subcutaneous injectable growth hormone for children with growth hormone deficiency (GHD).

The approval was based on the findings of the 52-week, phase 3 heiGHt trial in 161 treatment-naive pediatric patients with GHD, which was recently published in the Journal of Clinical Endocrinology & Metabolism.

Since 1987, the standard treatment for pediatric GHD, in which the pituitary gland does not produce enough growth hormone, has been a daily injection of somatropin (recombinant DNA human growth hormone).

“I am excited to be able to reduce the number of shots for some children requiring growth hormone therapy” with this new dosing option, Bradley S. Miller, MD, PhD, who was not involved with the research, said in an email.

“I am hopeful that a once-weekly growth hormone option will improve adherence to growth hormone therapy, leading to improved growth and metabolic outcomes,” added Dr. Miller, professor and division director, pediatric endocrinology, at the University of Minnesota Masonic Children’s Hospital, Minneapolis.

Lonapegsomatropin is approved for the treatment of pediatric patients age 1 year and older who weigh at least 11.5 kg (25.4 pounds) and have short stature due to inadequate secretion of endogenous growth hormone, according to the prescribing information.

The drug molecule consists of a prodrug of somatropin that is inactive when it is bound to a proprietary TransCon (transient conjugation) inert carrier using a TransCon linker. The three-part molecule breaks apart after injection, exposing the active somatropin that is slowly released.

The heiGHt trial demonstrated noninferiority of lonapegsomatropin to somatropin daily injections. Children who received weekly lonapegsomatropin grew 11.2 cm (4.4 inches) per year, whereas those who received an equivalent total dose of somatropin daily injections grew 10.3 cm (4.1 inches) per year.

Safety outcomes – the ratio of bone age to chronologic age, adverse events, tolerability, and immunogenicity – were similar in both groups.
 

Anticipated uptake, other drugs on horizon

Lonapegsomatropin is expected to be available shortly in the United States along with a suite of patient support programs, according to a company press release.

“The impact of the approval of lonapegsomatropin on clinical practice will depend upon its availability, coverage by insurance providers, and patient/provider comfort with using a new product,” Dr. Miller said.

For most pediatric endocrinologists, daily growth hormone has been available their entire careers, so he expects it will take some time for the pediatric endocrinology community to be comfortable prescribing long-acting growth hormone (LAGH), the name given to the once-weekly products.

In the meantime, an FDA decision on another once-weekly growth hormone, somatrogon (OPKO Health/Pfizer) for children with GHD is expected very soon, in October 2021.

And a weekly injectable somapacitan (Sogroya, Novo Nordisk), approved by the FDA in September last year for adults with GHD, is also being studied in children, with estimated study completion in 2024.

“Approval of more LAGH molecules, approval of LAGH for more indications, real-world evidence of safety, efficacy, and improved adherence, and personal experience with LAGH will all likely lead to increased LAGH use over time,” Dr. Miller speculated.

“Over the long-term, I expect insurance providers will cover LAGH products,” he surmised, “but that the price will be similar to or slightly higher than daily growth hormone.”

However, if improved adherence with LAGH is demonstrated and associated with better treatment outcomes, the price of LAGH will likely increase and use of daily growth hormone will decrease, he predicts.

Paul Saenger, MD, who was not involved with the research, believes “all three long-acting growth hormone drugs will eventually be approved for GHD in children.”

“The price will be the same or may be at most 10% more than daily growth hormone replacement,” Dr. Saenger, a pediatric endocrinologist and clinical assistant professor at NYU Long Island School of Medicine, New York, said in an email.

However, daily subcutaneous injections will still be warranted for certain children with GHD, Dr. Miller noted.

“Daily growth hormone may be better than LAGH for a small number of children who have severe GHD associated with hypoglycemia,” he said. “The low levels of growth hormone at the end of the weekly interval of LAGH may allow hypoglycemia to occur in this population.”
 

Phase 3 trial in 161 treatment-naive children with GHD

The heiGHt trial randomized treatment-naive prepubertal children with GHD 2:1 to weekly lonapegsomatropin or daily somatropin (Genotropin, Pfizer) at 73 sites in 15 countries.

The children were a mean age of 8.5 years (range, 3.2-13.1 years), 82% were boys, and 94% were White.

There were no reported serious adverse events or discontinuations related to lonapegsomatropin.

The most common adverse reactions in ≥5% of these pediatric patients were viral infection (15%), pyrexia (15%), cough (11%), nausea and vomiting (11%), hemorrhage (7%), diarrhea (6%), abdominal pain (6%), and arthralgia and arthritis (6%).

Both study groups reported low incidences of transient, non-neutralizing anti-hGH binding antibodies and no cases of persistent antibodies.

Trial limitations include the fact the study was not blinded (as patients received a weekly or daily injection) and drug doses were fixed at 0.24 mg human growth hormone/kg/week, although in real-world clinical practice, doses may be titrated.

Lonapegsomatropin has been studied in more than 300 children with GHD in the phase 3 program in the heiGHt trial (treatment-naive patients), fliGHt trial (treatment-experienced patients), and enliGHten trial (an ongoing long-term extension trial that includes some patients who have been taking lonapegsomatropin for more than 4 years).

The study was sponsored by Ascendis Pharma. Some of the phase 3 study authors are company employees.

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

The U.S. Food and Drug Administration has approved lonapegsomatropin (Skytrofa, Ascendis Pharma), the first weekly subcutaneous injectable growth hormone for children with growth hormone deficiency (GHD).

The approval was based on the findings of the 52-week, phase 3 heiGHt trial in 161 treatment-naive pediatric patients with GHD, which was recently published in the Journal of Clinical Endocrinology & Metabolism.

Since 1987, the standard treatment for pediatric GHD, in which the pituitary gland does not produce enough growth hormone, has been a daily injection of somatropin (recombinant DNA human growth hormone).

“I am excited to be able to reduce the number of shots for some children requiring growth hormone therapy” with this new dosing option, Bradley S. Miller, MD, PhD, who was not involved with the research, said in an email.

“I am hopeful that a once-weekly growth hormone option will improve adherence to growth hormone therapy, leading to improved growth and metabolic outcomes,” added Dr. Miller, professor and division director, pediatric endocrinology, at the University of Minnesota Masonic Children’s Hospital, Minneapolis.

Lonapegsomatropin is approved for the treatment of pediatric patients age 1 year and older who weigh at least 11.5 kg (25.4 pounds) and have short stature due to inadequate secretion of endogenous growth hormone, according to the prescribing information.

The drug molecule consists of a prodrug of somatropin that is inactive when it is bound to a proprietary TransCon (transient conjugation) inert carrier using a TransCon linker. The three-part molecule breaks apart after injection, exposing the active somatropin that is slowly released.

The heiGHt trial demonstrated noninferiority of lonapegsomatropin to somatropin daily injections. Children who received weekly lonapegsomatropin grew 11.2 cm (4.4 inches) per year, whereas those who received an equivalent total dose of somatropin daily injections grew 10.3 cm (4.1 inches) per year.

Safety outcomes – the ratio of bone age to chronologic age, adverse events, tolerability, and immunogenicity – were similar in both groups.
 

Anticipated uptake, other drugs on horizon

Lonapegsomatropin is expected to be available shortly in the United States along with a suite of patient support programs, according to a company press release.

“The impact of the approval of lonapegsomatropin on clinical practice will depend upon its availability, coverage by insurance providers, and patient/provider comfort with using a new product,” Dr. Miller said.

For most pediatric endocrinologists, daily growth hormone has been available their entire careers, so he expects it will take some time for the pediatric endocrinology community to be comfortable prescribing long-acting growth hormone (LAGH), the name given to the once-weekly products.

In the meantime, an FDA decision on another once-weekly growth hormone, somatrogon (OPKO Health/Pfizer) for children with GHD is expected very soon, in October 2021.

And a weekly injectable somapacitan (Sogroya, Novo Nordisk), approved by the FDA in September last year for adults with GHD, is also being studied in children, with estimated study completion in 2024.

“Approval of more LAGH molecules, approval of LAGH for more indications, real-world evidence of safety, efficacy, and improved adherence, and personal experience with LAGH will all likely lead to increased LAGH use over time,” Dr. Miller speculated.

“Over the long-term, I expect insurance providers will cover LAGH products,” he surmised, “but that the price will be similar to or slightly higher than daily growth hormone.”

However, if improved adherence with LAGH is demonstrated and associated with better treatment outcomes, the price of LAGH will likely increase and use of daily growth hormone will decrease, he predicts.

Paul Saenger, MD, who was not involved with the research, believes “all three long-acting growth hormone drugs will eventually be approved for GHD in children.”

“The price will be the same or may be at most 10% more than daily growth hormone replacement,” Dr. Saenger, a pediatric endocrinologist and clinical assistant professor at NYU Long Island School of Medicine, New York, said in an email.

However, daily subcutaneous injections will still be warranted for certain children with GHD, Dr. Miller noted.

“Daily growth hormone may be better than LAGH for a small number of children who have severe GHD associated with hypoglycemia,” he said. “The low levels of growth hormone at the end of the weekly interval of LAGH may allow hypoglycemia to occur in this population.”
 

Phase 3 trial in 161 treatment-naive children with GHD

The heiGHt trial randomized treatment-naive prepubertal children with GHD 2:1 to weekly lonapegsomatropin or daily somatropin (Genotropin, Pfizer) at 73 sites in 15 countries.

The children were a mean age of 8.5 years (range, 3.2-13.1 years), 82% were boys, and 94% were White.

There were no reported serious adverse events or discontinuations related to lonapegsomatropin.

The most common adverse reactions in ≥5% of these pediatric patients were viral infection (15%), pyrexia (15%), cough (11%), nausea and vomiting (11%), hemorrhage (7%), diarrhea (6%), abdominal pain (6%), and arthralgia and arthritis (6%).

Both study groups reported low incidences of transient, non-neutralizing anti-hGH binding antibodies and no cases of persistent antibodies.

Trial limitations include the fact the study was not blinded (as patients received a weekly or daily injection) and drug doses were fixed at 0.24 mg human growth hormone/kg/week, although in real-world clinical practice, doses may be titrated.

Lonapegsomatropin has been studied in more than 300 children with GHD in the phase 3 program in the heiGHt trial (treatment-naive patients), fliGHt trial (treatment-experienced patients), and enliGHten trial (an ongoing long-term extension trial that includes some patients who have been taking lonapegsomatropin for more than 4 years).

The study was sponsored by Ascendis Pharma. Some of the phase 3 study authors are company employees.

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

Many Americans are clamoring for a booster dose of a COVID-19 vaccine after reports of rising numbers of breakthrough infections, and demand increased after the Biden administration said those shots would be offered starting on Sept. 20.

That plan, which was first announced on Aug. 18, has raised eyebrows because it comes in advance of regulatory reviews by the Food and Drug Administration and recommendations from the Centers for Disease Control and Prevention. Those reviews are needed to determine whether third doses of these vaccines are effective or even safe. The move could have important legal ramifications for doctors and patients, too.

On Aug. 31, two high-level officials in the FDA’s Office of Vaccines Research and Review abruptly resigned amid reports that they were angry that the Biden administration was making decisions that should be left up to that agency.

So far, data show that the vaccines are highly effective at preventing the most severe consequences of COVID-19 – hospitalization and death – even regarding the Delta variant. The World Health Organization has urged wealthy nations such as the United States not to offer boosters so that the limited supply of vaccines can be directed to countries with fewer resources.
 

White House supports boosters

In a recent press briefing, Jeff Zients, the White House COVID-19 response coordinator, defended the move.

“You know, the booster decision, which you referenced ... was made by and announced by the nation’s leading public health officials, including Dr. Walensky; Dr. Fauci; Surgeon General Vivek Murthy; Dr. Janet Woodcock; the FDA acting commissioner, Dr. Francis Collins; Dr. Kessler; and others,” Mr. Zients said.

“And as our medical experts laid out, having reviewed all of the available data, it is in their clinical judgment that it is time to prepare Americans for a booster shot.”

He said a target date of Sept. 20 was announced so as to give states and practitioners time to prepare. He also said the move to give boosters was meant to help the United States stay ahead of a rapidly changing virus. Mr. Zients added that whether boosters will be administered starting on Sept. 20 depends on the FDA’s and CDC’s giving the go-ahead.

“Booster doses are going to be handled the same way all vaccines are handled,” said Kristen Nordlund, a CDC spokesperson. “Companies will have to provide data to FDA. FDA will have to make a decision and authorize the use of those, and ACIP [the Advisory Committee on Immunization Practices] will have to look at the evidence as well and make recommendations on top of FDA’s regulatory action,” she said.

Ms. Nordlund agreed that the planned Sept. 20 start date for boosters was something to which they aspired and was not necessarily set.

Historically, the FDA has needed at least 4 months to review a change to a vaccine’s approval, even on an accelerated schedule. Reviewers use that time to assess data regarding individual patients in a study, to review raw data, and essentially to check a drug company’s math and conclusions. The Biden administration’s timeline would shorten that review period from months to just a few weeks.
 

‘FDA in a very difficult position’

After the FDA approves, the ACIP of the CDC must meet to review the evidence and make recommendations on the use of the boosters in the United States.

Pfizer says it completed its submission for a supplemental biologics license application to the FDA on Aug. 27. To meet a Sept. 20 timeline, the entire process would have to be completed within 3 weeks.

“I don’t think that was handled, you know, ideally,” said Peter Lurie, MD, president of the Center for Science in the Public Interest and former associate commissioner of public health strategy and analysis at the FDA.

“It puts FDA in a very difficult position,” Dr. Lurie said. “It’s almost as if the decision has been made and they’re just checking a box, and that is, you know, contrary to the what FDA – at least the internal people at FDA – have been trying to do for ages.”

He said the agency took great pains with the emergency use authorizations and the full approvals of the vaccines to work as rapidly but thoroughly as possible. They did not skip steps.

“I think all of that reflected very well on the agency,” Dr. Lurie said. “And I think it worked out well in terms of trust in the vaccines.”

Although additional doses of vaccine are expected to be safe, little is known about side effects or adverse events after a third dose.

“It’s critical to wait for additional data and regulatory allowance for booster doses,” Sara Oliver, MD, a member of the CDC’s epidemic intelligence service, said in an Aug. 30 presentation to the ACIP, which is charged with making recommendations for use of all vaccines in the United States.
 

Boosters already being given

But after the White House announced that boosters were on the way, many people are not waiting.

Many health care practitioners and pharmacies have already been giving people third doses of vaccines, even if they are not among the immunocompromised – the group for which the shots are currently approved.

“You can walk into a pharmacy and ask for a third dose. Depending on which pharmacy you go to, you may get it,” said Helen Talbot, MD, associate professor of medicine at Vanderbilt University, Nashville, Tenn., and a member of the ACIP.

She says she has a friend who recently went for a checkup and was offered a third dose. His physician is already giving extra doses to everyone who is older than 65.

Dr. Talbot said that in fairness, pharmacies in the United States are throwing away doses of vaccine because they are expiring before they get used.

“Many of us may or may not be ready to give a third dose but would rather give someone a third dose than throw a vaccine away,” she said.
 

Consequences of a third shot

But giving or getting a third dose before approval by the FDA may have legal consequences.

In the ACIP meeting on Aug. 30, Demetre Daskalakis, MD, who leads vaccine equity efforts at the CDC, cautioned that physicians who give extra doses of the vaccine before the FDA and CDC have signed off may be in violation of practitioner agreements with the federal government and might not be covered by the federal PREP Act. The PREP Act provides immunity from lawsuits for people who administer COVID-19 vaccines and compensates patients in the event of injury. Patients who get a vaccine and suffer a rare but serious side effect may lose the ability to claim compensation offered by the act.

“Many of us gasped when he said that,” Dr. Talbot said, “because that’s a big deal.”

The ACIP signaled that it is considering recommending boosters for a much narrower slice of the American population than the Biden administration has suggested.

They said that so far, the data point only to the need for boosters for seniors, who are the patients most likely to experience breakthrough infections that require hospitalization, and health care workers, who are needed now more than ever and cannot work if they’re sick.

In a White House news briefing Aug. 31, CDC Director Rochelle Walensky, MD, was asked about the ACIP’s conclusions and whether she believed there were enough data to recommend booster shots for most Americans 8 months after their last dose.

“The ACIP did not review international data that actually has led us to be even more concerned about increased risk of vaccine effectiveness waning against hospitalization, severe disease, and death. They will be reviewing that as well,” she said.

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

Many Americans are clamoring for a booster dose of a COVID-19 vaccine after reports of rising numbers of breakthrough infections, and demand increased after the Biden administration said those shots would be offered starting on Sept. 20.

That plan, which was first announced on Aug. 18, has raised eyebrows because it comes in advance of regulatory reviews by the Food and Drug Administration and recommendations from the Centers for Disease Control and Prevention. Those reviews are needed to determine whether third doses of these vaccines are effective or even safe. The move could have important legal ramifications for doctors and patients, too.

On Aug. 31, two high-level officials in the FDA’s Office of Vaccines Research and Review abruptly resigned amid reports that they were angry that the Biden administration was making decisions that should be left up to that agency.

So far, data show that the vaccines are highly effective at preventing the most severe consequences of COVID-19 – hospitalization and death – even regarding the Delta variant. The World Health Organization has urged wealthy nations such as the United States not to offer boosters so that the limited supply of vaccines can be directed to countries with fewer resources.
 

White House supports boosters

In a recent press briefing, Jeff Zients, the White House COVID-19 response coordinator, defended the move.

“You know, the booster decision, which you referenced ... was made by and announced by the nation’s leading public health officials, including Dr. Walensky; Dr. Fauci; Surgeon General Vivek Murthy; Dr. Janet Woodcock; the FDA acting commissioner, Dr. Francis Collins; Dr. Kessler; and others,” Mr. Zients said.

“And as our medical experts laid out, having reviewed all of the available data, it is in their clinical judgment that it is time to prepare Americans for a booster shot.”

He said a target date of Sept. 20 was announced so as to give states and practitioners time to prepare. He also said the move to give boosters was meant to help the United States stay ahead of a rapidly changing virus. Mr. Zients added that whether boosters will be administered starting on Sept. 20 depends on the FDA’s and CDC’s giving the go-ahead.

“Booster doses are going to be handled the same way all vaccines are handled,” said Kristen Nordlund, a CDC spokesperson. “Companies will have to provide data to FDA. FDA will have to make a decision and authorize the use of those, and ACIP [the Advisory Committee on Immunization Practices] will have to look at the evidence as well and make recommendations on top of FDA’s regulatory action,” she said.

Ms. Nordlund agreed that the planned Sept. 20 start date for boosters was something to which they aspired and was not necessarily set.

Historically, the FDA has needed at least 4 months to review a change to a vaccine’s approval, even on an accelerated schedule. Reviewers use that time to assess data regarding individual patients in a study, to review raw data, and essentially to check a drug company’s math and conclusions. The Biden administration’s timeline would shorten that review period from months to just a few weeks.
 

‘FDA in a very difficult position’

After the FDA approves, the ACIP of the CDC must meet to review the evidence and make recommendations on the use of the boosters in the United States.

Pfizer says it completed its submission for a supplemental biologics license application to the FDA on Aug. 27. To meet a Sept. 20 timeline, the entire process would have to be completed within 3 weeks.

“I don’t think that was handled, you know, ideally,” said Peter Lurie, MD, president of the Center for Science in the Public Interest and former associate commissioner of public health strategy and analysis at the FDA.

“It puts FDA in a very difficult position,” Dr. Lurie said. “It’s almost as if the decision has been made and they’re just checking a box, and that is, you know, contrary to the what FDA – at least the internal people at FDA – have been trying to do for ages.”

He said the agency took great pains with the emergency use authorizations and the full approvals of the vaccines to work as rapidly but thoroughly as possible. They did not skip steps.

“I think all of that reflected very well on the agency,” Dr. Lurie said. “And I think it worked out well in terms of trust in the vaccines.”

Although additional doses of vaccine are expected to be safe, little is known about side effects or adverse events after a third dose.

“It’s critical to wait for additional data and regulatory allowance for booster doses,” Sara Oliver, MD, a member of the CDC’s epidemic intelligence service, said in an Aug. 30 presentation to the ACIP, which is charged with making recommendations for use of all vaccines in the United States.
 

Boosters already being given

But after the White House announced that boosters were on the way, many people are not waiting.

Many health care practitioners and pharmacies have already been giving people third doses of vaccines, even if they are not among the immunocompromised – the group for which the shots are currently approved.

“You can walk into a pharmacy and ask for a third dose. Depending on which pharmacy you go to, you may get it,” said Helen Talbot, MD, associate professor of medicine at Vanderbilt University, Nashville, Tenn., and a member of the ACIP.

She says she has a friend who recently went for a checkup and was offered a third dose. His physician is already giving extra doses to everyone who is older than 65.

Dr. Talbot said that in fairness, pharmacies in the United States are throwing away doses of vaccine because they are expiring before they get used.

“Many of us may or may not be ready to give a third dose but would rather give someone a third dose than throw a vaccine away,” she said.
 

Consequences of a third shot

But giving or getting a third dose before approval by the FDA may have legal consequences.

In the ACIP meeting on Aug. 30, Demetre Daskalakis, MD, who leads vaccine equity efforts at the CDC, cautioned that physicians who give extra doses of the vaccine before the FDA and CDC have signed off may be in violation of practitioner agreements with the federal government and might not be covered by the federal PREP Act. The PREP Act provides immunity from lawsuits for people who administer COVID-19 vaccines and compensates patients in the event of injury. Patients who get a vaccine and suffer a rare but serious side effect may lose the ability to claim compensation offered by the act.

“Many of us gasped when he said that,” Dr. Talbot said, “because that’s a big deal.”

The ACIP signaled that it is considering recommending boosters for a much narrower slice of the American population than the Biden administration has suggested.

They said that so far, the data point only to the need for boosters for seniors, who are the patients most likely to experience breakthrough infections that require hospitalization, and health care workers, who are needed now more than ever and cannot work if they’re sick.

In a White House news briefing Aug. 31, CDC Director Rochelle Walensky, MD, was asked about the ACIP’s conclusions and whether she believed there were enough data to recommend booster shots for most Americans 8 months after their last dose.

“The ACIP did not review international data that actually has led us to be even more concerned about increased risk of vaccine effectiveness waning against hospitalization, severe disease, and death. They will be reviewing that as well,” she said.

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

Many Americans are clamoring for a booster dose of a COVID-19 vaccine after reports of rising numbers of breakthrough infections, and demand increased after the Biden administration said those shots would be offered starting on Sept. 20.

That plan, which was first announced on Aug. 18, has raised eyebrows because it comes in advance of regulatory reviews by the Food and Drug Administration and recommendations from the Centers for Disease Control and Prevention. Those reviews are needed to determine whether third doses of these vaccines are effective or even safe. The move could have important legal ramifications for doctors and patients, too.

On Aug. 31, two high-level officials in the FDA’s Office of Vaccines Research and Review abruptly resigned amid reports that they were angry that the Biden administration was making decisions that should be left up to that agency.

So far, data show that the vaccines are highly effective at preventing the most severe consequences of COVID-19 – hospitalization and death – even regarding the Delta variant. The World Health Organization has urged wealthy nations such as the United States not to offer boosters so that the limited supply of vaccines can be directed to countries with fewer resources.
 

White House supports boosters

In a recent press briefing, Jeff Zients, the White House COVID-19 response coordinator, defended the move.

“You know, the booster decision, which you referenced ... was made by and announced by the nation’s leading public health officials, including Dr. Walensky; Dr. Fauci; Surgeon General Vivek Murthy; Dr. Janet Woodcock; the FDA acting commissioner, Dr. Francis Collins; Dr. Kessler; and others,” Mr. Zients said.

“And as our medical experts laid out, having reviewed all of the available data, it is in their clinical judgment that it is time to prepare Americans for a booster shot.”

He said a target date of Sept. 20 was announced so as to give states and practitioners time to prepare. He also said the move to give boosters was meant to help the United States stay ahead of a rapidly changing virus. Mr. Zients added that whether boosters will be administered starting on Sept. 20 depends on the FDA’s and CDC’s giving the go-ahead.

“Booster doses are going to be handled the same way all vaccines are handled,” said Kristen Nordlund, a CDC spokesperson. “Companies will have to provide data to FDA. FDA will have to make a decision and authorize the use of those, and ACIP [the Advisory Committee on Immunization Practices] will have to look at the evidence as well and make recommendations on top of FDA’s regulatory action,” she said.

Ms. Nordlund agreed that the planned Sept. 20 start date for boosters was something to which they aspired and was not necessarily set.

Historically, the FDA has needed at least 4 months to review a change to a vaccine’s approval, even on an accelerated schedule. Reviewers use that time to assess data regarding individual patients in a study, to review raw data, and essentially to check a drug company’s math and conclusions. The Biden administration’s timeline would shorten that review period from months to just a few weeks.
 

‘FDA in a very difficult position’

After the FDA approves, the ACIP of the CDC must meet to review the evidence and make recommendations on the use of the boosters in the United States.

Pfizer says it completed its submission for a supplemental biologics license application to the FDA on Aug. 27. To meet a Sept. 20 timeline, the entire process would have to be completed within 3 weeks.

“I don’t think that was handled, you know, ideally,” said Peter Lurie, MD, president of the Center for Science in the Public Interest and former associate commissioner of public health strategy and analysis at the FDA.

“It puts FDA in a very difficult position,” Dr. Lurie said. “It’s almost as if the decision has been made and they’re just checking a box, and that is, you know, contrary to the what FDA – at least the internal people at FDA – have been trying to do for ages.”

He said the agency took great pains with the emergency use authorizations and the full approvals of the vaccines to work as rapidly but thoroughly as possible. They did not skip steps.

“I think all of that reflected very well on the agency,” Dr. Lurie said. “And I think it worked out well in terms of trust in the vaccines.”

Although additional doses of vaccine are expected to be safe, little is known about side effects or adverse events after a third dose.

“It’s critical to wait for additional data and regulatory allowance for booster doses,” Sara Oliver, MD, a member of the CDC’s epidemic intelligence service, said in an Aug. 30 presentation to the ACIP, which is charged with making recommendations for use of all vaccines in the United States.
 

Boosters already being given

But after the White House announced that boosters were on the way, many people are not waiting.

Many health care practitioners and pharmacies have already been giving people third doses of vaccines, even if they are not among the immunocompromised – the group for which the shots are currently approved.

“You can walk into a pharmacy and ask for a third dose. Depending on which pharmacy you go to, you may get it,” said Helen Talbot, MD, associate professor of medicine at Vanderbilt University, Nashville, Tenn., and a member of the ACIP.

She says she has a friend who recently went for a checkup and was offered a third dose. His physician is already giving extra doses to everyone who is older than 65.

Dr. Talbot said that in fairness, pharmacies in the United States are throwing away doses of vaccine because they are expiring before they get used.

“Many of us may or may not be ready to give a third dose but would rather give someone a third dose than throw a vaccine away,” she said.
 

Consequences of a third shot

But giving or getting a third dose before approval by the FDA may have legal consequences.

In the ACIP meeting on Aug. 30, Demetre Daskalakis, MD, who leads vaccine equity efforts at the CDC, cautioned that physicians who give extra doses of the vaccine before the FDA and CDC have signed off may be in violation of practitioner agreements with the federal government and might not be covered by the federal PREP Act. The PREP Act provides immunity from lawsuits for people who administer COVID-19 vaccines and compensates patients in the event of injury. Patients who get a vaccine and suffer a rare but serious side effect may lose the ability to claim compensation offered by the act.

“Many of us gasped when he said that,” Dr. Talbot said, “because that’s a big deal.”

The ACIP signaled that it is considering recommending boosters for a much narrower slice of the American population than the Biden administration has suggested.

They said that so far, the data point only to the need for boosters for seniors, who are the patients most likely to experience breakthrough infections that require hospitalization, and health care workers, who are needed now more than ever and cannot work if they’re sick.

In a White House news briefing Aug. 31, CDC Director Rochelle Walensky, MD, was asked about the ACIP’s conclusions and whether she believed there were enough data to recommend booster shots for most Americans 8 months after their last dose.

“The ACIP did not review international data that actually has led us to be even more concerned about increased risk of vaccine effectiveness waning against hospitalization, severe disease, and death. They will be reviewing that as well,” she said.

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

The World Health Organization is tracking a new COVID-19 variant called Mu, which could be able to evade the immunity provided by the vaccines and prior infections.

The variant, also known as B.1.621, was first identified in Colombia in January. It has now been detected in 43 countries and was added to the WHO’s “variant of interest” list Aug. 30.

“The Mu variant has a constellation of mutations that indicate potential properties of immune escape,” the WHO wrote in its weekly COVID-19 update on Aug 31.

Preliminary data suggests that the Mu variant may be able to evade antibodies at levels similar to the Beta variant, the WHO wrote, though more studies are needed. The Beta variant, also known as B.1.351, was first detected in South Africa and has shown some ability to evade vaccines.

As of Aug. 29, the global prevalence of the Mu variant appears to be less than 0.1%. But its prevalence in South America has “consistently increased,” the WHO wrote, now making up 39% of cases in Colombia and 13% of cases in Ecuador.

More than 4,700 cases of the Mu variant have been identified worldwide through genomic sequencing, according to Outbreak.info, an open-source database operated by Scripps Research. The United States has identified 2,011 of these cases, with 348 in California. As of Sept. 2, only one state -- Nebraska -- had not yet reported a Mu case.

“At the moment, it looks like there’s genuine cause for concern in USA, Central America, and South America, but as we saw with Delta, a potent variant can traverse the globe in the blink of an eye,” Danny Altmann, PhD, an immunologist at Imperial College London, told The Telegraph.

The WHO is monitoring nine variants with genetic mutations that could make them more transmissible, lead to more severe disease, and help them evade vaccines. The Delta variant, which is now a dominant form of the virus in the United States and worldwide, has led to a surge in cases and hospitalizations this summer.

In its report, the WHO said it would monitor the Mu variant for changes, “particularly with the co-circulation of the Delta variant.”

“Mu looks potentially good at immune evasion,” Dr. Altmann told The Telegraph. “For my taste, it’s a stark reminder that this isn’t by any means over. On a planet of 4.4 million-plus new infections per week, there are new variants popping up all the time, and little reason to feel complacent.”

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

The World Health Organization is tracking a new COVID-19 variant called Mu, which could be able to evade the immunity provided by the vaccines and prior infections.

The variant, also known as B.1.621, was first identified in Colombia in January. It has now been detected in 43 countries and was added to the WHO’s “variant of interest” list Aug. 30.

“The Mu variant has a constellation of mutations that indicate potential properties of immune escape,” the WHO wrote in its weekly COVID-19 update on Aug 31.

Preliminary data suggests that the Mu variant may be able to evade antibodies at levels similar to the Beta variant, the WHO wrote, though more studies are needed. The Beta variant, also known as B.1.351, was first detected in South Africa and has shown some ability to evade vaccines.

As of Aug. 29, the global prevalence of the Mu variant appears to be less than 0.1%. But its prevalence in South America has “consistently increased,” the WHO wrote, now making up 39% of cases in Colombia and 13% of cases in Ecuador.

More than 4,700 cases of the Mu variant have been identified worldwide through genomic sequencing, according to Outbreak.info, an open-source database operated by Scripps Research. The United States has identified 2,011 of these cases, with 348 in California. As of Sept. 2, only one state -- Nebraska -- had not yet reported a Mu case.

“At the moment, it looks like there’s genuine cause for concern in USA, Central America, and South America, but as we saw with Delta, a potent variant can traverse the globe in the blink of an eye,” Danny Altmann, PhD, an immunologist at Imperial College London, told The Telegraph.

The WHO is monitoring nine variants with genetic mutations that could make them more transmissible, lead to more severe disease, and help them evade vaccines. The Delta variant, which is now a dominant form of the virus in the United States and worldwide, has led to a surge in cases and hospitalizations this summer.

In its report, the WHO said it would monitor the Mu variant for changes, “particularly with the co-circulation of the Delta variant.”

“Mu looks potentially good at immune evasion,” Dr. Altmann told The Telegraph. “For my taste, it’s a stark reminder that this isn’t by any means over. On a planet of 4.4 million-plus new infections per week, there are new variants popping up all the time, and little reason to feel complacent.”

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

The World Health Organization is tracking a new COVID-19 variant called Mu, which could be able to evade the immunity provided by the vaccines and prior infections.

The variant, also known as B.1.621, was first identified in Colombia in January. It has now been detected in 43 countries and was added to the WHO’s “variant of interest” list Aug. 30.

“The Mu variant has a constellation of mutations that indicate potential properties of immune escape,” the WHO wrote in its weekly COVID-19 update on Aug 31.

Preliminary data suggests that the Mu variant may be able to evade antibodies at levels similar to the Beta variant, the WHO wrote, though more studies are needed. The Beta variant, also known as B.1.351, was first detected in South Africa and has shown some ability to evade vaccines.

As of Aug. 29, the global prevalence of the Mu variant appears to be less than 0.1%. But its prevalence in South America has “consistently increased,” the WHO wrote, now making up 39% of cases in Colombia and 13% of cases in Ecuador.

More than 4,700 cases of the Mu variant have been identified worldwide through genomic sequencing, according to Outbreak.info, an open-source database operated by Scripps Research. The United States has identified 2,011 of these cases, with 348 in California. As of Sept. 2, only one state -- Nebraska -- had not yet reported a Mu case.

“At the moment, it looks like there’s genuine cause for concern in USA, Central America, and South America, but as we saw with Delta, a potent variant can traverse the globe in the blink of an eye,” Danny Altmann, PhD, an immunologist at Imperial College London, told The Telegraph.

The WHO is monitoring nine variants with genetic mutations that could make them more transmissible, lead to more severe disease, and help them evade vaccines. The Delta variant, which is now a dominant form of the virus in the United States and worldwide, has led to a surge in cases and hospitalizations this summer.

In its report, the WHO said it would monitor the Mu variant for changes, “particularly with the co-circulation of the Delta variant.”

“Mu looks potentially good at immune evasion,” Dr. Altmann told The Telegraph. “For my taste, it’s a stark reminder that this isn’t by any means over. On a planet of 4.4 million-plus new infections per week, there are new variants popping up all the time, and little reason to feel complacent.”

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

With the number of pediatric infections with SARS-CoV-2 rising it is not surprising that children with persistent symptoms are beginning to accumulate. Who are these pediatric “long haulers” and do they differ from their adult counterparts? The answer is far from clear because the terms “long COVID” and “long hauler” are not well defined. But, I suspect we will find that they will be similar in most respects.

In a recent Guest Essay in the New York Times, two medical school professors attempt to inject some common sense into the long hauler phenomenon. (“The Truth About Long Covid is Complicated. Better Treatment Isn’t,” Adam Gaffney and Zackary Berger, The New York Times, Aug. 18, 2021).

The authors divide the patients with long COVID into three categories. The first includes those who are complaining of persistent cough and fatigue for up to 3 months, a not unexpected course for patients recovering from a significant respiratory illness like pneumonia.

The second group comprises patients who developed acute respiratory distress syndrome during the course of their SARS-CoV-2 infection. These unfortunate individuals likely incurred lung damage that may have triggered renal damage and delirium and may never regain full function.

The third group of patients reports a wide variety of less specific symptoms including, but not limited to, severe fatigue, brain fog, shortness of breath, gastrointestinal symptoms, chronic pain, and palpitations.

The authors of the essay refer to several studies in which there was little if any correlation between these patients’ complaints and their antibody levels. In fact, one study of adolescents found that in a group with similar symptoms many of the individuals had no serologic evidence of SARS-CoV-2 infection.

Unfortunately, the lay public, the media, and some physicians make no distinction between these three groups and lump them all under the same long COVID umbrella. The resulting confusion seeds unwarranted anxiety among the first and third groups and may prevent some individuals from receiving the appropriate attention they deserve.

I suspect that like me, many of you see some similarities between this third group of long COVID patients and adolescents whose persistent symptoms don’t quite fit with their primary illness. Patients labeled as having post-concussion syndrome or “chronic Lyme disease” come immediately to mind. In both conditions, many of the patients had little if any evidence of severe insult from the initial event but continue to complain about a variety of symptoms including severe fatigue and brain fog.

We have done a very poor job of properly managing these patients. And there are a lot of them. A large part of the problem is labeling. In the old days one might have said these patients were having “psychosomatic” symptoms. But, while it may be an accurate description, like the term “retardation” it has been permanently tarnished. Fortunately, most of us are smart enough to avoid telling these patients that it is all in their heads.

However, convincing an individual that many of his symptoms may be the result of the psychological insult from the original disease compounded by other stresses and lifestyle factors can be a difficult sell. The task is made particularly difficult when there continue to be physicians who will miss or ignore the obvious and embark on therapeutic endeavors that are not only ineffective but can serve as a distraction from the real work of listening to and engaging these patients whose suffering may be just as real as that of those long haulers with structural damage.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

With the number of pediatric infections with SARS-CoV-2 rising it is not surprising that children with persistent symptoms are beginning to accumulate. Who are these pediatric “long haulers” and do they differ from their adult counterparts? The answer is far from clear because the terms “long COVID” and “long hauler” are not well defined. But, I suspect we will find that they will be similar in most respects.

In a recent Guest Essay in the New York Times, two medical school professors attempt to inject some common sense into the long hauler phenomenon. (“The Truth About Long Covid is Complicated. Better Treatment Isn’t,” Adam Gaffney and Zackary Berger, The New York Times, Aug. 18, 2021).

The authors divide the patients with long COVID into three categories. The first includes those who are complaining of persistent cough and fatigue for up to 3 months, a not unexpected course for patients recovering from a significant respiratory illness like pneumonia.

The second group comprises patients who developed acute respiratory distress syndrome during the course of their SARS-CoV-2 infection. These unfortunate individuals likely incurred lung damage that may have triggered renal damage and delirium and may never regain full function.

The third group of patients reports a wide variety of less specific symptoms including, but not limited to, severe fatigue, brain fog, shortness of breath, gastrointestinal symptoms, chronic pain, and palpitations.

The authors of the essay refer to several studies in which there was little if any correlation between these patients’ complaints and their antibody levels. In fact, one study of adolescents found that in a group with similar symptoms many of the individuals had no serologic evidence of SARS-CoV-2 infection.

Unfortunately, the lay public, the media, and some physicians make no distinction between these three groups and lump them all under the same long COVID umbrella. The resulting confusion seeds unwarranted anxiety among the first and third groups and may prevent some individuals from receiving the appropriate attention they deserve.

I suspect that like me, many of you see some similarities between this third group of long COVID patients and adolescents whose persistent symptoms don’t quite fit with their primary illness. Patients labeled as having post-concussion syndrome or “chronic Lyme disease” come immediately to mind. In both conditions, many of the patients had little if any evidence of severe insult from the initial event but continue to complain about a variety of symptoms including severe fatigue and brain fog.

We have done a very poor job of properly managing these patients. And there are a lot of them. A large part of the problem is labeling. In the old days one might have said these patients were having “psychosomatic” symptoms. But, while it may be an accurate description, like the term “retardation” it has been permanently tarnished. Fortunately, most of us are smart enough to avoid telling these patients that it is all in their heads.

However, convincing an individual that many of his symptoms may be the result of the psychological insult from the original disease compounded by other stresses and lifestyle factors can be a difficult sell. The task is made particularly difficult when there continue to be physicians who will miss or ignore the obvious and embark on therapeutic endeavors that are not only ineffective but can serve as a distraction from the real work of listening to and engaging these patients whose suffering may be just as real as that of those long haulers with structural damage.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

With the number of pediatric infections with SARS-CoV-2 rising it is not surprising that children with persistent symptoms are beginning to accumulate. Who are these pediatric “long haulers” and do they differ from their adult counterparts? The answer is far from clear because the terms “long COVID” and “long hauler” are not well defined. But, I suspect we will find that they will be similar in most respects.

In a recent Guest Essay in the New York Times, two medical school professors attempt to inject some common sense into the long hauler phenomenon. (“The Truth About Long Covid is Complicated. Better Treatment Isn’t,” Adam Gaffney and Zackary Berger, The New York Times, Aug. 18, 2021).

The authors divide the patients with long COVID into three categories. The first includes those who are complaining of persistent cough and fatigue for up to 3 months, a not unexpected course for patients recovering from a significant respiratory illness like pneumonia.

The second group comprises patients who developed acute respiratory distress syndrome during the course of their SARS-CoV-2 infection. These unfortunate individuals likely incurred lung damage that may have triggered renal damage and delirium and may never regain full function.

The third group of patients reports a wide variety of less specific symptoms including, but not limited to, severe fatigue, brain fog, shortness of breath, gastrointestinal symptoms, chronic pain, and palpitations.

The authors of the essay refer to several studies in which there was little if any correlation between these patients’ complaints and their antibody levels. In fact, one study of adolescents found that in a group with similar symptoms many of the individuals had no serologic evidence of SARS-CoV-2 infection.

Unfortunately, the lay public, the media, and some physicians make no distinction between these three groups and lump them all under the same long COVID umbrella. The resulting confusion seeds unwarranted anxiety among the first and third groups and may prevent some individuals from receiving the appropriate attention they deserve.

I suspect that like me, many of you see some similarities between this third group of long COVID patients and adolescents whose persistent symptoms don’t quite fit with their primary illness. Patients labeled as having post-concussion syndrome or “chronic Lyme disease” come immediately to mind. In both conditions, many of the patients had little if any evidence of severe insult from the initial event but continue to complain about a variety of symptoms including severe fatigue and brain fog.

We have done a very poor job of properly managing these patients. And there are a lot of them. A large part of the problem is labeling. In the old days one might have said these patients were having “psychosomatic” symptoms. But, while it may be an accurate description, like the term “retardation” it has been permanently tarnished. Fortunately, most of us are smart enough to avoid telling these patients that it is all in their heads.

However, convincing an individual that many of his symptoms may be the result of the psychological insult from the original disease compounded by other stresses and lifestyle factors can be a difficult sell. The task is made particularly difficult when there continue to be physicians who will miss or ignore the obvious and embark on therapeutic endeavors that are not only ineffective but can serve as a distraction from the real work of listening to and engaging these patients whose suffering may be just as real as that of those long haulers with structural damage.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

For patients who present with pesky vulvovaginal candidiasis, consider a course of ibrexafungerp, a first-in-class oral triterpenoid antifungal drug that was approved in June 2021, Aruna Venkatesan, MD, recommends.

“Ibrexafungerp, an inhibitor of beta (1-3)–glucan synthase, is important for many reasons,” Dr. Venkatesan, chief of dermatology and director of the genital dermatology clinic at Santa Clara Valley Medical Center, San Jose, Calif., said during the annual meeting of the Pacific Dermatologic Association. “It’s one of the few drugs that can be used to treat Candida glabrata when C. glabrata is resistant to azoles and echinocandins. As the second-most common Candida species after C. albicans, C. glabrata is more common in immunosuppressed patients and it can cause mucosal and invasive disease, so ibrexafungerp is a welcome addition to our treatment armamentarium,” said Dr. Venkatesan, clinical professor of dermatology (affiliated) at Stanford (Calif.) Hospital and Clinics, adding that that vulvovaginal candidiasis can be tricky to diagnose. “In medical school, we learned that yeast infection in a woman presents as white, curd-like discharge, but that’s actually a minority of patients.”

For a patient who is being treated with topical steroids or estrogen for a genital condition, but is experiencing worsening itch, redness, or thick white discharge, she recommends performing a KOH exam.

“Instead of using a 15-blade scalpel, as we are used to performing on the skin for tinea, take a sterile [cotton swab], and swab the affected area. You can then apply it to a slide and perform a KOH exam as you normally would. Then look for yeast elements under the microscope. I also find it helpful to send for fungal culture to get speciation, especially in someone who’s not responding to therapy. This is because non-albicans yeast can be more resistant to azoles and require a different treatment plan.”

Often, patients with vulvovaginal candidiasis who present to her clinic are referred from an ob.gyn. and other general practitioners because they have failed a topical or oral azole. “I tend to avoid the topicals,” said Dr. Venkatesan, who is also president-elect of the North American chapter of the International Society for the Study of Vulvovaginal Disease. “If the culture shows C. albicans, I usually treat with oral fluconazole, 150 mg or 200 mg once, and consider repeat weekly dosing. Many patients come to me because they have recurrent refractory disease, so giving it once weekly for 6-8 weeks while they work on their potential risk factors such as diabetic blood sugar control is sensible.”

Non-albicans yeast can be resistant to azoles. If the fungal culture shows C. glabrata in such patients, “consider a course of intravaginal boric acid suppositories,” she advised. “These used to be difficult to give patients, because you would either have to send the prescription to a compounding pharmacy, or have the patients buy the capsules and boric acid crystals separately and make them themselves. That always made me nervous because of the chance of errors. The safety and the concern of taking it by mouth is an issue.” But now, intravaginal boric acid suppositories are available on Amazon and other web sites, and are relatively affordable, she said, adding, “just make sure the patient doesn’t take it by mouth as this is very toxic.”

Dr. Venkatesan reported having no financial disclosures.

[email protected]

For patients who present with pesky vulvovaginal candidiasis, consider a course of ibrexafungerp, a first-in-class oral triterpenoid antifungal drug that was approved in June 2021, Aruna Venkatesan, MD, recommends.

“Ibrexafungerp, an inhibitor of beta (1-3)–glucan synthase, is important for many reasons,” Dr. Venkatesan, chief of dermatology and director of the genital dermatology clinic at Santa Clara Valley Medical Center, San Jose, Calif., said during the annual meeting of the Pacific Dermatologic Association. “It’s one of the few drugs that can be used to treat Candida glabrata when C. glabrata is resistant to azoles and echinocandins. As the second-most common Candida species after C. albicans, C. glabrata is more common in immunosuppressed patients and it can cause mucosal and invasive disease, so ibrexafungerp is a welcome addition to our treatment armamentarium,” said Dr. Venkatesan, clinical professor of dermatology (affiliated) at Stanford (Calif.) Hospital and Clinics, adding that that vulvovaginal candidiasis can be tricky to diagnose. “In medical school, we learned that yeast infection in a woman presents as white, curd-like discharge, but that’s actually a minority of patients.”

For a patient who is being treated with topical steroids or estrogen for a genital condition, but is experiencing worsening itch, redness, or thick white discharge, she recommends performing a KOH exam.

“Instead of using a 15-blade scalpel, as we are used to performing on the skin for tinea, take a sterile [cotton swab], and swab the affected area. You can then apply it to a slide and perform a KOH exam as you normally would. Then look for yeast elements under the microscope. I also find it helpful to send for fungal culture to get speciation, especially in someone who’s not responding to therapy. This is because non-albicans yeast can be more resistant to azoles and require a different treatment plan.”

Often, patients with vulvovaginal candidiasis who present to her clinic are referred from an ob.gyn. and other general practitioners because they have failed a topical or oral azole. “I tend to avoid the topicals,” said Dr. Venkatesan, who is also president-elect of the North American chapter of the International Society for the Study of Vulvovaginal Disease. “If the culture shows C. albicans, I usually treat with oral fluconazole, 150 mg or 200 mg once, and consider repeat weekly dosing. Many patients come to me because they have recurrent refractory disease, so giving it once weekly for 6-8 weeks while they work on their potential risk factors such as diabetic blood sugar control is sensible.”

Non-albicans yeast can be resistant to azoles. If the fungal culture shows C. glabrata in such patients, “consider a course of intravaginal boric acid suppositories,” she advised. “These used to be difficult to give patients, because you would either have to send the prescription to a compounding pharmacy, or have the patients buy the capsules and boric acid crystals separately and make them themselves. That always made me nervous because of the chance of errors. The safety and the concern of taking it by mouth is an issue.” But now, intravaginal boric acid suppositories are available on Amazon and other web sites, and are relatively affordable, she said, adding, “just make sure the patient doesn’t take it by mouth as this is very toxic.”

Dr. Venkatesan reported having no financial disclosures.

[email protected]

For patients who present with pesky vulvovaginal candidiasis, consider a course of ibrexafungerp, a first-in-class oral triterpenoid antifungal drug that was approved in June 2021, Aruna Venkatesan, MD, recommends.

“Ibrexafungerp, an inhibitor of beta (1-3)–glucan synthase, is important for many reasons,” Dr. Venkatesan, chief of dermatology and director of the genital dermatology clinic at Santa Clara Valley Medical Center, San Jose, Calif., said during the annual meeting of the Pacific Dermatologic Association. “It’s one of the few drugs that can be used to treat Candida glabrata when C. glabrata is resistant to azoles and echinocandins. As the second-most common Candida species after C. albicans, C. glabrata is more common in immunosuppressed patients and it can cause mucosal and invasive disease, so ibrexafungerp is a welcome addition to our treatment armamentarium,” said Dr. Venkatesan, clinical professor of dermatology (affiliated) at Stanford (Calif.) Hospital and Clinics, adding that that vulvovaginal candidiasis can be tricky to diagnose. “In medical school, we learned that yeast infection in a woman presents as white, curd-like discharge, but that’s actually a minority of patients.”

For a patient who is being treated with topical steroids or estrogen for a genital condition, but is experiencing worsening itch, redness, or thick white discharge, she recommends performing a KOH exam.

“Instead of using a 15-blade scalpel, as we are used to performing on the skin for tinea, take a sterile [cotton swab], and swab the affected area. You can then apply it to a slide and perform a KOH exam as you normally would. Then look for yeast elements under the microscope. I also find it helpful to send for fungal culture to get speciation, especially in someone who’s not responding to therapy. This is because non-albicans yeast can be more resistant to azoles and require a different treatment plan.”

Often, patients with vulvovaginal candidiasis who present to her clinic are referred from an ob.gyn. and other general practitioners because they have failed a topical or oral azole. “I tend to avoid the topicals,” said Dr. Venkatesan, who is also president-elect of the North American chapter of the International Society for the Study of Vulvovaginal Disease. “If the culture shows C. albicans, I usually treat with oral fluconazole, 150 mg or 200 mg once, and consider repeat weekly dosing. Many patients come to me because they have recurrent refractory disease, so giving it once weekly for 6-8 weeks while they work on their potential risk factors such as diabetic blood sugar control is sensible.”

Non-albicans yeast can be resistant to azoles. If the fungal culture shows C. glabrata in such patients, “consider a course of intravaginal boric acid suppositories,” she advised. “These used to be difficult to give patients, because you would either have to send the prescription to a compounding pharmacy, or have the patients buy the capsules and boric acid crystals separately and make them themselves. That always made me nervous because of the chance of errors. The safety and the concern of taking it by mouth is an issue.” But now, intravaginal boric acid suppositories are available on Amazon and other web sites, and are relatively affordable, she said, adding, “just make sure the patient doesn’t take it by mouth as this is very toxic.”

Dr. Venkatesan reported having no financial disclosures.

[email protected]

During the annual meeting of the Society for Pediatric Dermatology, Amy S. Paller, MD, MS, marveled on the remarkable advances in the treatment of inflammatory skin disorders during the past 2 decades.

“We’ve come a long way, from disease features being red, thick, and scaly and being treated with nonspecific therapy like topical steroids, keratolytics, and tar, to understanding disease pathogenesis and finding new targeted therapies for inflammatory skin disorders in children,” said Dr. Paller, professor and chair of the department of dermatology at Northwestern University, Chicago. “There are now studies moving forward with gene correction, gene replacement, the gene product replaced, or pathway inhibition to prevent the effects of genetic change.”

Technology is leading the way in generating new therapeutic advances, she continued, beyond traditional “omics” to lipidomics, metabolomics, glycomics, and kinomics. “This has enabled us to find new genetic disorders and their causes, to look at changes in gene expression patterns, and to look at changes in protein expression patterns that give us clues as to how to move forward with better therapy,” she said. “When we’re talking about new insights into pathogenesis-based therapy, we’re talking largely about understanding the pathways that lead to either inflammation or promoting cell proliferation and abnormal differentiation.”

Treating pediatric psoriasis

Dr. Paller discussed her approach to managing patients with pediatric psoriasis, an inflammatory disorder with IL-23/Th17 skewing. “First of all, ask about itch and pain with these patients,” she advised. “Interviews have shown that 61% of children experience some itch, 39% have pain or stinging, and in the ixekizumab trials, 72% had what’s considered meaningful itch, with at least 4 out of 10 (mean intensity 5.3) on the itch numeric rating scale. Little is known about the itch associated with psoriasis and its underlying cause – unrelated to the IL-4/IL-13 pathway activation of atopic dermatitis – but it’s worth asking about. I find that itch of the scalp is especially a problem in psoriasis.”

Physicians should also ask pediatric psoriasis patients about joint pain, because about 1% of them have psoriatic arthritis, which is much less common than in adults, “but important to find and manage,” she added. Dr. Paller recommends the new R-JET rapid joint exam technique, which is accompanied by a three-question survey and body diagram that facilitates identification of true arthritis, “so you can know how quickly to refer”.

Several studies have described an increased risk of metabolic syndrome in adolescents with pediatric psoriasis and now in prepubertal children with the disease. In a recent study of 60 consecutive prepubertal children with psoriasis, 70% of whom had mild disease, 40% were overweight or obese, 53% had central obesity, 27% had high levels of the HOMA-IR (homeostasis model assessment of insulin resistance) despite generally normal levels of fasting glucose, and 30% met criteria for metabolic syndrome.

“This really struck me because our AAD [American Academy of Dermatology] guidelines did not recommend screening for type 2 diabetes in prepubertal children, even if overweight, because the risk is so small,” Dr. Paller said. “This report suggests that we may need to reconsider this recommendation in prepubertal children with psoriasis.”

Meanwhile, the number of medications approved by the Food and Drug Administration and the European Medicines Agency for children with psoriasis who are 6 years of age and above continues to expand, including tumor necrosis factor (TNF) inhibitors, interleukin (IL)-23 inhibitors, and IL-17 inhibitors. Most children can now achieve a PASI 90 within 12 weeks with the IL-23 inhibitor ustekinumab and the IL-17 inhibitors ixekizumab and secukinumab, Dr. Paller said.

In the ixekizumab trial, there are head-to-head comparison data in a European arm that involved the use of etanercept, she said. “What’s most noticeable is the significant difference in those who were able to achieve PASI 90 or above with this IL-17 inhibitor, versus etanercept,” which she added, raises the question of whether aiming for a PASI 75 is adequate, "or should we strive for PASI 90?” A pediatric psoriasis study published in 2020 found that the greatest improvement in quality of life was associated with a PASI 90 and use of systemic treatments (JAMA Dermatol. 2020;156[1]:72-8).

Looking forward, phase 3 clinical trials are underway in pediatric patients with moderate to severe psoriasis for guselkumab, tildrakizumab, risankizumab, certolizumab, bimekizumab, and brodalumab. “The cost of all of these biologics is high, however. I remind everyone that we still have methotrexate,” she said. “The risk of side effects with our low-dose methotrexate treatment for psoriasis remains low, but methotrexate doesn’t hit these [high] PASI numbers and it’s much slower in its onset than biologics.”

Dr. Paller disclosed that she is a consultant to and/or an investigator for AbbVie, Arena, Bausch, Bristol Myers Squibb, Dermavant, Eli Lilly, Incyte, Forte, LEO Pharma, LifeMax, Pfizer, RAPT Therapeutics, Regeneron, and Sanofi.

Commentary by Robert Sidbury, MD, MPH

Dr. Paller reminds us of some essential features of pediatric psoriasis:
•    It can hurt. Ask your patients if it does.
•    It can itch. Look for excoriations, especially in the scalp.
•    It is often associated with metabolic syndrome, so check relevant biometrics and labs, and consider coincident insulin resistance.
•    Our traditional clinical trial target of PASI75, or a 75% reduction in body surface area involvement, is just not good enough. Studies have shown that the most meaningful quality-of-life gains come at PASI90 or above. 
•    With our newer biologics, such as IL-12/23 blockers (for instance, ustekinumab) and IL-17 blockers (for example, ixekizumab and secukinumab), PASI90 and better is a reasonable expectation, not a pipe dream. 

Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.

This article was updated 6/16/22.

During the annual meeting of the Society for Pediatric Dermatology, Amy S. Paller, MD, MS, marveled on the remarkable advances in the treatment of inflammatory skin disorders during the past 2 decades.

“We’ve come a long way, from disease features being red, thick, and scaly and being treated with nonspecific therapy like topical steroids, keratolytics, and tar, to understanding disease pathogenesis and finding new targeted therapies for inflammatory skin disorders in children,” said Dr. Paller, professor and chair of the department of dermatology at Northwestern University, Chicago. “There are now studies moving forward with gene correction, gene replacement, the gene product replaced, or pathway inhibition to prevent the effects of genetic change.”

Technology is leading the way in generating new therapeutic advances, she continued, beyond traditional “omics” to lipidomics, metabolomics, glycomics, and kinomics. “This has enabled us to find new genetic disorders and their causes, to look at changes in gene expression patterns, and to look at changes in protein expression patterns that give us clues as to how to move forward with better therapy,” she said. “When we’re talking about new insights into pathogenesis-based therapy, we’re talking largely about understanding the pathways that lead to either inflammation or promoting cell proliferation and abnormal differentiation.”

Treating pediatric psoriasis

Dr. Paller discussed her approach to managing patients with pediatric psoriasis, an inflammatory disorder with IL-23/Th17 skewing. “First of all, ask about itch and pain with these patients,” she advised. “Interviews have shown that 61% of children experience some itch, 39% have pain or stinging, and in the ixekizumab trials, 72% had what’s considered meaningful itch, with at least 4 out of 10 (mean intensity 5.3) on the itch numeric rating scale. Little is known about the itch associated with psoriasis and its underlying cause – unrelated to the IL-4/IL-13 pathway activation of atopic dermatitis – but it’s worth asking about. I find that itch of the scalp is especially a problem in psoriasis.”

Physicians should also ask pediatric psoriasis patients about joint pain, because about 1% of them have psoriatic arthritis, which is much less common than in adults, “but important to find and manage,” she added. Dr. Paller recommends the new R-JET rapid joint exam technique, which is accompanied by a three-question survey and body diagram that facilitates identification of true arthritis, “so you can know how quickly to refer”.

Several studies have described an increased risk of metabolic syndrome in adolescents with pediatric psoriasis and now in prepubertal children with the disease. In a recent study of 60 consecutive prepubertal children with psoriasis, 70% of whom had mild disease, 40% were overweight or obese, 53% had central obesity, 27% had high levels of the HOMA-IR (homeostasis model assessment of insulin resistance) despite generally normal levels of fasting glucose, and 30% met criteria for metabolic syndrome.

“This really struck me because our AAD [American Academy of Dermatology] guidelines did not recommend screening for type 2 diabetes in prepubertal children, even if overweight, because the risk is so small,” Dr. Paller said. “This report suggests that we may need to reconsider this recommendation in prepubertal children with psoriasis.”

Meanwhile, the number of medications approved by the Food and Drug Administration and the European Medicines Agency for children with psoriasis who are 6 years of age and above continues to expand, including tumor necrosis factor (TNF) inhibitors, interleukin (IL)-23 inhibitors, and IL-17 inhibitors. Most children can now achieve a PASI 90 within 12 weeks with the IL-23 inhibitor ustekinumab and the IL-17 inhibitors ixekizumab and secukinumab, Dr. Paller said.

In the ixekizumab trial, there are head-to-head comparison data in a European arm that involved the use of etanercept, she said. “What’s most noticeable is the significant difference in those who were able to achieve PASI 90 or above with this IL-17 inhibitor, versus etanercept,” which she added, raises the question of whether aiming for a PASI 75 is adequate, "or should we strive for PASI 90?” A pediatric psoriasis study published in 2020 found that the greatest improvement in quality of life was associated with a PASI 90 and use of systemic treatments (JAMA Dermatol. 2020;156[1]:72-8).

Looking forward, phase 3 clinical trials are underway in pediatric patients with moderate to severe psoriasis for guselkumab, tildrakizumab, risankizumab, certolizumab, bimekizumab, and brodalumab. “The cost of all of these biologics is high, however. I remind everyone that we still have methotrexate,” she said. “The risk of side effects with our low-dose methotrexate treatment for psoriasis remains low, but methotrexate doesn’t hit these [high] PASI numbers and it’s much slower in its onset than biologics.”

Dr. Paller disclosed that she is a consultant to and/or an investigator for AbbVie, Arena, Bausch, Bristol Myers Squibb, Dermavant, Eli Lilly, Incyte, Forte, LEO Pharma, LifeMax, Pfizer, RAPT Therapeutics, Regeneron, and Sanofi.

Commentary by Robert Sidbury, MD, MPH

Dr. Paller reminds us of some essential features of pediatric psoriasis:
•    It can hurt. Ask your patients if it does.
•    It can itch. Look for excoriations, especially in the scalp.
•    It is often associated with metabolic syndrome, so check relevant biometrics and labs, and consider coincident insulin resistance.
•    Our traditional clinical trial target of PASI75, or a 75% reduction in body surface area involvement, is just not good enough. Studies have shown that the most meaningful quality-of-life gains come at PASI90 or above. 
•    With our newer biologics, such as IL-12/23 blockers (for instance, ustekinumab) and IL-17 blockers (for example, ixekizumab and secukinumab), PASI90 and better is a reasonable expectation, not a pipe dream. 

Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.

This article was updated 6/16/22.

During the annual meeting of the Society for Pediatric Dermatology, Amy S. Paller, MD, MS, marveled on the remarkable advances in the treatment of inflammatory skin disorders during the past 2 decades.

“We’ve come a long way, from disease features being red, thick, and scaly and being treated with nonspecific therapy like topical steroids, keratolytics, and tar, to understanding disease pathogenesis and finding new targeted therapies for inflammatory skin disorders in children,” said Dr. Paller, professor and chair of the department of dermatology at Northwestern University, Chicago. “There are now studies moving forward with gene correction, gene replacement, the gene product replaced, or pathway inhibition to prevent the effects of genetic change.”

Technology is leading the way in generating new therapeutic advances, she continued, beyond traditional “omics” to lipidomics, metabolomics, glycomics, and kinomics. “This has enabled us to find new genetic disorders and their causes, to look at changes in gene expression patterns, and to look at changes in protein expression patterns that give us clues as to how to move forward with better therapy,” she said. “When we’re talking about new insights into pathogenesis-based therapy, we’re talking largely about understanding the pathways that lead to either inflammation or promoting cell proliferation and abnormal differentiation.”

Treating pediatric psoriasis

Dr. Paller discussed her approach to managing patients with pediatric psoriasis, an inflammatory disorder with IL-23/Th17 skewing. “First of all, ask about itch and pain with these patients,” she advised. “Interviews have shown that 61% of children experience some itch, 39% have pain or stinging, and in the ixekizumab trials, 72% had what’s considered meaningful itch, with at least 4 out of 10 (mean intensity 5.3) on the itch numeric rating scale. Little is known about the itch associated with psoriasis and its underlying cause – unrelated to the IL-4/IL-13 pathway activation of atopic dermatitis – but it’s worth asking about. I find that itch of the scalp is especially a problem in psoriasis.”

Physicians should also ask pediatric psoriasis patients about joint pain, because about 1% of them have psoriatic arthritis, which is much less common than in adults, “but important to find and manage,” she added. Dr. Paller recommends the new R-JET rapid joint exam technique, which is accompanied by a three-question survey and body diagram that facilitates identification of true arthritis, “so you can know how quickly to refer”.

Several studies have described an increased risk of metabolic syndrome in adolescents with pediatric psoriasis and now in prepubertal children with the disease. In a recent study of 60 consecutive prepubertal children with psoriasis, 70% of whom had mild disease, 40% were overweight or obese, 53% had central obesity, 27% had high levels of the HOMA-IR (homeostasis model assessment of insulin resistance) despite generally normal levels of fasting glucose, and 30% met criteria for metabolic syndrome.

“This really struck me because our AAD [American Academy of Dermatology] guidelines did not recommend screening for type 2 diabetes in prepubertal children, even if overweight, because the risk is so small,” Dr. Paller said. “This report suggests that we may need to reconsider this recommendation in prepubertal children with psoriasis.”

Meanwhile, the number of medications approved by the Food and Drug Administration and the European Medicines Agency for children with psoriasis who are 6 years of age and above continues to expand, including tumor necrosis factor (TNF) inhibitors, interleukin (IL)-23 inhibitors, and IL-17 inhibitors. Most children can now achieve a PASI 90 within 12 weeks with the IL-23 inhibitor ustekinumab and the IL-17 inhibitors ixekizumab and secukinumab, Dr. Paller said.

In the ixekizumab trial, there are head-to-head comparison data in a European arm that involved the use of etanercept, she said. “What’s most noticeable is the significant difference in those who were able to achieve PASI 90 or above with this IL-17 inhibitor, versus etanercept,” which she added, raises the question of whether aiming for a PASI 75 is adequate, "or should we strive for PASI 90?” A pediatric psoriasis study published in 2020 found that the greatest improvement in quality of life was associated with a PASI 90 and use of systemic treatments (JAMA Dermatol. 2020;156[1]:72-8).

Looking forward, phase 3 clinical trials are underway in pediatric patients with moderate to severe psoriasis for guselkumab, tildrakizumab, risankizumab, certolizumab, bimekizumab, and brodalumab. “The cost of all of these biologics is high, however. I remind everyone that we still have methotrexate,” she said. “The risk of side effects with our low-dose methotrexate treatment for psoriasis remains low, but methotrexate doesn’t hit these [high] PASI numbers and it’s much slower in its onset than biologics.”

Dr. Paller disclosed that she is a consultant to and/or an investigator for AbbVie, Arena, Bausch, Bristol Myers Squibb, Dermavant, Eli Lilly, Incyte, Forte, LEO Pharma, LifeMax, Pfizer, RAPT Therapeutics, Regeneron, and Sanofi.

Commentary by Robert Sidbury, MD, MPH

Dr. Paller reminds us of some essential features of pediatric psoriasis:
•    It can hurt. Ask your patients if it does.
•    It can itch. Look for excoriations, especially in the scalp.
•    It is often associated with metabolic syndrome, so check relevant biometrics and labs, and consider coincident insulin resistance.
•    Our traditional clinical trial target of PASI75, or a 75% reduction in body surface area involvement, is just not good enough. Studies have shown that the most meaningful quality-of-life gains come at PASI90 or above. 
•    With our newer biologics, such as IL-12/23 blockers (for instance, ustekinumab) and IL-17 blockers (for example, ixekizumab and secukinumab), PASI90 and better is a reasonable expectation, not a pipe dream. 

Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.

This article was updated 6/16/22.

If COVID-19 has caused millions of deaths, it may also have prevented or at least led to a postponement of many births.

In an assessment of the pandemic’s early effects, Arnstein Aassve, PhD, and colleagues found a significant COVID-19–related decline in crude birth rates (CBRs) in 7 of 22 high-income countries, particularly in Southwestern Europe.

Dr. Aassve, an economist at the Carlo F. Dondena Center for Research on Social Dynamics and Public Policy at the Università Commerciale Luigi Bocconi, Milan, and colleagues report the results in an article published online August 30 in the Proceedings of the National Academy of Sciences.

Defining the start of the COVID-19 pandemic as February 2020, the study identifies strong declines in Italy (-9.1%), Hungary (-8.5%), Spain (-8.4%), and Portugal (-6.6%) beyond those predicted by past trends. In the United States, CBRs fell by 7.1% relative to 2019 for births occurring in Nov. and Dec. 2020 following conceptions in February and March of that year.

Significant declines in CBR also occurred in Belgium, Austria, and Singapore.

A year-to-year comparison of the mean for monthly CBRs per 1,000 population before and during the pandemic suggests a negative difference for all countries studied except for Denmark, Finland, Germany, and the Netherlands, Dr. Aassve and colleagues write. These findings may have policy implications for childcare, housing, and the labor market.

The Milan researchers compared monthly vital statistics data on live births from the international Human Fertility Database for the period of Jan. 2016 to March 2021. These figures reflect conceptions carried to term between April 2015 and June 2020. The 22 countries in the analysis represent 37% of the total reported COVID-19 cases and 34% of deaths worldwide.

The study findings align with surveys on “fertility intentions” collected early in the first COVID-19 wave in Germany, France, Spain, and the United Kingdom. These surveys indicated that 73% of people who were planning pregnancies in 2020 either decided to delay the pregnancy or they abandoned their plans.

“The popular media speculated that the lockdown would lead to a baby boom, as couples spent more time together,” Dr. Aassve told this news organization. “There’s very little evidence of this when you look to previous disasters and shocks, and the first data suggest more of an immediate collapse than a boom. But as you also see from the paper, the collapse is not seen everywhere.” Other current studies suggest the fertility drop is immediate but temporary, says Dr. Aassve, who is also a professor of demography.

Interestingly, Dr. Aassve and colleagues found that CBRs were relatively stable in Northern Europe. The authors point to supportive social and family policies in that region that might have reduced the effect of the pandemic on births. “These factors are likely to affect CBRs in the subsequent pandemic waves,” they write. They call for future studies to assess the full population implications of the pandemic, the moderating impact of policy interventions, and the nexus between short- and long-run effects in relation to the various waves of the COVID-19 pandemic.
 

Rebounds

Some regions have already reported a rebound from the COVID-19 fertility trough. Molly J. Stout, MD, director of maternal fetal medicine at the University of Michigan, Ann Arbor, and colleagues used electronic medical records to predict a surge in births after the initial decline.

“The surge we’ve seen at the end of this summer is exceeding the usual annual birth rate, as predicted,” she said in an interview. “But I think there’ll be a return to normal after this transient escalation. I don’t think birth rates will stay elevated above the normal because the birth surge is a temporary response to an event, although there will likely be regional differences.”

Looking ahead, Dr. Stout, who was not involved in Dr. Aassve’s analysis, is not certain how a fourth pandemic wave might ultimately modify a couple’s overall family size. But the toll the health crisis has taken on working women who have been forced to withdraw from the economy because of a lack of childcare points to a societal need that should be addressed.

According to Philip N. Cohen, PhD, a professor of sociology at the University of Maryland, College Park, who’s been tracking fertility trends since the onset of the COVID-19 emergency, the pandemic has combined a health crisis with an economic crisis, along with “the additional factor of social distancing and isolation, which all contributed to the decline in birth rates. Some people changed their plans to hold off on having children, while others didn’t get pregnant because they weren’t socializing and meeting people as much.”

Dr. Cohen, who was not involved in the study by Dr. Aassve and associates, said his provisional data show that although in many places, birth rates have rebounded more or less to prepandemic levels after a nadir around Jan. 2021, some areas of the United States still show substantially lower rates, including California, Hawaii, and Oregon.

As to the duration of the pandemic effect, Dr. Aassve cautions that his group’s estimates refer to the first wave only. “We then have the second, third, and currently the fourth wave. We can’t be sure about the impact of these waves on fertility since the data are not there yet, but I’d be surprised if they didn’t continue to have an impact on fertility rates,” he said.

Dr. Cohen agreed: “Some people who delayed childbearing will make up the delay. However, whenever there’s a delay, there’s inevitably some portion of the decline that’s not recouped.”

As for the wider effect across the world, Dr. Aassve said his team’s figures derive from high-income countries where data are readily available. For middle- and low-income countries, fewer data exist, and the quality of those data is not as good.

The lessons from this and other upheavals teach us that unforeseen shocks almost always have a negative impact on fertility, says Dr. Aassve. “[B]ut these effects may be separate from existing declining trends. The issue here is that those overall declining trends may be driven by other factors. In contrast, the shock of the pandemic is short-lived, and we may return to normal rather quickly. But if the pandemic also impacts other societal structures, such as the occupational and industrial sectors, then the pandemic might exacerbate the negative trend.”

The study was supported by funding from the European Research Council for funding under the European Union’s Horizon 2020 Research and Innovation Programme. The study authors, Dr. Stout, and Dr. Cohen have disclosed no relevant financial relationships.

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

If COVID-19 has caused millions of deaths, it may also have prevented or at least led to a postponement of many births.

In an assessment of the pandemic’s early effects, Arnstein Aassve, PhD, and colleagues found a significant COVID-19–related decline in crude birth rates (CBRs) in 7 of 22 high-income countries, particularly in Southwestern Europe.

Dr. Aassve, an economist at the Carlo F. Dondena Center for Research on Social Dynamics and Public Policy at the Università Commerciale Luigi Bocconi, Milan, and colleagues report the results in an article published online August 30 in the Proceedings of the National Academy of Sciences.

Defining the start of the COVID-19 pandemic as February 2020, the study identifies strong declines in Italy (-9.1%), Hungary (-8.5%), Spain (-8.4%), and Portugal (-6.6%) beyond those predicted by past trends. In the United States, CBRs fell by 7.1% relative to 2019 for births occurring in Nov. and Dec. 2020 following conceptions in February and March of that year.

Significant declines in CBR also occurred in Belgium, Austria, and Singapore.

A year-to-year comparison of the mean for monthly CBRs per 1,000 population before and during the pandemic suggests a negative difference for all countries studied except for Denmark, Finland, Germany, and the Netherlands, Dr. Aassve and colleagues write. These findings may have policy implications for childcare, housing, and the labor market.

The Milan researchers compared monthly vital statistics data on live births from the international Human Fertility Database for the period of Jan. 2016 to March 2021. These figures reflect conceptions carried to term between April 2015 and June 2020. The 22 countries in the analysis represent 37% of the total reported COVID-19 cases and 34% of deaths worldwide.

The study findings align with surveys on “fertility intentions” collected early in the first COVID-19 wave in Germany, France, Spain, and the United Kingdom. These surveys indicated that 73% of people who were planning pregnancies in 2020 either decided to delay the pregnancy or they abandoned their plans.

“The popular media speculated that the lockdown would lead to a baby boom, as couples spent more time together,” Dr. Aassve told this news organization. “There’s very little evidence of this when you look to previous disasters and shocks, and the first data suggest more of an immediate collapse than a boom. But as you also see from the paper, the collapse is not seen everywhere.” Other current studies suggest the fertility drop is immediate but temporary, says Dr. Aassve, who is also a professor of demography.

Interestingly, Dr. Aassve and colleagues found that CBRs were relatively stable in Northern Europe. The authors point to supportive social and family policies in that region that might have reduced the effect of the pandemic on births. “These factors are likely to affect CBRs in the subsequent pandemic waves,” they write. They call for future studies to assess the full population implications of the pandemic, the moderating impact of policy interventions, and the nexus between short- and long-run effects in relation to the various waves of the COVID-19 pandemic.
 

Rebounds

Some regions have already reported a rebound from the COVID-19 fertility trough. Molly J. Stout, MD, director of maternal fetal medicine at the University of Michigan, Ann Arbor, and colleagues used electronic medical records to predict a surge in births after the initial decline.

“The surge we’ve seen at the end of this summer is exceeding the usual annual birth rate, as predicted,” she said in an interview. “But I think there’ll be a return to normal after this transient escalation. I don’t think birth rates will stay elevated above the normal because the birth surge is a temporary response to an event, although there will likely be regional differences.”

Looking ahead, Dr. Stout, who was not involved in Dr. Aassve’s analysis, is not certain how a fourth pandemic wave might ultimately modify a couple’s overall family size. But the toll the health crisis has taken on working women who have been forced to withdraw from the economy because of a lack of childcare points to a societal need that should be addressed.

According to Philip N. Cohen, PhD, a professor of sociology at the University of Maryland, College Park, who’s been tracking fertility trends since the onset of the COVID-19 emergency, the pandemic has combined a health crisis with an economic crisis, along with “the additional factor of social distancing and isolation, which all contributed to the decline in birth rates. Some people changed their plans to hold off on having children, while others didn’t get pregnant because they weren’t socializing and meeting people as much.”

Dr. Cohen, who was not involved in the study by Dr. Aassve and associates, said his provisional data show that although in many places, birth rates have rebounded more or less to prepandemic levels after a nadir around Jan. 2021, some areas of the United States still show substantially lower rates, including California, Hawaii, and Oregon.

As to the duration of the pandemic effect, Dr. Aassve cautions that his group’s estimates refer to the first wave only. “We then have the second, third, and currently the fourth wave. We can’t be sure about the impact of these waves on fertility since the data are not there yet, but I’d be surprised if they didn’t continue to have an impact on fertility rates,” he said.

Dr. Cohen agreed: “Some people who delayed childbearing will make up the delay. However, whenever there’s a delay, there’s inevitably some portion of the decline that’s not recouped.”

As for the wider effect across the world, Dr. Aassve said his team’s figures derive from high-income countries where data are readily available. For middle- and low-income countries, fewer data exist, and the quality of those data is not as good.

The lessons from this and other upheavals teach us that unforeseen shocks almost always have a negative impact on fertility, says Dr. Aassve. “[B]ut these effects may be separate from existing declining trends. The issue here is that those overall declining trends may be driven by other factors. In contrast, the shock of the pandemic is short-lived, and we may return to normal rather quickly. But if the pandemic also impacts other societal structures, such as the occupational and industrial sectors, then the pandemic might exacerbate the negative trend.”

The study was supported by funding from the European Research Council for funding under the European Union’s Horizon 2020 Research and Innovation Programme. The study authors, Dr. Stout, and Dr. Cohen have disclosed no relevant financial relationships.

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

If COVID-19 has caused millions of deaths, it may also have prevented or at least led to a postponement of many births.

In an assessment of the pandemic’s early effects, Arnstein Aassve, PhD, and colleagues found a significant COVID-19–related decline in crude birth rates (CBRs) in 7 of 22 high-income countries, particularly in Southwestern Europe.

Dr. Aassve, an economist at the Carlo F. Dondena Center for Research on Social Dynamics and Public Policy at the Università Commerciale Luigi Bocconi, Milan, and colleagues report the results in an article published online August 30 in the Proceedings of the National Academy of Sciences.

Defining the start of the COVID-19 pandemic as February 2020, the study identifies strong declines in Italy (-9.1%), Hungary (-8.5%), Spain (-8.4%), and Portugal (-6.6%) beyond those predicted by past trends. In the United States, CBRs fell by 7.1% relative to 2019 for births occurring in Nov. and Dec. 2020 following conceptions in February and March of that year.

Significant declines in CBR also occurred in Belgium, Austria, and Singapore.

A year-to-year comparison of the mean for monthly CBRs per 1,000 population before and during the pandemic suggests a negative difference for all countries studied except for Denmark, Finland, Germany, and the Netherlands, Dr. Aassve and colleagues write. These findings may have policy implications for childcare, housing, and the labor market.

The Milan researchers compared monthly vital statistics data on live births from the international Human Fertility Database for the period of Jan. 2016 to March 2021. These figures reflect conceptions carried to term between April 2015 and June 2020. The 22 countries in the analysis represent 37% of the total reported COVID-19 cases and 34% of deaths worldwide.

The study findings align with surveys on “fertility intentions” collected early in the first COVID-19 wave in Germany, France, Spain, and the United Kingdom. These surveys indicated that 73% of people who were planning pregnancies in 2020 either decided to delay the pregnancy or they abandoned their plans.

“The popular media speculated that the lockdown would lead to a baby boom, as couples spent more time together,” Dr. Aassve told this news organization. “There’s very little evidence of this when you look to previous disasters and shocks, and the first data suggest more of an immediate collapse than a boom. But as you also see from the paper, the collapse is not seen everywhere.” Other current studies suggest the fertility drop is immediate but temporary, says Dr. Aassve, who is also a professor of demography.

Interestingly, Dr. Aassve and colleagues found that CBRs were relatively stable in Northern Europe. The authors point to supportive social and family policies in that region that might have reduced the effect of the pandemic on births. “These factors are likely to affect CBRs in the subsequent pandemic waves,” they write. They call for future studies to assess the full population implications of the pandemic, the moderating impact of policy interventions, and the nexus between short- and long-run effects in relation to the various waves of the COVID-19 pandemic.
 

Rebounds

Some regions have already reported a rebound from the COVID-19 fertility trough. Molly J. Stout, MD, director of maternal fetal medicine at the University of Michigan, Ann Arbor, and colleagues used electronic medical records to predict a surge in births after the initial decline.

“The surge we’ve seen at the end of this summer is exceeding the usual annual birth rate, as predicted,” she said in an interview. “But I think there’ll be a return to normal after this transient escalation. I don’t think birth rates will stay elevated above the normal because the birth surge is a temporary response to an event, although there will likely be regional differences.”

Looking ahead, Dr. Stout, who was not involved in Dr. Aassve’s analysis, is not certain how a fourth pandemic wave might ultimately modify a couple’s overall family size. But the toll the health crisis has taken on working women who have been forced to withdraw from the economy because of a lack of childcare points to a societal need that should be addressed.

According to Philip N. Cohen, PhD, a professor of sociology at the University of Maryland, College Park, who’s been tracking fertility trends since the onset of the COVID-19 emergency, the pandemic has combined a health crisis with an economic crisis, along with “the additional factor of social distancing and isolation, which all contributed to the decline in birth rates. Some people changed their plans to hold off on having children, while others didn’t get pregnant because they weren’t socializing and meeting people as much.”

Dr. Cohen, who was not involved in the study by Dr. Aassve and associates, said his provisional data show that although in many places, birth rates have rebounded more or less to prepandemic levels after a nadir around Jan. 2021, some areas of the United States still show substantially lower rates, including California, Hawaii, and Oregon.

As to the duration of the pandemic effect, Dr. Aassve cautions that his group’s estimates refer to the first wave only. “We then have the second, third, and currently the fourth wave. We can’t be sure about the impact of these waves on fertility since the data are not there yet, but I’d be surprised if they didn’t continue to have an impact on fertility rates,” he said.

Dr. Cohen agreed: “Some people who delayed childbearing will make up the delay. However, whenever there’s a delay, there’s inevitably some portion of the decline that’s not recouped.”

As for the wider effect across the world, Dr. Aassve said his team’s figures derive from high-income countries where data are readily available. For middle- and low-income countries, fewer data exist, and the quality of those data is not as good.

The lessons from this and other upheavals teach us that unforeseen shocks almost always have a negative impact on fertility, says Dr. Aassve. “[B]ut these effects may be separate from existing declining trends. The issue here is that those overall declining trends may be driven by other factors. In contrast, the shock of the pandemic is short-lived, and we may return to normal rather quickly. But if the pandemic also impacts other societal structures, such as the occupational and industrial sectors, then the pandemic might exacerbate the negative trend.”

The study was supported by funding from the European Research Council for funding under the European Union’s Horizon 2020 Research and Innovation Programme. The study authors, Dr. Stout, and Dr. Cohen have disclosed no relevant financial relationships.

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

Climate change is a global threat, and it presents a dual problem to health care: The system must address health threats that may be caused or exacerbated by climate change, while at the same time minimizing its environmental impact, according to the authors of a paper in Techniques and Innovations in Gastrointestinal Endoscopy.

Because of how often it is performed, endoscopy may have one of the highest environmental impacts of any health care procedure. Waste produced by endoscopy is the third largest source in a typical hospital, equivalent yearly to burning 39 million pounds of coal or 13,500 tons of plastic. That makes endoscopy a key target in reducing the environmental footprint of health care, according to the authors, who were led by Rosemary Haddock, MBChB, MRCP, of Ninewells Hospital in Dundee, Scotland.

Climate change has direct impacts on health, ranging from the effects of wildfire smoke and pollution on respiratory and cardiac health to food insecurity, heat stroke, and alterations to the geographic ranges of vector-borne diseases. It also raises the risk of future pandemics like COVID-19. “Climate change is a major threat to health and threatens to undermine the last 50 years of public health gains,” the authors wrote.

Although the effects of climate change on gastrointestinal diseases has not been studied as extensively as other organ systems, there are known impacts. These include more gastrointestinal infections at higher temperatures, the risk of enteric pathogens and viral hepatitis as a result of flooding and higher water temperatures, and malnutrition caused by the disruption of food crops and distribution. “It seems a little unlikely that the organs which we are interested in as gastroenterologists and hepatologists are largely exempt from the direct effects of hotter temperatures, when every other human organ system appears to be affected almost without exception,” the authors wrote.

Those issues put an onus on health care to address climate change, not only in health care delivery but also to find ways to reduce emissions as an industry. Hospitals and other large facilities can act as “anchor institutions” that set an example within the community and influence others since they procure goods and services and own assets and land. To date, few institutions have adopted this stance.

A key question is how health care institutions can reduce resource use while maintaining quality of care. One approach is to identify areas of medical overuse, where wasteful practices have no patient benefit. The authors believe that a reduction in endoscopic procedures could have one of the largest impacts on carbon emissions. They emphasized that reduced numbers of procedures would likely have greater effect than making procedures “greener.”

Some endoscopic procedures offer little value to the patient. The approach of screening to combat disease, introduced in 1968, should be challenged in some patient groups because it can lead to unnecessary procedures.

The American Gastroenterological Association has identified some procedures as commonly overused, including screening colonoscopy in average-risk individuals, surveillance colonoscopy for low-risk polyps, and surveillance esophagogastroduodenoscopy in Barrett’s esophagus. The authors note that performing fewer endoscopies will require shifts in behavior, referral patterns, education, and culture, all of which will take time.

In the meantime, endoscopists can take some steps to reduce the footprint of existing procedures: source supplies through sustainable means, which is important because supply chain emissions account for more than half of health care emissions; seek out sources of renewable energy; use their institution’s status as an “anchor institution” to pressure suppliers into using sustainable practices; evaluate less invasive procedures, such as Cytosponge or fecal immunochemical test; employ reusable or recyclable equipment; minimize the use of nitrous oxide, which is a key greenhouse gas; segregate infectious waste; and develop multiple recycling streams.

The authors have no relevant financial disclosures.

Climate change is a global threat, and it presents a dual problem to health care: The system must address health threats that may be caused or exacerbated by climate change, while at the same time minimizing its environmental impact, according to the authors of a paper in Techniques and Innovations in Gastrointestinal Endoscopy.

Because of how often it is performed, endoscopy may have one of the highest environmental impacts of any health care procedure. Waste produced by endoscopy is the third largest source in a typical hospital, equivalent yearly to burning 39 million pounds of coal or 13,500 tons of plastic. That makes endoscopy a key target in reducing the environmental footprint of health care, according to the authors, who were led by Rosemary Haddock, MBChB, MRCP, of Ninewells Hospital in Dundee, Scotland.

Climate change has direct impacts on health, ranging from the effects of wildfire smoke and pollution on respiratory and cardiac health to food insecurity, heat stroke, and alterations to the geographic ranges of vector-borne diseases. It also raises the risk of future pandemics like COVID-19. “Climate change is a major threat to health and threatens to undermine the last 50 years of public health gains,” the authors wrote.

Although the effects of climate change on gastrointestinal diseases has not been studied as extensively as other organ systems, there are known impacts. These include more gastrointestinal infections at higher temperatures, the risk of enteric pathogens and viral hepatitis as a result of flooding and higher water temperatures, and malnutrition caused by the disruption of food crops and distribution. “It seems a little unlikely that the organs which we are interested in as gastroenterologists and hepatologists are largely exempt from the direct effects of hotter temperatures, when every other human organ system appears to be affected almost without exception,” the authors wrote.

Those issues put an onus on health care to address climate change, not only in health care delivery but also to find ways to reduce emissions as an industry. Hospitals and other large facilities can act as “anchor institutions” that set an example within the community and influence others since they procure goods and services and own assets and land. To date, few institutions have adopted this stance.

A key question is how health care institutions can reduce resource use while maintaining quality of care. One approach is to identify areas of medical overuse, where wasteful practices have no patient benefit. The authors believe that a reduction in endoscopic procedures could have one of the largest impacts on carbon emissions. They emphasized that reduced numbers of procedures would likely have greater effect than making procedures “greener.”

Some endoscopic procedures offer little value to the patient. The approach of screening to combat disease, introduced in 1968, should be challenged in some patient groups because it can lead to unnecessary procedures.

The American Gastroenterological Association has identified some procedures as commonly overused, including screening colonoscopy in average-risk individuals, surveillance colonoscopy for low-risk polyps, and surveillance esophagogastroduodenoscopy in Barrett’s esophagus. The authors note that performing fewer endoscopies will require shifts in behavior, referral patterns, education, and culture, all of which will take time.

In the meantime, endoscopists can take some steps to reduce the footprint of existing procedures: source supplies through sustainable means, which is important because supply chain emissions account for more than half of health care emissions; seek out sources of renewable energy; use their institution’s status as an “anchor institution” to pressure suppliers into using sustainable practices; evaluate less invasive procedures, such as Cytosponge or fecal immunochemical test; employ reusable or recyclable equipment; minimize the use of nitrous oxide, which is a key greenhouse gas; segregate infectious waste; and develop multiple recycling streams.

The authors have no relevant financial disclosures.

Climate change is a global threat, and it presents a dual problem to health care: The system must address health threats that may be caused or exacerbated by climate change, while at the same time minimizing its environmental impact, according to the authors of a paper in Techniques and Innovations in Gastrointestinal Endoscopy.

Because of how often it is performed, endoscopy may have one of the highest environmental impacts of any health care procedure. Waste produced by endoscopy is the third largest source in a typical hospital, equivalent yearly to burning 39 million pounds of coal or 13,500 tons of plastic. That makes endoscopy a key target in reducing the environmental footprint of health care, according to the authors, who were led by Rosemary Haddock, MBChB, MRCP, of Ninewells Hospital in Dundee, Scotland.

Climate change has direct impacts on health, ranging from the effects of wildfire smoke and pollution on respiratory and cardiac health to food insecurity, heat stroke, and alterations to the geographic ranges of vector-borne diseases. It also raises the risk of future pandemics like COVID-19. “Climate change is a major threat to health and threatens to undermine the last 50 years of public health gains,” the authors wrote.

Although the effects of climate change on gastrointestinal diseases has not been studied as extensively as other organ systems, there are known impacts. These include more gastrointestinal infections at higher temperatures, the risk of enteric pathogens and viral hepatitis as a result of flooding and higher water temperatures, and malnutrition caused by the disruption of food crops and distribution. “It seems a little unlikely that the organs which we are interested in as gastroenterologists and hepatologists are largely exempt from the direct effects of hotter temperatures, when every other human organ system appears to be affected almost without exception,” the authors wrote.

Those issues put an onus on health care to address climate change, not only in health care delivery but also to find ways to reduce emissions as an industry. Hospitals and other large facilities can act as “anchor institutions” that set an example within the community and influence others since they procure goods and services and own assets and land. To date, few institutions have adopted this stance.

A key question is how health care institutions can reduce resource use while maintaining quality of care. One approach is to identify areas of medical overuse, where wasteful practices have no patient benefit. The authors believe that a reduction in endoscopic procedures could have one of the largest impacts on carbon emissions. They emphasized that reduced numbers of procedures would likely have greater effect than making procedures “greener.”

Some endoscopic procedures offer little value to the patient. The approach of screening to combat disease, introduced in 1968, should be challenged in some patient groups because it can lead to unnecessary procedures.

The American Gastroenterological Association has identified some procedures as commonly overused, including screening colonoscopy in average-risk individuals, surveillance colonoscopy for low-risk polyps, and surveillance esophagogastroduodenoscopy in Barrett’s esophagus. The authors note that performing fewer endoscopies will require shifts in behavior, referral patterns, education, and culture, all of which will take time.

In the meantime, endoscopists can take some steps to reduce the footprint of existing procedures: source supplies through sustainable means, which is important because supply chain emissions account for more than half of health care emissions; seek out sources of renewable energy; use their institution’s status as an “anchor institution” to pressure suppliers into using sustainable practices; evaluate less invasive procedures, such as Cytosponge or fecal immunochemical test; employ reusable or recyclable equipment; minimize the use of nitrous oxide, which is a key greenhouse gas; segregate infectious waste; and develop multiple recycling streams.

The authors have no relevant financial disclosures.

In patients with moderate to severe ulcerative colitis (UC), treatment with vedolizumab leads to better histologic outcomes than treatment with adalimumab, according to findings from the VARSITY trial.

The findings come from an analysis in Gastroenterology of prespecified histologic exploratory endpoints from the phase 3, multicenter, randomized, controlled VARSITY trial, which was the first head-to-head comparison of two biologics in the treatment of UC. VARSITY demonstrated improved rates of clinical remission and endoscopic improvement at week 52 with vedolizumab.

The authors, led by Laurent Peyrin-Biroulet of the department of gastroenterology at Nancy (France) University Hospital, noted that there is general consensus that endoscopic improvement is considered the best endpoint for demonstrating effective maintenance therapy in UC. However, they added that “endoscopic changes do not necessarily reflect quiescent microscopic disease, and complete resolution of mucosal inflammation can only be confirmed by histologic assessment.” Still, histologic outcomes are not currently recommended as a goal of therapy in clinical practice, possibly due to a lack of standardized and validated scoring systems suitable for routine clinical use. Nevertheless, histologic outcomes have been shown to predict hospitalization, corticosteroid use, exacerbation, and the risk of advanced colorectal neoplasia.

To assess histologic outcomes in the two treatment regimens, the researchers included the Geboes Index score and the Robarts Histopathology Index (RHI) as two validated scoring systems.

During the 52-week study, 769 patients were assigned to vedolizumab (300 mg IV) or adalimumab (40 mg subcutaneously).

At week 14 and week 52, more patients in the vedolizumab group achieved histologic remission as determined by Geboes Index score less than 2 (week 52, 29.2% vs. 8.3%; difference, 20.9%; 95% confidence interval, 15.6%-26.2%; P < .0001) and RHI score of 2 or less (week 52, 37.6% vs. 19.9%; difference, 17.6%; 95% CI, 11.3%-23.8%; P < .0001).

At week 52, more patients in the vedolizumab group than in the adalimumab group achieved minimum histologic disease activity as determined by Geboes Index score of 3.1 or less (45.7% vs. 30.8%; difference, 14.8%; 95% CI, 8.0%-21.5%; P < .0001) and RHI score of 4 or less(42.3% vs. 25.6%; difference, 16.6%; 95% CI, 10.0%-23.1%; P < .0001).

The investigators performed post hoc analyses of mucosal healing, defined as a composite of the histologic and endoscopic outcomes, with the latter defined as Mayo endoscopic subscore of 1 or less. A greater proportion of patients treated with vedolizumab than with adalimumab met the composite of histologic remission on each score plus endoscopic improvement (Geboes, 35.0% vs. 20.2%; RHI, 33.7% vs. 18.1%), with similar findings for minimal histologic disease activity plus endoscopic improvement (Geboes, 35.0% vs. 20.2%; RHI, 33.7% vs. 18.1%).

The authors noted that the RHI scoring system revealed greater associations between histologic outcomes and endoscopic improvement than did the Geboes Index score, which is an important finding considering the European Crohn’s and Colitis Organisation’s stance recommending consideration of mucosal healing based on findings from endoscopy and histology.

Some study limitations included how the study design precluded dose escalation and a lack of long-term follow-up among these patients.

The researchers believe that the RHI score may be a better choice than the Geboes score for comparing efficacy in clinical trials because RHI is more reproducible, more sensitive to change, and is comparatively easy to interpret.

The study was funded by Takeda, which makes vedolizumab. The authors disclosed several relationships with industry, including some having stock options with or being employed by Takeda.

In patients with moderate to severe ulcerative colitis (UC), treatment with vedolizumab leads to better histologic outcomes than treatment with adalimumab, according to findings from the VARSITY trial.

The findings come from an analysis in Gastroenterology of prespecified histologic exploratory endpoints from the phase 3, multicenter, randomized, controlled VARSITY trial, which was the first head-to-head comparison of two biologics in the treatment of UC. VARSITY demonstrated improved rates of clinical remission and endoscopic improvement at week 52 with vedolizumab.

The authors, led by Laurent Peyrin-Biroulet of the department of gastroenterology at Nancy (France) University Hospital, noted that there is general consensus that endoscopic improvement is considered the best endpoint for demonstrating effective maintenance therapy in UC. However, they added that “endoscopic changes do not necessarily reflect quiescent microscopic disease, and complete resolution of mucosal inflammation can only be confirmed by histologic assessment.” Still, histologic outcomes are not currently recommended as a goal of therapy in clinical practice, possibly due to a lack of standardized and validated scoring systems suitable for routine clinical use. Nevertheless, histologic outcomes have been shown to predict hospitalization, corticosteroid use, exacerbation, and the risk of advanced colorectal neoplasia.

To assess histologic outcomes in the two treatment regimens, the researchers included the Geboes Index score and the Robarts Histopathology Index (RHI) as two validated scoring systems.

During the 52-week study, 769 patients were assigned to vedolizumab (300 mg IV) or adalimumab (40 mg subcutaneously).

At week 14 and week 52, more patients in the vedolizumab group achieved histologic remission as determined by Geboes Index score less than 2 (week 52, 29.2% vs. 8.3%; difference, 20.9%; 95% confidence interval, 15.6%-26.2%; P < .0001) and RHI score of 2 or less (week 52, 37.6% vs. 19.9%; difference, 17.6%; 95% CI, 11.3%-23.8%; P < .0001).

At week 52, more patients in the vedolizumab group than in the adalimumab group achieved minimum histologic disease activity as determined by Geboes Index score of 3.1 or less (45.7% vs. 30.8%; difference, 14.8%; 95% CI, 8.0%-21.5%; P < .0001) and RHI score of 4 or less(42.3% vs. 25.6%; difference, 16.6%; 95% CI, 10.0%-23.1%; P < .0001).

The investigators performed post hoc analyses of mucosal healing, defined as a composite of the histologic and endoscopic outcomes, with the latter defined as Mayo endoscopic subscore of 1 or less. A greater proportion of patients treated with vedolizumab than with adalimumab met the composite of histologic remission on each score plus endoscopic improvement (Geboes, 35.0% vs. 20.2%; RHI, 33.7% vs. 18.1%), with similar findings for minimal histologic disease activity plus endoscopic improvement (Geboes, 35.0% vs. 20.2%; RHI, 33.7% vs. 18.1%).

The authors noted that the RHI scoring system revealed greater associations between histologic outcomes and endoscopic improvement than did the Geboes Index score, which is an important finding considering the European Crohn’s and Colitis Organisation’s stance recommending consideration of mucosal healing based on findings from endoscopy and histology.

Some study limitations included how the study design precluded dose escalation and a lack of long-term follow-up among these patients.

The researchers believe that the RHI score may be a better choice than the Geboes score for comparing efficacy in clinical trials because RHI is more reproducible, more sensitive to change, and is comparatively easy to interpret.

The study was funded by Takeda, which makes vedolizumab. The authors disclosed several relationships with industry, including some having stock options with or being employed by Takeda.

In patients with moderate to severe ulcerative colitis (UC), treatment with vedolizumab leads to better histologic outcomes than treatment with adalimumab, according to findings from the VARSITY trial.

The findings come from an analysis in Gastroenterology of prespecified histologic exploratory endpoints from the phase 3, multicenter, randomized, controlled VARSITY trial, which was the first head-to-head comparison of two biologics in the treatment of UC. VARSITY demonstrated improved rates of clinical remission and endoscopic improvement at week 52 with vedolizumab.

The authors, led by Laurent Peyrin-Biroulet of the department of gastroenterology at Nancy (France) University Hospital, noted that there is general consensus that endoscopic improvement is considered the best endpoint for demonstrating effective maintenance therapy in UC. However, they added that “endoscopic changes do not necessarily reflect quiescent microscopic disease, and complete resolution of mucosal inflammation can only be confirmed by histologic assessment.” Still, histologic outcomes are not currently recommended as a goal of therapy in clinical practice, possibly due to a lack of standardized and validated scoring systems suitable for routine clinical use. Nevertheless, histologic outcomes have been shown to predict hospitalization, corticosteroid use, exacerbation, and the risk of advanced colorectal neoplasia.

To assess histologic outcomes in the two treatment regimens, the researchers included the Geboes Index score and the Robarts Histopathology Index (RHI) as two validated scoring systems.

During the 52-week study, 769 patients were assigned to vedolizumab (300 mg IV) or adalimumab (40 mg subcutaneously).

At week 14 and week 52, more patients in the vedolizumab group achieved histologic remission as determined by Geboes Index score less than 2 (week 52, 29.2% vs. 8.3%; difference, 20.9%; 95% confidence interval, 15.6%-26.2%; P < .0001) and RHI score of 2 or less (week 52, 37.6% vs. 19.9%; difference, 17.6%; 95% CI, 11.3%-23.8%; P < .0001).

At week 52, more patients in the vedolizumab group than in the adalimumab group achieved minimum histologic disease activity as determined by Geboes Index score of 3.1 or less (45.7% vs. 30.8%; difference, 14.8%; 95% CI, 8.0%-21.5%; P < .0001) and RHI score of 4 or less(42.3% vs. 25.6%; difference, 16.6%; 95% CI, 10.0%-23.1%; P < .0001).

The investigators performed post hoc analyses of mucosal healing, defined as a composite of the histologic and endoscopic outcomes, with the latter defined as Mayo endoscopic subscore of 1 or less. A greater proportion of patients treated with vedolizumab than with adalimumab met the composite of histologic remission on each score plus endoscopic improvement (Geboes, 35.0% vs. 20.2%; RHI, 33.7% vs. 18.1%), with similar findings for minimal histologic disease activity plus endoscopic improvement (Geboes, 35.0% vs. 20.2%; RHI, 33.7% vs. 18.1%).

The authors noted that the RHI scoring system revealed greater associations between histologic outcomes and endoscopic improvement than did the Geboes Index score, which is an important finding considering the European Crohn’s and Colitis Organisation’s stance recommending consideration of mucosal healing based on findings from endoscopy and histology.

Some study limitations included how the study design precluded dose escalation and a lack of long-term follow-up among these patients.

The researchers believe that the RHI score may be a better choice than the Geboes score for comparing efficacy in clinical trials because RHI is more reproducible, more sensitive to change, and is comparatively easy to interpret.

The study was funded by Takeda, which makes vedolizumab. The authors disclosed several relationships with industry, including some having stock options with or being employed by Takeda.