Pediatric News

Clinicians have numerous pharmacotherapy options available to treat ADHD in their toolbox. How do you know which formulation or combination of therapies is right for your patient with ADHD?

According to Jeffrey R. Strawn, MD, the answer depends on onset and duration of the medication and how that fits in to the patient’s current needs.

The most common treatment for ADHD, stimulants, are amphetamine-based and methylphenidate-based compounds known for improving core symptoms of inattention, impulsivity, and hyperactivity and are “probably associated with the most efficacy relative to the other interventions,” Dr. Strawn, associate professor of psychiatry, pediatrics, and clinical pharmacology at Cincinnati Children’s Hospital Medical Center, said at Psychopharmacology Update presented by Current Psychiatry and Global Academy for Medical Education. “But what I think is also really important for us to remember as clinicians is that they improve adherence, social interactions, [and] academic efficiency as well as accuracy.”

Other ADHD pharmacotherapy options include nonstimulant norepinephrine reuptake inhibitors (NRIs) like atomoxetine, and alpha-2 agonists like the extended-release forms of guanfacine and clonidine. All are Food and Drug Administration–approved for the treatment of ADHD, and the FDA has approved some combination alpha-2 agonists and stimulants treatments for ADHD as well.

When making decisions about formulations for ADHD pharmacotherapy, clinicians should think about whether the patient has issues swallowing tablets or capsules. Tablets, capsules, and chewable tablets may be appropriate for patients who can easily take these medications, while patients who have problems with swallowing pills may benefit from dissolvable tablets, solutions, and transdermal applications. Each of these options “have differences in terms of absorption, also differences in terms of intestinal transit time in younger children, as well as patients perhaps with irritable bowel, as well as other conditions that may affect absorption,” Dr. Strawn said. Different formulations have unique considerations: liquid formulations have the benefit of making precise adjustments, sublingual formulations may have quick absorption and onset, and oral dissolvable tablets can improve treatment adherence and reduce misuse of medication.

Formulations can be available as a delayed release, extended release, pulsatile release, targeted release, or a combination of immediate, delayed, and/or extended release. “Ultimately, what this gives rise to is differences in onset of action and duration, as well as differences in the elimination profile of the medication,” he said.

Transdermal formulations “avoid the first-pass metabolism, which may reduce side effects or increase efficacy,” but patients converting from an oral formulation may require reducing the dose. “It’s always important to remember, for example, with something like Daytrana, the transdermal methylphenidate formulation, if we’re converting a patient from an oral methylphenidate, we roughly need to use half the dose for the transdermal formulation,” Dr. Strawn explained. Transdermal formulations can carry benefits of steady plasma concentrations and longer duration of action but may cause skin irritation or accidentally be removed. “It’s really important they’re properly disposed of because oftentimes they do contain some active medication within the residual matrix.”
 

Methylphenidate, mixed amphetamine salt–based preparations

Modified-release formulations include matrix- or reservoir-based formulations and are most importantly differentiated from other formulations by their gastrointestinal (GI) transit time and the permeation through the GI membrane. When considering what formulation to choose, “it’s important to consider that, even with an ‘extended release formulation,’ all of these medications have some percentage that is immediately released, and that percentage varies considerably from formulation to formulation,” Dr. Strawn said.

He noted that brand names are sometimes used for formulations “because it’s often very difficult for us as clinicians and even for pharmacists to distinguish between these various formulations of the medication, which often have the same ‘extended’ or ‘delayed release’ modifying term within the name of the medication.”

Examples of medications that have greater immediate release include Metadate CD (30%), Aptensio XR (37%), long-acting methylphenidate (50%), dexmethylphenidate extended-release (50%), and Mixed Salts amphetamine extended release (50%). Formulations with a less immediate release include Quillivant solution or Quillichew chewable tablets (20%), Dyanaval XR solution (20%), OROS methylphenidate (22%), Daytrana that begins within 1 or 2 hours and lasts for 9 hours, or lisdexamfetamine that begins within 1 hour and lasts for 9 hours.

Depending on a patient’s needs, one particular formulation may work better than another. Dexmethylphenidate (Focalin XR) has a 50% immediate release and 50% extended release formulation, which “may be really important for a high school student who has first period precalculus followed by second period human geography,” Dr. Strawn said, while “a patient who may have first period study hall and second period art” may benefit from OROS methylphenidate.

Clinicians should also consider the effect of counterclockwise hysteresis when adding a short-acting stimulant later in the day. “There seems to be something really magic about having that ascending concentration time curve that, when we’re on the descending loop of that concentration time curve, we really seem to get a dramatic waning of the effect of the medication, even though technically the concentration is within the ‘therapeutic range,’ ” Dr. Strawn said. “With counterclockwise hysteresis, we see that the effect increases with time for a given concentration of the medication.”
 

Combining ADHD pharmacotherapies

For children and adolescents with ADHD, atomoxetine is a nonstimulant, FDA-approved treatment option. “It seems to be effective not just in terms of total ADHD symptoms, but also in terms of hyperactive and impulsive symptoms as well as the inattentive symptoms,” Dr. Strawn said.

Pharmacogenetics can be a guide for selecting an atomoxetine for a patient with ADHD, he noted. “What I think is most relevant here is the way in which pharmacogenetics can actually help guide our dosing, which then optimizes tolerability, potentially efficacy of atomoxetine,” he said. “Atomoxetine is pretty extensively metabolized by [CYP]2D6, and it’s one of about 300 medications that actually has specific labeling from the FDA on dosing based on genotype. It recommends a slower titration, as well as a lower target dose of atomoxetine in individuals who are P450 2D6 poor metabolizers relative to those patients who are ultra-rapid or normal metabolizers.”

Atomoxetine is most often combined with methylphenidate and has some evidence of benefit in children or adolescents who do not have an adequate response to stimulants alone. When combining stimulants with the alpha-2 agonists guanfacine or clonidine, “there are some improvements in terms of the combination treatment relative to the monotherapy,” Dr. Strawn said. He also emphasized that patients taking guanfacine immediate release tend to have better absorption and faster onset, compared with the extended release formulation. “This is something that potentially is very important when we think beyond steady state and we think about the practical use of this medication,” he said.
 

Baseline history is important

Overall, taking a baseline history of a patient with ADHD is “critically important” before starting them on stimulants, Dr. Strawn said. “Specifically, I would recommend documenting a negative history of syncope, family history of sudden cardiac death, as well as the lack of any known history of structural cardiac abnormalities,” he said. “Without a consultation with the cardiologist specifically around this question, I’m very, very, very hesitant – as in I don’t – use stimulants in patients who have histories of aortic stenosis, Wolff-Parkinson-White, as well as arrhythmogenic right ventricular dysplasia.”

Although patients with ADHD were typically followed with routine hemodynamic monitoring every 3 months prior to the COVID-19 pandemic, some clinicians see their patients with ADHD less frequently if they have been stabilized on a stimulant. “It is important to check not just with the patient, but also with parents and teachers as we’re adjusting medication dose and trying to optimize the treatment regimen, particularly in young children. In adults, it may also be very helpful to talk with spouses,” Dr. Strawn said.

Dr. Strawn also called attention to a recommendation to perform a routine electrocardiogram (EKG) in patients with ADHD who might receive stimulants. “At present, there is no recommendation to obtain a routine screening EKG in these patients, provided that we have an absence of those other red flags on the history,” he said. “Certainly, I would consider it in situations where I do have persistent tachycardia or hypertension, or there are other treatment-emergent symptoms, although really in many of these situations, I’m actually speaking on the phone with my pediatric or adult cardiology colleagues.”

Global Academy and this news organization are owned by the same parent company. Dr. Strawn reported receiving research support from Allergan, the FDA, the National Institutes of Health, Neuronetics, and Otsuka; serving as a consultant and receiving material support from Myriad; receiving royalties from Springer Publishing; and serving as a consultant for Intra-Cellular Therapies. In addition, he has been on the speaker’s bureau for the Neuroscience Education Institute and CMEology, and Medscape.

Clinicians have numerous pharmacotherapy options available to treat ADHD in their toolbox. How do you know which formulation or combination of therapies is right for your patient with ADHD?

According to Jeffrey R. Strawn, MD, the answer depends on onset and duration of the medication and how that fits in to the patient’s current needs.

The most common treatment for ADHD, stimulants, are amphetamine-based and methylphenidate-based compounds known for improving core symptoms of inattention, impulsivity, and hyperactivity and are “probably associated with the most efficacy relative to the other interventions,” Dr. Strawn, associate professor of psychiatry, pediatrics, and clinical pharmacology at Cincinnati Children’s Hospital Medical Center, said at Psychopharmacology Update presented by Current Psychiatry and Global Academy for Medical Education. “But what I think is also really important for us to remember as clinicians is that they improve adherence, social interactions, [and] academic efficiency as well as accuracy.”

Other ADHD pharmacotherapy options include nonstimulant norepinephrine reuptake inhibitors (NRIs) like atomoxetine, and alpha-2 agonists like the extended-release forms of guanfacine and clonidine. All are Food and Drug Administration–approved for the treatment of ADHD, and the FDA has approved some combination alpha-2 agonists and stimulants treatments for ADHD as well.

When making decisions about formulations for ADHD pharmacotherapy, clinicians should think about whether the patient has issues swallowing tablets or capsules. Tablets, capsules, and chewable tablets may be appropriate for patients who can easily take these medications, while patients who have problems with swallowing pills may benefit from dissolvable tablets, solutions, and transdermal applications. Each of these options “have differences in terms of absorption, also differences in terms of intestinal transit time in younger children, as well as patients perhaps with irritable bowel, as well as other conditions that may affect absorption,” Dr. Strawn said. Different formulations have unique considerations: liquid formulations have the benefit of making precise adjustments, sublingual formulations may have quick absorption and onset, and oral dissolvable tablets can improve treatment adherence and reduce misuse of medication.

Formulations can be available as a delayed release, extended release, pulsatile release, targeted release, or a combination of immediate, delayed, and/or extended release. “Ultimately, what this gives rise to is differences in onset of action and duration, as well as differences in the elimination profile of the medication,” he said.

Transdermal formulations “avoid the first-pass metabolism, which may reduce side effects or increase efficacy,” but patients converting from an oral formulation may require reducing the dose. “It’s always important to remember, for example, with something like Daytrana, the transdermal methylphenidate formulation, if we’re converting a patient from an oral methylphenidate, we roughly need to use half the dose for the transdermal formulation,” Dr. Strawn explained. Transdermal formulations can carry benefits of steady plasma concentrations and longer duration of action but may cause skin irritation or accidentally be removed. “It’s really important they’re properly disposed of because oftentimes they do contain some active medication within the residual matrix.”
 

Methylphenidate, mixed amphetamine salt–based preparations

Modified-release formulations include matrix- or reservoir-based formulations and are most importantly differentiated from other formulations by their gastrointestinal (GI) transit time and the permeation through the GI membrane. When considering what formulation to choose, “it’s important to consider that, even with an ‘extended release formulation,’ all of these medications have some percentage that is immediately released, and that percentage varies considerably from formulation to formulation,” Dr. Strawn said.

He noted that brand names are sometimes used for formulations “because it’s often very difficult for us as clinicians and even for pharmacists to distinguish between these various formulations of the medication, which often have the same ‘extended’ or ‘delayed release’ modifying term within the name of the medication.”

Examples of medications that have greater immediate release include Metadate CD (30%), Aptensio XR (37%), long-acting methylphenidate (50%), dexmethylphenidate extended-release (50%), and Mixed Salts amphetamine extended release (50%). Formulations with a less immediate release include Quillivant solution or Quillichew chewable tablets (20%), Dyanaval XR solution (20%), OROS methylphenidate (22%), Daytrana that begins within 1 or 2 hours and lasts for 9 hours, or lisdexamfetamine that begins within 1 hour and lasts for 9 hours.

Depending on a patient’s needs, one particular formulation may work better than another. Dexmethylphenidate (Focalin XR) has a 50% immediate release and 50% extended release formulation, which “may be really important for a high school student who has first period precalculus followed by second period human geography,” Dr. Strawn said, while “a patient who may have first period study hall and second period art” may benefit from OROS methylphenidate.

Clinicians should also consider the effect of counterclockwise hysteresis when adding a short-acting stimulant later in the day. “There seems to be something really magic about having that ascending concentration time curve that, when we’re on the descending loop of that concentration time curve, we really seem to get a dramatic waning of the effect of the medication, even though technically the concentration is within the ‘therapeutic range,’ ” Dr. Strawn said. “With counterclockwise hysteresis, we see that the effect increases with time for a given concentration of the medication.”
 

Combining ADHD pharmacotherapies

For children and adolescents with ADHD, atomoxetine is a nonstimulant, FDA-approved treatment option. “It seems to be effective not just in terms of total ADHD symptoms, but also in terms of hyperactive and impulsive symptoms as well as the inattentive symptoms,” Dr. Strawn said.

Pharmacogenetics can be a guide for selecting an atomoxetine for a patient with ADHD, he noted. “What I think is most relevant here is the way in which pharmacogenetics can actually help guide our dosing, which then optimizes tolerability, potentially efficacy of atomoxetine,” he said. “Atomoxetine is pretty extensively metabolized by [CYP]2D6, and it’s one of about 300 medications that actually has specific labeling from the FDA on dosing based on genotype. It recommends a slower titration, as well as a lower target dose of atomoxetine in individuals who are P450 2D6 poor metabolizers relative to those patients who are ultra-rapid or normal metabolizers.”

Atomoxetine is most often combined with methylphenidate and has some evidence of benefit in children or adolescents who do not have an adequate response to stimulants alone. When combining stimulants with the alpha-2 agonists guanfacine or clonidine, “there are some improvements in terms of the combination treatment relative to the monotherapy,” Dr. Strawn said. He also emphasized that patients taking guanfacine immediate release tend to have better absorption and faster onset, compared with the extended release formulation. “This is something that potentially is very important when we think beyond steady state and we think about the practical use of this medication,” he said.
 

Baseline history is important

Overall, taking a baseline history of a patient with ADHD is “critically important” before starting them on stimulants, Dr. Strawn said. “Specifically, I would recommend documenting a negative history of syncope, family history of sudden cardiac death, as well as the lack of any known history of structural cardiac abnormalities,” he said. “Without a consultation with the cardiologist specifically around this question, I’m very, very, very hesitant – as in I don’t – use stimulants in patients who have histories of aortic stenosis, Wolff-Parkinson-White, as well as arrhythmogenic right ventricular dysplasia.”

Although patients with ADHD were typically followed with routine hemodynamic monitoring every 3 months prior to the COVID-19 pandemic, some clinicians see their patients with ADHD less frequently if they have been stabilized on a stimulant. “It is important to check not just with the patient, but also with parents and teachers as we’re adjusting medication dose and trying to optimize the treatment regimen, particularly in young children. In adults, it may also be very helpful to talk with spouses,” Dr. Strawn said.

Dr. Strawn also called attention to a recommendation to perform a routine electrocardiogram (EKG) in patients with ADHD who might receive stimulants. “At present, there is no recommendation to obtain a routine screening EKG in these patients, provided that we have an absence of those other red flags on the history,” he said. “Certainly, I would consider it in situations where I do have persistent tachycardia or hypertension, or there are other treatment-emergent symptoms, although really in many of these situations, I’m actually speaking on the phone with my pediatric or adult cardiology colleagues.”

Global Academy and this news organization are owned by the same parent company. Dr. Strawn reported receiving research support from Allergan, the FDA, the National Institutes of Health, Neuronetics, and Otsuka; serving as a consultant and receiving material support from Myriad; receiving royalties from Springer Publishing; and serving as a consultant for Intra-Cellular Therapies. In addition, he has been on the speaker’s bureau for the Neuroscience Education Institute and CMEology, and Medscape.

Clinicians have numerous pharmacotherapy options available to treat ADHD in their toolbox. How do you know which formulation or combination of therapies is right for your patient with ADHD?

According to Jeffrey R. Strawn, MD, the answer depends on onset and duration of the medication and how that fits in to the patient’s current needs.

The most common treatment for ADHD, stimulants, are amphetamine-based and methylphenidate-based compounds known for improving core symptoms of inattention, impulsivity, and hyperactivity and are “probably associated with the most efficacy relative to the other interventions,” Dr. Strawn, associate professor of psychiatry, pediatrics, and clinical pharmacology at Cincinnati Children’s Hospital Medical Center, said at Psychopharmacology Update presented by Current Psychiatry and Global Academy for Medical Education. “But what I think is also really important for us to remember as clinicians is that they improve adherence, social interactions, [and] academic efficiency as well as accuracy.”

Other ADHD pharmacotherapy options include nonstimulant norepinephrine reuptake inhibitors (NRIs) like atomoxetine, and alpha-2 agonists like the extended-release forms of guanfacine and clonidine. All are Food and Drug Administration–approved for the treatment of ADHD, and the FDA has approved some combination alpha-2 agonists and stimulants treatments for ADHD as well.

When making decisions about formulations for ADHD pharmacotherapy, clinicians should think about whether the patient has issues swallowing tablets or capsules. Tablets, capsules, and chewable tablets may be appropriate for patients who can easily take these medications, while patients who have problems with swallowing pills may benefit from dissolvable tablets, solutions, and transdermal applications. Each of these options “have differences in terms of absorption, also differences in terms of intestinal transit time in younger children, as well as patients perhaps with irritable bowel, as well as other conditions that may affect absorption,” Dr. Strawn said. Different formulations have unique considerations: liquid formulations have the benefit of making precise adjustments, sublingual formulations may have quick absorption and onset, and oral dissolvable tablets can improve treatment adherence and reduce misuse of medication.

Formulations can be available as a delayed release, extended release, pulsatile release, targeted release, or a combination of immediate, delayed, and/or extended release. “Ultimately, what this gives rise to is differences in onset of action and duration, as well as differences in the elimination profile of the medication,” he said.

Transdermal formulations “avoid the first-pass metabolism, which may reduce side effects or increase efficacy,” but patients converting from an oral formulation may require reducing the dose. “It’s always important to remember, for example, with something like Daytrana, the transdermal methylphenidate formulation, if we’re converting a patient from an oral methylphenidate, we roughly need to use half the dose for the transdermal formulation,” Dr. Strawn explained. Transdermal formulations can carry benefits of steady plasma concentrations and longer duration of action but may cause skin irritation or accidentally be removed. “It’s really important they’re properly disposed of because oftentimes they do contain some active medication within the residual matrix.”
 

Methylphenidate, mixed amphetamine salt–based preparations

Modified-release formulations include matrix- or reservoir-based formulations and are most importantly differentiated from other formulations by their gastrointestinal (GI) transit time and the permeation through the GI membrane. When considering what formulation to choose, “it’s important to consider that, even with an ‘extended release formulation,’ all of these medications have some percentage that is immediately released, and that percentage varies considerably from formulation to formulation,” Dr. Strawn said.

He noted that brand names are sometimes used for formulations “because it’s often very difficult for us as clinicians and even for pharmacists to distinguish between these various formulations of the medication, which often have the same ‘extended’ or ‘delayed release’ modifying term within the name of the medication.”

Examples of medications that have greater immediate release include Metadate CD (30%), Aptensio XR (37%), long-acting methylphenidate (50%), dexmethylphenidate extended-release (50%), and Mixed Salts amphetamine extended release (50%). Formulations with a less immediate release include Quillivant solution or Quillichew chewable tablets (20%), Dyanaval XR solution (20%), OROS methylphenidate (22%), Daytrana that begins within 1 or 2 hours and lasts for 9 hours, or lisdexamfetamine that begins within 1 hour and lasts for 9 hours.

Depending on a patient’s needs, one particular formulation may work better than another. Dexmethylphenidate (Focalin XR) has a 50% immediate release and 50% extended release formulation, which “may be really important for a high school student who has first period precalculus followed by second period human geography,” Dr. Strawn said, while “a patient who may have first period study hall and second period art” may benefit from OROS methylphenidate.

Clinicians should also consider the effect of counterclockwise hysteresis when adding a short-acting stimulant later in the day. “There seems to be something really magic about having that ascending concentration time curve that, when we’re on the descending loop of that concentration time curve, we really seem to get a dramatic waning of the effect of the medication, even though technically the concentration is within the ‘therapeutic range,’ ” Dr. Strawn said. “With counterclockwise hysteresis, we see that the effect increases with time for a given concentration of the medication.”
 

Combining ADHD pharmacotherapies

For children and adolescents with ADHD, atomoxetine is a nonstimulant, FDA-approved treatment option. “It seems to be effective not just in terms of total ADHD symptoms, but also in terms of hyperactive and impulsive symptoms as well as the inattentive symptoms,” Dr. Strawn said.

Pharmacogenetics can be a guide for selecting an atomoxetine for a patient with ADHD, he noted. “What I think is most relevant here is the way in which pharmacogenetics can actually help guide our dosing, which then optimizes tolerability, potentially efficacy of atomoxetine,” he said. “Atomoxetine is pretty extensively metabolized by [CYP]2D6, and it’s one of about 300 medications that actually has specific labeling from the FDA on dosing based on genotype. It recommends a slower titration, as well as a lower target dose of atomoxetine in individuals who are P450 2D6 poor metabolizers relative to those patients who are ultra-rapid or normal metabolizers.”

Atomoxetine is most often combined with methylphenidate and has some evidence of benefit in children or adolescents who do not have an adequate response to stimulants alone. When combining stimulants with the alpha-2 agonists guanfacine or clonidine, “there are some improvements in terms of the combination treatment relative to the monotherapy,” Dr. Strawn said. He also emphasized that patients taking guanfacine immediate release tend to have better absorption and faster onset, compared with the extended release formulation. “This is something that potentially is very important when we think beyond steady state and we think about the practical use of this medication,” he said.
 

Baseline history is important

Overall, taking a baseline history of a patient with ADHD is “critically important” before starting them on stimulants, Dr. Strawn said. “Specifically, I would recommend documenting a negative history of syncope, family history of sudden cardiac death, as well as the lack of any known history of structural cardiac abnormalities,” he said. “Without a consultation with the cardiologist specifically around this question, I’m very, very, very hesitant – as in I don’t – use stimulants in patients who have histories of aortic stenosis, Wolff-Parkinson-White, as well as arrhythmogenic right ventricular dysplasia.”

Although patients with ADHD were typically followed with routine hemodynamic monitoring every 3 months prior to the COVID-19 pandemic, some clinicians see their patients with ADHD less frequently if they have been stabilized on a stimulant. “It is important to check not just with the patient, but also with parents and teachers as we’re adjusting medication dose and trying to optimize the treatment regimen, particularly in young children. In adults, it may also be very helpful to talk with spouses,” Dr. Strawn said.

Dr. Strawn also called attention to a recommendation to perform a routine electrocardiogram (EKG) in patients with ADHD who might receive stimulants. “At present, there is no recommendation to obtain a routine screening EKG in these patients, provided that we have an absence of those other red flags on the history,” he said. “Certainly, I would consider it in situations where I do have persistent tachycardia or hypertension, or there are other treatment-emergent symptoms, although really in many of these situations, I’m actually speaking on the phone with my pediatric or adult cardiology colleagues.”

Global Academy and this news organization are owned by the same parent company. Dr. Strawn reported receiving research support from Allergan, the FDA, the National Institutes of Health, Neuronetics, and Otsuka; serving as a consultant and receiving material support from Myriad; receiving royalties from Springer Publishing; and serving as a consultant for Intra-Cellular Therapies. In addition, he has been on the speaker’s bureau for the Neuroscience Education Institute and CMEology, and Medscape.

The United States just passed a dubious COVID-19 milestone: Just over 1% of all children have been infected by the coronavirus this year, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

There have been 1,052 cases of COVID-19 per 100,000 children as of Oct. 22, and that works out to 1.05% of all children in the country. The cumulative number of pediatric cases is 792,188, and children now represent 11% of all COVID-19 cases, the AAP and the CHA reported Oct. 26.

There were just over 50,000 new child cases reported in the week ending Oct. 22, which was 13.6% of the national total of almost 370,000. That’s up slightly from the 13.3% the previous week but still down from the spike seen in mid-September, based on the data collected from the websites of 49 state health departments (New York does not report ages), along with the District of Columbia, New York City, Puerto Rico, and Guam.

The state-level data show that California has had more COVID-19 cases in children (92,864) than any other state, although Texas has reported ages for only 7% of its confirmed cases. Illinois is next with 46,006 cases, followed by Florida at 45,575, although Florida is using an age range of 0-14 years to define a child case, the AAP and CHA noted.

Other measures largely put small states at the extremes:

• North Dakota has the highest cumulative rate: 2,954 cases per 100,000 children.
• Vermont has the lowest cumulative rate: 190.5 per 100,000.
• Wyoming has the highest proportion of cases in children: 27.7%.
• New Jersey has the lowest proportion of child cases: 4.6%.

There were no COVID-19–related deaths in children reported the week ending Oct. 22, so the total number remains at 120, which is just 0.06% of the total for all ages, based on data from 42 states and New York City. Hospitalization figures put admissions at almost 5,600 in children, or 1.7% of all hospitalizations, although those data come from just 24 states and New York City, the AAP and CHA said.

rfranki@mdedge.com

The United States just passed a dubious COVID-19 milestone: Just over 1% of all children have been infected by the coronavirus this year, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

There have been 1,052 cases of COVID-19 per 100,000 children as of Oct. 22, and that works out to 1.05% of all children in the country. The cumulative number of pediatric cases is 792,188, and children now represent 11% of all COVID-19 cases, the AAP and the CHA reported Oct. 26.

There were just over 50,000 new child cases reported in the week ending Oct. 22, which was 13.6% of the national total of almost 370,000. That’s up slightly from the 13.3% the previous week but still down from the spike seen in mid-September, based on the data collected from the websites of 49 state health departments (New York does not report ages), along with the District of Columbia, New York City, Puerto Rico, and Guam.

The state-level data show that California has had more COVID-19 cases in children (92,864) than any other state, although Texas has reported ages for only 7% of its confirmed cases. Illinois is next with 46,006 cases, followed by Florida at 45,575, although Florida is using an age range of 0-14 years to define a child case, the AAP and CHA noted.

Other measures largely put small states at the extremes:

• North Dakota has the highest cumulative rate: 2,954 cases per 100,000 children.
• Vermont has the lowest cumulative rate: 190.5 per 100,000.
• Wyoming has the highest proportion of cases in children: 27.7%.
• New Jersey has the lowest proportion of child cases: 4.6%.

There were no COVID-19–related deaths in children reported the week ending Oct. 22, so the total number remains at 120, which is just 0.06% of the total for all ages, based on data from 42 states and New York City. Hospitalization figures put admissions at almost 5,600 in children, or 1.7% of all hospitalizations, although those data come from just 24 states and New York City, the AAP and CHA said.

rfranki@mdedge.com

The United States just passed a dubious COVID-19 milestone: Just over 1% of all children have been infected by the coronavirus this year, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

There have been 1,052 cases of COVID-19 per 100,000 children as of Oct. 22, and that works out to 1.05% of all children in the country. The cumulative number of pediatric cases is 792,188, and children now represent 11% of all COVID-19 cases, the AAP and the CHA reported Oct. 26.

There were just over 50,000 new child cases reported in the week ending Oct. 22, which was 13.6% of the national total of almost 370,000. That’s up slightly from the 13.3% the previous week but still down from the spike seen in mid-September, based on the data collected from the websites of 49 state health departments (New York does not report ages), along with the District of Columbia, New York City, Puerto Rico, and Guam.

The state-level data show that California has had more COVID-19 cases in children (92,864) than any other state, although Texas has reported ages for only 7% of its confirmed cases. Illinois is next with 46,006 cases, followed by Florida at 45,575, although Florida is using an age range of 0-14 years to define a child case, the AAP and CHA noted.

Other measures largely put small states at the extremes:

• North Dakota has the highest cumulative rate: 2,954 cases per 100,000 children.
• Vermont has the lowest cumulative rate: 190.5 per 100,000.
• Wyoming has the highest proportion of cases in children: 27.7%.
• New Jersey has the lowest proportion of child cases: 4.6%.

There were no COVID-19–related deaths in children reported the week ending Oct. 22, so the total number remains at 120, which is just 0.06% of the total for all ages, based on data from 42 states and New York City. Hospitalization figures put admissions at almost 5,600 in children, or 1.7% of all hospitalizations, although those data come from just 24 states and New York City, the AAP and CHA said.

rfranki@mdedge.com

Antibody response to the SARS-CoV-2 virus wanes over time, latest research has suggested.

An ongoing study led by Imperial College London (ICL) found that the proportion of people testing positive for COVID-19 antibodies dropped by 26.5% over a 3-month period between June and September.

The findings from a non–peer reviewed preprint suggested that infection with SARS-CoV-2 confers only limited protection against reinfection.

Professor Paul Elliott, director of the REACT-2 programme at ICL, said: “Testing positive for antibodies does not mean you are immune to COVID-19.

“It remains unclear what level of immunity antibodies provide, or for how long this immunity lasts.”

Experts said that, while the findings suggested that immunity might fade over time, the severity of illness from further infections could be reduced.
 

Antibody prevalence declined in all adults

Results from cross-sectional studies over the 3-month period involved 365,104 adults who self-administered a lateral flow immunoassay test.

There were 17,576 positive tests over the three rounds.

Antibody prevalence, adjusted for test characteristics and weighted to the adult population of England, declined from 6.0% to 4.4%, a reduction of 26.5% over the 3 months.

The decline was seen in all age groups. However, the lowest prevalence of a positive test, and the largest fall, was seen in those aged 75 years and older.

No change was seen in positive antibody tests in health care workers over the 3 months.

The results suggested that people who did not show symptoms of COVID-19 were more likely to lose detectable antibodies sooner than those who did show symptoms.

Prof Helen Ward, one of the lead authors of the report said that, while it was clear that the proportion of people with antibodies was falling over time, “We don’t yet know whether this will leave these people at risk of reinfection with the virus that causes COVID-19, but it is essential that everyone continues to follow guidance to reduce the risk to themselves and others.”
 

Results ‘weaken argument for herd immunity’

Commenting on the results to the Science Media Centre, Rowland Kao, professor of veterinary epidemiology and data science at the University of Edinburgh, warned that, if the results were correct, “any strategy that relies on ‘herd immunity’ lacks credibility.”

However, he added that, “while the decline is substantial, nevertheless substantial proportions of the population do retain some immune response, over 4 months after the peak of the epidemic”.

Eleanor Riley, professor of immunology and infectious disease, also from the University of Edinburgh, said it was too early to assume that immunity to SARS-CoV-2 did not last because “the study does not look at antibody concentrations, antibody function, or other aspects of immunity such as T-cell immunity and does not look at the trajectory of antibody levels in the same individuals over time”.

However, she said the findings did not mean that a vaccine would be ineffective because vaccines contained adjuvants that could induce durable immune responses, particularly with multiple immunizations.

“What is not clear is how quickly antibody levels would rise again if a person encounters the SARS-CoV-2 virus a second time. It is possible they will still rapidly respond, and either have a milder illness, or remain protected through immune memory,” commented Dr. Alexander Edwards, associate professor in biomedical technology at the University of Reading.

Health Minister Lord Bethell said: “Regardless of the result of an antibody test, everyone must continue to comply with government guidelines including social distancing, self-isolating, and getting a test if you have symptoms, and always remember: hands, face, space.”
 

This article first appeared on Medscape.com.

Antibody response to the SARS-CoV-2 virus wanes over time, latest research has suggested.

An ongoing study led by Imperial College London (ICL) found that the proportion of people testing positive for COVID-19 antibodies dropped by 26.5% over a 3-month period between June and September.

The findings from a non–peer reviewed preprint suggested that infection with SARS-CoV-2 confers only limited protection against reinfection.

Professor Paul Elliott, director of the REACT-2 programme at ICL, said: “Testing positive for antibodies does not mean you are immune to COVID-19.

“It remains unclear what level of immunity antibodies provide, or for how long this immunity lasts.”

Experts said that, while the findings suggested that immunity might fade over time, the severity of illness from further infections could be reduced.
 

Antibody prevalence declined in all adults

Results from cross-sectional studies over the 3-month period involved 365,104 adults who self-administered a lateral flow immunoassay test.

There were 17,576 positive tests over the three rounds.

Antibody prevalence, adjusted for test characteristics and weighted to the adult population of England, declined from 6.0% to 4.4%, a reduction of 26.5% over the 3 months.

The decline was seen in all age groups. However, the lowest prevalence of a positive test, and the largest fall, was seen in those aged 75 years and older.

No change was seen in positive antibody tests in health care workers over the 3 months.

The results suggested that people who did not show symptoms of COVID-19 were more likely to lose detectable antibodies sooner than those who did show symptoms.

Prof Helen Ward, one of the lead authors of the report said that, while it was clear that the proportion of people with antibodies was falling over time, “We don’t yet know whether this will leave these people at risk of reinfection with the virus that causes COVID-19, but it is essential that everyone continues to follow guidance to reduce the risk to themselves and others.”
 

Results ‘weaken argument for herd immunity’

Commenting on the results to the Science Media Centre, Rowland Kao, professor of veterinary epidemiology and data science at the University of Edinburgh, warned that, if the results were correct, “any strategy that relies on ‘herd immunity’ lacks credibility.”

However, he added that, “while the decline is substantial, nevertheless substantial proportions of the population do retain some immune response, over 4 months after the peak of the epidemic”.

Eleanor Riley, professor of immunology and infectious disease, also from the University of Edinburgh, said it was too early to assume that immunity to SARS-CoV-2 did not last because “the study does not look at antibody concentrations, antibody function, or other aspects of immunity such as T-cell immunity and does not look at the trajectory of antibody levels in the same individuals over time”.

However, she said the findings did not mean that a vaccine would be ineffective because vaccines contained adjuvants that could induce durable immune responses, particularly with multiple immunizations.

“What is not clear is how quickly antibody levels would rise again if a person encounters the SARS-CoV-2 virus a second time. It is possible they will still rapidly respond, and either have a milder illness, or remain protected through immune memory,” commented Dr. Alexander Edwards, associate professor in biomedical technology at the University of Reading.

Health Minister Lord Bethell said: “Regardless of the result of an antibody test, everyone must continue to comply with government guidelines including social distancing, self-isolating, and getting a test if you have symptoms, and always remember: hands, face, space.”
 

This article first appeared on Medscape.com.

Antibody response to the SARS-CoV-2 virus wanes over time, latest research has suggested.

An ongoing study led by Imperial College London (ICL) found that the proportion of people testing positive for COVID-19 antibodies dropped by 26.5% over a 3-month period between June and September.

The findings from a non–peer reviewed preprint suggested that infection with SARS-CoV-2 confers only limited protection against reinfection.

Professor Paul Elliott, director of the REACT-2 programme at ICL, said: “Testing positive for antibodies does not mean you are immune to COVID-19.

“It remains unclear what level of immunity antibodies provide, or for how long this immunity lasts.”

Experts said that, while the findings suggested that immunity might fade over time, the severity of illness from further infections could be reduced.
 

Antibody prevalence declined in all adults

Results from cross-sectional studies over the 3-month period involved 365,104 adults who self-administered a lateral flow immunoassay test.

There were 17,576 positive tests over the three rounds.

Antibody prevalence, adjusted for test characteristics and weighted to the adult population of England, declined from 6.0% to 4.4%, a reduction of 26.5% over the 3 months.

The decline was seen in all age groups. However, the lowest prevalence of a positive test, and the largest fall, was seen in those aged 75 years and older.

No change was seen in positive antibody tests in health care workers over the 3 months.

The results suggested that people who did not show symptoms of COVID-19 were more likely to lose detectable antibodies sooner than those who did show symptoms.

Prof Helen Ward, one of the lead authors of the report said that, while it was clear that the proportion of people with antibodies was falling over time, “We don’t yet know whether this will leave these people at risk of reinfection with the virus that causes COVID-19, but it is essential that everyone continues to follow guidance to reduce the risk to themselves and others.”
 

Results ‘weaken argument for herd immunity’

Commenting on the results to the Science Media Centre, Rowland Kao, professor of veterinary epidemiology and data science at the University of Edinburgh, warned that, if the results were correct, “any strategy that relies on ‘herd immunity’ lacks credibility.”

However, he added that, “while the decline is substantial, nevertheless substantial proportions of the population do retain some immune response, over 4 months after the peak of the epidemic”.

Eleanor Riley, professor of immunology and infectious disease, also from the University of Edinburgh, said it was too early to assume that immunity to SARS-CoV-2 did not last because “the study does not look at antibody concentrations, antibody function, or other aspects of immunity such as T-cell immunity and does not look at the trajectory of antibody levels in the same individuals over time”.

However, she said the findings did not mean that a vaccine would be ineffective because vaccines contained adjuvants that could induce durable immune responses, particularly with multiple immunizations.

“What is not clear is how quickly antibody levels would rise again if a person encounters the SARS-CoV-2 virus a second time. It is possible they will still rapidly respond, and either have a milder illness, or remain protected through immune memory,” commented Dr. Alexander Edwards, associate professor in biomedical technology at the University of Reading.

Health Minister Lord Bethell said: “Regardless of the result of an antibody test, everyone must continue to comply with government guidelines including social distancing, self-isolating, and getting a test if you have symptoms, and always remember: hands, face, space.”
 

This article first appeared on Medscape.com.

Long-term treatment with ataluren delays loss of ambulation and may delay decline in pulmonary function in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD), according to study results presented at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year. Because so few patients in the study reached one of the negative pulmonary endpoints, longer follow-up will be needed to assess more conclusively the effect of ataluren on pulmonary function, said Francesco Bibbiani, MD, vice president of clinical development at PTC Therapeutics.

DMD is a rare and fatal neuromuscular disorder that causes progressive muscle weakness. Between 10% and 15% of patients with DMD have a nonsense mutation in the DMD gene. This mutation creates a premature stop codon that prevents the translation of a full-length dystrophin protein. Ataluren is designed to promote readthrough of this premature stop codon, thus enabling the production of a full-length dystrophin protein. An oral formulation of the drug has been approved in several European and South American countries.
 

Comparing treatment and standard of care

Study 019 was a phase 3, multicenter, open-label, long-term safety study of ataluren that enrolled international patients with nmDMD, most of whom had participated previously in a trial of ataluren. Dr. Bibbiani and colleagues conducted a post hoc analysis of Study 019 data to determine whether patients with nmDMD who received ataluren and standard of care for as long as 240 weeks had a different time to loss of ambulation and to decline of pulmonary function, compared with patients who received standard of care alone. Patients who were eligible to participate in Study 019 were male, had nmDMD, and had completed the blinded study drug treatment in a previous PTC-sponsored study. Treatment consisted of two 10-mg/kg doses and one 20-mg/kg dose of ataluren per day.

Dr. Bibbiani and colleagues used participants in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG DNHS) as a control group. CINRG DNHS was a prospective, longitudinal study of patients with DMD who received standard of care at 20 centers worldwide from 2006 to 2016. Dr. Bibbiani and colleagues used propensity-score matching to pair participants in this study with participants in Study 019. They matched patients with respect to age at onset of first symptoms, age at initiation of corticosteroid use, duration of deflazacort use, and duration of use of other corticosteroids. These factors are established predictors of disease progression in DMD.

Patients were eligible for inclusion in the post hoc analysis if they had available data for age, loss of ambulation, and the covariates selected for matching. Of 94 Study 019 participants, 60 were eligible for propensity-score matching with participants in CINRG DNHS. Forty-five nonambulatory patients were eligible for matching in the analysis of age at the decline in pulmonary function because data for age at loss of ambulation and for the three pulmonary endpoints measured were available for them. Thus, comparable population sizes were available for each analysis.
 

Treatment delayed disease milestones

Kaplan–Meier analysis indicated that the median age at various disease milestones was higher among patients who received ataluren and standard of care, compared with those who received standard of care alone. The median age at loss of ambulation was 15.5 years for Study 019 participants and 13.3 years for CINRG DNHS patients. The median age at predicted forced vital capacity (FVC) of less than 60% was 18.1 years for Study 019 participants and 15.8 years for CINRG DNHS participants. The median age at predicted FVC of less than 50% was 19.1 years for Study 019 participants and 17.9 years for CINRG DNHS participants. Finally, the median age at FVC of less than 1 L was not calculable for Study 019 participants and 23.8 years for CINRG DNHS participants.

The Study 019 and CINRG DNHS study groups are sponsored by PTC Therapeutics, which developed ataluren. Dr. Bibbiani is an employee of PTC Therapeutics.

egreb@mdedge.com

SOURCE: McDonald C, et al. CNS-ICNA 2020. Abstract PL69.

Long-term treatment with ataluren delays loss of ambulation and may delay decline in pulmonary function in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD), according to study results presented at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year. Because so few patients in the study reached one of the negative pulmonary endpoints, longer follow-up will be needed to assess more conclusively the effect of ataluren on pulmonary function, said Francesco Bibbiani, MD, vice president of clinical development at PTC Therapeutics.

DMD is a rare and fatal neuromuscular disorder that causes progressive muscle weakness. Between 10% and 15% of patients with DMD have a nonsense mutation in the DMD gene. This mutation creates a premature stop codon that prevents the translation of a full-length dystrophin protein. Ataluren is designed to promote readthrough of this premature stop codon, thus enabling the production of a full-length dystrophin protein. An oral formulation of the drug has been approved in several European and South American countries.
 

Comparing treatment and standard of care

Study 019 was a phase 3, multicenter, open-label, long-term safety study of ataluren that enrolled international patients with nmDMD, most of whom had participated previously in a trial of ataluren. Dr. Bibbiani and colleagues conducted a post hoc analysis of Study 019 data to determine whether patients with nmDMD who received ataluren and standard of care for as long as 240 weeks had a different time to loss of ambulation and to decline of pulmonary function, compared with patients who received standard of care alone. Patients who were eligible to participate in Study 019 were male, had nmDMD, and had completed the blinded study drug treatment in a previous PTC-sponsored study. Treatment consisted of two 10-mg/kg doses and one 20-mg/kg dose of ataluren per day.

Dr. Bibbiani and colleagues used participants in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG DNHS) as a control group. CINRG DNHS was a prospective, longitudinal study of patients with DMD who received standard of care at 20 centers worldwide from 2006 to 2016. Dr. Bibbiani and colleagues used propensity-score matching to pair participants in this study with participants in Study 019. They matched patients with respect to age at onset of first symptoms, age at initiation of corticosteroid use, duration of deflazacort use, and duration of use of other corticosteroids. These factors are established predictors of disease progression in DMD.

Patients were eligible for inclusion in the post hoc analysis if they had available data for age, loss of ambulation, and the covariates selected for matching. Of 94 Study 019 participants, 60 were eligible for propensity-score matching with participants in CINRG DNHS. Forty-five nonambulatory patients were eligible for matching in the analysis of age at the decline in pulmonary function because data for age at loss of ambulation and for the three pulmonary endpoints measured were available for them. Thus, comparable population sizes were available for each analysis.
 

Treatment delayed disease milestones

Kaplan–Meier analysis indicated that the median age at various disease milestones was higher among patients who received ataluren and standard of care, compared with those who received standard of care alone. The median age at loss of ambulation was 15.5 years for Study 019 participants and 13.3 years for CINRG DNHS patients. The median age at predicted forced vital capacity (FVC) of less than 60% was 18.1 years for Study 019 participants and 15.8 years for CINRG DNHS participants. The median age at predicted FVC of less than 50% was 19.1 years for Study 019 participants and 17.9 years for CINRG DNHS participants. Finally, the median age at FVC of less than 1 L was not calculable for Study 019 participants and 23.8 years for CINRG DNHS participants.

The Study 019 and CINRG DNHS study groups are sponsored by PTC Therapeutics, which developed ataluren. Dr. Bibbiani is an employee of PTC Therapeutics.

egreb@mdedge.com

SOURCE: McDonald C, et al. CNS-ICNA 2020. Abstract PL69.

Long-term treatment with ataluren delays loss of ambulation and may delay decline in pulmonary function in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD), according to study results presented at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year. Because so few patients in the study reached one of the negative pulmonary endpoints, longer follow-up will be needed to assess more conclusively the effect of ataluren on pulmonary function, said Francesco Bibbiani, MD, vice president of clinical development at PTC Therapeutics.

DMD is a rare and fatal neuromuscular disorder that causes progressive muscle weakness. Between 10% and 15% of patients with DMD have a nonsense mutation in the DMD gene. This mutation creates a premature stop codon that prevents the translation of a full-length dystrophin protein. Ataluren is designed to promote readthrough of this premature stop codon, thus enabling the production of a full-length dystrophin protein. An oral formulation of the drug has been approved in several European and South American countries.
 

Comparing treatment and standard of care

Study 019 was a phase 3, multicenter, open-label, long-term safety study of ataluren that enrolled international patients with nmDMD, most of whom had participated previously in a trial of ataluren. Dr. Bibbiani and colleagues conducted a post hoc analysis of Study 019 data to determine whether patients with nmDMD who received ataluren and standard of care for as long as 240 weeks had a different time to loss of ambulation and to decline of pulmonary function, compared with patients who received standard of care alone. Patients who were eligible to participate in Study 019 were male, had nmDMD, and had completed the blinded study drug treatment in a previous PTC-sponsored study. Treatment consisted of two 10-mg/kg doses and one 20-mg/kg dose of ataluren per day.

Dr. Bibbiani and colleagues used participants in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG DNHS) as a control group. CINRG DNHS was a prospective, longitudinal study of patients with DMD who received standard of care at 20 centers worldwide from 2006 to 2016. Dr. Bibbiani and colleagues used propensity-score matching to pair participants in this study with participants in Study 019. They matched patients with respect to age at onset of first symptoms, age at initiation of corticosteroid use, duration of deflazacort use, and duration of use of other corticosteroids. These factors are established predictors of disease progression in DMD.

Patients were eligible for inclusion in the post hoc analysis if they had available data for age, loss of ambulation, and the covariates selected for matching. Of 94 Study 019 participants, 60 were eligible for propensity-score matching with participants in CINRG DNHS. Forty-five nonambulatory patients were eligible for matching in the analysis of age at the decline in pulmonary function because data for age at loss of ambulation and for the three pulmonary endpoints measured were available for them. Thus, comparable population sizes were available for each analysis.
 

Treatment delayed disease milestones

Kaplan–Meier analysis indicated that the median age at various disease milestones was higher among patients who received ataluren and standard of care, compared with those who received standard of care alone. The median age at loss of ambulation was 15.5 years for Study 019 participants and 13.3 years for CINRG DNHS patients. The median age at predicted forced vital capacity (FVC) of less than 60% was 18.1 years for Study 019 participants and 15.8 years for CINRG DNHS participants. The median age at predicted FVC of less than 50% was 19.1 years for Study 019 participants and 17.9 years for CINRG DNHS participants. Finally, the median age at FVC of less than 1 L was not calculable for Study 019 participants and 23.8 years for CINRG DNHS participants.

The Study 019 and CINRG DNHS study groups are sponsored by PTC Therapeutics, which developed ataluren. Dr. Bibbiani is an employee of PTC Therapeutics.

egreb@mdedge.com

SOURCE: McDonald C, et al. CNS-ICNA 2020. Abstract PL69.

Among patients with pediatric-onset relapsing-remitting multiple sclerosis (MS), newer disease-modifying therapies (DMTs) reduce clinical and radiological disease activity more effectively than older injectable therapies. Nevertheless, all DMTs reduce children’s annualized relapse rate (ARR), according to results presented at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year.

“Our study adds weight to the argument for an imminent shift in clinical practice toward the use of newer, more efficacious DMTs in the first instance,” said Omar Abdel-Mannan, MD, of Great Ormond Street Hospital in London. MRI activity continues among patients treated with DMTs, and the number of relapses is highest in the period following diagnosis. But because the effect of treatment on brain atrophy is greatest in the initial period of disease, “this time period may represent a critical therapeutic window for the use of highly effective therapies,” said Dr. Abdel-Mannan.
 

An examination of medical records

MS is much less prevalent among children than among adults. Compared with adults with MS, children with MS have a higher relapse rate and slower accumulation of disability. The individual response to DMTs is variable, said Dr. Abdel-Mannan. Furthermore, current standards of care for pediatric MS vary by center and are based on adult protocols.

Dr. Abdel-Mannan and colleagues conducted a retrospective study to evaluate the real-world effectiveness of the newer oral and infusion DMTs, compared with the older injectable DMTs, in children with relapsing-remitting MS. They examined data from seven tertiary pediatric neurology centers in the United Kingdom and identified patients under age 18 years with relapsing-remitting MS who were treated with DMTs between 2012 and 2018. The investigators reviewed clinical and paraclinical data retrospectively using electronic medical records. They compared patients’ ARR, new radiological activity, and Expanded Disability Status Scale score pretreatment and on treatment.

The researchers included 103 patients in their analysis. The population’s median age was 14 years. The ratio of girls to boys was approximately 3:1. Whites and other races/ethnicities accounted for approximately equal groups of patients. About one-third of patients presented with a clinically isolated syndrome (CIS) in the form of transverse myelitis or optic neuritis. Two-thirds presented with other CIS phenotypes. Almost all children had an abnormal MRI at onset.
 

Most patients initiated injectable DMTs

Of the 103 patients, 89 started treatment with an injectable (e.g., glatiramer or interferon) or an older DMT. Fourteen patients began treatment with a newer DMT (e.g., dimethyl fumarate, fingolimod, natalizumab, and alemtuzumab). Three of the 89 patients on an injectable DMT switched to another injectable DMT, and two of these patients later escalated to a newer DMT. Thirty-five of the 89 patients who initiated an injectable DMT were escalated immediately to a newer DMT. One of these patients later switched to another newer DMT. Two of the 14 patients who started on a newer DMT as their first drug switched to another newer DMT.

The investigators observed a reduction in ARR for all DMTs used during the study period. Nevertheless, a significant number of patients receiving injectable DMTs continued to relapse on treatment. Almost all patients receiving newer DMTs, however, had a reduction in relapses. When Dr. Abdel-Mannan and colleagues performed Kaplan–Meier survival analysis, they found that patients receiving newer DMTs had a longer time to first relapse and a longer time to switch treatment over 2 years, compared with patients receiving injectable DMTs. In addition, patients receiving newer DMTs had a longer time to develop new radiological activity, compared with patients receiving injectables. The analysis also indicated that the proportion of patients with new radiological activity was higher than the proportion who had clinical relapses and an Expanded Disability Status Scale score increase of more than 1 point over 2 years.

In all, 55 of the children receiving injectable DMTs and 18 of the patients receiving newer DMTs had side effects. The most commonly reported side effects were flulike symptoms and injection-site reactions. Five patients discontinued or switched their DMTs because of side effects. “Reassuringly, no pediatric-specific side effects were reported,” said Dr. Abdel-Mannan. The newer DMTs had similar short-term safety, tolerability, and side-effect profiles in these children as in adult patients.

The study was conducted on behalf of the UK Childhood Inflammatory Demyelination Network. Dr. Abdel-Mannan had no relevant disclosures.

egreb@mdedge.com

SOURCE: Abdel-Mannan O et al. CNS-ICNA 2020, Abstract PL10.

Among patients with pediatric-onset relapsing-remitting multiple sclerosis (MS), newer disease-modifying therapies (DMTs) reduce clinical and radiological disease activity more effectively than older injectable therapies. Nevertheless, all DMTs reduce children’s annualized relapse rate (ARR), according to results presented at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year.

“Our study adds weight to the argument for an imminent shift in clinical practice toward the use of newer, more efficacious DMTs in the first instance,” said Omar Abdel-Mannan, MD, of Great Ormond Street Hospital in London. MRI activity continues among patients treated with DMTs, and the number of relapses is highest in the period following diagnosis. But because the effect of treatment on brain atrophy is greatest in the initial period of disease, “this time period may represent a critical therapeutic window for the use of highly effective therapies,” said Dr. Abdel-Mannan.
 

An examination of medical records

MS is much less prevalent among children than among adults. Compared with adults with MS, children with MS have a higher relapse rate and slower accumulation of disability. The individual response to DMTs is variable, said Dr. Abdel-Mannan. Furthermore, current standards of care for pediatric MS vary by center and are based on adult protocols.

Dr. Abdel-Mannan and colleagues conducted a retrospective study to evaluate the real-world effectiveness of the newer oral and infusion DMTs, compared with the older injectable DMTs, in children with relapsing-remitting MS. They examined data from seven tertiary pediatric neurology centers in the United Kingdom and identified patients under age 18 years with relapsing-remitting MS who were treated with DMTs between 2012 and 2018. The investigators reviewed clinical and paraclinical data retrospectively using electronic medical records. They compared patients’ ARR, new radiological activity, and Expanded Disability Status Scale score pretreatment and on treatment.

The researchers included 103 patients in their analysis. The population’s median age was 14 years. The ratio of girls to boys was approximately 3:1. Whites and other races/ethnicities accounted for approximately equal groups of patients. About one-third of patients presented with a clinically isolated syndrome (CIS) in the form of transverse myelitis or optic neuritis. Two-thirds presented with other CIS phenotypes. Almost all children had an abnormal MRI at onset.
 

Most patients initiated injectable DMTs

Of the 103 patients, 89 started treatment with an injectable (e.g., glatiramer or interferon) or an older DMT. Fourteen patients began treatment with a newer DMT (e.g., dimethyl fumarate, fingolimod, natalizumab, and alemtuzumab). Three of the 89 patients on an injectable DMT switched to another injectable DMT, and two of these patients later escalated to a newer DMT. Thirty-five of the 89 patients who initiated an injectable DMT were escalated immediately to a newer DMT. One of these patients later switched to another newer DMT. Two of the 14 patients who started on a newer DMT as their first drug switched to another newer DMT.

The investigators observed a reduction in ARR for all DMTs used during the study period. Nevertheless, a significant number of patients receiving injectable DMTs continued to relapse on treatment. Almost all patients receiving newer DMTs, however, had a reduction in relapses. When Dr. Abdel-Mannan and colleagues performed Kaplan–Meier survival analysis, they found that patients receiving newer DMTs had a longer time to first relapse and a longer time to switch treatment over 2 years, compared with patients receiving injectable DMTs. In addition, patients receiving newer DMTs had a longer time to develop new radiological activity, compared with patients receiving injectables. The analysis also indicated that the proportion of patients with new radiological activity was higher than the proportion who had clinical relapses and an Expanded Disability Status Scale score increase of more than 1 point over 2 years.

In all, 55 of the children receiving injectable DMTs and 18 of the patients receiving newer DMTs had side effects. The most commonly reported side effects were flulike symptoms and injection-site reactions. Five patients discontinued or switched their DMTs because of side effects. “Reassuringly, no pediatric-specific side effects were reported,” said Dr. Abdel-Mannan. The newer DMTs had similar short-term safety, tolerability, and side-effect profiles in these children as in adult patients.

The study was conducted on behalf of the UK Childhood Inflammatory Demyelination Network. Dr. Abdel-Mannan had no relevant disclosures.

egreb@mdedge.com

SOURCE: Abdel-Mannan O et al. CNS-ICNA 2020, Abstract PL10.

Among patients with pediatric-onset relapsing-remitting multiple sclerosis (MS), newer disease-modifying therapies (DMTs) reduce clinical and radiological disease activity more effectively than older injectable therapies. Nevertheless, all DMTs reduce children’s annualized relapse rate (ARR), according to results presented at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year.

“Our study adds weight to the argument for an imminent shift in clinical practice toward the use of newer, more efficacious DMTs in the first instance,” said Omar Abdel-Mannan, MD, of Great Ormond Street Hospital in London. MRI activity continues among patients treated with DMTs, and the number of relapses is highest in the period following diagnosis. But because the effect of treatment on brain atrophy is greatest in the initial period of disease, “this time period may represent a critical therapeutic window for the use of highly effective therapies,” said Dr. Abdel-Mannan.
 

An examination of medical records

MS is much less prevalent among children than among adults. Compared with adults with MS, children with MS have a higher relapse rate and slower accumulation of disability. The individual response to DMTs is variable, said Dr. Abdel-Mannan. Furthermore, current standards of care for pediatric MS vary by center and are based on adult protocols.

Dr. Abdel-Mannan and colleagues conducted a retrospective study to evaluate the real-world effectiveness of the newer oral and infusion DMTs, compared with the older injectable DMTs, in children with relapsing-remitting MS. They examined data from seven tertiary pediatric neurology centers in the United Kingdom and identified patients under age 18 years with relapsing-remitting MS who were treated with DMTs between 2012 and 2018. The investigators reviewed clinical and paraclinical data retrospectively using electronic medical records. They compared patients’ ARR, new radiological activity, and Expanded Disability Status Scale score pretreatment and on treatment.

The researchers included 103 patients in their analysis. The population’s median age was 14 years. The ratio of girls to boys was approximately 3:1. Whites and other races/ethnicities accounted for approximately equal groups of patients. About one-third of patients presented with a clinically isolated syndrome (CIS) in the form of transverse myelitis or optic neuritis. Two-thirds presented with other CIS phenotypes. Almost all children had an abnormal MRI at onset.
 

Most patients initiated injectable DMTs

Of the 103 patients, 89 started treatment with an injectable (e.g., glatiramer or interferon) or an older DMT. Fourteen patients began treatment with a newer DMT (e.g., dimethyl fumarate, fingolimod, natalizumab, and alemtuzumab). Three of the 89 patients on an injectable DMT switched to another injectable DMT, and two of these patients later escalated to a newer DMT. Thirty-five of the 89 patients who initiated an injectable DMT were escalated immediately to a newer DMT. One of these patients later switched to another newer DMT. Two of the 14 patients who started on a newer DMT as their first drug switched to another newer DMT.

The investigators observed a reduction in ARR for all DMTs used during the study period. Nevertheless, a significant number of patients receiving injectable DMTs continued to relapse on treatment. Almost all patients receiving newer DMTs, however, had a reduction in relapses. When Dr. Abdel-Mannan and colleagues performed Kaplan–Meier survival analysis, they found that patients receiving newer DMTs had a longer time to first relapse and a longer time to switch treatment over 2 years, compared with patients receiving injectable DMTs. In addition, patients receiving newer DMTs had a longer time to develop new radiological activity, compared with patients receiving injectables. The analysis also indicated that the proportion of patients with new radiological activity was higher than the proportion who had clinical relapses and an Expanded Disability Status Scale score increase of more than 1 point over 2 years.

In all, 55 of the children receiving injectable DMTs and 18 of the patients receiving newer DMTs had side effects. The most commonly reported side effects were flulike symptoms and injection-site reactions. Five patients discontinued or switched their DMTs because of side effects. “Reassuringly, no pediatric-specific side effects were reported,” said Dr. Abdel-Mannan. The newer DMTs had similar short-term safety, tolerability, and side-effect profiles in these children as in adult patients.

The study was conducted on behalf of the UK Childhood Inflammatory Demyelination Network. Dr. Abdel-Mannan had no relevant disclosures.

egreb@mdedge.com

SOURCE: Abdel-Mannan O et al. CNS-ICNA 2020, Abstract PL10.

Maintaining antiseizure medication in infants who have had acute symptomatic neonatal seizures has been standard practice, but a prospective, observational, comparative effectiveness study calls that practice into question, providing evidence that discontinuing therapy at discharge poses no harm to children and has no effect on the development of epilepsies.

“The balance of evidence supports discontinuing antiseizure medication after resolution of acute symptomatic neonatal seizures and before discharge home from the neonatal seizure admission,” said Hannah C. Glass, MDCM, MAS, of the University of California, San Francisco, Benioff Children’s Hospital, co-principal investigator, who presented results of the study at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year. Renee Shellhaas, MD, MS, clinical associate professor of pediatrics at C.S. Mott Children’s Hospital, University of Michigan, was the other co-principal investigator.

“Although other, smaller studies have suggested it is safe to discontinue antiseizure medication after resolution of acute symptomatic seizures, the practice of early discontinuation has been very variable and depends largely on individual provider preference,” Dr. Glass said in an interview. “In our study, two-thirds of newborns with acute symptomatic seizures were maintained on antiseizure medication at the time of hospital discharge. Thus, a change to early medication discontinuation represents a major shift.” 

The study evaluated 270 infants at nine centers enrolled in the Neonatal Seizure Registry and born from July 2015 through March 2018. Inclusion criteria were acute symptomatic seizures that occurred at up to 44 weeks postmenstrual age. In this cohort, 36% of patients had antiseizure medication discontinued after a median of 6 days; the remainder stayed on antiseizure medication after discharge at a median of 4 months.

The patients were followed for 2 years. The primary outcome was functional development measured by the Warner Initial Development Evaluation of Adaptive and Functional Skills (WIDEA-FS) assessment. The secondary outcome was epilepsy defined by International League Against Epilepsy (ILAE) criteria. Follow-up consisted of phone calls and chart reviews at 12, 18, and 24 months.

“The primary outcome, functional development, was not significantly different between those children who were maintained on antiseizure medication as compared with those who were discontinued,” Dr. Glass said.

After propensity adjustment, the discontinued ASM group had an estimated WIDEA-FS score 4 points higher on average, she said. “The confidence intervals met our a priori noninferiority limit, indicating no harm to neurodevelopment for discontinuing antiseizure medication before discharge home from the neonatal seizure admission,” Dr. Glass noted.

The study also found that 13% of all participants developed epilepsy at a median of 8 months. “There was no significant difference in the frequency or timing of epilepsy between the two groups,” she said.

“We conclude there is no clear rationale for antiseizure medication maintenance,” Dr. Glass said. “There is no benefit to neurodevelopment, it prolongs the exposure to potentially harmful antiseizure medications, it does not significantly delay the onset of epilepsy, and the earliest-onset epilepsies occur in spite of antiseizure medication.”

The Patient-Centered Outcomes Research Institute (PCORI) and Pediatric Epilepsy Research Foundation funded the study. Dr. Glass has no other financial relationships to disclose.

SOURCE: Glass HC et al. CNS-ICNA 2020. Presentation PL58.

Maintaining antiseizure medication in infants who have had acute symptomatic neonatal seizures has been standard practice, but a prospective, observational, comparative effectiveness study calls that practice into question, providing evidence that discontinuing therapy at discharge poses no harm to children and has no effect on the development of epilepsies.

“The balance of evidence supports discontinuing antiseizure medication after resolution of acute symptomatic neonatal seizures and before discharge home from the neonatal seizure admission,” said Hannah C. Glass, MDCM, MAS, of the University of California, San Francisco, Benioff Children’s Hospital, co-principal investigator, who presented results of the study at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year. Renee Shellhaas, MD, MS, clinical associate professor of pediatrics at C.S. Mott Children’s Hospital, University of Michigan, was the other co-principal investigator.

“Although other, smaller studies have suggested it is safe to discontinue antiseizure medication after resolution of acute symptomatic seizures, the practice of early discontinuation has been very variable and depends largely on individual provider preference,” Dr. Glass said in an interview. “In our study, two-thirds of newborns with acute symptomatic seizures were maintained on antiseizure medication at the time of hospital discharge. Thus, a change to early medication discontinuation represents a major shift.” 

The study evaluated 270 infants at nine centers enrolled in the Neonatal Seizure Registry and born from July 2015 through March 2018. Inclusion criteria were acute symptomatic seizures that occurred at up to 44 weeks postmenstrual age. In this cohort, 36% of patients had antiseizure medication discontinued after a median of 6 days; the remainder stayed on antiseizure medication after discharge at a median of 4 months.

The patients were followed for 2 years. The primary outcome was functional development measured by the Warner Initial Development Evaluation of Adaptive and Functional Skills (WIDEA-FS) assessment. The secondary outcome was epilepsy defined by International League Against Epilepsy (ILAE) criteria. Follow-up consisted of phone calls and chart reviews at 12, 18, and 24 months.

“The primary outcome, functional development, was not significantly different between those children who were maintained on antiseizure medication as compared with those who were discontinued,” Dr. Glass said.

After propensity adjustment, the discontinued ASM group had an estimated WIDEA-FS score 4 points higher on average, she said. “The confidence intervals met our a priori noninferiority limit, indicating no harm to neurodevelopment for discontinuing antiseizure medication before discharge home from the neonatal seizure admission,” Dr. Glass noted.

The study also found that 13% of all participants developed epilepsy at a median of 8 months. “There was no significant difference in the frequency or timing of epilepsy between the two groups,” she said.

“We conclude there is no clear rationale for antiseizure medication maintenance,” Dr. Glass said. “There is no benefit to neurodevelopment, it prolongs the exposure to potentially harmful antiseizure medications, it does not significantly delay the onset of epilepsy, and the earliest-onset epilepsies occur in spite of antiseizure medication.”

The Patient-Centered Outcomes Research Institute (PCORI) and Pediatric Epilepsy Research Foundation funded the study. Dr. Glass has no other financial relationships to disclose.

SOURCE: Glass HC et al. CNS-ICNA 2020. Presentation PL58.

Maintaining antiseizure medication in infants who have had acute symptomatic neonatal seizures has been standard practice, but a prospective, observational, comparative effectiveness study calls that practice into question, providing evidence that discontinuing therapy at discharge poses no harm to children and has no effect on the development of epilepsies.

“The balance of evidence supports discontinuing antiseizure medication after resolution of acute symptomatic neonatal seizures and before discharge home from the neonatal seizure admission,” said Hannah C. Glass, MDCM, MAS, of the University of California, San Francisco, Benioff Children’s Hospital, co-principal investigator, who presented results of the study at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year. Renee Shellhaas, MD, MS, clinical associate professor of pediatrics at C.S. Mott Children’s Hospital, University of Michigan, was the other co-principal investigator.

“Although other, smaller studies have suggested it is safe to discontinue antiseizure medication after resolution of acute symptomatic seizures, the practice of early discontinuation has been very variable and depends largely on individual provider preference,” Dr. Glass said in an interview. “In our study, two-thirds of newborns with acute symptomatic seizures were maintained on antiseizure medication at the time of hospital discharge. Thus, a change to early medication discontinuation represents a major shift.” 

The study evaluated 270 infants at nine centers enrolled in the Neonatal Seizure Registry and born from July 2015 through March 2018. Inclusion criteria were acute symptomatic seizures that occurred at up to 44 weeks postmenstrual age. In this cohort, 36% of patients had antiseizure medication discontinued after a median of 6 days; the remainder stayed on antiseizure medication after discharge at a median of 4 months.

The patients were followed for 2 years. The primary outcome was functional development measured by the Warner Initial Development Evaluation of Adaptive and Functional Skills (WIDEA-FS) assessment. The secondary outcome was epilepsy defined by International League Against Epilepsy (ILAE) criteria. Follow-up consisted of phone calls and chart reviews at 12, 18, and 24 months.

“The primary outcome, functional development, was not significantly different between those children who were maintained on antiseizure medication as compared with those who were discontinued,” Dr. Glass said.

After propensity adjustment, the discontinued ASM group had an estimated WIDEA-FS score 4 points higher on average, she said. “The confidence intervals met our a priori noninferiority limit, indicating no harm to neurodevelopment for discontinuing antiseizure medication before discharge home from the neonatal seizure admission,” Dr. Glass noted.

The study also found that 13% of all participants developed epilepsy at a median of 8 months. “There was no significant difference in the frequency or timing of epilepsy between the two groups,” she said.

“We conclude there is no clear rationale for antiseizure medication maintenance,” Dr. Glass said. “There is no benefit to neurodevelopment, it prolongs the exposure to potentially harmful antiseizure medications, it does not significantly delay the onset of epilepsy, and the earliest-onset epilepsies occur in spite of antiseizure medication.”

The Patient-Centered Outcomes Research Institute (PCORI) and Pediatric Epilepsy Research Foundation funded the study. Dr. Glass has no other financial relationships to disclose.

SOURCE: Glass HC et al. CNS-ICNA 2020. Presentation PL58.

Danny Dvir, MD, has a message for physicians who have patients with severe valvular heart disease who are deferring valve replacement or repair until after the COVID-19 pandemic: Urge them not to wait.

Data from the Multicenter International Valve Disease Registry vividly demonstrate that clinical outcomes are poor in patients with uncorrected valve disease who become hospitalized with COVID-19. Indeed, the mortality rate within 30 days after hospital admission in 136 such patients enrolled in the registry from centers in Europe, North America, and Israel was 42%, Dr. Dvir reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.

“That’s dramatically higher than for an age-matched population infected with COVID-19 without valvular heart disease, which is 10%-15%,” he noted at the meeting sponsored by the Cardiovascular Research Foundation.

The bright spot was that, in the small subgroup of 15 registry participants who underwent transcatheter or, much less frequently, surgical treatment of their failing valve while COVID-19 infected, 30-day mortality was far lower. In fact, it was comparable with the background rate in hospitalized COVID-19 patients without valve disease, according to Dr. Dvir, an interventional cardiologist at Shaare Zedek Medical Center, Hebrew University, Jerusalem.

He personally did several of the transcatheter aortic valve replacements.

“It’s doable. I truly believe that when you get a severe aortic stenosis patient who’s infected with the coronavirus, they get very unstable, but we can treat them. We can treat them even during the infection,” Dr. Dvir said.

The majority of patients in the registry had severe aortic stenosis. In the 42 such patients aged 80 years or more who didn’t undergo transcatheter aortic valve replacement (TAVR) or surgical valve replacement, 30-day mortality was 60%. In contrast, only one of the six patients in this advanced-age category who underwent valve replacement while infected died. Similarly, 30-day mortality was 24% among those younger than age 80 who valve remained untreated, but it dropped to 11% in those who received a prosthetic valve.

“We try our best to protect our patients through social distancing, but we have a treatment that can potentially reduce their mortality risk if they get infected later on. So I say to my patients: ‘Don’t wait at home. Do not wait! If you get infected when you have severe aortic stenosis, the clinical outcome is bad.’ But it seems reasonable that if they get infected when they’ve already been treated for their aortic stenosis or mitral regurgitation, they will do better.”

Dr. Dvir noted that, although the case numbers in the registry series were small and subject to potential bias, the data suggest this treatment approach may be lifesaving.

Session comoderator Timothy D. Henry, MD, commented that this registry study contains a great take-home point: “This is really consistent with what see in a lot of the other areas of COVID, that what we know to be best clinical care, we should do it, with or without the COVID.”

He asked Dr. Dvir about any special measures he takes while doing TAVR in this extreme setting. In the United States, for example, interventionalists are increasingly using transesophageal echocardiography to guide their procedures using conscious sedation, without intubation, noted Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research at the Christ Hospital, Cincinnati.

“We try to minimize the procedure time; that’s one of the important things,” Dr. Dvir replied. “And you need to be protected during the procedure in a very cautious and meticulous way. You need many fans in the room because you sweat a lot.”

Discussant Renu Virmani, MD, president of the CVPath Institute in Gaithersburg, Md., commented: “The main thing I get from this presentation is the need for patients to be educated that if you’ve got valve disease, you’re better off getting it treated before you’ve got COVID. Obviously, try to prevent getting COVID – that’s the best thing you can do – but you can’t always control that.”

Discussant Mamas Mamas, MD, professor of cardiology at Keele University, Staffordshire, England, said deferred treatment of severe valvular heart disease during the pandemic has created a looming public health crisis in the United Kingdom.

“We’ve analyzed the U.K. management of aortic stenosis, and what we’ve found is that during the COVID pandemic there have been 2,500 fewer cases of aortic stenosis that have been treated. We’ve got 2,500 patients on the waiting list, and we’ve got to work out how we’re going to treat them. We estimate with simulations that about 300 of them are going to die before we can get them treated for their aortic stenosis,” according to Dr. Mamas.

Dr. Henry commented that deferral of valve procedures is “really challenging” for a couple of reasons: Not only are patients scared to come into the hospital because they fear getting COVID, but they don’t want to be hospitalized during the pandemic because their family can’t visit them there.

“These patients are mostly over 80 years old. No one wants to come in the hospital when the family won’t be around, especially when you’re 90 years old,” the interventional cardiologist said.

Dr. Dvir reported serving as a consultant to Medtronic, Edwards Lifesciences, Abbott, and Jena.

bjancin@mdedge.com

Danny Dvir, MD, has a message for physicians who have patients with severe valvular heart disease who are deferring valve replacement or repair until after the COVID-19 pandemic: Urge them not to wait.

Data from the Multicenter International Valve Disease Registry vividly demonstrate that clinical outcomes are poor in patients with uncorrected valve disease who become hospitalized with COVID-19. Indeed, the mortality rate within 30 days after hospital admission in 136 such patients enrolled in the registry from centers in Europe, North America, and Israel was 42%, Dr. Dvir reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.

“That’s dramatically higher than for an age-matched population infected with COVID-19 without valvular heart disease, which is 10%-15%,” he noted at the meeting sponsored by the Cardiovascular Research Foundation.

The bright spot was that, in the small subgroup of 15 registry participants who underwent transcatheter or, much less frequently, surgical treatment of their failing valve while COVID-19 infected, 30-day mortality was far lower. In fact, it was comparable with the background rate in hospitalized COVID-19 patients without valve disease, according to Dr. Dvir, an interventional cardiologist at Shaare Zedek Medical Center, Hebrew University, Jerusalem.

He personally did several of the transcatheter aortic valve replacements.

“It’s doable. I truly believe that when you get a severe aortic stenosis patient who’s infected with the coronavirus, they get very unstable, but we can treat them. We can treat them even during the infection,” Dr. Dvir said.

The majority of patients in the registry had severe aortic stenosis. In the 42 such patients aged 80 years or more who didn’t undergo transcatheter aortic valve replacement (TAVR) or surgical valve replacement, 30-day mortality was 60%. In contrast, only one of the six patients in this advanced-age category who underwent valve replacement while infected died. Similarly, 30-day mortality was 24% among those younger than age 80 who valve remained untreated, but it dropped to 11% in those who received a prosthetic valve.

“We try our best to protect our patients through social distancing, but we have a treatment that can potentially reduce their mortality risk if they get infected later on. So I say to my patients: ‘Don’t wait at home. Do not wait! If you get infected when you have severe aortic stenosis, the clinical outcome is bad.’ But it seems reasonable that if they get infected when they’ve already been treated for their aortic stenosis or mitral regurgitation, they will do better.”

Dr. Dvir noted that, although the case numbers in the registry series were small and subject to potential bias, the data suggest this treatment approach may be lifesaving.

Session comoderator Timothy D. Henry, MD, commented that this registry study contains a great take-home point: “This is really consistent with what see in a lot of the other areas of COVID, that what we know to be best clinical care, we should do it, with or without the COVID.”

He asked Dr. Dvir about any special measures he takes while doing TAVR in this extreme setting. In the United States, for example, interventionalists are increasingly using transesophageal echocardiography to guide their procedures using conscious sedation, without intubation, noted Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research at the Christ Hospital, Cincinnati.

“We try to minimize the procedure time; that’s one of the important things,” Dr. Dvir replied. “And you need to be protected during the procedure in a very cautious and meticulous way. You need many fans in the room because you sweat a lot.”

Discussant Renu Virmani, MD, president of the CVPath Institute in Gaithersburg, Md., commented: “The main thing I get from this presentation is the need for patients to be educated that if you’ve got valve disease, you’re better off getting it treated before you’ve got COVID. Obviously, try to prevent getting COVID – that’s the best thing you can do – but you can’t always control that.”

Discussant Mamas Mamas, MD, professor of cardiology at Keele University, Staffordshire, England, said deferred treatment of severe valvular heart disease during the pandemic has created a looming public health crisis in the United Kingdom.

“We’ve analyzed the U.K. management of aortic stenosis, and what we’ve found is that during the COVID pandemic there have been 2,500 fewer cases of aortic stenosis that have been treated. We’ve got 2,500 patients on the waiting list, and we’ve got to work out how we’re going to treat them. We estimate with simulations that about 300 of them are going to die before we can get them treated for their aortic stenosis,” according to Dr. Mamas.

Dr. Henry commented that deferral of valve procedures is “really challenging” for a couple of reasons: Not only are patients scared to come into the hospital because they fear getting COVID, but they don’t want to be hospitalized during the pandemic because their family can’t visit them there.

“These patients are mostly over 80 years old. No one wants to come in the hospital when the family won’t be around, especially when you’re 90 years old,” the interventional cardiologist said.

Dr. Dvir reported serving as a consultant to Medtronic, Edwards Lifesciences, Abbott, and Jena.

bjancin@mdedge.com

Danny Dvir, MD, has a message for physicians who have patients with severe valvular heart disease who are deferring valve replacement or repair until after the COVID-19 pandemic: Urge them not to wait.

Data from the Multicenter International Valve Disease Registry vividly demonstrate that clinical outcomes are poor in patients with uncorrected valve disease who become hospitalized with COVID-19. Indeed, the mortality rate within 30 days after hospital admission in 136 such patients enrolled in the registry from centers in Europe, North America, and Israel was 42%, Dr. Dvir reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.

“That’s dramatically higher than for an age-matched population infected with COVID-19 without valvular heart disease, which is 10%-15%,” he noted at the meeting sponsored by the Cardiovascular Research Foundation.

The bright spot was that, in the small subgroup of 15 registry participants who underwent transcatheter or, much less frequently, surgical treatment of their failing valve while COVID-19 infected, 30-day mortality was far lower. In fact, it was comparable with the background rate in hospitalized COVID-19 patients without valve disease, according to Dr. Dvir, an interventional cardiologist at Shaare Zedek Medical Center, Hebrew University, Jerusalem.

He personally did several of the transcatheter aortic valve replacements.

“It’s doable. I truly believe that when you get a severe aortic stenosis patient who’s infected with the coronavirus, they get very unstable, but we can treat them. We can treat them even during the infection,” Dr. Dvir said.

The majority of patients in the registry had severe aortic stenosis. In the 42 such patients aged 80 years or more who didn’t undergo transcatheter aortic valve replacement (TAVR) or surgical valve replacement, 30-day mortality was 60%. In contrast, only one of the six patients in this advanced-age category who underwent valve replacement while infected died. Similarly, 30-day mortality was 24% among those younger than age 80 who valve remained untreated, but it dropped to 11% in those who received a prosthetic valve.

“We try our best to protect our patients through social distancing, but we have a treatment that can potentially reduce their mortality risk if they get infected later on. So I say to my patients: ‘Don’t wait at home. Do not wait! If you get infected when you have severe aortic stenosis, the clinical outcome is bad.’ But it seems reasonable that if they get infected when they’ve already been treated for their aortic stenosis or mitral regurgitation, they will do better.”

Dr. Dvir noted that, although the case numbers in the registry series were small and subject to potential bias, the data suggest this treatment approach may be lifesaving.

Session comoderator Timothy D. Henry, MD, commented that this registry study contains a great take-home point: “This is really consistent with what see in a lot of the other areas of COVID, that what we know to be best clinical care, we should do it, with or without the COVID.”

He asked Dr. Dvir about any special measures he takes while doing TAVR in this extreme setting. In the United States, for example, interventionalists are increasingly using transesophageal echocardiography to guide their procedures using conscious sedation, without intubation, noted Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research at the Christ Hospital, Cincinnati.

“We try to minimize the procedure time; that’s one of the important things,” Dr. Dvir replied. “And you need to be protected during the procedure in a very cautious and meticulous way. You need many fans in the room because you sweat a lot.”

Discussant Renu Virmani, MD, president of the CVPath Institute in Gaithersburg, Md., commented: “The main thing I get from this presentation is the need for patients to be educated that if you’ve got valve disease, you’re better off getting it treated before you’ve got COVID. Obviously, try to prevent getting COVID – that’s the best thing you can do – but you can’t always control that.”

Discussant Mamas Mamas, MD, professor of cardiology at Keele University, Staffordshire, England, said deferred treatment of severe valvular heart disease during the pandemic has created a looming public health crisis in the United Kingdom.

“We’ve analyzed the U.K. management of aortic stenosis, and what we’ve found is that during the COVID pandemic there have been 2,500 fewer cases of aortic stenosis that have been treated. We’ve got 2,500 patients on the waiting list, and we’ve got to work out how we’re going to treat them. We estimate with simulations that about 300 of them are going to die before we can get them treated for their aortic stenosis,” according to Dr. Mamas.

Dr. Henry commented that deferral of valve procedures is “really challenging” for a couple of reasons: Not only are patients scared to come into the hospital because they fear getting COVID, but they don’t want to be hospitalized during the pandemic because their family can’t visit them there.

“These patients are mostly over 80 years old. No one wants to come in the hospital when the family won’t be around, especially when you’re 90 years old,” the interventional cardiologist said.

Dr. Dvir reported serving as a consultant to Medtronic, Edwards Lifesciences, Abbott, and Jena.

bjancin@mdedge.com

Major thromboembolic complications and adverse cardiovascular events occurred with high frequency in patients with COVID-19, especially in the intensive care setting, despite a high use of thromboprophylaxis, in a new large observational U.S. study.

“Despite very high rate of antithrombotic prophylaxis there were a high rate of thromboembolic events suggesting that we are probably not providing enough thromboprophylaxis,” lead author Gregory Piazza, MD, Brigham and Women’s Hospital, Boston, said in an interview. 

“Standard prophylaxis as recommended in the guidelines is a low dose of low-molecular-weight heparin once daily, but these results suggest [patients] probably need higher doses,” he added.

However, Dr. Piazza cautioned that this is an observational study and randomized trials are needed to make changes in treatment strategies. Several such trials are currently underway.

The current study was published online ahead of print in the Nov. 3 issue of the Journal of the American College of Cardiology.
 

Rates similar to other very sick patients

The study showed that while thromboembolic complications were high, they were not as high as seen in some of the earlier studies from Asia and Europe, Dr. Piazza noted.

“The numbers we were seeing in early reports were so high we couldn’t figure out how that was possible,” he said. “Our study suggests that, in a U.S. population receiving thromboprophylaxis, the rate of thromboembolic complications [are] more in line with what we would expect to see in other very sick patients who end up in ICU.”

He suggested that the very high rates of thromboembolic complications in the early studies from Asia may have been because of the lack of thromboprophylaxis, which is not routine in hospitalized patients there. “Some of the earlier studies also used routine ultrasound and so picked up asymptomatic thrombotic events, which was not the case in our study. So our results are more representative of the U.S. population.”

Dr. Piazza attributed the high rate of thromboembolic complications being reported with COVID-19 to the sheer number of very sick patients being admitted to the hospital.

“We are accustomed to seeing a rare case of thrombosis despite prophylaxis in hospitalized patients, but we are seeing more in COVID patients. This is probably just because we have more critically ill patients,” he said.

“We are seeing an incredible influx of patients to the ICU that we have never experienced before, so the increase in thromboembolic complications is more obvious. In prior years we probably haven’t had enough critically ill patients at any one time to raise the flag about thromboprophylaxis,” he commented.

The study also found a high rate of cardiovascular complications. They are seeing an increase in the risk of MI, which is to be expected in such sick patients, but they also see quite a bit of new atrial fibrillation, myocarditis, and heart failure in patients who don’t always have underlying cardiovascular disease, he said.

“So this virus does appear to have a predilection to causing cardiovascular complications, but this is probably because it is making patients so sick,” Dr. Piazza said. “If flu was this virulent and resulted in such high rates of acute respiratory distress syndrome (ARDS), we would probably see similar cardiovascular complication rates.”

For the current report, the researchers analyzed a retrospective cohort of 1,114 patients with COVID-19 diagnosed through the Mass General Brigham integrated health network. Of these, 170 had been admitted to the ICU, 229 had been hospitalized but not treated in ICU, and 715 were outpatients. In terms of ethnicity, 22% were Hispanic/Latino and 44% were non-White. 

Cardiovascular risk factors were common, with 36% of patients having hypertension, 29% hyperlipidemia, and 18% diabetes. Prophylactic anticoagulation was prescribed in 89% of patients with COVID-19 in the intensive care cohort and 85% of those in the hospitalized non–intensive care setting.

Results showed that major arterial or venous thromboembolism (VTE) occurred in 35% of the intensive care cohort, 2.6% of those hospitalized but not treated in ICU, and 0% of outpatients.

Major adverse cardiovascular events occurred in 46% of the intensive care cohort, 6.1% of those hospitalized but non-ICU, and 0% of outpatients.

Symptomatic VTE occurred in 27% of those admitted to ICU, 2.2% of those hospitalized but non-ICU, and 0% of outpatients.

“We found that outpatients had a very low rate of thromboembolic complications, with the vast majority of the risk being in hospitalized patients, especially those in ICU,” Dr. Piazza said.

“These results suggest that we don’t need routine thromboprophylaxis for all outpatients with COVID-19, but there will probably be some patients who need it – those with risk factors for thromboembolism.”

Catheter- and device-associated deep vein thrombosis accounted for 76.9% of the DVTs observed in the study.

“Our finding of high frequency of catheter-associated DVT supports the judicious use of central venous catheters that have been widely implemented, especially in the ICU, to minimize recurrent health care team exposure and facilitate monitoring,” the researchers wrote.
 

ARDS biggest risk factor

Of all the markers of disease severity, the presence of ARDS had the strongest association with adverse outcomes, including major arterial or VTE, major adverse cardiovascular events, symptomatic VTE, and death.

“The severe inflammatory state associated with ARDS and other complications of COVID-19 and its resultant hypercoagulability may explain, at least in part, the high frequency of thromboembolic events. Improved risk stratification, utilizing biochemical markers of inflammation and activated coagulation as well as clinical indicators, such as ARDS, may play an important role in the early identification of patients with an increased likelihood of developing symptomatic VTE or arterial thrombosis,” the researchers wrote. “They may benefit from full- or intermediate-intensity antithrombotic therapy rather than prophylactic anticoagulation.”

They point out that this study provides a cross-sectional view of the cardiovascular complications of COVID-19 in a large health care network, consisting of two academic medical centers serving the greater Boston area, several community hospitals, and numerous outpatient care sites.

“The study incorporates a wide scope of clinically meaningful cardiovascular endpoints and utilizes a rigorous process of event adjudication. Although data on patients with COVID-19 in the ICU have been the subject of most reports, our study provides insights into the broad spectrum of all hospitalized and outpatient populations,” the authors noted.

“The high frequency of arterial or venous thromboembolism in hospitalized patients despite routine thromboprophylaxis suggests the need for improved risk stratification and enhanced preventive efforts,” they concluded.

The study is continuing, and the researchers expect to have data on 10,000 patients by the end of winter.
 

Wait for randomized trials

In an accompanying editorial, Robert McBane, MD, Mayo Clinic, Rochester, Minn., said that these data provide important real-world arterial and venous thrombotic event rates across a large, integrated health care network and an experienced roster of clinician-scientists devoted to thrombosis research.

Noting that whether to interpret these results as alarming or reassuring requires a comparison of expected thromboembolic event rates separate from the pandemic, he pointed out that, while the overall VTE rate among ICU patients was high, the vast majority of these events were attributable to central venous lines, and apart from these, the event rates do not appear inflated relative to prior published incidence rates from the pre–COVID-19 era.

“It is therefore important to resist the urge to overprevent or overtreat patients and expose them to the serious risks of major bleeding,” Dr. McBane wrote, adding that “the systematized approach to delivery of guideline-driven VTE prophylaxis across this large, integrated health network likely contributed to the relatively low rates of serious thrombotic outcomes reported.”

He further noted that, as the majority of VTE events were related to central venous lines in ICU patients, “this underscores the importance of a bundled care approach to central venous line management with daily assessment of the continued necessity of central access.

“A number of important clinical trials aimed at optimizing thromboprophylaxis during hospitalization, following hospital dismissal, and in ambulatory settings are underway. Until available, the lessons of thoughtful anticoagulant prophylaxis and treatment guidelines harvested from years of clinical research appear to apply,” he concluded.

This study was funded, in part, by a research grant from Janssen Pharmaceuticals. Dr. Piazza has received research grant support from EKOS Corporation, Bayer, Bristol-Myers Squibb/Pfizer, Portola Pharmaceuticals, and Janssen Pharmaceuticals; and has received consulting fees from Amgen, Pfizer, Boston Scientific, Agile, and Thrombolex. Dr. McBane reported no relevant disclosures.

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

Major thromboembolic complications and adverse cardiovascular events occurred with high frequency in patients with COVID-19, especially in the intensive care setting, despite a high use of thromboprophylaxis, in a new large observational U.S. study.

“Despite very high rate of antithrombotic prophylaxis there were a high rate of thromboembolic events suggesting that we are probably not providing enough thromboprophylaxis,” lead author Gregory Piazza, MD, Brigham and Women’s Hospital, Boston, said in an interview. 

“Standard prophylaxis as recommended in the guidelines is a low dose of low-molecular-weight heparin once daily, but these results suggest [patients] probably need higher doses,” he added.

However, Dr. Piazza cautioned that this is an observational study and randomized trials are needed to make changes in treatment strategies. Several such trials are currently underway.

The current study was published online ahead of print in the Nov. 3 issue of the Journal of the American College of Cardiology.
 

Rates similar to other very sick patients

The study showed that while thromboembolic complications were high, they were not as high as seen in some of the earlier studies from Asia and Europe, Dr. Piazza noted.

“The numbers we were seeing in early reports were so high we couldn’t figure out how that was possible,” he said. “Our study suggests that, in a U.S. population receiving thromboprophylaxis, the rate of thromboembolic complications [are] more in line with what we would expect to see in other very sick patients who end up in ICU.”

He suggested that the very high rates of thromboembolic complications in the early studies from Asia may have been because of the lack of thromboprophylaxis, which is not routine in hospitalized patients there. “Some of the earlier studies also used routine ultrasound and so picked up asymptomatic thrombotic events, which was not the case in our study. So our results are more representative of the U.S. population.”

Dr. Piazza attributed the high rate of thromboembolic complications being reported with COVID-19 to the sheer number of very sick patients being admitted to the hospital.

“We are accustomed to seeing a rare case of thrombosis despite prophylaxis in hospitalized patients, but we are seeing more in COVID patients. This is probably just because we have more critically ill patients,” he said.

“We are seeing an incredible influx of patients to the ICU that we have never experienced before, so the increase in thromboembolic complications is more obvious. In prior years we probably haven’t had enough critically ill patients at any one time to raise the flag about thromboprophylaxis,” he commented.

The study also found a high rate of cardiovascular complications. They are seeing an increase in the risk of MI, which is to be expected in such sick patients, but they also see quite a bit of new atrial fibrillation, myocarditis, and heart failure in patients who don’t always have underlying cardiovascular disease, he said.

“So this virus does appear to have a predilection to causing cardiovascular complications, but this is probably because it is making patients so sick,” Dr. Piazza said. “If flu was this virulent and resulted in such high rates of acute respiratory distress syndrome (ARDS), we would probably see similar cardiovascular complication rates.”

For the current report, the researchers analyzed a retrospective cohort of 1,114 patients with COVID-19 diagnosed through the Mass General Brigham integrated health network. Of these, 170 had been admitted to the ICU, 229 had been hospitalized but not treated in ICU, and 715 were outpatients. In terms of ethnicity, 22% were Hispanic/Latino and 44% were non-White. 

Cardiovascular risk factors were common, with 36% of patients having hypertension, 29% hyperlipidemia, and 18% diabetes. Prophylactic anticoagulation was prescribed in 89% of patients with COVID-19 in the intensive care cohort and 85% of those in the hospitalized non–intensive care setting.

Results showed that major arterial or venous thromboembolism (VTE) occurred in 35% of the intensive care cohort, 2.6% of those hospitalized but not treated in ICU, and 0% of outpatients.

Major adverse cardiovascular events occurred in 46% of the intensive care cohort, 6.1% of those hospitalized but non-ICU, and 0% of outpatients.

Symptomatic VTE occurred in 27% of those admitted to ICU, 2.2% of those hospitalized but non-ICU, and 0% of outpatients.

“We found that outpatients had a very low rate of thromboembolic complications, with the vast majority of the risk being in hospitalized patients, especially those in ICU,” Dr. Piazza said.

“These results suggest that we don’t need routine thromboprophylaxis for all outpatients with COVID-19, but there will probably be some patients who need it – those with risk factors for thromboembolism.”

Catheter- and device-associated deep vein thrombosis accounted for 76.9% of the DVTs observed in the study.

“Our finding of high frequency of catheter-associated DVT supports the judicious use of central venous catheters that have been widely implemented, especially in the ICU, to minimize recurrent health care team exposure and facilitate monitoring,” the researchers wrote.
 

ARDS biggest risk factor

Of all the markers of disease severity, the presence of ARDS had the strongest association with adverse outcomes, including major arterial or VTE, major adverse cardiovascular events, symptomatic VTE, and death.

“The severe inflammatory state associated with ARDS and other complications of COVID-19 and its resultant hypercoagulability may explain, at least in part, the high frequency of thromboembolic events. Improved risk stratification, utilizing biochemical markers of inflammation and activated coagulation as well as clinical indicators, such as ARDS, may play an important role in the early identification of patients with an increased likelihood of developing symptomatic VTE or arterial thrombosis,” the researchers wrote. “They may benefit from full- or intermediate-intensity antithrombotic therapy rather than prophylactic anticoagulation.”

They point out that this study provides a cross-sectional view of the cardiovascular complications of COVID-19 in a large health care network, consisting of two academic medical centers serving the greater Boston area, several community hospitals, and numerous outpatient care sites.

“The study incorporates a wide scope of clinically meaningful cardiovascular endpoints and utilizes a rigorous process of event adjudication. Although data on patients with COVID-19 in the ICU have been the subject of most reports, our study provides insights into the broad spectrum of all hospitalized and outpatient populations,” the authors noted.

“The high frequency of arterial or venous thromboembolism in hospitalized patients despite routine thromboprophylaxis suggests the need for improved risk stratification and enhanced preventive efforts,” they concluded.

The study is continuing, and the researchers expect to have data on 10,000 patients by the end of winter.
 

Wait for randomized trials

In an accompanying editorial, Robert McBane, MD, Mayo Clinic, Rochester, Minn., said that these data provide important real-world arterial and venous thrombotic event rates across a large, integrated health care network and an experienced roster of clinician-scientists devoted to thrombosis research.

Noting that whether to interpret these results as alarming or reassuring requires a comparison of expected thromboembolic event rates separate from the pandemic, he pointed out that, while the overall VTE rate among ICU patients was high, the vast majority of these events were attributable to central venous lines, and apart from these, the event rates do not appear inflated relative to prior published incidence rates from the pre–COVID-19 era.

“It is therefore important to resist the urge to overprevent or overtreat patients and expose them to the serious risks of major bleeding,” Dr. McBane wrote, adding that “the systematized approach to delivery of guideline-driven VTE prophylaxis across this large, integrated health network likely contributed to the relatively low rates of serious thrombotic outcomes reported.”

He further noted that, as the majority of VTE events were related to central venous lines in ICU patients, “this underscores the importance of a bundled care approach to central venous line management with daily assessment of the continued necessity of central access.

“A number of important clinical trials aimed at optimizing thromboprophylaxis during hospitalization, following hospital dismissal, and in ambulatory settings are underway. Until available, the lessons of thoughtful anticoagulant prophylaxis and treatment guidelines harvested from years of clinical research appear to apply,” he concluded.

This study was funded, in part, by a research grant from Janssen Pharmaceuticals. Dr. Piazza has received research grant support from EKOS Corporation, Bayer, Bristol-Myers Squibb/Pfizer, Portola Pharmaceuticals, and Janssen Pharmaceuticals; and has received consulting fees from Amgen, Pfizer, Boston Scientific, Agile, and Thrombolex. Dr. McBane reported no relevant disclosures.

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

Major thromboembolic complications and adverse cardiovascular events occurred with high frequency in patients with COVID-19, especially in the intensive care setting, despite a high use of thromboprophylaxis, in a new large observational U.S. study.

“Despite very high rate of antithrombotic prophylaxis there were a high rate of thromboembolic events suggesting that we are probably not providing enough thromboprophylaxis,” lead author Gregory Piazza, MD, Brigham and Women’s Hospital, Boston, said in an interview. 

“Standard prophylaxis as recommended in the guidelines is a low dose of low-molecular-weight heparin once daily, but these results suggest [patients] probably need higher doses,” he added.

However, Dr. Piazza cautioned that this is an observational study and randomized trials are needed to make changes in treatment strategies. Several such trials are currently underway.

The current study was published online ahead of print in the Nov. 3 issue of the Journal of the American College of Cardiology.
 

Rates similar to other very sick patients

The study showed that while thromboembolic complications were high, they were not as high as seen in some of the earlier studies from Asia and Europe, Dr. Piazza noted.

“The numbers we were seeing in early reports were so high we couldn’t figure out how that was possible,” he said. “Our study suggests that, in a U.S. population receiving thromboprophylaxis, the rate of thromboembolic complications [are] more in line with what we would expect to see in other very sick patients who end up in ICU.”

He suggested that the very high rates of thromboembolic complications in the early studies from Asia may have been because of the lack of thromboprophylaxis, which is not routine in hospitalized patients there. “Some of the earlier studies also used routine ultrasound and so picked up asymptomatic thrombotic events, which was not the case in our study. So our results are more representative of the U.S. population.”

Dr. Piazza attributed the high rate of thromboembolic complications being reported with COVID-19 to the sheer number of very sick patients being admitted to the hospital.

“We are accustomed to seeing a rare case of thrombosis despite prophylaxis in hospitalized patients, but we are seeing more in COVID patients. This is probably just because we have more critically ill patients,” he said.

“We are seeing an incredible influx of patients to the ICU that we have never experienced before, so the increase in thromboembolic complications is more obvious. In prior years we probably haven’t had enough critically ill patients at any one time to raise the flag about thromboprophylaxis,” he commented.

The study also found a high rate of cardiovascular complications. They are seeing an increase in the risk of MI, which is to be expected in such sick patients, but they also see quite a bit of new atrial fibrillation, myocarditis, and heart failure in patients who don’t always have underlying cardiovascular disease, he said.

“So this virus does appear to have a predilection to causing cardiovascular complications, but this is probably because it is making patients so sick,” Dr. Piazza said. “If flu was this virulent and resulted in such high rates of acute respiratory distress syndrome (ARDS), we would probably see similar cardiovascular complication rates.”

For the current report, the researchers analyzed a retrospective cohort of 1,114 patients with COVID-19 diagnosed through the Mass General Brigham integrated health network. Of these, 170 had been admitted to the ICU, 229 had been hospitalized but not treated in ICU, and 715 were outpatients. In terms of ethnicity, 22% were Hispanic/Latino and 44% were non-White. 

Cardiovascular risk factors were common, with 36% of patients having hypertension, 29% hyperlipidemia, and 18% diabetes. Prophylactic anticoagulation was prescribed in 89% of patients with COVID-19 in the intensive care cohort and 85% of those in the hospitalized non–intensive care setting.

Results showed that major arterial or venous thromboembolism (VTE) occurred in 35% of the intensive care cohort, 2.6% of those hospitalized but not treated in ICU, and 0% of outpatients.

Major adverse cardiovascular events occurred in 46% of the intensive care cohort, 6.1% of those hospitalized but non-ICU, and 0% of outpatients.

Symptomatic VTE occurred in 27% of those admitted to ICU, 2.2% of those hospitalized but non-ICU, and 0% of outpatients.

“We found that outpatients had a very low rate of thromboembolic complications, with the vast majority of the risk being in hospitalized patients, especially those in ICU,” Dr. Piazza said.

“These results suggest that we don’t need routine thromboprophylaxis for all outpatients with COVID-19, but there will probably be some patients who need it – those with risk factors for thromboembolism.”

Catheter- and device-associated deep vein thrombosis accounted for 76.9% of the DVTs observed in the study.

“Our finding of high frequency of catheter-associated DVT supports the judicious use of central venous catheters that have been widely implemented, especially in the ICU, to minimize recurrent health care team exposure and facilitate monitoring,” the researchers wrote.
 

ARDS biggest risk factor

Of all the markers of disease severity, the presence of ARDS had the strongest association with adverse outcomes, including major arterial or VTE, major adverse cardiovascular events, symptomatic VTE, and death.

“The severe inflammatory state associated with ARDS and other complications of COVID-19 and its resultant hypercoagulability may explain, at least in part, the high frequency of thromboembolic events. Improved risk stratification, utilizing biochemical markers of inflammation and activated coagulation as well as clinical indicators, such as ARDS, may play an important role in the early identification of patients with an increased likelihood of developing symptomatic VTE or arterial thrombosis,” the researchers wrote. “They may benefit from full- or intermediate-intensity antithrombotic therapy rather than prophylactic anticoagulation.”

They point out that this study provides a cross-sectional view of the cardiovascular complications of COVID-19 in a large health care network, consisting of two academic medical centers serving the greater Boston area, several community hospitals, and numerous outpatient care sites.

“The study incorporates a wide scope of clinically meaningful cardiovascular endpoints and utilizes a rigorous process of event adjudication. Although data on patients with COVID-19 in the ICU have been the subject of most reports, our study provides insights into the broad spectrum of all hospitalized and outpatient populations,” the authors noted.

“The high frequency of arterial or venous thromboembolism in hospitalized patients despite routine thromboprophylaxis suggests the need for improved risk stratification and enhanced preventive efforts,” they concluded.

The study is continuing, and the researchers expect to have data on 10,000 patients by the end of winter.
 

Wait for randomized trials

In an accompanying editorial, Robert McBane, MD, Mayo Clinic, Rochester, Minn., said that these data provide important real-world arterial and venous thrombotic event rates across a large, integrated health care network and an experienced roster of clinician-scientists devoted to thrombosis research.

Noting that whether to interpret these results as alarming or reassuring requires a comparison of expected thromboembolic event rates separate from the pandemic, he pointed out that, while the overall VTE rate among ICU patients was high, the vast majority of these events were attributable to central venous lines, and apart from these, the event rates do not appear inflated relative to prior published incidence rates from the pre–COVID-19 era.

“It is therefore important to resist the urge to overprevent or overtreat patients and expose them to the serious risks of major bleeding,” Dr. McBane wrote, adding that “the systematized approach to delivery of guideline-driven VTE prophylaxis across this large, integrated health network likely contributed to the relatively low rates of serious thrombotic outcomes reported.”

He further noted that, as the majority of VTE events were related to central venous lines in ICU patients, “this underscores the importance of a bundled care approach to central venous line management with daily assessment of the continued necessity of central access.

“A number of important clinical trials aimed at optimizing thromboprophylaxis during hospitalization, following hospital dismissal, and in ambulatory settings are underway. Until available, the lessons of thoughtful anticoagulant prophylaxis and treatment guidelines harvested from years of clinical research appear to apply,” he concluded.

This study was funded, in part, by a research grant from Janssen Pharmaceuticals. Dr. Piazza has received research grant support from EKOS Corporation, Bayer, Bristol-Myers Squibb/Pfizer, Portola Pharmaceuticals, and Janssen Pharmaceuticals; and has received consulting fees from Amgen, Pfizer, Boston Scientific, Agile, and Thrombolex. Dr. McBane reported no relevant disclosures.

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

Children with juvenile idiopathic arthritis–associated uveitis (JIA-U) are significantly more likely to experience a flare in their eye disease if their arthritis is also worsening, a team of U.S.-based researchers has found.

Jonathan Trobe, M.D./Wikimedia Commons/CC BY-SA 3.0

In a longitudinal cohort study, children with active arthritis at the time of a routine rheumatology assessment had an almost 2.5-fold increased risk of also having active uveitis 45 days before or after the assessment than did children whose arthritis was not flaring at the rheumatology assessment.

“We demonstrate that the two diseases often run parallel courses,” corresponding author Emily J. Liebling, MD, of the Children’s Hospital of Philadelphia and associates state in Arthritis Care & Research, noting that the magnitude of the association is striking.

“Although there are known risk factors associated with uveitis development in children with JIA, less data are available about factors associated with uveitis flare or activity,” said Sheila T. Angeles-Han, MD, MSc, of the departments of pediatrics and ophthalmology at Cincinnati Children’s Hospital Medical Center who commented on the study in an interview.

“If proven, this knowledge has the potential to impact practice patterns and current guidelines wherein a pediatric rheumatologist who evaluates a child with JIA-associated uveitis and finds active arthritis would request an expedited ophthalmic examination,” Dr. Angeles-Han suggested.

Dr. Angeles-Han led the development of the first American College of Rheumatology/Arthritis Foundation Guideline for the Screening, Monitoring, and Treatment of JIA-Associated Uveitis, which recommends regular screening for uveitis in all children with JIA. Children found to have uveitis should then be screened at least every 3 months, and more frequently if they are taking glucocorticoids and treatment is being tapered.

JIA-associated uveitis accounts for around 20%-40% of all cases of noninfectious childhood eye inflammation, and it can run an insidious and chronic course.

“Children with acute anterior uveitis are symptomatic and tend to have a painful red eye, thus prompting an ophthalmic evaluation,” Dr. Angeles-Han explained. “This is different from children with chronic anterior uveitis who tend not to have any symptoms, thus a screening examination is critical to detect ocular inflammation.”

While the ACR/AF guideline distinguishes between acute and chronic uveitis, Dr. Liebling and colleagues explain that they did not because their experience shows that “even patients with chronic anterior uveitis, typically thought to have silent disease, may exhibit symptoms of eye pain, redness, vision changes, and photophobia.”

Conversely, they say “the JIA subtypes usually associated with acute anterior uveitis may instead manifest as asymptomatic eye disease.”

For their study, Dr. Liebling and coinvestigators examined the records of children seen at the Children’s Hospital of Philadelphia over a 6.5-year period. For inclusion, children had to have a physician diagnosis of JIA of any subtype and a history of uveitis.

A total of 98 children were included in the retrospective evaluation; the median age at diagnosis of JIA was 3.3 years, and the median age at first uveitis diagnosis was 5.1 years. The majority (82%) were female, 69% were antinuclear antibody (ANA) positive, and 60% had oligoarthritis – all of which have been associated with having a higher risk for developing uveitis.

However, independent of these and several other factors, the probability of having active uveitis within 45 days of a rheumatology assessment was 65% in those with active arthritis versus 42% for those with no active joints.

Their data are based on 1,229 rheumatology visits that occurred between 2013 and 2019, with a median of 13 visits per patient. Overall, arthritis was defined as being active in 17% of visits, and active uveitis was observed in 18% of rheumatology visits.

Concordance between arthritis and uveitis activity was observed 73% of the time, the researchers reported. A sensitivity analysis that excluded children with the enthesitis-related arthritis subtype of JIA, who may not undergo frequent eye exams, did not change their findings.

Decreased odds of active uveitis at any time point were seen with the use of combination biologic and nonbiologic disease-modifying antirheumatic drugs. Years from uveitis diagnosis was also associated with lower odds of active uveitis over time.

Other factors associated with lower odds of uveitis were female sex, HLA-B27 positivity, and having any subtype of JIA other than the oligoarticular subtype.

Dr. Liebling and coinvestigators concluded that, contrary to the historical dogma, arthritis and uveitis do not run distinct and unrelated courses: “In patients with JIA-U, there is a significant temporal association between arthritis and uveitis disease activity.”

The study was sponsored by the Children’s Hospital of Philadelphia Rheumatology Research Fund. The investigators for the study had no financial support from commercial sources or any other potential conflicts of interest. Dr. Angeles-Han had no conflicts of interest to disclose.

SOURCE: Liebling EJ et al. Arthritis Care Res. 2020 Oct 12. doi: 10.1002/acr.24483.

Children with juvenile idiopathic arthritis–associated uveitis (JIA-U) are significantly more likely to experience a flare in their eye disease if their arthritis is also worsening, a team of U.S.-based researchers has found.

Jonathan Trobe, M.D./Wikimedia Commons/CC BY-SA 3.0

In a longitudinal cohort study, children with active arthritis at the time of a routine rheumatology assessment had an almost 2.5-fold increased risk of also having active uveitis 45 days before or after the assessment than did children whose arthritis was not flaring at the rheumatology assessment.

“We demonstrate that the two diseases often run parallel courses,” corresponding author Emily J. Liebling, MD, of the Children’s Hospital of Philadelphia and associates state in Arthritis Care & Research, noting that the magnitude of the association is striking.

“Although there are known risk factors associated with uveitis development in children with JIA, less data are available about factors associated with uveitis flare or activity,” said Sheila T. Angeles-Han, MD, MSc, of the departments of pediatrics and ophthalmology at Cincinnati Children’s Hospital Medical Center who commented on the study in an interview.

“If proven, this knowledge has the potential to impact practice patterns and current guidelines wherein a pediatric rheumatologist who evaluates a child with JIA-associated uveitis and finds active arthritis would request an expedited ophthalmic examination,” Dr. Angeles-Han suggested.

Dr. Angeles-Han led the development of the first American College of Rheumatology/Arthritis Foundation Guideline for the Screening, Monitoring, and Treatment of JIA-Associated Uveitis, which recommends regular screening for uveitis in all children with JIA. Children found to have uveitis should then be screened at least every 3 months, and more frequently if they are taking glucocorticoids and treatment is being tapered.

JIA-associated uveitis accounts for around 20%-40% of all cases of noninfectious childhood eye inflammation, and it can run an insidious and chronic course.

“Children with acute anterior uveitis are symptomatic and tend to have a painful red eye, thus prompting an ophthalmic evaluation,” Dr. Angeles-Han explained. “This is different from children with chronic anterior uveitis who tend not to have any symptoms, thus a screening examination is critical to detect ocular inflammation.”

While the ACR/AF guideline distinguishes between acute and chronic uveitis, Dr. Liebling and colleagues explain that they did not because their experience shows that “even patients with chronic anterior uveitis, typically thought to have silent disease, may exhibit symptoms of eye pain, redness, vision changes, and photophobia.”

Conversely, they say “the JIA subtypes usually associated with acute anterior uveitis may instead manifest as asymptomatic eye disease.”

For their study, Dr. Liebling and coinvestigators examined the records of children seen at the Children’s Hospital of Philadelphia over a 6.5-year period. For inclusion, children had to have a physician diagnosis of JIA of any subtype and a history of uveitis.

A total of 98 children were included in the retrospective evaluation; the median age at diagnosis of JIA was 3.3 years, and the median age at first uveitis diagnosis was 5.1 years. The majority (82%) were female, 69% were antinuclear antibody (ANA) positive, and 60% had oligoarthritis – all of which have been associated with having a higher risk for developing uveitis.

However, independent of these and several other factors, the probability of having active uveitis within 45 days of a rheumatology assessment was 65% in those with active arthritis versus 42% for those with no active joints.

Their data are based on 1,229 rheumatology visits that occurred between 2013 and 2019, with a median of 13 visits per patient. Overall, arthritis was defined as being active in 17% of visits, and active uveitis was observed in 18% of rheumatology visits.

Concordance between arthritis and uveitis activity was observed 73% of the time, the researchers reported. A sensitivity analysis that excluded children with the enthesitis-related arthritis subtype of JIA, who may not undergo frequent eye exams, did not change their findings.

Decreased odds of active uveitis at any time point were seen with the use of combination biologic and nonbiologic disease-modifying antirheumatic drugs. Years from uveitis diagnosis was also associated with lower odds of active uveitis over time.

Other factors associated with lower odds of uveitis were female sex, HLA-B27 positivity, and having any subtype of JIA other than the oligoarticular subtype.

Dr. Liebling and coinvestigators concluded that, contrary to the historical dogma, arthritis and uveitis do not run distinct and unrelated courses: “In patients with JIA-U, there is a significant temporal association between arthritis and uveitis disease activity.”

The study was sponsored by the Children’s Hospital of Philadelphia Rheumatology Research Fund. The investigators for the study had no financial support from commercial sources or any other potential conflicts of interest. Dr. Angeles-Han had no conflicts of interest to disclose.

SOURCE: Liebling EJ et al. Arthritis Care Res. 2020 Oct 12. doi: 10.1002/acr.24483.

Children with juvenile idiopathic arthritis–associated uveitis (JIA-U) are significantly more likely to experience a flare in their eye disease if their arthritis is also worsening, a team of U.S.-based researchers has found.

Jonathan Trobe, M.D./Wikimedia Commons/CC BY-SA 3.0

In a longitudinal cohort study, children with active arthritis at the time of a routine rheumatology assessment had an almost 2.5-fold increased risk of also having active uveitis 45 days before or after the assessment than did children whose arthritis was not flaring at the rheumatology assessment.

“We demonstrate that the two diseases often run parallel courses,” corresponding author Emily J. Liebling, MD, of the Children’s Hospital of Philadelphia and associates state in Arthritis Care & Research, noting that the magnitude of the association is striking.

“Although there are known risk factors associated with uveitis development in children with JIA, less data are available about factors associated with uveitis flare or activity,” said Sheila T. Angeles-Han, MD, MSc, of the departments of pediatrics and ophthalmology at Cincinnati Children’s Hospital Medical Center who commented on the study in an interview.

“If proven, this knowledge has the potential to impact practice patterns and current guidelines wherein a pediatric rheumatologist who evaluates a child with JIA-associated uveitis and finds active arthritis would request an expedited ophthalmic examination,” Dr. Angeles-Han suggested.

Dr. Angeles-Han led the development of the first American College of Rheumatology/Arthritis Foundation Guideline for the Screening, Monitoring, and Treatment of JIA-Associated Uveitis, which recommends regular screening for uveitis in all children with JIA. Children found to have uveitis should then be screened at least every 3 months, and more frequently if they are taking glucocorticoids and treatment is being tapered.

JIA-associated uveitis accounts for around 20%-40% of all cases of noninfectious childhood eye inflammation, and it can run an insidious and chronic course.

“Children with acute anterior uveitis are symptomatic and tend to have a painful red eye, thus prompting an ophthalmic evaluation,” Dr. Angeles-Han explained. “This is different from children with chronic anterior uveitis who tend not to have any symptoms, thus a screening examination is critical to detect ocular inflammation.”

While the ACR/AF guideline distinguishes between acute and chronic uveitis, Dr. Liebling and colleagues explain that they did not because their experience shows that “even patients with chronic anterior uveitis, typically thought to have silent disease, may exhibit symptoms of eye pain, redness, vision changes, and photophobia.”

Conversely, they say “the JIA subtypes usually associated with acute anterior uveitis may instead manifest as asymptomatic eye disease.”

For their study, Dr. Liebling and coinvestigators examined the records of children seen at the Children’s Hospital of Philadelphia over a 6.5-year period. For inclusion, children had to have a physician diagnosis of JIA of any subtype and a history of uveitis.

A total of 98 children were included in the retrospective evaluation; the median age at diagnosis of JIA was 3.3 years, and the median age at first uveitis diagnosis was 5.1 years. The majority (82%) were female, 69% were antinuclear antibody (ANA) positive, and 60% had oligoarthritis – all of which have been associated with having a higher risk for developing uveitis.

However, independent of these and several other factors, the probability of having active uveitis within 45 days of a rheumatology assessment was 65% in those with active arthritis versus 42% for those with no active joints.

Their data are based on 1,229 rheumatology visits that occurred between 2013 and 2019, with a median of 13 visits per patient. Overall, arthritis was defined as being active in 17% of visits, and active uveitis was observed in 18% of rheumatology visits.

Concordance between arthritis and uveitis activity was observed 73% of the time, the researchers reported. A sensitivity analysis that excluded children with the enthesitis-related arthritis subtype of JIA, who may not undergo frequent eye exams, did not change their findings.

Decreased odds of active uveitis at any time point were seen with the use of combination biologic and nonbiologic disease-modifying antirheumatic drugs. Years from uveitis diagnosis was also associated with lower odds of active uveitis over time.

Other factors associated with lower odds of uveitis were female sex, HLA-B27 positivity, and having any subtype of JIA other than the oligoarticular subtype.

Dr. Liebling and coinvestigators concluded that, contrary to the historical dogma, arthritis and uveitis do not run distinct and unrelated courses: “In patients with JIA-U, there is a significant temporal association between arthritis and uveitis disease activity.”

The study was sponsored by the Children’s Hospital of Philadelphia Rheumatology Research Fund. The investigators for the study had no financial support from commercial sources or any other potential conflicts of interest. Dr. Angeles-Han had no conflicts of interest to disclose.

SOURCE: Liebling EJ et al. Arthritis Care Res. 2020 Oct 12. doi: 10.1002/acr.24483.

Last spring, when Cliff Willmeng, RN, was working at United Hospital in St. Paul, Minnesota, he’d take off his personal protective equipment (PPE) in the same hallway where children were transported from ambulances to the neighboring Children’s Hospital emergency department. Stretchers would roll across red tape on the floor that designated the area as a “hot zone.” The door from a break room was about 10 feet away.

Willmeng has been a union activist all his life, but he’d never filed a complaint with the Occupational Safety and Health Administration (OSHA) until the COVID-19 pandemic hit.

Concerned about the inadequate space for doffing PPE and other situations in which the spread of SARS-CoV-2 seemed possible, Willmeng and other colleagues filed multiple OSHA complaints with the Minnesota Department of Labor in March and April. Willmeng was also worried about bringing SARS-CoV-2 on his scrubs home to his wife and kids, and he started wearing hospital-supplied scrubs that were meant for doctors and that were washed on site, which was against hospital policy. The hospital fired Willmeng on May 8, citing code of conduct and respectful workplace violations arising from the uniform dispute.

In August, the state agency issued Willmeng’s hospital a $2,100 fine for failure to comply with guidance regarding “respiratory protection” in response to worker complaints over the fact that they were instructed to restaple elastic bands on N95 masks early in the pandemic. In a statement, United Hospital said it contested the citation, and it is in discussions with Minnesota OSHA. “We have and continue to instruct employees not to alter N95 respirators or reuse damaged or soiled N95 respirators,” such as when the straps are broken, the statement says.

Minnesota OSHA has received three times as many emails and phone calls from workers and employers requesting information and assistance during the pandemic, compared with last year, said spokesperson James Honerman. “If Minnesota OSHA is made aware of a workplace safety or health issue, it assesses the situation and determines how best to respond, including conducting a workplace investigation.”

But Willmeng, who has been out of work since he was fired, says that without a receipt or confirmation from OSHA, he has no way of knowing whether there has been any follow-up regarding his complaints. Minnesota OSHA said workers should receive a letter once a case is resolved.

Like Willmeng’s case, none of the more than 10,000 COVID-related complaints the federal OSHA office has received from across the country have resulted in meaningful sanctions. Unions have picketed local OSHA offices and publicized complaints on behalf of their members to protest what they see as a lack of oversight. Legislators have called on US Department of Labor Secretary Eugene Scalia to step up enforcement.

For many health care workers, complaining to OSHA is a last resort after failing to get satisfactory responses from supervisors and appealing to unions for help. But with such minimal oversight from OSHA, some union leaders and legislators say it’s actually more dangerous than not having workplace safety enforcement at all. Lack of directives from the Trump administration has left the agency without the teeth it has cut under previous administrations, and recent changes to the agency’s rules raise questions about whether companies are ever required to report workers’ hospitalizations due to COVID-19.

“It’s so ineffective that it’s more dangerous to workers,” said Kim Cordova, president of United Food and Commercial Workers (UFCW) Local 7, which represents 22,000 health care and other workers in Colorado and Wyoming. “Employers only do what they’re forced to do.” Instead of deterring a multi-billion-dollar company, she said, such low fines signal that a company doesn’t need to worry about COVID-related safety.

“OSHA is doing a lamentably poor job protecting workers during the pandemic,” said James Brudney, JD, a professor at Fordham Law School, in New York, and former chief counsel of the U.S. Senate Subcommittee on Labor. “I’m not alone in saying that the agency has performed so badly.”

Former government officials writing in JAMA were similarly critical: “In the face of the greatest worker health crisis in recent history, OSHA, the lead government agency responsible for worker health and safety, has not fulfilled its responsibilities.”
 

What could have been

There were early signs that the agency wouldn’t be heavy-handed about COVID-19 safety concerns, Brudney said.

The agency could have issued Emergency Temporary Standards, rules it can put in place during pandemics that address specific short-term concerns. These rules could have required employers to take infection-control measures to protect workers, including mask wearing, providing proper PPE, and screening for COVID-19 symptoms. “That’s what the agency is supposed to do. They’re supposed to respond to an emergency with emergency measures,” Brudney said.

But despite legislative pressure and a court case, Secretary of Labor Eugene Scalia has declined to do so, saying that the agency would instead rely on its regular general duty clause, which is always in place to keep workplaces free from hazards that “cause death or serious physical harm.” The agency invoked the general duty clause for COVID-19–related violations for the first time in September to levy modest fines.

In response to a request for an interview, a Department of Labor spokesperson said that preexisting OSHA requirements apply to workers during the pandemic, including providing PPE for workers and assessing sanitation and cleanliness standards. The agency has issued specific guidance to companies on pandemic preparedness, she said, and that it responds to all complaints. Additionally, she cited whistleblower laws that make it illegal for employers to retaliate against employees for making safety and health complaints.

The federal OSHA office received 10,868 COVID-related complaints from Feb. 1 through Oct. 20, citing issues ranging from failure to provide proper PPE to not informing workers about exposures. As of Oct. 22, a total of 2,349 of the complaints involved healthcare workers. This count doesn’t include the untold number of “informal” complaints handled by state OSHA offices.

In a recent JAMA opinion piece, two former government officials agreed that “the federal government has not fully utilized OSHA’s public safety authority” and called the issuing of an Emergency Temporary Standard that would require employers to develop and implement infection control plans “the most important action the federal government could take” to protect workers.

“Employers are more likely to implement these controls if they are mandated by a government agency that has adequate enforcement tools to ensure compliance,” wrote former Assistant Secretary of Labor David Michaels, PhD, MPH, now at the Milken Institute School of Public Health of the George Washington University, Washington, and Gregory Wagner, MD, a former senior adviser at the National Institute for Occupational Safety and Health at the Centers for Disease Control and Prevention, now at the Harvard T.H. Chan School of Public Health, Boston.

They cited the success of a standard that OSHA issued in 1991 in response to the HIV/AIDS crisis. “The bloodborne pathogens standard has contributed to a substantial decline in health care worker risk for bloodborne diseases like HIV and hepatitis B and C,” they wrote. In a new report for the Century Foundation, the pair offered recommendations to the federal government for controlling the spread of the disease by ramping up OSHA’s role.

OSHA did issue a response plan that requires employers to report in regard to employees who experienced workplace exposures to SARS-CoV-2 and who were hospitalized with COVID-19 or died of the disease within certain time frames, but recent changes to these rules make experts question whether companies are in fact required to report hospitalizations.

In its second revision of guidelines, added to its FAQ page on Sept. 30, the agency said that, in order to be reportable, “an in-patient hospitalization due to COVID-19 must occur within 24 hours of an exposure to SARS-CoV-2 at work” and that the employer must report the hospitalization within 24 hours of learning both that the employee has been hospitalized and that the reason for the hospitalization was a work-related case of COVID-19. Previously, the 24-hour hospitalization window started at the time of diagnosis of the disease, rather than the work-related exposure.

The agency subsequently dropped the first citation it had issued for a COVID-related violation, even though the company, a nursing home, had already agreed to pay $3,904 for reporting employee hospitalizations late.

“It’s a step backwards from an important workplace and public health function that OSHA should be doing,” said Wagner, coauthor of the JAMA opinion piece.

Even without issuing Emergency Temporary Standards, critics say OSHA could have acted much earlier. OSHA issued its first COVID-related federal citation, the one against the nursing home that was dropped, in May for events that occurred in mid-April. The second COVID-related federal citation came in July.

The agency could also charge much more substantial fines for the citations it has issued. If a medical facility was cited for a PPE violation, such as the Minnesota hospital where workers were told to restaple the elastic bands on N95s, the agency could have cited the hospital for one violation per employee. Such fines based on multiple violations could add up to the hundreds of thousands to millions of dollars.

“It would send a signal to the highest-risk employers that these are violations that need to be addressed immediately,” Brudney said.

Many of the 22 state OSHA offices appear to be more responsive to COVID-related complaints than the federal agency, creating a system in which health care workers have substantially different rights from one state to the next. The governor of California, for example, recently authorized California’s OSHA division to consider COVID-19 an imminent hazard, to prohibit workers from entering areas where the hazard exists, and to require employers to disclose exposures. The state also recently issued large fines for COVID safety issues: $222,075 to frozen food manufacturer Overhill Farms and $214,080 to employment agency Jobsource North America.

Elsewhere, state laws such as New Jersey’s Conscientious Employee Protection Act give workers the right to refuse to work in unsafe situations, Brudney said. “A lot more action is going on at the state level because so little is being done at the federal level,” he said. “Some of it is governors committed to protecting essential workers and their families.”
 

Unions call for sanctions

Unions are both decrying the lack of enforcement thus far and seeking more oversight going forward.

In August, the National Nurses’ United (NNU) union filed a complaint to implore OSHA to investigate the country’s biggest hospital systems, HCA Healthcare, which operates 184 hospitals and about 2,000 other care sites in 21 states and the United Kingdom. The union describes how, throughout HCA hospitals, there is an environment conducive to the spread of coronavirus. Nurses share space and equipment, such as computers, desks, phones, bathrooms, and break rooms, where staff take off masks to eat and drink. The complaint also describes how there is resistance to testing nurses and a lack of communication about infections among colleagues.

“When they have total disregard for safety, they should be punished to the utmost,” said Markowitz, noting that HCA Healthcare is worth $40 billion. “They can penalize them, but if it’s unsafe conditions for RNs and healthcare workers, we know it’s unsafe for the patients. There needs to be drastic measures to prevent hospital corporations from behaving that way.”

In a statement, HCA spokesman Harlow Sumerford said the company has followed CDC guidance for protecting frontline caregivers. “We’re proud of our response and the significant resources we’ve deployed to help protect our colleagues. Meanwhile, the NNU has chosen to use this pandemic as an opportunity to gain publicity by attacking hospitals across the country,” Sumerford said.

Members of the union recently protested in front of the federal OSHA offices in Denver.

After several months, OSHA finally penalized a meat packing plant where eight workers (six union members) had died of COVID-19 last spring. But the amount – $15,615 – was so low that Cordova worries it will actually have a worse impact than no fine.

“It’s more dangerous to workers because now employers know [they won’t be punished meaningfully],” she said. “During the pandemic, OSHA has been absolutely absent.”

Thus, the recent picketing outside the offices in Denver. But, Cordova noted, it’s unlikely OSHA employees saw them. Their own offices were deemed too risky to stay open during the pandemic. They were vacant.
 

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

Last spring, when Cliff Willmeng, RN, was working at United Hospital in St. Paul, Minnesota, he’d take off his personal protective equipment (PPE) in the same hallway where children were transported from ambulances to the neighboring Children’s Hospital emergency department. Stretchers would roll across red tape on the floor that designated the area as a “hot zone.” The door from a break room was about 10 feet away.

Willmeng has been a union activist all his life, but he’d never filed a complaint with the Occupational Safety and Health Administration (OSHA) until the COVID-19 pandemic hit.

Concerned about the inadequate space for doffing PPE and other situations in which the spread of SARS-CoV-2 seemed possible, Willmeng and other colleagues filed multiple OSHA complaints with the Minnesota Department of Labor in March and April. Willmeng was also worried about bringing SARS-CoV-2 on his scrubs home to his wife and kids, and he started wearing hospital-supplied scrubs that were meant for doctors and that were washed on site, which was against hospital policy. The hospital fired Willmeng on May 8, citing code of conduct and respectful workplace violations arising from the uniform dispute.

In August, the state agency issued Willmeng’s hospital a $2,100 fine for failure to comply with guidance regarding “respiratory protection” in response to worker complaints over the fact that they were instructed to restaple elastic bands on N95 masks early in the pandemic. In a statement, United Hospital said it contested the citation, and it is in discussions with Minnesota OSHA. “We have and continue to instruct employees not to alter N95 respirators or reuse damaged or soiled N95 respirators,” such as when the straps are broken, the statement says.

Minnesota OSHA has received three times as many emails and phone calls from workers and employers requesting information and assistance during the pandemic, compared with last year, said spokesperson James Honerman. “If Minnesota OSHA is made aware of a workplace safety or health issue, it assesses the situation and determines how best to respond, including conducting a workplace investigation.”

But Willmeng, who has been out of work since he was fired, says that without a receipt or confirmation from OSHA, he has no way of knowing whether there has been any follow-up regarding his complaints. Minnesota OSHA said workers should receive a letter once a case is resolved.

Like Willmeng’s case, none of the more than 10,000 COVID-related complaints the federal OSHA office has received from across the country have resulted in meaningful sanctions. Unions have picketed local OSHA offices and publicized complaints on behalf of their members to protest what they see as a lack of oversight. Legislators have called on US Department of Labor Secretary Eugene Scalia to step up enforcement.

For many health care workers, complaining to OSHA is a last resort after failing to get satisfactory responses from supervisors and appealing to unions for help. But with such minimal oversight from OSHA, some union leaders and legislators say it’s actually more dangerous than not having workplace safety enforcement at all. Lack of directives from the Trump administration has left the agency without the teeth it has cut under previous administrations, and recent changes to the agency’s rules raise questions about whether companies are ever required to report workers’ hospitalizations due to COVID-19.

“It’s so ineffective that it’s more dangerous to workers,” said Kim Cordova, president of United Food and Commercial Workers (UFCW) Local 7, which represents 22,000 health care and other workers in Colorado and Wyoming. “Employers only do what they’re forced to do.” Instead of deterring a multi-billion-dollar company, she said, such low fines signal that a company doesn’t need to worry about COVID-related safety.

“OSHA is doing a lamentably poor job protecting workers during the pandemic,” said James Brudney, JD, a professor at Fordham Law School, in New York, and former chief counsel of the U.S. Senate Subcommittee on Labor. “I’m not alone in saying that the agency has performed so badly.”

Former government officials writing in JAMA were similarly critical: “In the face of the greatest worker health crisis in recent history, OSHA, the lead government agency responsible for worker health and safety, has not fulfilled its responsibilities.”
 

What could have been

There were early signs that the agency wouldn’t be heavy-handed about COVID-19 safety concerns, Brudney said.

The agency could have issued Emergency Temporary Standards, rules it can put in place during pandemics that address specific short-term concerns. These rules could have required employers to take infection-control measures to protect workers, including mask wearing, providing proper PPE, and screening for COVID-19 symptoms. “That’s what the agency is supposed to do. They’re supposed to respond to an emergency with emergency measures,” Brudney said.

But despite legislative pressure and a court case, Secretary of Labor Eugene Scalia has declined to do so, saying that the agency would instead rely on its regular general duty clause, which is always in place to keep workplaces free from hazards that “cause death or serious physical harm.” The agency invoked the general duty clause for COVID-19–related violations for the first time in September to levy modest fines.

In response to a request for an interview, a Department of Labor spokesperson said that preexisting OSHA requirements apply to workers during the pandemic, including providing PPE for workers and assessing sanitation and cleanliness standards. The agency has issued specific guidance to companies on pandemic preparedness, she said, and that it responds to all complaints. Additionally, she cited whistleblower laws that make it illegal for employers to retaliate against employees for making safety and health complaints.

The federal OSHA office received 10,868 COVID-related complaints from Feb. 1 through Oct. 20, citing issues ranging from failure to provide proper PPE to not informing workers about exposures. As of Oct. 22, a total of 2,349 of the complaints involved healthcare workers. This count doesn’t include the untold number of “informal” complaints handled by state OSHA offices.

In a recent JAMA opinion piece, two former government officials agreed that “the federal government has not fully utilized OSHA’s public safety authority” and called the issuing of an Emergency Temporary Standard that would require employers to develop and implement infection control plans “the most important action the federal government could take” to protect workers.

“Employers are more likely to implement these controls if they are mandated by a government agency that has adequate enforcement tools to ensure compliance,” wrote former Assistant Secretary of Labor David Michaels, PhD, MPH, now at the Milken Institute School of Public Health of the George Washington University, Washington, and Gregory Wagner, MD, a former senior adviser at the National Institute for Occupational Safety and Health at the Centers for Disease Control and Prevention, now at the Harvard T.H. Chan School of Public Health, Boston.

They cited the success of a standard that OSHA issued in 1991 in response to the HIV/AIDS crisis. “The bloodborne pathogens standard has contributed to a substantial decline in health care worker risk for bloodborne diseases like HIV and hepatitis B and C,” they wrote. In a new report for the Century Foundation, the pair offered recommendations to the federal government for controlling the spread of the disease by ramping up OSHA’s role.

OSHA did issue a response plan that requires employers to report in regard to employees who experienced workplace exposures to SARS-CoV-2 and who were hospitalized with COVID-19 or died of the disease within certain time frames, but recent changes to these rules make experts question whether companies are in fact required to report hospitalizations.

In its second revision of guidelines, added to its FAQ page on Sept. 30, the agency said that, in order to be reportable, “an in-patient hospitalization due to COVID-19 must occur within 24 hours of an exposure to SARS-CoV-2 at work” and that the employer must report the hospitalization within 24 hours of learning both that the employee has been hospitalized and that the reason for the hospitalization was a work-related case of COVID-19. Previously, the 24-hour hospitalization window started at the time of diagnosis of the disease, rather than the work-related exposure.

The agency subsequently dropped the first citation it had issued for a COVID-related violation, even though the company, a nursing home, had already agreed to pay $3,904 for reporting employee hospitalizations late.

“It’s a step backwards from an important workplace and public health function that OSHA should be doing,” said Wagner, coauthor of the JAMA opinion piece.

Even without issuing Emergency Temporary Standards, critics say OSHA could have acted much earlier. OSHA issued its first COVID-related federal citation, the one against the nursing home that was dropped, in May for events that occurred in mid-April. The second COVID-related federal citation came in July.

The agency could also charge much more substantial fines for the citations it has issued. If a medical facility was cited for a PPE violation, such as the Minnesota hospital where workers were told to restaple the elastic bands on N95s, the agency could have cited the hospital for one violation per employee. Such fines based on multiple violations could add up to the hundreds of thousands to millions of dollars.

“It would send a signal to the highest-risk employers that these are violations that need to be addressed immediately,” Brudney said.

Many of the 22 state OSHA offices appear to be more responsive to COVID-related complaints than the federal agency, creating a system in which health care workers have substantially different rights from one state to the next. The governor of California, for example, recently authorized California’s OSHA division to consider COVID-19 an imminent hazard, to prohibit workers from entering areas where the hazard exists, and to require employers to disclose exposures. The state also recently issued large fines for COVID safety issues: $222,075 to frozen food manufacturer Overhill Farms and $214,080 to employment agency Jobsource North America.

Elsewhere, state laws such as New Jersey’s Conscientious Employee Protection Act give workers the right to refuse to work in unsafe situations, Brudney said. “A lot more action is going on at the state level because so little is being done at the federal level,” he said. “Some of it is governors committed to protecting essential workers and their families.”
 

Unions call for sanctions

Unions are both decrying the lack of enforcement thus far and seeking more oversight going forward.

In August, the National Nurses’ United (NNU) union filed a complaint to implore OSHA to investigate the country’s biggest hospital systems, HCA Healthcare, which operates 184 hospitals and about 2,000 other care sites in 21 states and the United Kingdom. The union describes how, throughout HCA hospitals, there is an environment conducive to the spread of coronavirus. Nurses share space and equipment, such as computers, desks, phones, bathrooms, and break rooms, where staff take off masks to eat and drink. The complaint also describes how there is resistance to testing nurses and a lack of communication about infections among colleagues.

“When they have total disregard for safety, they should be punished to the utmost,” said Markowitz, noting that HCA Healthcare is worth $40 billion. “They can penalize them, but if it’s unsafe conditions for RNs and healthcare workers, we know it’s unsafe for the patients. There needs to be drastic measures to prevent hospital corporations from behaving that way.”

In a statement, HCA spokesman Harlow Sumerford said the company has followed CDC guidance for protecting frontline caregivers. “We’re proud of our response and the significant resources we’ve deployed to help protect our colleagues. Meanwhile, the NNU has chosen to use this pandemic as an opportunity to gain publicity by attacking hospitals across the country,” Sumerford said.

Members of the union recently protested in front of the federal OSHA offices in Denver.

After several months, OSHA finally penalized a meat packing plant where eight workers (six union members) had died of COVID-19 last spring. But the amount – $15,615 – was so low that Cordova worries it will actually have a worse impact than no fine.

“It’s more dangerous to workers because now employers know [they won’t be punished meaningfully],” she said. “During the pandemic, OSHA has been absolutely absent.”

Thus, the recent picketing outside the offices in Denver. But, Cordova noted, it’s unlikely OSHA employees saw them. Their own offices were deemed too risky to stay open during the pandemic. They were vacant.
 

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

Last spring, when Cliff Willmeng, RN, was working at United Hospital in St. Paul, Minnesota, he’d take off his personal protective equipment (PPE) in the same hallway where children were transported from ambulances to the neighboring Children’s Hospital emergency department. Stretchers would roll across red tape on the floor that designated the area as a “hot zone.” The door from a break room was about 10 feet away.

Willmeng has been a union activist all his life, but he’d never filed a complaint with the Occupational Safety and Health Administration (OSHA) until the COVID-19 pandemic hit.

Concerned about the inadequate space for doffing PPE and other situations in which the spread of SARS-CoV-2 seemed possible, Willmeng and other colleagues filed multiple OSHA complaints with the Minnesota Department of Labor in March and April. Willmeng was also worried about bringing SARS-CoV-2 on his scrubs home to his wife and kids, and he started wearing hospital-supplied scrubs that were meant for doctors and that were washed on site, which was against hospital policy. The hospital fired Willmeng on May 8, citing code of conduct and respectful workplace violations arising from the uniform dispute.

In August, the state agency issued Willmeng’s hospital a $2,100 fine for failure to comply with guidance regarding “respiratory protection” in response to worker complaints over the fact that they were instructed to restaple elastic bands on N95 masks early in the pandemic. In a statement, United Hospital said it contested the citation, and it is in discussions with Minnesota OSHA. “We have and continue to instruct employees not to alter N95 respirators or reuse damaged or soiled N95 respirators,” such as when the straps are broken, the statement says.

Minnesota OSHA has received three times as many emails and phone calls from workers and employers requesting information and assistance during the pandemic, compared with last year, said spokesperson James Honerman. “If Minnesota OSHA is made aware of a workplace safety or health issue, it assesses the situation and determines how best to respond, including conducting a workplace investigation.”

But Willmeng, who has been out of work since he was fired, says that without a receipt or confirmation from OSHA, he has no way of knowing whether there has been any follow-up regarding his complaints. Minnesota OSHA said workers should receive a letter once a case is resolved.

Like Willmeng’s case, none of the more than 10,000 COVID-related complaints the federal OSHA office has received from across the country have resulted in meaningful sanctions. Unions have picketed local OSHA offices and publicized complaints on behalf of their members to protest what they see as a lack of oversight. Legislators have called on US Department of Labor Secretary Eugene Scalia to step up enforcement.

For many health care workers, complaining to OSHA is a last resort after failing to get satisfactory responses from supervisors and appealing to unions for help. But with such minimal oversight from OSHA, some union leaders and legislators say it’s actually more dangerous than not having workplace safety enforcement at all. Lack of directives from the Trump administration has left the agency without the teeth it has cut under previous administrations, and recent changes to the agency’s rules raise questions about whether companies are ever required to report workers’ hospitalizations due to COVID-19.

“It’s so ineffective that it’s more dangerous to workers,” said Kim Cordova, president of United Food and Commercial Workers (UFCW) Local 7, which represents 22,000 health care and other workers in Colorado and Wyoming. “Employers only do what they’re forced to do.” Instead of deterring a multi-billion-dollar company, she said, such low fines signal that a company doesn’t need to worry about COVID-related safety.

“OSHA is doing a lamentably poor job protecting workers during the pandemic,” said James Brudney, JD, a professor at Fordham Law School, in New York, and former chief counsel of the U.S. Senate Subcommittee on Labor. “I’m not alone in saying that the agency has performed so badly.”

Former government officials writing in JAMA were similarly critical: “In the face of the greatest worker health crisis in recent history, OSHA, the lead government agency responsible for worker health and safety, has not fulfilled its responsibilities.”
 

What could have been

There were early signs that the agency wouldn’t be heavy-handed about COVID-19 safety concerns, Brudney said.

The agency could have issued Emergency Temporary Standards, rules it can put in place during pandemics that address specific short-term concerns. These rules could have required employers to take infection-control measures to protect workers, including mask wearing, providing proper PPE, and screening for COVID-19 symptoms. “That’s what the agency is supposed to do. They’re supposed to respond to an emergency with emergency measures,” Brudney said.

But despite legislative pressure and a court case, Secretary of Labor Eugene Scalia has declined to do so, saying that the agency would instead rely on its regular general duty clause, which is always in place to keep workplaces free from hazards that “cause death or serious physical harm.” The agency invoked the general duty clause for COVID-19–related violations for the first time in September to levy modest fines.

In response to a request for an interview, a Department of Labor spokesperson said that preexisting OSHA requirements apply to workers during the pandemic, including providing PPE for workers and assessing sanitation and cleanliness standards. The agency has issued specific guidance to companies on pandemic preparedness, she said, and that it responds to all complaints. Additionally, she cited whistleblower laws that make it illegal for employers to retaliate against employees for making safety and health complaints.

The federal OSHA office received 10,868 COVID-related complaints from Feb. 1 through Oct. 20, citing issues ranging from failure to provide proper PPE to not informing workers about exposures. As of Oct. 22, a total of 2,349 of the complaints involved healthcare workers. This count doesn’t include the untold number of “informal” complaints handled by state OSHA offices.

In a recent JAMA opinion piece, two former government officials agreed that “the federal government has not fully utilized OSHA’s public safety authority” and called the issuing of an Emergency Temporary Standard that would require employers to develop and implement infection control plans “the most important action the federal government could take” to protect workers.

“Employers are more likely to implement these controls if they are mandated by a government agency that has adequate enforcement tools to ensure compliance,” wrote former Assistant Secretary of Labor David Michaels, PhD, MPH, now at the Milken Institute School of Public Health of the George Washington University, Washington, and Gregory Wagner, MD, a former senior adviser at the National Institute for Occupational Safety and Health at the Centers for Disease Control and Prevention, now at the Harvard T.H. Chan School of Public Health, Boston.

They cited the success of a standard that OSHA issued in 1991 in response to the HIV/AIDS crisis. “The bloodborne pathogens standard has contributed to a substantial decline in health care worker risk for bloodborne diseases like HIV and hepatitis B and C,” they wrote. In a new report for the Century Foundation, the pair offered recommendations to the federal government for controlling the spread of the disease by ramping up OSHA’s role.

OSHA did issue a response plan that requires employers to report in regard to employees who experienced workplace exposures to SARS-CoV-2 and who were hospitalized with COVID-19 or died of the disease within certain time frames, but recent changes to these rules make experts question whether companies are in fact required to report hospitalizations.

In its second revision of guidelines, added to its FAQ page on Sept. 30, the agency said that, in order to be reportable, “an in-patient hospitalization due to COVID-19 must occur within 24 hours of an exposure to SARS-CoV-2 at work” and that the employer must report the hospitalization within 24 hours of learning both that the employee has been hospitalized and that the reason for the hospitalization was a work-related case of COVID-19. Previously, the 24-hour hospitalization window started at the time of diagnosis of the disease, rather than the work-related exposure.

The agency subsequently dropped the first citation it had issued for a COVID-related violation, even though the company, a nursing home, had already agreed to pay $3,904 for reporting employee hospitalizations late.

“It’s a step backwards from an important workplace and public health function that OSHA should be doing,” said Wagner, coauthor of the JAMA opinion piece.

Even without issuing Emergency Temporary Standards, critics say OSHA could have acted much earlier. OSHA issued its first COVID-related federal citation, the one against the nursing home that was dropped, in May for events that occurred in mid-April. The second COVID-related federal citation came in July.

The agency could also charge much more substantial fines for the citations it has issued. If a medical facility was cited for a PPE violation, such as the Minnesota hospital where workers were told to restaple the elastic bands on N95s, the agency could have cited the hospital for one violation per employee. Such fines based on multiple violations could add up to the hundreds of thousands to millions of dollars.

“It would send a signal to the highest-risk employers that these are violations that need to be addressed immediately,” Brudney said.

Many of the 22 state OSHA offices appear to be more responsive to COVID-related complaints than the federal agency, creating a system in which health care workers have substantially different rights from one state to the next. The governor of California, for example, recently authorized California’s OSHA division to consider COVID-19 an imminent hazard, to prohibit workers from entering areas where the hazard exists, and to require employers to disclose exposures. The state also recently issued large fines for COVID safety issues: $222,075 to frozen food manufacturer Overhill Farms and $214,080 to employment agency Jobsource North America.

Elsewhere, state laws such as New Jersey’s Conscientious Employee Protection Act give workers the right to refuse to work in unsafe situations, Brudney said. “A lot more action is going on at the state level because so little is being done at the federal level,” he said. “Some of it is governors committed to protecting essential workers and their families.”
 

Unions call for sanctions

Unions are both decrying the lack of enforcement thus far and seeking more oversight going forward.

In August, the National Nurses’ United (NNU) union filed a complaint to implore OSHA to investigate the country’s biggest hospital systems, HCA Healthcare, which operates 184 hospitals and about 2,000 other care sites in 21 states and the United Kingdom. The union describes how, throughout HCA hospitals, there is an environment conducive to the spread of coronavirus. Nurses share space and equipment, such as computers, desks, phones, bathrooms, and break rooms, where staff take off masks to eat and drink. The complaint also describes how there is resistance to testing nurses and a lack of communication about infections among colleagues.

“When they have total disregard for safety, they should be punished to the utmost,” said Markowitz, noting that HCA Healthcare is worth $40 billion. “They can penalize them, but if it’s unsafe conditions for RNs and healthcare workers, we know it’s unsafe for the patients. There needs to be drastic measures to prevent hospital corporations from behaving that way.”

In a statement, HCA spokesman Harlow Sumerford said the company has followed CDC guidance for protecting frontline caregivers. “We’re proud of our response and the significant resources we’ve deployed to help protect our colleagues. Meanwhile, the NNU has chosen to use this pandemic as an opportunity to gain publicity by attacking hospitals across the country,” Sumerford said.

Members of the union recently protested in front of the federal OSHA offices in Denver.

After several months, OSHA finally penalized a meat packing plant where eight workers (six union members) had died of COVID-19 last spring. But the amount – $15,615 – was so low that Cordova worries it will actually have a worse impact than no fine.

“It’s more dangerous to workers because now employers know [they won’t be punished meaningfully],” she said. “During the pandemic, OSHA has been absolutely absent.”

Thus, the recent picketing outside the offices in Denver. But, Cordova noted, it’s unlikely OSHA employees saw them. Their own offices were deemed too risky to stay open during the pandemic. They were vacant.
 

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