MDedge Pediatrics

The Food and Drug Administration has approved the nonstimulant medication viloxazine extended-release capsules (Qelbree, Supernus Pharmaceuticals) for the treatment of attention deficit hyperactivity disorder (ADHD) in children aged 6-17 years, the company has announced.

Viloxazine (formerly SPN-812) is a selective norepinephrine reuptake inhibitor. Capsules may be swallowed whole or opened and the entire contents sprinkled onto applesauce, as needed.

The approval of viloxazine is supported by data from four phase 3 clinical trials involving more than 1,000 pediatric patients aged 6-17 years, the company said.

In one randomized, placebo-controlled phase 3 study that included more than 400 children, viloxazine reduced symptoms of ADHD as soon as 1 week after dosing and was well tolerated.

As reported by this news organization, the study was published last July in Clinical Therapeutics.

In addition to its fast onset of action, the fact that it was effective for both inattentive and hyperactive/impulsive clusters of symptoms is “impressive,” study investigator Andrew Cutler, MD, clinical associate professor of psychiatry, SUNY Upstate Medical University, Syracuse, N.Y., said in an interview.

Also noteworthy was the improvement in measures of quality of life and function, “especially function in the areas of school, home life, family relations, and peer relationships, which can be really disrupted with ADHD,” Dr. Cutler said.

The prescribing label for viloxazine includes a boxed warning regarding the potential for suicidal thoughts and behaviors in some children with ADHD treated with the drug, especially within the first few months of treatment or when the dose is changed. 

In clinical trials, higher rates of suicidal thoughts and behavior were reported in pediatric patients treated with viloxazine than in patients treated with placebo. Patients taking viloxazine should be closely monitored for any new or sudden changes in mood, behavior, thoughts, and feelings.

Viloxazine has shown promise in a phase 3 trial involving adults with ADHD.

The company plans to submit a supplemental new drug application to the FDA for viloxazine in adults later this year.

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

The Food and Drug Administration has approved the nonstimulant medication viloxazine extended-release capsules (Qelbree, Supernus Pharmaceuticals) for the treatment of attention deficit hyperactivity disorder (ADHD) in children aged 6-17 years, the company has announced.

Viloxazine (formerly SPN-812) is a selective norepinephrine reuptake inhibitor. Capsules may be swallowed whole or opened and the entire contents sprinkled onto applesauce, as needed.

The approval of viloxazine is supported by data from four phase 3 clinical trials involving more than 1,000 pediatric patients aged 6-17 years, the company said.

In one randomized, placebo-controlled phase 3 study that included more than 400 children, viloxazine reduced symptoms of ADHD as soon as 1 week after dosing and was well tolerated.

As reported by this news organization, the study was published last July in Clinical Therapeutics.

In addition to its fast onset of action, the fact that it was effective for both inattentive and hyperactive/impulsive clusters of symptoms is “impressive,” study investigator Andrew Cutler, MD, clinical associate professor of psychiatry, SUNY Upstate Medical University, Syracuse, N.Y., said in an interview.

Also noteworthy was the improvement in measures of quality of life and function, “especially function in the areas of school, home life, family relations, and peer relationships, which can be really disrupted with ADHD,” Dr. Cutler said.

The prescribing label for viloxazine includes a boxed warning regarding the potential for suicidal thoughts and behaviors in some children with ADHD treated with the drug, especially within the first few months of treatment or when the dose is changed. 

In clinical trials, higher rates of suicidal thoughts and behavior were reported in pediatric patients treated with viloxazine than in patients treated with placebo. Patients taking viloxazine should be closely monitored for any new or sudden changes in mood, behavior, thoughts, and feelings.

Viloxazine has shown promise in a phase 3 trial involving adults with ADHD.

The company plans to submit a supplemental new drug application to the FDA for viloxazine in adults later this year.

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

The Food and Drug Administration has approved the nonstimulant medication viloxazine extended-release capsules (Qelbree, Supernus Pharmaceuticals) for the treatment of attention deficit hyperactivity disorder (ADHD) in children aged 6-17 years, the company has announced.

Viloxazine (formerly SPN-812) is a selective norepinephrine reuptake inhibitor. Capsules may be swallowed whole or opened and the entire contents sprinkled onto applesauce, as needed.

The approval of viloxazine is supported by data from four phase 3 clinical trials involving more than 1,000 pediatric patients aged 6-17 years, the company said.

In one randomized, placebo-controlled phase 3 study that included more than 400 children, viloxazine reduced symptoms of ADHD as soon as 1 week after dosing and was well tolerated.

As reported by this news organization, the study was published last July in Clinical Therapeutics.

In addition to its fast onset of action, the fact that it was effective for both inattentive and hyperactive/impulsive clusters of symptoms is “impressive,” study investigator Andrew Cutler, MD, clinical associate professor of psychiatry, SUNY Upstate Medical University, Syracuse, N.Y., said in an interview.

Also noteworthy was the improvement in measures of quality of life and function, “especially function in the areas of school, home life, family relations, and peer relationships, which can be really disrupted with ADHD,” Dr. Cutler said.

The prescribing label for viloxazine includes a boxed warning regarding the potential for suicidal thoughts and behaviors in some children with ADHD treated with the drug, especially within the first few months of treatment or when the dose is changed. 

In clinical trials, higher rates of suicidal thoughts and behavior were reported in pediatric patients treated with viloxazine than in patients treated with placebo. Patients taking viloxazine should be closely monitored for any new or sudden changes in mood, behavior, thoughts, and feelings.

Viloxazine has shown promise in a phase 3 trial involving adults with ADHD.

The company plans to submit a supplemental new drug application to the FDA for viloxazine in adults later this year.

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

Children and adolescents with Prader-Willi syndrome (PWS) who received three daily, intranasal doses of carbetocin, an investigational, long-acting oxytocin analogue, had significant improvement in hyperphagia and anxiety during 8 weeks on treatment, compared with placebo in a multicenter, phase 3 trial with 119 patients.

The treatment also appeared safe during up to 56 additional weeks on active treatment, with no serious adverse effects nor “unexpected” events, and once completing the study about 95% of enrolled patients opted to remain on active treatment, Cheri L. Deal, MD, PhD, said at the annual meeting of the Endocrine Society.

Based on “the significant results for the placebo-controlled period, as well as for those finishing the 56-week extension, we may well have a new armament for helping these kids and their families deal with the unrelenting hunger of patients with PWS as well as some of the behavioral symptoms,” Dr. Deal, chief of endocrinology and diabetes at the Sainte-Justine Mother-Child University of Montreal Hospital, said in an interview. No treatment currently has labeling for addressing the hyperphagia or anxiety that is characteristic and often problematic for children and adolescents with PWS, an autosomal dominant genetic disease with an incidence of about 1 in 15,000 births and an estimated U.S. prevalence of about 9,000 cases, or about 1 case for every 37,000 people.
 

‘Gorgeous’ safety

“The results looked pretty positive, and we’re encouraged by what appears to be a good safety profile, so overall I think the PWS community is very excited by the results and is very interested in getting access to this drug,” commented Theresa V. Strong, PhD, director of research programs for the Foundation for Prader-Willi Research in Walnut, Calif., a group not involved with the study. Currently, “we have no effective treatments for these difficult behaviors” of hyperphagia and anxiety. Surveys and studies run by the foundation have documented that hyperphagia and anxiety “were the two most important symptoms that families would like to see treated,” Dr. Strong added in an interview.

PWS “is complex and affects almost every aspect of the lives of affected people and their families. Any treatment that can chip away at some of the problems these patients have can be a huge benefit to the patients and their families,” said Jennifer L. Miller, MD, a professor of pediatric endocrinology at the University of Florida, Gainesville, and a coinvestigator on the study.

But the finding that carbetocin appeared to address, at least in part, this unmet need while compiling a safety record that Dr. Miller called “gorgeous” and “remarkable,” also came with a few limitations.
 

Fewer patients than planned, and muddled outcomes

The CARE-PWS trial aimed to enroll 175 patients, but fell short once the COVID-19 pandemic hit. Plus the trial had two prespecified primary endpoints – improvements in a measure of hyperphagia, and in a measure of obsessive and compulsive behaviors – specifically in the 40 patients who received the higher of the two dosages studied, 9.6 mg t.i.d. intranasally. Neither endpoint showed significant improvement among the patients on this dosage, compared with the 40 patients who received placebo, although both outcomes trended in the right direction in the actively treated patients.

The study’s positive results came in a secondary treatment group, 39 patients who received 3.2 mg t.i.d., also intranasally. This subgroup had significant benefit, compared with placebo, for reducing hyperphagia symptoms as measured on the Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Total Score. After the first 8 weeks on treatment, patients on the lower carbetocin dosage had an average reduction in their HQ-CT score of greater than 5 points, more than double the reduction seen among control patients who received placebo.

Those on the 3.2-mg t.i.d. dosage also showed significant improvements, compared with placebo, for anxiety, measured by the PWS Anxiety and Distress Questionnaire Total Score, as well as on measures of clinical global impression of severity, and of clinical global impression of change. Like the higher-dosage patients the lower-dosage subgroup did not show a significant difference compared with placebo for the other primary endpoint, change in obsessive and compulsive behaviors as measured by the Children’s Yale-Brown Obsessive-Compulsive Scale Total Score, although also like the higher dosage the effect from the lower dosage trended toward benefit.

A further limitation was that, at the time of her report, presented in abstract OR16-3 at the meeting, Dr. Deal could only present complete 64-week follow-up for 72 patients, although this reassuringly showed that, as time on the 9.6-mg t.i.d. dosage continued beyond 8 weeks, patients gradually improved their HQ-CT response so that by 64 weeks on treatment their hyperphagia score had improved as much as in the patients who received the lower dosage.

In short, documented benefits occurred on the lower dosage, especially for clinically meaningful symptoms like hyperphagia and anxiety, but the study’s overall results were not fully consistent by statistical criteria.

Benefiting an unmet need?

“While it is regrettable that we did not get to 175 patients because of COVID-19, the dataset is significant enough for me to feel that the FDA [Food and Drug Administration] needs to take a very serious look and consider approval,” Dr. Deal said in an interview. “Once safety is assured, which I think it is, I can only hope that regulatory officials understand their unmet needs of this rare disease community and will allow the drug to move to the next stage.”

“This is a very rare disease, and having families participate in trials is really challenging,” especially while the COVID-19 pandemic continues, Dr. Strong said. For the pediatric and adolescent patients targeted in this study “it will take a while for COVID to go away and for families to feel safe again being in a trial, so a real concern is that a need for more clinical trials is not terribly feasible now. Given that the safety profile looked good and one dose seemed to have good efficacy, as long as the long-term data continue to look good we’d love for the FDA to look at the existing data and see whether there is a path forward.”

Dr. Miller highlighted the limitations of what the CARE-PWS findings show.

“Given that it was only an 8-week trial of drug against placebo, and the fact that the primary outcomes weren’t met for the higher dose, my thought is that potentially we need to study more patients for a longer period at the 3.2-mg dose,” she said. She acknowledged that the metric used in the study to assess obsessive and compulsive behaviors is “very difficult” to apply to patients with PWS because of uncertainties in scoring obsessions in patients “who are not very good at telling you what they’re thinking.” Plus, “it’s absolutely not a problem that we did not see an effect on obsession and compulsions if the treatment potentially improves anxiety and hyperphagia, which are very common.” A treatment that reliably reduces these symptoms “would be amazing,” Dr. Miller added.

“PWS is very rare, so it’s very hard to do trials. Maybe the FDA will approve carbetocin because it was safe and gave a signal of efficacy at the lower dose. But my thought is that additional treatment trials are needed with only the lower dose and with longer duration,” she said.

CARE-PWS enrolled patients with nutritional phase 3 PWS who were aged 7-18 years at any of 24 sites in the United States, Canada, or Australia during 2018-2020. They averaged about 12 years of age, and 56% were girls.

The most common adverse effect from carbetocin was flushing, occurring in 14% of those on the lower dose and 21% on the higher dose, but not in any placebo patient. Other adverse effects more common on the lower dose than in the placebo group included headache in 16%, and diarrhea in 9%.

Carbetocin is not only long-lasting in circulation, it also has better affinity for oxytocin receptors than for vasopressin receptors, reducing the potential for causing hyponatremia. The idea to use it in patients with PWS followed prior studies with oxytocin, which had shown dopamine interactions that reduced anxiety and influenced food ingestion behavior. Brain autopsy studies had shown that patients with Prader-Willi syndrome have substantially fewer neurons than usual producing oxytocin. Treatment with intranasal carbetocin had shown efficacy for improving hyperphagia and behavior in a controlled phase 2 study with 37 patients.

Carbetocin is approved for use in reducing excessive bleeding after childbirth, particularly cesarean, in more than 20 countries outside the United States.

CARE-PWS was sponsored by Levo Therapeutics, the company developing carbetocin. Dr. Deal has been an adviser to Levo Therapeutics. Dr. Strong is an employee of the Foundation for Prader-Willi Research, which has received support from Levo Therapeutics as well as from other drug companies, but which receives most of its funding from individuals. Dr. Miller has received research funding from Levo Therapeutics and also from Harmony Biosciences, Rhythm Pharmaceuticals, and Soleno Therapeutics.

[email protected]

Children and adolescents with Prader-Willi syndrome (PWS) who received three daily, intranasal doses of carbetocin, an investigational, long-acting oxytocin analogue, had significant improvement in hyperphagia and anxiety during 8 weeks on treatment, compared with placebo in a multicenter, phase 3 trial with 119 patients.

The treatment also appeared safe during up to 56 additional weeks on active treatment, with no serious adverse effects nor “unexpected” events, and once completing the study about 95% of enrolled patients opted to remain on active treatment, Cheri L. Deal, MD, PhD, said at the annual meeting of the Endocrine Society.

Based on “the significant results for the placebo-controlled period, as well as for those finishing the 56-week extension, we may well have a new armament for helping these kids and their families deal with the unrelenting hunger of patients with PWS as well as some of the behavioral symptoms,” Dr. Deal, chief of endocrinology and diabetes at the Sainte-Justine Mother-Child University of Montreal Hospital, said in an interview. No treatment currently has labeling for addressing the hyperphagia or anxiety that is characteristic and often problematic for children and adolescents with PWS, an autosomal dominant genetic disease with an incidence of about 1 in 15,000 births and an estimated U.S. prevalence of about 9,000 cases, or about 1 case for every 37,000 people.
 

‘Gorgeous’ safety

“The results looked pretty positive, and we’re encouraged by what appears to be a good safety profile, so overall I think the PWS community is very excited by the results and is very interested in getting access to this drug,” commented Theresa V. Strong, PhD, director of research programs for the Foundation for Prader-Willi Research in Walnut, Calif., a group not involved with the study. Currently, “we have no effective treatments for these difficult behaviors” of hyperphagia and anxiety. Surveys and studies run by the foundation have documented that hyperphagia and anxiety “were the two most important symptoms that families would like to see treated,” Dr. Strong added in an interview.

PWS “is complex and affects almost every aspect of the lives of affected people and their families. Any treatment that can chip away at some of the problems these patients have can be a huge benefit to the patients and their families,” said Jennifer L. Miller, MD, a professor of pediatric endocrinology at the University of Florida, Gainesville, and a coinvestigator on the study.

But the finding that carbetocin appeared to address, at least in part, this unmet need while compiling a safety record that Dr. Miller called “gorgeous” and “remarkable,” also came with a few limitations.
 

Fewer patients than planned, and muddled outcomes

The CARE-PWS trial aimed to enroll 175 patients, but fell short once the COVID-19 pandemic hit. Plus the trial had two prespecified primary endpoints – improvements in a measure of hyperphagia, and in a measure of obsessive and compulsive behaviors – specifically in the 40 patients who received the higher of the two dosages studied, 9.6 mg t.i.d. intranasally. Neither endpoint showed significant improvement among the patients on this dosage, compared with the 40 patients who received placebo, although both outcomes trended in the right direction in the actively treated patients.

The study’s positive results came in a secondary treatment group, 39 patients who received 3.2 mg t.i.d., also intranasally. This subgroup had significant benefit, compared with placebo, for reducing hyperphagia symptoms as measured on the Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Total Score. After the first 8 weeks on treatment, patients on the lower carbetocin dosage had an average reduction in their HQ-CT score of greater than 5 points, more than double the reduction seen among control patients who received placebo.

Those on the 3.2-mg t.i.d. dosage also showed significant improvements, compared with placebo, for anxiety, measured by the PWS Anxiety and Distress Questionnaire Total Score, as well as on measures of clinical global impression of severity, and of clinical global impression of change. Like the higher-dosage patients the lower-dosage subgroup did not show a significant difference compared with placebo for the other primary endpoint, change in obsessive and compulsive behaviors as measured by the Children’s Yale-Brown Obsessive-Compulsive Scale Total Score, although also like the higher dosage the effect from the lower dosage trended toward benefit.

A further limitation was that, at the time of her report, presented in abstract OR16-3 at the meeting, Dr. Deal could only present complete 64-week follow-up for 72 patients, although this reassuringly showed that, as time on the 9.6-mg t.i.d. dosage continued beyond 8 weeks, patients gradually improved their HQ-CT response so that by 64 weeks on treatment their hyperphagia score had improved as much as in the patients who received the lower dosage.

In short, documented benefits occurred on the lower dosage, especially for clinically meaningful symptoms like hyperphagia and anxiety, but the study’s overall results were not fully consistent by statistical criteria.

Benefiting an unmet need?

“While it is regrettable that we did not get to 175 patients because of COVID-19, the dataset is significant enough for me to feel that the FDA [Food and Drug Administration] needs to take a very serious look and consider approval,” Dr. Deal said in an interview. “Once safety is assured, which I think it is, I can only hope that regulatory officials understand their unmet needs of this rare disease community and will allow the drug to move to the next stage.”

“This is a very rare disease, and having families participate in trials is really challenging,” especially while the COVID-19 pandemic continues, Dr. Strong said. For the pediatric and adolescent patients targeted in this study “it will take a while for COVID to go away and for families to feel safe again being in a trial, so a real concern is that a need for more clinical trials is not terribly feasible now. Given that the safety profile looked good and one dose seemed to have good efficacy, as long as the long-term data continue to look good we’d love for the FDA to look at the existing data and see whether there is a path forward.”

Dr. Miller highlighted the limitations of what the CARE-PWS findings show.

“Given that it was only an 8-week trial of drug against placebo, and the fact that the primary outcomes weren’t met for the higher dose, my thought is that potentially we need to study more patients for a longer period at the 3.2-mg dose,” she said. She acknowledged that the metric used in the study to assess obsessive and compulsive behaviors is “very difficult” to apply to patients with PWS because of uncertainties in scoring obsessions in patients “who are not very good at telling you what they’re thinking.” Plus, “it’s absolutely not a problem that we did not see an effect on obsession and compulsions if the treatment potentially improves anxiety and hyperphagia, which are very common.” A treatment that reliably reduces these symptoms “would be amazing,” Dr. Miller added.

“PWS is very rare, so it’s very hard to do trials. Maybe the FDA will approve carbetocin because it was safe and gave a signal of efficacy at the lower dose. But my thought is that additional treatment trials are needed with only the lower dose and with longer duration,” she said.

CARE-PWS enrolled patients with nutritional phase 3 PWS who were aged 7-18 years at any of 24 sites in the United States, Canada, or Australia during 2018-2020. They averaged about 12 years of age, and 56% were girls.

The most common adverse effect from carbetocin was flushing, occurring in 14% of those on the lower dose and 21% on the higher dose, but not in any placebo patient. Other adverse effects more common on the lower dose than in the placebo group included headache in 16%, and diarrhea in 9%.

Carbetocin is not only long-lasting in circulation, it also has better affinity for oxytocin receptors than for vasopressin receptors, reducing the potential for causing hyponatremia. The idea to use it in patients with PWS followed prior studies with oxytocin, which had shown dopamine interactions that reduced anxiety and influenced food ingestion behavior. Brain autopsy studies had shown that patients with Prader-Willi syndrome have substantially fewer neurons than usual producing oxytocin. Treatment with intranasal carbetocin had shown efficacy for improving hyperphagia and behavior in a controlled phase 2 study with 37 patients.

Carbetocin is approved for use in reducing excessive bleeding after childbirth, particularly cesarean, in more than 20 countries outside the United States.

CARE-PWS was sponsored by Levo Therapeutics, the company developing carbetocin. Dr. Deal has been an adviser to Levo Therapeutics. Dr. Strong is an employee of the Foundation for Prader-Willi Research, which has received support from Levo Therapeutics as well as from other drug companies, but which receives most of its funding from individuals. Dr. Miller has received research funding from Levo Therapeutics and also from Harmony Biosciences, Rhythm Pharmaceuticals, and Soleno Therapeutics.

[email protected]

Children and adolescents with Prader-Willi syndrome (PWS) who received three daily, intranasal doses of carbetocin, an investigational, long-acting oxytocin analogue, had significant improvement in hyperphagia and anxiety during 8 weeks on treatment, compared with placebo in a multicenter, phase 3 trial with 119 patients.

The treatment also appeared safe during up to 56 additional weeks on active treatment, with no serious adverse effects nor “unexpected” events, and once completing the study about 95% of enrolled patients opted to remain on active treatment, Cheri L. Deal, MD, PhD, said at the annual meeting of the Endocrine Society.

Based on “the significant results for the placebo-controlled period, as well as for those finishing the 56-week extension, we may well have a new armament for helping these kids and their families deal with the unrelenting hunger of patients with PWS as well as some of the behavioral symptoms,” Dr. Deal, chief of endocrinology and diabetes at the Sainte-Justine Mother-Child University of Montreal Hospital, said in an interview. No treatment currently has labeling for addressing the hyperphagia or anxiety that is characteristic and often problematic for children and adolescents with PWS, an autosomal dominant genetic disease with an incidence of about 1 in 15,000 births and an estimated U.S. prevalence of about 9,000 cases, or about 1 case for every 37,000 people.
 

‘Gorgeous’ safety

“The results looked pretty positive, and we’re encouraged by what appears to be a good safety profile, so overall I think the PWS community is very excited by the results and is very interested in getting access to this drug,” commented Theresa V. Strong, PhD, director of research programs for the Foundation for Prader-Willi Research in Walnut, Calif., a group not involved with the study. Currently, “we have no effective treatments for these difficult behaviors” of hyperphagia and anxiety. Surveys and studies run by the foundation have documented that hyperphagia and anxiety “were the two most important symptoms that families would like to see treated,” Dr. Strong added in an interview.

PWS “is complex and affects almost every aspect of the lives of affected people and their families. Any treatment that can chip away at some of the problems these patients have can be a huge benefit to the patients and their families,” said Jennifer L. Miller, MD, a professor of pediatric endocrinology at the University of Florida, Gainesville, and a coinvestigator on the study.

But the finding that carbetocin appeared to address, at least in part, this unmet need while compiling a safety record that Dr. Miller called “gorgeous” and “remarkable,” also came with a few limitations.
 

Fewer patients than planned, and muddled outcomes

The CARE-PWS trial aimed to enroll 175 patients, but fell short once the COVID-19 pandemic hit. Plus the trial had two prespecified primary endpoints – improvements in a measure of hyperphagia, and in a measure of obsessive and compulsive behaviors – specifically in the 40 patients who received the higher of the two dosages studied, 9.6 mg t.i.d. intranasally. Neither endpoint showed significant improvement among the patients on this dosage, compared with the 40 patients who received placebo, although both outcomes trended in the right direction in the actively treated patients.

The study’s positive results came in a secondary treatment group, 39 patients who received 3.2 mg t.i.d., also intranasally. This subgroup had significant benefit, compared with placebo, for reducing hyperphagia symptoms as measured on the Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Total Score. After the first 8 weeks on treatment, patients on the lower carbetocin dosage had an average reduction in their HQ-CT score of greater than 5 points, more than double the reduction seen among control patients who received placebo.

Those on the 3.2-mg t.i.d. dosage also showed significant improvements, compared with placebo, for anxiety, measured by the PWS Anxiety and Distress Questionnaire Total Score, as well as on measures of clinical global impression of severity, and of clinical global impression of change. Like the higher-dosage patients the lower-dosage subgroup did not show a significant difference compared with placebo for the other primary endpoint, change in obsessive and compulsive behaviors as measured by the Children’s Yale-Brown Obsessive-Compulsive Scale Total Score, although also like the higher dosage the effect from the lower dosage trended toward benefit.

A further limitation was that, at the time of her report, presented in abstract OR16-3 at the meeting, Dr. Deal could only present complete 64-week follow-up for 72 patients, although this reassuringly showed that, as time on the 9.6-mg t.i.d. dosage continued beyond 8 weeks, patients gradually improved their HQ-CT response so that by 64 weeks on treatment their hyperphagia score had improved as much as in the patients who received the lower dosage.

In short, documented benefits occurred on the lower dosage, especially for clinically meaningful symptoms like hyperphagia and anxiety, but the study’s overall results were not fully consistent by statistical criteria.

Benefiting an unmet need?

“While it is regrettable that we did not get to 175 patients because of COVID-19, the dataset is significant enough for me to feel that the FDA [Food and Drug Administration] needs to take a very serious look and consider approval,” Dr. Deal said in an interview. “Once safety is assured, which I think it is, I can only hope that regulatory officials understand their unmet needs of this rare disease community and will allow the drug to move to the next stage.”

“This is a very rare disease, and having families participate in trials is really challenging,” especially while the COVID-19 pandemic continues, Dr. Strong said. For the pediatric and adolescent patients targeted in this study “it will take a while for COVID to go away and for families to feel safe again being in a trial, so a real concern is that a need for more clinical trials is not terribly feasible now. Given that the safety profile looked good and one dose seemed to have good efficacy, as long as the long-term data continue to look good we’d love for the FDA to look at the existing data and see whether there is a path forward.”

Dr. Miller highlighted the limitations of what the CARE-PWS findings show.

“Given that it was only an 8-week trial of drug against placebo, and the fact that the primary outcomes weren’t met for the higher dose, my thought is that potentially we need to study more patients for a longer period at the 3.2-mg dose,” she said. She acknowledged that the metric used in the study to assess obsessive and compulsive behaviors is “very difficult” to apply to patients with PWS because of uncertainties in scoring obsessions in patients “who are not very good at telling you what they’re thinking.” Plus, “it’s absolutely not a problem that we did not see an effect on obsession and compulsions if the treatment potentially improves anxiety and hyperphagia, which are very common.” A treatment that reliably reduces these symptoms “would be amazing,” Dr. Miller added.

“PWS is very rare, so it’s very hard to do trials. Maybe the FDA will approve carbetocin because it was safe and gave a signal of efficacy at the lower dose. But my thought is that additional treatment trials are needed with only the lower dose and with longer duration,” she said.

CARE-PWS enrolled patients with nutritional phase 3 PWS who were aged 7-18 years at any of 24 sites in the United States, Canada, or Australia during 2018-2020. They averaged about 12 years of age, and 56% were girls.

The most common adverse effect from carbetocin was flushing, occurring in 14% of those on the lower dose and 21% on the higher dose, but not in any placebo patient. Other adverse effects more common on the lower dose than in the placebo group included headache in 16%, and diarrhea in 9%.

Carbetocin is not only long-lasting in circulation, it also has better affinity for oxytocin receptors than for vasopressin receptors, reducing the potential for causing hyponatremia. The idea to use it in patients with PWS followed prior studies with oxytocin, which had shown dopamine interactions that reduced anxiety and influenced food ingestion behavior. Brain autopsy studies had shown that patients with Prader-Willi syndrome have substantially fewer neurons than usual producing oxytocin. Treatment with intranasal carbetocin had shown efficacy for improving hyperphagia and behavior in a controlled phase 2 study with 37 patients.

Carbetocin is approved for use in reducing excessive bleeding after childbirth, particularly cesarean, in more than 20 countries outside the United States.

CARE-PWS was sponsored by Levo Therapeutics, the company developing carbetocin. Dr. Deal has been an adviser to Levo Therapeutics. Dr. Strong is an employee of the Foundation for Prader-Willi Research, which has received support from Levo Therapeutics as well as from other drug companies, but which receives most of its funding from individuals. Dr. Miller has received research funding from Levo Therapeutics and also from Harmony Biosciences, Rhythm Pharmaceuticals, and Soleno Therapeutics.

[email protected]

New cases of COVID-19 in children in the United States fell slightly, but even that small dip was enough to reverse 2 straight weeks of increases, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

New cases totaled 63,862 for the latest reporting week, March 26 to April 1, compared with 64,029 for the previous week, the AAP and the CHA said in their weekly COVID-19 report. For the week ending April 1, children represented 18.1% of all new cases reported in the United States, down from a pandemic-high 19.1% the week before.

COVID-19 cases in children now total just under 3.47 million, which works out to 13.4% of reported cases for all ages and 4,610 cases per 100,000 children since the beginning of the pandemic, the AAP and the CHA said based on data from 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam.

Among those jurisdictions, Vermont has the highest proportion of its cases occurring in children at 21.0%, and North Dakota has the highest cumulative rate at 8,958 cases per 100,000 children. Looking at those states from the bottoms of their respective lists are Florida, where children aged 0-14 years represent 8.4% of all cases, and Hawaii, with 1,133 cases per 100,000 children aged 0-17 years, the AAP/CHA report shows.

The data on more serious illness show that Minnesota has the highest proportion of hospitalizations occurring in children at 3.1%, while New York City has the highest hospitalization rate among infected children, 2.0%. Among the other 23 states reporting on such admissions, children make up only 1.3% of hospitalizations in Florida and in New Hampshire, which also has the lowest hospitalization rate at 0.1%, the AAP and CHA said.

Five more deaths were reported in children during the week ending April 1, bringing the total to 284 in the 43 states, along with New York City, Puerto Rico, and Guam, that are sharing age-distribution data on mortality.

[email protected]

New cases of COVID-19 in children in the United States fell slightly, but even that small dip was enough to reverse 2 straight weeks of increases, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

New cases totaled 63,862 for the latest reporting week, March 26 to April 1, compared with 64,029 for the previous week, the AAP and the CHA said in their weekly COVID-19 report. For the week ending April 1, children represented 18.1% of all new cases reported in the United States, down from a pandemic-high 19.1% the week before.

COVID-19 cases in children now total just under 3.47 million, which works out to 13.4% of reported cases for all ages and 4,610 cases per 100,000 children since the beginning of the pandemic, the AAP and the CHA said based on data from 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam.

Among those jurisdictions, Vermont has the highest proportion of its cases occurring in children at 21.0%, and North Dakota has the highest cumulative rate at 8,958 cases per 100,000 children. Looking at those states from the bottoms of their respective lists are Florida, where children aged 0-14 years represent 8.4% of all cases, and Hawaii, with 1,133 cases per 100,000 children aged 0-17 years, the AAP/CHA report shows.

The data on more serious illness show that Minnesota has the highest proportion of hospitalizations occurring in children at 3.1%, while New York City has the highest hospitalization rate among infected children, 2.0%. Among the other 23 states reporting on such admissions, children make up only 1.3% of hospitalizations in Florida and in New Hampshire, which also has the lowest hospitalization rate at 0.1%, the AAP and CHA said.

Five more deaths were reported in children during the week ending April 1, bringing the total to 284 in the 43 states, along with New York City, Puerto Rico, and Guam, that are sharing age-distribution data on mortality.

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New cases of COVID-19 in children in the United States fell slightly, but even that small dip was enough to reverse 2 straight weeks of increases, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

New cases totaled 63,862 for the latest reporting week, March 26 to April 1, compared with 64,029 for the previous week, the AAP and the CHA said in their weekly COVID-19 report. For the week ending April 1, children represented 18.1% of all new cases reported in the United States, down from a pandemic-high 19.1% the week before.

COVID-19 cases in children now total just under 3.47 million, which works out to 13.4% of reported cases for all ages and 4,610 cases per 100,000 children since the beginning of the pandemic, the AAP and the CHA said based on data from 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam.

Among those jurisdictions, Vermont has the highest proportion of its cases occurring in children at 21.0%, and North Dakota has the highest cumulative rate at 8,958 cases per 100,000 children. Looking at those states from the bottoms of their respective lists are Florida, where children aged 0-14 years represent 8.4% of all cases, and Hawaii, with 1,133 cases per 100,000 children aged 0-17 years, the AAP/CHA report shows.

The data on more serious illness show that Minnesota has the highest proportion of hospitalizations occurring in children at 3.1%, while New York City has the highest hospitalization rate among infected children, 2.0%. Among the other 23 states reporting on such admissions, children make up only 1.3% of hospitalizations in Florida and in New Hampshire, which also has the lowest hospitalization rate at 0.1%, the AAP and CHA said.

Five more deaths were reported in children during the week ending April 1, bringing the total to 284 in the 43 states, along with New York City, Puerto Rico, and Guam, that are sharing age-distribution data on mortality.

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The United States saw nearly 23% more deaths than expected during the first 9 months of the pandemic, and almost three-quarters of those deaths involved COVID-19.

For comparison, the death rate increased by 2.5% or less annually in recent years.

At the same time, rates of deaths from heart disease, Alzheimer’s disease or dementia, and diabetes also increased from March 1, 2020, to Jan. 2, 2021, especially during COVID-19 surges.

“Excess deaths surged in the east in April, followed by extended summer and early winter surges concentrated in Southern and Western states, respectively. Many of these states weakly embraced, or discouraged, pandemic control measures and lifted restrictions earlier than other states,” lead author Steven H. Woolf, MD, MPH, from the Virginia Commonwealth University, Richmond, and colleagues wrote in a research letter published online April 2, 2021, in JAMA.

COVID-19 mortality included all deaths for which it was cited as an underlying or contributing cause in records from the District of Columbia and 49 states. North Carolina was excluded for insufficient data.
 

More than half a million excess deaths

Between March 1, 2020, and Jan. 2, 2021, the United States experienced 2,801,439 deaths, or 522,368 excess deaths. A total 72.4% of these events were attributed to COVID-19.

Not all racial and ethnic groups were equally represented. For example, the rate of excess deaths was higher among non-Hispanic Black populations, at 208.4 deaths per 100,000. Non-Hispanic White populations experienced 157 deaths per 100,000, and Hispanic populations experienced 139.8 deaths per 100,000.

Further, non-Hispanic Black individuals accounted for 16.9% of the excess deaths but only 12.5% of the U.S. population, which reflects “racial disparities in COVID-19 mortality,” the authors noted.

Not adjusting for population aging is a potential limitation, as was reliance on provisional data and the likelihood that some death certificates were inaccurate.

In February, Anthony S. Fauci, MD, chief medical adviser to President Joe Biden, stated that political divisions likely played a role in the 500,000-plus COVID-19–related deaths in the United States. 

Then a report came out on March 26 indicating that a different U.S. response to the pandemic could have avoided almost 400,000 COVID-19 deaths. In addition, an April 1 study in the CDC’s Morbidity and Mortality Weekly Report revealed that COVID-19 is now the third leading cause of death in the United States, after heart disease and cancer.
 

‘Massive’ excessive mortality

“There is no more visible or alarming manifestation of the toll of the COVID-19 pandemic than the deaths it has caused. In this issue of JAMA, Dr. Woolf and colleagues provide updated analyses that demonstrate that the excess mortality in the U.S. between March 1, 2020, and Jan. 2, 2021, has been massive,” Alan Garber, MD, PhD, wrote in an accompanying editorial.

“It seems likely that COVID-19 will have contributed to nearly as many deaths in the U.S. as the great influenza pandemic of 1918, and more than in any influenza outbreak in the U.S. since then,” added Dr. Garber, provost of Harvard University in Cambridge, Mass.

This study of excess mortality illustrates what is at stake, he added. “Despite the scientific, medical and public health progress of recent decades, the loss of life attributable to the COVID-19 pandemic exceeds the mortality of major wars. No nation should squander this opportunity to do what it takes to prepare for the next one.”

Dr. Woolf and Dr. Garber disclosed no relevant financial relationships. The National Institutes of Health supported the research through its National Center for Advancing Translational Sciences and the National Institute on Aging.

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

The United States saw nearly 23% more deaths than expected during the first 9 months of the pandemic, and almost three-quarters of those deaths involved COVID-19.

For comparison, the death rate increased by 2.5% or less annually in recent years.

At the same time, rates of deaths from heart disease, Alzheimer’s disease or dementia, and diabetes also increased from March 1, 2020, to Jan. 2, 2021, especially during COVID-19 surges.

“Excess deaths surged in the east in April, followed by extended summer and early winter surges concentrated in Southern and Western states, respectively. Many of these states weakly embraced, or discouraged, pandemic control measures and lifted restrictions earlier than other states,” lead author Steven H. Woolf, MD, MPH, from the Virginia Commonwealth University, Richmond, and colleagues wrote in a research letter published online April 2, 2021, in JAMA.

COVID-19 mortality included all deaths for which it was cited as an underlying or contributing cause in records from the District of Columbia and 49 states. North Carolina was excluded for insufficient data.
 

More than half a million excess deaths

Between March 1, 2020, and Jan. 2, 2021, the United States experienced 2,801,439 deaths, or 522,368 excess deaths. A total 72.4% of these events were attributed to COVID-19.

Not all racial and ethnic groups were equally represented. For example, the rate of excess deaths was higher among non-Hispanic Black populations, at 208.4 deaths per 100,000. Non-Hispanic White populations experienced 157 deaths per 100,000, and Hispanic populations experienced 139.8 deaths per 100,000.

Further, non-Hispanic Black individuals accounted for 16.9% of the excess deaths but only 12.5% of the U.S. population, which reflects “racial disparities in COVID-19 mortality,” the authors noted.

Not adjusting for population aging is a potential limitation, as was reliance on provisional data and the likelihood that some death certificates were inaccurate.

In February, Anthony S. Fauci, MD, chief medical adviser to President Joe Biden, stated that political divisions likely played a role in the 500,000-plus COVID-19–related deaths in the United States. 

Then a report came out on March 26 indicating that a different U.S. response to the pandemic could have avoided almost 400,000 COVID-19 deaths. In addition, an April 1 study in the CDC’s Morbidity and Mortality Weekly Report revealed that COVID-19 is now the third leading cause of death in the United States, after heart disease and cancer.
 

‘Massive’ excessive mortality

“There is no more visible or alarming manifestation of the toll of the COVID-19 pandemic than the deaths it has caused. In this issue of JAMA, Dr. Woolf and colleagues provide updated analyses that demonstrate that the excess mortality in the U.S. between March 1, 2020, and Jan. 2, 2021, has been massive,” Alan Garber, MD, PhD, wrote in an accompanying editorial.

“It seems likely that COVID-19 will have contributed to nearly as many deaths in the U.S. as the great influenza pandemic of 1918, and more than in any influenza outbreak in the U.S. since then,” added Dr. Garber, provost of Harvard University in Cambridge, Mass.

This study of excess mortality illustrates what is at stake, he added. “Despite the scientific, medical and public health progress of recent decades, the loss of life attributable to the COVID-19 pandemic exceeds the mortality of major wars. No nation should squander this opportunity to do what it takes to prepare for the next one.”

Dr. Woolf and Dr. Garber disclosed no relevant financial relationships. The National Institutes of Health supported the research through its National Center for Advancing Translational Sciences and the National Institute on Aging.

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

The United States saw nearly 23% more deaths than expected during the first 9 months of the pandemic, and almost three-quarters of those deaths involved COVID-19.

For comparison, the death rate increased by 2.5% or less annually in recent years.

At the same time, rates of deaths from heart disease, Alzheimer’s disease or dementia, and diabetes also increased from March 1, 2020, to Jan. 2, 2021, especially during COVID-19 surges.

“Excess deaths surged in the east in April, followed by extended summer and early winter surges concentrated in Southern and Western states, respectively. Many of these states weakly embraced, or discouraged, pandemic control measures and lifted restrictions earlier than other states,” lead author Steven H. Woolf, MD, MPH, from the Virginia Commonwealth University, Richmond, and colleagues wrote in a research letter published online April 2, 2021, in JAMA.

COVID-19 mortality included all deaths for which it was cited as an underlying or contributing cause in records from the District of Columbia and 49 states. North Carolina was excluded for insufficient data.
 

More than half a million excess deaths

Between March 1, 2020, and Jan. 2, 2021, the United States experienced 2,801,439 deaths, or 522,368 excess deaths. A total 72.4% of these events were attributed to COVID-19.

Not all racial and ethnic groups were equally represented. For example, the rate of excess deaths was higher among non-Hispanic Black populations, at 208.4 deaths per 100,000. Non-Hispanic White populations experienced 157 deaths per 100,000, and Hispanic populations experienced 139.8 deaths per 100,000.

Further, non-Hispanic Black individuals accounted for 16.9% of the excess deaths but only 12.5% of the U.S. population, which reflects “racial disparities in COVID-19 mortality,” the authors noted.

Not adjusting for population aging is a potential limitation, as was reliance on provisional data and the likelihood that some death certificates were inaccurate.

In February, Anthony S. Fauci, MD, chief medical adviser to President Joe Biden, stated that political divisions likely played a role in the 500,000-plus COVID-19–related deaths in the United States. 

Then a report came out on March 26 indicating that a different U.S. response to the pandemic could have avoided almost 400,000 COVID-19 deaths. In addition, an April 1 study in the CDC’s Morbidity and Mortality Weekly Report revealed that COVID-19 is now the third leading cause of death in the United States, after heart disease and cancer.
 

‘Massive’ excessive mortality

“There is no more visible or alarming manifestation of the toll of the COVID-19 pandemic than the deaths it has caused. In this issue of JAMA, Dr. Woolf and colleagues provide updated analyses that demonstrate that the excess mortality in the U.S. between March 1, 2020, and Jan. 2, 2021, has been massive,” Alan Garber, MD, PhD, wrote in an accompanying editorial.

“It seems likely that COVID-19 will have contributed to nearly as many deaths in the U.S. as the great influenza pandemic of 1918, and more than in any influenza outbreak in the U.S. since then,” added Dr. Garber, provost of Harvard University in Cambridge, Mass.

This study of excess mortality illustrates what is at stake, he added. “Despite the scientific, medical and public health progress of recent decades, the loss of life attributable to the COVID-19 pandemic exceeds the mortality of major wars. No nation should squander this opportunity to do what it takes to prepare for the next one.”

Dr. Woolf and Dr. Garber disclosed no relevant financial relationships. The National Institutes of Health supported the research through its National Center for Advancing Translational Sciences and the National Institute on Aging.

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

Public health officials in the Midwest and Northeast are sounding the alarm about steep new increases in COVID-19 cases in children.
 

South_agency/Getty Images

The increases seem to be driven by greater circulation of more contagious variants, just as children and teens have returned to in-person activities such as sports, parties, and classes.

“I can just tell you from my 46 years in the business, I’ve never seen dynamic transmission in kids like we’re seeing right now, younger kids,” said Michael Osterholm, PhD, who directs the Center for Infectious Disease Research and Policy at the University of Minnesota, Minneapolis.

In earlier surges, children – especially younger children – played only minor roles in transmitting the infection. When they were diagnosed with COVID-19, their symptoms tended to be mild or even absent, and for reasons that aren’t well understood, they haven’t usually been the first cases in households or clusters. 

Now, as more SARS-CoV-2 variants have begun to dominate, and seniors gain protection from vaccines, that pattern may be changing. Infectious disease experts are watching to see if COVID-19 will start to spread in a pattern more similar to influenza, with children becoming infected first and bringing the infection home to their parents.
 

Michigan sees jump in cases

Governors in some hard-hit states are pleading with a pandemic-weary public to keep up mask-wearing and social distancing and avoid unnecessary travel and large gatherings in order to protect in-person classes. 

In Michigan, many schools reopened and youth sports resumed just as the more contagious B.1.1.7 variant spread widely. There, cases are rising among all age groups, but the largest number of new COVID-19 cases is among children aged 10-19, the first time that’s happened since the start of the pandemic.

Over the month of March, incidence in this age group had more than doubled in the state. Cases among younger children – infants through 9-year-olds – are also going up, increasing by more than 230% since Feb. 19, according to data from the Michigan Department of Health and Human Services. 

The increases have prompted some schools to pause in-person learning for a time after spring break to slow transmission, according to Natasha Bagdasarian, MD, senior public health physician with the Michigan health department in Ann Arbor.

In Minnesota, on a recent call with reporters, Ruth Lynfield, MD, state epidemiologist, said the B.1.1.7 variant, which has rapidly risen in the state, has a higher attack rate among children than that of earlier versions of the virus, meaning they’re more likely to be infected when exposed.

“We certainly get the sense that youth are what we might refer to as the leading edge of the spread of variants,” she said.

Dr. Lynfield said they were tracking cases spreading through youth sports, classrooms, and daycare centers.

In Massachusetts, the largest number of new COVID-19 infections in the last 2 weeks of March was among children and teens. Massachusetts has the fifth-highest number of recorded B.1.1.7 cases in the United States, according to CDC data.

Although most COVID-19 cases in children and teens are mild, the disease can be severe for those who have underlying medical conditions. Even in healthy children, it can trigger a serious postviral syndrome called MIS-C that requires hospitalization. 

Emerging studies show that children, like adults, can develop the lingering symptoms of long COVID-19. Recent data from the United Kingdom show 10%-15% of children younger than 16 infected with COVID-19 still had at least one symptom 5 weeks later.

Dr. Osterholm said it remains to be seen whether more cases in children will also mean a rise in more serious outcomes for children, as it has in Europe and Israel.

In Israel, the B.1.1.7 variant arrived at the end of December and became dominant in January. By the end of January, Hadassah Ein Kerem Medical Center in Jerusalem had four patients in its newly opened pediatric COVID-19 ICU unit. They ranged in age from 13 days to 2 years.

By early February, the Ministry of Health warned the country’s doctors to prepare for an “imminent upward trend” in pediatric COVID-19 cases. They notified hospitals to be ready to open more ICU beds for children with COVID-19, according to Cyrille Cohen, PhD, head of the laboratory of immunotherapy at Bar-Ilan University in Ramat Gan, Israel.

On March 31, French President Emmanuel Macron ordered France into its third national lockdown and closed schools for 3 weeks to try to hold off a third wave of COVID-19. President Macron had been a staunch defender of keeping schools open, but said the closure was necessary. 

“It is the best solution to slow down the virus,” he said, according to Reuters.

German Chancellor Angela Merkel recently announced a new lockdown for Germany as the spread of the variants has led to rising cases there.

“I think what we’re seeing here is this is going to play out over the country,” said Dr. Osterholm. “Before this time, we didn’t see major transmission in younger kids particularly K through eighth grade, and now we’re seeing that happening with many school outbreaks, particularly in the Northeast and in the Midwest.” He added that it will spread through southern states as well.
 

Fall surge all over again

“It’s starting to feel an awful lot like déjà vu, where the hospitalization numbers, the positivity rate, all of the metrics that we track are trending up significantly, and it’s feeling like the fall surge,” said Brian Peters, CEO of the Michigan Hospital Association. “It’s feeling in many ways like the initial surge a year ago.”

Mr. Peters said that in January and February, COVID-19 hospitalizations in Michigan were less than 1,000 a day. Recently, he said, there were 2,558 people hospitalized with COVID-19 in Michigan.

About half of adults aged 65 and older have been fully vaccinated in Michigan. That’s led to a dramatic drop in cases and hospitalizations among seniors, who are at highest risk of death. At the same time, Gov. Gretchen Whitmer and health officials with the Biden administration have encouraged schools to reopen for in-person learning, and extracurricular activities have largely resumed.

The same circumstances – students in classrooms, combined with the arrival of the variants – resulted in COVID-19 cases caused by the B.1.1.7 variant increasing  among younger age groups in the United Kingdom. 

When schools were locked down again, however, cases caused by variant and wild type viruses both dropped in children, suggesting that there wasn’t anything that made B.1.1.7 extra risky for children, but that the strain is more contagious for everyone. Sports, extracurricular activities, and classrooms offered the virus plenty of opportunities to spread.

In Michigan, Dr. Bagdasarian said the outbreaks in children started with winter sports.

“Not necessarily transmission on the field, but we’re really talking about social gatherings that were happening in and around sports,” like the pizza party to celebrate a team win, she said, “and I think those social gatherings were a big driver.”

“Outbreaks are trickling over into teams and trickling over into schools, which is exactly what we want to avoid,” she added.

Thus far, Michigan has been reserving vaccine doses for older adults but will open eligibility to anyone age 16 and older starting on April 6.

Until younger age groups can be vaccinated, Mr. Peters said people need to continue to be careful.

“We see people letting their guard down and it’s to be expected,” Mr. Peters said. “People have COVID fatigue, and they are eager to get together with their friends. We’re not out of the woods yet.”
 

Children ‘heavily impacted’

In Nebraska, Alice Sato, MD, PhD, hospital epidemiologist at Children’s Hospital and Medical Center in Omaha, said they saw an increase in MIS-C cases after the winter surges, and she’s watching the data carefully as COVID-19 cases tick up in other midwestern states.

Dr. Sato got so tired of hearing people compare COVID-19 to the flu that she pulled some numbers on pediatric deaths.

While COVID-19 fatality rates in children are much lower than they are for adults, at least 279 children have died across the United States since the start of the pandemic. The highest number of confirmed pediatric deaths recorded during any of the previous 10 flu seasons was 188, according to the CDC.

“So while children are relatively spared, they’re still heavily impacted,” said Dr. Sato.

She was thrilled to hear the recent news that the Pfizer vaccine works well in children aged 12-15, but because Pfizer’s cold-chain requirements make it one the trickiest to store, the Food and Drug Administration hasn’t given the go-ahead yet. She said it will be months before she has any to offer to teens in her state. 

In the meantime, genetic testing has shown that the variants are already circulating there.

“We really want parents and family members who are eligible to be vaccinated because that is a great way to protect children that I cannot vaccinate yet,” Dr. Sato said. “The best way for me to protect children is to prevent the adults around them from being infected.”

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

Public health officials in the Midwest and Northeast are sounding the alarm about steep new increases in COVID-19 cases in children.
 

South_agency/Getty Images

The increases seem to be driven by greater circulation of more contagious variants, just as children and teens have returned to in-person activities such as sports, parties, and classes.

“I can just tell you from my 46 years in the business, I’ve never seen dynamic transmission in kids like we’re seeing right now, younger kids,” said Michael Osterholm, PhD, who directs the Center for Infectious Disease Research and Policy at the University of Minnesota, Minneapolis.

In earlier surges, children – especially younger children – played only minor roles in transmitting the infection. When they were diagnosed with COVID-19, their symptoms tended to be mild or even absent, and for reasons that aren’t well understood, they haven’t usually been the first cases in households or clusters. 

Now, as more SARS-CoV-2 variants have begun to dominate, and seniors gain protection from vaccines, that pattern may be changing. Infectious disease experts are watching to see if COVID-19 will start to spread in a pattern more similar to influenza, with children becoming infected first and bringing the infection home to their parents.
 

Michigan sees jump in cases

Governors in some hard-hit states are pleading with a pandemic-weary public to keep up mask-wearing and social distancing and avoid unnecessary travel and large gatherings in order to protect in-person classes. 

In Michigan, many schools reopened and youth sports resumed just as the more contagious B.1.1.7 variant spread widely. There, cases are rising among all age groups, but the largest number of new COVID-19 cases is among children aged 10-19, the first time that’s happened since the start of the pandemic.

Over the month of March, incidence in this age group had more than doubled in the state. Cases among younger children – infants through 9-year-olds – are also going up, increasing by more than 230% since Feb. 19, according to data from the Michigan Department of Health and Human Services. 

The increases have prompted some schools to pause in-person learning for a time after spring break to slow transmission, according to Natasha Bagdasarian, MD, senior public health physician with the Michigan health department in Ann Arbor.

In Minnesota, on a recent call with reporters, Ruth Lynfield, MD, state epidemiologist, said the B.1.1.7 variant, which has rapidly risen in the state, has a higher attack rate among children than that of earlier versions of the virus, meaning they’re more likely to be infected when exposed.

“We certainly get the sense that youth are what we might refer to as the leading edge of the spread of variants,” she said.

Dr. Lynfield said they were tracking cases spreading through youth sports, classrooms, and daycare centers.

In Massachusetts, the largest number of new COVID-19 infections in the last 2 weeks of March was among children and teens. Massachusetts has the fifth-highest number of recorded B.1.1.7 cases in the United States, according to CDC data.

Although most COVID-19 cases in children and teens are mild, the disease can be severe for those who have underlying medical conditions. Even in healthy children, it can trigger a serious postviral syndrome called MIS-C that requires hospitalization. 

Emerging studies show that children, like adults, can develop the lingering symptoms of long COVID-19. Recent data from the United Kingdom show 10%-15% of children younger than 16 infected with COVID-19 still had at least one symptom 5 weeks later.

Dr. Osterholm said it remains to be seen whether more cases in children will also mean a rise in more serious outcomes for children, as it has in Europe and Israel.

In Israel, the B.1.1.7 variant arrived at the end of December and became dominant in January. By the end of January, Hadassah Ein Kerem Medical Center in Jerusalem had four patients in its newly opened pediatric COVID-19 ICU unit. They ranged in age from 13 days to 2 years.

By early February, the Ministry of Health warned the country’s doctors to prepare for an “imminent upward trend” in pediatric COVID-19 cases. They notified hospitals to be ready to open more ICU beds for children with COVID-19, according to Cyrille Cohen, PhD, head of the laboratory of immunotherapy at Bar-Ilan University in Ramat Gan, Israel.

On March 31, French President Emmanuel Macron ordered France into its third national lockdown and closed schools for 3 weeks to try to hold off a third wave of COVID-19. President Macron had been a staunch defender of keeping schools open, but said the closure was necessary. 

“It is the best solution to slow down the virus,” he said, according to Reuters.

German Chancellor Angela Merkel recently announced a new lockdown for Germany as the spread of the variants has led to rising cases there.

“I think what we’re seeing here is this is going to play out over the country,” said Dr. Osterholm. “Before this time, we didn’t see major transmission in younger kids particularly K through eighth grade, and now we’re seeing that happening with many school outbreaks, particularly in the Northeast and in the Midwest.” He added that it will spread through southern states as well.
 

Fall surge all over again

“It’s starting to feel an awful lot like déjà vu, where the hospitalization numbers, the positivity rate, all of the metrics that we track are trending up significantly, and it’s feeling like the fall surge,” said Brian Peters, CEO of the Michigan Hospital Association. “It’s feeling in many ways like the initial surge a year ago.”

Mr. Peters said that in January and February, COVID-19 hospitalizations in Michigan were less than 1,000 a day. Recently, he said, there were 2,558 people hospitalized with COVID-19 in Michigan.

About half of adults aged 65 and older have been fully vaccinated in Michigan. That’s led to a dramatic drop in cases and hospitalizations among seniors, who are at highest risk of death. At the same time, Gov. Gretchen Whitmer and health officials with the Biden administration have encouraged schools to reopen for in-person learning, and extracurricular activities have largely resumed.

The same circumstances – students in classrooms, combined with the arrival of the variants – resulted in COVID-19 cases caused by the B.1.1.7 variant increasing  among younger age groups in the United Kingdom. 

When schools were locked down again, however, cases caused by variant and wild type viruses both dropped in children, suggesting that there wasn’t anything that made B.1.1.7 extra risky for children, but that the strain is more contagious for everyone. Sports, extracurricular activities, and classrooms offered the virus plenty of opportunities to spread.

In Michigan, Dr. Bagdasarian said the outbreaks in children started with winter sports.

“Not necessarily transmission on the field, but we’re really talking about social gatherings that were happening in and around sports,” like the pizza party to celebrate a team win, she said, “and I think those social gatherings were a big driver.”

“Outbreaks are trickling over into teams and trickling over into schools, which is exactly what we want to avoid,” she added.

Thus far, Michigan has been reserving vaccine doses for older adults but will open eligibility to anyone age 16 and older starting on April 6.

Until younger age groups can be vaccinated, Mr. Peters said people need to continue to be careful.

“We see people letting their guard down and it’s to be expected,” Mr. Peters said. “People have COVID fatigue, and they are eager to get together with their friends. We’re not out of the woods yet.”
 

Children ‘heavily impacted’

In Nebraska, Alice Sato, MD, PhD, hospital epidemiologist at Children’s Hospital and Medical Center in Omaha, said they saw an increase in MIS-C cases after the winter surges, and she’s watching the data carefully as COVID-19 cases tick up in other midwestern states.

Dr. Sato got so tired of hearing people compare COVID-19 to the flu that she pulled some numbers on pediatric deaths.

While COVID-19 fatality rates in children are much lower than they are for adults, at least 279 children have died across the United States since the start of the pandemic. The highest number of confirmed pediatric deaths recorded during any of the previous 10 flu seasons was 188, according to the CDC.

“So while children are relatively spared, they’re still heavily impacted,” said Dr. Sato.

She was thrilled to hear the recent news that the Pfizer vaccine works well in children aged 12-15, but because Pfizer’s cold-chain requirements make it one the trickiest to store, the Food and Drug Administration hasn’t given the go-ahead yet. She said it will be months before she has any to offer to teens in her state. 

In the meantime, genetic testing has shown that the variants are already circulating there.

“We really want parents and family members who are eligible to be vaccinated because that is a great way to protect children that I cannot vaccinate yet,” Dr. Sato said. “The best way for me to protect children is to prevent the adults around them from being infected.”

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

Public health officials in the Midwest and Northeast are sounding the alarm about steep new increases in COVID-19 cases in children.
 

South_agency/Getty Images

The increases seem to be driven by greater circulation of more contagious variants, just as children and teens have returned to in-person activities such as sports, parties, and classes.

“I can just tell you from my 46 years in the business, I’ve never seen dynamic transmission in kids like we’re seeing right now, younger kids,” said Michael Osterholm, PhD, who directs the Center for Infectious Disease Research and Policy at the University of Minnesota, Minneapolis.

In earlier surges, children – especially younger children – played only minor roles in transmitting the infection. When they were diagnosed with COVID-19, their symptoms tended to be mild or even absent, and for reasons that aren’t well understood, they haven’t usually been the first cases in households or clusters. 

Now, as more SARS-CoV-2 variants have begun to dominate, and seniors gain protection from vaccines, that pattern may be changing. Infectious disease experts are watching to see if COVID-19 will start to spread in a pattern more similar to influenza, with children becoming infected first and bringing the infection home to their parents.
 

Michigan sees jump in cases

Governors in some hard-hit states are pleading with a pandemic-weary public to keep up mask-wearing and social distancing and avoid unnecessary travel and large gatherings in order to protect in-person classes. 

In Michigan, many schools reopened and youth sports resumed just as the more contagious B.1.1.7 variant spread widely. There, cases are rising among all age groups, but the largest number of new COVID-19 cases is among children aged 10-19, the first time that’s happened since the start of the pandemic.

Over the month of March, incidence in this age group had more than doubled in the state. Cases among younger children – infants through 9-year-olds – are also going up, increasing by more than 230% since Feb. 19, according to data from the Michigan Department of Health and Human Services. 

The increases have prompted some schools to pause in-person learning for a time after spring break to slow transmission, according to Natasha Bagdasarian, MD, senior public health physician with the Michigan health department in Ann Arbor.

In Minnesota, on a recent call with reporters, Ruth Lynfield, MD, state epidemiologist, said the B.1.1.7 variant, which has rapidly risen in the state, has a higher attack rate among children than that of earlier versions of the virus, meaning they’re more likely to be infected when exposed.

“We certainly get the sense that youth are what we might refer to as the leading edge of the spread of variants,” she said.

Dr. Lynfield said they were tracking cases spreading through youth sports, classrooms, and daycare centers.

In Massachusetts, the largest number of new COVID-19 infections in the last 2 weeks of March was among children and teens. Massachusetts has the fifth-highest number of recorded B.1.1.7 cases in the United States, according to CDC data.

Although most COVID-19 cases in children and teens are mild, the disease can be severe for those who have underlying medical conditions. Even in healthy children, it can trigger a serious postviral syndrome called MIS-C that requires hospitalization. 

Emerging studies show that children, like adults, can develop the lingering symptoms of long COVID-19. Recent data from the United Kingdom show 10%-15% of children younger than 16 infected with COVID-19 still had at least one symptom 5 weeks later.

Dr. Osterholm said it remains to be seen whether more cases in children will also mean a rise in more serious outcomes for children, as it has in Europe and Israel.

In Israel, the B.1.1.7 variant arrived at the end of December and became dominant in January. By the end of January, Hadassah Ein Kerem Medical Center in Jerusalem had four patients in its newly opened pediatric COVID-19 ICU unit. They ranged in age from 13 days to 2 years.

By early February, the Ministry of Health warned the country’s doctors to prepare for an “imminent upward trend” in pediatric COVID-19 cases. They notified hospitals to be ready to open more ICU beds for children with COVID-19, according to Cyrille Cohen, PhD, head of the laboratory of immunotherapy at Bar-Ilan University in Ramat Gan, Israel.

On March 31, French President Emmanuel Macron ordered France into its third national lockdown and closed schools for 3 weeks to try to hold off a third wave of COVID-19. President Macron had been a staunch defender of keeping schools open, but said the closure was necessary. 

“It is the best solution to slow down the virus,” he said, according to Reuters.

German Chancellor Angela Merkel recently announced a new lockdown for Germany as the spread of the variants has led to rising cases there.

“I think what we’re seeing here is this is going to play out over the country,” said Dr. Osterholm. “Before this time, we didn’t see major transmission in younger kids particularly K through eighth grade, and now we’re seeing that happening with many school outbreaks, particularly in the Northeast and in the Midwest.” He added that it will spread through southern states as well.
 

Fall surge all over again

“It’s starting to feel an awful lot like déjà vu, where the hospitalization numbers, the positivity rate, all of the metrics that we track are trending up significantly, and it’s feeling like the fall surge,” said Brian Peters, CEO of the Michigan Hospital Association. “It’s feeling in many ways like the initial surge a year ago.”

Mr. Peters said that in January and February, COVID-19 hospitalizations in Michigan were less than 1,000 a day. Recently, he said, there were 2,558 people hospitalized with COVID-19 in Michigan.

About half of adults aged 65 and older have been fully vaccinated in Michigan. That’s led to a dramatic drop in cases and hospitalizations among seniors, who are at highest risk of death. At the same time, Gov. Gretchen Whitmer and health officials with the Biden administration have encouraged schools to reopen for in-person learning, and extracurricular activities have largely resumed.

The same circumstances – students in classrooms, combined with the arrival of the variants – resulted in COVID-19 cases caused by the B.1.1.7 variant increasing  among younger age groups in the United Kingdom. 

When schools were locked down again, however, cases caused by variant and wild type viruses both dropped in children, suggesting that there wasn’t anything that made B.1.1.7 extra risky for children, but that the strain is more contagious for everyone. Sports, extracurricular activities, and classrooms offered the virus plenty of opportunities to spread.

In Michigan, Dr. Bagdasarian said the outbreaks in children started with winter sports.

“Not necessarily transmission on the field, but we’re really talking about social gatherings that were happening in and around sports,” like the pizza party to celebrate a team win, she said, “and I think those social gatherings were a big driver.”

“Outbreaks are trickling over into teams and trickling over into schools, which is exactly what we want to avoid,” she added.

Thus far, Michigan has been reserving vaccine doses for older adults but will open eligibility to anyone age 16 and older starting on April 6.

Until younger age groups can be vaccinated, Mr. Peters said people need to continue to be careful.

“We see people letting their guard down and it’s to be expected,” Mr. Peters said. “People have COVID fatigue, and they are eager to get together with their friends. We’re not out of the woods yet.”
 

Children ‘heavily impacted’

In Nebraska, Alice Sato, MD, PhD, hospital epidemiologist at Children’s Hospital and Medical Center in Omaha, said they saw an increase in MIS-C cases after the winter surges, and she’s watching the data carefully as COVID-19 cases tick up in other midwestern states.

Dr. Sato got so tired of hearing people compare COVID-19 to the flu that she pulled some numbers on pediatric deaths.

While COVID-19 fatality rates in children are much lower than they are for adults, at least 279 children have died across the United States since the start of the pandemic. The highest number of confirmed pediatric deaths recorded during any of the previous 10 flu seasons was 188, according to the CDC.

“So while children are relatively spared, they’re still heavily impacted,” said Dr. Sato.

She was thrilled to hear the recent news that the Pfizer vaccine works well in children aged 12-15, but because Pfizer’s cold-chain requirements make it one the trickiest to store, the Food and Drug Administration hasn’t given the go-ahead yet. She said it will be months before she has any to offer to teens in her state. 

In the meantime, genetic testing has shown that the variants are already circulating there.

“We really want parents and family members who are eligible to be vaccinated because that is a great way to protect children that I cannot vaccinate yet,” Dr. Sato said. “The best way for me to protect children is to prevent the adults around them from being infected.”

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

Screen time may be associated with a range of psychosocial symptoms at age 5 years, according to a study of Finnish children that was published online in BMJ Open

Janette Niiranen, a researcher in the department of public health solutions at the Finnish Institute for Health and Welfare in Helsinki, and colleagues examined the frequency of electronic media use by 699 preschool children.

They analyzed longitudinal associations between media use at age 18 months and psychosocial symptoms at age 5 years. They also looked at whether media use at age 5 years was associated with the presence of psychosocial symptoms at that time.

The study relied on data collected between 2011 and 2017 as part of the Finnish CHILD-SLEEP longitudinal birth cohort study. Parents reported child media use via questionnaires at age 18 months and age 5 years. Researchers measured psychosocial symptoms at age 5 years using two parent-reported questionnaires: Five-to-Fifteen (FTF) and the Strengths and Difficulties Questionnaire (SDQ).

At age 5 years, a high amount of total screen time – at least 135 minutes per day, representing the 75th percentile of use – was associated with increased likelihood of attention and concentration difficulties, hyperactivity and impulsivity, emotional internalizing and externalizing symptoms, and conduct problems, the researchers reported. Odds ratios ranged from 1.57 to 2.18. In a model that adjusted for confounding factors, internalizing symptoms was the only symptom significantly associated with screen time (OR, 2.01).

In a longitudinal analysis, increased media use at 18 months was associated with peer problems at age 5 years (OR, 1.59).

Compared with program viewing, electronic game playing at age 5 years appeared to be associated with fewer psychosocial risks, the researchers noted. In an unadjusted model, a high amount of game playing was associated with hyperactivity, whereas program viewing was associated with a broad range of symptoms.

Use of electronic media beyond recommended amounts was common.

“The results of our study show that 95% of preschool aged children exceed the recommended daily e-media use of 1 hour,” the authors wrote.
 

No causal link

Amy Orben, DPhil, a researcher at Emmanuel College and the MRC Cognition and Brain Sciences Unit, University of Cambridge (England) highlighted limitations of the research.

The study is “purely observational” and does not “establish a causal link between time spent on electronic media and developmental outcomes in small children,” Dr. Orben said. Factors that may influence how much time a child spends on electronic media – such as whether both parents work and where a child lives – may also influence psychosocial symptoms.

“This means that an association can exist even if no causal link is present,” Dr. Orben said. Furthermore, the statistically significant associations found in the study “could well be noise,” she added.

As the study authors note, associations between screen time and children’s psychosocial well-being “may be bidirectional,” commented Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn.

“There is no way to tell if the families who allow more screen time are doing that because the child already has some psychosocial issues like hyperactivity or dysregulation, and they are using media to calm them,” Dr. Kinsella said. “Or perhaps parents do not have the ability to interact as much with the child due to lack of time/work.” The lack of interaction, rather than electronic media use, may interfere with typical development.

“The end result is still pertinent, as we know children learn through play and social interaction,” Dr. Kinsella added. “I did find it interesting that electronic game playing when played with friends or family was less of a risk.”
 

Brainstorming alternatives

Libby Matile Milkovich, MD, a developmental pediatrician at Children’s Mercy Hospital, Kansas City, Mo., sees family electronic media use as an environmental factor that has significant variability for each patient.

“The need for electronic media to connect to others, to access entertainment, and to learn intensified with the pandemic,” Dr. Milkovich said. “In practice, after I identify concerning media habits, I try to help families create alternatives to their current habits as opposed to being prescriptive and saying to stop or limit media use. ... An alternative may not be limiting screen time but may be changing to more appropriate media content or sharing the media as a family activity.”

Seeing media use in the clinic can provide useful information and opportunities for discussion, Dr. Milkovich noted.

“When I see parents in the clinic room using media to calm a toddler or using their own media, these are great opportunities to open the door to brainstorming alternatives,” Dr. Milkovich said. “Commonly, family media use comes up when children have difficulty sleeping or disruptive behaviors related to media use, but I would challenge medical providers to think about problematic media use in all chief complaints where a behavioral component exists like toileting and feeding.”

The research was supported by the Academy of Finland, the Signe and Ane Gyllenberg Foundation, the Yrjö Jahnsson Foundation, the Foundation for Pediatric Research, the Finnish Cultural Foundation, and the Tampere University Hospital and Doctors’ Association in Tampere. The study authors, Dr. Milkovich, Dr. Orben, and Dr. Kinsella had no relevant financial disclosures. Dr. Kinsella serves on the Pediatric News editorial advisory board.

[email protected]

Screen time may be associated with a range of psychosocial symptoms at age 5 years, according to a study of Finnish children that was published online in BMJ Open

Janette Niiranen, a researcher in the department of public health solutions at the Finnish Institute for Health and Welfare in Helsinki, and colleagues examined the frequency of electronic media use by 699 preschool children.

They analyzed longitudinal associations between media use at age 18 months and psychosocial symptoms at age 5 years. They also looked at whether media use at age 5 years was associated with the presence of psychosocial symptoms at that time.

The study relied on data collected between 2011 and 2017 as part of the Finnish CHILD-SLEEP longitudinal birth cohort study. Parents reported child media use via questionnaires at age 18 months and age 5 years. Researchers measured psychosocial symptoms at age 5 years using two parent-reported questionnaires: Five-to-Fifteen (FTF) and the Strengths and Difficulties Questionnaire (SDQ).

At age 5 years, a high amount of total screen time – at least 135 minutes per day, representing the 75th percentile of use – was associated with increased likelihood of attention and concentration difficulties, hyperactivity and impulsivity, emotional internalizing and externalizing symptoms, and conduct problems, the researchers reported. Odds ratios ranged from 1.57 to 2.18. In a model that adjusted for confounding factors, internalizing symptoms was the only symptom significantly associated with screen time (OR, 2.01).

In a longitudinal analysis, increased media use at 18 months was associated with peer problems at age 5 years (OR, 1.59).

Compared with program viewing, electronic game playing at age 5 years appeared to be associated with fewer psychosocial risks, the researchers noted. In an unadjusted model, a high amount of game playing was associated with hyperactivity, whereas program viewing was associated with a broad range of symptoms.

Use of electronic media beyond recommended amounts was common.

“The results of our study show that 95% of preschool aged children exceed the recommended daily e-media use of 1 hour,” the authors wrote.
 

No causal link

Amy Orben, DPhil, a researcher at Emmanuel College and the MRC Cognition and Brain Sciences Unit, University of Cambridge (England) highlighted limitations of the research.

The study is “purely observational” and does not “establish a causal link between time spent on electronic media and developmental outcomes in small children,” Dr. Orben said. Factors that may influence how much time a child spends on electronic media – such as whether both parents work and where a child lives – may also influence psychosocial symptoms.

“This means that an association can exist even if no causal link is present,” Dr. Orben said. Furthermore, the statistically significant associations found in the study “could well be noise,” she added.

As the study authors note, associations between screen time and children’s psychosocial well-being “may be bidirectional,” commented Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn.

“There is no way to tell if the families who allow more screen time are doing that because the child already has some psychosocial issues like hyperactivity or dysregulation, and they are using media to calm them,” Dr. Kinsella said. “Or perhaps parents do not have the ability to interact as much with the child due to lack of time/work.” The lack of interaction, rather than electronic media use, may interfere with typical development.

“The end result is still pertinent, as we know children learn through play and social interaction,” Dr. Kinsella added. “I did find it interesting that electronic game playing when played with friends or family was less of a risk.”
 

Brainstorming alternatives

Libby Matile Milkovich, MD, a developmental pediatrician at Children’s Mercy Hospital, Kansas City, Mo., sees family electronic media use as an environmental factor that has significant variability for each patient.

“The need for electronic media to connect to others, to access entertainment, and to learn intensified with the pandemic,” Dr. Milkovich said. “In practice, after I identify concerning media habits, I try to help families create alternatives to their current habits as opposed to being prescriptive and saying to stop or limit media use. ... An alternative may not be limiting screen time but may be changing to more appropriate media content or sharing the media as a family activity.”

Seeing media use in the clinic can provide useful information and opportunities for discussion, Dr. Milkovich noted.

“When I see parents in the clinic room using media to calm a toddler or using their own media, these are great opportunities to open the door to brainstorming alternatives,” Dr. Milkovich said. “Commonly, family media use comes up when children have difficulty sleeping or disruptive behaviors related to media use, but I would challenge medical providers to think about problematic media use in all chief complaints where a behavioral component exists like toileting and feeding.”

The research was supported by the Academy of Finland, the Signe and Ane Gyllenberg Foundation, the Yrjö Jahnsson Foundation, the Foundation for Pediatric Research, the Finnish Cultural Foundation, and the Tampere University Hospital and Doctors’ Association in Tampere. The study authors, Dr. Milkovich, Dr. Orben, and Dr. Kinsella had no relevant financial disclosures. Dr. Kinsella serves on the Pediatric News editorial advisory board.

[email protected]

Screen time may be associated with a range of psychosocial symptoms at age 5 years, according to a study of Finnish children that was published online in BMJ Open

Janette Niiranen, a researcher in the department of public health solutions at the Finnish Institute for Health and Welfare in Helsinki, and colleagues examined the frequency of electronic media use by 699 preschool children.

They analyzed longitudinal associations between media use at age 18 months and psychosocial symptoms at age 5 years. They also looked at whether media use at age 5 years was associated with the presence of psychosocial symptoms at that time.

The study relied on data collected between 2011 and 2017 as part of the Finnish CHILD-SLEEP longitudinal birth cohort study. Parents reported child media use via questionnaires at age 18 months and age 5 years. Researchers measured psychosocial symptoms at age 5 years using two parent-reported questionnaires: Five-to-Fifteen (FTF) and the Strengths and Difficulties Questionnaire (SDQ).

At age 5 years, a high amount of total screen time – at least 135 minutes per day, representing the 75th percentile of use – was associated with increased likelihood of attention and concentration difficulties, hyperactivity and impulsivity, emotional internalizing and externalizing symptoms, and conduct problems, the researchers reported. Odds ratios ranged from 1.57 to 2.18. In a model that adjusted for confounding factors, internalizing symptoms was the only symptom significantly associated with screen time (OR, 2.01).

In a longitudinal analysis, increased media use at 18 months was associated with peer problems at age 5 years (OR, 1.59).

Compared with program viewing, electronic game playing at age 5 years appeared to be associated with fewer psychosocial risks, the researchers noted. In an unadjusted model, a high amount of game playing was associated with hyperactivity, whereas program viewing was associated with a broad range of symptoms.

Use of electronic media beyond recommended amounts was common.

“The results of our study show that 95% of preschool aged children exceed the recommended daily e-media use of 1 hour,” the authors wrote.
 

No causal link

Amy Orben, DPhil, a researcher at Emmanuel College and the MRC Cognition and Brain Sciences Unit, University of Cambridge (England) highlighted limitations of the research.

The study is “purely observational” and does not “establish a causal link between time spent on electronic media and developmental outcomes in small children,” Dr. Orben said. Factors that may influence how much time a child spends on electronic media – such as whether both parents work and where a child lives – may also influence psychosocial symptoms.

“This means that an association can exist even if no causal link is present,” Dr. Orben said. Furthermore, the statistically significant associations found in the study “could well be noise,” she added.

As the study authors note, associations between screen time and children’s psychosocial well-being “may be bidirectional,” commented Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn.

“There is no way to tell if the families who allow more screen time are doing that because the child already has some psychosocial issues like hyperactivity or dysregulation, and they are using media to calm them,” Dr. Kinsella said. “Or perhaps parents do not have the ability to interact as much with the child due to lack of time/work.” The lack of interaction, rather than electronic media use, may interfere with typical development.

“The end result is still pertinent, as we know children learn through play and social interaction,” Dr. Kinsella added. “I did find it interesting that electronic game playing when played with friends or family was less of a risk.”
 

Brainstorming alternatives

Libby Matile Milkovich, MD, a developmental pediatrician at Children’s Mercy Hospital, Kansas City, Mo., sees family electronic media use as an environmental factor that has significant variability for each patient.

“The need for electronic media to connect to others, to access entertainment, and to learn intensified with the pandemic,” Dr. Milkovich said. “In practice, after I identify concerning media habits, I try to help families create alternatives to their current habits as opposed to being prescriptive and saying to stop or limit media use. ... An alternative may not be limiting screen time but may be changing to more appropriate media content or sharing the media as a family activity.”

Seeing media use in the clinic can provide useful information and opportunities for discussion, Dr. Milkovich noted.

“When I see parents in the clinic room using media to calm a toddler or using their own media, these are great opportunities to open the door to brainstorming alternatives,” Dr. Milkovich said. “Commonly, family media use comes up when children have difficulty sleeping or disruptive behaviors related to media use, but I would challenge medical providers to think about problematic media use in all chief complaints where a behavioral component exists like toileting and feeding.”

The research was supported by the Academy of Finland, the Signe and Ane Gyllenberg Foundation, the Yrjö Jahnsson Foundation, the Foundation for Pediatric Research, the Finnish Cultural Foundation, and the Tampere University Hospital and Doctors’ Association in Tampere. The study authors, Dr. Milkovich, Dr. Orben, and Dr. Kinsella had no relevant financial disclosures. Dr. Kinsella serves on the Pediatric News editorial advisory board.

[email protected]

The Food and Drug Administration has approved dasiglucagon (Zegalogue 0.6 mg/0.6 mL, Zealand Pharma) autoinjector and prefilled syringe for the treatment of severe hypoglycemia in people with diabetes aged 6 years and older.

Olivier Le Moal/Getty Images

The product has a shelf-life of 36 months at refrigerated temperatures and is stable for up to 12 months at room temperature.

“This approval will help enable appropriate children and adults with diabetes to be able to address sudden and severe hypoglycemia, which can quickly progress from a mild event to an emergency,” Jeremy Pettus, MD, assistant professor of medicine at the University of California, San Diego, said in a company statement.

The approval marks the latest step in the development of newer glucagon formulations that are easier to use in hypoglycemic emergencies than the traditional formulation that requires several steps for reconstitution.

The first intranasal glucagon (Baqsimi, Eli Lilly) was approved in the United States in July 2019 for people with diabetes age 4 years and older.

In September 2019, the FDA approved another prefilled glucagon rescue pen (Gvoke HypoPen, Xeris Pharmaceuticals) for the treatment of severe hypoglycemia in adult and pediatric patients age 2 years and older with diabetes.

Dasiglucagon is currently in phase 3 trials as a subcutaneous infusion for treating congenital hyperinsulinemia, and in phase 2 trials as part of a bihormonal artificial pancreas pump system.

The FDA approval was based on results from three randomized, double-blind, placebo-controlled, phase 3 studies of dasiglucagon in children age 6-17 years and adults with type 1 diabetes.

The primary endpoint was time to achieving an increase in blood glucose of 20 mg/dL or greater from time of administration without additional intervention within 45 minutes. That endpoint was achieved in all three studies, with a median time to blood glucose recovery of 10 minutes overall, with 99% of adults recovering within 15 minutes.

The most common adverse events reported in 2% or more of study participants were nausea, vomiting, headache, and injection-site pain in both children and adults. Diarrhea was also reported in adults.  

Full launch is expected in late June 2021.

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

The Food and Drug Administration has approved dasiglucagon (Zegalogue 0.6 mg/0.6 mL, Zealand Pharma) autoinjector and prefilled syringe for the treatment of severe hypoglycemia in people with diabetes aged 6 years and older.

Olivier Le Moal/Getty Images

The product has a shelf-life of 36 months at refrigerated temperatures and is stable for up to 12 months at room temperature.

“This approval will help enable appropriate children and adults with diabetes to be able to address sudden and severe hypoglycemia, which can quickly progress from a mild event to an emergency,” Jeremy Pettus, MD, assistant professor of medicine at the University of California, San Diego, said in a company statement.

The approval marks the latest step in the development of newer glucagon formulations that are easier to use in hypoglycemic emergencies than the traditional formulation that requires several steps for reconstitution.

The first intranasal glucagon (Baqsimi, Eli Lilly) was approved in the United States in July 2019 for people with diabetes age 4 years and older.

In September 2019, the FDA approved another prefilled glucagon rescue pen (Gvoke HypoPen, Xeris Pharmaceuticals) for the treatment of severe hypoglycemia in adult and pediatric patients age 2 years and older with diabetes.

Dasiglucagon is currently in phase 3 trials as a subcutaneous infusion for treating congenital hyperinsulinemia, and in phase 2 trials as part of a bihormonal artificial pancreas pump system.

The FDA approval was based on results from three randomized, double-blind, placebo-controlled, phase 3 studies of dasiglucagon in children age 6-17 years and adults with type 1 diabetes.

The primary endpoint was time to achieving an increase in blood glucose of 20 mg/dL or greater from time of administration without additional intervention within 45 minutes. That endpoint was achieved in all three studies, with a median time to blood glucose recovery of 10 minutes overall, with 99% of adults recovering within 15 minutes.

The most common adverse events reported in 2% or more of study participants were nausea, vomiting, headache, and injection-site pain in both children and adults. Diarrhea was also reported in adults.  

Full launch is expected in late June 2021.

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

The Food and Drug Administration has approved dasiglucagon (Zegalogue 0.6 mg/0.6 mL, Zealand Pharma) autoinjector and prefilled syringe for the treatment of severe hypoglycemia in people with diabetes aged 6 years and older.

Olivier Le Moal/Getty Images

The product has a shelf-life of 36 months at refrigerated temperatures and is stable for up to 12 months at room temperature.

“This approval will help enable appropriate children and adults with diabetes to be able to address sudden and severe hypoglycemia, which can quickly progress from a mild event to an emergency,” Jeremy Pettus, MD, assistant professor of medicine at the University of California, San Diego, said in a company statement.

The approval marks the latest step in the development of newer glucagon formulations that are easier to use in hypoglycemic emergencies than the traditional formulation that requires several steps for reconstitution.

The first intranasal glucagon (Baqsimi, Eli Lilly) was approved in the United States in July 2019 for people with diabetes age 4 years and older.

In September 2019, the FDA approved another prefilled glucagon rescue pen (Gvoke HypoPen, Xeris Pharmaceuticals) for the treatment of severe hypoglycemia in adult and pediatric patients age 2 years and older with diabetes.

Dasiglucagon is currently in phase 3 trials as a subcutaneous infusion for treating congenital hyperinsulinemia, and in phase 2 trials as part of a bihormonal artificial pancreas pump system.

The FDA approval was based on results from three randomized, double-blind, placebo-controlled, phase 3 studies of dasiglucagon in children age 6-17 years and adults with type 1 diabetes.

The primary endpoint was time to achieving an increase in blood glucose of 20 mg/dL or greater from time of administration without additional intervention within 45 minutes. That endpoint was achieved in all three studies, with a median time to blood glucose recovery of 10 minutes overall, with 99% of adults recovering within 15 minutes.

The most common adverse events reported in 2% or more of study participants were nausea, vomiting, headache, and injection-site pain in both children and adults. Diarrhea was also reported in adults.  

Full launch is expected in late June 2021.

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

Patients at very high risk for melanoma, including those with a family history or with inherited pathogenic variants of genes that increase the risk, likely benefit from routine whole-body screening for melanoma and education about UV protection.

Those are key findings from the first prospective cohort study to quantify the benefit of screening in melanoma-prone families, which was published online April 2 in Cancer Epidemiology, Biomarkers & Prevention.

“Whole-body screening for melanoma is currently routine for individuals at high risk for melanoma, which includes people from melanoma-prone families (at least two relatives who have had melanoma) and those with inherited pathogenic gene variants of the CDKN2A or CDK4 genes, which increase risk for melanoma,” lead author Michael R. Sargen, MD, said in an interview. “In our study, we investigated whether screening and educational interventions, including education about the appearance of melanoma and strategies for protecting skin from ultraviolet damage, contributed to early diagnosis of melanoma in individuals from melanoma-prone families.”

Of the 293 individuals who enrolled in the study between 1976 and 2014, 246 were diagnosed with melanoma before enrollment (the prestudy cohort) and 47 were diagnosed after enrollment (the prospective cohort). The researchers compared differences in melanoma thickness and tumor stage between participants in the prestudy and prospective cohorts, and compared tumor-thickness trends between participants in their study and cases in the general population using data from Surveillance, Epidemiology, and End Results (SEER) registries between 1973 and 2016. Because information on melanoma thickness was missing for 24% of melanoma cases in the NCI Familial Melanoma Study and 8.7% of melanoma cases found in the SEER registry, the researchers imputed the missing data.

After adjusting for gender and age, Dr. Sargen and his colleagues found that participants in the prospective cohort had significantly thinner melanomas, compared with those in the prestudy cohort (0.6 mm vs. 1.1 mm, respectively; P < .001). In addition, 83% of those in the prospective cohort were significantly more likely to be diagnosed at the early T1 stage, compared with 40% of those in the prestudy cohort (P < .001).

In their analysis, they also determined that after adjusting for gender and age, “all NCI family cases had systematically lower thickness than SEER cases during the study period.” The reductions in melanoma thickness and tumor stage, they concluded, “were not fully explained by calendar period effects of decreasing thickness in the general population and point to the potential benefit of skin cancer screening for patients with a family history of melanoma and those with pathogenic germline variants of melanoma-susceptibility genes.”

“Our data provide reassuring evidence that screening, alongside education about proper UV protection and the appearance of melanoma, is likely benefiting patients with a significantly elevated risk for melanoma,” Dr. Sargen said in the interview “Further studies are needed to determine whether individuals without a family history of melanoma may benefit from whole-body screening, and whether the benefits vary by ethnicity.”

He acknowledged certain limitations of the study, including the relatively small sample size of melanoma cases in the NCI Familial Melanoma Study and the imputation of missing melanoma-thickness data. “Additionally, since this was a prospective cohort study, we were not able to distinguish the independent effect of each intervention,” he said. “Randomized controlled studies are needed to understand the impact of each aspect of the intervention, such as whole-body screening, melanoma education, or strategies for skin protection.”

In an interview, Maryam M. Asgari, MD, professor of dermatology at Harvard University, Boston, called the analysis “well done,” but commented on the potential role of selection bias impacting the findings. “People who have a strong family history of melanoma and who are opting to engage in an NCI study and come in for full-body skin checks and go through that education process may have very different health-seeking behaviors than individuals in the general population that would be reported to SEER,” she said.

She also raised the question of whether the results were driven by the early detection through the NCI’s program of provider screening or through the educational component that enables earlier self-detection. “If you’re an individual involved in a study and that brings attention to your moles and you have a strong family history of melanoma to begin with, it is not surprising that you are going to have heightened awareness of any changing mole and therefore are more likely to have melanoma detected at an earlier stage,” Dr. Asgari said.

The study was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute. Dr. Sargen reported having no financial disclosures.
Dr. Asgari disclosed that she has received research support from the Melanoma Research Alliance.
 

[email protected]

Patients at very high risk for melanoma, including those with a family history or with inherited pathogenic variants of genes that increase the risk, likely benefit from routine whole-body screening for melanoma and education about UV protection.

Those are key findings from the first prospective cohort study to quantify the benefit of screening in melanoma-prone families, which was published online April 2 in Cancer Epidemiology, Biomarkers & Prevention.

“Whole-body screening for melanoma is currently routine for individuals at high risk for melanoma, which includes people from melanoma-prone families (at least two relatives who have had melanoma) and those with inherited pathogenic gene variants of the CDKN2A or CDK4 genes, which increase risk for melanoma,” lead author Michael R. Sargen, MD, said in an interview. “In our study, we investigated whether screening and educational interventions, including education about the appearance of melanoma and strategies for protecting skin from ultraviolet damage, contributed to early diagnosis of melanoma in individuals from melanoma-prone families.”

Of the 293 individuals who enrolled in the study between 1976 and 2014, 246 were diagnosed with melanoma before enrollment (the prestudy cohort) and 47 were diagnosed after enrollment (the prospective cohort). The researchers compared differences in melanoma thickness and tumor stage between participants in the prestudy and prospective cohorts, and compared tumor-thickness trends between participants in their study and cases in the general population using data from Surveillance, Epidemiology, and End Results (SEER) registries between 1973 and 2016. Because information on melanoma thickness was missing for 24% of melanoma cases in the NCI Familial Melanoma Study and 8.7% of melanoma cases found in the SEER registry, the researchers imputed the missing data.

After adjusting for gender and age, Dr. Sargen and his colleagues found that participants in the prospective cohort had significantly thinner melanomas, compared with those in the prestudy cohort (0.6 mm vs. 1.1 mm, respectively; P < .001). In addition, 83% of those in the prospective cohort were significantly more likely to be diagnosed at the early T1 stage, compared with 40% of those in the prestudy cohort (P < .001).

In their analysis, they also determined that after adjusting for gender and age, “all NCI family cases had systematically lower thickness than SEER cases during the study period.” The reductions in melanoma thickness and tumor stage, they concluded, “were not fully explained by calendar period effects of decreasing thickness in the general population and point to the potential benefit of skin cancer screening for patients with a family history of melanoma and those with pathogenic germline variants of melanoma-susceptibility genes.”

“Our data provide reassuring evidence that screening, alongside education about proper UV protection and the appearance of melanoma, is likely benefiting patients with a significantly elevated risk for melanoma,” Dr. Sargen said in the interview “Further studies are needed to determine whether individuals without a family history of melanoma may benefit from whole-body screening, and whether the benefits vary by ethnicity.”

He acknowledged certain limitations of the study, including the relatively small sample size of melanoma cases in the NCI Familial Melanoma Study and the imputation of missing melanoma-thickness data. “Additionally, since this was a prospective cohort study, we were not able to distinguish the independent effect of each intervention,” he said. “Randomized controlled studies are needed to understand the impact of each aspect of the intervention, such as whole-body screening, melanoma education, or strategies for skin protection.”

In an interview, Maryam M. Asgari, MD, professor of dermatology at Harvard University, Boston, called the analysis “well done,” but commented on the potential role of selection bias impacting the findings. “People who have a strong family history of melanoma and who are opting to engage in an NCI study and come in for full-body skin checks and go through that education process may have very different health-seeking behaviors than individuals in the general population that would be reported to SEER,” she said.

She also raised the question of whether the results were driven by the early detection through the NCI’s program of provider screening or through the educational component that enables earlier self-detection. “If you’re an individual involved in a study and that brings attention to your moles and you have a strong family history of melanoma to begin with, it is not surprising that you are going to have heightened awareness of any changing mole and therefore are more likely to have melanoma detected at an earlier stage,” Dr. Asgari said.

The study was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute. Dr. Sargen reported having no financial disclosures.
Dr. Asgari disclosed that she has received research support from the Melanoma Research Alliance.
 

[email protected]

Patients at very high risk for melanoma, including those with a family history or with inherited pathogenic variants of genes that increase the risk, likely benefit from routine whole-body screening for melanoma and education about UV protection.

Those are key findings from the first prospective cohort study to quantify the benefit of screening in melanoma-prone families, which was published online April 2 in Cancer Epidemiology, Biomarkers & Prevention.

“Whole-body screening for melanoma is currently routine for individuals at high risk for melanoma, which includes people from melanoma-prone families (at least two relatives who have had melanoma) and those with inherited pathogenic gene variants of the CDKN2A or CDK4 genes, which increase risk for melanoma,” lead author Michael R. Sargen, MD, said in an interview. “In our study, we investigated whether screening and educational interventions, including education about the appearance of melanoma and strategies for protecting skin from ultraviolet damage, contributed to early diagnosis of melanoma in individuals from melanoma-prone families.”

Of the 293 individuals who enrolled in the study between 1976 and 2014, 246 were diagnosed with melanoma before enrollment (the prestudy cohort) and 47 were diagnosed after enrollment (the prospective cohort). The researchers compared differences in melanoma thickness and tumor stage between participants in the prestudy and prospective cohorts, and compared tumor-thickness trends between participants in their study and cases in the general population using data from Surveillance, Epidemiology, and End Results (SEER) registries between 1973 and 2016. Because information on melanoma thickness was missing for 24% of melanoma cases in the NCI Familial Melanoma Study and 8.7% of melanoma cases found in the SEER registry, the researchers imputed the missing data.

After adjusting for gender and age, Dr. Sargen and his colleagues found that participants in the prospective cohort had significantly thinner melanomas, compared with those in the prestudy cohort (0.6 mm vs. 1.1 mm, respectively; P < .001). In addition, 83% of those in the prospective cohort were significantly more likely to be diagnosed at the early T1 stage, compared with 40% of those in the prestudy cohort (P < .001).

In their analysis, they also determined that after adjusting for gender and age, “all NCI family cases had systematically lower thickness than SEER cases during the study period.” The reductions in melanoma thickness and tumor stage, they concluded, “were not fully explained by calendar period effects of decreasing thickness in the general population and point to the potential benefit of skin cancer screening for patients with a family history of melanoma and those with pathogenic germline variants of melanoma-susceptibility genes.”

“Our data provide reassuring evidence that screening, alongside education about proper UV protection and the appearance of melanoma, is likely benefiting patients with a significantly elevated risk for melanoma,” Dr. Sargen said in the interview “Further studies are needed to determine whether individuals without a family history of melanoma may benefit from whole-body screening, and whether the benefits vary by ethnicity.”

He acknowledged certain limitations of the study, including the relatively small sample size of melanoma cases in the NCI Familial Melanoma Study and the imputation of missing melanoma-thickness data. “Additionally, since this was a prospective cohort study, we were not able to distinguish the independent effect of each intervention,” he said. “Randomized controlled studies are needed to understand the impact of each aspect of the intervention, such as whole-body screening, melanoma education, or strategies for skin protection.”

In an interview, Maryam M. Asgari, MD, professor of dermatology at Harvard University, Boston, called the analysis “well done,” but commented on the potential role of selection bias impacting the findings. “People who have a strong family history of melanoma and who are opting to engage in an NCI study and come in for full-body skin checks and go through that education process may have very different health-seeking behaviors than individuals in the general population that would be reported to SEER,” she said.

She also raised the question of whether the results were driven by the early detection through the NCI’s program of provider screening or through the educational component that enables earlier self-detection. “If you’re an individual involved in a study and that brings attention to your moles and you have a strong family history of melanoma to begin with, it is not surprising that you are going to have heightened awareness of any changing mole and therefore are more likely to have melanoma detected at an earlier stage,” Dr. Asgari said.

The study was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute. Dr. Sargen reported having no financial disclosures.
Dr. Asgari disclosed that she has received research support from the Melanoma Research Alliance.
 

[email protected]

April 5 is the official start date of a U.S. law requiring health care organizations to provide patients with free, full, and immediate electronic access to their doctor’s clinical notes as well as test results and reports from pathology and imaging.

The mandate, called “open notes” by many, is part of the 21st Century Cures Act, a wide-ranging piece of federal health care legislation. The previous deadline of Nov. 2, 2020, for enacting open notes was extended last year because of the exigencies of the COVID-19 pandemic.

Organizations must provide access via patient portals to the following types of notes: consultations, discharge summaries, histories, physical examination findings, imaging narratives, laboratory and pathology report narratives, and procedure and progress notes. Noncompliant organizations will eventually be subject to fines from the Department of Health & Human Services for “information blocking.”

This news organization reported on the mandate in 2020, and some readers said it was an unwelcome intrusion into practice. Since then, this news organization has run additional open notes stories about physician concerns, a perspective essay addressing those fears, and a reader poll about the phenomenon.

Now, as the legislation turns into a practical clinical matter, there are five key points clinicians should consider.
 

Clinicians don’t have to change writing style.

The new law mandates timely patient access to notes and test results, but it doesn’t require that clinicians alter their writing, said Scott MacDonald, MD, an internist and electronic health record medical director at University of California Davis Health in Sacramento.

“You don’t have to change your notes,” he said. However, patients are now part of the note audience and some health care systems are directing clinicians to make patient-friendly style changes.

Everyday experience should guide clinicians when writing notes, said one expert.

“When you’re not sure [of how to write a note], just mirror the way you would speak in the office – that’s going to get you right, including for mental health issues,” advised Leonor Fernandez, MD, an internist at Beth Deaconess Israel Medical Center, Boston, in her “take-away” comments in the online video, How to Write an Open Note.

According to a 2020 Medscape poll of 1,050 physicians, a majority (56%) anticipate that they will write notes differently, knowing that patients can read them via open notes. Nearly two-thirds (64%) believe that this new wrinkle in medical records will increase their workload. However, actual practice suggests that this is true for a minority of practitioners, according to the results from a recent study of more than 1,000 physicians in Boston, Seattle, and rural Pennsylvania, who already work in open notes settings. Only about one-third (37%) reported “spending more time on documentation.”

Note writing is going to change because of the addition of the patient reader, and something will be lost, argued Steven Reidbord, MD, a psychiatrist in private practice in San Francisco. By watering down the language for patients, “you are trading away the technical precision and other advantages of having a professional language,” commented Dr. Reidbord, who blogs for Psychology Today and has criticized the open notes movement in the past.

However, years of investigation from OpenNotes, the Boston-based advocacy and research organization, indicates that there are many gains with patient-accessible notes, including improved medical record accuracy, greater medication adherence, and potentially improved health care disparities among a range of patient types. In a 2019 study, researchers said that worry and confusion among note-reading patients are uncommon (5% and 3%, respectively), which addresses two criticisms voiced by multiple people last year.
 

Some clinical notes can be withheld. 

The new rules from the federal government permit information blocking if there is clear evidence that doing so “will substantially reduce the risk of harm” to patients or to other third parties, Tom Delbanco, MD, and Charlotte Blease, PhD, of OpenNotes in Boston wrote in a commentary in February 2021.

There are also state-level laws that can supersede the new U.S. law and block access to notes, points out MacDonald. For example, California law dictates that providers cannot post cancer test results without talking with the patient first.

The OpenNotes organization also points out that, with regard to sensitive psychotherapy notes that are separated from the rest of a medical record, those notes “can be kept from patients without their permission, and such rules vary state by state.”
 

Some patients are more likely readers. 

Some patients are more likely to peer into their files than others, said Liz Salmi, senior strategist at OpenNotes, who is also a brain cancer patient.

“Those patients who have more serious or chronic conditions ... are more likely to read their notes,” she said in an interview.

A new study of nearly 6,000 medical oncology patients at the University of Wisconsin confirmed that opinion. Patients with incurable metastatic disease were much more likely than those with early-stage, curable disease to read notes. Notably, younger patients were more likely than older ones to access notes, likely the result of generational tech savvy.

Despite the unpredictability of serious disease such as cancer, oncology patients find satisfaction in reading their notes, say experts. “We’ve overwhelmingly heard that patients like it,” Thomas LeBlanc, MD, medical oncologist at Duke University, Durham, N.C., where all patients already have access to clinicians’ notes, told this news organization in 2018.
 

You are part of the avant garde. 

The United States and Scandinavian countries are the world leaders in implementing open notes in clinical practice, Dr. Blease said in an interview.

“It’s a phenomenal achievement” to have enacted open notes nationally, she said. For example, there are no open notes in Northern Ireland, Dr. Blease’s home country, or most of Europe.

In the United States, there are more than 200 medical organizations, including at least one in every state, that were voluntarily providing open notes before April 5, including interstate giants such as Banner Health and big-name medical centers such as Cleveland Clinic.

It may be hard for the United States to top Sweden’s embrace of the practice. The national open notes program now has 7.2 million patient accounts in a country of 10 million people, noted Maria Häggland, PhD, of Uppsala (Sweden) MedTech Science Innovation Center during a webinar last year.
 

The start day will come, and you may not notice. 

“When April 5 happens, something brand new is going to happen symbolically,” Ms. Salmi said. Its importance is hard to measure.

“Patients say they trust their doctor more because they understand their thinking with open notes. How do you value that? We don’t have metrics for that,” she said.

Dr. MacDonald suggested that open notes are both new and not new. In the fall of 2020, he predicted that the launch day would come, and few clinicians would notice, in part because many patients already access truncated information via patient portals.

However, there are “sensitive issues,” such as with adolescents and reproductive health, where “we know that some parents have sign-in information for their teen’s portal,” he commented. With clinical notes now on full display, potential problems “may be out of our control.”

Still, the Sacramento-based physician and IT officer acknowledged that concerns about open notes may be a bit inflated. “I’ve been more worried about reassuring physicians that everything will be okay than what’s actually going to happen [as the law takes effect],” Dr. MacDonald said.

The OpenNotes organization is grant funded, and staff disclosed no relevant financial relationships.

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

April 5 is the official start date of a U.S. law requiring health care organizations to provide patients with free, full, and immediate electronic access to their doctor’s clinical notes as well as test results and reports from pathology and imaging.

The mandate, called “open notes” by many, is part of the 21st Century Cures Act, a wide-ranging piece of federal health care legislation. The previous deadline of Nov. 2, 2020, for enacting open notes was extended last year because of the exigencies of the COVID-19 pandemic.

Organizations must provide access via patient portals to the following types of notes: consultations, discharge summaries, histories, physical examination findings, imaging narratives, laboratory and pathology report narratives, and procedure and progress notes. Noncompliant organizations will eventually be subject to fines from the Department of Health & Human Services for “information blocking.”

This news organization reported on the mandate in 2020, and some readers said it was an unwelcome intrusion into practice. Since then, this news organization has run additional open notes stories about physician concerns, a perspective essay addressing those fears, and a reader poll about the phenomenon.

Now, as the legislation turns into a practical clinical matter, there are five key points clinicians should consider.
 

Clinicians don’t have to change writing style.

The new law mandates timely patient access to notes and test results, but it doesn’t require that clinicians alter their writing, said Scott MacDonald, MD, an internist and electronic health record medical director at University of California Davis Health in Sacramento.

“You don’t have to change your notes,” he said. However, patients are now part of the note audience and some health care systems are directing clinicians to make patient-friendly style changes.

Everyday experience should guide clinicians when writing notes, said one expert.

“When you’re not sure [of how to write a note], just mirror the way you would speak in the office – that’s going to get you right, including for mental health issues,” advised Leonor Fernandez, MD, an internist at Beth Deaconess Israel Medical Center, Boston, in her “take-away” comments in the online video, How to Write an Open Note.

According to a 2020 Medscape poll of 1,050 physicians, a majority (56%) anticipate that they will write notes differently, knowing that patients can read them via open notes. Nearly two-thirds (64%) believe that this new wrinkle in medical records will increase their workload. However, actual practice suggests that this is true for a minority of practitioners, according to the results from a recent study of more than 1,000 physicians in Boston, Seattle, and rural Pennsylvania, who already work in open notes settings. Only about one-third (37%) reported “spending more time on documentation.”

Note writing is going to change because of the addition of the patient reader, and something will be lost, argued Steven Reidbord, MD, a psychiatrist in private practice in San Francisco. By watering down the language for patients, “you are trading away the technical precision and other advantages of having a professional language,” commented Dr. Reidbord, who blogs for Psychology Today and has criticized the open notes movement in the past.

However, years of investigation from OpenNotes, the Boston-based advocacy and research organization, indicates that there are many gains with patient-accessible notes, including improved medical record accuracy, greater medication adherence, and potentially improved health care disparities among a range of patient types. In a 2019 study, researchers said that worry and confusion among note-reading patients are uncommon (5% and 3%, respectively), which addresses two criticisms voiced by multiple people last year.
 

Some clinical notes can be withheld. 

The new rules from the federal government permit information blocking if there is clear evidence that doing so “will substantially reduce the risk of harm” to patients or to other third parties, Tom Delbanco, MD, and Charlotte Blease, PhD, of OpenNotes in Boston wrote in a commentary in February 2021.

There are also state-level laws that can supersede the new U.S. law and block access to notes, points out MacDonald. For example, California law dictates that providers cannot post cancer test results without talking with the patient first.

The OpenNotes organization also points out that, with regard to sensitive psychotherapy notes that are separated from the rest of a medical record, those notes “can be kept from patients without their permission, and such rules vary state by state.”
 

Some patients are more likely readers. 

Some patients are more likely to peer into their files than others, said Liz Salmi, senior strategist at OpenNotes, who is also a brain cancer patient.

“Those patients who have more serious or chronic conditions ... are more likely to read their notes,” she said in an interview.

A new study of nearly 6,000 medical oncology patients at the University of Wisconsin confirmed that opinion. Patients with incurable metastatic disease were much more likely than those with early-stage, curable disease to read notes. Notably, younger patients were more likely than older ones to access notes, likely the result of generational tech savvy.

Despite the unpredictability of serious disease such as cancer, oncology patients find satisfaction in reading their notes, say experts. “We’ve overwhelmingly heard that patients like it,” Thomas LeBlanc, MD, medical oncologist at Duke University, Durham, N.C., where all patients already have access to clinicians’ notes, told this news organization in 2018.
 

You are part of the avant garde. 

The United States and Scandinavian countries are the world leaders in implementing open notes in clinical practice, Dr. Blease said in an interview.

“It’s a phenomenal achievement” to have enacted open notes nationally, she said. For example, there are no open notes in Northern Ireland, Dr. Blease’s home country, or most of Europe.

In the United States, there are more than 200 medical organizations, including at least one in every state, that were voluntarily providing open notes before April 5, including interstate giants such as Banner Health and big-name medical centers such as Cleveland Clinic.

It may be hard for the United States to top Sweden’s embrace of the practice. The national open notes program now has 7.2 million patient accounts in a country of 10 million people, noted Maria Häggland, PhD, of Uppsala (Sweden) MedTech Science Innovation Center during a webinar last year.
 

The start day will come, and you may not notice. 

“When April 5 happens, something brand new is going to happen symbolically,” Ms. Salmi said. Its importance is hard to measure.

“Patients say they trust their doctor more because they understand their thinking with open notes. How do you value that? We don’t have metrics for that,” she said.

Dr. MacDonald suggested that open notes are both new and not new. In the fall of 2020, he predicted that the launch day would come, and few clinicians would notice, in part because many patients already access truncated information via patient portals.

However, there are “sensitive issues,” such as with adolescents and reproductive health, where “we know that some parents have sign-in information for their teen’s portal,” he commented. With clinical notes now on full display, potential problems “may be out of our control.”

Still, the Sacramento-based physician and IT officer acknowledged that concerns about open notes may be a bit inflated. “I’ve been more worried about reassuring physicians that everything will be okay than what’s actually going to happen [as the law takes effect],” Dr. MacDonald said.

The OpenNotes organization is grant funded, and staff disclosed no relevant financial relationships.

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

April 5 is the official start date of a U.S. law requiring health care organizations to provide patients with free, full, and immediate electronic access to their doctor’s clinical notes as well as test results and reports from pathology and imaging.

The mandate, called “open notes” by many, is part of the 21st Century Cures Act, a wide-ranging piece of federal health care legislation. The previous deadline of Nov. 2, 2020, for enacting open notes was extended last year because of the exigencies of the COVID-19 pandemic.

Organizations must provide access via patient portals to the following types of notes: consultations, discharge summaries, histories, physical examination findings, imaging narratives, laboratory and pathology report narratives, and procedure and progress notes. Noncompliant organizations will eventually be subject to fines from the Department of Health & Human Services for “information blocking.”

This news organization reported on the mandate in 2020, and some readers said it was an unwelcome intrusion into practice. Since then, this news organization has run additional open notes stories about physician concerns, a perspective essay addressing those fears, and a reader poll about the phenomenon.

Now, as the legislation turns into a practical clinical matter, there are five key points clinicians should consider.
 

Clinicians don’t have to change writing style.

The new law mandates timely patient access to notes and test results, but it doesn’t require that clinicians alter their writing, said Scott MacDonald, MD, an internist and electronic health record medical director at University of California Davis Health in Sacramento.

“You don’t have to change your notes,” he said. However, patients are now part of the note audience and some health care systems are directing clinicians to make patient-friendly style changes.

Everyday experience should guide clinicians when writing notes, said one expert.

“When you’re not sure [of how to write a note], just mirror the way you would speak in the office – that’s going to get you right, including for mental health issues,” advised Leonor Fernandez, MD, an internist at Beth Deaconess Israel Medical Center, Boston, in her “take-away” comments in the online video, How to Write an Open Note.

According to a 2020 Medscape poll of 1,050 physicians, a majority (56%) anticipate that they will write notes differently, knowing that patients can read them via open notes. Nearly two-thirds (64%) believe that this new wrinkle in medical records will increase their workload. However, actual practice suggests that this is true for a minority of practitioners, according to the results from a recent study of more than 1,000 physicians in Boston, Seattle, and rural Pennsylvania, who already work in open notes settings. Only about one-third (37%) reported “spending more time on documentation.”

Note writing is going to change because of the addition of the patient reader, and something will be lost, argued Steven Reidbord, MD, a psychiatrist in private practice in San Francisco. By watering down the language for patients, “you are trading away the technical precision and other advantages of having a professional language,” commented Dr. Reidbord, who blogs for Psychology Today and has criticized the open notes movement in the past.

However, years of investigation from OpenNotes, the Boston-based advocacy and research organization, indicates that there are many gains with patient-accessible notes, including improved medical record accuracy, greater medication adherence, and potentially improved health care disparities among a range of patient types. In a 2019 study, researchers said that worry and confusion among note-reading patients are uncommon (5% and 3%, respectively), which addresses two criticisms voiced by multiple people last year.
 

Some clinical notes can be withheld. 

The new rules from the federal government permit information blocking if there is clear evidence that doing so “will substantially reduce the risk of harm” to patients or to other third parties, Tom Delbanco, MD, and Charlotte Blease, PhD, of OpenNotes in Boston wrote in a commentary in February 2021.

There are also state-level laws that can supersede the new U.S. law and block access to notes, points out MacDonald. For example, California law dictates that providers cannot post cancer test results without talking with the patient first.

The OpenNotes organization also points out that, with regard to sensitive psychotherapy notes that are separated from the rest of a medical record, those notes “can be kept from patients without their permission, and such rules vary state by state.”
 

Some patients are more likely readers. 

Some patients are more likely to peer into their files than others, said Liz Salmi, senior strategist at OpenNotes, who is also a brain cancer patient.

“Those patients who have more serious or chronic conditions ... are more likely to read their notes,” she said in an interview.

A new study of nearly 6,000 medical oncology patients at the University of Wisconsin confirmed that opinion. Patients with incurable metastatic disease were much more likely than those with early-stage, curable disease to read notes. Notably, younger patients were more likely than older ones to access notes, likely the result of generational tech savvy.

Despite the unpredictability of serious disease such as cancer, oncology patients find satisfaction in reading their notes, say experts. “We’ve overwhelmingly heard that patients like it,” Thomas LeBlanc, MD, medical oncologist at Duke University, Durham, N.C., where all patients already have access to clinicians’ notes, told this news organization in 2018.
 

You are part of the avant garde. 

The United States and Scandinavian countries are the world leaders in implementing open notes in clinical practice, Dr. Blease said in an interview.

“It’s a phenomenal achievement” to have enacted open notes nationally, she said. For example, there are no open notes in Northern Ireland, Dr. Blease’s home country, or most of Europe.

In the United States, there are more than 200 medical organizations, including at least one in every state, that were voluntarily providing open notes before April 5, including interstate giants such as Banner Health and big-name medical centers such as Cleveland Clinic.

It may be hard for the United States to top Sweden’s embrace of the practice. The national open notes program now has 7.2 million patient accounts in a country of 10 million people, noted Maria Häggland, PhD, of Uppsala (Sweden) MedTech Science Innovation Center during a webinar last year.
 

The start day will come, and you may not notice. 

“When April 5 happens, something brand new is going to happen symbolically,” Ms. Salmi said. Its importance is hard to measure.

“Patients say they trust their doctor more because they understand their thinking with open notes. How do you value that? We don’t have metrics for that,” she said.

Dr. MacDonald suggested that open notes are both new and not new. In the fall of 2020, he predicted that the launch day would come, and few clinicians would notice, in part because many patients already access truncated information via patient portals.

However, there are “sensitive issues,” such as with adolescents and reproductive health, where “we know that some parents have sign-in information for their teen’s portal,” he commented. With clinical notes now on full display, potential problems “may be out of our control.”

Still, the Sacramento-based physician and IT officer acknowledged that concerns about open notes may be a bit inflated. “I’ve been more worried about reassuring physicians that everything will be okay than what’s actually going to happen [as the law takes effect],” Dr. MacDonald said.

The OpenNotes organization is grant funded, and staff disclosed no relevant financial relationships.

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

COVID-19 was the third-leading cause of death in the United States in 2020, but that mortality burden did not fall evenly along racial/ethnic lines, according to a provisional report from the Centers for Disease Control and Prevention.

Only heart disease and cancer caused more deaths than SARS-CoV-2, which took the lives of almost 378,000 Americans last year, Farida B. Ahmad, MPH, and associates at the National Center for Health Statistics noted March 31 in the Morbidity and Mortality Weekly Report.

That represents 11.2% of the almost 3.36 million total deaths recorded in 2020. The racial/ethnics demographics, however, show that 22.4% of all deaths among Hispanic Americans were COVID-19–related, as were 18.6% of deaths in American Indians/Alaska Natives. Deaths among Asian persons, at 14.7%, and African Americans, at 13.5%, were closer but still above the national figure, while Whites (9.3%) were the only major subgroup below it, based on data from the National Vital Statistics System.

Age-adjusted death rates tell a somewhat different story: American Indian/Alaska native persons were highest with a rate of 187.8 COVID-19–associated deaths per 100,000 standard population, with Hispanic persons second at 164.3 per 100,000. Blacks were next at 151.1 deaths per 100,000, but Whites had a higher rate (72.5) than did Asian Americans (66.7), the CDC investigators reported.

“During January-December 2020, the estimated 2020 age-adjusted death rate increased for the first time since 2017, with an increase of 15.9% compared with 2019, from 715.2 to 828.7 deaths per 100,000 population,” they wrote, noting that “certain categories of race (i.e., AI/AN and Asian) and Hispanic ethnicity reported on death certificates might have been misclassified, possibly resulting in underestimates of death rates for some groups.”

[email protected]

COVID-19 was the third-leading cause of death in the United States in 2020, but that mortality burden did not fall evenly along racial/ethnic lines, according to a provisional report from the Centers for Disease Control and Prevention.

Only heart disease and cancer caused more deaths than SARS-CoV-2, which took the lives of almost 378,000 Americans last year, Farida B. Ahmad, MPH, and associates at the National Center for Health Statistics noted March 31 in the Morbidity and Mortality Weekly Report.

That represents 11.2% of the almost 3.36 million total deaths recorded in 2020. The racial/ethnics demographics, however, show that 22.4% of all deaths among Hispanic Americans were COVID-19–related, as were 18.6% of deaths in American Indians/Alaska Natives. Deaths among Asian persons, at 14.7%, and African Americans, at 13.5%, were closer but still above the national figure, while Whites (9.3%) were the only major subgroup below it, based on data from the National Vital Statistics System.

Age-adjusted death rates tell a somewhat different story: American Indian/Alaska native persons were highest with a rate of 187.8 COVID-19–associated deaths per 100,000 standard population, with Hispanic persons second at 164.3 per 100,000. Blacks were next at 151.1 deaths per 100,000, but Whites had a higher rate (72.5) than did Asian Americans (66.7), the CDC investigators reported.

“During January-December 2020, the estimated 2020 age-adjusted death rate increased for the first time since 2017, with an increase of 15.9% compared with 2019, from 715.2 to 828.7 deaths per 100,000 population,” they wrote, noting that “certain categories of race (i.e., AI/AN and Asian) and Hispanic ethnicity reported on death certificates might have been misclassified, possibly resulting in underestimates of death rates for some groups.”

[email protected]

COVID-19 was the third-leading cause of death in the United States in 2020, but that mortality burden did not fall evenly along racial/ethnic lines, according to a provisional report from the Centers for Disease Control and Prevention.

Only heart disease and cancer caused more deaths than SARS-CoV-2, which took the lives of almost 378,000 Americans last year, Farida B. Ahmad, MPH, and associates at the National Center for Health Statistics noted March 31 in the Morbidity and Mortality Weekly Report.

That represents 11.2% of the almost 3.36 million total deaths recorded in 2020. The racial/ethnics demographics, however, show that 22.4% of all deaths among Hispanic Americans were COVID-19–related, as were 18.6% of deaths in American Indians/Alaska Natives. Deaths among Asian persons, at 14.7%, and African Americans, at 13.5%, were closer but still above the national figure, while Whites (9.3%) were the only major subgroup below it, based on data from the National Vital Statistics System.

Age-adjusted death rates tell a somewhat different story: American Indian/Alaska native persons were highest with a rate of 187.8 COVID-19–associated deaths per 100,000 standard population, with Hispanic persons second at 164.3 per 100,000. Blacks were next at 151.1 deaths per 100,000, but Whites had a higher rate (72.5) than did Asian Americans (66.7), the CDC investigators reported.

“During January-December 2020, the estimated 2020 age-adjusted death rate increased for the first time since 2017, with an increase of 15.9% compared with 2019, from 715.2 to 828.7 deaths per 100,000 population,” they wrote, noting that “certain categories of race (i.e., AI/AN and Asian) and Hispanic ethnicity reported on death certificates might have been misclassified, possibly resulting in underestimates of death rates for some groups.”

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