Clinician Reviews

Researchers have developed a quick and easy scoring system to predict which hospitalized COVID-19 patients are more at risk for stroke.

“The system is simple. You can calculate the points in 5 seconds and then predict the chances the patient will have a stroke,” Alexander E. Merkler, MD, assistant professor of neurology at Weill Cornell Medical College/NewYork-Presbyterian Hospital, and lead author of a study of the system, told this news organization.

The new system will allow clinicians to stratify patients and lead to closer monitoring of those at highest risk for stroke, said Dr. Merkler.

The study was presented during the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.

Some, but not all, studies suggest COVID-19 increases the risk of stroke and worsens stroke outcomes, and the association isn’t clear, investigators note.

Researchers used the American Heart Association Get With the Guidelines COVID-19 cardiovascular disease registry for this analysis. They evaluated 21,420 adult patients (mean age 61 years, 54% men), who were hospitalized with COVID-19 at 122 centers from March 2020 to March 2021.

Investigators tapped into the vast amounts of data in this registry on different variables, including demographics, comorbidities, and lab values.

The outcome was a cerebrovascular event, defined as any ischemic or hemorrhagic stroke, transient ischemic attack (TIA), or cerebral vein thrombosis. Of the total hospitalized COVID-19 population, 312 (1.5%) had a cerebrovascular event.

Researchers first used standard statistical models to determine which risk factors are most associated with the development of stroke. They identified six such factors:

• history of stroke
• no fever at the time of hospital admission
• no history of pulmonary disease
• high white blood cell count
• history of hypertension
• high systolic blood pressure at the time of hospital admission

That the list of risk factors included absence of fever and no history of pulmonary disease was somewhat surprising, said Dr. Merkler, but there may be possible explanations, he added.

A high fever is an inflammatory response, and perhaps patients who aren’t responding appropriately “could be sicker in general and have a poor immune system, and thereby be at increased risk for stroke,” said Dr. Merkler.

In the case of pulmonary disease, patients without a history who are admitted for COVID “may have an extremely high burden of COVID, or are extremely sick, and that’s why they’re at higher risk for stroke.”

The scoring system assigns points for each variable, with more points conferring a higher risk of stroke. For example, someone who has 0-1 points has 0.2% risk of having a stroke, and someone with 4-6 points has 2% to 3% risk, said Dr. Merkler.

“So, we’re talking about a 10- to 15-fold increased risk of having a stroke with 4 to 6 versus 0 to 1 variables.”

The accuracy of the risk stratification score (C-statistic of 0.66; 95% confidence interval, 0.60-0.72) is “fairly good or modestly good,” said Dr. Merkler.

A patient with a score of 5 or 6 may need more vigilant monitoring to make sure symptoms are caught early and therapies such as thrombolytics and thrombectomy are readily available, he added.

Researchers also used a sophisticated machine-learning approach where a computer takes all the variables and identifies the best algorithm to predict stroke.

“The machine-learning algorithm was basically just as good as our standard model; it was almost identical,” said Dr. Merkler.

Outside of COVID, other scoring systems are used to predict stroke. For example, the ABCD2 score uses various factors to predict risk of recurrent stroke.

Philip B. Gorelick, MD, adjunct professor, Northwestern University Feinberg School of Medicine, Chicago, said the results are promising, as they may lead to identifying modifiable factors to prevent stroke.

Dr. Gorelick noted that the authors identified risk factors to predict risk of stroke “after an extensive analysis of baseline factors that included an internal validation process.”

The finding that no fever and no history of pulmonary disease were included in those risk factors was “unexpected,” said Dr. Gorelick, who is also medical director of the Hauenstein Neuroscience Center in Grand Rapids, Michigan. “This may reflect the baseline timing of data collection.”

He added further validation of the results in other data sets “will be useful to determine the consistency of the predictive model and its potential value in general practice.”

Louise D. McCullough, MD, PhD, professor and chair of neurology, McGovern Medical School, The University of Texas Health Science Center, Houston, said the association between stroke risk and COVID exposure “has been very unclear.”

“Some people find a very strong association between stroke and COVID, some do not,” said Dr. McCullough, who served as the chair of the ISC 2022 meeting.

This new study looking at a risk stratification model for COVID patients was “very nicely done,” she added.

“They used the American Heart Association Get With The Guidelines COVID registry, which was an amazing feat that was done very quickly by the AHA to establish COVID reporting in the Get With The Guidelines data, allowing us to really look at other factors related to stroke that are in this unique database.”

The study received funding support from the American Stroke Association. Dr. Merkler has received funding from the American Heart Association and the Leon Levy Foundation. Dr. Gorelick was not involved in the study and has disclosed no relevant financial relationships.

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

Researchers have developed a quick and easy scoring system to predict which hospitalized COVID-19 patients are more at risk for stroke.

“The system is simple. You can calculate the points in 5 seconds and then predict the chances the patient will have a stroke,” Alexander E. Merkler, MD, assistant professor of neurology at Weill Cornell Medical College/NewYork-Presbyterian Hospital, and lead author of a study of the system, told this news organization.

The new system will allow clinicians to stratify patients and lead to closer monitoring of those at highest risk for stroke, said Dr. Merkler.

The study was presented during the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.

Some, but not all, studies suggest COVID-19 increases the risk of stroke and worsens stroke outcomes, and the association isn’t clear, investigators note.

Researchers used the American Heart Association Get With the Guidelines COVID-19 cardiovascular disease registry for this analysis. They evaluated 21,420 adult patients (mean age 61 years, 54% men), who were hospitalized with COVID-19 at 122 centers from March 2020 to March 2021.

Investigators tapped into the vast amounts of data in this registry on different variables, including demographics, comorbidities, and lab values.

The outcome was a cerebrovascular event, defined as any ischemic or hemorrhagic stroke, transient ischemic attack (TIA), or cerebral vein thrombosis. Of the total hospitalized COVID-19 population, 312 (1.5%) had a cerebrovascular event.

Researchers first used standard statistical models to determine which risk factors are most associated with the development of stroke. They identified six such factors:

• history of stroke
• no fever at the time of hospital admission
• no history of pulmonary disease
• high white blood cell count
• history of hypertension
• high systolic blood pressure at the time of hospital admission

That the list of risk factors included absence of fever and no history of pulmonary disease was somewhat surprising, said Dr. Merkler, but there may be possible explanations, he added.

A high fever is an inflammatory response, and perhaps patients who aren’t responding appropriately “could be sicker in general and have a poor immune system, and thereby be at increased risk for stroke,” said Dr. Merkler.

In the case of pulmonary disease, patients without a history who are admitted for COVID “may have an extremely high burden of COVID, or are extremely sick, and that’s why they’re at higher risk for stroke.”

The scoring system assigns points for each variable, with more points conferring a higher risk of stroke. For example, someone who has 0-1 points has 0.2% risk of having a stroke, and someone with 4-6 points has 2% to 3% risk, said Dr. Merkler.

“So, we’re talking about a 10- to 15-fold increased risk of having a stroke with 4 to 6 versus 0 to 1 variables.”

The accuracy of the risk stratification score (C-statistic of 0.66; 95% confidence interval, 0.60-0.72) is “fairly good or modestly good,” said Dr. Merkler.

A patient with a score of 5 or 6 may need more vigilant monitoring to make sure symptoms are caught early and therapies such as thrombolytics and thrombectomy are readily available, he added.

Researchers also used a sophisticated machine-learning approach where a computer takes all the variables and identifies the best algorithm to predict stroke.

“The machine-learning algorithm was basically just as good as our standard model; it was almost identical,” said Dr. Merkler.

Outside of COVID, other scoring systems are used to predict stroke. For example, the ABCD2 score uses various factors to predict risk of recurrent stroke.

Philip B. Gorelick, MD, adjunct professor, Northwestern University Feinberg School of Medicine, Chicago, said the results are promising, as they may lead to identifying modifiable factors to prevent stroke.

Dr. Gorelick noted that the authors identified risk factors to predict risk of stroke “after an extensive analysis of baseline factors that included an internal validation process.”

The finding that no fever and no history of pulmonary disease were included in those risk factors was “unexpected,” said Dr. Gorelick, who is also medical director of the Hauenstein Neuroscience Center in Grand Rapids, Michigan. “This may reflect the baseline timing of data collection.”

He added further validation of the results in other data sets “will be useful to determine the consistency of the predictive model and its potential value in general practice.”

Louise D. McCullough, MD, PhD, professor and chair of neurology, McGovern Medical School, The University of Texas Health Science Center, Houston, said the association between stroke risk and COVID exposure “has been very unclear.”

“Some people find a very strong association between stroke and COVID, some do not,” said Dr. McCullough, who served as the chair of the ISC 2022 meeting.

This new study looking at a risk stratification model for COVID patients was “very nicely done,” she added.

“They used the American Heart Association Get With The Guidelines COVID registry, which was an amazing feat that was done very quickly by the AHA to establish COVID reporting in the Get With The Guidelines data, allowing us to really look at other factors related to stroke that are in this unique database.”

The study received funding support from the American Stroke Association. Dr. Merkler has received funding from the American Heart Association and the Leon Levy Foundation. Dr. Gorelick was not involved in the study and has disclosed no relevant financial relationships.

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

Researchers have developed a quick and easy scoring system to predict which hospitalized COVID-19 patients are more at risk for stroke.

“The system is simple. You can calculate the points in 5 seconds and then predict the chances the patient will have a stroke,” Alexander E. Merkler, MD, assistant professor of neurology at Weill Cornell Medical College/NewYork-Presbyterian Hospital, and lead author of a study of the system, told this news organization.

The new system will allow clinicians to stratify patients and lead to closer monitoring of those at highest risk for stroke, said Dr. Merkler.

The study was presented during the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.

Some, but not all, studies suggest COVID-19 increases the risk of stroke and worsens stroke outcomes, and the association isn’t clear, investigators note.

Researchers used the American Heart Association Get With the Guidelines COVID-19 cardiovascular disease registry for this analysis. They evaluated 21,420 adult patients (mean age 61 years, 54% men), who were hospitalized with COVID-19 at 122 centers from March 2020 to March 2021.

Investigators tapped into the vast amounts of data in this registry on different variables, including demographics, comorbidities, and lab values.

The outcome was a cerebrovascular event, defined as any ischemic or hemorrhagic stroke, transient ischemic attack (TIA), or cerebral vein thrombosis. Of the total hospitalized COVID-19 population, 312 (1.5%) had a cerebrovascular event.

Researchers first used standard statistical models to determine which risk factors are most associated with the development of stroke. They identified six such factors:

• history of stroke
• no fever at the time of hospital admission
• no history of pulmonary disease
• high white blood cell count
• history of hypertension
• high systolic blood pressure at the time of hospital admission

That the list of risk factors included absence of fever and no history of pulmonary disease was somewhat surprising, said Dr. Merkler, but there may be possible explanations, he added.

A high fever is an inflammatory response, and perhaps patients who aren’t responding appropriately “could be sicker in general and have a poor immune system, and thereby be at increased risk for stroke,” said Dr. Merkler.

In the case of pulmonary disease, patients without a history who are admitted for COVID “may have an extremely high burden of COVID, or are extremely sick, and that’s why they’re at higher risk for stroke.”

The scoring system assigns points for each variable, with more points conferring a higher risk of stroke. For example, someone who has 0-1 points has 0.2% risk of having a stroke, and someone with 4-6 points has 2% to 3% risk, said Dr. Merkler.

“So, we’re talking about a 10- to 15-fold increased risk of having a stroke with 4 to 6 versus 0 to 1 variables.”

The accuracy of the risk stratification score (C-statistic of 0.66; 95% confidence interval, 0.60-0.72) is “fairly good or modestly good,” said Dr. Merkler.

A patient with a score of 5 or 6 may need more vigilant monitoring to make sure symptoms are caught early and therapies such as thrombolytics and thrombectomy are readily available, he added.

Researchers also used a sophisticated machine-learning approach where a computer takes all the variables and identifies the best algorithm to predict stroke.

“The machine-learning algorithm was basically just as good as our standard model; it was almost identical,” said Dr. Merkler.

Outside of COVID, other scoring systems are used to predict stroke. For example, the ABCD2 score uses various factors to predict risk of recurrent stroke.

Philip B. Gorelick, MD, adjunct professor, Northwestern University Feinberg School of Medicine, Chicago, said the results are promising, as they may lead to identifying modifiable factors to prevent stroke.

Dr. Gorelick noted that the authors identified risk factors to predict risk of stroke “after an extensive analysis of baseline factors that included an internal validation process.”

The finding that no fever and no history of pulmonary disease were included in those risk factors was “unexpected,” said Dr. Gorelick, who is also medical director of the Hauenstein Neuroscience Center in Grand Rapids, Michigan. “This may reflect the baseline timing of data collection.”

He added further validation of the results in other data sets “will be useful to determine the consistency of the predictive model and its potential value in general practice.”

Louise D. McCullough, MD, PhD, professor and chair of neurology, McGovern Medical School, The University of Texas Health Science Center, Houston, said the association between stroke risk and COVID exposure “has been very unclear.”

“Some people find a very strong association between stroke and COVID, some do not,” said Dr. McCullough, who served as the chair of the ISC 2022 meeting.

This new study looking at a risk stratification model for COVID patients was “very nicely done,” she added.

“They used the American Heart Association Get With The Guidelines COVID registry, which was an amazing feat that was done very quickly by the AHA to establish COVID reporting in the Get With The Guidelines data, allowing us to really look at other factors related to stroke that are in this unique database.”

The study received funding support from the American Stroke Association. Dr. Merkler has received funding from the American Heart Association and the Leon Levy Foundation. Dr. Gorelick was not involved in the study and has disclosed no relevant financial relationships.

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

Vaccination against SARS-CoV-2 appears to protect people with inflammatory bowel disease (IBD) from the more serious consequences of breakthrough COVID-19 infections, but results may vary by which vaccine was received, results of a small study suggest.

In a study of patients with IBD who had completed a primary vaccine series but went on to develop COVID-19, there were trends toward worse outcomes for patients who received a non-mRNA vaccine, older patients, and those who were on combination therapy rather than monotherapy, reported Emily Spiera, a medical student at the Icahn School of Medicine at Mount Sinai, New York.

peterschreiber_media/iStock/Getty Images

“Overall, we saw that vaccinated patients who subsequently developed COVID-19 had low rates of hospitalization, severe COVID, and death,” she said in an oral abstract at the annual Crohn’s & Colitis Congress^®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

The study was conducted before the highly infectious Omicron variant of SARS-CoV-2 became dominant, however, and the sample size of 88 patients, combined with a low number of study events, was too small for statistical significance to emerge for most measures, Ms. Spiera acknowledged.

Nonetheless, the findings support the protective benefit of vaccines in this population, said Freddy Caldera, DO, associate professor of gastroenterology at the University of Wisconsin–Madison, who was not involved in the study.

“In my mind, when we think about COVID vaccines, the whole goal is to prevent severe disease,” he said.

Dr. Caldera and colleagues conducted an earlier study of humoral immunogenicity of mRNA COVID-19 vaccines in 122 patients with IBD and 60 healthy controls, and found that all controls and 97% of patients with IBD developed antibodies, although antibody concentrations were lower in patients with IBD, compared with controls (P < .001). Those who received the mRNA-1273 (Moderna) COVID-19 had significantly higher antibody concentrations than those who received the Pfizer-BNT vaccine series (P < .001).

They also found that patients on immune-modifying therapy had lower antibody concentrations, compared with those who were not on such therapy, or those who received aminosalicylates or vedolizumab (Entyvio; P = .003).

The protective effect of vaccines in this population became even more apparent after patients received an additional vaccine dose.

“We actually have a study in preprint of what happens after a third dose, where everyone made antibodies,” he said. “What we tell patients is that vaccines work.”
 

SECURE-IBD data

The investigators at Mount Sinai, the University of North Carolina at Chapel Hill, and Tel Aviv University analyzed data from the Surveillance Epidemiology of Coronavirus Under Research Exclusion in Inflammatory Bowel Disease (SECURE-IBD) database, an international web-based registry that includes reports from 74 countries, with data reported by 48 U.S. states.

The study sample consisted of patients enrolled from Dec. 12, 2020, to Oct. 1, 2021, who had completed a primary vaccination series with either mRNA vaccines (Pfizer or Moderna) adenoviral vector-based vaccines (AstraZeneca, Sputnik, CanSino, or Janssen/Johnson & Johnson), or an inactivated SARS-CoV-2 vaccine (Sinovac).

Of 2,477 patients with COVID-19 infections reported to SECURE-IBD, 160 reported being vaccinated. Of this group, 53 were excluded because they were only partially vaccinated, and 19 were excluded because of missing data on either vaccine type, number of doses, or COVID-19 outcomes, leaving 88 patients with completed primary vaccination series at the time of COVID-19 infection.

The median patient age was 40.1 years. Nearly two-thirds of the patients had a diagnosis of Crohn’s disease, and slightly more than one-third has a diagnosis of ulcerative colitis. The patients came from 18 countries, with 45.3% of the sample in the United States.

A total of 58% of patients were on biologic monotherapy, with either a tumor necrosis factor antagonist, integrin antagonist, or anti–interleukin-12/13. In addition, 3.4% were on immunomodulator monotherapy, 21.6% were on combination therapy, and 5.7% were receiving corticosteroids.
 

Lower severity

COVID-19 severity was numerically but not significantly lower among the 88 vaccinated patients, with a rate of 5.7%, compared with 9.3% among 2,317 patients with COVID-19 infections in the database who were not vaccinated.

COVID-19 severity defined as a composite of ICU admission, need for mechanical ventilation and/or death was actually slightly higher among the vaccinated patients, with a rate of 3.4% versus 1.9% for nonvaccinated patients, but this difference was not statistically significant.

There was 1 death among vaccinated patients (1.1%) versus 29 among the unvaccinated (1.2%).

There were trends toward fewer hospitalizations and less-frequent severe COVID-19 infection among patients who received a mRNA vaccine, compared with other vaccine types, but again these differences did not reach statistical significance.

As noted before, there was a higher frequency of severe COVID-19 among patients on combination therapy than on monotherapy, but this difference too was not statistically significant.

As seen with COVID-19 in the general population older patients tended to have worse outcomes, with a mean age of 53 for patients requiring hospitalization, compared with 39 years for patients who stayed out of the hospital (P = .04), and a mean age of 59 among patients with severe COVID-19 infections, compared with 39 for patients with moderate or mild infections (P = .03).

Ms. Spiera described the case of the single vaccinated patient who died. The 63-year-old woman had moderately active Crohn’s disease treated with corticosteroids, adalimumab (Humira) and azathioprine at the time of COVID-19 infection. She had received the AstraZeneca adenoviral-based vaccine more than 30 days prior to infection. She was hospitalized and intubated, and died from gastrointestinal bleeding.

Ms. Spiera noted that, although the sample size was small, and only patients known to have COVID-19 were included, it is one of the largest cohorts to date of vaccinated patients with IBD who developed COVID-19. She said that the study supports prior studies showing that combination therapy and tumor necrosis factor antagonists may result in reduced immunity, and that mRNA vaccines may offer better protection against severe illness in this population.

The study was supported by a Digestive Disease Research Foundation Fellowship. Ms. Spiera and Dr. Caldera reported no relevant disclosures.

Vaccination against SARS-CoV-2 appears to protect people with inflammatory bowel disease (IBD) from the more serious consequences of breakthrough COVID-19 infections, but results may vary by which vaccine was received, results of a small study suggest.

In a study of patients with IBD who had completed a primary vaccine series but went on to develop COVID-19, there were trends toward worse outcomes for patients who received a non-mRNA vaccine, older patients, and those who were on combination therapy rather than monotherapy, reported Emily Spiera, a medical student at the Icahn School of Medicine at Mount Sinai, New York.

peterschreiber_media/iStock/Getty Images

“Overall, we saw that vaccinated patients who subsequently developed COVID-19 had low rates of hospitalization, severe COVID, and death,” she said in an oral abstract at the annual Crohn’s & Colitis Congress^®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

The study was conducted before the highly infectious Omicron variant of SARS-CoV-2 became dominant, however, and the sample size of 88 patients, combined with a low number of study events, was too small for statistical significance to emerge for most measures, Ms. Spiera acknowledged.

Nonetheless, the findings support the protective benefit of vaccines in this population, said Freddy Caldera, DO, associate professor of gastroenterology at the University of Wisconsin–Madison, who was not involved in the study.

“In my mind, when we think about COVID vaccines, the whole goal is to prevent severe disease,” he said.

Dr. Caldera and colleagues conducted an earlier study of humoral immunogenicity of mRNA COVID-19 vaccines in 122 patients with IBD and 60 healthy controls, and found that all controls and 97% of patients with IBD developed antibodies, although antibody concentrations were lower in patients with IBD, compared with controls (P < .001). Those who received the mRNA-1273 (Moderna) COVID-19 had significantly higher antibody concentrations than those who received the Pfizer-BNT vaccine series (P < .001).

They also found that patients on immune-modifying therapy had lower antibody concentrations, compared with those who were not on such therapy, or those who received aminosalicylates or vedolizumab (Entyvio; P = .003).

The protective effect of vaccines in this population became even more apparent after patients received an additional vaccine dose.

“We actually have a study in preprint of what happens after a third dose, where everyone made antibodies,” he said. “What we tell patients is that vaccines work.”
 

SECURE-IBD data

The investigators at Mount Sinai, the University of North Carolina at Chapel Hill, and Tel Aviv University analyzed data from the Surveillance Epidemiology of Coronavirus Under Research Exclusion in Inflammatory Bowel Disease (SECURE-IBD) database, an international web-based registry that includes reports from 74 countries, with data reported by 48 U.S. states.

The study sample consisted of patients enrolled from Dec. 12, 2020, to Oct. 1, 2021, who had completed a primary vaccination series with either mRNA vaccines (Pfizer or Moderna) adenoviral vector-based vaccines (AstraZeneca, Sputnik, CanSino, or Janssen/Johnson & Johnson), or an inactivated SARS-CoV-2 vaccine (Sinovac).

Of 2,477 patients with COVID-19 infections reported to SECURE-IBD, 160 reported being vaccinated. Of this group, 53 were excluded because they were only partially vaccinated, and 19 were excluded because of missing data on either vaccine type, number of doses, or COVID-19 outcomes, leaving 88 patients with completed primary vaccination series at the time of COVID-19 infection.

The median patient age was 40.1 years. Nearly two-thirds of the patients had a diagnosis of Crohn’s disease, and slightly more than one-third has a diagnosis of ulcerative colitis. The patients came from 18 countries, with 45.3% of the sample in the United States.

A total of 58% of patients were on biologic monotherapy, with either a tumor necrosis factor antagonist, integrin antagonist, or anti–interleukin-12/13. In addition, 3.4% were on immunomodulator monotherapy, 21.6% were on combination therapy, and 5.7% were receiving corticosteroids.
 

Lower severity

COVID-19 severity was numerically but not significantly lower among the 88 vaccinated patients, with a rate of 5.7%, compared with 9.3% among 2,317 patients with COVID-19 infections in the database who were not vaccinated.

COVID-19 severity defined as a composite of ICU admission, need for mechanical ventilation and/or death was actually slightly higher among the vaccinated patients, with a rate of 3.4% versus 1.9% for nonvaccinated patients, but this difference was not statistically significant.

There was 1 death among vaccinated patients (1.1%) versus 29 among the unvaccinated (1.2%).

There were trends toward fewer hospitalizations and less-frequent severe COVID-19 infection among patients who received a mRNA vaccine, compared with other vaccine types, but again these differences did not reach statistical significance.

As noted before, there was a higher frequency of severe COVID-19 among patients on combination therapy than on monotherapy, but this difference too was not statistically significant.

As seen with COVID-19 in the general population older patients tended to have worse outcomes, with a mean age of 53 for patients requiring hospitalization, compared with 39 years for patients who stayed out of the hospital (P = .04), and a mean age of 59 among patients with severe COVID-19 infections, compared with 39 for patients with moderate or mild infections (P = .03).

Ms. Spiera described the case of the single vaccinated patient who died. The 63-year-old woman had moderately active Crohn’s disease treated with corticosteroids, adalimumab (Humira) and azathioprine at the time of COVID-19 infection. She had received the AstraZeneca adenoviral-based vaccine more than 30 days prior to infection. She was hospitalized and intubated, and died from gastrointestinal bleeding.

Ms. Spiera noted that, although the sample size was small, and only patients known to have COVID-19 were included, it is one of the largest cohorts to date of vaccinated patients with IBD who developed COVID-19. She said that the study supports prior studies showing that combination therapy and tumor necrosis factor antagonists may result in reduced immunity, and that mRNA vaccines may offer better protection against severe illness in this population.

The study was supported by a Digestive Disease Research Foundation Fellowship. Ms. Spiera and Dr. Caldera reported no relevant disclosures.

Vaccination against SARS-CoV-2 appears to protect people with inflammatory bowel disease (IBD) from the more serious consequences of breakthrough COVID-19 infections, but results may vary by which vaccine was received, results of a small study suggest.

In a study of patients with IBD who had completed a primary vaccine series but went on to develop COVID-19, there were trends toward worse outcomes for patients who received a non-mRNA vaccine, older patients, and those who were on combination therapy rather than monotherapy, reported Emily Spiera, a medical student at the Icahn School of Medicine at Mount Sinai, New York.

peterschreiber_media/iStock/Getty Images

“Overall, we saw that vaccinated patients who subsequently developed COVID-19 had low rates of hospitalization, severe COVID, and death,” she said in an oral abstract at the annual Crohn’s & Colitis Congress^®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

The study was conducted before the highly infectious Omicron variant of SARS-CoV-2 became dominant, however, and the sample size of 88 patients, combined with a low number of study events, was too small for statistical significance to emerge for most measures, Ms. Spiera acknowledged.

Nonetheless, the findings support the protective benefit of vaccines in this population, said Freddy Caldera, DO, associate professor of gastroenterology at the University of Wisconsin–Madison, who was not involved in the study.

“In my mind, when we think about COVID vaccines, the whole goal is to prevent severe disease,” he said.

Dr. Caldera and colleagues conducted an earlier study of humoral immunogenicity of mRNA COVID-19 vaccines in 122 patients with IBD and 60 healthy controls, and found that all controls and 97% of patients with IBD developed antibodies, although antibody concentrations were lower in patients with IBD, compared with controls (P < .001). Those who received the mRNA-1273 (Moderna) COVID-19 had significantly higher antibody concentrations than those who received the Pfizer-BNT vaccine series (P < .001).

They also found that patients on immune-modifying therapy had lower antibody concentrations, compared with those who were not on such therapy, or those who received aminosalicylates or vedolizumab (Entyvio; P = .003).

The protective effect of vaccines in this population became even more apparent after patients received an additional vaccine dose.

“We actually have a study in preprint of what happens after a third dose, where everyone made antibodies,” he said. “What we tell patients is that vaccines work.”
 

SECURE-IBD data

The investigators at Mount Sinai, the University of North Carolina at Chapel Hill, and Tel Aviv University analyzed data from the Surveillance Epidemiology of Coronavirus Under Research Exclusion in Inflammatory Bowel Disease (SECURE-IBD) database, an international web-based registry that includes reports from 74 countries, with data reported by 48 U.S. states.

The study sample consisted of patients enrolled from Dec. 12, 2020, to Oct. 1, 2021, who had completed a primary vaccination series with either mRNA vaccines (Pfizer or Moderna) adenoviral vector-based vaccines (AstraZeneca, Sputnik, CanSino, or Janssen/Johnson & Johnson), or an inactivated SARS-CoV-2 vaccine (Sinovac).

Of 2,477 patients with COVID-19 infections reported to SECURE-IBD, 160 reported being vaccinated. Of this group, 53 were excluded because they were only partially vaccinated, and 19 were excluded because of missing data on either vaccine type, number of doses, or COVID-19 outcomes, leaving 88 patients with completed primary vaccination series at the time of COVID-19 infection.

The median patient age was 40.1 years. Nearly two-thirds of the patients had a diagnosis of Crohn’s disease, and slightly more than one-third has a diagnosis of ulcerative colitis. The patients came from 18 countries, with 45.3% of the sample in the United States.

A total of 58% of patients were on biologic monotherapy, with either a tumor necrosis factor antagonist, integrin antagonist, or anti–interleukin-12/13. In addition, 3.4% were on immunomodulator monotherapy, 21.6% were on combination therapy, and 5.7% were receiving corticosteroids.
 

Lower severity

COVID-19 severity was numerically but not significantly lower among the 88 vaccinated patients, with a rate of 5.7%, compared with 9.3% among 2,317 patients with COVID-19 infections in the database who were not vaccinated.

COVID-19 severity defined as a composite of ICU admission, need for mechanical ventilation and/or death was actually slightly higher among the vaccinated patients, with a rate of 3.4% versus 1.9% for nonvaccinated patients, but this difference was not statistically significant.

There was 1 death among vaccinated patients (1.1%) versus 29 among the unvaccinated (1.2%).

There were trends toward fewer hospitalizations and less-frequent severe COVID-19 infection among patients who received a mRNA vaccine, compared with other vaccine types, but again these differences did not reach statistical significance.

As noted before, there was a higher frequency of severe COVID-19 among patients on combination therapy than on monotherapy, but this difference too was not statistically significant.

As seen with COVID-19 in the general population older patients tended to have worse outcomes, with a mean age of 53 for patients requiring hospitalization, compared with 39 years for patients who stayed out of the hospital (P = .04), and a mean age of 59 among patients with severe COVID-19 infections, compared with 39 for patients with moderate or mild infections (P = .03).

Ms. Spiera described the case of the single vaccinated patient who died. The 63-year-old woman had moderately active Crohn’s disease treated with corticosteroids, adalimumab (Humira) and azathioprine at the time of COVID-19 infection. She had received the AstraZeneca adenoviral-based vaccine more than 30 days prior to infection. She was hospitalized and intubated, and died from gastrointestinal bleeding.

Ms. Spiera noted that, although the sample size was small, and only patients known to have COVID-19 were included, it is one of the largest cohorts to date of vaccinated patients with IBD who developed COVID-19. She said that the study supports prior studies showing that combination therapy and tumor necrosis factor antagonists may result in reduced immunity, and that mRNA vaccines may offer better protection against severe illness in this population.

The study was supported by a Digestive Disease Research Foundation Fellowship. Ms. Spiera and Dr. Caldera reported no relevant disclosures.

Adding the investigational twincretin tirzepatide (Eli Lilly) to insulin glargine significantly improves blood glucose control after 40 weeks, compared with placebo among patients with type 2 diabetes, new research shows.  

The novel once-weekly injectable agent is nicknamed a twincretin because it combines two different gut-hormone activities. It works both as a glucagonlike peptide-1 (GLP-1) receptor agonist and as an agent that mimics the glucose-dependent insulinotropic polypeptide (GIP).

Findings from the randomized phase 3 SURPASS-5 clinical trial were published online Feb. 8 in JAMA.

This is the latest in a series of SURPASS trials of tirzepatide in individuals with type 2 diabetes for which results have been presented at various conferences, announced by the company, and/or published since late 2020.

SURPASS-5 specifically investigated the effect on glycemic control of adding three different doses of once-weekly subcutaneous tirzepatide compared with placebo in 475 adults who hadn’t achieved target A1c levels using insulin glargine with or without metformin. Statistically significant reductions in A1c were found at 40 weeks for all three doses.

Moreover, authors Dominik Dahl, MD, group practice for internal medicine and diabetology, Hamburg, Germany, and colleagues note that the improvements in the tirzepatide groups “were associated with significantly lower insulin glargine use and significant bodyweight reduction compared with placebo.”

“Despite the differences in glycemic control between the tirzepatide and placebo groups, the rate of clinically significant or severe hypoglycemia was below one event per patient-year in all treatment groups,” they add.

However, concerns about the study protocol and generalizability were raised in an accompanying editorial by Stuart R. Chipkin, MD, of the School of Public Health & Health Sciences, University of Massachusetts Amherst.

“Importantly, the study did not compare tirzepatide with other treatments that could have been used to target the postprandial glycemic pattern of the study population,” he writes.

And ultimately, he says: “Even though the results of this investigation are important for demonstrating the potential clinical benefit of [tirzepatide], and may help to advance the goal of achieving U.S. Food and Drug Administration approval, the study may leave clinicians uncertain about when and how to best use tirzepatide to improve clinical outcomes for patients with type 2 diabetes.”

Significant A1c, weight reductions when added to insulin glargine

The randomized, phase 3 SURPASS-5 trial was conducted at 45 centers in eight countries between August 2019 and January 2021. The 475 adult participants had type 2 diabetes inadequately controlled (baseline A1c, 7.0%-10.5%) with once-daily insulin glargine, with or without metformin. They were randomized to receive once-weekly subcutaneous injections of tirzepatide in doses of 5 mg, 10 mg, or 15 mg, or volume-matched placebo injections over 40 weeks.

The mean changes from baseline in A1c at week 40, the primary study endpoint, were –2.11, –2.40, and –2.34 percentage points for the 5 mg, 10 mg, and 15 mg doses of tirzepatide, respectively (P < .001), versus a nonsignificant change of –0.86 percentage points with placebo. The differences from placebo at week 40 were also significant for the 10-mg and 15-mg doses (both P < .001).  

Significantly higher proportions of patients receiving 5 mg, 10 mg, and 15 mg tirzepatide met the A1c target of less than 7% at week 40, compared with placebo (85%-90% vs. 34%; P < .001). Significantly higher proportions of patients in the 10-mg and 15-mg dose groups also achieved A1c less than 5.7% (42% and 50%, respectively, vs. 3%).

Mean fasting glucose was also reduced significantly with all doses of tirzepatide by 58.2 mg/dL, 64.0 mg/dL, and 62.6 mg/dL, respectively, versus 39.2 mg/dL with placebo (all P <0.001 vs. placebo).

At week 40, mean body weight reductions from baseline were 5.4 kg (11.9 lbs), 7.5 kg, and 8.8 kg versus just 1.6 kg with placebo (all P <0.001 vs. placebo).

All three tirzepatide doses were also associated with significant improvements from baseline in total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and triglycerides.  
 

Gastrointestinal adverse events, hypoglycemia seen in minority

The most common treatment-emergent adverse events in the tirzepatide groups versus placebo were gastrointestinal, including diarrhea (12%-21% vs. 10%), nausea (13%-18% vs. 2.5%), vomiting (7%-13% vs. 2.5%), and decreased appetite (7%-14% vs. 1.7%). Most of these adverse events were mild to moderate in intensity and decreased over time in the tirzepatide groups.

There were no deaths in the study. Serious adverse events were reported by 8%-11% in the tirzepatide groups, compared with 8% in the placebo group. Drug discontinuation due to adverse events occurred in 6.0%, 8.4%, and 10.8% of the 5-mg, 10-mg, and 15-mg dose groups, respectively, versus 2.5% in the placebo group.

Rates of hypoglycemia (less than or equal to 70 mg/dL) ranged from 14.2% to 19.3% with tirzepatide versus 12.5% with placebo. There were three episodes of severe hypoglycemia (less than 54 mg/dL), two with 10 mg tirzepatide and one with 15 mg tirzepatide.
 

Editorial raises questions

In his editorial, Dr. Chipkin writes that the study “demonstrated that use of tirzepatide was associated with significant reductions in A1c and weight in a fairly homogeneous cohort of patients with type 2 diabetes who were receiving insulin glargine with or without metformin.”

“The protocol answered questions about efficacy but left open questions about generalizability and effectiveness in different populations, especially patients with certain complications or comorbid chronic diseases.” He also notes that younger adults and Black patients were not well-represented.

And the study didn’t allow for dividing up the glargine dose or for adding short-acting insulin before meals or any other pre-meal medications and “thus may represent a departure from usual care” in the setting of rising glucose levels.

The authors themselves acknowledge that “the postprandial glucose excursions observed in the placebo group suggest an additional prandial intervention was likely needed in some patients, despite the strict inclusion criteria and the treat-to-target-approach used in the study.”

Dr. Chipkin concludes that “although patients are likely to embrace a medication with weight loss outcomes, the protocol also leaves unanswered questions about reducing insulin and evaluating the comparative risk of adverse effects.”

The study was sponsored by Eli Lilly. Dr. Dahl has reported receiving personal fees from Eli Lilly during the conduct of the study and personal fees from Afimmune, Novo Nordisk, and Novartis outside the submitted work. Dr. Chipkin has reported no relevant financial relationships.

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

Adding the investigational twincretin tirzepatide (Eli Lilly) to insulin glargine significantly improves blood glucose control after 40 weeks, compared with placebo among patients with type 2 diabetes, new research shows.  

The novel once-weekly injectable agent is nicknamed a twincretin because it combines two different gut-hormone activities. It works both as a glucagonlike peptide-1 (GLP-1) receptor agonist and as an agent that mimics the glucose-dependent insulinotropic polypeptide (GIP).

Findings from the randomized phase 3 SURPASS-5 clinical trial were published online Feb. 8 in JAMA.

This is the latest in a series of SURPASS trials of tirzepatide in individuals with type 2 diabetes for which results have been presented at various conferences, announced by the company, and/or published since late 2020.

SURPASS-5 specifically investigated the effect on glycemic control of adding three different doses of once-weekly subcutaneous tirzepatide compared with placebo in 475 adults who hadn’t achieved target A1c levels using insulin glargine with or without metformin. Statistically significant reductions in A1c were found at 40 weeks for all three doses.

Moreover, authors Dominik Dahl, MD, group practice for internal medicine and diabetology, Hamburg, Germany, and colleagues note that the improvements in the tirzepatide groups “were associated with significantly lower insulin glargine use and significant bodyweight reduction compared with placebo.”

“Despite the differences in glycemic control between the tirzepatide and placebo groups, the rate of clinically significant or severe hypoglycemia was below one event per patient-year in all treatment groups,” they add.

However, concerns about the study protocol and generalizability were raised in an accompanying editorial by Stuart R. Chipkin, MD, of the School of Public Health & Health Sciences, University of Massachusetts Amherst.

“Importantly, the study did not compare tirzepatide with other treatments that could have been used to target the postprandial glycemic pattern of the study population,” he writes.

And ultimately, he says: “Even though the results of this investigation are important for demonstrating the potential clinical benefit of [tirzepatide], and may help to advance the goal of achieving U.S. Food and Drug Administration approval, the study may leave clinicians uncertain about when and how to best use tirzepatide to improve clinical outcomes for patients with type 2 diabetes.”

Significant A1c, weight reductions when added to insulin glargine

The randomized, phase 3 SURPASS-5 trial was conducted at 45 centers in eight countries between August 2019 and January 2021. The 475 adult participants had type 2 diabetes inadequately controlled (baseline A1c, 7.0%-10.5%) with once-daily insulin glargine, with or without metformin. They were randomized to receive once-weekly subcutaneous injections of tirzepatide in doses of 5 mg, 10 mg, or 15 mg, or volume-matched placebo injections over 40 weeks.

The mean changes from baseline in A1c at week 40, the primary study endpoint, were –2.11, –2.40, and –2.34 percentage points for the 5 mg, 10 mg, and 15 mg doses of tirzepatide, respectively (P < .001), versus a nonsignificant change of –0.86 percentage points with placebo. The differences from placebo at week 40 were also significant for the 10-mg and 15-mg doses (both P < .001).  

Significantly higher proportions of patients receiving 5 mg, 10 mg, and 15 mg tirzepatide met the A1c target of less than 7% at week 40, compared with placebo (85%-90% vs. 34%; P < .001). Significantly higher proportions of patients in the 10-mg and 15-mg dose groups also achieved A1c less than 5.7% (42% and 50%, respectively, vs. 3%).

Mean fasting glucose was also reduced significantly with all doses of tirzepatide by 58.2 mg/dL, 64.0 mg/dL, and 62.6 mg/dL, respectively, versus 39.2 mg/dL with placebo (all P <0.001 vs. placebo).

At week 40, mean body weight reductions from baseline were 5.4 kg (11.9 lbs), 7.5 kg, and 8.8 kg versus just 1.6 kg with placebo (all P <0.001 vs. placebo).

All three tirzepatide doses were also associated with significant improvements from baseline in total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and triglycerides.  
 

Gastrointestinal adverse events, hypoglycemia seen in minority

The most common treatment-emergent adverse events in the tirzepatide groups versus placebo were gastrointestinal, including diarrhea (12%-21% vs. 10%), nausea (13%-18% vs. 2.5%), vomiting (7%-13% vs. 2.5%), and decreased appetite (7%-14% vs. 1.7%). Most of these adverse events were mild to moderate in intensity and decreased over time in the tirzepatide groups.

There were no deaths in the study. Serious adverse events were reported by 8%-11% in the tirzepatide groups, compared with 8% in the placebo group. Drug discontinuation due to adverse events occurred in 6.0%, 8.4%, and 10.8% of the 5-mg, 10-mg, and 15-mg dose groups, respectively, versus 2.5% in the placebo group.

Rates of hypoglycemia (less than or equal to 70 mg/dL) ranged from 14.2% to 19.3% with tirzepatide versus 12.5% with placebo. There were three episodes of severe hypoglycemia (less than 54 mg/dL), two with 10 mg tirzepatide and one with 15 mg tirzepatide.
 

Editorial raises questions

In his editorial, Dr. Chipkin writes that the study “demonstrated that use of tirzepatide was associated with significant reductions in A1c and weight in a fairly homogeneous cohort of patients with type 2 diabetes who were receiving insulin glargine with or without metformin.”

“The protocol answered questions about efficacy but left open questions about generalizability and effectiveness in different populations, especially patients with certain complications or comorbid chronic diseases.” He also notes that younger adults and Black patients were not well-represented.

And the study didn’t allow for dividing up the glargine dose or for adding short-acting insulin before meals or any other pre-meal medications and “thus may represent a departure from usual care” in the setting of rising glucose levels.

The authors themselves acknowledge that “the postprandial glucose excursions observed in the placebo group suggest an additional prandial intervention was likely needed in some patients, despite the strict inclusion criteria and the treat-to-target-approach used in the study.”

Dr. Chipkin concludes that “although patients are likely to embrace a medication with weight loss outcomes, the protocol also leaves unanswered questions about reducing insulin and evaluating the comparative risk of adverse effects.”

The study was sponsored by Eli Lilly. Dr. Dahl has reported receiving personal fees from Eli Lilly during the conduct of the study and personal fees from Afimmune, Novo Nordisk, and Novartis outside the submitted work. Dr. Chipkin has reported no relevant financial relationships.

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

Adding the investigational twincretin tirzepatide (Eli Lilly) to insulin glargine significantly improves blood glucose control after 40 weeks, compared with placebo among patients with type 2 diabetes, new research shows.  

The novel once-weekly injectable agent is nicknamed a twincretin because it combines two different gut-hormone activities. It works both as a glucagonlike peptide-1 (GLP-1) receptor agonist and as an agent that mimics the glucose-dependent insulinotropic polypeptide (GIP).

Findings from the randomized phase 3 SURPASS-5 clinical trial were published online Feb. 8 in JAMA.

This is the latest in a series of SURPASS trials of tirzepatide in individuals with type 2 diabetes for which results have been presented at various conferences, announced by the company, and/or published since late 2020.

SURPASS-5 specifically investigated the effect on glycemic control of adding three different doses of once-weekly subcutaneous tirzepatide compared with placebo in 475 adults who hadn’t achieved target A1c levels using insulin glargine with or without metformin. Statistically significant reductions in A1c were found at 40 weeks for all three doses.

Moreover, authors Dominik Dahl, MD, group practice for internal medicine and diabetology, Hamburg, Germany, and colleagues note that the improvements in the tirzepatide groups “were associated with significantly lower insulin glargine use and significant bodyweight reduction compared with placebo.”

“Despite the differences in glycemic control between the tirzepatide and placebo groups, the rate of clinically significant or severe hypoglycemia was below one event per patient-year in all treatment groups,” they add.

However, concerns about the study protocol and generalizability were raised in an accompanying editorial by Stuart R. Chipkin, MD, of the School of Public Health & Health Sciences, University of Massachusetts Amherst.

“Importantly, the study did not compare tirzepatide with other treatments that could have been used to target the postprandial glycemic pattern of the study population,” he writes.

And ultimately, he says: “Even though the results of this investigation are important for demonstrating the potential clinical benefit of [tirzepatide], and may help to advance the goal of achieving U.S. Food and Drug Administration approval, the study may leave clinicians uncertain about when and how to best use tirzepatide to improve clinical outcomes for patients with type 2 diabetes.”

Significant A1c, weight reductions when added to insulin glargine

The randomized, phase 3 SURPASS-5 trial was conducted at 45 centers in eight countries between August 2019 and January 2021. The 475 adult participants had type 2 diabetes inadequately controlled (baseline A1c, 7.0%-10.5%) with once-daily insulin glargine, with or without metformin. They were randomized to receive once-weekly subcutaneous injections of tirzepatide in doses of 5 mg, 10 mg, or 15 mg, or volume-matched placebo injections over 40 weeks.

The mean changes from baseline in A1c at week 40, the primary study endpoint, were –2.11, –2.40, and –2.34 percentage points for the 5 mg, 10 mg, and 15 mg doses of tirzepatide, respectively (P < .001), versus a nonsignificant change of –0.86 percentage points with placebo. The differences from placebo at week 40 were also significant for the 10-mg and 15-mg doses (both P < .001).  

Significantly higher proportions of patients receiving 5 mg, 10 mg, and 15 mg tirzepatide met the A1c target of less than 7% at week 40, compared with placebo (85%-90% vs. 34%; P < .001). Significantly higher proportions of patients in the 10-mg and 15-mg dose groups also achieved A1c less than 5.7% (42% and 50%, respectively, vs. 3%).

Mean fasting glucose was also reduced significantly with all doses of tirzepatide by 58.2 mg/dL, 64.0 mg/dL, and 62.6 mg/dL, respectively, versus 39.2 mg/dL with placebo (all P <0.001 vs. placebo).

At week 40, mean body weight reductions from baseline were 5.4 kg (11.9 lbs), 7.5 kg, and 8.8 kg versus just 1.6 kg with placebo (all P <0.001 vs. placebo).

All three tirzepatide doses were also associated with significant improvements from baseline in total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and triglycerides.  
 

Gastrointestinal adverse events, hypoglycemia seen in minority

The most common treatment-emergent adverse events in the tirzepatide groups versus placebo were gastrointestinal, including diarrhea (12%-21% vs. 10%), nausea (13%-18% vs. 2.5%), vomiting (7%-13% vs. 2.5%), and decreased appetite (7%-14% vs. 1.7%). Most of these adverse events were mild to moderate in intensity and decreased over time in the tirzepatide groups.

There were no deaths in the study. Serious adverse events were reported by 8%-11% in the tirzepatide groups, compared with 8% in the placebo group. Drug discontinuation due to adverse events occurred in 6.0%, 8.4%, and 10.8% of the 5-mg, 10-mg, and 15-mg dose groups, respectively, versus 2.5% in the placebo group.

Rates of hypoglycemia (less than or equal to 70 mg/dL) ranged from 14.2% to 19.3% with tirzepatide versus 12.5% with placebo. There were three episodes of severe hypoglycemia (less than 54 mg/dL), two with 10 mg tirzepatide and one with 15 mg tirzepatide.
 

Editorial raises questions

In his editorial, Dr. Chipkin writes that the study “demonstrated that use of tirzepatide was associated with significant reductions in A1c and weight in a fairly homogeneous cohort of patients with type 2 diabetes who were receiving insulin glargine with or without metformin.”

“The protocol answered questions about efficacy but left open questions about generalizability and effectiveness in different populations, especially patients with certain complications or comorbid chronic diseases.” He also notes that younger adults and Black patients were not well-represented.

And the study didn’t allow for dividing up the glargine dose or for adding short-acting insulin before meals or any other pre-meal medications and “thus may represent a departure from usual care” in the setting of rising glucose levels.

The authors themselves acknowledge that “the postprandial glucose excursions observed in the placebo group suggest an additional prandial intervention was likely needed in some patients, despite the strict inclusion criteria and the treat-to-target-approach used in the study.”

Dr. Chipkin concludes that “although patients are likely to embrace a medication with weight loss outcomes, the protocol also leaves unanswered questions about reducing insulin and evaluating the comparative risk of adverse effects.”

The study was sponsored by Eli Lilly. Dr. Dahl has reported receiving personal fees from Eli Lilly during the conduct of the study and personal fees from Afimmune, Novo Nordisk, and Novartis outside the submitted work. Dr. Chipkin has reported no relevant financial relationships.

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

Group A streptococcus (GAS) infection is not associated with new-onset tic disorders in at-risk children, findings from a large prospective study show.

The results mean that if preteens present with a new-onset tic condition, “they’re unlikely to have it as a result of a group A streptococcal throat infection,” study author Anette Eleonore Schrag, MD, PhD, professor, department of clinical neuroscience, Institute of Neurology, University College London, told this news organization.

Therefore, clinicians should not automatically prescribe antibiotics for children with tics, which sometimes occurs, said Dr. Schrag.

The study was published online Feb. 2 in Neurology.
 

Ongoing controversy

Research shows that genetic and environmental factors contribute to chronic tic disorders (CTDs) and Tourette syndrome (TS). Prenatal exposure to maternal smoking and central nervous system (CNS) stimulants, as well as psychosocial stress, may play a role.

There has been an ongoing controversy regarding the possible role of GAS in tics, with some studies showing an association and others not showing a link. However, previous studies have been retrospective, registry based, or had limited sample size.

This new prospective study is the first in children without a tic disorder but who were at relatively high risk of developing one. The children were followed to assess development of streptococcal infections and tics, said Dr. Schrag.

The study included 259 children aged 3-10 years (mean baseline age, 6.8 years; over half female) who had a first-degree relative such as a parent or sibling with TS or CTD.

The average age at TS onset is 7 years, peaking in prevalence and severity at about 9-12 years. GAS throat infections are common in this age group.

Although study participants did not have tics themselves, they represented “an enriched group,” said Dr. Schrag. “Because they had family history, we knew they were at increased risk for developing tics.”

Participants were evaluated every 2 months, alternating between scheduled hospital visits and telephone interviews. Parents kept a weekly diary and were instructed to bring their child in for assessment if they showed any signs of tics.

The average follow-up period was 1.6 years, but some of the children were followed for up to 48 months. During the study, there were a total of 1,944 assessments, including 939 telephone interviews and 1,005 clinical visits.
 

More common in boys

Investigators defined tic onset as the first occurrence of any sudden, rapid, recurrent, nonrhythmic involuntary movement and/or vocalization on at least three separate days within a period of 3 weeks.

The investigators assessed GAS exposure using parameters from throat swabs, serum anti-streptolysin O titers, and anti-DNAse B titers.

They used multiple definitions and combinations of GAS exposures “to make sure we weren’t missing any association because we didn’t use the right definition,” said Dr. Schrag. She explained a definitive strep infection is not always clear-cut.

At baseline, 17.0% participants tested positive for GAS, and 78.8% tested negative. No throat swab was available from 4.2% of participants.

During follow-up, the number of confirmed positive GAS exposures was 59, 102, 125, and 138, depending on the definition.

Researchers identified 61 tic cases during the study period. There was no evidence of an association of tic onset with GAS exposure after adjusting for age, sex, and parental education level.

However, there was a strong association between tic onset and sex, with girls being 60% less likely to develop tics than boys (hazard ratio, 0.4; 95% CI, 0.2-0.7; P < .01).

This result wasn’t particularly surprising, as it’s known that more boys develop tics than girls. “We just confirmed that in a prospective way,” said Dr. Schrag.

Results from sensitivity analyses confirmed the results. This was also the case with analyses that excluded visits with missing data on GAS exposure and that further adjusted for clinical site and psychotropic medication use.
 

Other pathogens?

Although the results showed no association between strep and tics in this population, it does not “close the door completely” on a potential relationship, said Dr. Schrag.

“By and large, the development of tics in children is not associated with group A strep, but differences in small subgroups can never be excluded by a study like this.”

Participants in this study were part of the European Multicentre Tics in Children Studies (EMTICS), a prospective cohort study exploring the role of environmental and genetic factors in pediatric CTD. That project is also looking at immune system factors, “which might play a role in the development of chronic tic disorder and associated conditions,” said Dr. Schrag.

It’s still possible, she added, that other pathogens could play a role in tic development. “That’s going to be the subject of further analysis and future studies,” she said.

Tamara Pringsheim, MD, professor of clinical neurosciences, psychiatry, pediatrics, and community health sciences, University of Calgary (Alta.), praised the research.

“This was a well-designed study, with a large sample of 260 children followed for up to 4 years, using a standardized protocol to assess for group A streptococcal infection and new onset of tics.”

The study, which did not uncover an association between GAS exposure and tic onset, “provides high level evidence that group A streptococcal exposure is not an important risk factor for the new onset of tics in children with a family history of tic disorders.”

The study received funding from the European Union Seventh Framework Program for research technological development and demonstration. Dr. Schrag reports receiving consultancy or advisory board honoraria from Biogen, Abbvie, Bial, and Neurotechnology; research support from the National Institute of Health Research, Parkinsons UK, and the Economic and Social Research Council and the European Commission; and Royalties from Oxford University Press. Dr. Pringsheim reports no relevant financial relationships.

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

Group A streptococcus (GAS) infection is not associated with new-onset tic disorders in at-risk children, findings from a large prospective study show.

The results mean that if preteens present with a new-onset tic condition, “they’re unlikely to have it as a result of a group A streptococcal throat infection,” study author Anette Eleonore Schrag, MD, PhD, professor, department of clinical neuroscience, Institute of Neurology, University College London, told this news organization.

Therefore, clinicians should not automatically prescribe antibiotics for children with tics, which sometimes occurs, said Dr. Schrag.

The study was published online Feb. 2 in Neurology.
 

Ongoing controversy

Research shows that genetic and environmental factors contribute to chronic tic disorders (CTDs) and Tourette syndrome (TS). Prenatal exposure to maternal smoking and central nervous system (CNS) stimulants, as well as psychosocial stress, may play a role.

There has been an ongoing controversy regarding the possible role of GAS in tics, with some studies showing an association and others not showing a link. However, previous studies have been retrospective, registry based, or had limited sample size.

This new prospective study is the first in children without a tic disorder but who were at relatively high risk of developing one. The children were followed to assess development of streptococcal infections and tics, said Dr. Schrag.

The study included 259 children aged 3-10 years (mean baseline age, 6.8 years; over half female) who had a first-degree relative such as a parent or sibling with TS or CTD.

The average age at TS onset is 7 years, peaking in prevalence and severity at about 9-12 years. GAS throat infections are common in this age group.

Although study participants did not have tics themselves, they represented “an enriched group,” said Dr. Schrag. “Because they had family history, we knew they were at increased risk for developing tics.”

Participants were evaluated every 2 months, alternating between scheduled hospital visits and telephone interviews. Parents kept a weekly diary and were instructed to bring their child in for assessment if they showed any signs of tics.

The average follow-up period was 1.6 years, but some of the children were followed for up to 48 months. During the study, there were a total of 1,944 assessments, including 939 telephone interviews and 1,005 clinical visits.
 

More common in boys

Investigators defined tic onset as the first occurrence of any sudden, rapid, recurrent, nonrhythmic involuntary movement and/or vocalization on at least three separate days within a period of 3 weeks.

The investigators assessed GAS exposure using parameters from throat swabs, serum anti-streptolysin O titers, and anti-DNAse B titers.

They used multiple definitions and combinations of GAS exposures “to make sure we weren’t missing any association because we didn’t use the right definition,” said Dr. Schrag. She explained a definitive strep infection is not always clear-cut.

At baseline, 17.0% participants tested positive for GAS, and 78.8% tested negative. No throat swab was available from 4.2% of participants.

During follow-up, the number of confirmed positive GAS exposures was 59, 102, 125, and 138, depending on the definition.

Researchers identified 61 tic cases during the study period. There was no evidence of an association of tic onset with GAS exposure after adjusting for age, sex, and parental education level.

However, there was a strong association between tic onset and sex, with girls being 60% less likely to develop tics than boys (hazard ratio, 0.4; 95% CI, 0.2-0.7; P < .01).

This result wasn’t particularly surprising, as it’s known that more boys develop tics than girls. “We just confirmed that in a prospective way,” said Dr. Schrag.

Results from sensitivity analyses confirmed the results. This was also the case with analyses that excluded visits with missing data on GAS exposure and that further adjusted for clinical site and psychotropic medication use.
 

Other pathogens?

Although the results showed no association between strep and tics in this population, it does not “close the door completely” on a potential relationship, said Dr. Schrag.

“By and large, the development of tics in children is not associated with group A strep, but differences in small subgroups can never be excluded by a study like this.”

Participants in this study were part of the European Multicentre Tics in Children Studies (EMTICS), a prospective cohort study exploring the role of environmental and genetic factors in pediatric CTD. That project is also looking at immune system factors, “which might play a role in the development of chronic tic disorder and associated conditions,” said Dr. Schrag.

It’s still possible, she added, that other pathogens could play a role in tic development. “That’s going to be the subject of further analysis and future studies,” she said.

Tamara Pringsheim, MD, professor of clinical neurosciences, psychiatry, pediatrics, and community health sciences, University of Calgary (Alta.), praised the research.

“This was a well-designed study, with a large sample of 260 children followed for up to 4 years, using a standardized protocol to assess for group A streptococcal infection and new onset of tics.”

The study, which did not uncover an association between GAS exposure and tic onset, “provides high level evidence that group A streptococcal exposure is not an important risk factor for the new onset of tics in children with a family history of tic disorders.”

The study received funding from the European Union Seventh Framework Program for research technological development and demonstration. Dr. Schrag reports receiving consultancy or advisory board honoraria from Biogen, Abbvie, Bial, and Neurotechnology; research support from the National Institute of Health Research, Parkinsons UK, and the Economic and Social Research Council and the European Commission; and Royalties from Oxford University Press. Dr. Pringsheim reports no relevant financial relationships.

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

Group A streptococcus (GAS) infection is not associated with new-onset tic disorders in at-risk children, findings from a large prospective study show.

The results mean that if preteens present with a new-onset tic condition, “they’re unlikely to have it as a result of a group A streptococcal throat infection,” study author Anette Eleonore Schrag, MD, PhD, professor, department of clinical neuroscience, Institute of Neurology, University College London, told this news organization.

Therefore, clinicians should not automatically prescribe antibiotics for children with tics, which sometimes occurs, said Dr. Schrag.

The study was published online Feb. 2 in Neurology.
 

Ongoing controversy

Research shows that genetic and environmental factors contribute to chronic tic disorders (CTDs) and Tourette syndrome (TS). Prenatal exposure to maternal smoking and central nervous system (CNS) stimulants, as well as psychosocial stress, may play a role.

There has been an ongoing controversy regarding the possible role of GAS in tics, with some studies showing an association and others not showing a link. However, previous studies have been retrospective, registry based, or had limited sample size.

This new prospective study is the first in children without a tic disorder but who were at relatively high risk of developing one. The children were followed to assess development of streptococcal infections and tics, said Dr. Schrag.

The study included 259 children aged 3-10 years (mean baseline age, 6.8 years; over half female) who had a first-degree relative such as a parent or sibling with TS or CTD.

The average age at TS onset is 7 years, peaking in prevalence and severity at about 9-12 years. GAS throat infections are common in this age group.

Although study participants did not have tics themselves, they represented “an enriched group,” said Dr. Schrag. “Because they had family history, we knew they were at increased risk for developing tics.”

Participants were evaluated every 2 months, alternating between scheduled hospital visits and telephone interviews. Parents kept a weekly diary and were instructed to bring their child in for assessment if they showed any signs of tics.

The average follow-up period was 1.6 years, but some of the children were followed for up to 48 months. During the study, there were a total of 1,944 assessments, including 939 telephone interviews and 1,005 clinical visits.
 

More common in boys

Investigators defined tic onset as the first occurrence of any sudden, rapid, recurrent, nonrhythmic involuntary movement and/or vocalization on at least three separate days within a period of 3 weeks.

The investigators assessed GAS exposure using parameters from throat swabs, serum anti-streptolysin O titers, and anti-DNAse B titers.

They used multiple definitions and combinations of GAS exposures “to make sure we weren’t missing any association because we didn’t use the right definition,” said Dr. Schrag. She explained a definitive strep infection is not always clear-cut.

At baseline, 17.0% participants tested positive for GAS, and 78.8% tested negative. No throat swab was available from 4.2% of participants.

During follow-up, the number of confirmed positive GAS exposures was 59, 102, 125, and 138, depending on the definition.

Researchers identified 61 tic cases during the study period. There was no evidence of an association of tic onset with GAS exposure after adjusting for age, sex, and parental education level.

However, there was a strong association between tic onset and sex, with girls being 60% less likely to develop tics than boys (hazard ratio, 0.4; 95% CI, 0.2-0.7; P < .01).

This result wasn’t particularly surprising, as it’s known that more boys develop tics than girls. “We just confirmed that in a prospective way,” said Dr. Schrag.

Results from sensitivity analyses confirmed the results. This was also the case with analyses that excluded visits with missing data on GAS exposure and that further adjusted for clinical site and psychotropic medication use.
 

Other pathogens?

Although the results showed no association between strep and tics in this population, it does not “close the door completely” on a potential relationship, said Dr. Schrag.

“By and large, the development of tics in children is not associated with group A strep, but differences in small subgroups can never be excluded by a study like this.”

Participants in this study were part of the European Multicentre Tics in Children Studies (EMTICS), a prospective cohort study exploring the role of environmental and genetic factors in pediatric CTD. That project is also looking at immune system factors, “which might play a role in the development of chronic tic disorder and associated conditions,” said Dr. Schrag.

It’s still possible, she added, that other pathogens could play a role in tic development. “That’s going to be the subject of further analysis and future studies,” she said.

Tamara Pringsheim, MD, professor of clinical neurosciences, psychiatry, pediatrics, and community health sciences, University of Calgary (Alta.), praised the research.

“This was a well-designed study, with a large sample of 260 children followed for up to 4 years, using a standardized protocol to assess for group A streptococcal infection and new onset of tics.”

The study, which did not uncover an association between GAS exposure and tic onset, “provides high level evidence that group A streptococcal exposure is not an important risk factor for the new onset of tics in children with a family history of tic disorders.”

The study received funding from the European Union Seventh Framework Program for research technological development and demonstration. Dr. Schrag reports receiving consultancy or advisory board honoraria from Biogen, Abbvie, Bial, and Neurotechnology; research support from the National Institute of Health Research, Parkinsons UK, and the Economic and Social Research Council and the European Commission; and Royalties from Oxford University Press. Dr. Pringsheim reports no relevant financial relationships.

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

The picture of rebellious teenagers sneaking “shots” has widened beyond breaking into Mom and Dad’s liquor cabinet. For some teens now, it means getting a COVID-19 vaccination without their parents’ consent – and, unlike the cabinet raids for the booze, they have adults willing to endorse the practice.

Since the U.S. Food and Drug Administration first granted emergency use authorization to Pfizer’s COVID-19 vaccine for teenagers in mid-2021, health officials have had to deal with a small subset of vaccine hesitancy where minors want the shot over the objections of their reluctant parents. The split has buoyed groups that were formed initially to convince teenagers to get vaccinated against other diseases.

When 14-year-old Arin Parsa of San Jose, California founded Teens for Vaccines in 2019 after a measles outbreak among unvaccinated children, “hardly anyone was interested,” he said. “Many teens were into climate change and other causes. Then, when the pandemic hit, so many were suddenly aware.”
 

Heavy toll on teens

Mr. Parsa’s parents fully supported Teens for Vaccines, he said, but he quickly found out how “politicized” COVID shots had become.

“We find people who are sad, angry, and frustrated at this stage of the pandemic,” he told this news organization. “The anti-vax lobby is riding the coat-tails of other movements. It has a very severe effect on their mental health. They can’t go out with their friends and socialize.”

In the pandemic’s initial stages, children were less likely to fall sick with COVID, but the Omicron variant led to a dramatic increase in illnesses among young people. The American Academy of Pediatrics has found that 3.5 million of the 11.4 million pediatric cases of the virus in the United States were reported in January 2022 alone. Meanwhile, vaccination rates for children aged 12-17, which were only 34% in June 2021 and lagged through the fall, are now at about 61% thanks to a sharp uptick during the Omicron surge, according to polling by the Kaiser Family Foundation.

No statistics are available on how many minors have received a COVID vaccine against their parents’ wishes.

“It’s not like there’s a big movement,” said Arthur Caplan, PhD, who heads the Division of Medical Ethics at the NYU Grossman School of Medicine. He said he noticed a divide around the HPV and hepatitis B vaccines. “They were tied up with sexual behavior,” he said, but “there were also some kids whose parents were really antivaxxers.”

Mr. Parsa said his and similar teen-oriented groups, such as VaxTeen, seek to educate their teen cohort, convince family members of the vaccines’ benefits, and to connect them with resources to get a shot. They also strive to change laws to make it easier for teenagers to receive the vaccine.

Consent laws vary from state to state (and within states), and proposed changes are afoot – some to loosen the laws and some to tighten them. Currently a 14-year-old in Alabama may get a COVID shot without parental permission, according to VaxTeen. In California, minors may receive the HPV shot without parental consent but not a COVID vaccine, although groups like Teens for Vaccines are pushing to change that. A bill now before the state legislature, the Teens Choose Vaccines Act (Senate Bill 866), would allow adolescents aged 12 and older to be able receive any FDA-approved vaccine – including COVID vaccines – without parental consent.

A second bill in California, the Keep Schools Open and Safe Act, would add the COVID-19 vaccines to the required list of immunizations needed to attend school in the state as well as eliminate the “personal belief” exemption against immunization. 

California Sen. Richard Pan, MD (D-6th District), cowrote both bills with fellow Democrat Sen. Scott Wiener (D-11th District) and teen advocates from Teens for Vaccines and Generation Up, who helped draft the language in consultation with the lawmakers.  

“As a pediatrician, I have seen all manner of situations where the requirement for a signed form has prevented teens from being able to get a vaccine that otherwise they and their guardians approved of them getting,” Dr. Pan told this news organization. “As a father, I don’t want to see my kids or any teen that wishes to protect themselves from deadly diseases unable to do so, particularly as we continue to fight off the dangers of the COVID-19 pandemic. I always encourage parents or teens that have questions about vaccines to speak directly with their pediatrician.”

Lawmakers in Philadelphia passed a provision last year to allow anyone age 11 or over to get the COVID vaccine without parental permission, keeping it in line with other vaccinations like hepatitis or HPV. “People from surrounding counties have come into the city, but it hasn’t been a huge rush,” says James Garrow, MPH, a spokesman for the city’s Department of Health.
 

Strive for collaboration, but listen to the children

Experts say the best solution is to for a doctor to meet with minors and their reluctant parents to get them on board for a COVID shot.

“Physicians are still the trusted messengers,” said Emma Olivera, MD, a pediatrician in suburban Chicago who advises groups that combat COVID misinformation.

Dr. Olivera said she often finds that internet-savvy teenagers have access to more information than older people, including their parents.  

Thanks to COVID policies, office meetings are “difficult to do,” NYU’s Dr. Caplan added. In such a meeting, Dr. Caplan said he would try to convince the parents that the shots are needed for their children to stay in school or play sports. In the end, he said minors should get the shot but would also notify the parents before that happens: “My duty is to them.”

If parents take opposite stances, the pro-vaccine side is likely to prevail, even in California, said Patrick Baghdaserians, JD, a family law attorney in Pasadena. Mr. Baghdaserians said he is now representing a father who wants his teenager to get vaccinated but the mother doesn’t. “The court will fall on our side,” he predicted.

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

The picture of rebellious teenagers sneaking “shots” has widened beyond breaking into Mom and Dad’s liquor cabinet. For some teens now, it means getting a COVID-19 vaccination without their parents’ consent – and, unlike the cabinet raids for the booze, they have adults willing to endorse the practice.

Since the U.S. Food and Drug Administration first granted emergency use authorization to Pfizer’s COVID-19 vaccine for teenagers in mid-2021, health officials have had to deal with a small subset of vaccine hesitancy where minors want the shot over the objections of their reluctant parents. The split has buoyed groups that were formed initially to convince teenagers to get vaccinated against other diseases.

When 14-year-old Arin Parsa of San Jose, California founded Teens for Vaccines in 2019 after a measles outbreak among unvaccinated children, “hardly anyone was interested,” he said. “Many teens were into climate change and other causes. Then, when the pandemic hit, so many were suddenly aware.”
 

Heavy toll on teens

Mr. Parsa’s parents fully supported Teens for Vaccines, he said, but he quickly found out how “politicized” COVID shots had become.

“We find people who are sad, angry, and frustrated at this stage of the pandemic,” he told this news organization. “The anti-vax lobby is riding the coat-tails of other movements. It has a very severe effect on their mental health. They can’t go out with their friends and socialize.”

In the pandemic’s initial stages, children were less likely to fall sick with COVID, but the Omicron variant led to a dramatic increase in illnesses among young people. The American Academy of Pediatrics has found that 3.5 million of the 11.4 million pediatric cases of the virus in the United States were reported in January 2022 alone. Meanwhile, vaccination rates for children aged 12-17, which were only 34% in June 2021 and lagged through the fall, are now at about 61% thanks to a sharp uptick during the Omicron surge, according to polling by the Kaiser Family Foundation.

No statistics are available on how many minors have received a COVID vaccine against their parents’ wishes.

“It’s not like there’s a big movement,” said Arthur Caplan, PhD, who heads the Division of Medical Ethics at the NYU Grossman School of Medicine. He said he noticed a divide around the HPV and hepatitis B vaccines. “They were tied up with sexual behavior,” he said, but “there were also some kids whose parents were really antivaxxers.”

Mr. Parsa said his and similar teen-oriented groups, such as VaxTeen, seek to educate their teen cohort, convince family members of the vaccines’ benefits, and to connect them with resources to get a shot. They also strive to change laws to make it easier for teenagers to receive the vaccine.

Consent laws vary from state to state (and within states), and proposed changes are afoot – some to loosen the laws and some to tighten them. Currently a 14-year-old in Alabama may get a COVID shot without parental permission, according to VaxTeen. In California, minors may receive the HPV shot without parental consent but not a COVID vaccine, although groups like Teens for Vaccines are pushing to change that. A bill now before the state legislature, the Teens Choose Vaccines Act (Senate Bill 866), would allow adolescents aged 12 and older to be able receive any FDA-approved vaccine – including COVID vaccines – without parental consent.

A second bill in California, the Keep Schools Open and Safe Act, would add the COVID-19 vaccines to the required list of immunizations needed to attend school in the state as well as eliminate the “personal belief” exemption against immunization. 

California Sen. Richard Pan, MD (D-6th District), cowrote both bills with fellow Democrat Sen. Scott Wiener (D-11th District) and teen advocates from Teens for Vaccines and Generation Up, who helped draft the language in consultation with the lawmakers.  

“As a pediatrician, I have seen all manner of situations where the requirement for a signed form has prevented teens from being able to get a vaccine that otherwise they and their guardians approved of them getting,” Dr. Pan told this news organization. “As a father, I don’t want to see my kids or any teen that wishes to protect themselves from deadly diseases unable to do so, particularly as we continue to fight off the dangers of the COVID-19 pandemic. I always encourage parents or teens that have questions about vaccines to speak directly with their pediatrician.”

Lawmakers in Philadelphia passed a provision last year to allow anyone age 11 or over to get the COVID vaccine without parental permission, keeping it in line with other vaccinations like hepatitis or HPV. “People from surrounding counties have come into the city, but it hasn’t been a huge rush,” says James Garrow, MPH, a spokesman for the city’s Department of Health.
 

Strive for collaboration, but listen to the children

Experts say the best solution is to for a doctor to meet with minors and their reluctant parents to get them on board for a COVID shot.

“Physicians are still the trusted messengers,” said Emma Olivera, MD, a pediatrician in suburban Chicago who advises groups that combat COVID misinformation.

Dr. Olivera said she often finds that internet-savvy teenagers have access to more information than older people, including their parents.  

Thanks to COVID policies, office meetings are “difficult to do,” NYU’s Dr. Caplan added. In such a meeting, Dr. Caplan said he would try to convince the parents that the shots are needed for their children to stay in school or play sports. In the end, he said minors should get the shot but would also notify the parents before that happens: “My duty is to them.”

If parents take opposite stances, the pro-vaccine side is likely to prevail, even in California, said Patrick Baghdaserians, JD, a family law attorney in Pasadena. Mr. Baghdaserians said he is now representing a father who wants his teenager to get vaccinated but the mother doesn’t. “The court will fall on our side,” he predicted.

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

The picture of rebellious teenagers sneaking “shots” has widened beyond breaking into Mom and Dad’s liquor cabinet. For some teens now, it means getting a COVID-19 vaccination without their parents’ consent – and, unlike the cabinet raids for the booze, they have adults willing to endorse the practice.

Since the U.S. Food and Drug Administration first granted emergency use authorization to Pfizer’s COVID-19 vaccine for teenagers in mid-2021, health officials have had to deal with a small subset of vaccine hesitancy where minors want the shot over the objections of their reluctant parents. The split has buoyed groups that were formed initially to convince teenagers to get vaccinated against other diseases.

When 14-year-old Arin Parsa of San Jose, California founded Teens for Vaccines in 2019 after a measles outbreak among unvaccinated children, “hardly anyone was interested,” he said. “Many teens were into climate change and other causes. Then, when the pandemic hit, so many were suddenly aware.”
 

Heavy toll on teens

Mr. Parsa’s parents fully supported Teens for Vaccines, he said, but he quickly found out how “politicized” COVID shots had become.

“We find people who are sad, angry, and frustrated at this stage of the pandemic,” he told this news organization. “The anti-vax lobby is riding the coat-tails of other movements. It has a very severe effect on their mental health. They can’t go out with their friends and socialize.”

In the pandemic’s initial stages, children were less likely to fall sick with COVID, but the Omicron variant led to a dramatic increase in illnesses among young people. The American Academy of Pediatrics has found that 3.5 million of the 11.4 million pediatric cases of the virus in the United States were reported in January 2022 alone. Meanwhile, vaccination rates for children aged 12-17, which were only 34% in June 2021 and lagged through the fall, are now at about 61% thanks to a sharp uptick during the Omicron surge, according to polling by the Kaiser Family Foundation.

No statistics are available on how many minors have received a COVID vaccine against their parents’ wishes.

“It’s not like there’s a big movement,” said Arthur Caplan, PhD, who heads the Division of Medical Ethics at the NYU Grossman School of Medicine. He said he noticed a divide around the HPV and hepatitis B vaccines. “They were tied up with sexual behavior,” he said, but “there were also some kids whose parents were really antivaxxers.”

Mr. Parsa said his and similar teen-oriented groups, such as VaxTeen, seek to educate their teen cohort, convince family members of the vaccines’ benefits, and to connect them with resources to get a shot. They also strive to change laws to make it easier for teenagers to receive the vaccine.

Consent laws vary from state to state (and within states), and proposed changes are afoot – some to loosen the laws and some to tighten them. Currently a 14-year-old in Alabama may get a COVID shot without parental permission, according to VaxTeen. In California, minors may receive the HPV shot without parental consent but not a COVID vaccine, although groups like Teens for Vaccines are pushing to change that. A bill now before the state legislature, the Teens Choose Vaccines Act (Senate Bill 866), would allow adolescents aged 12 and older to be able receive any FDA-approved vaccine – including COVID vaccines – without parental consent.

A second bill in California, the Keep Schools Open and Safe Act, would add the COVID-19 vaccines to the required list of immunizations needed to attend school in the state as well as eliminate the “personal belief” exemption against immunization. 

California Sen. Richard Pan, MD (D-6th District), cowrote both bills with fellow Democrat Sen. Scott Wiener (D-11th District) and teen advocates from Teens for Vaccines and Generation Up, who helped draft the language in consultation with the lawmakers.  

“As a pediatrician, I have seen all manner of situations where the requirement for a signed form has prevented teens from being able to get a vaccine that otherwise they and their guardians approved of them getting,” Dr. Pan told this news organization. “As a father, I don’t want to see my kids or any teen that wishes to protect themselves from deadly diseases unable to do so, particularly as we continue to fight off the dangers of the COVID-19 pandemic. I always encourage parents or teens that have questions about vaccines to speak directly with their pediatrician.”

Lawmakers in Philadelphia passed a provision last year to allow anyone age 11 or over to get the COVID vaccine without parental permission, keeping it in line with other vaccinations like hepatitis or HPV. “People from surrounding counties have come into the city, but it hasn’t been a huge rush,” says James Garrow, MPH, a spokesman for the city’s Department of Health.
 

Strive for collaboration, but listen to the children

Experts say the best solution is to for a doctor to meet with minors and their reluctant parents to get them on board for a COVID shot.

“Physicians are still the trusted messengers,” said Emma Olivera, MD, a pediatrician in suburban Chicago who advises groups that combat COVID misinformation.

Dr. Olivera said she often finds that internet-savvy teenagers have access to more information than older people, including their parents.  

Thanks to COVID policies, office meetings are “difficult to do,” NYU’s Dr. Caplan added. In such a meeting, Dr. Caplan said he would try to convince the parents that the shots are needed for their children to stay in school or play sports. In the end, he said minors should get the shot but would also notify the parents before that happens: “My duty is to them.”

If parents take opposite stances, the pro-vaccine side is likely to prevail, even in California, said Patrick Baghdaserians, JD, a family law attorney in Pasadena. Mr. Baghdaserians said he is now representing a father who wants his teenager to get vaccinated but the mother doesn’t. “The court will fall on our side,” he predicted.

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

Models using novel kidney and cardiac biomarkers were the most effective predictors of 10-year risk for atherosclerotic cardiovascular disease in chronic kidney disease patients, in a new study.

Chronic kidney disease (CKD) patients may be at increased risk for atherosclerotic cardiovascular disease, but no ASCVD risk prediction models are currently in place to inform clinical care and prevention strategies, Joshua Bundy, PhD, of Tulane University, New Orleans, and colleagues wrote in their paper, published in the Journal of the American Society of Nephrology.

To improve the accuracy of ASCVD risk prediction, the researchers developed several models using data from the Chronic Renal Insufficiency Cohort (CRIC) study. This longitudinal cohort study included more than 2,500 adult CKD patients. The participants’ ages ranged from 21-74 years, with the mean age having been 55.8 years, and 52.0% of the cohort was male.

Kidney function was defined using the glomerular filtration rate; the mean estimated glomerular filtration rate (eGFR) of the study participants was 56.0 mL/min per 1.73m². The primary endpoint for the prediction models was incident ASCVD, defined as a composite of incident fatal or nonfatal stroke or MI.

A total of 252 incident ASCVD events occurred during the first 10 years of follow-up from baseline (1.9 events per 1,000 person-years). Patients with ASCVD events were more likely to be older, Black, and current smokers. They also were more likely than those who did not experience ASCVD events to have less than a college level education, to have a history of diabetes, and to use blood pressure–lowering medications.

“In our study, we created two new prediction tools for patients with CKD: the first is a simple model that includes factors routinely measured by health care providers and the second is an expanded model with additional variables particularly important to patients with CKD, including measures of long-term blood sugar, inflammation, and kidney and heart injury,” he explained. “We found that the new models are better able to classify patients who will or will not have a stroke or heart attack within 10 years, compared with the standard models. The new tools may better assist health care providers and patients with CKD in shared decision-making for prevention of heart disease.”
 

Results

The area under the curve for a prediction model using coefficients estimated within the CRIC sample was 0.736. This represented an accuracy higher than the American College of Cardiology/American Heart Association Pooled Cohort Equations (PCE), which have shown an AUC of 0.730 (P = .03). The PCE were developed by the ACC and the AHA in 2013 to estimate ASCVD risk in the primary prevention population.

The second CRIC model that was developed using clinically available variables had an AUC of 0.760. However, the third CRIC biomarker-enriched model was even more effective, with an AUC of 0.771 – significantly higher than the clinical model (P = .001).

Model 1 included the ACC/AHA PCE variables with coefficients recalculated in the CRIC study sample. Model 2 (the CRIC Clinical Model) included age, HDL cholesterol, systolic BP, current smoking, urinary albumin-to-creatinine ratio (ACR), hemoglobin A1c, and hemoglobin. Model 3 (the CRIC Enriched Model) included age, total cholesterol, HDL cholesterol, current smoking, urinary ACR, A1c, apolipoprotein B, high-sensitivity C-reactive protein (hsCRP), troponin T, and N-terminal of the prohormone brain natriuretic peptide (NT-proBNP).

Both the clinical and biomarker models improved reclassification of non-ASCVD events, compared with the PCEs (6.6% and 10.0%, respectively).

Several factors not included in prior prediction models were important for atherosclerotic CVD prediction among patients with CKD, the researchers noted. These included variables routinely measured in clinical practice as well as biomarkers: measures of long-term glycemia (A1c), inflammation (hsCRP), kidney injury (urinary ACR), and cardiac injury (troponin T and NT-proBNP).

Patients who had an ASCVD event had higher levels of A1c, systolic and diastolic BP, urinary ACR, troponin T, and NT-proBNP; these patients also had lower levels of HDL cholesterol, eGFR, and hemoglobin, compared with those who did not have an event.

The study findings were limited by several factors including the selection of study participants based on a single assessment of kidney function, who had an above average baseline ASCVD risk, the researchers noted. Other limitations included the inability to include imaging variables in the models, and the overestimated risk in the highest predicted probability groups in the CRIC study.

However, the models significantly improve prediction beyond the ACC/AHA PCE in patients with CKD, they concluded.

 

Models may inform shared decision-making

The development of new prediction models is important, because cardiovascular disease is the leading cause of death among U.S. adults and preventing CVD is a major public health challenge, lead author Dr. Bundy said in an interview.

“In an effort to prevent CVD, risk prediction equations can help identify patients who are at high risk for developing CVD and who may benefit from initiation or intensification of preventive and/or therapeutic measures. Simultaneously, chronic kidney disease is prevalent and those with CKD are often considered at high risk for CVD,” he said.

“However, common risk prediction tools were developed for the general population and may not work as well in patients with CKD, who may have different risk factors. Improving risk prediction in patients with CKD may help identify those among this growing population who are truly at high risk, as well as identify those who are at low risk and less likely to benefit from invasive procedures,” Dr. Bundy explained.
 

Glomerular filtration rate was not a strong predictor of atherosclerotic CVD

“One of the surprising findings was that estimated glomerular filtration rate was not a strong predictor and was not included in our final models,” Dr. Bundy said.

“We know that eGFR is a very important measurement in this population, but our results suggest that, at least in our sample, urinary albumin-to-creatinine ratio and cardiac biomarkers like troponin T and NT-proBNP are stronger predictors of atherosclerotic CVD in a population with reduced kidney function,” he said.

“Patient characteristics like age, blood pressure, and cholesterol are used by health care providers to predict whether a person will have a heart attack or stroke. However, most currently available prediction tools were not made for use in patients with CKD, which is a condition that is becoming more common and is likely to be seen by more health care providers in family practice,” said Dr. Bundy. “These people with CKD may have different risk factors for heart disease.”
 

Models are useful for clinical practice

“We are seeing rising numbers of patients with CKD in the population because of increasing age, rising rates of diabetes, and hypertension,” Noel Deep, MD, said in an interview. “The current practice of medicine does not have CKD-specific prediction models for ASCVD development, and current risks are calculated based on prediction models developed for the general population.”

Courtesy Dr. Noel Deep

“Having a prediction model that incorporates criteria/variables associated with CKD improves our ability to accurately identify and address the risk of ASCVD in this particular patient population,” said Dr. Deep, who is a general internist in a multispecialty group practice with Aspirus Antigo (Wisc.) Clinic and the chief medical officer and a staff physician at Aspirus Langlade Hospital, also in Antigo.

“We always knew that CKD does place the individual at higher risk for developing ASCVD, but I was impressed by the significant improvement in the prediction models using CKD specific tools, such as cardiac biomarkers (NT-proBNP), intensity of diabetes control (A1c), tobacco use, urinary albuminuria, in addition to advancing age,” he said. “Many of the laboratory tests listed in this study are commonly available and can be easily incorporated into our evaluation for and management of ASCVD in our patients with CKD.”

“As a practicing primary care physician, I would say that this study emphasizes the importance of identifying and working toward mitigating the associated health risks that our patients with CKD might have coexisting and that significantly contribute to progression of CKD,” said Dr. Deep, who is also assistant clinical professor at the Medical College of Wisconsin, Wausau. “By addressing these risk factors, we can positively impact the health of our patients with CKD and decrease the morbidity and mortality, and health care costs. These predictive models can hopefully help us more accurately identify the risk of ASCVD thereby decreasing unnecessary diagnostic procedures and interventions which carry their own risks and morbidity.”

Looking ahead, “these predictive models should be assessed and validated in large studies in diverse populations and those with different risk factors for ASCVD because CKD can be caused by several different medical conditions each with potential to contribute to ASCVD,” Dr. Deep added.
 

Limitations and next steps

“Although we externally validated our models in two population-based cohort studies, the individuals in these datasets were selected based on only one assessment of kidney function,” Dr. Bundy noted. “Furthermore, the best practices for implementing risk prediction models in the clinic remain to be determined, especially as new models are developed.

“While our models show promising performance for predicting 10-year risk of atherosclerotic CVD, more clinical trials are needed to test implementation of these models for improving patient care and disease prevention.”

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Additional support came from the University of Pennsylvania Clinical and Translational Science Award, Johns Hopkins University, the University of Maryland, Clinical and Translational Science Collaborative of Cleveland, the National Center for Advancing Translational Sciences component of the National Institutes of Health and NIH roadmap for Medical Research, Michigan Institute for Clinical and Health Research, University of Illinois at Chicago, Tulane COBRE for Clinical and Translational Research in Cardiometabolic Diseases, Kaiser Permanente, and the University of New Mexico. Lead author Dr. Bundy was supported by the National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development. The researchers had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose.

This article was updated on 2/17/2021.

Models using novel kidney and cardiac biomarkers were the most effective predictors of 10-year risk for atherosclerotic cardiovascular disease in chronic kidney disease patients, in a new study.

Chronic kidney disease (CKD) patients may be at increased risk for atherosclerotic cardiovascular disease, but no ASCVD risk prediction models are currently in place to inform clinical care and prevention strategies, Joshua Bundy, PhD, of Tulane University, New Orleans, and colleagues wrote in their paper, published in the Journal of the American Society of Nephrology.

To improve the accuracy of ASCVD risk prediction, the researchers developed several models using data from the Chronic Renal Insufficiency Cohort (CRIC) study. This longitudinal cohort study included more than 2,500 adult CKD patients. The participants’ ages ranged from 21-74 years, with the mean age having been 55.8 years, and 52.0% of the cohort was male.

Kidney function was defined using the glomerular filtration rate; the mean estimated glomerular filtration rate (eGFR) of the study participants was 56.0 mL/min per 1.73m². The primary endpoint for the prediction models was incident ASCVD, defined as a composite of incident fatal or nonfatal stroke or MI.

A total of 252 incident ASCVD events occurred during the first 10 years of follow-up from baseline (1.9 events per 1,000 person-years). Patients with ASCVD events were more likely to be older, Black, and current smokers. They also were more likely than those who did not experience ASCVD events to have less than a college level education, to have a history of diabetes, and to use blood pressure–lowering medications.

“In our study, we created two new prediction tools for patients with CKD: the first is a simple model that includes factors routinely measured by health care providers and the second is an expanded model with additional variables particularly important to patients with CKD, including measures of long-term blood sugar, inflammation, and kidney and heart injury,” he explained. “We found that the new models are better able to classify patients who will or will not have a stroke or heart attack within 10 years, compared with the standard models. The new tools may better assist health care providers and patients with CKD in shared decision-making for prevention of heart disease.”
 

Results

The area under the curve for a prediction model using coefficients estimated within the CRIC sample was 0.736. This represented an accuracy higher than the American College of Cardiology/American Heart Association Pooled Cohort Equations (PCE), which have shown an AUC of 0.730 (P = .03). The PCE were developed by the ACC and the AHA in 2013 to estimate ASCVD risk in the primary prevention population.

The second CRIC model that was developed using clinically available variables had an AUC of 0.760. However, the third CRIC biomarker-enriched model was even more effective, with an AUC of 0.771 – significantly higher than the clinical model (P = .001).

Model 1 included the ACC/AHA PCE variables with coefficients recalculated in the CRIC study sample. Model 2 (the CRIC Clinical Model) included age, HDL cholesterol, systolic BP, current smoking, urinary albumin-to-creatinine ratio (ACR), hemoglobin A1c, and hemoglobin. Model 3 (the CRIC Enriched Model) included age, total cholesterol, HDL cholesterol, current smoking, urinary ACR, A1c, apolipoprotein B, high-sensitivity C-reactive protein (hsCRP), troponin T, and N-terminal of the prohormone brain natriuretic peptide (NT-proBNP).

Both the clinical and biomarker models improved reclassification of non-ASCVD events, compared with the PCEs (6.6% and 10.0%, respectively).

Several factors not included in prior prediction models were important for atherosclerotic CVD prediction among patients with CKD, the researchers noted. These included variables routinely measured in clinical practice as well as biomarkers: measures of long-term glycemia (A1c), inflammation (hsCRP), kidney injury (urinary ACR), and cardiac injury (troponin T and NT-proBNP).

Patients who had an ASCVD event had higher levels of A1c, systolic and diastolic BP, urinary ACR, troponin T, and NT-proBNP; these patients also had lower levels of HDL cholesterol, eGFR, and hemoglobin, compared with those who did not have an event.

The study findings were limited by several factors including the selection of study participants based on a single assessment of kidney function, who had an above average baseline ASCVD risk, the researchers noted. Other limitations included the inability to include imaging variables in the models, and the overestimated risk in the highest predicted probability groups in the CRIC study.

However, the models significantly improve prediction beyond the ACC/AHA PCE in patients with CKD, they concluded.

 

Models may inform shared decision-making

The development of new prediction models is important, because cardiovascular disease is the leading cause of death among U.S. adults and preventing CVD is a major public health challenge, lead author Dr. Bundy said in an interview.

“In an effort to prevent CVD, risk prediction equations can help identify patients who are at high risk for developing CVD and who may benefit from initiation or intensification of preventive and/or therapeutic measures. Simultaneously, chronic kidney disease is prevalent and those with CKD are often considered at high risk for CVD,” he said.

“However, common risk prediction tools were developed for the general population and may not work as well in patients with CKD, who may have different risk factors. Improving risk prediction in patients with CKD may help identify those among this growing population who are truly at high risk, as well as identify those who are at low risk and less likely to benefit from invasive procedures,” Dr. Bundy explained.
 

Glomerular filtration rate was not a strong predictor of atherosclerotic CVD

“One of the surprising findings was that estimated glomerular filtration rate was not a strong predictor and was not included in our final models,” Dr. Bundy said.

“We know that eGFR is a very important measurement in this population, but our results suggest that, at least in our sample, urinary albumin-to-creatinine ratio and cardiac biomarkers like troponin T and NT-proBNP are stronger predictors of atherosclerotic CVD in a population with reduced kidney function,” he said.

“Patient characteristics like age, blood pressure, and cholesterol are used by health care providers to predict whether a person will have a heart attack or stroke. However, most currently available prediction tools were not made for use in patients with CKD, which is a condition that is becoming more common and is likely to be seen by more health care providers in family practice,” said Dr. Bundy. “These people with CKD may have different risk factors for heart disease.”
 

Models are useful for clinical practice

“We are seeing rising numbers of patients with CKD in the population because of increasing age, rising rates of diabetes, and hypertension,” Noel Deep, MD, said in an interview. “The current practice of medicine does not have CKD-specific prediction models for ASCVD development, and current risks are calculated based on prediction models developed for the general population.”

Courtesy Dr. Noel Deep

“Having a prediction model that incorporates criteria/variables associated with CKD improves our ability to accurately identify and address the risk of ASCVD in this particular patient population,” said Dr. Deep, who is a general internist in a multispecialty group practice with Aspirus Antigo (Wisc.) Clinic and the chief medical officer and a staff physician at Aspirus Langlade Hospital, also in Antigo.

“We always knew that CKD does place the individual at higher risk for developing ASCVD, but I was impressed by the significant improvement in the prediction models using CKD specific tools, such as cardiac biomarkers (NT-proBNP), intensity of diabetes control (A1c), tobacco use, urinary albuminuria, in addition to advancing age,” he said. “Many of the laboratory tests listed in this study are commonly available and can be easily incorporated into our evaluation for and management of ASCVD in our patients with CKD.”

“As a practicing primary care physician, I would say that this study emphasizes the importance of identifying and working toward mitigating the associated health risks that our patients with CKD might have coexisting and that significantly contribute to progression of CKD,” said Dr. Deep, who is also assistant clinical professor at the Medical College of Wisconsin, Wausau. “By addressing these risk factors, we can positively impact the health of our patients with CKD and decrease the morbidity and mortality, and health care costs. These predictive models can hopefully help us more accurately identify the risk of ASCVD thereby decreasing unnecessary diagnostic procedures and interventions which carry their own risks and morbidity.”

Looking ahead, “these predictive models should be assessed and validated in large studies in diverse populations and those with different risk factors for ASCVD because CKD can be caused by several different medical conditions each with potential to contribute to ASCVD,” Dr. Deep added.
 

Limitations and next steps

“Although we externally validated our models in two population-based cohort studies, the individuals in these datasets were selected based on only one assessment of kidney function,” Dr. Bundy noted. “Furthermore, the best practices for implementing risk prediction models in the clinic remain to be determined, especially as new models are developed.

“While our models show promising performance for predicting 10-year risk of atherosclerotic CVD, more clinical trials are needed to test implementation of these models for improving patient care and disease prevention.”

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Additional support came from the University of Pennsylvania Clinical and Translational Science Award, Johns Hopkins University, the University of Maryland, Clinical and Translational Science Collaborative of Cleveland, the National Center for Advancing Translational Sciences component of the National Institutes of Health and NIH roadmap for Medical Research, Michigan Institute for Clinical and Health Research, University of Illinois at Chicago, Tulane COBRE for Clinical and Translational Research in Cardiometabolic Diseases, Kaiser Permanente, and the University of New Mexico. Lead author Dr. Bundy was supported by the National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development. The researchers had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose.

This article was updated on 2/17/2021.

Models using novel kidney and cardiac biomarkers were the most effective predictors of 10-year risk for atherosclerotic cardiovascular disease in chronic kidney disease patients, in a new study.

Chronic kidney disease (CKD) patients may be at increased risk for atherosclerotic cardiovascular disease, but no ASCVD risk prediction models are currently in place to inform clinical care and prevention strategies, Joshua Bundy, PhD, of Tulane University, New Orleans, and colleagues wrote in their paper, published in the Journal of the American Society of Nephrology.

To improve the accuracy of ASCVD risk prediction, the researchers developed several models using data from the Chronic Renal Insufficiency Cohort (CRIC) study. This longitudinal cohort study included more than 2,500 adult CKD patients. The participants’ ages ranged from 21-74 years, with the mean age having been 55.8 years, and 52.0% of the cohort was male.

Kidney function was defined using the glomerular filtration rate; the mean estimated glomerular filtration rate (eGFR) of the study participants was 56.0 mL/min per 1.73m². The primary endpoint for the prediction models was incident ASCVD, defined as a composite of incident fatal or nonfatal stroke or MI.

A total of 252 incident ASCVD events occurred during the first 10 years of follow-up from baseline (1.9 events per 1,000 person-years). Patients with ASCVD events were more likely to be older, Black, and current smokers. They also were more likely than those who did not experience ASCVD events to have less than a college level education, to have a history of diabetes, and to use blood pressure–lowering medications.

“In our study, we created two new prediction tools for patients with CKD: the first is a simple model that includes factors routinely measured by health care providers and the second is an expanded model with additional variables particularly important to patients with CKD, including measures of long-term blood sugar, inflammation, and kidney and heart injury,” he explained. “We found that the new models are better able to classify patients who will or will not have a stroke or heart attack within 10 years, compared with the standard models. The new tools may better assist health care providers and patients with CKD in shared decision-making for prevention of heart disease.”
 

Results

The area under the curve for a prediction model using coefficients estimated within the CRIC sample was 0.736. This represented an accuracy higher than the American College of Cardiology/American Heart Association Pooled Cohort Equations (PCE), which have shown an AUC of 0.730 (P = .03). The PCE were developed by the ACC and the AHA in 2013 to estimate ASCVD risk in the primary prevention population.

The second CRIC model that was developed using clinically available variables had an AUC of 0.760. However, the third CRIC biomarker-enriched model was even more effective, with an AUC of 0.771 – significantly higher than the clinical model (P = .001).

Model 1 included the ACC/AHA PCE variables with coefficients recalculated in the CRIC study sample. Model 2 (the CRIC Clinical Model) included age, HDL cholesterol, systolic BP, current smoking, urinary albumin-to-creatinine ratio (ACR), hemoglobin A1c, and hemoglobin. Model 3 (the CRIC Enriched Model) included age, total cholesterol, HDL cholesterol, current smoking, urinary ACR, A1c, apolipoprotein B, high-sensitivity C-reactive protein (hsCRP), troponin T, and N-terminal of the prohormone brain natriuretic peptide (NT-proBNP).

Both the clinical and biomarker models improved reclassification of non-ASCVD events, compared with the PCEs (6.6% and 10.0%, respectively).

Several factors not included in prior prediction models were important for atherosclerotic CVD prediction among patients with CKD, the researchers noted. These included variables routinely measured in clinical practice as well as biomarkers: measures of long-term glycemia (A1c), inflammation (hsCRP), kidney injury (urinary ACR), and cardiac injury (troponin T and NT-proBNP).

Patients who had an ASCVD event had higher levels of A1c, systolic and diastolic BP, urinary ACR, troponin T, and NT-proBNP; these patients also had lower levels of HDL cholesterol, eGFR, and hemoglobin, compared with those who did not have an event.

The study findings were limited by several factors including the selection of study participants based on a single assessment of kidney function, who had an above average baseline ASCVD risk, the researchers noted. Other limitations included the inability to include imaging variables in the models, and the overestimated risk in the highest predicted probability groups in the CRIC study.

However, the models significantly improve prediction beyond the ACC/AHA PCE in patients with CKD, they concluded.

 

Models may inform shared decision-making

The development of new prediction models is important, because cardiovascular disease is the leading cause of death among U.S. adults and preventing CVD is a major public health challenge, lead author Dr. Bundy said in an interview.

“In an effort to prevent CVD, risk prediction equations can help identify patients who are at high risk for developing CVD and who may benefit from initiation or intensification of preventive and/or therapeutic measures. Simultaneously, chronic kidney disease is prevalent and those with CKD are often considered at high risk for CVD,” he said.

“However, common risk prediction tools were developed for the general population and may not work as well in patients with CKD, who may have different risk factors. Improving risk prediction in patients with CKD may help identify those among this growing population who are truly at high risk, as well as identify those who are at low risk and less likely to benefit from invasive procedures,” Dr. Bundy explained.
 

Glomerular filtration rate was not a strong predictor of atherosclerotic CVD

“One of the surprising findings was that estimated glomerular filtration rate was not a strong predictor and was not included in our final models,” Dr. Bundy said.

“We know that eGFR is a very important measurement in this population, but our results suggest that, at least in our sample, urinary albumin-to-creatinine ratio and cardiac biomarkers like troponin T and NT-proBNP are stronger predictors of atherosclerotic CVD in a population with reduced kidney function,” he said.

“Patient characteristics like age, blood pressure, and cholesterol are used by health care providers to predict whether a person will have a heart attack or stroke. However, most currently available prediction tools were not made for use in patients with CKD, which is a condition that is becoming more common and is likely to be seen by more health care providers in family practice,” said Dr. Bundy. “These people with CKD may have different risk factors for heart disease.”
 

Models are useful for clinical practice

“We are seeing rising numbers of patients with CKD in the population because of increasing age, rising rates of diabetes, and hypertension,” Noel Deep, MD, said in an interview. “The current practice of medicine does not have CKD-specific prediction models for ASCVD development, and current risks are calculated based on prediction models developed for the general population.”

Courtesy Dr. Noel Deep

“Having a prediction model that incorporates criteria/variables associated with CKD improves our ability to accurately identify and address the risk of ASCVD in this particular patient population,” said Dr. Deep, who is a general internist in a multispecialty group practice with Aspirus Antigo (Wisc.) Clinic and the chief medical officer and a staff physician at Aspirus Langlade Hospital, also in Antigo.

“We always knew that CKD does place the individual at higher risk for developing ASCVD, but I was impressed by the significant improvement in the prediction models using CKD specific tools, such as cardiac biomarkers (NT-proBNP), intensity of diabetes control (A1c), tobacco use, urinary albuminuria, in addition to advancing age,” he said. “Many of the laboratory tests listed in this study are commonly available and can be easily incorporated into our evaluation for and management of ASCVD in our patients with CKD.”

“As a practicing primary care physician, I would say that this study emphasizes the importance of identifying and working toward mitigating the associated health risks that our patients with CKD might have coexisting and that significantly contribute to progression of CKD,” said Dr. Deep, who is also assistant clinical professor at the Medical College of Wisconsin, Wausau. “By addressing these risk factors, we can positively impact the health of our patients with CKD and decrease the morbidity and mortality, and health care costs. These predictive models can hopefully help us more accurately identify the risk of ASCVD thereby decreasing unnecessary diagnostic procedures and interventions which carry their own risks and morbidity.”

Looking ahead, “these predictive models should be assessed and validated in large studies in diverse populations and those with different risk factors for ASCVD because CKD can be caused by several different medical conditions each with potential to contribute to ASCVD,” Dr. Deep added.
 

Limitations and next steps

“Although we externally validated our models in two population-based cohort studies, the individuals in these datasets were selected based on only one assessment of kidney function,” Dr. Bundy noted. “Furthermore, the best practices for implementing risk prediction models in the clinic remain to be determined, especially as new models are developed.

“While our models show promising performance for predicting 10-year risk of atherosclerotic CVD, more clinical trials are needed to test implementation of these models for improving patient care and disease prevention.”

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Additional support came from the University of Pennsylvania Clinical and Translational Science Award, Johns Hopkins University, the University of Maryland, Clinical and Translational Science Collaborative of Cleveland, the National Center for Advancing Translational Sciences component of the National Institutes of Health and NIH roadmap for Medical Research, Michigan Institute for Clinical and Health Research, University of Illinois at Chicago, Tulane COBRE for Clinical and Translational Research in Cardiometabolic Diseases, Kaiser Permanente, and the University of New Mexico. Lead author Dr. Bundy was supported by the National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development. The researchers had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose.

This article was updated on 2/17/2021.

The Food and Drug Administration said Feb. 11 it would delay a decision on authorizing the use of the Pfizer vaccine for younger children until data on the effects of three doses is available.

Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research, said the plan for a meeting the week of Feb. 14 of the FDA’s Vaccines and Related Biological Products Advisory Committee was to “understand if two doses would provide sufficient protection to move forward.”

Pfizer has asked the FDA to authorize the use of its mRNA vaccine for children under the age of 5. But, Dr. Marks said, “in looking through the data we realized now … that at this time it makes sense for us to wait until we have the data of the evaluation of a third dose before taking action.”

The Food and Drug Administration said Feb. 11 it would delay a decision on authorizing the use of the Pfizer vaccine for younger children until data on the effects of three doses is available.

Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research, said the plan for a meeting the week of Feb. 14 of the FDA’s Vaccines and Related Biological Products Advisory Committee was to “understand if two doses would provide sufficient protection to move forward.”

Pfizer has asked the FDA to authorize the use of its mRNA vaccine for children under the age of 5. But, Dr. Marks said, “in looking through the data we realized now … that at this time it makes sense for us to wait until we have the data of the evaluation of a third dose before taking action.”

The Food and Drug Administration said Feb. 11 it would delay a decision on authorizing the use of the Pfizer vaccine for younger children until data on the effects of three doses is available.

Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research, said the plan for a meeting the week of Feb. 14 of the FDA’s Vaccines and Related Biological Products Advisory Committee was to “understand if two doses would provide sufficient protection to move forward.”

Pfizer has asked the FDA to authorize the use of its mRNA vaccine for children under the age of 5. But, Dr. Marks said, “in looking through the data we realized now … that at this time it makes sense for us to wait until we have the data of the evaluation of a third dose before taking action.”

Current interventions to tackle Staphylococcus aureus in patients with atopic eczema have little impact on symptoms, based on data from a Cochrane Review of 41 studies published in Clinical and Experimental Allergy.

Eczema remains a huge disease burden worldwide, and colonization with S. aureus in eczema patients is common, but no standard intervention exists to relieve symptoms, wrote Nandini Banerjee, MD, of Addenbrooke’s Hospital, Cambridge, England. “While antibiotic treatment of clinically obvious infections such as cellulitis is beneficial, it is not clear whether antibiotic treatment of eczema influences eczema severity,” Dr. Banerjee noted.

The 41 studies included 1,753 participants and 10 treatment categories. Most of the studies were conducted in secondary care centers in Western Europe, North America, and the Far East. Twelve studies included children, four included only adults, 19 included children and adults, and in six studies, the participant age range was unclear. Among the studies with reported ages, the mean age ranged from 1.1 to 34.6 years. Eczema severity ranged from mild to severe, and treatment durations ranged from 10 minutes to 3 months.

The review presented comparisons of topical steroid/antibiotic combinations, oral antibiotics, and bleach baths. In 14 studies that compared topical steroid/antibiotic combinations to topical steroids alone, patients showed slightly greater global improvement in symptoms with the combination, but the impact on quality of life was not significantly different. Severe adverse events, including flare of dermatitis, worsening of eczema, and folliculitis, were reported by the patients who received the combination and the topical steroid–only patients. One study reported similar rates of antibiotic resistance in children treated with steroid only and with an antibiotic/steroid combination at 3 months’ follow-up.

In four studies, oral antibiotics “may make no difference in terms of good or excellent global improvement in infants and children at 14 to 28 days follow-up compared to placebo,” according to the review. The reviewers said that there was likely little or no difference in quality of life for infants and children given oral antibiotics, although they noted the low quality of evidence on this topic.

Five studies evaluated the impact of bleach baths on eczema patients with and without S. aureus infections. These studies showed no difference in global improvement measures compared with placebo and little or no difference in quality of life. Also, patients who underwent bleach baths compared with placebo patients reported similar adverse events of burning/stinging or dry skin at 2 months’ follow-up.

“Low-quality evidence, due to risk of bias, imprecise effect estimates, and heterogeneity, made pooling of results difficult,” Dr. Banerjee wrote. “Topical steroid/antibiotic combinations may be associated with possible small improvements in good or excellent signs/symptoms compared with topical steroid alone. High-quality trials evaluating efficacy, QOL, and antibiotic resistance are required,” she concluded.

In a commentary section after the review, Dr. Banerjee and colleagues noted that the United Kingdom’s NICE guidelines for managing atopic eczema in children younger than 12 years of age, published in March 2021, include evidence from the current updated Cochrane Review. The NICE guidelines emphasize that “in people who are not systemically unwell, clinicians should not routinely offer either a topical or oral antibiotic for secondary bacterial infection of eczema,” the Cochrane authors said. They added in their commentary that the use of antibiotics in cases of nonsevere infections can worsen eczema. Also, “the risk of antimicrobial resistance is high with topical antibiotics, and therefore extended doses of the same antibiotics should be avoided to prevent resistance,” they said. However, the authors acknowledged a role for antibiotics in certain situations. “In patients with systemic signs of infection such as cellulitis, systemic antibiotics have an important role in helping clear infection,” they noted.

Reasons for varying disease severity elude research

The current study is important because of the abundance of preclinical and clinical data that implicate S. aureus in atopic dermatitis pathogenesis, Brian Kim, MD, of the Icahn School of Medicine at Mount Sinai, New York, said in an interview.

Dr. Kim said that he was surprised by some of the study findings but not others. “On the one hand, I thought there would be data supporting antimicrobial therapy, albeit not strong support,” he said. “However, AD is a very complex disease, and understanding what a disease modifier does to it is hard to capture across studies of various different designs,” he said.

“The data supporting antimicrobial therapy for S. aureus in AD is not as clear as our clinical impressions may indicate,” said Dr. Kim. “We need to understand the relationship better, perhaps in particular subsets of patients,” he emphasized. In addition, “We need a better understanding of why some people are colonized with S. aureus, yet with little effect on AD itself, while others experience severe exacerbation of disease,” said Dr. Kim. Therefore, a key research question for future studies is whether the exacerbation is caused by the particular strain of the bug, the host susceptibility, or both, he said.

The review received no outside funding. Dr. Banerjee and Dr. Kim have disclosed that they had no relevant financial relationships.

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

Current interventions to tackle Staphylococcus aureus in patients with atopic eczema have little impact on symptoms, based on data from a Cochrane Review of 41 studies published in Clinical and Experimental Allergy.

Eczema remains a huge disease burden worldwide, and colonization with S. aureus in eczema patients is common, but no standard intervention exists to relieve symptoms, wrote Nandini Banerjee, MD, of Addenbrooke’s Hospital, Cambridge, England. “While antibiotic treatment of clinically obvious infections such as cellulitis is beneficial, it is not clear whether antibiotic treatment of eczema influences eczema severity,” Dr. Banerjee noted.

The 41 studies included 1,753 participants and 10 treatment categories. Most of the studies were conducted in secondary care centers in Western Europe, North America, and the Far East. Twelve studies included children, four included only adults, 19 included children and adults, and in six studies, the participant age range was unclear. Among the studies with reported ages, the mean age ranged from 1.1 to 34.6 years. Eczema severity ranged from mild to severe, and treatment durations ranged from 10 minutes to 3 months.

The review presented comparisons of topical steroid/antibiotic combinations, oral antibiotics, and bleach baths. In 14 studies that compared topical steroid/antibiotic combinations to topical steroids alone, patients showed slightly greater global improvement in symptoms with the combination, but the impact on quality of life was not significantly different. Severe adverse events, including flare of dermatitis, worsening of eczema, and folliculitis, were reported by the patients who received the combination and the topical steroid–only patients. One study reported similar rates of antibiotic resistance in children treated with steroid only and with an antibiotic/steroid combination at 3 months’ follow-up.

In four studies, oral antibiotics “may make no difference in terms of good or excellent global improvement in infants and children at 14 to 28 days follow-up compared to placebo,” according to the review. The reviewers said that there was likely little or no difference in quality of life for infants and children given oral antibiotics, although they noted the low quality of evidence on this topic.

Five studies evaluated the impact of bleach baths on eczema patients with and without S. aureus infections. These studies showed no difference in global improvement measures compared with placebo and little or no difference in quality of life. Also, patients who underwent bleach baths compared with placebo patients reported similar adverse events of burning/stinging or dry skin at 2 months’ follow-up.

“Low-quality evidence, due to risk of bias, imprecise effect estimates, and heterogeneity, made pooling of results difficult,” Dr. Banerjee wrote. “Topical steroid/antibiotic combinations may be associated with possible small improvements in good or excellent signs/symptoms compared with topical steroid alone. High-quality trials evaluating efficacy, QOL, and antibiotic resistance are required,” she concluded.

In a commentary section after the review, Dr. Banerjee and colleagues noted that the United Kingdom’s NICE guidelines for managing atopic eczema in children younger than 12 years of age, published in March 2021, include evidence from the current updated Cochrane Review. The NICE guidelines emphasize that “in people who are not systemically unwell, clinicians should not routinely offer either a topical or oral antibiotic for secondary bacterial infection of eczema,” the Cochrane authors said. They added in their commentary that the use of antibiotics in cases of nonsevere infections can worsen eczema. Also, “the risk of antimicrobial resistance is high with topical antibiotics, and therefore extended doses of the same antibiotics should be avoided to prevent resistance,” they said. However, the authors acknowledged a role for antibiotics in certain situations. “In patients with systemic signs of infection such as cellulitis, systemic antibiotics have an important role in helping clear infection,” they noted.

Reasons for varying disease severity elude research

The current study is important because of the abundance of preclinical and clinical data that implicate S. aureus in atopic dermatitis pathogenesis, Brian Kim, MD, of the Icahn School of Medicine at Mount Sinai, New York, said in an interview.

Dr. Kim said that he was surprised by some of the study findings but not others. “On the one hand, I thought there would be data supporting antimicrobial therapy, albeit not strong support,” he said. “However, AD is a very complex disease, and understanding what a disease modifier does to it is hard to capture across studies of various different designs,” he said.

“The data supporting antimicrobial therapy for S. aureus in AD is not as clear as our clinical impressions may indicate,” said Dr. Kim. “We need to understand the relationship better, perhaps in particular subsets of patients,” he emphasized. In addition, “We need a better understanding of why some people are colonized with S. aureus, yet with little effect on AD itself, while others experience severe exacerbation of disease,” said Dr. Kim. Therefore, a key research question for future studies is whether the exacerbation is caused by the particular strain of the bug, the host susceptibility, or both, he said.

The review received no outside funding. Dr. Banerjee and Dr. Kim have disclosed that they had no relevant financial relationships.

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

Current interventions to tackle Staphylococcus aureus in patients with atopic eczema have little impact on symptoms, based on data from a Cochrane Review of 41 studies published in Clinical and Experimental Allergy.

Eczema remains a huge disease burden worldwide, and colonization with S. aureus in eczema patients is common, but no standard intervention exists to relieve symptoms, wrote Nandini Banerjee, MD, of Addenbrooke’s Hospital, Cambridge, England. “While antibiotic treatment of clinically obvious infections such as cellulitis is beneficial, it is not clear whether antibiotic treatment of eczema influences eczema severity,” Dr. Banerjee noted.

The 41 studies included 1,753 participants and 10 treatment categories. Most of the studies were conducted in secondary care centers in Western Europe, North America, and the Far East. Twelve studies included children, four included only adults, 19 included children and adults, and in six studies, the participant age range was unclear. Among the studies with reported ages, the mean age ranged from 1.1 to 34.6 years. Eczema severity ranged from mild to severe, and treatment durations ranged from 10 minutes to 3 months.

The review presented comparisons of topical steroid/antibiotic combinations, oral antibiotics, and bleach baths. In 14 studies that compared topical steroid/antibiotic combinations to topical steroids alone, patients showed slightly greater global improvement in symptoms with the combination, but the impact on quality of life was not significantly different. Severe adverse events, including flare of dermatitis, worsening of eczema, and folliculitis, were reported by the patients who received the combination and the topical steroid–only patients. One study reported similar rates of antibiotic resistance in children treated with steroid only and with an antibiotic/steroid combination at 3 months’ follow-up.

In four studies, oral antibiotics “may make no difference in terms of good or excellent global improvement in infants and children at 14 to 28 days follow-up compared to placebo,” according to the review. The reviewers said that there was likely little or no difference in quality of life for infants and children given oral antibiotics, although they noted the low quality of evidence on this topic.

Five studies evaluated the impact of bleach baths on eczema patients with and without S. aureus infections. These studies showed no difference in global improvement measures compared with placebo and little or no difference in quality of life. Also, patients who underwent bleach baths compared with placebo patients reported similar adverse events of burning/stinging or dry skin at 2 months’ follow-up.

“Low-quality evidence, due to risk of bias, imprecise effect estimates, and heterogeneity, made pooling of results difficult,” Dr. Banerjee wrote. “Topical steroid/antibiotic combinations may be associated with possible small improvements in good or excellent signs/symptoms compared with topical steroid alone. High-quality trials evaluating efficacy, QOL, and antibiotic resistance are required,” she concluded.

In a commentary section after the review, Dr. Banerjee and colleagues noted that the United Kingdom’s NICE guidelines for managing atopic eczema in children younger than 12 years of age, published in March 2021, include evidence from the current updated Cochrane Review. The NICE guidelines emphasize that “in people who are not systemically unwell, clinicians should not routinely offer either a topical or oral antibiotic for secondary bacterial infection of eczema,” the Cochrane authors said. They added in their commentary that the use of antibiotics in cases of nonsevere infections can worsen eczema. Also, “the risk of antimicrobial resistance is high with topical antibiotics, and therefore extended doses of the same antibiotics should be avoided to prevent resistance,” they said. However, the authors acknowledged a role for antibiotics in certain situations. “In patients with systemic signs of infection such as cellulitis, systemic antibiotics have an important role in helping clear infection,” they noted.

Reasons for varying disease severity elude research

The current study is important because of the abundance of preclinical and clinical data that implicate S. aureus in atopic dermatitis pathogenesis, Brian Kim, MD, of the Icahn School of Medicine at Mount Sinai, New York, said in an interview.

Dr. Kim said that he was surprised by some of the study findings but not others. “On the one hand, I thought there would be data supporting antimicrobial therapy, albeit not strong support,” he said. “However, AD is a very complex disease, and understanding what a disease modifier does to it is hard to capture across studies of various different designs,” he said.

“The data supporting antimicrobial therapy for S. aureus in AD is not as clear as our clinical impressions may indicate,” said Dr. Kim. “We need to understand the relationship better, perhaps in particular subsets of patients,” he emphasized. In addition, “We need a better understanding of why some people are colonized with S. aureus, yet with little effect on AD itself, while others experience severe exacerbation of disease,” said Dr. Kim. Therefore, a key research question for future studies is whether the exacerbation is caused by the particular strain of the bug, the host susceptibility, or both, he said.

The review received no outside funding. Dr. Banerjee and Dr. Kim have disclosed that they had no relevant financial relationships.

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

With the Omicron variant now accounting for almost 100% of COVID-19 cases in the United States, the 7-day average of daily COVID-related deaths hit 2,600 recently, the highest rate in about a year, the Washington Post reported.

That’s higher than the approximately 2,000 daily deaths in fall 2021 during the Delta surge, but less than the 3,000 daily deaths in January 2021, when COVID vaccines were not widely available, the Post’s data analysis said.

The Omicron variant generally causes less severe disease than other strains of COVID, but because it is so transmissible, Omicron is infecting higher raw numbers of people that previous strains.

“Even if on a per-case basis fewer people develop severe illness and die, when you apply a small percentage to a very large number, you get a substantial number,” Jennifer Nuzzo, DrPH, an epidemiologist at the Johns Hopkins University, Baltimore, told the Post.

The unvaccinated, people over 75, and people with underlying medical conditions are the groups most endangered by Omicron, the Post said. About half of the deaths in January 2022 were among people over 75, compared with about a third in September 2021 during the Delta surge.

The age trend is seen in Florida, said Jason Salemi, PhD, an epidemiologist at the University of South Florida, Tampa. He told the Post that seniors accounted for about 85% of deaths in the winter of 2020-2021, about 60% during the Delta surge, and about 80% now during the Omicron surge.

The uptick in senior deaths may have occurred because seniors who got vaccinated in early 2021 didn’t get boosted ahead of the Omicron surge, he said.

“Omicron may be less severe for younger people, but it will still find vulnerable seniors in our community,” Dr. Salemi said. “That vaccination back in February isn’t as effective now if you aren’t boosted.”

CDC data shows that 95% of people in the United States over 65 have gotten at least one dose of vaccine, 88.5% are fully vaccinated, but only 62.5% have gotten a booster dose.

The COVID death rate is highest in the Midwest. During the last 2 months, Chicago reported more than 1,000 COVID deaths, almost as much as the December 2020 peak, The Post said. Minorities have been hit hard. About third of the city’s population is Black but about half the COVID victims are Black, the Post said.

“It’s been challenging because it goes up against the national narrative that omicron is nothing dangerous,” said Allison Arwady, commissioner of the Chicago Department of Public Health.

In a Feb. 9 news briefing at the White House, CDC Director Rochelle Walensky, MD, provided slightly different statistics on COVID-related deaths. She said that the 7-day average of daily deaths was about 2,400, up 3% from the previous week.

The 7-day daily average of cases is about 247,300 cases per day, down 44% from the previous week, she said. Hospital admissions are about 13,000 daily, down 25% from the previous week.

Dr. Walensky said the Omicron variant now accounts for almost 100% of COVID viruses circulating in the United States.

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

With the Omicron variant now accounting for almost 100% of COVID-19 cases in the United States, the 7-day average of daily COVID-related deaths hit 2,600 recently, the highest rate in about a year, the Washington Post reported.

That’s higher than the approximately 2,000 daily deaths in fall 2021 during the Delta surge, but less than the 3,000 daily deaths in January 2021, when COVID vaccines were not widely available, the Post’s data analysis said.

The Omicron variant generally causes less severe disease than other strains of COVID, but because it is so transmissible, Omicron is infecting higher raw numbers of people that previous strains.

“Even if on a per-case basis fewer people develop severe illness and die, when you apply a small percentage to a very large number, you get a substantial number,” Jennifer Nuzzo, DrPH, an epidemiologist at the Johns Hopkins University, Baltimore, told the Post.

The unvaccinated, people over 75, and people with underlying medical conditions are the groups most endangered by Omicron, the Post said. About half of the deaths in January 2022 were among people over 75, compared with about a third in September 2021 during the Delta surge.

The age trend is seen in Florida, said Jason Salemi, PhD, an epidemiologist at the University of South Florida, Tampa. He told the Post that seniors accounted for about 85% of deaths in the winter of 2020-2021, about 60% during the Delta surge, and about 80% now during the Omicron surge.

The uptick in senior deaths may have occurred because seniors who got vaccinated in early 2021 didn’t get boosted ahead of the Omicron surge, he said.

“Omicron may be less severe for younger people, but it will still find vulnerable seniors in our community,” Dr. Salemi said. “That vaccination back in February isn’t as effective now if you aren’t boosted.”

CDC data shows that 95% of people in the United States over 65 have gotten at least one dose of vaccine, 88.5% are fully vaccinated, but only 62.5% have gotten a booster dose.

The COVID death rate is highest in the Midwest. During the last 2 months, Chicago reported more than 1,000 COVID deaths, almost as much as the December 2020 peak, The Post said. Minorities have been hit hard. About third of the city’s population is Black but about half the COVID victims are Black, the Post said.

“It’s been challenging because it goes up against the national narrative that omicron is nothing dangerous,” said Allison Arwady, commissioner of the Chicago Department of Public Health.

In a Feb. 9 news briefing at the White House, CDC Director Rochelle Walensky, MD, provided slightly different statistics on COVID-related deaths. She said that the 7-day average of daily deaths was about 2,400, up 3% from the previous week.

The 7-day daily average of cases is about 247,300 cases per day, down 44% from the previous week, she said. Hospital admissions are about 13,000 daily, down 25% from the previous week.

Dr. Walensky said the Omicron variant now accounts for almost 100% of COVID viruses circulating in the United States.

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

With the Omicron variant now accounting for almost 100% of COVID-19 cases in the United States, the 7-day average of daily COVID-related deaths hit 2,600 recently, the highest rate in about a year, the Washington Post reported.

That’s higher than the approximately 2,000 daily deaths in fall 2021 during the Delta surge, but less than the 3,000 daily deaths in January 2021, when COVID vaccines were not widely available, the Post’s data analysis said.

The Omicron variant generally causes less severe disease than other strains of COVID, but because it is so transmissible, Omicron is infecting higher raw numbers of people that previous strains.

“Even if on a per-case basis fewer people develop severe illness and die, when you apply a small percentage to a very large number, you get a substantial number,” Jennifer Nuzzo, DrPH, an epidemiologist at the Johns Hopkins University, Baltimore, told the Post.

The unvaccinated, people over 75, and people with underlying medical conditions are the groups most endangered by Omicron, the Post said. About half of the deaths in January 2022 were among people over 75, compared with about a third in September 2021 during the Delta surge.

The age trend is seen in Florida, said Jason Salemi, PhD, an epidemiologist at the University of South Florida, Tampa. He told the Post that seniors accounted for about 85% of deaths in the winter of 2020-2021, about 60% during the Delta surge, and about 80% now during the Omicron surge.

The uptick in senior deaths may have occurred because seniors who got vaccinated in early 2021 didn’t get boosted ahead of the Omicron surge, he said.

“Omicron may be less severe for younger people, but it will still find vulnerable seniors in our community,” Dr. Salemi said. “That vaccination back in February isn’t as effective now if you aren’t boosted.”

CDC data shows that 95% of people in the United States over 65 have gotten at least one dose of vaccine, 88.5% are fully vaccinated, but only 62.5% have gotten a booster dose.

The COVID death rate is highest in the Midwest. During the last 2 months, Chicago reported more than 1,000 COVID deaths, almost as much as the December 2020 peak, The Post said. Minorities have been hit hard. About third of the city’s population is Black but about half the COVID victims are Black, the Post said.

“It’s been challenging because it goes up against the national narrative that omicron is nothing dangerous,” said Allison Arwady, commissioner of the Chicago Department of Public Health.

In a Feb. 9 news briefing at the White House, CDC Director Rochelle Walensky, MD, provided slightly different statistics on COVID-related deaths. She said that the 7-day average of daily deaths was about 2,400, up 3% from the previous week.

The 7-day daily average of cases is about 247,300 cases per day, down 44% from the previous week, she said. Hospital admissions are about 13,000 daily, down 25% from the previous week.

Dr. Walensky said the Omicron variant now accounts for almost 100% of COVID viruses circulating in the United States.

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

Recent evidence has shown that women who contract COVID-19 during pregnancy are at increased risk for pregnancy loss and neonatal death. Now, an analysis of pathology data from dozens of perinatal deaths shows how.

Unlike numerous pathogens that kill the fetus by infecting it directly, SARS-CoV-2 causes “widespread and severe” destruction of the placenta that deprives the fetus of oxygen, a team of 44 researchers in 12 countries concluded after examining 64 stillbirths and four neonatal deaths in which the placentas were infected with the virus. They noted that such damage occurs in a small percentage of pregnant women with COVID and that all the women in the study had not been vaccinated against the disease.

The findings were published online Feb. 10 in the Archives of Pathology & Laboratory Medicine.

Nearly all placentas had each of three features that pathologists have dubbed SARS-CoV-2 placentitis: large deposits of fibrin, a clotting protein that obstructs the flow of blood, death of cells in the trophoblast, and an unusual form of inflammation called chronic histiocytic intervillositis. Some had other abnormalities that could have exacerbated the condition.

The researchers called the extent of damage “striking,” affecting 77.7% of the placenta on average. The virus did not appear to harm fetal tissue, but placental damage “was extensive and highly destructive,” they write. Notably, none of the women in the analysis were known to have severe COVID.
 

Virus seen ‘chewing up the placenta’

David Schwartz, MD, a pathologist in Atlanta, and the lead author of the study, said COVID appears to be unique in destroying the placenta.

“I don’t know of any infection that does that to this degree or with this uniformity,” Dr. Schwartz told this news organization. “The simple message is that this infection is chewing up the placenta and destroying its capability to oxygenate the fetus.”

In November, the Centers for Disease Control and Prevention reported that maternal COVID increases the risk of losing a pregnancy. From March 2020 to September 2021, 8,154 stillbirths were reported, affecting 0.65% of births by women without COVID and 1.26% of births by women with COVID, for a relative risk of 1.90 (95% confidence interval, 1.69-2.15).

Delta, the variant that dominated in mid-2021, appears to have been particularly harmful. The CDC reported that the relative risk for stillbirth for mothers with COVID-19 during that period increased to 4.04 (95% CI, 3.28-4.97). Many cases in the new analysis coincided with Delta.

Dr. Schwartz and his colleagues said immunization, along with antiviral therapy, might reduce the chance of SARS-CoV-2 infecting the placenta. None of the mothers in the analysis was vaccinated, and Dr. Schwartz said he is not aware of a single case in a vaccinated woman.

The analysis comes on the heels of a study from the National Institutes of Health linking severe to moderate COVID infection to greater risk of other pregnancy complications: cesarean and preterm delivery, death during childbirth, postpartum hemorrhaging, and non-COVID infections.

Diana Bianchi, MD, director of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development, said those findings underscore the need for pregnant women to be vaccinated. (The shots have been shown to be safe for pregnant women.)

Denise Jamieson, MD, MPH, chair of the department of gynecology and obstetrics at Emory University, Atlanta, who was not involved in the new analysis, said the findings may have important clinical implications. In addition to ensuring that pregnant patients are fully vaccinated, she said “there may be opportunities to more closely monitor the placenta during pregnancy using imaging modalities such as ultrasound.”

Even in the presence of severe abnormalities, a fetus that has reached a viable gestational age could potentially be delivered prior to stillbirth, Dr. Jamieson said. The 64 stillbirths in the analysis ranged from 15 to 39.2 weeks of gestation, with an average of 30 weeks. Eight were delivered at full term.

However, additional studies are needed to support monitoring of placental changes, she said: “It is not ready for prime time now.”

Christopher Zahn, MD, vice president of practice activities the American College of Obstetricians and Gynecologists, cautioned that data on COVID and pregnancy complications remain limited.

The findings in this analysis “do not prove the association between COVID-19 infection and neonatal outcomes,” Dr. Zahn said. “While stillbirth could potentially be another adverse outcome for pregnant people who contract COVID-19, currently we don’t have enough data to confirm that a COVID-19 infection at any point in pregnancy indicates increased risk of stillbirth.”

He added that ACOG continues to strongly recommend vaccination against COVID for women who are pregnant, recently pregnant, or planning to be pregnant.

Dr. Schwartz and Dr. Jamieson have disclosed no relevant financial relationships. One author reported receiving financial support from the Slovak Research and Development Agency. Another reported funding from the Belgian Fund for Scientific Research and the Fetus for Life charity.

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

Recent evidence has shown that women who contract COVID-19 during pregnancy are at increased risk for pregnancy loss and neonatal death. Now, an analysis of pathology data from dozens of perinatal deaths shows how.

Unlike numerous pathogens that kill the fetus by infecting it directly, SARS-CoV-2 causes “widespread and severe” destruction of the placenta that deprives the fetus of oxygen, a team of 44 researchers in 12 countries concluded after examining 64 stillbirths and four neonatal deaths in which the placentas were infected with the virus. They noted that such damage occurs in a small percentage of pregnant women with COVID and that all the women in the study had not been vaccinated against the disease.

The findings were published online Feb. 10 in the Archives of Pathology & Laboratory Medicine.

Nearly all placentas had each of three features that pathologists have dubbed SARS-CoV-2 placentitis: large deposits of fibrin, a clotting protein that obstructs the flow of blood, death of cells in the trophoblast, and an unusual form of inflammation called chronic histiocytic intervillositis. Some had other abnormalities that could have exacerbated the condition.

The researchers called the extent of damage “striking,” affecting 77.7% of the placenta on average. The virus did not appear to harm fetal tissue, but placental damage “was extensive and highly destructive,” they write. Notably, none of the women in the analysis were known to have severe COVID.
 

Virus seen ‘chewing up the placenta’

David Schwartz, MD, a pathologist in Atlanta, and the lead author of the study, said COVID appears to be unique in destroying the placenta.

“I don’t know of any infection that does that to this degree or with this uniformity,” Dr. Schwartz told this news organization. “The simple message is that this infection is chewing up the placenta and destroying its capability to oxygenate the fetus.”

In November, the Centers for Disease Control and Prevention reported that maternal COVID increases the risk of losing a pregnancy. From March 2020 to September 2021, 8,154 stillbirths were reported, affecting 0.65% of births by women without COVID and 1.26% of births by women with COVID, for a relative risk of 1.90 (95% confidence interval, 1.69-2.15).

Delta, the variant that dominated in mid-2021, appears to have been particularly harmful. The CDC reported that the relative risk for stillbirth for mothers with COVID-19 during that period increased to 4.04 (95% CI, 3.28-4.97). Many cases in the new analysis coincided with Delta.

Dr. Schwartz and his colleagues said immunization, along with antiviral therapy, might reduce the chance of SARS-CoV-2 infecting the placenta. None of the mothers in the analysis was vaccinated, and Dr. Schwartz said he is not aware of a single case in a vaccinated woman.

The analysis comes on the heels of a study from the National Institutes of Health linking severe to moderate COVID infection to greater risk of other pregnancy complications: cesarean and preterm delivery, death during childbirth, postpartum hemorrhaging, and non-COVID infections.

Diana Bianchi, MD, director of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development, said those findings underscore the need for pregnant women to be vaccinated. (The shots have been shown to be safe for pregnant women.)

Denise Jamieson, MD, MPH, chair of the department of gynecology and obstetrics at Emory University, Atlanta, who was not involved in the new analysis, said the findings may have important clinical implications. In addition to ensuring that pregnant patients are fully vaccinated, she said “there may be opportunities to more closely monitor the placenta during pregnancy using imaging modalities such as ultrasound.”

Even in the presence of severe abnormalities, a fetus that has reached a viable gestational age could potentially be delivered prior to stillbirth, Dr. Jamieson said. The 64 stillbirths in the analysis ranged from 15 to 39.2 weeks of gestation, with an average of 30 weeks. Eight were delivered at full term.

However, additional studies are needed to support monitoring of placental changes, she said: “It is not ready for prime time now.”

Christopher Zahn, MD, vice president of practice activities the American College of Obstetricians and Gynecologists, cautioned that data on COVID and pregnancy complications remain limited.

The findings in this analysis “do not prove the association between COVID-19 infection and neonatal outcomes,” Dr. Zahn said. “While stillbirth could potentially be another adverse outcome for pregnant people who contract COVID-19, currently we don’t have enough data to confirm that a COVID-19 infection at any point in pregnancy indicates increased risk of stillbirth.”

He added that ACOG continues to strongly recommend vaccination against COVID for women who are pregnant, recently pregnant, or planning to be pregnant.

Dr. Schwartz and Dr. Jamieson have disclosed no relevant financial relationships. One author reported receiving financial support from the Slovak Research and Development Agency. Another reported funding from the Belgian Fund for Scientific Research and the Fetus for Life charity.

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

Recent evidence has shown that women who contract COVID-19 during pregnancy are at increased risk for pregnancy loss and neonatal death. Now, an analysis of pathology data from dozens of perinatal deaths shows how.

Unlike numerous pathogens that kill the fetus by infecting it directly, SARS-CoV-2 causes “widespread and severe” destruction of the placenta that deprives the fetus of oxygen, a team of 44 researchers in 12 countries concluded after examining 64 stillbirths and four neonatal deaths in which the placentas were infected with the virus. They noted that such damage occurs in a small percentage of pregnant women with COVID and that all the women in the study had not been vaccinated against the disease.

The findings were published online Feb. 10 in the Archives of Pathology & Laboratory Medicine.

Nearly all placentas had each of three features that pathologists have dubbed SARS-CoV-2 placentitis: large deposits of fibrin, a clotting protein that obstructs the flow of blood, death of cells in the trophoblast, and an unusual form of inflammation called chronic histiocytic intervillositis. Some had other abnormalities that could have exacerbated the condition.

The researchers called the extent of damage “striking,” affecting 77.7% of the placenta on average. The virus did not appear to harm fetal tissue, but placental damage “was extensive and highly destructive,” they write. Notably, none of the women in the analysis were known to have severe COVID.
 

Virus seen ‘chewing up the placenta’

David Schwartz, MD, a pathologist in Atlanta, and the lead author of the study, said COVID appears to be unique in destroying the placenta.

“I don’t know of any infection that does that to this degree or with this uniformity,” Dr. Schwartz told this news organization. “The simple message is that this infection is chewing up the placenta and destroying its capability to oxygenate the fetus.”

In November, the Centers for Disease Control and Prevention reported that maternal COVID increases the risk of losing a pregnancy. From March 2020 to September 2021, 8,154 stillbirths were reported, affecting 0.65% of births by women without COVID and 1.26% of births by women with COVID, for a relative risk of 1.90 (95% confidence interval, 1.69-2.15).

Delta, the variant that dominated in mid-2021, appears to have been particularly harmful. The CDC reported that the relative risk for stillbirth for mothers with COVID-19 during that period increased to 4.04 (95% CI, 3.28-4.97). Many cases in the new analysis coincided with Delta.

Dr. Schwartz and his colleagues said immunization, along with antiviral therapy, might reduce the chance of SARS-CoV-2 infecting the placenta. None of the mothers in the analysis was vaccinated, and Dr. Schwartz said he is not aware of a single case in a vaccinated woman.

The analysis comes on the heels of a study from the National Institutes of Health linking severe to moderate COVID infection to greater risk of other pregnancy complications: cesarean and preterm delivery, death during childbirth, postpartum hemorrhaging, and non-COVID infections.

Diana Bianchi, MD, director of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development, said those findings underscore the need for pregnant women to be vaccinated. (The shots have been shown to be safe for pregnant women.)

Denise Jamieson, MD, MPH, chair of the department of gynecology and obstetrics at Emory University, Atlanta, who was not involved in the new analysis, said the findings may have important clinical implications. In addition to ensuring that pregnant patients are fully vaccinated, she said “there may be opportunities to more closely monitor the placenta during pregnancy using imaging modalities such as ultrasound.”

Even in the presence of severe abnormalities, a fetus that has reached a viable gestational age could potentially be delivered prior to stillbirth, Dr. Jamieson said. The 64 stillbirths in the analysis ranged from 15 to 39.2 weeks of gestation, with an average of 30 weeks. Eight were delivered at full term.

However, additional studies are needed to support monitoring of placental changes, she said: “It is not ready for prime time now.”

Christopher Zahn, MD, vice president of practice activities the American College of Obstetricians and Gynecologists, cautioned that data on COVID and pregnancy complications remain limited.

The findings in this analysis “do not prove the association between COVID-19 infection and neonatal outcomes,” Dr. Zahn said. “While stillbirth could potentially be another adverse outcome for pregnant people who contract COVID-19, currently we don’t have enough data to confirm that a COVID-19 infection at any point in pregnancy indicates increased risk of stillbirth.”

He added that ACOG continues to strongly recommend vaccination against COVID for women who are pregnant, recently pregnant, or planning to be pregnant.

Dr. Schwartz and Dr. Jamieson have disclosed no relevant financial relationships. One author reported receiving financial support from the Slovak Research and Development Agency. Another reported funding from the Belgian Fund for Scientific Research and the Fetus for Life charity.

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