MDedge Pediatrics

Obese or overweight children with asthma could be using inhaled corticosteroids (ICS) to no avail, combined results from observational studies suggest.

Using Mendelian randomization, a method for reducing bias in observational studies, investigators from the University of Amsterdam Medical Center performed an analysis of data from four cross-sectional studies and one cohort study on a total of 1,511 children with asthma.

They showed that every 1-unit increase in the body mass index (BMI) z score was associated with a more than twofold higher odds ratio for exacerbation, reported Cristina Longo, PhD, a former postdoctoral fellow at AMC, and assistant professor of medicine at the University of Montreal.

“In this large, multicenter Mendelian randomization study, our findings support current evidence that children with higher BMI status respond inadequately to inhaled corticosteroids, and that this association is likely not explained by measured confounding or reverse causation,” she said in an oral abstract presentation during the European Respiratory Society International Congress.
 

Unmeasured confounding

The obese-asthma phenotype in children is characterized by reduced lung function, high symptom expression, poor response to ICS, and high health care utilization.

“While most observational studies suggest that weight status is associated with asthma exacerbations, despite using inhaled corticosteroids, it’s unclear whether these associations may be due to unmeasured confounding or reverse causation, which captures the idea that perhaps obesity is a consequence rather than a cause of uncontrolled severe asthma,” she said.

Traditional observational studies of the obesity-asthma link rely on comparing data on asthma in a target population and comparing nonobese patients with obese patients. The problem with this method, Dr. Longo contended, is that the exposure assignment – weight status – is not random, and could lead to bias from potential imbalance of confounders, leading to unintentionally biased results.

In contrast, Mendelian randomization uses genetic data to approximate random assignment of exposures, using a risk score for BMI based on genetic susceptibility. The score is based on the accumulation of genetic variants (single-nucleotide polymorphisms, or SNPs) that predispose individuals to obesity, with higher numbers of variants results in a higher risk score.

The scores are then used to determine the comparison groups for evaluating the obesity-asthma association.
 

Alphabet soup

Dr. Longo and colleagues analyzed data on a total 1,511 children enrolled in four observational studies (PACMAN, PAGES, HPR, CLARA) and one cohort study (ALSPAC).

They included children with an asthma diagnosis who used ICS and had available information on both BMI and genetics.

The Mendelian randomization analysis was based on a weighted allele score based on 97 SNPs predictive of BMI based on large-scale genomewide association studies. The exposure for the analysis was age- and sex-adjusted BMI z scores based on World Health Organization growth charts for children.

They found that using the Mendelian randomization approach, for each standard deviation increase in BMI, the OR for any parent-reported asthma exacerbations, including urgent care visits or use of oral corticosteroids, was 2.31 (95% confidence interval, 1.26-4.25).

In contrast, if the traditional observational model had been used, the OR would be a nonsignificant 1.10 (95% CI, 0.99-1.22).

“Treatment guidelines recommend steroids for children with asthma who have a higher-than-normal BMI,” Dr. Longo said in a statement. “Our research group felt that the one-size fits-all approach to treating children with asthma with inhaled steroids as their first-line treatment, particularly those with excess weight, warrants revision. At the very least, research identifying potential alternative treatments should be encouraged and prioritized, especially since 30% of children with asthma are also obese. With the childhood obesity epidemic rising, we expect this percentage to increase meaning this problem of poor control will be seen more frequently in routine clinical practice.”

Christopher E. Brightling, PhD, professor of respiratory medicine at the University of Leicester (England), commented that “this is very good and fascinating research with findings that are important and novel.

“It sheds light on the complex interplay between genes, weight, and response to inhaled corticosteroids, underscoring the need to combine drug treatments with lifestyle and diet modifications. Policy makers, health care providers and families need to do much more to tackle the growing obesity epidemic in young people,” he said.

Dr. Brightling was not involved in the study.

The study was supported by the ERS and the European Union’s H2020 research and innovation program. Dr. Longo was a Horizon 2020 Marie-Sklodowska Cure Respire-3 fellow. Dr. Brightling reported no relevant disclosures.

Obese or overweight children with asthma could be using inhaled corticosteroids (ICS) to no avail, combined results from observational studies suggest.

Using Mendelian randomization, a method for reducing bias in observational studies, investigators from the University of Amsterdam Medical Center performed an analysis of data from four cross-sectional studies and one cohort study on a total of 1,511 children with asthma.

They showed that every 1-unit increase in the body mass index (BMI) z score was associated with a more than twofold higher odds ratio for exacerbation, reported Cristina Longo, PhD, a former postdoctoral fellow at AMC, and assistant professor of medicine at the University of Montreal.

“In this large, multicenter Mendelian randomization study, our findings support current evidence that children with higher BMI status respond inadequately to inhaled corticosteroids, and that this association is likely not explained by measured confounding or reverse causation,” she said in an oral abstract presentation during the European Respiratory Society International Congress.
 

Unmeasured confounding

The obese-asthma phenotype in children is characterized by reduced lung function, high symptom expression, poor response to ICS, and high health care utilization.

“While most observational studies suggest that weight status is associated with asthma exacerbations, despite using inhaled corticosteroids, it’s unclear whether these associations may be due to unmeasured confounding or reverse causation, which captures the idea that perhaps obesity is a consequence rather than a cause of uncontrolled severe asthma,” she said.

Traditional observational studies of the obesity-asthma link rely on comparing data on asthma in a target population and comparing nonobese patients with obese patients. The problem with this method, Dr. Longo contended, is that the exposure assignment – weight status – is not random, and could lead to bias from potential imbalance of confounders, leading to unintentionally biased results.

In contrast, Mendelian randomization uses genetic data to approximate random assignment of exposures, using a risk score for BMI based on genetic susceptibility. The score is based on the accumulation of genetic variants (single-nucleotide polymorphisms, or SNPs) that predispose individuals to obesity, with higher numbers of variants results in a higher risk score.

The scores are then used to determine the comparison groups for evaluating the obesity-asthma association.
 

Alphabet soup

Dr. Longo and colleagues analyzed data on a total 1,511 children enrolled in four observational studies (PACMAN, PAGES, HPR, CLARA) and one cohort study (ALSPAC).

They included children with an asthma diagnosis who used ICS and had available information on both BMI and genetics.

The Mendelian randomization analysis was based on a weighted allele score based on 97 SNPs predictive of BMI based on large-scale genomewide association studies. The exposure for the analysis was age- and sex-adjusted BMI z scores based on World Health Organization growth charts for children.

They found that using the Mendelian randomization approach, for each standard deviation increase in BMI, the OR for any parent-reported asthma exacerbations, including urgent care visits or use of oral corticosteroids, was 2.31 (95% confidence interval, 1.26-4.25).

In contrast, if the traditional observational model had been used, the OR would be a nonsignificant 1.10 (95% CI, 0.99-1.22).

“Treatment guidelines recommend steroids for children with asthma who have a higher-than-normal BMI,” Dr. Longo said in a statement. “Our research group felt that the one-size fits-all approach to treating children with asthma with inhaled steroids as their first-line treatment, particularly those with excess weight, warrants revision. At the very least, research identifying potential alternative treatments should be encouraged and prioritized, especially since 30% of children with asthma are also obese. With the childhood obesity epidemic rising, we expect this percentage to increase meaning this problem of poor control will be seen more frequently in routine clinical practice.”

Christopher E. Brightling, PhD, professor of respiratory medicine at the University of Leicester (England), commented that “this is very good and fascinating research with findings that are important and novel.

“It sheds light on the complex interplay between genes, weight, and response to inhaled corticosteroids, underscoring the need to combine drug treatments with lifestyle and diet modifications. Policy makers, health care providers and families need to do much more to tackle the growing obesity epidemic in young people,” he said.

Dr. Brightling was not involved in the study.

The study was supported by the ERS and the European Union’s H2020 research and innovation program. Dr. Longo was a Horizon 2020 Marie-Sklodowska Cure Respire-3 fellow. Dr. Brightling reported no relevant disclosures.

Obese or overweight children with asthma could be using inhaled corticosteroids (ICS) to no avail, combined results from observational studies suggest.

Using Mendelian randomization, a method for reducing bias in observational studies, investigators from the University of Amsterdam Medical Center performed an analysis of data from four cross-sectional studies and one cohort study on a total of 1,511 children with asthma.

They showed that every 1-unit increase in the body mass index (BMI) z score was associated with a more than twofold higher odds ratio for exacerbation, reported Cristina Longo, PhD, a former postdoctoral fellow at AMC, and assistant professor of medicine at the University of Montreal.

“In this large, multicenter Mendelian randomization study, our findings support current evidence that children with higher BMI status respond inadequately to inhaled corticosteroids, and that this association is likely not explained by measured confounding or reverse causation,” she said in an oral abstract presentation during the European Respiratory Society International Congress.
 

Unmeasured confounding

The obese-asthma phenotype in children is characterized by reduced lung function, high symptom expression, poor response to ICS, and high health care utilization.

“While most observational studies suggest that weight status is associated with asthma exacerbations, despite using inhaled corticosteroids, it’s unclear whether these associations may be due to unmeasured confounding or reverse causation, which captures the idea that perhaps obesity is a consequence rather than a cause of uncontrolled severe asthma,” she said.

Traditional observational studies of the obesity-asthma link rely on comparing data on asthma in a target population and comparing nonobese patients with obese patients. The problem with this method, Dr. Longo contended, is that the exposure assignment – weight status – is not random, and could lead to bias from potential imbalance of confounders, leading to unintentionally biased results.

In contrast, Mendelian randomization uses genetic data to approximate random assignment of exposures, using a risk score for BMI based on genetic susceptibility. The score is based on the accumulation of genetic variants (single-nucleotide polymorphisms, or SNPs) that predispose individuals to obesity, with higher numbers of variants results in a higher risk score.

The scores are then used to determine the comparison groups for evaluating the obesity-asthma association.
 

Alphabet soup

Dr. Longo and colleagues analyzed data on a total 1,511 children enrolled in four observational studies (PACMAN, PAGES, HPR, CLARA) and one cohort study (ALSPAC).

They included children with an asthma diagnosis who used ICS and had available information on both BMI and genetics.

The Mendelian randomization analysis was based on a weighted allele score based on 97 SNPs predictive of BMI based on large-scale genomewide association studies. The exposure for the analysis was age- and sex-adjusted BMI z scores based on World Health Organization growth charts for children.

They found that using the Mendelian randomization approach, for each standard deviation increase in BMI, the OR for any parent-reported asthma exacerbations, including urgent care visits or use of oral corticosteroids, was 2.31 (95% confidence interval, 1.26-4.25).

In contrast, if the traditional observational model had been used, the OR would be a nonsignificant 1.10 (95% CI, 0.99-1.22).

“Treatment guidelines recommend steroids for children with asthma who have a higher-than-normal BMI,” Dr. Longo said in a statement. “Our research group felt that the one-size fits-all approach to treating children with asthma with inhaled steroids as their first-line treatment, particularly those with excess weight, warrants revision. At the very least, research identifying potential alternative treatments should be encouraged and prioritized, especially since 30% of children with asthma are also obese. With the childhood obesity epidemic rising, we expect this percentage to increase meaning this problem of poor control will be seen more frequently in routine clinical practice.”

Christopher E. Brightling, PhD, professor of respiratory medicine at the University of Leicester (England), commented that “this is very good and fascinating research with findings that are important and novel.

“It sheds light on the complex interplay between genes, weight, and response to inhaled corticosteroids, underscoring the need to combine drug treatments with lifestyle and diet modifications. Policy makers, health care providers and families need to do much more to tackle the growing obesity epidemic in young people,” he said.

Dr. Brightling was not involved in the study.

The study was supported by the ERS and the European Union’s H2020 research and innovation program. Dr. Longo was a Horizon 2020 Marie-Sklodowska Cure Respire-3 fellow. Dr. Brightling reported no relevant disclosures.

Pediatric urine sampling should be used more frequently than current guidelines suggest for ruling out urinary tract infection (UTI), according to a systematic review and meta-analysis of diagnostic test accuracy studies in ambulatory care (Ann Fam Med 2021;19:437-46).

“Urine sampling is often restricted to children with clinical features such as pain while urinating, frequent urination or children presenting with fever without any abnormalities found on clinical examination,” said lead author Jan Y. Verbakel, MD, PhD, from the University of Leuven (Belgium) in an interview. “Our study findings suggest that, in children, pain while urinating or frequent urination are less accurate than in adults and increase the probability of UTI only moderately.”

Urine sampling “should be applied more broadly in ambulatory care, given that appropriate sampling techniques are available,” he and his coauthors advised in the paper.

Methods and results

The analysis included 35 studies, involving a total of 78,427 patients, which provided information on 58 clinical features and 6 prediction rules of UTI, compared with urine culture. For urine sampling, most studies used catheterization (n = 23), suprapubic aspiration (n = 17), or midstream catch (n = 14), and fewer studies used clean catch (n = 7), bag specimens (n = 5), or diaper pads (n = 2).

The study showed that only three features substantially decreased the likelihood of UTI: being circumcised, the presence of stridor, and the presence of diaper rash. “In febrile children, finding an apparent source of infection decreased the probability of UTI; however, this was not useful for ruling out UTI by itself,” the authors noted.

Additionally, they found that red flags for UTI were cloudy or malodorous urine, hematuria, no fluid intake, suprapubic tenderness, and loin tenderness.

Study implications

“We recommend to sample urine in children that have one or more features that increase the probability of UTI … and less so pain while urinating, frequent urination, urgency, bed wetting, or previous UTI history,” said Dr. Verbakel, who is also a researcher at the University of Oxford (England).

In terms of prediction rules, the analysis showed the Diagnosis of Urinary Tract Infection in Young Children (DUTY) score, Gorelick Scale score, and UTIcalc might be useful to identify which children should have urine sampling, the authors stated in the paper.

Specifically, a DUTY clean-catch score of less than one point was useful for ruling out UTI in children aged less than 5 years, and in girls aged less than 3 years with unexplained fever. The Gorelick Scale score was useful for ruling out UTI when less than two of five variables were present.

“The present meta-analyses confirm that few clinical features are useful for diagnosing or ruling out UTI without further urine analysis. Signs and symptoms combined in a clinical prediction rule, such as with the DUTY or UTIcalc score, might increase accuracy for ruling out UTI; however, these should be validated externally,” Dr. Verbakel said in an interview.

Is urine sampling guideline too broad?

Commenting on the new paper, Martin Koyle, MD, former division chief of urology at the Hospital for Sick Children and professor of surgery at the University of Toronto, expressed concern that unexplained fever is not included as a “differentiating” red flag.

“Many contemporary guidelines define fever as an important diagnostic symptom, as the goal truly is to differentiate lower urinary tract from actual kidney infection, the latter thought to be more important for severity of illness, and potential for developing kidney damage,” he said in an interview. “It begs the question as to which nonfebrile patients who don’t have symptoms related to the respiratory tract for instance [for example, stridor], should be under suspicion for an afebrile urinary tract infection, and have their urine sampled. This paper does not answer that question.”

Dr. Koyle added that an overly broad guideline for urine sampling could come at a cost, and he raised the following questions.

“Will there be an overdiagnosis based on urines alone? Will this lead to overtreatment, often unnecessary, just because there is a positive urine specimen or asymptomatic bacteriuria? Will overtreatment lead to resistant bacteria and side effects related to antibiotics? Will such treatment actually prevent clinical illness and/or renal damage?”

The study authors and Dr. Koyle reported no conflicts of interest.

Pediatric urine sampling should be used more frequently than current guidelines suggest for ruling out urinary tract infection (UTI), according to a systematic review and meta-analysis of diagnostic test accuracy studies in ambulatory care (Ann Fam Med 2021;19:437-46).

“Urine sampling is often restricted to children with clinical features such as pain while urinating, frequent urination or children presenting with fever without any abnormalities found on clinical examination,” said lead author Jan Y. Verbakel, MD, PhD, from the University of Leuven (Belgium) in an interview. “Our study findings suggest that, in children, pain while urinating or frequent urination are less accurate than in adults and increase the probability of UTI only moderately.”

Urine sampling “should be applied more broadly in ambulatory care, given that appropriate sampling techniques are available,” he and his coauthors advised in the paper.

Methods and results

The analysis included 35 studies, involving a total of 78,427 patients, which provided information on 58 clinical features and 6 prediction rules of UTI, compared with urine culture. For urine sampling, most studies used catheterization (n = 23), suprapubic aspiration (n = 17), or midstream catch (n = 14), and fewer studies used clean catch (n = 7), bag specimens (n = 5), or diaper pads (n = 2).

The study showed that only three features substantially decreased the likelihood of UTI: being circumcised, the presence of stridor, and the presence of diaper rash. “In febrile children, finding an apparent source of infection decreased the probability of UTI; however, this was not useful for ruling out UTI by itself,” the authors noted.

Additionally, they found that red flags for UTI were cloudy or malodorous urine, hematuria, no fluid intake, suprapubic tenderness, and loin tenderness.

Study implications

“We recommend to sample urine in children that have one or more features that increase the probability of UTI … and less so pain while urinating, frequent urination, urgency, bed wetting, or previous UTI history,” said Dr. Verbakel, who is also a researcher at the University of Oxford (England).

In terms of prediction rules, the analysis showed the Diagnosis of Urinary Tract Infection in Young Children (DUTY) score, Gorelick Scale score, and UTIcalc might be useful to identify which children should have urine sampling, the authors stated in the paper.

Specifically, a DUTY clean-catch score of less than one point was useful for ruling out UTI in children aged less than 5 years, and in girls aged less than 3 years with unexplained fever. The Gorelick Scale score was useful for ruling out UTI when less than two of five variables were present.

“The present meta-analyses confirm that few clinical features are useful for diagnosing or ruling out UTI without further urine analysis. Signs and symptoms combined in a clinical prediction rule, such as with the DUTY or UTIcalc score, might increase accuracy for ruling out UTI; however, these should be validated externally,” Dr. Verbakel said in an interview.

Is urine sampling guideline too broad?

Commenting on the new paper, Martin Koyle, MD, former division chief of urology at the Hospital for Sick Children and professor of surgery at the University of Toronto, expressed concern that unexplained fever is not included as a “differentiating” red flag.

“Many contemporary guidelines define fever as an important diagnostic symptom, as the goal truly is to differentiate lower urinary tract from actual kidney infection, the latter thought to be more important for severity of illness, and potential for developing kidney damage,” he said in an interview. “It begs the question as to which nonfebrile patients who don’t have symptoms related to the respiratory tract for instance [for example, stridor], should be under suspicion for an afebrile urinary tract infection, and have their urine sampled. This paper does not answer that question.”

Dr. Koyle added that an overly broad guideline for urine sampling could come at a cost, and he raised the following questions.

“Will there be an overdiagnosis based on urines alone? Will this lead to overtreatment, often unnecessary, just because there is a positive urine specimen or asymptomatic bacteriuria? Will overtreatment lead to resistant bacteria and side effects related to antibiotics? Will such treatment actually prevent clinical illness and/or renal damage?”

The study authors and Dr. Koyle reported no conflicts of interest.

Pediatric urine sampling should be used more frequently than current guidelines suggest for ruling out urinary tract infection (UTI), according to a systematic review and meta-analysis of diagnostic test accuracy studies in ambulatory care (Ann Fam Med 2021;19:437-46).

“Urine sampling is often restricted to children with clinical features such as pain while urinating, frequent urination or children presenting with fever without any abnormalities found on clinical examination,” said lead author Jan Y. Verbakel, MD, PhD, from the University of Leuven (Belgium) in an interview. “Our study findings suggest that, in children, pain while urinating or frequent urination are less accurate than in adults and increase the probability of UTI only moderately.”

Urine sampling “should be applied more broadly in ambulatory care, given that appropriate sampling techniques are available,” he and his coauthors advised in the paper.

Methods and results

The analysis included 35 studies, involving a total of 78,427 patients, which provided information on 58 clinical features and 6 prediction rules of UTI, compared with urine culture. For urine sampling, most studies used catheterization (n = 23), suprapubic aspiration (n = 17), or midstream catch (n = 14), and fewer studies used clean catch (n = 7), bag specimens (n = 5), or diaper pads (n = 2).

The study showed that only three features substantially decreased the likelihood of UTI: being circumcised, the presence of stridor, and the presence of diaper rash. “In febrile children, finding an apparent source of infection decreased the probability of UTI; however, this was not useful for ruling out UTI by itself,” the authors noted.

Additionally, they found that red flags for UTI were cloudy or malodorous urine, hematuria, no fluid intake, suprapubic tenderness, and loin tenderness.

Study implications

“We recommend to sample urine in children that have one or more features that increase the probability of UTI … and less so pain while urinating, frequent urination, urgency, bed wetting, or previous UTI history,” said Dr. Verbakel, who is also a researcher at the University of Oxford (England).

In terms of prediction rules, the analysis showed the Diagnosis of Urinary Tract Infection in Young Children (DUTY) score, Gorelick Scale score, and UTIcalc might be useful to identify which children should have urine sampling, the authors stated in the paper.

Specifically, a DUTY clean-catch score of less than one point was useful for ruling out UTI in children aged less than 5 years, and in girls aged less than 3 years with unexplained fever. The Gorelick Scale score was useful for ruling out UTI when less than two of five variables were present.

“The present meta-analyses confirm that few clinical features are useful for diagnosing or ruling out UTI without further urine analysis. Signs and symptoms combined in a clinical prediction rule, such as with the DUTY or UTIcalc score, might increase accuracy for ruling out UTI; however, these should be validated externally,” Dr. Verbakel said in an interview.

Is urine sampling guideline too broad?

Commenting on the new paper, Martin Koyle, MD, former division chief of urology at the Hospital for Sick Children and professor of surgery at the University of Toronto, expressed concern that unexplained fever is not included as a “differentiating” red flag.

“Many contemporary guidelines define fever as an important diagnostic symptom, as the goal truly is to differentiate lower urinary tract from actual kidney infection, the latter thought to be more important for severity of illness, and potential for developing kidney damage,” he said in an interview. “It begs the question as to which nonfebrile patients who don’t have symptoms related to the respiratory tract for instance [for example, stridor], should be under suspicion for an afebrile urinary tract infection, and have their urine sampled. This paper does not answer that question.”

Dr. Koyle added that an overly broad guideline for urine sampling could come at a cost, and he raised the following questions.

“Will there be an overdiagnosis based on urines alone? Will this lead to overtreatment, often unnecessary, just because there is a positive urine specimen or asymptomatic bacteriuria? Will overtreatment lead to resistant bacteria and side effects related to antibiotics? Will such treatment actually prevent clinical illness and/or renal damage?”

The study authors and Dr. Koyle reported no conflicts of interest.

A new study may help doctors assess the long-term risk for major bleeding if anticoagulation for unprovoked venous thromboembolisms (VTE) is continued beyond 3-6 months.

The meta-analysis of data from 27 studies with 17,202 patients was published in the Annals of Internal Medicine. According to two of the paper’s coauthors, Faizan Khan, MSc, and Marc A. Rodger, MD, it “provides best available estimates of long-term bleeding risk with different anticoagulants in patients with unprovoked VTE,” including subgroups at increased risk.

Patients at increased risk for major bleeding include those who are older; those using antiplatelet therapy; and patients with kidney disease, a history of bleeding, or anemia, noted the coauthors, who work for the Ottawa Hospital Research Institute.

The researchers focused on randomized controlled trials (RCTs) and prospective cohort studies that reported major bleeding among patients with a first unprovoked or weakly provoked VTE who received oral anticoagulation for at least 6 months beyond an initial anticoagulant treatment course of at least 3 months.

The investigators analyzed data from 14 RCTs and 13 cohort studies. In all, 9,982 patients received a vitamin K antagonist (VKA), and 7,220 received a direct oral anticoagulant (DOAC).

The incidence of major bleeding per 100 person-years was 1.7 events with VKAs, compared with 1.1 events with DOACs. The researchers estimated that the 5-year cumulative incidence of major bleeding with VKAs was 6.3%. The available data for DOACs were insufficient to estimate the incidence of major bleeding beyond 1 year.

“This information can help clinicians counsel patients and inform shared decision-making about extended therapy,” the researchers said.

Risks of serious bleeding ‘not trivial’

Margaret Fang, MD, with the University of California, San Francisco, agreed that the study can help clinicians and patients weigh the risks of extended anticoagulation for common types of VTE.

The study also “highlights that the risks of serious bleeding are not trivial” and points out gaps in the literature regarding the long-term use of DOACs for extended VTE therapy, Dr. Fang said.

Better ways to predict which patients will develop bleeding on anticoagulants are needed, Dr. Fang added. “It will also be important to establish which of the various therapies for preventing recurrent VTE – full dose versus lowered dose, or even aspirin – has the best balance of safety and efficacy,” she said.

‘Standardized approach’ for identifying high-risk patients lacking

Clinical practice guidelines recommend indefinite anticoagulation for an unprovoked VTE, except when patients are at high risk of bleeding, the authors noted. But clinicians lack a “standardized approach to identify patients at high risk of bleeding,” Mr. Khan and Dr. Rodger said. “Evidence from randomized trials on net long-term benefit of extended therapy is limited, and current guideline recommendations are largely based on expert consensus opinion. Major bleeding events are two to three times more likely to be fatal than recurrent VTE events, so extended therapy is not always associated with a net mortality benefit, particularly in patients at low risk of recurrent VTE or high risk of bleeding.”

The analysis indicates that there is “a clinically meaningful difference in long-term risk for anticoagulant-related major bleeding among patients with a first unprovoked VTE stratified according to presence or absence of the following risk factors: age older than 65 years, creatinine clearance less than 50 mL/min, history of bleeding, concomitant use of antiplatelet therapy, and hemoglobin level less than 100 g/L,” the authors said.

For example, the researchers found that the incidence of major bleeding was higher among those older than 65 years, compared with younger patients (incidence rate ratio, 1.84 with VKAs and 2.92 with DOACs), and among those with creatinine clearance less than 50 mL/min (IRR, 2.83 with VKAs and 3.71 with DOACs).

The case-fatality rate of major bleeding was 8.3% with VKAs and 9.7% with DOACs.

The study received funding from the Canadian Institutes of Health Research. Some of the coauthors are employees of or have financial ties to pharmaceutical companies. Mr. Khan, Dr. Rodger, and Dr. Fang had no relevant disclosures.

jremaly@mdedge.com

A new study may help doctors assess the long-term risk for major bleeding if anticoagulation for unprovoked venous thromboembolisms (VTE) is continued beyond 3-6 months.

The meta-analysis of data from 27 studies with 17,202 patients was published in the Annals of Internal Medicine. According to two of the paper’s coauthors, Faizan Khan, MSc, and Marc A. Rodger, MD, it “provides best available estimates of long-term bleeding risk with different anticoagulants in patients with unprovoked VTE,” including subgroups at increased risk.

Patients at increased risk for major bleeding include those who are older; those using antiplatelet therapy; and patients with kidney disease, a history of bleeding, or anemia, noted the coauthors, who work for the Ottawa Hospital Research Institute.

The researchers focused on randomized controlled trials (RCTs) and prospective cohort studies that reported major bleeding among patients with a first unprovoked or weakly provoked VTE who received oral anticoagulation for at least 6 months beyond an initial anticoagulant treatment course of at least 3 months.

The investigators analyzed data from 14 RCTs and 13 cohort studies. In all, 9,982 patients received a vitamin K antagonist (VKA), and 7,220 received a direct oral anticoagulant (DOAC).

The incidence of major bleeding per 100 person-years was 1.7 events with VKAs, compared with 1.1 events with DOACs. The researchers estimated that the 5-year cumulative incidence of major bleeding with VKAs was 6.3%. The available data for DOACs were insufficient to estimate the incidence of major bleeding beyond 1 year.

“This information can help clinicians counsel patients and inform shared decision-making about extended therapy,” the researchers said.

Risks of serious bleeding ‘not trivial’

Margaret Fang, MD, with the University of California, San Francisco, agreed that the study can help clinicians and patients weigh the risks of extended anticoagulation for common types of VTE.

The study also “highlights that the risks of serious bleeding are not trivial” and points out gaps in the literature regarding the long-term use of DOACs for extended VTE therapy, Dr. Fang said.

Better ways to predict which patients will develop bleeding on anticoagulants are needed, Dr. Fang added. “It will also be important to establish which of the various therapies for preventing recurrent VTE – full dose versus lowered dose, or even aspirin – has the best balance of safety and efficacy,” she said.

‘Standardized approach’ for identifying high-risk patients lacking

Clinical practice guidelines recommend indefinite anticoagulation for an unprovoked VTE, except when patients are at high risk of bleeding, the authors noted. But clinicians lack a “standardized approach to identify patients at high risk of bleeding,” Mr. Khan and Dr. Rodger said. “Evidence from randomized trials on net long-term benefit of extended therapy is limited, and current guideline recommendations are largely based on expert consensus opinion. Major bleeding events are two to three times more likely to be fatal than recurrent VTE events, so extended therapy is not always associated with a net mortality benefit, particularly in patients at low risk of recurrent VTE or high risk of bleeding.”

The analysis indicates that there is “a clinically meaningful difference in long-term risk for anticoagulant-related major bleeding among patients with a first unprovoked VTE stratified according to presence or absence of the following risk factors: age older than 65 years, creatinine clearance less than 50 mL/min, history of bleeding, concomitant use of antiplatelet therapy, and hemoglobin level less than 100 g/L,” the authors said.

For example, the researchers found that the incidence of major bleeding was higher among those older than 65 years, compared with younger patients (incidence rate ratio, 1.84 with VKAs and 2.92 with DOACs), and among those with creatinine clearance less than 50 mL/min (IRR, 2.83 with VKAs and 3.71 with DOACs).

The case-fatality rate of major bleeding was 8.3% with VKAs and 9.7% with DOACs.

The study received funding from the Canadian Institutes of Health Research. Some of the coauthors are employees of or have financial ties to pharmaceutical companies. Mr. Khan, Dr. Rodger, and Dr. Fang had no relevant disclosures.

jremaly@mdedge.com

A new study may help doctors assess the long-term risk for major bleeding if anticoagulation for unprovoked venous thromboembolisms (VTE) is continued beyond 3-6 months.

The meta-analysis of data from 27 studies with 17,202 patients was published in the Annals of Internal Medicine. According to two of the paper’s coauthors, Faizan Khan, MSc, and Marc A. Rodger, MD, it “provides best available estimates of long-term bleeding risk with different anticoagulants in patients with unprovoked VTE,” including subgroups at increased risk.

Patients at increased risk for major bleeding include those who are older; those using antiplatelet therapy; and patients with kidney disease, a history of bleeding, or anemia, noted the coauthors, who work for the Ottawa Hospital Research Institute.

The researchers focused on randomized controlled trials (RCTs) and prospective cohort studies that reported major bleeding among patients with a first unprovoked or weakly provoked VTE who received oral anticoagulation for at least 6 months beyond an initial anticoagulant treatment course of at least 3 months.

The investigators analyzed data from 14 RCTs and 13 cohort studies. In all, 9,982 patients received a vitamin K antagonist (VKA), and 7,220 received a direct oral anticoagulant (DOAC).

The incidence of major bleeding per 100 person-years was 1.7 events with VKAs, compared with 1.1 events with DOACs. The researchers estimated that the 5-year cumulative incidence of major bleeding with VKAs was 6.3%. The available data for DOACs were insufficient to estimate the incidence of major bleeding beyond 1 year.

“This information can help clinicians counsel patients and inform shared decision-making about extended therapy,” the researchers said.

Risks of serious bleeding ‘not trivial’

Margaret Fang, MD, with the University of California, San Francisco, agreed that the study can help clinicians and patients weigh the risks of extended anticoagulation for common types of VTE.

The study also “highlights that the risks of serious bleeding are not trivial” and points out gaps in the literature regarding the long-term use of DOACs for extended VTE therapy, Dr. Fang said.

Better ways to predict which patients will develop bleeding on anticoagulants are needed, Dr. Fang added. “It will also be important to establish which of the various therapies for preventing recurrent VTE – full dose versus lowered dose, or even aspirin – has the best balance of safety and efficacy,” she said.

‘Standardized approach’ for identifying high-risk patients lacking

Clinical practice guidelines recommend indefinite anticoagulation for an unprovoked VTE, except when patients are at high risk of bleeding, the authors noted. But clinicians lack a “standardized approach to identify patients at high risk of bleeding,” Mr. Khan and Dr. Rodger said. “Evidence from randomized trials on net long-term benefit of extended therapy is limited, and current guideline recommendations are largely based on expert consensus opinion. Major bleeding events are two to three times more likely to be fatal than recurrent VTE events, so extended therapy is not always associated with a net mortality benefit, particularly in patients at low risk of recurrent VTE or high risk of bleeding.”

The analysis indicates that there is “a clinically meaningful difference in long-term risk for anticoagulant-related major bleeding among patients with a first unprovoked VTE stratified according to presence or absence of the following risk factors: age older than 65 years, creatinine clearance less than 50 mL/min, history of bleeding, concomitant use of antiplatelet therapy, and hemoglobin level less than 100 g/L,” the authors said.

For example, the researchers found that the incidence of major bleeding was higher among those older than 65 years, compared with younger patients (incidence rate ratio, 1.84 with VKAs and 2.92 with DOACs), and among those with creatinine clearance less than 50 mL/min (IRR, 2.83 with VKAs and 3.71 with DOACs).

The case-fatality rate of major bleeding was 8.3% with VKAs and 9.7% with DOACs.

The study received funding from the Canadian Institutes of Health Research. Some of the coauthors are employees of or have financial ties to pharmaceutical companies. Mr. Khan, Dr. Rodger, and Dr. Fang had no relevant disclosures.

jremaly@mdedge.com

Pfizer’s COVID-19 vaccine could be authorized for ages 5-11 by the end of October, according to Reuters.

The timeline is based on the expectation that Pfizer will have enough data from clinical trials to request Food and Drug Administration emergency use authorization for the age group near the end of September. Then the FDA would likely make a decision about the vaccine’s safety and effectiveness in children within about 3 weeks, two sources told Reuters.

Anthony Fauci, MD, chief medical adviser to President Joe Biden and director of the National Institute of Allergy and Infectious Diseases, spoke about the timeline during an online town hall meeting Friday, Reuters reported. The meeting was attended by thousands of staff members at the National Institutes of Health.

If Pfizer submits paperwork to the FDA by the end of September, the vaccine could be available for kids around mid-October, Dr. Fauci said, and approval for the Moderna vaccine could come in November. Moderna will take about 3 weeks longer to collect and analyze data for ages 5-11.

Pfizer has said it would have enough data for ages 5-11 in September and would submit its documentation for FDA authorization soon after. Moderna told investors on Sept. 9 that data for ages 6-11 would be available by the end of the year.

On Sept. 10, the FDA said it would work to approve COVID-19 vaccines for children quickly once companies submit their data, according to Reuters. The agency said it would consider applications for emergency use, which would allow for faster approval.

Pfizer’s vaccine is the only one to receive full FDA approval, but only for people ages 16 and older. Adolescents ages 12-15 can receive the Pfizer vaccine under the FDA’s emergency use authorization.

For emergency use authorization, companies must submit 2 months of safety data versus 6 months for full approval. The FDA said on Sept. 10 that children in clinical trials should be monitored for at least 2 months to observe side effects.

BioNTech, Pfizer’s vaccine manufacturing partner, told a news outlet in Germany that it plans to request authorization globally for ages 5-11 in coming weeks, according to Reuters.

“Already over the next few weeks, we will file the results of our trial in 5- to 11-year-olds with regulators across the world and will request approval of the vaccine in this age group, also here in Europe,” Oezlem Tuereci, MD, the chief medical officer for BioNTech, told Der Spiegel.

The company is completing the final production steps to make the vaccine at lower doses for the younger age group, she said. Pfizer and BioNTech will also seek vaccine approval for ages 6 months to 2 years later this year.

“Things are looking good, everything is going according to plan,” Ugur Sahin, MD, the CEO of BioNTech, told Der Spiegel.

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

Pfizer’s COVID-19 vaccine could be authorized for ages 5-11 by the end of October, according to Reuters.

The timeline is based on the expectation that Pfizer will have enough data from clinical trials to request Food and Drug Administration emergency use authorization for the age group near the end of September. Then the FDA would likely make a decision about the vaccine’s safety and effectiveness in children within about 3 weeks, two sources told Reuters.

Anthony Fauci, MD, chief medical adviser to President Joe Biden and director of the National Institute of Allergy and Infectious Diseases, spoke about the timeline during an online town hall meeting Friday, Reuters reported. The meeting was attended by thousands of staff members at the National Institutes of Health.

If Pfizer submits paperwork to the FDA by the end of September, the vaccine could be available for kids around mid-October, Dr. Fauci said, and approval for the Moderna vaccine could come in November. Moderna will take about 3 weeks longer to collect and analyze data for ages 5-11.

Pfizer has said it would have enough data for ages 5-11 in September and would submit its documentation for FDA authorization soon after. Moderna told investors on Sept. 9 that data for ages 6-11 would be available by the end of the year.

On Sept. 10, the FDA said it would work to approve COVID-19 vaccines for children quickly once companies submit their data, according to Reuters. The agency said it would consider applications for emergency use, which would allow for faster approval.

Pfizer’s vaccine is the only one to receive full FDA approval, but only for people ages 16 and older. Adolescents ages 12-15 can receive the Pfizer vaccine under the FDA’s emergency use authorization.

For emergency use authorization, companies must submit 2 months of safety data versus 6 months for full approval. The FDA said on Sept. 10 that children in clinical trials should be monitored for at least 2 months to observe side effects.

BioNTech, Pfizer’s vaccine manufacturing partner, told a news outlet in Germany that it plans to request authorization globally for ages 5-11 in coming weeks, according to Reuters.

“Already over the next few weeks, we will file the results of our trial in 5- to 11-year-olds with regulators across the world and will request approval of the vaccine in this age group, also here in Europe,” Oezlem Tuereci, MD, the chief medical officer for BioNTech, told Der Spiegel.

The company is completing the final production steps to make the vaccine at lower doses for the younger age group, she said. Pfizer and BioNTech will also seek vaccine approval for ages 6 months to 2 years later this year.

“Things are looking good, everything is going according to plan,” Ugur Sahin, MD, the CEO of BioNTech, told Der Spiegel.

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

Pfizer’s COVID-19 vaccine could be authorized for ages 5-11 by the end of October, according to Reuters.

The timeline is based on the expectation that Pfizer will have enough data from clinical trials to request Food and Drug Administration emergency use authorization for the age group near the end of September. Then the FDA would likely make a decision about the vaccine’s safety and effectiveness in children within about 3 weeks, two sources told Reuters.

Anthony Fauci, MD, chief medical adviser to President Joe Biden and director of the National Institute of Allergy and Infectious Diseases, spoke about the timeline during an online town hall meeting Friday, Reuters reported. The meeting was attended by thousands of staff members at the National Institutes of Health.

If Pfizer submits paperwork to the FDA by the end of September, the vaccine could be available for kids around mid-October, Dr. Fauci said, and approval for the Moderna vaccine could come in November. Moderna will take about 3 weeks longer to collect and analyze data for ages 5-11.

Pfizer has said it would have enough data for ages 5-11 in September and would submit its documentation for FDA authorization soon after. Moderna told investors on Sept. 9 that data for ages 6-11 would be available by the end of the year.

On Sept. 10, the FDA said it would work to approve COVID-19 vaccines for children quickly once companies submit their data, according to Reuters. The agency said it would consider applications for emergency use, which would allow for faster approval.

Pfizer’s vaccine is the only one to receive full FDA approval, but only for people ages 16 and older. Adolescents ages 12-15 can receive the Pfizer vaccine under the FDA’s emergency use authorization.

For emergency use authorization, companies must submit 2 months of safety data versus 6 months for full approval. The FDA said on Sept. 10 that children in clinical trials should be monitored for at least 2 months to observe side effects.

BioNTech, Pfizer’s vaccine manufacturing partner, told a news outlet in Germany that it plans to request authorization globally for ages 5-11 in coming weeks, according to Reuters.

“Already over the next few weeks, we will file the results of our trial in 5- to 11-year-olds with regulators across the world and will request approval of the vaccine in this age group, also here in Europe,” Oezlem Tuereci, MD, the chief medical officer for BioNTech, told Der Spiegel.

The company is completing the final production steps to make the vaccine at lower doses for the younger age group, she said. Pfizer and BioNTech will also seek vaccine approval for ages 6 months to 2 years later this year.

“Things are looking good, everything is going according to plan,” Ugur Sahin, MD, the CEO of BioNTech, told Der Spiegel.

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

The White House has filled in more details of its newly announced plans to blunt the impact of COVID-19 in the United States.

The emergency rule ordering large employers to require COVID-19 vaccines or weekly tests for their workers could be ready “within weeks,” officials said in a news briefing Sept. 10.

Labor Secretary Martin Walsh will oversee the Occupational Safety and Health Administration as the agency drafts what’s known as an emergency temporary standard, similar to the one that was issued a few months ago to protect health care workers during the pandemic.

The rule should be ready within weeks, said Jeff Zients, coordinator of the White House COVID-19 response team.

He said the ultimate goal of the president’s plan is to increase vaccinations as quickly as possible to keep schools open, the economy recovering, and to decrease hospitalizations and deaths from COVID.

Mr. Zients declined to set hard numbers around those goals, but other experts did.

“What we need to get to is 85% to 90% population immunity, and that’s going to be immunity both from vaccines and infections, before that really begins to have a substantial dampening effect on viral spread,” Ashish Jha, MD, dean of the Brown University School of Public Health, Providence, R.I., said on a call with reporters Sept. 9.

He said immunity needs to be that high because the Delta variant is so contagious.

Mandates are seen as the most effective way to increase immunity and do it quickly.

David Michaels, PhD, an epidemiologist and professor at George Washington University, Washington, says OSHA will have to work through a number of steps to develop the rule.

“OSHA will have to write a preamble explaining the standard, its justifications, its costs, and how it will be enforced,” says Dr. Michaels, who led OSHA for the Obama administration. After that, the rule will be reviewed by the White House. Then employers will have some time – typically 30 days – to comply.

In addition to drafting the standard, OSHA will oversee its enforcement.

Companies that refuse to follow the standard could be fined $13,600 per violation, Mr. Zients said.

Dr. Michaels said he doesn’t expect enforcement to be a big issue, and he said we’re likely to see the rule well before it is final.

“Most employers are law-abiding. When OSHA issues a standard, they try to meet whatever those requirements are, and generally that starts to happen when the rule is announced, even before it goes into effect,” he said.

The rule may face legal challenges as well. Several governors and state attorneys general, as well as the Republican National Committee, have promised lawsuits to stop the vaccine mandates.

Critics of the new mandates say they impinge on personal freedom and impose burdens on businesses.

But the president hit back at that notion Sept. 10.

“Look, I am so disappointed that, particularly some of the Republican governors, have been so cavalier with the health of these kids, so cavalier of the health of their communities,” President Biden told reporters.

“I don’t know of any scientist out there in this field who doesn’t think it makes considerable sense to do the six things I’ve suggested.”

Yet, others feel the new requirements didn’t go far enough.

“These are good steps in the right direction, but they’re not enough to get the job done,” said Leana Wen, MD, in an op-ed for The Washington Post.

Dr. Wen, an expert in public health, wondered why President Biden didn’t mandate vaccinations for plane and train travel. She was disappointed that children 12 and older weren’t required to be vaccinated, too.

“There are mandates for childhood immunizations in every state. The coronavirus vaccine should be no different,” she wrote.

Vaccines remain the cornerstone of U.S. plans to control the pandemic.

On Sept. 10, there was new research from the CDC and state health departments showing that the COVID-19 vaccines continue to be highly effective at preventing severe illness and death.

But the study also found that the vaccines became less effective in the United States after Delta became the dominant cause of infections here.

The study, which included more than 600,000 COVID-19 cases, analyzed breakthrough infections – cases where people got sick despite being fully vaccinated – in 13 jurisdictions in the United States between April 4 and July 17, 2021.

Epidemiologists compared breakthrough infections between two distinct points in time: Before and after the period when the Delta variant began causing most infections.

From April 4 to June 19, fully vaccinated people made up just 5% of cases, 7% of hospitalizations, and 8% of deaths. From June 20 to July 17, 18% of cases, 14% of hospitalizations, and 16% of deaths occurred in fully vaccinated people.

“After the week of June 20, 2021, when the SARS-CoV-2 Delta variant became predominant, the percentage of fully vaccinated persons among cases increased more than expected,” the study authors wrote.

Even after Delta swept the United States, fully vaccinated people were 5 times less likely to get a COVID-19 infection and more than 10 times less likely to be hospitalized or die from one.

“As we have shown in study after study, vaccination works,” CDC Director Rochelle Walensky, MD, said during the White House news briefing.

“We have the scientific tools we need to turn the corner on this pandemic. Vaccination works and will protect us from the severe complications of COVID-19,” she said.

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

The White House has filled in more details of its newly announced plans to blunt the impact of COVID-19 in the United States.

The emergency rule ordering large employers to require COVID-19 vaccines or weekly tests for their workers could be ready “within weeks,” officials said in a news briefing Sept. 10.

Labor Secretary Martin Walsh will oversee the Occupational Safety and Health Administration as the agency drafts what’s known as an emergency temporary standard, similar to the one that was issued a few months ago to protect health care workers during the pandemic.

The rule should be ready within weeks, said Jeff Zients, coordinator of the White House COVID-19 response team.

He said the ultimate goal of the president’s plan is to increase vaccinations as quickly as possible to keep schools open, the economy recovering, and to decrease hospitalizations and deaths from COVID.

Mr. Zients declined to set hard numbers around those goals, but other experts did.

“What we need to get to is 85% to 90% population immunity, and that’s going to be immunity both from vaccines and infections, before that really begins to have a substantial dampening effect on viral spread,” Ashish Jha, MD, dean of the Brown University School of Public Health, Providence, R.I., said on a call with reporters Sept. 9.

He said immunity needs to be that high because the Delta variant is so contagious.

Mandates are seen as the most effective way to increase immunity and do it quickly.

David Michaels, PhD, an epidemiologist and professor at George Washington University, Washington, says OSHA will have to work through a number of steps to develop the rule.

“OSHA will have to write a preamble explaining the standard, its justifications, its costs, and how it will be enforced,” says Dr. Michaels, who led OSHA for the Obama administration. After that, the rule will be reviewed by the White House. Then employers will have some time – typically 30 days – to comply.

In addition to drafting the standard, OSHA will oversee its enforcement.

Companies that refuse to follow the standard could be fined $13,600 per violation, Mr. Zients said.

Dr. Michaels said he doesn’t expect enforcement to be a big issue, and he said we’re likely to see the rule well before it is final.

“Most employers are law-abiding. When OSHA issues a standard, they try to meet whatever those requirements are, and generally that starts to happen when the rule is announced, even before it goes into effect,” he said.

The rule may face legal challenges as well. Several governors and state attorneys general, as well as the Republican National Committee, have promised lawsuits to stop the vaccine mandates.

Critics of the new mandates say they impinge on personal freedom and impose burdens on businesses.

But the president hit back at that notion Sept. 10.

“Look, I am so disappointed that, particularly some of the Republican governors, have been so cavalier with the health of these kids, so cavalier of the health of their communities,” President Biden told reporters.

“I don’t know of any scientist out there in this field who doesn’t think it makes considerable sense to do the six things I’ve suggested.”

Yet, others feel the new requirements didn’t go far enough.

“These are good steps in the right direction, but they’re not enough to get the job done,” said Leana Wen, MD, in an op-ed for The Washington Post.

Dr. Wen, an expert in public health, wondered why President Biden didn’t mandate vaccinations for plane and train travel. She was disappointed that children 12 and older weren’t required to be vaccinated, too.

“There are mandates for childhood immunizations in every state. The coronavirus vaccine should be no different,” she wrote.

Vaccines remain the cornerstone of U.S. plans to control the pandemic.

On Sept. 10, there was new research from the CDC and state health departments showing that the COVID-19 vaccines continue to be highly effective at preventing severe illness and death.

But the study also found that the vaccines became less effective in the United States after Delta became the dominant cause of infections here.

The study, which included more than 600,000 COVID-19 cases, analyzed breakthrough infections – cases where people got sick despite being fully vaccinated – in 13 jurisdictions in the United States between April 4 and July 17, 2021.

Epidemiologists compared breakthrough infections between two distinct points in time: Before and after the period when the Delta variant began causing most infections.

From April 4 to June 19, fully vaccinated people made up just 5% of cases, 7% of hospitalizations, and 8% of deaths. From June 20 to July 17, 18% of cases, 14% of hospitalizations, and 16% of deaths occurred in fully vaccinated people.

“After the week of June 20, 2021, when the SARS-CoV-2 Delta variant became predominant, the percentage of fully vaccinated persons among cases increased more than expected,” the study authors wrote.

Even after Delta swept the United States, fully vaccinated people were 5 times less likely to get a COVID-19 infection and more than 10 times less likely to be hospitalized or die from one.

“As we have shown in study after study, vaccination works,” CDC Director Rochelle Walensky, MD, said during the White House news briefing.

“We have the scientific tools we need to turn the corner on this pandemic. Vaccination works and will protect us from the severe complications of COVID-19,” she said.

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

The White House has filled in more details of its newly announced plans to blunt the impact of COVID-19 in the United States.

The emergency rule ordering large employers to require COVID-19 vaccines or weekly tests for their workers could be ready “within weeks,” officials said in a news briefing Sept. 10.

Labor Secretary Martin Walsh will oversee the Occupational Safety and Health Administration as the agency drafts what’s known as an emergency temporary standard, similar to the one that was issued a few months ago to protect health care workers during the pandemic.

The rule should be ready within weeks, said Jeff Zients, coordinator of the White House COVID-19 response team.

He said the ultimate goal of the president’s plan is to increase vaccinations as quickly as possible to keep schools open, the economy recovering, and to decrease hospitalizations and deaths from COVID.

Mr. Zients declined to set hard numbers around those goals, but other experts did.

“What we need to get to is 85% to 90% population immunity, and that’s going to be immunity both from vaccines and infections, before that really begins to have a substantial dampening effect on viral spread,” Ashish Jha, MD, dean of the Brown University School of Public Health, Providence, R.I., said on a call with reporters Sept. 9.

He said immunity needs to be that high because the Delta variant is so contagious.

Mandates are seen as the most effective way to increase immunity and do it quickly.

David Michaels, PhD, an epidemiologist and professor at George Washington University, Washington, says OSHA will have to work through a number of steps to develop the rule.

“OSHA will have to write a preamble explaining the standard, its justifications, its costs, and how it will be enforced,” says Dr. Michaels, who led OSHA for the Obama administration. After that, the rule will be reviewed by the White House. Then employers will have some time – typically 30 days – to comply.

In addition to drafting the standard, OSHA will oversee its enforcement.

Companies that refuse to follow the standard could be fined $13,600 per violation, Mr. Zients said.

Dr. Michaels said he doesn’t expect enforcement to be a big issue, and he said we’re likely to see the rule well before it is final.

“Most employers are law-abiding. When OSHA issues a standard, they try to meet whatever those requirements are, and generally that starts to happen when the rule is announced, even before it goes into effect,” he said.

The rule may face legal challenges as well. Several governors and state attorneys general, as well as the Republican National Committee, have promised lawsuits to stop the vaccine mandates.

Critics of the new mandates say they impinge on personal freedom and impose burdens on businesses.

But the president hit back at that notion Sept. 10.

“Look, I am so disappointed that, particularly some of the Republican governors, have been so cavalier with the health of these kids, so cavalier of the health of their communities,” President Biden told reporters.

“I don’t know of any scientist out there in this field who doesn’t think it makes considerable sense to do the six things I’ve suggested.”

Yet, others feel the new requirements didn’t go far enough.

“These are good steps in the right direction, but they’re not enough to get the job done,” said Leana Wen, MD, in an op-ed for The Washington Post.

Dr. Wen, an expert in public health, wondered why President Biden didn’t mandate vaccinations for plane and train travel. She was disappointed that children 12 and older weren’t required to be vaccinated, too.

“There are mandates for childhood immunizations in every state. The coronavirus vaccine should be no different,” she wrote.

Vaccines remain the cornerstone of U.S. plans to control the pandemic.

On Sept. 10, there was new research from the CDC and state health departments showing that the COVID-19 vaccines continue to be highly effective at preventing severe illness and death.

But the study also found that the vaccines became less effective in the United States after Delta became the dominant cause of infections here.

The study, which included more than 600,000 COVID-19 cases, analyzed breakthrough infections – cases where people got sick despite being fully vaccinated – in 13 jurisdictions in the United States between April 4 and July 17, 2021.

Epidemiologists compared breakthrough infections between two distinct points in time: Before and after the period when the Delta variant began causing most infections.

From April 4 to June 19, fully vaccinated people made up just 5% of cases, 7% of hospitalizations, and 8% of deaths. From June 20 to July 17, 18% of cases, 14% of hospitalizations, and 16% of deaths occurred in fully vaccinated people.

“After the week of June 20, 2021, when the SARS-CoV-2 Delta variant became predominant, the percentage of fully vaccinated persons among cases increased more than expected,” the study authors wrote.

Even after Delta swept the United States, fully vaccinated people were 5 times less likely to get a COVID-19 infection and more than 10 times less likely to be hospitalized or die from one.

“As we have shown in study after study, vaccination works,” CDC Director Rochelle Walensky, MD, said during the White House news briefing.

“We have the scientific tools we need to turn the corner on this pandemic. Vaccination works and will protect us from the severe complications of COVID-19,” she said.

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

Patients can now receive their COVID-19 vaccine and flu shot during the same visit, according to updated recommendations by the Centers for Disease Control and Prevention.

Esben H/iStock/Getty Images

Previously, the CDC recommended that people receive their COVID-19 vaccinations alone and schedule any other vaccinations at least 2 weeks before or after their COVID-19 immunization. “This was out of an abundance of caution during a period when these vaccines were new and not due to any known safety or immunogenicity concerns,” the CDC guidance states. “However, substantial data have now been collected regarding the safety of COVID-19 vaccines currently approved or authorized by FDA.”

The guidance allowing for coadministration of COVID-19 vaccines with other immunizations, including the flu shot, was issued in mid-May 2021, and was restated in influenza vaccine recommendations released Aug. 27. The American Academy of Pediatrics soon followed suit, announcing that, for children eligible for the COVID-19 vaccine (age 12 and older), AAP recommendations allow for both the influenza and COVID-19 vaccines to be administered during the same visit.

Although there is limited data around giving COVID-19 vaccines with other vaccines, “extensive experience with non–COVID-19 vaccines has demonstrated that immunogenicity and adverse-event profiles are generally similar when vaccines are administered simultaneously as when they are administered alone,” the recommendations state. If administering other immunizations along with COVID-19 vaccines, providers should separate injection sites by at least 1 inch, the CDC recommends, and influenza vaccines that are more likely to cause a local reaction, like high-dose or the adjuvanted inactivated flu vaccine, should be administered in different limbs, if possible.

Whether someone should get their flu vaccine at the same time or separate from a COVID-19 vaccination or booster is a matter of personal preference as well as convenience, Susan Coffin, MD, MPH, an attending physician in the division of infectious diseases at Children’s Hospital of Philadelphia, said in an interview. “It basically boils down to: Will you be able to get your flu shot without any difficulty in 2 weeks’ time?” she said. “We don’t want inconvenience or difficulties in access to get the way of people getting their flu shot this year.”

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

Patients can now receive their COVID-19 vaccine and flu shot during the same visit, according to updated recommendations by the Centers for Disease Control and Prevention.

Esben H/iStock/Getty Images

Previously, the CDC recommended that people receive their COVID-19 vaccinations alone and schedule any other vaccinations at least 2 weeks before or after their COVID-19 immunization. “This was out of an abundance of caution during a period when these vaccines were new and not due to any known safety or immunogenicity concerns,” the CDC guidance states. “However, substantial data have now been collected regarding the safety of COVID-19 vaccines currently approved or authorized by FDA.”

The guidance allowing for coadministration of COVID-19 vaccines with other immunizations, including the flu shot, was issued in mid-May 2021, and was restated in influenza vaccine recommendations released Aug. 27. The American Academy of Pediatrics soon followed suit, announcing that, for children eligible for the COVID-19 vaccine (age 12 and older), AAP recommendations allow for both the influenza and COVID-19 vaccines to be administered during the same visit.

Although there is limited data around giving COVID-19 vaccines with other vaccines, “extensive experience with non–COVID-19 vaccines has demonstrated that immunogenicity and adverse-event profiles are generally similar when vaccines are administered simultaneously as when they are administered alone,” the recommendations state. If administering other immunizations along with COVID-19 vaccines, providers should separate injection sites by at least 1 inch, the CDC recommends, and influenza vaccines that are more likely to cause a local reaction, like high-dose or the adjuvanted inactivated flu vaccine, should be administered in different limbs, if possible.

Whether someone should get their flu vaccine at the same time or separate from a COVID-19 vaccination or booster is a matter of personal preference as well as convenience, Susan Coffin, MD, MPH, an attending physician in the division of infectious diseases at Children’s Hospital of Philadelphia, said in an interview. “It basically boils down to: Will you be able to get your flu shot without any difficulty in 2 weeks’ time?” she said. “We don’t want inconvenience or difficulties in access to get the way of people getting their flu shot this year.”

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

Patients can now receive their COVID-19 vaccine and flu shot during the same visit, according to updated recommendations by the Centers for Disease Control and Prevention.

Esben H/iStock/Getty Images

Previously, the CDC recommended that people receive their COVID-19 vaccinations alone and schedule any other vaccinations at least 2 weeks before or after their COVID-19 immunization. “This was out of an abundance of caution during a period when these vaccines were new and not due to any known safety or immunogenicity concerns,” the CDC guidance states. “However, substantial data have now been collected regarding the safety of COVID-19 vaccines currently approved or authorized by FDA.”

The guidance allowing for coadministration of COVID-19 vaccines with other immunizations, including the flu shot, was issued in mid-May 2021, and was restated in influenza vaccine recommendations released Aug. 27. The American Academy of Pediatrics soon followed suit, announcing that, for children eligible for the COVID-19 vaccine (age 12 and older), AAP recommendations allow for both the influenza and COVID-19 vaccines to be administered during the same visit.

Although there is limited data around giving COVID-19 vaccines with other vaccines, “extensive experience with non–COVID-19 vaccines has demonstrated that immunogenicity and adverse-event profiles are generally similar when vaccines are administered simultaneously as when they are administered alone,” the recommendations state. If administering other immunizations along with COVID-19 vaccines, providers should separate injection sites by at least 1 inch, the CDC recommends, and influenza vaccines that are more likely to cause a local reaction, like high-dose or the adjuvanted inactivated flu vaccine, should be administered in different limbs, if possible.

Whether someone should get their flu vaccine at the same time or separate from a COVID-19 vaccination or booster is a matter of personal preference as well as convenience, Susan Coffin, MD, MPH, an attending physician in the division of infectious diseases at Children’s Hospital of Philadelphia, said in an interview. “It basically boils down to: Will you be able to get your flu shot without any difficulty in 2 weeks’ time?” she said. “We don’t want inconvenience or difficulties in access to get the way of people getting their flu shot this year.”

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

Lung function in early infancy may be influenced by the mother’s level of physical activity during pregnancy, results of a study from Sweden suggest.

Low-lung function at 3 months of age, as measured by the ratio of time to peak tidal expiratory flow to expiratory time (tPTEF/tE), was more frequent among children whose mothers were physically inactive during the first half of pregnancy compared with those who exercised either moderately or strenuously, reported Hrefna Katrin Gudmundsdottir, MD, a pediatrician and PhD candidate at the University of Oslo, Norway. The results were based on a prospective observational study of 841 mother-child pairs.

“The potential link between maternal inactivity and low lung function in infancy adds to the importance of advising pregnant women and women of childbearing age on physical activity,” she said in an oral abstract presented during the virtual European Respiratory Society (ERS) International Congress.

Jonathan Grigg, MD, professor of pediatric respiratory and environmental medicine at Queen Mary University of London, who was not involved in the study, commented that it “offers a fascinating hint that increased physical activity of mothers is associated with better lung function in their babies and, therefore, possibly their health in later life. More research is needed to confirm this link, but it is important that women feel supported by their health care providers to be active in a way that is comfortable and accessible to them.”

Impaired lung function in infancy is associated with wheezing and asthma in childhood, and lower lung function later in life, Dr. Gudmundsdottir said. She also noted that impaired lung function begins in utero and is related to fetal and infant size, family history of asthma, and/or maternal smoking.

Physical activity during pregnancy has been demonstrated to reduce the risk of preterm birth and cesarean birth and of children being born either abnormally small or abnormally large for their gestational age, she explained.

To see where physical inactivity in the first half of pregnancy is associated with lower lung function in otherwise healthy 3-month old infants, Dr. Gudmundsdottir and colleagues looked at data on a mother-child cohort from the prospective population-based PreventADALL study, which was designed to study prevention of atopic dermatitis and allergies in children in Norway and Sweden.

A total of 814 infants (49% female) had available measures of tidal flow volume in the awake state at 3 months, as well as mother-reported data on physical activity at 18 weeks of pregnancy.

The investigators categorized the mothers as inactive, with either no or only low-intensity physical activity, “fairly” active, or “very” active based on self reporting.

The average tPTEF/tE value among all infants in the study was 0.391. The average value for 290 infants born to inactive mothers was 0.387, compared with 0.394 for 299 infants born to very active mothers, a difference that was not statistically significant.

Maternal physical activity level was not significantly associated with continuous tPTEF/tE, but the investigators did find that the offspring of inactive mothers were significantly more likely than the children of fairly or very active mothers to have a tPTEF/tE below 0.25 in both univariate analysis (odds ratio, 2.15; P = .011), and in multivariate analysis controlling for maternal age, education, parity, prepregnancy body-mass index, parental atopy, and in-utero exposure to nicotine (OR, 2.18; P = .013).

In univariate but not multivariate analysis, children of inactive mothers were significantly more likely than infants of more active mothers to have tPTEF/tE values below the 50th percentile (OR, 1.35; P = .042).

“We observed a trend that adds to the importance of advising women of childbearing age and pregnant women about physical activity. However, there may be factors that affect both maternal physical activity and lung function in offspring that we have not accounted for and could affect the results, so more research is needed,” Dr. Gudmundsdottir said in a statement.

Dr. Grigg pointed out that “it’s also worth keeping in mind that the single most important thing that mothers can do for their own health and that of their baby is to ensure that they do not smoke or use other tobacco products before, during, and after pregnancy. A smoke-free home has the biggest impact on lung function and health in childhood and later life.”

The study was supported by the University of Oslo. Dr. Gudmundsdottir and Dr. Grigg have disclosed no relevant financial relationships.

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

Lung function in early infancy may be influenced by the mother’s level of physical activity during pregnancy, results of a study from Sweden suggest.

Low-lung function at 3 months of age, as measured by the ratio of time to peak tidal expiratory flow to expiratory time (tPTEF/tE), was more frequent among children whose mothers were physically inactive during the first half of pregnancy compared with those who exercised either moderately or strenuously, reported Hrefna Katrin Gudmundsdottir, MD, a pediatrician and PhD candidate at the University of Oslo, Norway. The results were based on a prospective observational study of 841 mother-child pairs.

“The potential link between maternal inactivity and low lung function in infancy adds to the importance of advising pregnant women and women of childbearing age on physical activity,” she said in an oral abstract presented during the virtual European Respiratory Society (ERS) International Congress.

Jonathan Grigg, MD, professor of pediatric respiratory and environmental medicine at Queen Mary University of London, who was not involved in the study, commented that it “offers a fascinating hint that increased physical activity of mothers is associated with better lung function in their babies and, therefore, possibly their health in later life. More research is needed to confirm this link, but it is important that women feel supported by their health care providers to be active in a way that is comfortable and accessible to them.”

Impaired lung function in infancy is associated with wheezing and asthma in childhood, and lower lung function later in life, Dr. Gudmundsdottir said. She also noted that impaired lung function begins in utero and is related to fetal and infant size, family history of asthma, and/or maternal smoking.

Physical activity during pregnancy has been demonstrated to reduce the risk of preterm birth and cesarean birth and of children being born either abnormally small or abnormally large for their gestational age, she explained.

To see where physical inactivity in the first half of pregnancy is associated with lower lung function in otherwise healthy 3-month old infants, Dr. Gudmundsdottir and colleagues looked at data on a mother-child cohort from the prospective population-based PreventADALL study, which was designed to study prevention of atopic dermatitis and allergies in children in Norway and Sweden.

A total of 814 infants (49% female) had available measures of tidal flow volume in the awake state at 3 months, as well as mother-reported data on physical activity at 18 weeks of pregnancy.

The investigators categorized the mothers as inactive, with either no or only low-intensity physical activity, “fairly” active, or “very” active based on self reporting.

The average tPTEF/tE value among all infants in the study was 0.391. The average value for 290 infants born to inactive mothers was 0.387, compared with 0.394 for 299 infants born to very active mothers, a difference that was not statistically significant.

Maternal physical activity level was not significantly associated with continuous tPTEF/tE, but the investigators did find that the offspring of inactive mothers were significantly more likely than the children of fairly or very active mothers to have a tPTEF/tE below 0.25 in both univariate analysis (odds ratio, 2.15; P = .011), and in multivariate analysis controlling for maternal age, education, parity, prepregnancy body-mass index, parental atopy, and in-utero exposure to nicotine (OR, 2.18; P = .013).

In univariate but not multivariate analysis, children of inactive mothers were significantly more likely than infants of more active mothers to have tPTEF/tE values below the 50th percentile (OR, 1.35; P = .042).

“We observed a trend that adds to the importance of advising women of childbearing age and pregnant women about physical activity. However, there may be factors that affect both maternal physical activity and lung function in offspring that we have not accounted for and could affect the results, so more research is needed,” Dr. Gudmundsdottir said in a statement.

Dr. Grigg pointed out that “it’s also worth keeping in mind that the single most important thing that mothers can do for their own health and that of their baby is to ensure that they do not smoke or use other tobacco products before, during, and after pregnancy. A smoke-free home has the biggest impact on lung function and health in childhood and later life.”

The study was supported by the University of Oslo. Dr. Gudmundsdottir and Dr. Grigg have disclosed no relevant financial relationships.

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

Lung function in early infancy may be influenced by the mother’s level of physical activity during pregnancy, results of a study from Sweden suggest.

Low-lung function at 3 months of age, as measured by the ratio of time to peak tidal expiratory flow to expiratory time (tPTEF/tE), was more frequent among children whose mothers were physically inactive during the first half of pregnancy compared with those who exercised either moderately or strenuously, reported Hrefna Katrin Gudmundsdottir, MD, a pediatrician and PhD candidate at the University of Oslo, Norway. The results were based on a prospective observational study of 841 mother-child pairs.

“The potential link between maternal inactivity and low lung function in infancy adds to the importance of advising pregnant women and women of childbearing age on physical activity,” she said in an oral abstract presented during the virtual European Respiratory Society (ERS) International Congress.

Jonathan Grigg, MD, professor of pediatric respiratory and environmental medicine at Queen Mary University of London, who was not involved in the study, commented that it “offers a fascinating hint that increased physical activity of mothers is associated with better lung function in their babies and, therefore, possibly their health in later life. More research is needed to confirm this link, but it is important that women feel supported by their health care providers to be active in a way that is comfortable and accessible to them.”

Impaired lung function in infancy is associated with wheezing and asthma in childhood, and lower lung function later in life, Dr. Gudmundsdottir said. She also noted that impaired lung function begins in utero and is related to fetal and infant size, family history of asthma, and/or maternal smoking.

Physical activity during pregnancy has been demonstrated to reduce the risk of preterm birth and cesarean birth and of children being born either abnormally small or abnormally large for their gestational age, she explained.

To see where physical inactivity in the first half of pregnancy is associated with lower lung function in otherwise healthy 3-month old infants, Dr. Gudmundsdottir and colleagues looked at data on a mother-child cohort from the prospective population-based PreventADALL study, which was designed to study prevention of atopic dermatitis and allergies in children in Norway and Sweden.

A total of 814 infants (49% female) had available measures of tidal flow volume in the awake state at 3 months, as well as mother-reported data on physical activity at 18 weeks of pregnancy.

The investigators categorized the mothers as inactive, with either no or only low-intensity physical activity, “fairly” active, or “very” active based on self reporting.

The average tPTEF/tE value among all infants in the study was 0.391. The average value for 290 infants born to inactive mothers was 0.387, compared with 0.394 for 299 infants born to very active mothers, a difference that was not statistically significant.

Maternal physical activity level was not significantly associated with continuous tPTEF/tE, but the investigators did find that the offspring of inactive mothers were significantly more likely than the children of fairly or very active mothers to have a tPTEF/tE below 0.25 in both univariate analysis (odds ratio, 2.15; P = .011), and in multivariate analysis controlling for maternal age, education, parity, prepregnancy body-mass index, parental atopy, and in-utero exposure to nicotine (OR, 2.18; P = .013).

In univariate but not multivariate analysis, children of inactive mothers were significantly more likely than infants of more active mothers to have tPTEF/tE values below the 50th percentile (OR, 1.35; P = .042).

“We observed a trend that adds to the importance of advising women of childbearing age and pregnant women about physical activity. However, there may be factors that affect both maternal physical activity and lung function in offspring that we have not accounted for and could affect the results, so more research is needed,” Dr. Gudmundsdottir said in a statement.

Dr. Grigg pointed out that “it’s also worth keeping in mind that the single most important thing that mothers can do for their own health and that of their baby is to ensure that they do not smoke or use other tobacco products before, during, and after pregnancy. A smoke-free home has the biggest impact on lung function and health in childhood and later life.”

The study was supported by the University of Oslo. Dr. Gudmundsdottir and Dr. Grigg have disclosed no relevant financial relationships.

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

Unlike in adults, seizures, including status epilepticus (SE), may be the first and main manifestation of COVID-19 in children, new research suggests.

Seizures may occur even in children with no history of epilepsy and in the absence of fever or severe COVID-19 illness, necessitating a “high index” of suspicion for the virus to make an early diagnosis and allow for appropriate infection control measures, say the researchers.

“We hope to increase physicians’ awareness of noninfluenza-like presentations of COVID in children. In areas with a high prevalence of COVID, we suggest that children with seizures be tested for COVID,” Tal Gilboa, MD, director of the child neurology unit and codirector of epilepsy, Hadassah Medical Center, Jerusalem, told this news organization.

The study was published online August 27 in the journal Seizure.
 

Presenting symptom

Among 175 children diagnosed with acute SARS-CoV-2 infection in the emergency department over 10 months in 2020, 11 (6%) presented with seizures. Studies in adults with COVID-19 have reported seizures in 0% to 2% of cases, the investigators note.

The 11 children with seizures (seven boys) ranged in age from 6 months to 17 years (median age, 11.5 years). All of them had seizures as the presenting sign of infection and none had severe COVID-19 requiring ventilatory or hemodynamic support. Six of the 11 children presented with fever.

Seven of the children had a prior history of neurological disorder: Five had epilepsy, one had a single unprovoked seizure 3 years before admission, and one had an intellectual disability. Three of the children had uncontrolled seizures despite appropriate treatment with antiseizure medication.

Nine of the 11 children presented with generalized tonic-clonic seizures. One child with a prior history of uncontrolled epilepsy with multiple seizure types had a focal tonic seizure. The youngest patient, a 5-month-old infant, presented with bilateral asymmetrical tonic-clonic seizure.

Of note, say the investigators, five of the 11 children presented with convulsive SE; none had a history of prior SE, and one had no history of seizures.

Although young age, especially under 12 months, is a known risk factor for SE, four of the five patients with SE were between 5 and 17 years old. All five children with SE responded to treatment with antiseizure medications.

All 11 children made a full recovery while in hospital, although further follow-up is essential to determine long-term outcomes, the researchers report.

“Children with no prior history of epilepsy and those with well-controlled epilepsy who present with breakthrough seizures, regardless of their body temperature, should be considered as potentially infected by SARS-CoV-2,” said Dr. Gilboa.

“It is possible, however unlikely, that a child, especially with prior epilepsy, may have an unprovoked seizure while being asymptomatically infected by SARS-CoV-2; in any case, infection control measures should be taken,” Dr. Gilboa added.
 

Need for replication

Weighing in on the study, Carl E. Stafstrom, MD, PhD, professor of neurology and pediatrics, Johns Hopkins University, Baltimore, said it’s important to note that “about half of the children had had epilepsy already, and for whatever reason, had a seizure, which required an ED visit, and then they found COVID.”

“Nevertheless, this article is interesting and surprising in what they found because nobody else has found nearly as frequent a seizure presentation,” said Dr. Stafstrom, director of the John M. Freeman Pediatric Epilepsy Center, Johns Hopkins Medicine.

“We would want to see some replication from other institutions and other populations,” he added.

The study had no specific funding. Dr. Gilboa and Dr. Stafstrom have reported no relevant financial relationships.

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

Unlike in adults, seizures, including status epilepticus (SE), may be the first and main manifestation of COVID-19 in children, new research suggests.

Seizures may occur even in children with no history of epilepsy and in the absence of fever or severe COVID-19 illness, necessitating a “high index” of suspicion for the virus to make an early diagnosis and allow for appropriate infection control measures, say the researchers.

“We hope to increase physicians’ awareness of noninfluenza-like presentations of COVID in children. In areas with a high prevalence of COVID, we suggest that children with seizures be tested for COVID,” Tal Gilboa, MD, director of the child neurology unit and codirector of epilepsy, Hadassah Medical Center, Jerusalem, told this news organization.

The study was published online August 27 in the journal Seizure.
 

Presenting symptom

Among 175 children diagnosed with acute SARS-CoV-2 infection in the emergency department over 10 months in 2020, 11 (6%) presented with seizures. Studies in adults with COVID-19 have reported seizures in 0% to 2% of cases, the investigators note.

The 11 children with seizures (seven boys) ranged in age from 6 months to 17 years (median age, 11.5 years). All of them had seizures as the presenting sign of infection and none had severe COVID-19 requiring ventilatory or hemodynamic support. Six of the 11 children presented with fever.

Seven of the children had a prior history of neurological disorder: Five had epilepsy, one had a single unprovoked seizure 3 years before admission, and one had an intellectual disability. Three of the children had uncontrolled seizures despite appropriate treatment with antiseizure medication.

Nine of the 11 children presented with generalized tonic-clonic seizures. One child with a prior history of uncontrolled epilepsy with multiple seizure types had a focal tonic seizure. The youngest patient, a 5-month-old infant, presented with bilateral asymmetrical tonic-clonic seizure.

Of note, say the investigators, five of the 11 children presented with convulsive SE; none had a history of prior SE, and one had no history of seizures.

Although young age, especially under 12 months, is a known risk factor for SE, four of the five patients with SE were between 5 and 17 years old. All five children with SE responded to treatment with antiseizure medications.

All 11 children made a full recovery while in hospital, although further follow-up is essential to determine long-term outcomes, the researchers report.

“Children with no prior history of epilepsy and those with well-controlled epilepsy who present with breakthrough seizures, regardless of their body temperature, should be considered as potentially infected by SARS-CoV-2,” said Dr. Gilboa.

“It is possible, however unlikely, that a child, especially with prior epilepsy, may have an unprovoked seizure while being asymptomatically infected by SARS-CoV-2; in any case, infection control measures should be taken,” Dr. Gilboa added.
 

Need for replication

Weighing in on the study, Carl E. Stafstrom, MD, PhD, professor of neurology and pediatrics, Johns Hopkins University, Baltimore, said it’s important to note that “about half of the children had had epilepsy already, and for whatever reason, had a seizure, which required an ED visit, and then they found COVID.”

“Nevertheless, this article is interesting and surprising in what they found because nobody else has found nearly as frequent a seizure presentation,” said Dr. Stafstrom, director of the John M. Freeman Pediatric Epilepsy Center, Johns Hopkins Medicine.

“We would want to see some replication from other institutions and other populations,” he added.

The study had no specific funding. Dr. Gilboa and Dr. Stafstrom have reported no relevant financial relationships.

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

Unlike in adults, seizures, including status epilepticus (SE), may be the first and main manifestation of COVID-19 in children, new research suggests.

Seizures may occur even in children with no history of epilepsy and in the absence of fever or severe COVID-19 illness, necessitating a “high index” of suspicion for the virus to make an early diagnosis and allow for appropriate infection control measures, say the researchers.

“We hope to increase physicians’ awareness of noninfluenza-like presentations of COVID in children. In areas with a high prevalence of COVID, we suggest that children with seizures be tested for COVID,” Tal Gilboa, MD, director of the child neurology unit and codirector of epilepsy, Hadassah Medical Center, Jerusalem, told this news organization.

The study was published online August 27 in the journal Seizure.
 

Presenting symptom

Among 175 children diagnosed with acute SARS-CoV-2 infection in the emergency department over 10 months in 2020, 11 (6%) presented with seizures. Studies in adults with COVID-19 have reported seizures in 0% to 2% of cases, the investigators note.

The 11 children with seizures (seven boys) ranged in age from 6 months to 17 years (median age, 11.5 years). All of them had seizures as the presenting sign of infection and none had severe COVID-19 requiring ventilatory or hemodynamic support. Six of the 11 children presented with fever.

Seven of the children had a prior history of neurological disorder: Five had epilepsy, one had a single unprovoked seizure 3 years before admission, and one had an intellectual disability. Three of the children had uncontrolled seizures despite appropriate treatment with antiseizure medication.

Nine of the 11 children presented with generalized tonic-clonic seizures. One child with a prior history of uncontrolled epilepsy with multiple seizure types had a focal tonic seizure. The youngest patient, a 5-month-old infant, presented with bilateral asymmetrical tonic-clonic seizure.

Of note, say the investigators, five of the 11 children presented with convulsive SE; none had a history of prior SE, and one had no history of seizures.

Although young age, especially under 12 months, is a known risk factor for SE, four of the five patients with SE were between 5 and 17 years old. All five children with SE responded to treatment with antiseizure medications.

All 11 children made a full recovery while in hospital, although further follow-up is essential to determine long-term outcomes, the researchers report.

“Children with no prior history of epilepsy and those with well-controlled epilepsy who present with breakthrough seizures, regardless of their body temperature, should be considered as potentially infected by SARS-CoV-2,” said Dr. Gilboa.

“It is possible, however unlikely, that a child, especially with prior epilepsy, may have an unprovoked seizure while being asymptomatically infected by SARS-CoV-2; in any case, infection control measures should be taken,” Dr. Gilboa added.
 

Need for replication

Weighing in on the study, Carl E. Stafstrom, MD, PhD, professor of neurology and pediatrics, Johns Hopkins University, Baltimore, said it’s important to note that “about half of the children had had epilepsy already, and for whatever reason, had a seizure, which required an ED visit, and then they found COVID.”

“Nevertheless, this article is interesting and surprising in what they found because nobody else has found nearly as frequent a seizure presentation,” said Dr. Stafstrom, director of the John M. Freeman Pediatric Epilepsy Center, Johns Hopkins Medicine.

“We would want to see some replication from other institutions and other populations,” he added.

The study had no specific funding. Dr. Gilboa and Dr. Stafstrom have reported no relevant financial relationships.

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

Three primary care boards have issued a joint statement backing the Federation of State Medical Boards’ recent statement saying that, if physicians spread misinformation about COVID-19, their medical license could be suspended or revoked.

Leaders of the American Board of Family Medicine, the American Board of Internal Medicine, and the American Board of Pediatrics said Sept. 9 that they support FSMB’s position.

“We also want all physicians certified by our boards to know that such unethical or unprofessional conduct may prompt their respective Board to take action that could put their certification at risk,” a statement read. 

“Expertise matters, and board-certified physicians have demonstrated that they have stayed current in their field. Spreading misinformation or falsehoods to the public during a time of a public health emergency goes against everything our boards and our community of board-certified physicians stand for,” the leaders wrote.

“The evidence that we have safe, effective, and widely available vaccines against COVID-19 is overwhelming. We are particularly concerned about physicians who use their authority to denigrate vaccination at a time when vaccines continue to demonstrate excellent effectiveness against severe illness, hospitalization, and death.”
 

Small number spread false information

However, a small number of doctors continue to spread misinformation against the vaccines and communicate other false information surrounding COVID-19.

Some of the misinformation spreaders have had ultra-viral reach.

Among them is Daniel Stock, MD, a family physician in Indiana who has come out against COVID-19 vaccines. At a recent meeting of the Mt. Vernon Community School board in Indiana, he gave a speech urging the board to ignore the prevailing recommendations around COVID-19, such as test-and-trace measures.

Forbes reported in August that versions of the video of Stock›s speech on Facebook “have collected a total of 90 million engagements – a metric encompassing things such as comments, likes and shares – according to data collected by Media Matters for America, a liberal tech-watchdog group.”

This news organization published a story in August asking whether physicians who spread such information should lose their license and the question drew rapid-fire comments.

Commenters who argued with potential disciplinary actions raised questions about where the line will be drawn between misinformation and deeply held beliefs in terms of care.

Several comments centered on ivermectin, which is not approved by the Food and Drug Administration to treat COVID-19 but is enthusiastically supported as a COVID-19 treatment by a group of physicians called the Front Line COVID-19 Critical Care Alliance, whose website includes requests for donations.

Some cited free speech protections.
 

‘Not consistent with standards’

As for ivermectin, David G. Nichols, MD, president and CEO of the American Board of Pediatrics, gave this news organization an example: “Spreading the notion that one would not need to get vaccinated because if you get sick you could take ivermectin is a very dangerous statement. That is not consistent with the standards of professionalism required for certification or licensure.”

Ivermectin, he noted, is not an approved treatment for COVID-19.

“To say that it is or has any benefit is a false statement. We’re not willing to allow individuals who make false statements to devalue the terrific work of tens of thousands of physicians across the United States doing work under very difficult circumstances,” Dr. Nichols said.

He continued: “To suggest treatments that are known not to be effective in exchange for treatment that is known to be effective is dangerous – and ivermectin falls under that category.”

Asked whether such suggestions could result in suspension or revocation of a physician’s license, Dr. Nichols said, “It’s the kind of thing that would certainly trigger a review.”

He said the standard for separating misinformation from personal beliefs is based on whether there is scientific evidence to support the belief.

The boards are not, with this statement, attempting to referee legitimate scientific debate, he said.

The misinformation the boards are referring to, Dr. Nichols said, is “where the evidence is 100% on one side and zero on another. And the zero is not only that the opinions or beliefs are unsupported or unsubstantiated, they are indeed harmful if followed. That’s the distinction we’re trying to make here.”

As for free-speech arguments, he said, “Free speech is a constitutional right. You can say whatever you want. The issue here is you do not have the right to expect continued professional sanction of a board certificate if you are lying to the public.”

The board statement also said: “We all look to board-certified physicians to provide outstanding care and guidance; providing misinformation about a lethal disease is unethical, unprofessional, and dangerous. In times of medical emergency, the community of expert physicians committed to science and evidence collectively shares a responsibility for giving the public the most accurate and timely health information available, so they can make decisions that work best for themselves and their families.”

In addition to Dr. Nichols, the statement was signed by Warren Newton, MD, MPH, president and CEO of the American Board of Family Medicine, and Richard J. Baron, MD, president and CEO of the American Board of Internal Medicine.

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

Three primary care boards have issued a joint statement backing the Federation of State Medical Boards’ recent statement saying that, if physicians spread misinformation about COVID-19, their medical license could be suspended or revoked.

Leaders of the American Board of Family Medicine, the American Board of Internal Medicine, and the American Board of Pediatrics said Sept. 9 that they support FSMB’s position.

“We also want all physicians certified by our boards to know that such unethical or unprofessional conduct may prompt their respective Board to take action that could put their certification at risk,” a statement read. 

“Expertise matters, and board-certified physicians have demonstrated that they have stayed current in their field. Spreading misinformation or falsehoods to the public during a time of a public health emergency goes against everything our boards and our community of board-certified physicians stand for,” the leaders wrote.

“The evidence that we have safe, effective, and widely available vaccines against COVID-19 is overwhelming. We are particularly concerned about physicians who use their authority to denigrate vaccination at a time when vaccines continue to demonstrate excellent effectiveness against severe illness, hospitalization, and death.”
 

Small number spread false information

However, a small number of doctors continue to spread misinformation against the vaccines and communicate other false information surrounding COVID-19.

Some of the misinformation spreaders have had ultra-viral reach.

Among them is Daniel Stock, MD, a family physician in Indiana who has come out against COVID-19 vaccines. At a recent meeting of the Mt. Vernon Community School board in Indiana, he gave a speech urging the board to ignore the prevailing recommendations around COVID-19, such as test-and-trace measures.

Forbes reported in August that versions of the video of Stock›s speech on Facebook “have collected a total of 90 million engagements – a metric encompassing things such as comments, likes and shares – according to data collected by Media Matters for America, a liberal tech-watchdog group.”

This news organization published a story in August asking whether physicians who spread such information should lose their license and the question drew rapid-fire comments.

Commenters who argued with potential disciplinary actions raised questions about where the line will be drawn between misinformation and deeply held beliefs in terms of care.

Several comments centered on ivermectin, which is not approved by the Food and Drug Administration to treat COVID-19 but is enthusiastically supported as a COVID-19 treatment by a group of physicians called the Front Line COVID-19 Critical Care Alliance, whose website includes requests for donations.

Some cited free speech protections.
 

‘Not consistent with standards’

As for ivermectin, David G. Nichols, MD, president and CEO of the American Board of Pediatrics, gave this news organization an example: “Spreading the notion that one would not need to get vaccinated because if you get sick you could take ivermectin is a very dangerous statement. That is not consistent with the standards of professionalism required for certification or licensure.”

Ivermectin, he noted, is not an approved treatment for COVID-19.

“To say that it is or has any benefit is a false statement. We’re not willing to allow individuals who make false statements to devalue the terrific work of tens of thousands of physicians across the United States doing work under very difficult circumstances,” Dr. Nichols said.

He continued: “To suggest treatments that are known not to be effective in exchange for treatment that is known to be effective is dangerous – and ivermectin falls under that category.”

Asked whether such suggestions could result in suspension or revocation of a physician’s license, Dr. Nichols said, “It’s the kind of thing that would certainly trigger a review.”

He said the standard for separating misinformation from personal beliefs is based on whether there is scientific evidence to support the belief.

The boards are not, with this statement, attempting to referee legitimate scientific debate, he said.

The misinformation the boards are referring to, Dr. Nichols said, is “where the evidence is 100% on one side and zero on another. And the zero is not only that the opinions or beliefs are unsupported or unsubstantiated, they are indeed harmful if followed. That’s the distinction we’re trying to make here.”

As for free-speech arguments, he said, “Free speech is a constitutional right. You can say whatever you want. The issue here is you do not have the right to expect continued professional sanction of a board certificate if you are lying to the public.”

The board statement also said: “We all look to board-certified physicians to provide outstanding care and guidance; providing misinformation about a lethal disease is unethical, unprofessional, and dangerous. In times of medical emergency, the community of expert physicians committed to science and evidence collectively shares a responsibility for giving the public the most accurate and timely health information available, so they can make decisions that work best for themselves and their families.”

In addition to Dr. Nichols, the statement was signed by Warren Newton, MD, MPH, president and CEO of the American Board of Family Medicine, and Richard J. Baron, MD, president and CEO of the American Board of Internal Medicine.

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

Three primary care boards have issued a joint statement backing the Federation of State Medical Boards’ recent statement saying that, if physicians spread misinformation about COVID-19, their medical license could be suspended or revoked.

Leaders of the American Board of Family Medicine, the American Board of Internal Medicine, and the American Board of Pediatrics said Sept. 9 that they support FSMB’s position.

“We also want all physicians certified by our boards to know that such unethical or unprofessional conduct may prompt their respective Board to take action that could put their certification at risk,” a statement read. 

“Expertise matters, and board-certified physicians have demonstrated that they have stayed current in their field. Spreading misinformation or falsehoods to the public during a time of a public health emergency goes against everything our boards and our community of board-certified physicians stand for,” the leaders wrote.

“The evidence that we have safe, effective, and widely available vaccines against COVID-19 is overwhelming. We are particularly concerned about physicians who use their authority to denigrate vaccination at a time when vaccines continue to demonstrate excellent effectiveness against severe illness, hospitalization, and death.”
 

Small number spread false information

However, a small number of doctors continue to spread misinformation against the vaccines and communicate other false information surrounding COVID-19.

Some of the misinformation spreaders have had ultra-viral reach.

Among them is Daniel Stock, MD, a family physician in Indiana who has come out against COVID-19 vaccines. At a recent meeting of the Mt. Vernon Community School board in Indiana, he gave a speech urging the board to ignore the prevailing recommendations around COVID-19, such as test-and-trace measures.

Forbes reported in August that versions of the video of Stock›s speech on Facebook “have collected a total of 90 million engagements – a metric encompassing things such as comments, likes and shares – according to data collected by Media Matters for America, a liberal tech-watchdog group.”

This news organization published a story in August asking whether physicians who spread such information should lose their license and the question drew rapid-fire comments.

Commenters who argued with potential disciplinary actions raised questions about where the line will be drawn between misinformation and deeply held beliefs in terms of care.

Several comments centered on ivermectin, which is not approved by the Food and Drug Administration to treat COVID-19 but is enthusiastically supported as a COVID-19 treatment by a group of physicians called the Front Line COVID-19 Critical Care Alliance, whose website includes requests for donations.

Some cited free speech protections.
 

‘Not consistent with standards’

As for ivermectin, David G. Nichols, MD, president and CEO of the American Board of Pediatrics, gave this news organization an example: “Spreading the notion that one would not need to get vaccinated because if you get sick you could take ivermectin is a very dangerous statement. That is not consistent with the standards of professionalism required for certification or licensure.”

Ivermectin, he noted, is not an approved treatment for COVID-19.

“To say that it is or has any benefit is a false statement. We’re not willing to allow individuals who make false statements to devalue the terrific work of tens of thousands of physicians across the United States doing work under very difficult circumstances,” Dr. Nichols said.

He continued: “To suggest treatments that are known not to be effective in exchange for treatment that is known to be effective is dangerous – and ivermectin falls under that category.”

Asked whether such suggestions could result in suspension or revocation of a physician’s license, Dr. Nichols said, “It’s the kind of thing that would certainly trigger a review.”

He said the standard for separating misinformation from personal beliefs is based on whether there is scientific evidence to support the belief.

The boards are not, with this statement, attempting to referee legitimate scientific debate, he said.

The misinformation the boards are referring to, Dr. Nichols said, is “where the evidence is 100% on one side and zero on another. And the zero is not only that the opinions or beliefs are unsupported or unsubstantiated, they are indeed harmful if followed. That’s the distinction we’re trying to make here.”

As for free-speech arguments, he said, “Free speech is a constitutional right. You can say whatever you want. The issue here is you do not have the right to expect continued professional sanction of a board certificate if you are lying to the public.”

The board statement also said: “We all look to board-certified physicians to provide outstanding care and guidance; providing misinformation about a lethal disease is unethical, unprofessional, and dangerous. In times of medical emergency, the community of expert physicians committed to science and evidence collectively shares a responsibility for giving the public the most accurate and timely health information available, so they can make decisions that work best for themselves and their families.”

In addition to Dr. Nichols, the statement was signed by Warren Newton, MD, MPH, president and CEO of the American Board of Family Medicine, and Richard J. Baron, MD, president and CEO of the American Board of Internal Medicine.

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

Cannabis-based medicinal products (CBMPs) have shown early promise for refractory childhood epilepsy, but positive media attention, as well as pressure from politicians and marijuana advocacy groups, should not supplant clinical trials and acceptable standards of evidence, according to two leading experts.

In a recent invited review article, Martin Kirkpatrick, MD, of the University of Dundee (Scotland), and Finbar O’Callaghan, MD, PhD, of University College London suggested that childhood epilepsy may be easy terrain for commercial interests to break ground, and from there, build their presence.

“Children with epilepsy are at risk of being used as the ‘Trojan horse’ for the cannabis industry,” Dr. Kirkpatrick and Dr. O’Callaghan wrote in Developmental Medicine & Child Neurology.

They noted that some of the first publicized success stories involving cannabis oil for epilepsy coincided with the rise of the medicinal and recreational cannabis markets, which will constitute an estimated 55-billion-dollar industry by 2027.

“Pediatric neurologists, imbued with the need to practice evidence-based medicine and wary of prescribing unlicensed medicines that had inadequate safety data, suddenly found themselves at odds with an array of vested interests and, most unfortunately, with the families of patients who were keen to try anything that would alleviate the effects of their child’s seizures,” the investigators wrote.

According to the review, fundamental questions about cannabis remain unanswered, including concerns about safety with long-term use, and the medicinal value of various plant components, such as myrcene, a terpene that gives cannabis its characteristic smell.

“A widely discussed issue is whether the terpenes add any therapeutic benefit, contributing to the so-called entourage effect of ‘whole-plant’ medicines,” the investigators wrote. “The concept is that all the constituents of the plant together create ‘the sum of all the parts that leads to the magic or power of cannabis.’ Although commonly referred to, there is little or no robust evidence to support the entourage effect as a credible clinical concept.”

Clinical evidence for treatment of pediatric epilepsy is also lacking, according to Dr. Kirkpatrick and Dr. O’Callaghan.

“Unfortunately, apart from the studies of pure cannabidiol (CBD) in Lennox–Gastaut and Dravet syndromes and tuberous sclerosis complex, level I evidence in the field of CBMPs and refractory epilepsy is lacking,” they wrote.

While other experts have pointed out that lower-level evidence – such as patient-reported outcomes and observational data – have previously been sufficient for drug licensing, Dr. Kirkpatrick and Dr. O’Callaghan noted that such exceptions “almost always” involve conditions without any effective treatments, or drugs that are undeniably effective.

“This is not the scenario with CBMPs,” they wrote, referring to current clinical data as “low-level” evidence “suggesting … possible efficacy.”

They highlighted concerns about placebo effect with open-label epilepsy studies, citing a randomized controlled trial for Dravet syndrome, in which 27% of patients given placebo had a 50% reduction in seizure frequency.

“We need carefully designed, good-quality CBMP studies that produce results on which we can rely,” Dr. Kirkpatrick and Dr. O’Callaghan concluded. “We can then work with families to choose the best treatments for children and young people with epilepsy. We owe this to them.”
 

A therapy of last resort

Jerzy P. Szaflarski, MD, PhD, of the University of Alabama at Birmingham, agreed that data are lacking for the use of CBMPs with patients who have epilepsy and other neurologic conditions; however, he also suggested that Dr. Kirkpatrick and Dr. O’Callaghan did not provide adequate real-world clinical context.

“Medical cannabis is not used as a first-, second-, or third-line therapy,” Dr. Szaflarski said. “It’s mostly used as a last resort in the sense that patients have already failed multiple other therapies.” In that respect, patients and parents are desperate to try anything that might work. “We have medical cannabis, and our patients want to try it, and at the point when multiple therapies have failed, it’s a reasonable option.”

While Dr. Szaflarski agreed that more high-quality clinical trials are needed, he also noted the practical challenges involved in such trials, largely because of variations in cannabis plants.

“The content of the cannabis plant changes depending on the day that it’s collected and the exposure to sun and how much water it has and what’s in the soil and many other things,” Dr. Szaflarski said. “It’s hard to get a very good, standardized product, and that’s why there needs to be a good-quality product delivered by the industry, which I have not seen thus far.”

For this reason, Dr. Szaflarski steers parents and patients away from over-the-counter CBMPs and toward Epidiolex, the only FDA-approved form of CBD.

“There is evidence that Epidiolex works,” he said. “I don’t know whether the products that are sold in a local cannabis store have the same high purity as Epidiolex. I tell [parents] that we should try Epidiolex first because it’s the one that is approved. But if it doesn’t work, we can go in that [other] direction.”

For those going the commercial route, Dr. Szaflarski advised close attention to product ingredients, to ensure that CBMPs are “devoid of any impurities, pesticides, fungicides, and other products that could be potentially dangerous.”

Parents considering CBMPs for their children also need to weigh concerns about long-term neurological safety, he added, noting that, on one hand, commercial products lack data, while on the other, epilepsy itself may cause harm.

“They need to consider the potential effects [of CBMPs] on their child’s brain and development versus … the effects of seizures on the brain,” Dr. Szaflarski said.

Dr. Kirkpatrick and Dr. O’Callaghan disclosed an application for a National Institute for Health Research–funded randomized controlled trial on CBMPs and joint authorship of British Paediatric Neurology Association Guidance on the use of CBMPs in children and young people with epilepsy. Dr. Szaflarski disclosed a relationship with Greenwich Biosciences and several other cannabis companies.

Cannabis-based medicinal products (CBMPs) have shown early promise for refractory childhood epilepsy, but positive media attention, as well as pressure from politicians and marijuana advocacy groups, should not supplant clinical trials and acceptable standards of evidence, according to two leading experts.

In a recent invited review article, Martin Kirkpatrick, MD, of the University of Dundee (Scotland), and Finbar O’Callaghan, MD, PhD, of University College London suggested that childhood epilepsy may be easy terrain for commercial interests to break ground, and from there, build their presence.

“Children with epilepsy are at risk of being used as the ‘Trojan horse’ for the cannabis industry,” Dr. Kirkpatrick and Dr. O’Callaghan wrote in Developmental Medicine & Child Neurology.

They noted that some of the first publicized success stories involving cannabis oil for epilepsy coincided with the rise of the medicinal and recreational cannabis markets, which will constitute an estimated 55-billion-dollar industry by 2027.

“Pediatric neurologists, imbued with the need to practice evidence-based medicine and wary of prescribing unlicensed medicines that had inadequate safety data, suddenly found themselves at odds with an array of vested interests and, most unfortunately, with the families of patients who were keen to try anything that would alleviate the effects of their child’s seizures,” the investigators wrote.

According to the review, fundamental questions about cannabis remain unanswered, including concerns about safety with long-term use, and the medicinal value of various plant components, such as myrcene, a terpene that gives cannabis its characteristic smell.

“A widely discussed issue is whether the terpenes add any therapeutic benefit, contributing to the so-called entourage effect of ‘whole-plant’ medicines,” the investigators wrote. “The concept is that all the constituents of the plant together create ‘the sum of all the parts that leads to the magic or power of cannabis.’ Although commonly referred to, there is little or no robust evidence to support the entourage effect as a credible clinical concept.”

Clinical evidence for treatment of pediatric epilepsy is also lacking, according to Dr. Kirkpatrick and Dr. O’Callaghan.

“Unfortunately, apart from the studies of pure cannabidiol (CBD) in Lennox–Gastaut and Dravet syndromes and tuberous sclerosis complex, level I evidence in the field of CBMPs and refractory epilepsy is lacking,” they wrote.

While other experts have pointed out that lower-level evidence – such as patient-reported outcomes and observational data – have previously been sufficient for drug licensing, Dr. Kirkpatrick and Dr. O’Callaghan noted that such exceptions “almost always” involve conditions without any effective treatments, or drugs that are undeniably effective.

“This is not the scenario with CBMPs,” they wrote, referring to current clinical data as “low-level” evidence “suggesting … possible efficacy.”

They highlighted concerns about placebo effect with open-label epilepsy studies, citing a randomized controlled trial for Dravet syndrome, in which 27% of patients given placebo had a 50% reduction in seizure frequency.

“We need carefully designed, good-quality CBMP studies that produce results on which we can rely,” Dr. Kirkpatrick and Dr. O’Callaghan concluded. “We can then work with families to choose the best treatments for children and young people with epilepsy. We owe this to them.”
 

A therapy of last resort

Jerzy P. Szaflarski, MD, PhD, of the University of Alabama at Birmingham, agreed that data are lacking for the use of CBMPs with patients who have epilepsy and other neurologic conditions; however, he also suggested that Dr. Kirkpatrick and Dr. O’Callaghan did not provide adequate real-world clinical context.

“Medical cannabis is not used as a first-, second-, or third-line therapy,” Dr. Szaflarski said. “It’s mostly used as a last resort in the sense that patients have already failed multiple other therapies.” In that respect, patients and parents are desperate to try anything that might work. “We have medical cannabis, and our patients want to try it, and at the point when multiple therapies have failed, it’s a reasonable option.”

While Dr. Szaflarski agreed that more high-quality clinical trials are needed, he also noted the practical challenges involved in such trials, largely because of variations in cannabis plants.

“The content of the cannabis plant changes depending on the day that it’s collected and the exposure to sun and how much water it has and what’s in the soil and many other things,” Dr. Szaflarski said. “It’s hard to get a very good, standardized product, and that’s why there needs to be a good-quality product delivered by the industry, which I have not seen thus far.”

For this reason, Dr. Szaflarski steers parents and patients away from over-the-counter CBMPs and toward Epidiolex, the only FDA-approved form of CBD.

“There is evidence that Epidiolex works,” he said. “I don’t know whether the products that are sold in a local cannabis store have the same high purity as Epidiolex. I tell [parents] that we should try Epidiolex first because it’s the one that is approved. But if it doesn’t work, we can go in that [other] direction.”

For those going the commercial route, Dr. Szaflarski advised close attention to product ingredients, to ensure that CBMPs are “devoid of any impurities, pesticides, fungicides, and other products that could be potentially dangerous.”

Parents considering CBMPs for their children also need to weigh concerns about long-term neurological safety, he added, noting that, on one hand, commercial products lack data, while on the other, epilepsy itself may cause harm.

“They need to consider the potential effects [of CBMPs] on their child’s brain and development versus … the effects of seizures on the brain,” Dr. Szaflarski said.

Dr. Kirkpatrick and Dr. O’Callaghan disclosed an application for a National Institute for Health Research–funded randomized controlled trial on CBMPs and joint authorship of British Paediatric Neurology Association Guidance on the use of CBMPs in children and young people with epilepsy. Dr. Szaflarski disclosed a relationship with Greenwich Biosciences and several other cannabis companies.

Cannabis-based medicinal products (CBMPs) have shown early promise for refractory childhood epilepsy, but positive media attention, as well as pressure from politicians and marijuana advocacy groups, should not supplant clinical trials and acceptable standards of evidence, according to two leading experts.

In a recent invited review article, Martin Kirkpatrick, MD, of the University of Dundee (Scotland), and Finbar O’Callaghan, MD, PhD, of University College London suggested that childhood epilepsy may be easy terrain for commercial interests to break ground, and from there, build their presence.

“Children with epilepsy are at risk of being used as the ‘Trojan horse’ for the cannabis industry,” Dr. Kirkpatrick and Dr. O’Callaghan wrote in Developmental Medicine & Child Neurology.

They noted that some of the first publicized success stories involving cannabis oil for epilepsy coincided with the rise of the medicinal and recreational cannabis markets, which will constitute an estimated 55-billion-dollar industry by 2027.

“Pediatric neurologists, imbued with the need to practice evidence-based medicine and wary of prescribing unlicensed medicines that had inadequate safety data, suddenly found themselves at odds with an array of vested interests and, most unfortunately, with the families of patients who were keen to try anything that would alleviate the effects of their child’s seizures,” the investigators wrote.

According to the review, fundamental questions about cannabis remain unanswered, including concerns about safety with long-term use, and the medicinal value of various plant components, such as myrcene, a terpene that gives cannabis its characteristic smell.

“A widely discussed issue is whether the terpenes add any therapeutic benefit, contributing to the so-called entourage effect of ‘whole-plant’ medicines,” the investigators wrote. “The concept is that all the constituents of the plant together create ‘the sum of all the parts that leads to the magic or power of cannabis.’ Although commonly referred to, there is little or no robust evidence to support the entourage effect as a credible clinical concept.”

Clinical evidence for treatment of pediatric epilepsy is also lacking, according to Dr. Kirkpatrick and Dr. O’Callaghan.

“Unfortunately, apart from the studies of pure cannabidiol (CBD) in Lennox–Gastaut and Dravet syndromes and tuberous sclerosis complex, level I evidence in the field of CBMPs and refractory epilepsy is lacking,” they wrote.

While other experts have pointed out that lower-level evidence – such as patient-reported outcomes and observational data – have previously been sufficient for drug licensing, Dr. Kirkpatrick and Dr. O’Callaghan noted that such exceptions “almost always” involve conditions without any effective treatments, or drugs that are undeniably effective.

“This is not the scenario with CBMPs,” they wrote, referring to current clinical data as “low-level” evidence “suggesting … possible efficacy.”

They highlighted concerns about placebo effect with open-label epilepsy studies, citing a randomized controlled trial for Dravet syndrome, in which 27% of patients given placebo had a 50% reduction in seizure frequency.

“We need carefully designed, good-quality CBMP studies that produce results on which we can rely,” Dr. Kirkpatrick and Dr. O’Callaghan concluded. “We can then work with families to choose the best treatments for children and young people with epilepsy. We owe this to them.”
 

A therapy of last resort

Jerzy P. Szaflarski, MD, PhD, of the University of Alabama at Birmingham, agreed that data are lacking for the use of CBMPs with patients who have epilepsy and other neurologic conditions; however, he also suggested that Dr. Kirkpatrick and Dr. O’Callaghan did not provide adequate real-world clinical context.

“Medical cannabis is not used as a first-, second-, or third-line therapy,” Dr. Szaflarski said. “It’s mostly used as a last resort in the sense that patients have already failed multiple other therapies.” In that respect, patients and parents are desperate to try anything that might work. “We have medical cannabis, and our patients want to try it, and at the point when multiple therapies have failed, it’s a reasonable option.”

While Dr. Szaflarski agreed that more high-quality clinical trials are needed, he also noted the practical challenges involved in such trials, largely because of variations in cannabis plants.

“The content of the cannabis plant changes depending on the day that it’s collected and the exposure to sun and how much water it has and what’s in the soil and many other things,” Dr. Szaflarski said. “It’s hard to get a very good, standardized product, and that’s why there needs to be a good-quality product delivered by the industry, which I have not seen thus far.”

For this reason, Dr. Szaflarski steers parents and patients away from over-the-counter CBMPs and toward Epidiolex, the only FDA-approved form of CBD.

“There is evidence that Epidiolex works,” he said. “I don’t know whether the products that are sold in a local cannabis store have the same high purity as Epidiolex. I tell [parents] that we should try Epidiolex first because it’s the one that is approved. But if it doesn’t work, we can go in that [other] direction.”

For those going the commercial route, Dr. Szaflarski advised close attention to product ingredients, to ensure that CBMPs are “devoid of any impurities, pesticides, fungicides, and other products that could be potentially dangerous.”

Parents considering CBMPs for their children also need to weigh concerns about long-term neurological safety, he added, noting that, on one hand, commercial products lack data, while on the other, epilepsy itself may cause harm.

“They need to consider the potential effects [of CBMPs] on their child’s brain and development versus … the effects of seizures on the brain,” Dr. Szaflarski said.

Dr. Kirkpatrick and Dr. O’Callaghan disclosed an application for a National Institute for Health Research–funded randomized controlled trial on CBMPs and joint authorship of British Paediatric Neurology Association Guidance on the use of CBMPs in children and young people with epilepsy. Dr. Szaflarski disclosed a relationship with Greenwich Biosciences and several other cannabis companies.