Functional abdominal pain in childhood and adolescence is extremely stressful for patients and a therapeutic challenge for the physicians treating them. A meta-analysis of 33 randomized-controlled studies published in JAMA Pediatrics shows that cognitive-behavioral therapy or hypnotherapy promises the greatest therapy success.

“If children or adolescents complain about chronic abdominal pain and a detailed diagnostic does not reveal any somatic cause, this is referred to as functional abdominal pain,” Burkhard Rodeck, MD, general secretary of the German Society of Pediatrics and Adolescent Medicine in Berlin, told this news organization.
 

Signal perception disorder

It is still not completely clear what causes functional abdominal pain. But it is assumed to be a disruption in the communication between the gastrointestinal tract and the brain. “These patients are experiencing a signal perception disorder: normal body signals, such as a slight stomach rumble, are assigned to the pain category for them much more quickly than for other people,” said Dr. Rodeck. “The meta-analysis provides confirmation of this – functional abdominal pain is actually a biopsychosocial matter.”

In the standard therapy of functional abdominal pain, however, it is also possible to choose a medicinal approach. “Studies show that herbal preparations such as peppermint oil capsules have some efficacy, since they attenuate the strength of the signals being sent from the gastrointestinal tract to the brain, with the result that they are not perceived so quickly as pain. Probiotics can also potentially help,” added Dr. Rodeck.

“If this is unsuccessful, the child must be offered a psychologic/psychotherapeutic measure, usually cognitive-behavioral therapy.”
 

Comparison of psychosocial therapies

The meta-analysis was carried out by a research team at the University of Central Lancashire, Preston, United Kingdom. It included 2,657 children and adolescents between the ages of 7 and 17 years, of which two-thirds were girls.

Various psychosocial therapy approaches for functional abdominal pain, such as cognitive-behavioral therapy, educational assistance, hypnotherapy (directed at the digestive system), guided meditation with relaxation, yoga, or (visceral) osteopathy were investigated and compared in the studies – sometimes against each other and sometimes against no intervention.

Lead author Morris Gordon, MBChB, PhD, professor of evidence synthesis and systematic review at the University of Central Lancashire, and his colleagues reported that cognitive-behavioral therapy was 2.37-times more likely to result in therapy success than no intervention. To treat functional abdominal pain successfully in one child or adolescent, five children needed to be treated with cognitive-behavioral therapy.
 

Rarer, milder pain

The children and adolescents treated with cognitive-behavioral therapy also experienced less frequent and less severe abdominal pain than the children and adolescents who did not receive any intervention. The rate of side effect–related therapy discontinuations did not differ between the groups.

Hypnotherapy could also be associated with an improved outcome, compared with no intervention, added Dr. Gordon and his colleagues. Hypnotherapy was 2.86-times more likely to result in therapy success, and the number needed to treat was five.

The other therapeutic approaches investigated did not perform any better in the studies than no intervention. However, the authors noted that evidence of the effectiveness of cognitive-behavioral therapy and hypnotherapy is moderate or weak, especially owing to the high bias risk.

“The therapy for functional abdominal pain cannot be compared with the therapy for scarlet fever, for example, where penicillin is administered in the knowledge that recovery is guaranteed. There is evidence that cognitive-behavioral therapy and possibly also hypnotherapy may help, but this is not true for every patient,” said Dr. Rodeck.
 

Start with the pediatrician

Dr. Gordon and his co-authors suggested considering cognitive-behavioral therapy and hypnotherapy for the treatment of functional abdominal pain in children and adolescents. But they added that further randomized controlled studies are necessary to improve the quality of evidence and therefore the reliability of these results.

Children and adolescents with functional abdominal pain do not need to be sent directly to the psychologist for treatment, said Dr. Rodeck. The pediatric or adolescent medicine specialist can also administer the initial behavioral therapy measures. “Some patients manage with the behavioral therapy approaches we offer as pediatric and adolescent medicine specialists; others require professional support with psychologic expertise,” said Dr. Rodeck. Should outpatient treatment be unsuccessful, inpatient therapy in special psychosomatic clinics or wards remains an option.
 

Education offers relief

For many patients, being informed about the connections and mechanisms that play a role in functional abdominal pain can offer a lot of relief, said Dr. Rodeck. Offering coping strategies that can be used in the event of acute symptoms is also a part of this education.

“If patients have functional abdominal pain for which no organic cause can be found, this can lead to frustration, sadness, and despair. The problem can become even worse if they feel that they are not being taken seriously by the physician,” said Dr. Rodeck. These negative experiences can further exacerbate the pain perception disorder. The aim of behavioral therapy measures is therefore to interrupt and downregulate this vicious cycle.

“Constant investigations are not always helpful for patients with functional abdominal pain. Time must be taken with these patients to talk and explore the options. They have definite abdominal pain, they are not imagining it. They must be taken seriously,” he emphasized.

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

Functional abdominal pain in childhood and adolescence is extremely stressful for patients and a therapeutic challenge for the physicians treating them. A meta-analysis of 33 randomized-controlled studies published in JAMA Pediatrics shows that cognitive-behavioral therapy or hypnotherapy promises the greatest therapy success.

“If children or adolescents complain about chronic abdominal pain and a detailed diagnostic does not reveal any somatic cause, this is referred to as functional abdominal pain,” Burkhard Rodeck, MD, general secretary of the German Society of Pediatrics and Adolescent Medicine in Berlin, told this news organization.
 

Signal perception disorder

It is still not completely clear what causes functional abdominal pain. But it is assumed to be a disruption in the communication between the gastrointestinal tract and the brain. “These patients are experiencing a signal perception disorder: normal body signals, such as a slight stomach rumble, are assigned to the pain category for them much more quickly than for other people,” said Dr. Rodeck. “The meta-analysis provides confirmation of this – functional abdominal pain is actually a biopsychosocial matter.”

In the standard therapy of functional abdominal pain, however, it is also possible to choose a medicinal approach. “Studies show that herbal preparations such as peppermint oil capsules have some efficacy, since they attenuate the strength of the signals being sent from the gastrointestinal tract to the brain, with the result that they are not perceived so quickly as pain. Probiotics can also potentially help,” added Dr. Rodeck.

“If this is unsuccessful, the child must be offered a psychologic/psychotherapeutic measure, usually cognitive-behavioral therapy.”
 

Comparison of psychosocial therapies

The meta-analysis was carried out by a research team at the University of Central Lancashire, Preston, United Kingdom. It included 2,657 children and adolescents between the ages of 7 and 17 years, of which two-thirds were girls.

Various psychosocial therapy approaches for functional abdominal pain, such as cognitive-behavioral therapy, educational assistance, hypnotherapy (directed at the digestive system), guided meditation with relaxation, yoga, or (visceral) osteopathy were investigated and compared in the studies – sometimes against each other and sometimes against no intervention.

Lead author Morris Gordon, MBChB, PhD, professor of evidence synthesis and systematic review at the University of Central Lancashire, and his colleagues reported that cognitive-behavioral therapy was 2.37-times more likely to result in therapy success than no intervention. To treat functional abdominal pain successfully in one child or adolescent, five children needed to be treated with cognitive-behavioral therapy.
 

Rarer, milder pain

The children and adolescents treated with cognitive-behavioral therapy also experienced less frequent and less severe abdominal pain than the children and adolescents who did not receive any intervention. The rate of side effect–related therapy discontinuations did not differ between the groups.

Hypnotherapy could also be associated with an improved outcome, compared with no intervention, added Dr. Gordon and his colleagues. Hypnotherapy was 2.86-times more likely to result in therapy success, and the number needed to treat was five.

The other therapeutic approaches investigated did not perform any better in the studies than no intervention. However, the authors noted that evidence of the effectiveness of cognitive-behavioral therapy and hypnotherapy is moderate or weak, especially owing to the high bias risk.

“The therapy for functional abdominal pain cannot be compared with the therapy for scarlet fever, for example, where penicillin is administered in the knowledge that recovery is guaranteed. There is evidence that cognitive-behavioral therapy and possibly also hypnotherapy may help, but this is not true for every patient,” said Dr. Rodeck.
 

Start with the pediatrician

Dr. Gordon and his co-authors suggested considering cognitive-behavioral therapy and hypnotherapy for the treatment of functional abdominal pain in children and adolescents. But they added that further randomized controlled studies are necessary to improve the quality of evidence and therefore the reliability of these results.

Children and adolescents with functional abdominal pain do not need to be sent directly to the psychologist for treatment, said Dr. Rodeck. The pediatric or adolescent medicine specialist can also administer the initial behavioral therapy measures. “Some patients manage with the behavioral therapy approaches we offer as pediatric and adolescent medicine specialists; others require professional support with psychologic expertise,” said Dr. Rodeck. Should outpatient treatment be unsuccessful, inpatient therapy in special psychosomatic clinics or wards remains an option.
 

Education offers relief

For many patients, being informed about the connections and mechanisms that play a role in functional abdominal pain can offer a lot of relief, said Dr. Rodeck. Offering coping strategies that can be used in the event of acute symptoms is also a part of this education.

“If patients have functional abdominal pain for which no organic cause can be found, this can lead to frustration, sadness, and despair. The problem can become even worse if they feel that they are not being taken seriously by the physician,” said Dr. Rodeck. These negative experiences can further exacerbate the pain perception disorder. The aim of behavioral therapy measures is therefore to interrupt and downregulate this vicious cycle.

“Constant investigations are not always helpful for patients with functional abdominal pain. Time must be taken with these patients to talk and explore the options. They have definite abdominal pain, they are not imagining it. They must be taken seriously,” he emphasized.

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

Functional abdominal pain in childhood and adolescence is extremely stressful for patients and a therapeutic challenge for the physicians treating them. A meta-analysis of 33 randomized-controlled studies published in JAMA Pediatrics shows that cognitive-behavioral therapy or hypnotherapy promises the greatest therapy success.

“If children or adolescents complain about chronic abdominal pain and a detailed diagnostic does not reveal any somatic cause, this is referred to as functional abdominal pain,” Burkhard Rodeck, MD, general secretary of the German Society of Pediatrics and Adolescent Medicine in Berlin, told this news organization.
 

Signal perception disorder

It is still not completely clear what causes functional abdominal pain. But it is assumed to be a disruption in the communication between the gastrointestinal tract and the brain. “These patients are experiencing a signal perception disorder: normal body signals, such as a slight stomach rumble, are assigned to the pain category for them much more quickly than for other people,” said Dr. Rodeck. “The meta-analysis provides confirmation of this – functional abdominal pain is actually a biopsychosocial matter.”

In the standard therapy of functional abdominal pain, however, it is also possible to choose a medicinal approach. “Studies show that herbal preparations such as peppermint oil capsules have some efficacy, since they attenuate the strength of the signals being sent from the gastrointestinal tract to the brain, with the result that they are not perceived so quickly as pain. Probiotics can also potentially help,” added Dr. Rodeck.

“If this is unsuccessful, the child must be offered a psychologic/psychotherapeutic measure, usually cognitive-behavioral therapy.”
 

Comparison of psychosocial therapies

The meta-analysis was carried out by a research team at the University of Central Lancashire, Preston, United Kingdom. It included 2,657 children and adolescents between the ages of 7 and 17 years, of which two-thirds were girls.

Various psychosocial therapy approaches for functional abdominal pain, such as cognitive-behavioral therapy, educational assistance, hypnotherapy (directed at the digestive system), guided meditation with relaxation, yoga, or (visceral) osteopathy were investigated and compared in the studies – sometimes against each other and sometimes against no intervention.

Lead author Morris Gordon, MBChB, PhD, professor of evidence synthesis and systematic review at the University of Central Lancashire, and his colleagues reported that cognitive-behavioral therapy was 2.37-times more likely to result in therapy success than no intervention. To treat functional abdominal pain successfully in one child or adolescent, five children needed to be treated with cognitive-behavioral therapy.
 

Rarer, milder pain

The children and adolescents treated with cognitive-behavioral therapy also experienced less frequent and less severe abdominal pain than the children and adolescents who did not receive any intervention. The rate of side effect–related therapy discontinuations did not differ between the groups.

Hypnotherapy could also be associated with an improved outcome, compared with no intervention, added Dr. Gordon and his colleagues. Hypnotherapy was 2.86-times more likely to result in therapy success, and the number needed to treat was five.

The other therapeutic approaches investigated did not perform any better in the studies than no intervention. However, the authors noted that evidence of the effectiveness of cognitive-behavioral therapy and hypnotherapy is moderate or weak, especially owing to the high bias risk.

“The therapy for functional abdominal pain cannot be compared with the therapy for scarlet fever, for example, where penicillin is administered in the knowledge that recovery is guaranteed. There is evidence that cognitive-behavioral therapy and possibly also hypnotherapy may help, but this is not true for every patient,” said Dr. Rodeck.
 

Start with the pediatrician

Dr. Gordon and his co-authors suggested considering cognitive-behavioral therapy and hypnotherapy for the treatment of functional abdominal pain in children and adolescents. But they added that further randomized controlled studies are necessary to improve the quality of evidence and therefore the reliability of these results.

Children and adolescents with functional abdominal pain do not need to be sent directly to the psychologist for treatment, said Dr. Rodeck. The pediatric or adolescent medicine specialist can also administer the initial behavioral therapy measures. “Some patients manage with the behavioral therapy approaches we offer as pediatric and adolescent medicine specialists; others require professional support with psychologic expertise,” said Dr. Rodeck. Should outpatient treatment be unsuccessful, inpatient therapy in special psychosomatic clinics or wards remains an option.
 

Education offers relief

For many patients, being informed about the connections and mechanisms that play a role in functional abdominal pain can offer a lot of relief, said Dr. Rodeck. Offering coping strategies that can be used in the event of acute symptoms is also a part of this education.

“If patients have functional abdominal pain for which no organic cause can be found, this can lead to frustration, sadness, and despair. The problem can become even worse if they feel that they are not being taken seriously by the physician,” said Dr. Rodeck. These negative experiences can further exacerbate the pain perception disorder. The aim of behavioral therapy measures is therefore to interrupt and downregulate this vicious cycle.

“Constant investigations are not always helpful for patients with functional abdominal pain. Time must be taken with these patients to talk and explore the options. They have definite abdominal pain, they are not imagining it. They must be taken seriously,” he emphasized.

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

New research suggests physicians face a Herculean task to get Americans with atherosclerotic cardiovascular disease (ASCVD) to take high-intensity statins, despite multiple professional guidelines giving the therapy their highest level recommendation.

Results from more 600,000 commercially insured patients with established ASCVD showed:

• Only one in five patients (22.5%) were taking a high-intensity statin.
• 27.6% were taking a low- or moderate-intensity statin.
• One-half (49.9%) were not taking any statin.

“It’s embarrassing,” senior author Christopher B. Granger, MD, Duke Clinical Research Institute, Durham, N.C., told this news organization. “It should be embarrassing for anybody in health care that we do such a terrible job with something so simple and effective.”

The results were published in the Journal of the American College of Cardiology.

Statins have been shown to reduce the risk for ASCVD events by about 30%, with an added 15% reduction with a high-intensity formulation. The class I recommendation for high-intensity statin use in ASCVD patients younger than 75 years in the 2013 American College of Cardiology/American Heart Association cholesterol guidelines prompted a jump in prescriptions that plateaued by 2017.

A class II recommendation was added to the 2018 guideline update for high-intensity statins in adults older than 75 years with ASCVD. But underuse persists, despite falling prices with generic availability and initiatives to improve statin adoption, the authors noted.

“There are a lot of barriers for patients to statin use, including the misinformation on the Internet and elsewhere that statins have all kinds of side effects,” Dr. Granger said. “They have uncommon side effects, but when we look at it carefully, only about 10% of patients, even with statin intolerance, have true intolerance.”

Efforts are needed to better understand and address these barriers, particularly for younger and female patients, he noted.

In multivariate analyses, patients who were middle-aged (odds ratio, 2.66) or at least 75 years of age (OR, 2.09) were more than twice as likely as patients younger than 45 years to be on any statin.

Not surprisingly, women were 30% less likely than men to receive a statin (OR, 0.70), Dr. Granger said. A high Charlson comorbidity score (OR, 0.72) and peripheral artery disease (OR, 0.55) also reduced the odds of a statin prescription.

Among statin users, middle-aged (OR, 0.83) and older (OR, 0.44) patients were less likely to be on a high-intensity statin, as were women (OR, 0.68) and patients with peripheral artery disease (OR, 0.43).

Visiting a cardiologist in the previous 12 months, however, increased the odds a patient was on a high-intensity statin (OR, 1.21), as did the use of other LDL-cholesterol-lowering drugs (OR, 1.44).

“With no evidence of heterogeneity in efficacy by sex, ongoing work must not only address misperceptions and barriers to the prescription of high-intensity statins in women, but also further understand (and address) differences in tolerability, which may be related to sex-based variation in statin metabolism,” wrote the authors, led by Adam J. Nelson, MBBS, MBA, MPH, also from Duke.

The study involved 601,934 patients (mean age, 67.5 years) who had a diagnosis of ASCVD between Jan. 31, 2018, and an index date of Jan. 31, 2019, and were enrolled in the HealthCore Integrated Research Environment database.

Two-thirds (70.9%) of patients visited a cardiologist in the 12 months prior to the index date, and three-fourths (81.3%) visited a primary care provider.

Pharmacy claims for the 12 months after the index date showed 82.8% of high-intensity users at index achieved coverage for at least 75% of days. Those with the least adherence (< 50% of days covered) included younger patients, as well as those with chronic kidney disease or depression.

“We need implementation research. What are the tools and the methods that we can use to improve the proportion of patients who are having the life-saving benefits from statins?” Dr. Granger said.

He noted that the team has submitted a National Institutes of Health grant to try to use pharmacists, as a mechanism within the context of health systems and payer systems, to improve the appropriate use of statins in a randomized trial. “I think that’s a win.”

Salim S. Virani, MD, PhD, Baylor College of Medicine, and Michael DeBakey VA Medical Center, Houston, and colleagues point out in a related editorial that the rates of statin usage in the study are “considerably lower” than in other contemporary studies, where about 80% and 50% of ASCVD patients are receiving statins and high-intensity statins, respectively.

Possible explanations are the use of rule-out codes, a short medication fill window from the index date, or issues with medication capture, they said. “Nevertheless, the findings are largely consistent with other work highlighting low use of statin therapy.”

The editorialists said social media, statin-related adverse effects, and therapeutic inertia are key drivers of non–guideline-concordant statin use. Possible solutions include improving guideline dissemination, leveraging team-based care, using smart clinical decision-support tools at the point of care, and identifying trustworthy and easily understood sources of information for patients.

“We can only hope that the fate of statin therapy is not repeated with sodium-glucose cotranspoerter-2 inhibitors or glucagon-like peptide-1 receptor agonists in another 30 years, or worse yet, that continued gaps in statin therapy use in patients with ASCVD persist 30 years from now,” Dr. Virani and colleagues concluded.

A sliver of optimism?

A research letter by Colantonio et al. in the same issue of JACC points to some positive steps, at least among patients having a myocardial infarction (MI). It reported that the percentage of patients who received a high-intensity statin as their first statin prescription 30 days after MI jumped from 30.7% in the first quarter of 2011 to 78.6% in the fourth quarter of 2019.

Similar increases were reported by race/ethnicity, despite statin use previously shown to be lower among non-Hispanic Black patients with ASCVD. In each calendar year, however, high-intensity statin therapy was lower among patients older than 75 years and among women.

Dr. Granger disclosed ties with Boehringer Ingelheim, Bristol Myers Squibb, Janssen Pharmaceuticals, Pfizer, AKROS, Apple, AstraZeneca, Daiichi Sankyo, Food and Drug Administration, GlaxoSmithKline, Medtronic Foundation, Novartis Pharmaceuticals, AbbVie, Bayer, Boston Scientific, CeleCor Therapeutics, Correvio, Espero BioPharma, Medscape, Medtronic, Merck, National Institutes of Health, Novo Nordisk, Rhoshan Pharmaceuticals, and Roche Diagnostics. Dr. Virani disclosed ties with the Department of Veterans Affairs, the National Institutes of Health, the World Heart Federation, and the Jooma and Tahir Family, and the American College of Cardiology.

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

New research suggests physicians face a Herculean task to get Americans with atherosclerotic cardiovascular disease (ASCVD) to take high-intensity statins, despite multiple professional guidelines giving the therapy their highest level recommendation.

Results from more 600,000 commercially insured patients with established ASCVD showed:

• Only one in five patients (22.5%) were taking a high-intensity statin.
• 27.6% were taking a low- or moderate-intensity statin.
• One-half (49.9%) were not taking any statin.

“It’s embarrassing,” senior author Christopher B. Granger, MD, Duke Clinical Research Institute, Durham, N.C., told this news organization. “It should be embarrassing for anybody in health care that we do such a terrible job with something so simple and effective.”

The results were published in the Journal of the American College of Cardiology.

Statins have been shown to reduce the risk for ASCVD events by about 30%, with an added 15% reduction with a high-intensity formulation. The class I recommendation for high-intensity statin use in ASCVD patients younger than 75 years in the 2013 American College of Cardiology/American Heart Association cholesterol guidelines prompted a jump in prescriptions that plateaued by 2017.

A class II recommendation was added to the 2018 guideline update for high-intensity statins in adults older than 75 years with ASCVD. But underuse persists, despite falling prices with generic availability and initiatives to improve statin adoption, the authors noted.

“There are a lot of barriers for patients to statin use, including the misinformation on the Internet and elsewhere that statins have all kinds of side effects,” Dr. Granger said. “They have uncommon side effects, but when we look at it carefully, only about 10% of patients, even with statin intolerance, have true intolerance.”

Efforts are needed to better understand and address these barriers, particularly for younger and female patients, he noted.

In multivariate analyses, patients who were middle-aged (odds ratio, 2.66) or at least 75 years of age (OR, 2.09) were more than twice as likely as patients younger than 45 years to be on any statin.

Not surprisingly, women were 30% less likely than men to receive a statin (OR, 0.70), Dr. Granger said. A high Charlson comorbidity score (OR, 0.72) and peripheral artery disease (OR, 0.55) also reduced the odds of a statin prescription.

Among statin users, middle-aged (OR, 0.83) and older (OR, 0.44) patients were less likely to be on a high-intensity statin, as were women (OR, 0.68) and patients with peripheral artery disease (OR, 0.43).

Visiting a cardiologist in the previous 12 months, however, increased the odds a patient was on a high-intensity statin (OR, 1.21), as did the use of other LDL-cholesterol-lowering drugs (OR, 1.44).

“With no evidence of heterogeneity in efficacy by sex, ongoing work must not only address misperceptions and barriers to the prescription of high-intensity statins in women, but also further understand (and address) differences in tolerability, which may be related to sex-based variation in statin metabolism,” wrote the authors, led by Adam J. Nelson, MBBS, MBA, MPH, also from Duke.

The study involved 601,934 patients (mean age, 67.5 years) who had a diagnosis of ASCVD between Jan. 31, 2018, and an index date of Jan. 31, 2019, and were enrolled in the HealthCore Integrated Research Environment database.

Two-thirds (70.9%) of patients visited a cardiologist in the 12 months prior to the index date, and three-fourths (81.3%) visited a primary care provider.

Pharmacy claims for the 12 months after the index date showed 82.8% of high-intensity users at index achieved coverage for at least 75% of days. Those with the least adherence (< 50% of days covered) included younger patients, as well as those with chronic kidney disease or depression.

“We need implementation research. What are the tools and the methods that we can use to improve the proportion of patients who are having the life-saving benefits from statins?” Dr. Granger said.

He noted that the team has submitted a National Institutes of Health grant to try to use pharmacists, as a mechanism within the context of health systems and payer systems, to improve the appropriate use of statins in a randomized trial. “I think that’s a win.”

Salim S. Virani, MD, PhD, Baylor College of Medicine, and Michael DeBakey VA Medical Center, Houston, and colleagues point out in a related editorial that the rates of statin usage in the study are “considerably lower” than in other contemporary studies, where about 80% and 50% of ASCVD patients are receiving statins and high-intensity statins, respectively.

Possible explanations are the use of rule-out codes, a short medication fill window from the index date, or issues with medication capture, they said. “Nevertheless, the findings are largely consistent with other work highlighting low use of statin therapy.”

The editorialists said social media, statin-related adverse effects, and therapeutic inertia are key drivers of non–guideline-concordant statin use. Possible solutions include improving guideline dissemination, leveraging team-based care, using smart clinical decision-support tools at the point of care, and identifying trustworthy and easily understood sources of information for patients.

“We can only hope that the fate of statin therapy is not repeated with sodium-glucose cotranspoerter-2 inhibitors or glucagon-like peptide-1 receptor agonists in another 30 years, or worse yet, that continued gaps in statin therapy use in patients with ASCVD persist 30 years from now,” Dr. Virani and colleagues concluded.

A sliver of optimism?

A research letter by Colantonio et al. in the same issue of JACC points to some positive steps, at least among patients having a myocardial infarction (MI). It reported that the percentage of patients who received a high-intensity statin as their first statin prescription 30 days after MI jumped from 30.7% in the first quarter of 2011 to 78.6% in the fourth quarter of 2019.

Similar increases were reported by race/ethnicity, despite statin use previously shown to be lower among non-Hispanic Black patients with ASCVD. In each calendar year, however, high-intensity statin therapy was lower among patients older than 75 years and among women.

Dr. Granger disclosed ties with Boehringer Ingelheim, Bristol Myers Squibb, Janssen Pharmaceuticals, Pfizer, AKROS, Apple, AstraZeneca, Daiichi Sankyo, Food and Drug Administration, GlaxoSmithKline, Medtronic Foundation, Novartis Pharmaceuticals, AbbVie, Bayer, Boston Scientific, CeleCor Therapeutics, Correvio, Espero BioPharma, Medscape, Medtronic, Merck, National Institutes of Health, Novo Nordisk, Rhoshan Pharmaceuticals, and Roche Diagnostics. Dr. Virani disclosed ties with the Department of Veterans Affairs, the National Institutes of Health, the World Heart Federation, and the Jooma and Tahir Family, and the American College of Cardiology.

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

New research suggests physicians face a Herculean task to get Americans with atherosclerotic cardiovascular disease (ASCVD) to take high-intensity statins, despite multiple professional guidelines giving the therapy their highest level recommendation.

Results from more 600,000 commercially insured patients with established ASCVD showed:

• Only one in five patients (22.5%) were taking a high-intensity statin.
• 27.6% were taking a low- or moderate-intensity statin.
• One-half (49.9%) were not taking any statin.

“It’s embarrassing,” senior author Christopher B. Granger, MD, Duke Clinical Research Institute, Durham, N.C., told this news organization. “It should be embarrassing for anybody in health care that we do such a terrible job with something so simple and effective.”

The results were published in the Journal of the American College of Cardiology.

Statins have been shown to reduce the risk for ASCVD events by about 30%, with an added 15% reduction with a high-intensity formulation. The class I recommendation for high-intensity statin use in ASCVD patients younger than 75 years in the 2013 American College of Cardiology/American Heart Association cholesterol guidelines prompted a jump in prescriptions that plateaued by 2017.

A class II recommendation was added to the 2018 guideline update for high-intensity statins in adults older than 75 years with ASCVD. But underuse persists, despite falling prices with generic availability and initiatives to improve statin adoption, the authors noted.

“There are a lot of barriers for patients to statin use, including the misinformation on the Internet and elsewhere that statins have all kinds of side effects,” Dr. Granger said. “They have uncommon side effects, but when we look at it carefully, only about 10% of patients, even with statin intolerance, have true intolerance.”

Efforts are needed to better understand and address these barriers, particularly for younger and female patients, he noted.

In multivariate analyses, patients who were middle-aged (odds ratio, 2.66) or at least 75 years of age (OR, 2.09) were more than twice as likely as patients younger than 45 years to be on any statin.

Not surprisingly, women were 30% less likely than men to receive a statin (OR, 0.70), Dr. Granger said. A high Charlson comorbidity score (OR, 0.72) and peripheral artery disease (OR, 0.55) also reduced the odds of a statin prescription.

Among statin users, middle-aged (OR, 0.83) and older (OR, 0.44) patients were less likely to be on a high-intensity statin, as were women (OR, 0.68) and patients with peripheral artery disease (OR, 0.43).

Visiting a cardiologist in the previous 12 months, however, increased the odds a patient was on a high-intensity statin (OR, 1.21), as did the use of other LDL-cholesterol-lowering drugs (OR, 1.44).

“With no evidence of heterogeneity in efficacy by sex, ongoing work must not only address misperceptions and barriers to the prescription of high-intensity statins in women, but also further understand (and address) differences in tolerability, which may be related to sex-based variation in statin metabolism,” wrote the authors, led by Adam J. Nelson, MBBS, MBA, MPH, also from Duke.

The study involved 601,934 patients (mean age, 67.5 years) who had a diagnosis of ASCVD between Jan. 31, 2018, and an index date of Jan. 31, 2019, and were enrolled in the HealthCore Integrated Research Environment database.

Two-thirds (70.9%) of patients visited a cardiologist in the 12 months prior to the index date, and three-fourths (81.3%) visited a primary care provider.

Pharmacy claims for the 12 months after the index date showed 82.8% of high-intensity users at index achieved coverage for at least 75% of days. Those with the least adherence (< 50% of days covered) included younger patients, as well as those with chronic kidney disease or depression.

“We need implementation research. What are the tools and the methods that we can use to improve the proportion of patients who are having the life-saving benefits from statins?” Dr. Granger said.

He noted that the team has submitted a National Institutes of Health grant to try to use pharmacists, as a mechanism within the context of health systems and payer systems, to improve the appropriate use of statins in a randomized trial. “I think that’s a win.”

Salim S. Virani, MD, PhD, Baylor College of Medicine, and Michael DeBakey VA Medical Center, Houston, and colleagues point out in a related editorial that the rates of statin usage in the study are “considerably lower” than in other contemporary studies, where about 80% and 50% of ASCVD patients are receiving statins and high-intensity statins, respectively.

Possible explanations are the use of rule-out codes, a short medication fill window from the index date, or issues with medication capture, they said. “Nevertheless, the findings are largely consistent with other work highlighting low use of statin therapy.”

The editorialists said social media, statin-related adverse effects, and therapeutic inertia are key drivers of non–guideline-concordant statin use. Possible solutions include improving guideline dissemination, leveraging team-based care, using smart clinical decision-support tools at the point of care, and identifying trustworthy and easily understood sources of information for patients.

“We can only hope that the fate of statin therapy is not repeated with sodium-glucose cotranspoerter-2 inhibitors or glucagon-like peptide-1 receptor agonists in another 30 years, or worse yet, that continued gaps in statin therapy use in patients with ASCVD persist 30 years from now,” Dr. Virani and colleagues concluded.

A sliver of optimism?

A research letter by Colantonio et al. in the same issue of JACC points to some positive steps, at least among patients having a myocardial infarction (MI). It reported that the percentage of patients who received a high-intensity statin as their first statin prescription 30 days after MI jumped from 30.7% in the first quarter of 2011 to 78.6% in the fourth quarter of 2019.

Similar increases were reported by race/ethnicity, despite statin use previously shown to be lower among non-Hispanic Black patients with ASCVD. In each calendar year, however, high-intensity statin therapy was lower among patients older than 75 years and among women.

Dr. Granger disclosed ties with Boehringer Ingelheim, Bristol Myers Squibb, Janssen Pharmaceuticals, Pfizer, AKROS, Apple, AstraZeneca, Daiichi Sankyo, Food and Drug Administration, GlaxoSmithKline, Medtronic Foundation, Novartis Pharmaceuticals, AbbVie, Bayer, Boston Scientific, CeleCor Therapeutics, Correvio, Espero BioPharma, Medscape, Medtronic, Merck, National Institutes of Health, Novo Nordisk, Rhoshan Pharmaceuticals, and Roche Diagnostics. Dr. Virani disclosed ties with the Department of Veterans Affairs, the National Institutes of Health, the World Heart Federation, and the Jooma and Tahir Family, and the American College of Cardiology.

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

Symptom timelines surrounding COVID infection tend to center on either the immediate 5-day quarantine protocols for acute infection or the long-COVID symptoms that can last a month or potentially far longer.

But some patients report a “middle-range” COVID that will resolve before it becomes long COVID, yet still lasts longer than is typical for viral infections. People may return to work or daily routines, but something is off: What had been simple exercise regimens become onerous. Everyday tasks take more effort.

Does this ill-defined subset point to a “medium COVID?”

Farha Ikramuddin, MD, MHA, a physiatrist and rehabilitation specialist at the University of Minnesota and M Health Fairview in Minneapolis, points out there is no definition or diagnostic code or shared official understanding of a middle category for COVID.

“But am I seeing that? Absolutely,” she said in an interview.

“I have seen patients who are younger, healthier, [and] with not so many comorbidities have either persistence of symptoms or reappearance after the initial infection is done,” she said.

Some patients report they had very low infection or were nonsymptomatic and returned to their normal health fairly quickly after infection. Then a week later they began experiencing fatigue, lost appetite, loss of smell, and feeling full after a few bites, Dr. Ikramuddin said.

Part of the trouble in categorizing the space between returning to normal after a week and having symptoms for months is that organizations can’t agree on a timeline for when symptoms warrant a “long-COVID” label.

For instance, the Centers for Disease Control and Prevention defines it as 4 or more weeks after infection. The World Health Organization defines it as starting 3 months after COVID-19 symptom onset.

“I’m seeing ‘medium COVID’ – as one would call it – in younger and healthier patients. I’m also noticing that these symptoms are not severe enough to warrant stopping their job or changing their job schedules,” Dr. Ikramuddin said.

They go back to work, she said, but start noticing something is off.

“I am seeing that.”

“I discharge at least two patients a week from my clinic because they have moved on and no longer have symptoms,” Dr. Ikramuddin said.

In a story from Kaiser Health News published last month, WHYY health reporter Nina Feldman writes: “What I’ve come to think of as my ‘medium COVID’ affected my life. I couldn’t socialize much, drink, or stay up past 9:30 p.m. It took me 10 weeks to go for my first run – I’d been too afraid to try.”

She described a dinner with a friend after ending initial isolation protocols: “One glass of wine left me feeling like I’d had a whole bottle. I was bone-achingly exhausted but couldn’t sleep.”
 

Medical mystery

Dr. Ikramuddin notes the mechanism behind prolonged COVID-19 symptoms is still a medical mystery.

“In one scenario,” she said, “the question is being asked about whether the virus is staying dormant, similar to herpes zoster or HIV.”

“Right now, instead of getting more answers, we’re getting more questions,” Dr. Ikramuddin  said.

Mouhib Naddour, MD, a pulmonary specialist with Sharp HealthCare in San Diego, said he’s seeing that it’s taking some patients who have had COVID longer to recover than it would for other viral infections.

Some patients fall between those recovering within 2-3 weeks and patients having long COVID. Those patients in the gap could be lumped into a middle-range COVID, he told this news organization.

“We try to put things into tables and boxes but it is hard with this disease,” Dr. Naddour said.

He agrees there’s no medical definition for “medium” COVID, but he said the idea should bring hope for patients to know that, if their symptoms are persisting they don’t necessarily have long COVID – and their symptoms may still disappear.

“This is an illness that may take longer to completely recover from,” he said. “The majority of patients we’re seeing in this group could be healthy young patients who get COVID, then 2-3 weeks after they test negative, still have lingering symptoms.”
 

Common symptoms

Some commonly reported symptoms of those with enduring illness, which often overlap with other stages of COVID, are difficulty breathing, chest tightness, dry cough, chest pain, muscle and joint pain, fatigue, difficulty sleeping, and mood swings, Dr. Naddour said. 

“We need to do an extensive assessment to make sure there’s no other problem causing these symptoms,” he said.

Still, there is no set timeline for the medium-COVID range, he noted, so checking in with a primary care physician is important for people experiencing symptoms.
 

It’s a continuum, not a category

Fernando Carnavali, MD, coordinator for Mount Sinai’s Center for Post-COVID Care in New York, said he is not ready to recognize a separate category for a “medium” COVID.

He noted that science can’t even agree on a name for lasting post-COVID symptoms, whether it’s “long COVID” or “long-haul COVID,” “post-COVID syndrome” or “post-acute sequelae of COVID-19 (PASC ).” There’s no agreed-upon pathophysiology or biomarker.

“That creates these gaps of understanding on where we are,” Dr. Carnavali said in an interview.

He said he understands people’s need to categorize symptoms, but rather than a middle ground he sees a continuum.

It doesn’t mean what others may call COVID’s middle ground doesn’t exist, Dr. Carnavali said: “We are in the infancy of defining this. Trying to classify them may create more anxiety.”

The clinicians interviewed for this story report no relevant financial relationships.

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

Symptom timelines surrounding COVID infection tend to center on either the immediate 5-day quarantine protocols for acute infection or the long-COVID symptoms that can last a month or potentially far longer.

But some patients report a “middle-range” COVID that will resolve before it becomes long COVID, yet still lasts longer than is typical for viral infections. People may return to work or daily routines, but something is off: What had been simple exercise regimens become onerous. Everyday tasks take more effort.

Does this ill-defined subset point to a “medium COVID?”

Farha Ikramuddin, MD, MHA, a physiatrist and rehabilitation specialist at the University of Minnesota and M Health Fairview in Minneapolis, points out there is no definition or diagnostic code or shared official understanding of a middle category for COVID.

“But am I seeing that? Absolutely,” she said in an interview.

“I have seen patients who are younger, healthier, [and] with not so many comorbidities have either persistence of symptoms or reappearance after the initial infection is done,” she said.

Some patients report they had very low infection or were nonsymptomatic and returned to their normal health fairly quickly after infection. Then a week later they began experiencing fatigue, lost appetite, loss of smell, and feeling full after a few bites, Dr. Ikramuddin said.

Part of the trouble in categorizing the space between returning to normal after a week and having symptoms for months is that organizations can’t agree on a timeline for when symptoms warrant a “long-COVID” label.

For instance, the Centers for Disease Control and Prevention defines it as 4 or more weeks after infection. The World Health Organization defines it as starting 3 months after COVID-19 symptom onset.

“I’m seeing ‘medium COVID’ – as one would call it – in younger and healthier patients. I’m also noticing that these symptoms are not severe enough to warrant stopping their job or changing their job schedules,” Dr. Ikramuddin said.

They go back to work, she said, but start noticing something is off.

“I am seeing that.”

“I discharge at least two patients a week from my clinic because they have moved on and no longer have symptoms,” Dr. Ikramuddin said.

In a story from Kaiser Health News published last month, WHYY health reporter Nina Feldman writes: “What I’ve come to think of as my ‘medium COVID’ affected my life. I couldn’t socialize much, drink, or stay up past 9:30 p.m. It took me 10 weeks to go for my first run – I’d been too afraid to try.”

She described a dinner with a friend after ending initial isolation protocols: “One glass of wine left me feeling like I’d had a whole bottle. I was bone-achingly exhausted but couldn’t sleep.”
 

Medical mystery

Dr. Ikramuddin notes the mechanism behind prolonged COVID-19 symptoms is still a medical mystery.

“In one scenario,” she said, “the question is being asked about whether the virus is staying dormant, similar to herpes zoster or HIV.”

“Right now, instead of getting more answers, we’re getting more questions,” Dr. Ikramuddin  said.

Mouhib Naddour, MD, a pulmonary specialist with Sharp HealthCare in San Diego, said he’s seeing that it’s taking some patients who have had COVID longer to recover than it would for other viral infections.

Some patients fall between those recovering within 2-3 weeks and patients having long COVID. Those patients in the gap could be lumped into a middle-range COVID, he told this news organization.

“We try to put things into tables and boxes but it is hard with this disease,” Dr. Naddour said.

He agrees there’s no medical definition for “medium” COVID, but he said the idea should bring hope for patients to know that, if their symptoms are persisting they don’t necessarily have long COVID – and their symptoms may still disappear.

“This is an illness that may take longer to completely recover from,” he said. “The majority of patients we’re seeing in this group could be healthy young patients who get COVID, then 2-3 weeks after they test negative, still have lingering symptoms.”
 

Common symptoms

Some commonly reported symptoms of those with enduring illness, which often overlap with other stages of COVID, are difficulty breathing, chest tightness, dry cough, chest pain, muscle and joint pain, fatigue, difficulty sleeping, and mood swings, Dr. Naddour said. 

“We need to do an extensive assessment to make sure there’s no other problem causing these symptoms,” he said.

Still, there is no set timeline for the medium-COVID range, he noted, so checking in with a primary care physician is important for people experiencing symptoms.
 

It’s a continuum, not a category

Fernando Carnavali, MD, coordinator for Mount Sinai’s Center for Post-COVID Care in New York, said he is not ready to recognize a separate category for a “medium” COVID.

He noted that science can’t even agree on a name for lasting post-COVID symptoms, whether it’s “long COVID” or “long-haul COVID,” “post-COVID syndrome” or “post-acute sequelae of COVID-19 (PASC ).” There’s no agreed-upon pathophysiology or biomarker.

“That creates these gaps of understanding on where we are,” Dr. Carnavali said in an interview.

He said he understands people’s need to categorize symptoms, but rather than a middle ground he sees a continuum.

It doesn’t mean what others may call COVID’s middle ground doesn’t exist, Dr. Carnavali said: “We are in the infancy of defining this. Trying to classify them may create more anxiety.”

The clinicians interviewed for this story report no relevant financial relationships.

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

Symptom timelines surrounding COVID infection tend to center on either the immediate 5-day quarantine protocols for acute infection or the long-COVID symptoms that can last a month or potentially far longer.

But some patients report a “middle-range” COVID that will resolve before it becomes long COVID, yet still lasts longer than is typical for viral infections. People may return to work or daily routines, but something is off: What had been simple exercise regimens become onerous. Everyday tasks take more effort.

Does this ill-defined subset point to a “medium COVID?”

Farha Ikramuddin, MD, MHA, a physiatrist and rehabilitation specialist at the University of Minnesota and M Health Fairview in Minneapolis, points out there is no definition or diagnostic code or shared official understanding of a middle category for COVID.

“But am I seeing that? Absolutely,” she said in an interview.

“I have seen patients who are younger, healthier, [and] with not so many comorbidities have either persistence of symptoms or reappearance after the initial infection is done,” she said.

Some patients report they had very low infection or were nonsymptomatic and returned to their normal health fairly quickly after infection. Then a week later they began experiencing fatigue, lost appetite, loss of smell, and feeling full after a few bites, Dr. Ikramuddin said.

Part of the trouble in categorizing the space between returning to normal after a week and having symptoms for months is that organizations can’t agree on a timeline for when symptoms warrant a “long-COVID” label.

For instance, the Centers for Disease Control and Prevention defines it as 4 or more weeks after infection. The World Health Organization defines it as starting 3 months after COVID-19 symptom onset.

“I’m seeing ‘medium COVID’ – as one would call it – in younger and healthier patients. I’m also noticing that these symptoms are not severe enough to warrant stopping their job or changing their job schedules,” Dr. Ikramuddin said.

They go back to work, she said, but start noticing something is off.

“I am seeing that.”

“I discharge at least two patients a week from my clinic because they have moved on and no longer have symptoms,” Dr. Ikramuddin said.

In a story from Kaiser Health News published last month, WHYY health reporter Nina Feldman writes: “What I’ve come to think of as my ‘medium COVID’ affected my life. I couldn’t socialize much, drink, or stay up past 9:30 p.m. It took me 10 weeks to go for my first run – I’d been too afraid to try.”

She described a dinner with a friend after ending initial isolation protocols: “One glass of wine left me feeling like I’d had a whole bottle. I was bone-achingly exhausted but couldn’t sleep.”
 

Medical mystery

Dr. Ikramuddin notes the mechanism behind prolonged COVID-19 symptoms is still a medical mystery.

“In one scenario,” she said, “the question is being asked about whether the virus is staying dormant, similar to herpes zoster or HIV.”

“Right now, instead of getting more answers, we’re getting more questions,” Dr. Ikramuddin  said.

Mouhib Naddour, MD, a pulmonary specialist with Sharp HealthCare in San Diego, said he’s seeing that it’s taking some patients who have had COVID longer to recover than it would for other viral infections.

Some patients fall between those recovering within 2-3 weeks and patients having long COVID. Those patients in the gap could be lumped into a middle-range COVID, he told this news organization.

“We try to put things into tables and boxes but it is hard with this disease,” Dr. Naddour said.

He agrees there’s no medical definition for “medium” COVID, but he said the idea should bring hope for patients to know that, if their symptoms are persisting they don’t necessarily have long COVID – and their symptoms may still disappear.

“This is an illness that may take longer to completely recover from,” he said. “The majority of patients we’re seeing in this group could be healthy young patients who get COVID, then 2-3 weeks after they test negative, still have lingering symptoms.”
 

Common symptoms

Some commonly reported symptoms of those with enduring illness, which often overlap with other stages of COVID, are difficulty breathing, chest tightness, dry cough, chest pain, muscle and joint pain, fatigue, difficulty sleeping, and mood swings, Dr. Naddour said. 

“We need to do an extensive assessment to make sure there’s no other problem causing these symptoms,” he said.

Still, there is no set timeline for the medium-COVID range, he noted, so checking in with a primary care physician is important for people experiencing symptoms.
 

It’s a continuum, not a category

Fernando Carnavali, MD, coordinator for Mount Sinai’s Center for Post-COVID Care in New York, said he is not ready to recognize a separate category for a “medium” COVID.

He noted that science can’t even agree on a name for lasting post-COVID symptoms, whether it’s “long COVID” or “long-haul COVID,” “post-COVID syndrome” or “post-acute sequelae of COVID-19 (PASC ).” There’s no agreed-upon pathophysiology or biomarker.

“That creates these gaps of understanding on where we are,” Dr. Carnavali said in an interview.

He said he understands people’s need to categorize symptoms, but rather than a middle ground he sees a continuum.

It doesn’t mean what others may call COVID’s middle ground doesn’t exist, Dr. Carnavali said: “We are in the infancy of defining this. Trying to classify them may create more anxiety.”

The clinicians interviewed for this story report no relevant financial relationships.

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

New surveillance data from the Vaccine Adverse Event Reporting System (VAERS) confirm a small but statistically significant increased risk for Guillain-Barré syndrome (GBS) in the 3 weeks after receipt of the Janssen/Johnson & Johnson COVID-19 vaccine.

The Janssen vaccine (Ad26.COV2.S) is a replication-incompetent adenoviral vector vaccine.

The data show no increased risk of GBS with the Pfizer (BNT162b2) or Moderna (mRNA-1273) shots – both mRNA vaccines.

“Our findings support the current guidance from U.S. health officials that preferentially recommend use of mRNA COVID-19 vaccines for primary and booster doses,” Nicola Klein, MD, PhD, with Kaiser Permanente Vaccine Study Center, Oakland, Calif., told this news organization.

“Individuals who choose to receive Janssen/J&J COVID-19 vaccine should be informed of the potential safety risks, including GBS,” Dr. Klein said.

The study was published online in JAMA Network Open.
 

Eleven cases

Between mid-December 2020 and mid-November 2021, roughly 15.1 million doses of COVID-19 vaccine were administered to nearly 7.9 million adults in the United States.

This includes roughly 483,000 doses of the Janssen vaccine, 8.8 million doses of the Pfizer vaccine, and 5.8 million doses of the Moderna vaccine.

The researchers confirmed 11 cases of GBS after the Janssen vaccine.

The unadjusted incidence of GBS (per 100,000 person-years) was 32.4 in the first 21 days after the Janssen vaccine – substantially higher than the expected background rate of 1 to 2 cases per 100,000 person-years.

There were 36 confirmed cases of GBS after mRNA vaccines. The unadjusted incidence in the first 21 days after mRNA vaccination was 1.3 per 100,000 person-years, similar to the overall expected background rate.

In an adjusted head-to-head comparison, GBS incidence during the 21 days after receipt of the Janssen vaccine was 20.6 times higher than the GBS incidence during the 21 days after the Pfizer or Moderna mRNA vaccines, amounting to 15.5 excess cases per million Janssen vaccine recipients.

Most cases of GBS after the Janssen vaccine occurred during the 1- to 21-day risk interval, with the period of greatest risk in the 1-14 days after vaccination.

The findings of this analysis of surveillance data of COVID-19 vaccines are “consistent with an elevated risk of GBS after primary Ad26.COV2.S vaccination,” the authors wrote.
 

Novel presentation?

The researchers note that nearly all individuals who developed GBS after the Janssen vaccine had facial weakness or paralysis, in addition to weakness and decreased reflexes in the limbs, suggesting that the presentation of GBS after COVID-19 adenoviral vector vaccine may be novel.

“More research is needed to determine if the presentation of GBS after adenoviral vector vaccine differs from GBS after other exposures such as Campylobacter jejuni, and to investigate the mechanism for how adenoviral vector vaccines may cause GBS,” Dr. Klein and colleagues said.

“The Vaccine Safety Datalink continues to conduct safety surveillance for all COVID-19 vaccines, including monitoring for GBS and other serious health outcomes after vaccination,” Dr. Klein said in an interview.

This study was supported by the Centers for Disease Control and Prevention. Dr. Klein reported receiving grants from Pfizer research support for a COVID vaccine clinical trial as well as other unrelated studies, grants from Merck, grants from GlaxoSmithKline, grants from Sanofi Pasteur, and grants from Protein Science (now Sanofi Pasteur) outside the submitted work.

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

New surveillance data from the Vaccine Adverse Event Reporting System (VAERS) confirm a small but statistically significant increased risk for Guillain-Barré syndrome (GBS) in the 3 weeks after receipt of the Janssen/Johnson & Johnson COVID-19 vaccine.

The Janssen vaccine (Ad26.COV2.S) is a replication-incompetent adenoviral vector vaccine.

The data show no increased risk of GBS with the Pfizer (BNT162b2) or Moderna (mRNA-1273) shots – both mRNA vaccines.

“Our findings support the current guidance from U.S. health officials that preferentially recommend use of mRNA COVID-19 vaccines for primary and booster doses,” Nicola Klein, MD, PhD, with Kaiser Permanente Vaccine Study Center, Oakland, Calif., told this news organization.

“Individuals who choose to receive Janssen/J&J COVID-19 vaccine should be informed of the potential safety risks, including GBS,” Dr. Klein said.

The study was published online in JAMA Network Open.
 

Eleven cases

Between mid-December 2020 and mid-November 2021, roughly 15.1 million doses of COVID-19 vaccine were administered to nearly 7.9 million adults in the United States.

This includes roughly 483,000 doses of the Janssen vaccine, 8.8 million doses of the Pfizer vaccine, and 5.8 million doses of the Moderna vaccine.

The researchers confirmed 11 cases of GBS after the Janssen vaccine.

The unadjusted incidence of GBS (per 100,000 person-years) was 32.4 in the first 21 days after the Janssen vaccine – substantially higher than the expected background rate of 1 to 2 cases per 100,000 person-years.

There were 36 confirmed cases of GBS after mRNA vaccines. The unadjusted incidence in the first 21 days after mRNA vaccination was 1.3 per 100,000 person-years, similar to the overall expected background rate.

In an adjusted head-to-head comparison, GBS incidence during the 21 days after receipt of the Janssen vaccine was 20.6 times higher than the GBS incidence during the 21 days after the Pfizer or Moderna mRNA vaccines, amounting to 15.5 excess cases per million Janssen vaccine recipients.

Most cases of GBS after the Janssen vaccine occurred during the 1- to 21-day risk interval, with the period of greatest risk in the 1-14 days after vaccination.

The findings of this analysis of surveillance data of COVID-19 vaccines are “consistent with an elevated risk of GBS after primary Ad26.COV2.S vaccination,” the authors wrote.
 

Novel presentation?

The researchers note that nearly all individuals who developed GBS after the Janssen vaccine had facial weakness or paralysis, in addition to weakness and decreased reflexes in the limbs, suggesting that the presentation of GBS after COVID-19 adenoviral vector vaccine may be novel.

“More research is needed to determine if the presentation of GBS after adenoviral vector vaccine differs from GBS after other exposures such as Campylobacter jejuni, and to investigate the mechanism for how adenoviral vector vaccines may cause GBS,” Dr. Klein and colleagues said.

“The Vaccine Safety Datalink continues to conduct safety surveillance for all COVID-19 vaccines, including monitoring for GBS and other serious health outcomes after vaccination,” Dr. Klein said in an interview.

This study was supported by the Centers for Disease Control and Prevention. Dr. Klein reported receiving grants from Pfizer research support for a COVID vaccine clinical trial as well as other unrelated studies, grants from Merck, grants from GlaxoSmithKline, grants from Sanofi Pasteur, and grants from Protein Science (now Sanofi Pasteur) outside the submitted work.

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

New surveillance data from the Vaccine Adverse Event Reporting System (VAERS) confirm a small but statistically significant increased risk for Guillain-Barré syndrome (GBS) in the 3 weeks after receipt of the Janssen/Johnson & Johnson COVID-19 vaccine.

The Janssen vaccine (Ad26.COV2.S) is a replication-incompetent adenoviral vector vaccine.

The data show no increased risk of GBS with the Pfizer (BNT162b2) or Moderna (mRNA-1273) shots – both mRNA vaccines.

“Our findings support the current guidance from U.S. health officials that preferentially recommend use of mRNA COVID-19 vaccines for primary and booster doses,” Nicola Klein, MD, PhD, with Kaiser Permanente Vaccine Study Center, Oakland, Calif., told this news organization.

“Individuals who choose to receive Janssen/J&J COVID-19 vaccine should be informed of the potential safety risks, including GBS,” Dr. Klein said.

The study was published online in JAMA Network Open.
 

Eleven cases

Between mid-December 2020 and mid-November 2021, roughly 15.1 million doses of COVID-19 vaccine were administered to nearly 7.9 million adults in the United States.

This includes roughly 483,000 doses of the Janssen vaccine, 8.8 million doses of the Pfizer vaccine, and 5.8 million doses of the Moderna vaccine.

The researchers confirmed 11 cases of GBS after the Janssen vaccine.

The unadjusted incidence of GBS (per 100,000 person-years) was 32.4 in the first 21 days after the Janssen vaccine – substantially higher than the expected background rate of 1 to 2 cases per 100,000 person-years.

There were 36 confirmed cases of GBS after mRNA vaccines. The unadjusted incidence in the first 21 days after mRNA vaccination was 1.3 per 100,000 person-years, similar to the overall expected background rate.

In an adjusted head-to-head comparison, GBS incidence during the 21 days after receipt of the Janssen vaccine was 20.6 times higher than the GBS incidence during the 21 days after the Pfizer or Moderna mRNA vaccines, amounting to 15.5 excess cases per million Janssen vaccine recipients.

Most cases of GBS after the Janssen vaccine occurred during the 1- to 21-day risk interval, with the period of greatest risk in the 1-14 days after vaccination.

The findings of this analysis of surveillance data of COVID-19 vaccines are “consistent with an elevated risk of GBS after primary Ad26.COV2.S vaccination,” the authors wrote.
 

Novel presentation?

The researchers note that nearly all individuals who developed GBS after the Janssen vaccine had facial weakness or paralysis, in addition to weakness and decreased reflexes in the limbs, suggesting that the presentation of GBS after COVID-19 adenoviral vector vaccine may be novel.

“More research is needed to determine if the presentation of GBS after adenoviral vector vaccine differs from GBS after other exposures such as Campylobacter jejuni, and to investigate the mechanism for how adenoviral vector vaccines may cause GBS,” Dr. Klein and colleagues said.

“The Vaccine Safety Datalink continues to conduct safety surveillance for all COVID-19 vaccines, including monitoring for GBS and other serious health outcomes after vaccination,” Dr. Klein said in an interview.

This study was supported by the Centers for Disease Control and Prevention. Dr. Klein reported receiving grants from Pfizer research support for a COVID vaccine clinical trial as well as other unrelated studies, grants from Merck, grants from GlaxoSmithKline, grants from Sanofi Pasteur, and grants from Protein Science (now Sanofi Pasteur) outside the submitted work.

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

Mental disorders were significantly more likely in children whose mothers had one of five common autoimmune diseases, a new study found.

Previous research has linked both maternal and paternal autoimmune diseases and specific mental disorders, such as attention-deficit/hyperactivity disorder (ADHD), but most of these studies focused on specific conditions in relatively small populations. The new study included data on more than 2 million births, making it one of the largest efforts to date to examine the association, according to the researchers, whose findings were published in JAMA Network Open.

Previous evidence of the possible association between certain maternal autoimmune diseases and mental disorders in offspring has been “scattered and limited,” which “hampered an overall understanding” of the link, Fei Li, MD, the corresponding author of the study, told this news organization.

Dr. Li, of Shanghai Jiao Tong University China, and colleagues reviewed data from a Danish registry cohort of singleton births with up to 38 years of follow-up. They explored associations between a range of maternal autoimmune diseases diagnosed before childbirth and the risks of mental disorders in children in early childhood through young adulthood.

The study population included 2,254,234 births and 38,916,359 person-years. Data on mental health were collected from the Psychiatric Central Research Register and the country’s National Patient Register. The median age of the children at the time of assessment was 16.7 years; approximately half were male.

A total of 50,863 children (2.26%) were born to mothers who had been diagnosed with autoimmune diseases before childbirth. During the follow-up period, 5,460 children of mothers with autoimmune diseases and 303,092 children of mothers without autoimmune diseases were diagnosed with a mental disorder (10.73% vs. 13.76%), according to the researchers.

The risk of being diagnosed with a mental disorder was significantly higher among children of mothers with any autoimmune disease (hazard ratio [HR,], 1.16), with an incidence of 9.38 vs. 7.91 per 1,000 person-years, the researchers reported.

The increased risk persisted when the results were classified by organ system, including connective tissue (HR, 1.11), endocrine (HR, 1.19), gastrointestinal (HR, 1.11), blood (HR, 1.10), nervous (HR, 1.17), and skin (HR, 1.19).

The five autoimmune diseases in mothers that were most commonly associated mental health disorders in children were type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and psoriasis vulgaris.

The greatest risk for children of mothers with any autoimmune disease was observed for organic conditions such as delirium, (HR, 1.54), followed by obsessive-compulsive disorder (HR, 1.42), schizophrenia (HR, 1.54), and mood problems (HR, 1.12).

Children of mothers with any autoimmune disorder also had a significantly increased risk of autism (HR, 1.21), intellectual disability (HR, 1.19), and ADHD (HR, 1.19).

The results add to evidence that activation of the maternal immune system may drive changes in the brain and behavioral problems, which has been observed in animal studies, the researchers wrote.

Potential underlying mechanisms in need of more exploration include genetic risk factors, maternal transmission of autoantibodies to the fetus during pregnancy, and the increased risk of obstetric complications, such as preterm birth, for women with autoimmune disorders that could affect mental development in children, they added.

The study findings were limited by several factors, including the lack of data on potential exacerbation of autoimmune disease activity during pregnancy and its effect on the fetus, the researchers noted. Other limitations included potential detection bias, lack of data on mental disorders in adulthood, and potential changes in diagnostic criteria over the long study period.

The results were strengthened by the use of a population-based registry, the large sample size, and ability to consider a range of confounders, the researchers said.

“This study could help acquire a comprehensive compilation of the associations between maternal autoimmune disorders diagnosed before childbirth and offspring’s mental disorders from childhood through early adulthood,” Dr. Li said in an interview.

For clinicians, Dr. Li said, the findings suggest that the offspring of mothers with autoimmune diseases may benefit from long-term surveillance for mental health disorders.

“Further studies should provide more evidence on the detailed associations of specific maternal autoimmune diseases with a full spectrum of mental disorders in offspring, and more research on underlying mechanisms is needed as well,” she said.
 

Pay early attention

M. Susan Jay, MD, an adjunct professor of pediatrics at the Medical College of Wisconsin, Milwaukee, said previous efforts to examine the association between maternal autoimmunity were hampered by study design, small samples, and self-report of disease history – problems the new research avoids.

The large patient population allowed for detailed subgroup analysis of different conditions and outcomes. Another advantage was the availability of sociodemographic and clinical information, which allowed for the elimination of confounding factors, said Dr. Jay, who was not involved in the research.

“It would be prudent to follow children of mothers with autoimmune disorders before or during pregnancy for mental health issues, and if identified clinically, to offer psychological and developmental behavioral support options,” Dr. Jay added.

The authors have reported no relevant financial relationships.

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

Mental disorders were significantly more likely in children whose mothers had one of five common autoimmune diseases, a new study found.

Previous research has linked both maternal and paternal autoimmune diseases and specific mental disorders, such as attention-deficit/hyperactivity disorder (ADHD), but most of these studies focused on specific conditions in relatively small populations. The new study included data on more than 2 million births, making it one of the largest efforts to date to examine the association, according to the researchers, whose findings were published in JAMA Network Open.

Previous evidence of the possible association between certain maternal autoimmune diseases and mental disorders in offspring has been “scattered and limited,” which “hampered an overall understanding” of the link, Fei Li, MD, the corresponding author of the study, told this news organization.

Dr. Li, of Shanghai Jiao Tong University China, and colleagues reviewed data from a Danish registry cohort of singleton births with up to 38 years of follow-up. They explored associations between a range of maternal autoimmune diseases diagnosed before childbirth and the risks of mental disorders in children in early childhood through young adulthood.

The study population included 2,254,234 births and 38,916,359 person-years. Data on mental health were collected from the Psychiatric Central Research Register and the country’s National Patient Register. The median age of the children at the time of assessment was 16.7 years; approximately half were male.

A total of 50,863 children (2.26%) were born to mothers who had been diagnosed with autoimmune diseases before childbirth. During the follow-up period, 5,460 children of mothers with autoimmune diseases and 303,092 children of mothers without autoimmune diseases were diagnosed with a mental disorder (10.73% vs. 13.76%), according to the researchers.

The risk of being diagnosed with a mental disorder was significantly higher among children of mothers with any autoimmune disease (hazard ratio [HR,], 1.16), with an incidence of 9.38 vs. 7.91 per 1,000 person-years, the researchers reported.

The increased risk persisted when the results were classified by organ system, including connective tissue (HR, 1.11), endocrine (HR, 1.19), gastrointestinal (HR, 1.11), blood (HR, 1.10), nervous (HR, 1.17), and skin (HR, 1.19).

The five autoimmune diseases in mothers that were most commonly associated mental health disorders in children were type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and psoriasis vulgaris.

The greatest risk for children of mothers with any autoimmune disease was observed for organic conditions such as delirium, (HR, 1.54), followed by obsessive-compulsive disorder (HR, 1.42), schizophrenia (HR, 1.54), and mood problems (HR, 1.12).

Children of mothers with any autoimmune disorder also had a significantly increased risk of autism (HR, 1.21), intellectual disability (HR, 1.19), and ADHD (HR, 1.19).

The results add to evidence that activation of the maternal immune system may drive changes in the brain and behavioral problems, which has been observed in animal studies, the researchers wrote.

Potential underlying mechanisms in need of more exploration include genetic risk factors, maternal transmission of autoantibodies to the fetus during pregnancy, and the increased risk of obstetric complications, such as preterm birth, for women with autoimmune disorders that could affect mental development in children, they added.

The study findings were limited by several factors, including the lack of data on potential exacerbation of autoimmune disease activity during pregnancy and its effect on the fetus, the researchers noted. Other limitations included potential detection bias, lack of data on mental disorders in adulthood, and potential changes in diagnostic criteria over the long study period.

The results were strengthened by the use of a population-based registry, the large sample size, and ability to consider a range of confounders, the researchers said.

“This study could help acquire a comprehensive compilation of the associations between maternal autoimmune disorders diagnosed before childbirth and offspring’s mental disorders from childhood through early adulthood,” Dr. Li said in an interview.

For clinicians, Dr. Li said, the findings suggest that the offspring of mothers with autoimmune diseases may benefit from long-term surveillance for mental health disorders.

“Further studies should provide more evidence on the detailed associations of specific maternal autoimmune diseases with a full spectrum of mental disorders in offspring, and more research on underlying mechanisms is needed as well,” she said.
 

Pay early attention

M. Susan Jay, MD, an adjunct professor of pediatrics at the Medical College of Wisconsin, Milwaukee, said previous efforts to examine the association between maternal autoimmunity were hampered by study design, small samples, and self-report of disease history – problems the new research avoids.

The large patient population allowed for detailed subgroup analysis of different conditions and outcomes. Another advantage was the availability of sociodemographic and clinical information, which allowed for the elimination of confounding factors, said Dr. Jay, who was not involved in the research.

“It would be prudent to follow children of mothers with autoimmune disorders before or during pregnancy for mental health issues, and if identified clinically, to offer psychological and developmental behavioral support options,” Dr. Jay added.

The authors have reported no relevant financial relationships.

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

Mental disorders were significantly more likely in children whose mothers had one of five common autoimmune diseases, a new study found.

Previous research has linked both maternal and paternal autoimmune diseases and specific mental disorders, such as attention-deficit/hyperactivity disorder (ADHD), but most of these studies focused on specific conditions in relatively small populations. The new study included data on more than 2 million births, making it one of the largest efforts to date to examine the association, according to the researchers, whose findings were published in JAMA Network Open.

Previous evidence of the possible association between certain maternal autoimmune diseases and mental disorders in offspring has been “scattered and limited,” which “hampered an overall understanding” of the link, Fei Li, MD, the corresponding author of the study, told this news organization.

Dr. Li, of Shanghai Jiao Tong University China, and colleagues reviewed data from a Danish registry cohort of singleton births with up to 38 years of follow-up. They explored associations between a range of maternal autoimmune diseases diagnosed before childbirth and the risks of mental disorders in children in early childhood through young adulthood.

The study population included 2,254,234 births and 38,916,359 person-years. Data on mental health were collected from the Psychiatric Central Research Register and the country’s National Patient Register. The median age of the children at the time of assessment was 16.7 years; approximately half were male.

A total of 50,863 children (2.26%) were born to mothers who had been diagnosed with autoimmune diseases before childbirth. During the follow-up period, 5,460 children of mothers with autoimmune diseases and 303,092 children of mothers without autoimmune diseases were diagnosed with a mental disorder (10.73% vs. 13.76%), according to the researchers.

The risk of being diagnosed with a mental disorder was significantly higher among children of mothers with any autoimmune disease (hazard ratio [HR,], 1.16), with an incidence of 9.38 vs. 7.91 per 1,000 person-years, the researchers reported.

The increased risk persisted when the results were classified by organ system, including connective tissue (HR, 1.11), endocrine (HR, 1.19), gastrointestinal (HR, 1.11), blood (HR, 1.10), nervous (HR, 1.17), and skin (HR, 1.19).

The five autoimmune diseases in mothers that were most commonly associated mental health disorders in children were type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and psoriasis vulgaris.

The greatest risk for children of mothers with any autoimmune disease was observed for organic conditions such as delirium, (HR, 1.54), followed by obsessive-compulsive disorder (HR, 1.42), schizophrenia (HR, 1.54), and mood problems (HR, 1.12).

Children of mothers with any autoimmune disorder also had a significantly increased risk of autism (HR, 1.21), intellectual disability (HR, 1.19), and ADHD (HR, 1.19).

The results add to evidence that activation of the maternal immune system may drive changes in the brain and behavioral problems, which has been observed in animal studies, the researchers wrote.

Potential underlying mechanisms in need of more exploration include genetic risk factors, maternal transmission of autoantibodies to the fetus during pregnancy, and the increased risk of obstetric complications, such as preterm birth, for women with autoimmune disorders that could affect mental development in children, they added.

The study findings were limited by several factors, including the lack of data on potential exacerbation of autoimmune disease activity during pregnancy and its effect on the fetus, the researchers noted. Other limitations included potential detection bias, lack of data on mental disorders in adulthood, and potential changes in diagnostic criteria over the long study period.

The results were strengthened by the use of a population-based registry, the large sample size, and ability to consider a range of confounders, the researchers said.

“This study could help acquire a comprehensive compilation of the associations between maternal autoimmune disorders diagnosed before childbirth and offspring’s mental disorders from childhood through early adulthood,” Dr. Li said in an interview.

For clinicians, Dr. Li said, the findings suggest that the offspring of mothers with autoimmune diseases may benefit from long-term surveillance for mental health disorders.

“Further studies should provide more evidence on the detailed associations of specific maternal autoimmune diseases with a full spectrum of mental disorders in offspring, and more research on underlying mechanisms is needed as well,” she said.
 

Pay early attention

M. Susan Jay, MD, an adjunct professor of pediatrics at the Medical College of Wisconsin, Milwaukee, said previous efforts to examine the association between maternal autoimmunity were hampered by study design, small samples, and self-report of disease history – problems the new research avoids.

The large patient population allowed for detailed subgroup analysis of different conditions and outcomes. Another advantage was the availability of sociodemographic and clinical information, which allowed for the elimination of confounding factors, said Dr. Jay, who was not involved in the research.

“It would be prudent to follow children of mothers with autoimmune disorders before or during pregnancy for mental health issues, and if identified clinically, to offer psychological and developmental behavioral support options,” Dr. Jay added.

The authors have reported no relevant financial relationships.

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

LISBON – A shift toward broader-spectrum antibiotics and increasing antibiotic resistance has led to high levels of mortality and neurodevelopmental impacts in surviving babies, according to a large international study conducted on four continents.

Results of the 3-year study were presented at this week’s European Congress of Clinical Microbiology & Infectious Diseases (ECCMID).

The observational study, NeoOBS, conducted by the Global Antibiotic Research and Development Partnership (GARDP) and key partners from 2018 to 2020, explored the outcomes of more than 3,200 newborns, finding an overall mortality of 11% in those with suspected neonatal sepsis. The mortality rate increased to 18% in newborns in whom a pathogen was detected in blood culture.

More than half of infection-related deaths (59%) were due to hospital-acquired infections. Klebsiella pneumoniae was the most common pathogen isolated and is usually associated with hospital-acquired infections, which are increasingly resistant to existing antibiotic treatments, said a report produced by GARDP to accompany the results.

The study also identified a worrying trend: Hospitals are frequently using last-line agents such as carbapenems because of the high degree of antibiotic resistance in their facilities. Of note, 15% of babies with neonatal sepsis were given last-line antibiotics.

Pediatrician Julia Bielicki, MD, PhD, senior lecturer, Paediatric Infectious Diseases Research Group, St. George’s University of London, and clinician at the University of Basel Children’s Hospital, Switzerland, was a coinvestigator on the NeoOBS study.

In an interview, she explained that, as well as reducing mortality, the research is about managing infections better to prevent long-term events and improve the quality of life for survivors of neonatal sepsis. “It can have life-changing impacts for so many babies,” Dr. Bielicki said. “Improving care is much more than just making sure the baby survives the episode of sepsis – it’s about ensuring these babies can become children and adults and go on to lead productive lives.”

Also, only a minority of patients (13%) received the World Health Organization guidelines for standard of care use of ampicillin and gentamicin, and there was increasing use of last-line agents such as carbapenems and even polymyxins in some settings in low- and middle-income countries. “This is alarming and foretells the impending crisis of a lack of antibiotics to treat sepsis caused by multidrug-resistant organisms,” according to the GARDP report.

There was wide variability in antibiotic combinations used across sites in Bangladesh, Brazil, China, Greece, India, Italy, Kenya, South Africa, Thailand, Uganda, and Vietnam, and often such use was not supported by underlying data.

Dr. Bielicki remarked that there was a shift toward broad-spectrum antibiotic use. “In a high-income country, you have more restrictive patterns of antibiotic use, but it isn’t necessarily less antibiotic exposure of neonates to antibiotics, but on the whole, usually narrow-spectrum agents are used.”

In Africa and Asia, on the other hand, clinicians often have to use a broader-spectrum antibiotic empirically and may need to switch to another antibiotic very quickly. “Sometimes alternatives are not available,” she pointed out.

“Local physicians are very perceptive of this problem of antibiotic resistance in their daily practice, especially in centers with high mortality,” said Dr. Bielicki, emphasizing that it is not their fault, but is “due to the limitations in terms of the weapons available to treat these babies, which strongly demonstrates the growing problem of antimicrobial resistance affecting these babies on a global scale.”

Tim Jinks, PhD, Head of Drug Resistant Infections Priority Program at Wellcome Trust, commented on the study in a series of text messages to this news organization. “This research provides further demonstration of the urgent need for improved treatment of newborns suffering with sepsis and particularly the requirement for new antibiotics that overcome the burden of drug-resistant infections caused by [antimicrobial resistance].”

“The study is a hugely important contribution to our understanding of the burden of neonatal sepsis in low- and middle- income countries,” he added, “and points toward ways that patient treatment can be improved to save more lives.”
 

High-, middle-, and low-income countries

The NeoOBS study gathered data from 19 hospitals in 11 high-, middle-, and low-income countries and assessed which antibiotics are currently being used to treat neonatal sepsis, as well as the degree of drug resistance associated with them. Sites included some in Italy and Greece, where most of the neonatal sepsis data currently originate, and this helped to anchor the data, Dr. Bielicki said.

The study identified babies with clinical sepsis over a 4-week period and observed how these patients were managed, particularly with respect to antibiotics, as well as outcomes including whether they recovered, remained in hospital, or died. Investigators obtained bacterial cultures from the patients and grew them to identify which organisms were causing the sepsis.

Of note, mortality varied widely between hospitals, ranging from 1% to 27%. Dr. Bielicki explained that the investigators were currently exploring the reasons behind this wide range of mortality. “There are lots of possible reasons for this, including structural factors such as how care is delivered, which is complex to measure,” she said. “It isn’t trivial to measure why, in a certain setting, mortality is low and why in another setting of comparable income range, mortality is much higher.”

Aside from the mortality results, Dr. Bielicki also emphasized that the survivors of neonatal sepsis frequently experience neurodevelopmental impacts. “A hospital may have low mortality, but many of these babies may have neurodevelopment problems, and this has a long-term impact.”

“Even though mortality might be low in a certain hospital, it might not be low in terms of morbidity,” she added.

The researchers also collected isolates from the cohort of neonates to determine which antibiotic combinations work against the pathogens. “This will help us define what sort of antibiotic regimen warrants further investigation,” Dr. Bielicki said.

Principal Investigator, Mike Sharland, MD, also from St. George’s, University of London, who is also the Antimicrobial Resistance Program Lead at Penta Child Health Research, said, in a press release, that the study had shown that antibiotic resistance is now one of the major threats to neonatal health globally. “There are virtually no studies underway on developing novel antibiotic treatments for babies with sepsis caused by multidrug-resistant infections.”

“This is a major problem for babies in all countries, both rich and poor,” he stressed.
 

NeoSep-1 trial to compare multiple different treatments

The results have paved the way for a major new global trial of multiple established and new antibiotics with the goal of reducing mortality from neonatal sepsis – the NeoSep1 trial.

“This is a randomized trial with a specific design that allows us to rank different treatments against each other in terms of effectiveness, safety, and costs,” Dr. Bielicki explained.

Among the antibiotics in the study are amikacin, flomoxef and amikacin, or fosfomycin and flomoxef in babies with sepsis 28 days old or younger. Similar to the NeoOBS study, patients will be recruited from all over the world, and in particular from low- and middle-income countries such as Kenya, South Africa, and other countries in Africa and Southeast Asia.

Ultimately, the researchers want to identify modifiable risk factors and enact change in practice. But Dr. Bielicki was quick to point out that it was difficult to disentangle those factors that can easily be changed. “Some can be changed in theory, but in practice it is actually difficult to change them. One modifiable risk factor that can be changed is probably infection control, so when resistant bacteria appear in a unit, we need to ensure that there is no or minimal transmission between babies.”

Luregn Schlapbach, MD, PhD, Head, department of intensive care and neonatology, University Children’s Hospital Zurich, Switzerland, welcomed the study, saying recent recognition of pediatric and neonatal sepsis was an urgent problem worldwide.

She referred to the 2017 WHO resolution recognizing that sepsis represents a leading cause of mortality and morbidity worldwide, affecting patients of all ages, across all continents and health care systems but that many were pediatric. “At that time, our understanding of the true burden of sepsis was limited, as was our knowledge of current epidemiology,” she said in an email interview. “The Global Burden of Disease study in 2020 revealed that about half of the approximatively 50 million global sepsis cases affect pediatric age groups, many of those during neonatal age.”

The formal acknowledgment of this extensive need emphasizes the “urgency to design preventive and therapeutic interventions to reduce this devastating burden,” Dr. Schlapbach said. “In this context, the work led by GARDP is of great importance – it is designed to improve our understanding of current practice, risk factors, and burden of neonatal sepsis across low- to middle-income settings and is essential to design adequately powered trials testing interventions such as antimicrobials to improve patient outcomes and reduce the further emergence of antimicrobial resistance.”

Dr. Bielicki and Dr. Schlapbach have disclosed no relevant financial relationships.

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

LISBON – A shift toward broader-spectrum antibiotics and increasing antibiotic resistance has led to high levels of mortality and neurodevelopmental impacts in surviving babies, according to a large international study conducted on four continents.

Results of the 3-year study were presented at this week’s European Congress of Clinical Microbiology & Infectious Diseases (ECCMID).

The observational study, NeoOBS, conducted by the Global Antibiotic Research and Development Partnership (GARDP) and key partners from 2018 to 2020, explored the outcomes of more than 3,200 newborns, finding an overall mortality of 11% in those with suspected neonatal sepsis. The mortality rate increased to 18% in newborns in whom a pathogen was detected in blood culture.

More than half of infection-related deaths (59%) were due to hospital-acquired infections. Klebsiella pneumoniae was the most common pathogen isolated and is usually associated with hospital-acquired infections, which are increasingly resistant to existing antibiotic treatments, said a report produced by GARDP to accompany the results.

The study also identified a worrying trend: Hospitals are frequently using last-line agents such as carbapenems because of the high degree of antibiotic resistance in their facilities. Of note, 15% of babies with neonatal sepsis were given last-line antibiotics.

Pediatrician Julia Bielicki, MD, PhD, senior lecturer, Paediatric Infectious Diseases Research Group, St. George’s University of London, and clinician at the University of Basel Children’s Hospital, Switzerland, was a coinvestigator on the NeoOBS study.

In an interview, she explained that, as well as reducing mortality, the research is about managing infections better to prevent long-term events and improve the quality of life for survivors of neonatal sepsis. “It can have life-changing impacts for so many babies,” Dr. Bielicki said. “Improving care is much more than just making sure the baby survives the episode of sepsis – it’s about ensuring these babies can become children and adults and go on to lead productive lives.”

Also, only a minority of patients (13%) received the World Health Organization guidelines for standard of care use of ampicillin and gentamicin, and there was increasing use of last-line agents such as carbapenems and even polymyxins in some settings in low- and middle-income countries. “This is alarming and foretells the impending crisis of a lack of antibiotics to treat sepsis caused by multidrug-resistant organisms,” according to the GARDP report.

There was wide variability in antibiotic combinations used across sites in Bangladesh, Brazil, China, Greece, India, Italy, Kenya, South Africa, Thailand, Uganda, and Vietnam, and often such use was not supported by underlying data.

Dr. Bielicki remarked that there was a shift toward broad-spectrum antibiotic use. “In a high-income country, you have more restrictive patterns of antibiotic use, but it isn’t necessarily less antibiotic exposure of neonates to antibiotics, but on the whole, usually narrow-spectrum agents are used.”

In Africa and Asia, on the other hand, clinicians often have to use a broader-spectrum antibiotic empirically and may need to switch to another antibiotic very quickly. “Sometimes alternatives are not available,” she pointed out.

“Local physicians are very perceptive of this problem of antibiotic resistance in their daily practice, especially in centers with high mortality,” said Dr. Bielicki, emphasizing that it is not their fault, but is “due to the limitations in terms of the weapons available to treat these babies, which strongly demonstrates the growing problem of antimicrobial resistance affecting these babies on a global scale.”

Tim Jinks, PhD, Head of Drug Resistant Infections Priority Program at Wellcome Trust, commented on the study in a series of text messages to this news organization. “This research provides further demonstration of the urgent need for improved treatment of newborns suffering with sepsis and particularly the requirement for new antibiotics that overcome the burden of drug-resistant infections caused by [antimicrobial resistance].”

“The study is a hugely important contribution to our understanding of the burden of neonatal sepsis in low- and middle- income countries,” he added, “and points toward ways that patient treatment can be improved to save more lives.”
 

High-, middle-, and low-income countries

The NeoOBS study gathered data from 19 hospitals in 11 high-, middle-, and low-income countries and assessed which antibiotics are currently being used to treat neonatal sepsis, as well as the degree of drug resistance associated with them. Sites included some in Italy and Greece, where most of the neonatal sepsis data currently originate, and this helped to anchor the data, Dr. Bielicki said.

The study identified babies with clinical sepsis over a 4-week period and observed how these patients were managed, particularly with respect to antibiotics, as well as outcomes including whether they recovered, remained in hospital, or died. Investigators obtained bacterial cultures from the patients and grew them to identify which organisms were causing the sepsis.

Of note, mortality varied widely between hospitals, ranging from 1% to 27%. Dr. Bielicki explained that the investigators were currently exploring the reasons behind this wide range of mortality. “There are lots of possible reasons for this, including structural factors such as how care is delivered, which is complex to measure,” she said. “It isn’t trivial to measure why, in a certain setting, mortality is low and why in another setting of comparable income range, mortality is much higher.”

Aside from the mortality results, Dr. Bielicki also emphasized that the survivors of neonatal sepsis frequently experience neurodevelopmental impacts. “A hospital may have low mortality, but many of these babies may have neurodevelopment problems, and this has a long-term impact.”

“Even though mortality might be low in a certain hospital, it might not be low in terms of morbidity,” she added.

The researchers also collected isolates from the cohort of neonates to determine which antibiotic combinations work against the pathogens. “This will help us define what sort of antibiotic regimen warrants further investigation,” Dr. Bielicki said.

Principal Investigator, Mike Sharland, MD, also from St. George’s, University of London, who is also the Antimicrobial Resistance Program Lead at Penta Child Health Research, said, in a press release, that the study had shown that antibiotic resistance is now one of the major threats to neonatal health globally. “There are virtually no studies underway on developing novel antibiotic treatments for babies with sepsis caused by multidrug-resistant infections.”

“This is a major problem for babies in all countries, both rich and poor,” he stressed.
 

NeoSep-1 trial to compare multiple different treatments

The results have paved the way for a major new global trial of multiple established and new antibiotics with the goal of reducing mortality from neonatal sepsis – the NeoSep1 trial.

“This is a randomized trial with a specific design that allows us to rank different treatments against each other in terms of effectiveness, safety, and costs,” Dr. Bielicki explained.

Among the antibiotics in the study are amikacin, flomoxef and amikacin, or fosfomycin and flomoxef in babies with sepsis 28 days old or younger. Similar to the NeoOBS study, patients will be recruited from all over the world, and in particular from low- and middle-income countries such as Kenya, South Africa, and other countries in Africa and Southeast Asia.

Ultimately, the researchers want to identify modifiable risk factors and enact change in practice. But Dr. Bielicki was quick to point out that it was difficult to disentangle those factors that can easily be changed. “Some can be changed in theory, but in practice it is actually difficult to change them. One modifiable risk factor that can be changed is probably infection control, so when resistant bacteria appear in a unit, we need to ensure that there is no or minimal transmission between babies.”

Luregn Schlapbach, MD, PhD, Head, department of intensive care and neonatology, University Children’s Hospital Zurich, Switzerland, welcomed the study, saying recent recognition of pediatric and neonatal sepsis was an urgent problem worldwide.

She referred to the 2017 WHO resolution recognizing that sepsis represents a leading cause of mortality and morbidity worldwide, affecting patients of all ages, across all continents and health care systems but that many were pediatric. “At that time, our understanding of the true burden of sepsis was limited, as was our knowledge of current epidemiology,” she said in an email interview. “The Global Burden of Disease study in 2020 revealed that about half of the approximatively 50 million global sepsis cases affect pediatric age groups, many of those during neonatal age.”

The formal acknowledgment of this extensive need emphasizes the “urgency to design preventive and therapeutic interventions to reduce this devastating burden,” Dr. Schlapbach said. “In this context, the work led by GARDP is of great importance – it is designed to improve our understanding of current practice, risk factors, and burden of neonatal sepsis across low- to middle-income settings and is essential to design adequately powered trials testing interventions such as antimicrobials to improve patient outcomes and reduce the further emergence of antimicrobial resistance.”

Dr. Bielicki and Dr. Schlapbach have disclosed no relevant financial relationships.

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

LISBON – A shift toward broader-spectrum antibiotics and increasing antibiotic resistance has led to high levels of mortality and neurodevelopmental impacts in surviving babies, according to a large international study conducted on four continents.

Results of the 3-year study were presented at this week’s European Congress of Clinical Microbiology & Infectious Diseases (ECCMID).

The observational study, NeoOBS, conducted by the Global Antibiotic Research and Development Partnership (GARDP) and key partners from 2018 to 2020, explored the outcomes of more than 3,200 newborns, finding an overall mortality of 11% in those with suspected neonatal sepsis. The mortality rate increased to 18% in newborns in whom a pathogen was detected in blood culture.

More than half of infection-related deaths (59%) were due to hospital-acquired infections. Klebsiella pneumoniae was the most common pathogen isolated and is usually associated with hospital-acquired infections, which are increasingly resistant to existing antibiotic treatments, said a report produced by GARDP to accompany the results.

The study also identified a worrying trend: Hospitals are frequently using last-line agents such as carbapenems because of the high degree of antibiotic resistance in their facilities. Of note, 15% of babies with neonatal sepsis were given last-line antibiotics.

Pediatrician Julia Bielicki, MD, PhD, senior lecturer, Paediatric Infectious Diseases Research Group, St. George’s University of London, and clinician at the University of Basel Children’s Hospital, Switzerland, was a coinvestigator on the NeoOBS study.

In an interview, she explained that, as well as reducing mortality, the research is about managing infections better to prevent long-term events and improve the quality of life for survivors of neonatal sepsis. “It can have life-changing impacts for so many babies,” Dr. Bielicki said. “Improving care is much more than just making sure the baby survives the episode of sepsis – it’s about ensuring these babies can become children and adults and go on to lead productive lives.”

Also, only a minority of patients (13%) received the World Health Organization guidelines for standard of care use of ampicillin and gentamicin, and there was increasing use of last-line agents such as carbapenems and even polymyxins in some settings in low- and middle-income countries. “This is alarming and foretells the impending crisis of a lack of antibiotics to treat sepsis caused by multidrug-resistant organisms,” according to the GARDP report.

There was wide variability in antibiotic combinations used across sites in Bangladesh, Brazil, China, Greece, India, Italy, Kenya, South Africa, Thailand, Uganda, and Vietnam, and often such use was not supported by underlying data.

Dr. Bielicki remarked that there was a shift toward broad-spectrum antibiotic use. “In a high-income country, you have more restrictive patterns of antibiotic use, but it isn’t necessarily less antibiotic exposure of neonates to antibiotics, but on the whole, usually narrow-spectrum agents are used.”

In Africa and Asia, on the other hand, clinicians often have to use a broader-spectrum antibiotic empirically and may need to switch to another antibiotic very quickly. “Sometimes alternatives are not available,” she pointed out.

“Local physicians are very perceptive of this problem of antibiotic resistance in their daily practice, especially in centers with high mortality,” said Dr. Bielicki, emphasizing that it is not their fault, but is “due to the limitations in terms of the weapons available to treat these babies, which strongly demonstrates the growing problem of antimicrobial resistance affecting these babies on a global scale.”

Tim Jinks, PhD, Head of Drug Resistant Infections Priority Program at Wellcome Trust, commented on the study in a series of text messages to this news organization. “This research provides further demonstration of the urgent need for improved treatment of newborns suffering with sepsis and particularly the requirement for new antibiotics that overcome the burden of drug-resistant infections caused by [antimicrobial resistance].”

“The study is a hugely important contribution to our understanding of the burden of neonatal sepsis in low- and middle- income countries,” he added, “and points toward ways that patient treatment can be improved to save more lives.”
 

High-, middle-, and low-income countries

The NeoOBS study gathered data from 19 hospitals in 11 high-, middle-, and low-income countries and assessed which antibiotics are currently being used to treat neonatal sepsis, as well as the degree of drug resistance associated with them. Sites included some in Italy and Greece, where most of the neonatal sepsis data currently originate, and this helped to anchor the data, Dr. Bielicki said.

The study identified babies with clinical sepsis over a 4-week period and observed how these patients were managed, particularly with respect to antibiotics, as well as outcomes including whether they recovered, remained in hospital, or died. Investigators obtained bacterial cultures from the patients and grew them to identify which organisms were causing the sepsis.

Of note, mortality varied widely between hospitals, ranging from 1% to 27%. Dr. Bielicki explained that the investigators were currently exploring the reasons behind this wide range of mortality. “There are lots of possible reasons for this, including structural factors such as how care is delivered, which is complex to measure,” she said. “It isn’t trivial to measure why, in a certain setting, mortality is low and why in another setting of comparable income range, mortality is much higher.”

Aside from the mortality results, Dr. Bielicki also emphasized that the survivors of neonatal sepsis frequently experience neurodevelopmental impacts. “A hospital may have low mortality, but many of these babies may have neurodevelopment problems, and this has a long-term impact.”

“Even though mortality might be low in a certain hospital, it might not be low in terms of morbidity,” she added.

The researchers also collected isolates from the cohort of neonates to determine which antibiotic combinations work against the pathogens. “This will help us define what sort of antibiotic regimen warrants further investigation,” Dr. Bielicki said.

Principal Investigator, Mike Sharland, MD, also from St. George’s, University of London, who is also the Antimicrobial Resistance Program Lead at Penta Child Health Research, said, in a press release, that the study had shown that antibiotic resistance is now one of the major threats to neonatal health globally. “There are virtually no studies underway on developing novel antibiotic treatments for babies with sepsis caused by multidrug-resistant infections.”

“This is a major problem for babies in all countries, both rich and poor,” he stressed.
 

NeoSep-1 trial to compare multiple different treatments

The results have paved the way for a major new global trial of multiple established and new antibiotics with the goal of reducing mortality from neonatal sepsis – the NeoSep1 trial.

“This is a randomized trial with a specific design that allows us to rank different treatments against each other in terms of effectiveness, safety, and costs,” Dr. Bielicki explained.

Among the antibiotics in the study are amikacin, flomoxef and amikacin, or fosfomycin and flomoxef in babies with sepsis 28 days old or younger. Similar to the NeoOBS study, patients will be recruited from all over the world, and in particular from low- and middle-income countries such as Kenya, South Africa, and other countries in Africa and Southeast Asia.

Ultimately, the researchers want to identify modifiable risk factors and enact change in practice. But Dr. Bielicki was quick to point out that it was difficult to disentangle those factors that can easily be changed. “Some can be changed in theory, but in practice it is actually difficult to change them. One modifiable risk factor that can be changed is probably infection control, so when resistant bacteria appear in a unit, we need to ensure that there is no or minimal transmission between babies.”

Luregn Schlapbach, MD, PhD, Head, department of intensive care and neonatology, University Children’s Hospital Zurich, Switzerland, welcomed the study, saying recent recognition of pediatric and neonatal sepsis was an urgent problem worldwide.

She referred to the 2017 WHO resolution recognizing that sepsis represents a leading cause of mortality and morbidity worldwide, affecting patients of all ages, across all continents and health care systems but that many were pediatric. “At that time, our understanding of the true burden of sepsis was limited, as was our knowledge of current epidemiology,” she said in an email interview. “The Global Burden of Disease study in 2020 revealed that about half of the approximatively 50 million global sepsis cases affect pediatric age groups, many of those during neonatal age.”

The formal acknowledgment of this extensive need emphasizes the “urgency to design preventive and therapeutic interventions to reduce this devastating burden,” Dr. Schlapbach said. “In this context, the work led by GARDP is of great importance – it is designed to improve our understanding of current practice, risk factors, and burden of neonatal sepsis across low- to middle-income settings and is essential to design adequately powered trials testing interventions such as antimicrobials to improve patient outcomes and reduce the further emergence of antimicrobial resistance.”

Dr. Bielicki and Dr. Schlapbach have disclosed no relevant financial relationships.

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

The risk for dementia goes up in patients with atrial fibrillation (AFib), but some evidence suggests that risk can be blunted with therapies that restore sinus rhythm. However, a new cohort study suggests that the treatment effect’s magnitude might depend on the rhythm control strategy. It hinted that AFib catheter ablation might be more effective than pharmacologic rhythm control alone at cutting the risk for dementia.

The case-matched study of more than 38,000 adults with AFib saw a 41% reduction (P < .0001) in risk for dementia among those who underwent catheter ablation after attempted rhythm control with antiarrhythmic drugs (AAD), compared with those managed with pharmacologic rhythm control therapy alone.

The observational study comprising 20 years of data comes with big limitations and can’t say for sure whether catheter ablation is better than AAD-only at cutting the dementia risk in AFib. But it and other evidence support the idea, which has yet to be explored in a randomized fashion.

In a secondary finding, the analysis showed a similar reduction in dementia risk from catheter ablation, compared with AAD, in women and in men by 40% and 45%, respectively (P < .0001 for both). The findings are particularly relevant “given the higher life-long risk of dementia among women and the lower likelihood that women will be offered ablation, which has been demonstrated repeatedly,” Emily P. Zeitler, MD, MHS, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, told this news organization. “I think this is another reason to try to be more generous in offering ablation to women.”

Management of AFib certainly evolved in important ways from 2000 to 2021, the period covered by the study. But a sensitivity analysis based on data from 2010 to 2021 showed “no meaningful differences” in the results, said Dr. Zeitler, who is slated to present the findings April 30 at the Heart Rhythm Society 2022 Scientific Sessions, conducted virtually and live in San Francisco.

Dr. Zeitler acknowledged that the observational study, even with its propensity-matched ablation and AAD cohorts, can only hint at a preference for ablation over AAD for lowering risk for AFib-associated dementia. “We know there’s unmeasured and unfixable confounding between those two groups, so we see this really as hypothesis-generating.”

It was “a well-done analysis,” and the conclusion that the dementia risk was lower with catheter ablation is “absolutely correct,” but only as far as the study and its limitations allow, agreed David Conen, MD, MPH, McMaster University, Hamilton, Ontario, who is not a coauthor.

“Even with propensity matching, you can get rid of some sorts of confounding, but you can never get rid of all selection bias issues.” That, he said when interviewed, takes randomized trials.

Dr. Conen, who is studying cognitive decline in AFib as a SWISS-AF trial principal investigator, pointed to a secondary finding of the analysis as evidence for such confounding. He said the ablation group’s nearly 50% drop (P < .0001) in competing risk for death, compared with patients managed with AAD, isn’t plausible.

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

The risk for dementia goes up in patients with atrial fibrillation (AFib), but some evidence suggests that risk can be blunted with therapies that restore sinus rhythm. However, a new cohort study suggests that the treatment effect’s magnitude might depend on the rhythm control strategy. It hinted that AFib catheter ablation might be more effective than pharmacologic rhythm control alone at cutting the risk for dementia.

The case-matched study of more than 38,000 adults with AFib saw a 41% reduction (P < .0001) in risk for dementia among those who underwent catheter ablation after attempted rhythm control with antiarrhythmic drugs (AAD), compared with those managed with pharmacologic rhythm control therapy alone.

The observational study comprising 20 years of data comes with big limitations and can’t say for sure whether catheter ablation is better than AAD-only at cutting the dementia risk in AFib. But it and other evidence support the idea, which has yet to be explored in a randomized fashion.

In a secondary finding, the analysis showed a similar reduction in dementia risk from catheter ablation, compared with AAD, in women and in men by 40% and 45%, respectively (P < .0001 for both). The findings are particularly relevant “given the higher life-long risk of dementia among women and the lower likelihood that women will be offered ablation, which has been demonstrated repeatedly,” Emily P. Zeitler, MD, MHS, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, told this news organization. “I think this is another reason to try to be more generous in offering ablation to women.”

Management of AFib certainly evolved in important ways from 2000 to 2021, the period covered by the study. But a sensitivity analysis based on data from 2010 to 2021 showed “no meaningful differences” in the results, said Dr. Zeitler, who is slated to present the findings April 30 at the Heart Rhythm Society 2022 Scientific Sessions, conducted virtually and live in San Francisco.

Dr. Zeitler acknowledged that the observational study, even with its propensity-matched ablation and AAD cohorts, can only hint at a preference for ablation over AAD for lowering risk for AFib-associated dementia. “We know there’s unmeasured and unfixable confounding between those two groups, so we see this really as hypothesis-generating.”

It was “a well-done analysis,” and the conclusion that the dementia risk was lower with catheter ablation is “absolutely correct,” but only as far as the study and its limitations allow, agreed David Conen, MD, MPH, McMaster University, Hamilton, Ontario, who is not a coauthor.

“Even with propensity matching, you can get rid of some sorts of confounding, but you can never get rid of all selection bias issues.” That, he said when interviewed, takes randomized trials.

Dr. Conen, who is studying cognitive decline in AFib as a SWISS-AF trial principal investigator, pointed to a secondary finding of the analysis as evidence for such confounding. He said the ablation group’s nearly 50% drop (P < .0001) in competing risk for death, compared with patients managed with AAD, isn’t plausible.

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

The risk for dementia goes up in patients with atrial fibrillation (AFib), but some evidence suggests that risk can be blunted with therapies that restore sinus rhythm. However, a new cohort study suggests that the treatment effect’s magnitude might depend on the rhythm control strategy. It hinted that AFib catheter ablation might be more effective than pharmacologic rhythm control alone at cutting the risk for dementia.

The case-matched study of more than 38,000 adults with AFib saw a 41% reduction (P < .0001) in risk for dementia among those who underwent catheter ablation after attempted rhythm control with antiarrhythmic drugs (AAD), compared with those managed with pharmacologic rhythm control therapy alone.

The observational study comprising 20 years of data comes with big limitations and can’t say for sure whether catheter ablation is better than AAD-only at cutting the dementia risk in AFib. But it and other evidence support the idea, which has yet to be explored in a randomized fashion.

In a secondary finding, the analysis showed a similar reduction in dementia risk from catheter ablation, compared with AAD, in women and in men by 40% and 45%, respectively (P < .0001 for both). The findings are particularly relevant “given the higher life-long risk of dementia among women and the lower likelihood that women will be offered ablation, which has been demonstrated repeatedly,” Emily P. Zeitler, MD, MHS, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, told this news organization. “I think this is another reason to try to be more generous in offering ablation to women.”

Management of AFib certainly evolved in important ways from 2000 to 2021, the period covered by the study. But a sensitivity analysis based on data from 2010 to 2021 showed “no meaningful differences” in the results, said Dr. Zeitler, who is slated to present the findings April 30 at the Heart Rhythm Society 2022 Scientific Sessions, conducted virtually and live in San Francisco.

Dr. Zeitler acknowledged that the observational study, even with its propensity-matched ablation and AAD cohorts, can only hint at a preference for ablation over AAD for lowering risk for AFib-associated dementia. “We know there’s unmeasured and unfixable confounding between those two groups, so we see this really as hypothesis-generating.”

It was “a well-done analysis,” and the conclusion that the dementia risk was lower with catheter ablation is “absolutely correct,” but only as far as the study and its limitations allow, agreed David Conen, MD, MPH, McMaster University, Hamilton, Ontario, who is not a coauthor.

“Even with propensity matching, you can get rid of some sorts of confounding, but you can never get rid of all selection bias issues.” That, he said when interviewed, takes randomized trials.

Dr. Conen, who is studying cognitive decline in AFib as a SWISS-AF trial principal investigator, pointed to a secondary finding of the analysis as evidence for such confounding. He said the ablation group’s nearly 50% drop (P < .0001) in competing risk for death, compared with patients managed with AAD, isn’t plausible.

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

The latest upward trend in new COVID-19 cases among children picked up steam, but there was also some movement in the vaccination effort in the past week.

Moderna submitted a request to the Food and Drug administration for emergency use authorization of its COVID-19 vaccine in children under the age of 6 years, according to this news organization, and Pfizer/BioNTech officially applied for authorization of a booster dose in children aged 5-11, the companies announced.

The FDA has tentatively scheduled meetings of its Vaccines and Related Biological Products Advisory Committee in June to consider the applications, saying that it “understands the urgency to authorize a vaccine for age groups who are not currently eligible for vaccination and will work diligently to complete our evaluation of the data. Should any of the submissions be completed in a timely manner and the data support a clear path forward following our evaluation, the FDA will act quickly” to convene the necessary meetings.

The need for greater access to vaccines seems to be increasing, as new pediatric COVID cases rose for the third consecutive week. April 22-28 saw over 53,000 new cases reported in children, up 43.5% from the previous week and up 105% since cases started rising again after dipping under 26,000 during the week of April 1-7, based on data from the American Academy of Pediatrics and the Children’s Hospital Association.

Hospital admissions involving diagnosed COVID also ticked up over the latter half of April, although the most recent 7-day average (April 24-30) of 112 per day was lower than the 117 reported for the previous week (April 17-23), the Centers for Disease Control and Prevention said, also noting that figures for the latest week “should be interpreted with caution.”

Vaccinations also were up slightly in children aged 5-11 years, with 52,000 receiving their first dose during the week of April 21-27, compared with 48,000 the week before. There was a slight dip, however, among 12- to 17-year-olds, who received 34,000 first doses during April 21-27, versus 35,000 the previous week, the AAP said in a separate report.

Cumulatively, almost 69% of all children aged 12-17 years have received at least one dose of the COVID-19 vaccine and 59% are fully vaccinated. Those aged 5-11 are well short of those figures, with just over 35% having received at least one dose and 28.5% fully vaccinated, the CDC said on its COVID Data Tracker.

A look at recent activity shows that children are not gaining on adults, who are much more likely to be vaccinated – full vaccination in those aged 50-64, for example, is 80%. During the 2 weeks from April 17-30, the 5- to 11-year-olds represented 10.5% of those who had initiated a first dose and 12.4% of those who gained full-vaccination status, both of which were well below the oldest age groups, the CDC reported.

rfranki@mdedge.com

The latest upward trend in new COVID-19 cases among children picked up steam, but there was also some movement in the vaccination effort in the past week.

Moderna submitted a request to the Food and Drug administration for emergency use authorization of its COVID-19 vaccine in children under the age of 6 years, according to this news organization, and Pfizer/BioNTech officially applied for authorization of a booster dose in children aged 5-11, the companies announced.

The FDA has tentatively scheduled meetings of its Vaccines and Related Biological Products Advisory Committee in June to consider the applications, saying that it “understands the urgency to authorize a vaccine for age groups who are not currently eligible for vaccination and will work diligently to complete our evaluation of the data. Should any of the submissions be completed in a timely manner and the data support a clear path forward following our evaluation, the FDA will act quickly” to convene the necessary meetings.

The need for greater access to vaccines seems to be increasing, as new pediatric COVID cases rose for the third consecutive week. April 22-28 saw over 53,000 new cases reported in children, up 43.5% from the previous week and up 105% since cases started rising again after dipping under 26,000 during the week of April 1-7, based on data from the American Academy of Pediatrics and the Children’s Hospital Association.

Hospital admissions involving diagnosed COVID also ticked up over the latter half of April, although the most recent 7-day average (April 24-30) of 112 per day was lower than the 117 reported for the previous week (April 17-23), the Centers for Disease Control and Prevention said, also noting that figures for the latest week “should be interpreted with caution.”

Vaccinations also were up slightly in children aged 5-11 years, with 52,000 receiving their first dose during the week of April 21-27, compared with 48,000 the week before. There was a slight dip, however, among 12- to 17-year-olds, who received 34,000 first doses during April 21-27, versus 35,000 the previous week, the AAP said in a separate report.

Cumulatively, almost 69% of all children aged 12-17 years have received at least one dose of the COVID-19 vaccine and 59% are fully vaccinated. Those aged 5-11 are well short of those figures, with just over 35% having received at least one dose and 28.5% fully vaccinated, the CDC said on its COVID Data Tracker.

A look at recent activity shows that children are not gaining on adults, who are much more likely to be vaccinated – full vaccination in those aged 50-64, for example, is 80%. During the 2 weeks from April 17-30, the 5- to 11-year-olds represented 10.5% of those who had initiated a first dose and 12.4% of those who gained full-vaccination status, both of which were well below the oldest age groups, the CDC reported.

rfranki@mdedge.com

The latest upward trend in new COVID-19 cases among children picked up steam, but there was also some movement in the vaccination effort in the past week.

Moderna submitted a request to the Food and Drug administration for emergency use authorization of its COVID-19 vaccine in children under the age of 6 years, according to this news organization, and Pfizer/BioNTech officially applied for authorization of a booster dose in children aged 5-11, the companies announced.

The FDA has tentatively scheduled meetings of its Vaccines and Related Biological Products Advisory Committee in June to consider the applications, saying that it “understands the urgency to authorize a vaccine for age groups who are not currently eligible for vaccination and will work diligently to complete our evaluation of the data. Should any of the submissions be completed in a timely manner and the data support a clear path forward following our evaluation, the FDA will act quickly” to convene the necessary meetings.

The need for greater access to vaccines seems to be increasing, as new pediatric COVID cases rose for the third consecutive week. April 22-28 saw over 53,000 new cases reported in children, up 43.5% from the previous week and up 105% since cases started rising again after dipping under 26,000 during the week of April 1-7, based on data from the American Academy of Pediatrics and the Children’s Hospital Association.

Hospital admissions involving diagnosed COVID also ticked up over the latter half of April, although the most recent 7-day average (April 24-30) of 112 per day was lower than the 117 reported for the previous week (April 17-23), the Centers for Disease Control and Prevention said, also noting that figures for the latest week “should be interpreted with caution.”

Vaccinations also were up slightly in children aged 5-11 years, with 52,000 receiving their first dose during the week of April 21-27, compared with 48,000 the week before. There was a slight dip, however, among 12- to 17-year-olds, who received 34,000 first doses during April 21-27, versus 35,000 the previous week, the AAP said in a separate report.

Cumulatively, almost 69% of all children aged 12-17 years have received at least one dose of the COVID-19 vaccine and 59% are fully vaccinated. Those aged 5-11 are well short of those figures, with just over 35% having received at least one dose and 28.5% fully vaccinated, the CDC said on its COVID Data Tracker.

A look at recent activity shows that children are not gaining on adults, who are much more likely to be vaccinated – full vaccination in those aged 50-64, for example, is 80%. During the 2 weeks from April 17-30, the 5- to 11-year-olds represented 10.5% of those who had initiated a first dose and 12.4% of those who gained full-vaccination status, both of which were well below the oldest age groups, the CDC reported.

rfranki@mdedge.com

CHICAGO – Recent research has changed at least one physician’s understanding of obesity and boosted her hope for fighting it.

Caroline Apovian, MD, codirector of the Center for Weight Management and Wellness at Brigham and Women’s Hospital, described some of the new insights about obesity she has gained during her talk at the annual meeting of the American College of Physicians.

“When I was a medical student a while back, I learned that fat tissue just sat there and stored fat,” she said. “Now we know it’s an endocrine organ.”

This tissue secretes hormones, such as leptin, and other factors that have an array of effects on the brain, pancreas, heart, liver, and muscles. Moreover, it has plasticity, with the ability to change, constantly adjusting our metabolism as nutrient supply and demand changes, she continued.

Obesity leads to a decline in this plasticity, leading to fibrosis and inflammation and other problems. These changes can further impair the function of adipose tissue, leading to metabolic disease. But the central role of adipose tissue, and its dynamic nature, presents an opportunity for treatment, Dr. Apovian said, during her talk.
 

Hints to why obesity has become more common

More than 42% of the U.S. population – “unbelievably,” Dr. Apovian said – is obese, meaning they have a BMI over 30, according to the Centers for Disease Control and Prevention. That’s up by about 25% since 1960, although calories eaten hasn’t increased, and physical activity has increased somewhat, she said.

The root cause is still a bit of a mystery, but according to “good hints and clues” from animal models that are starting to be translated to the study of human obesity, “it has to do with epigenetics and how our brains and our bodies are perceiving the environment,” she noted, during her presentation.

“Our genes haven’t changed. Our environment has changed,” she said.

The industrialization of the food supply, the use of pesticides and preservatives, the dawn of fast food have all combined, most likely, to do “a number on our bodies,” Dr. Apovian said.

But not all hope is lost thanks to new research, Dr. Apovian suggested.
 

New treatments show promise for helping patients’ obesity

New research that has increased Dr. Apovian’s understanding of the sophisticated role of adipose tissue may be helpful for treating patients with obesity, offering more targets for intervention, she told the audience.

Some treatment avenues already identified have started producing results, Dr. Apovian noted.

Gastric bypass surgery typically leads to a loss of 25% of body weight, but is often shunned by patients, she said. “With such a great surgical procedure, we still only do 256,000 procedures and we have millions of Americans with a BMI over 30.”

Weight control with obsessive dieting, meal-planning and calorie-counting, “can be done, but it’s really hard,” Dr. Apovian noted.

More appealing therapies targeting hormones and appetite suppression have produced impressive results. Recently approved semaglutide produced 14% weight loss, compared with about 2% for placebo, she said.

Results just released for tirzepatide, a dual agonist of gut hormones GLP-1 and GIP, show a 22% total weight loss, compared with about 2% for placebo, with about 56% of patients losing more than 20% of their body weight, Dr. Apovian said.

Referencing studies finding that several hormones are altered during weight loss, she predicted that targeting multiple hormones with drug treatment will also be necessary for best results.

But, she noted, “we’re treating obesity now with one- or two-drug combos.”
 

Medication costs are too high for many patients

Isis Smith, MD, an internist at University Medical Center in New Orleans, said in an interview that the cost of the most effective medications – which are not covered by Medicaid – means that many of her patients don’t have access to these treatments.

“We’re talking about $1,000 a month. And so there is no way they can afford [them]. I can prescribe phentermine [but] unless a patient has another indication, Medicaid will not pay for it,” she explained.

“I love hearing about all of the new developments. ... It’s interesting to hear, but we need to get insurance to pay so that I can actually prescribe,” Dr. Smith noted.

Dr. Apovian reports financial relationships with Xeno Biosciences, Cowen, Allergan, Novo Nordisk, Abbott Nutrition, and other companies.

CHICAGO – Recent research has changed at least one physician’s understanding of obesity and boosted her hope for fighting it.

Caroline Apovian, MD, codirector of the Center for Weight Management and Wellness at Brigham and Women’s Hospital, described some of the new insights about obesity she has gained during her talk at the annual meeting of the American College of Physicians.

“When I was a medical student a while back, I learned that fat tissue just sat there and stored fat,” she said. “Now we know it’s an endocrine organ.”

This tissue secretes hormones, such as leptin, and other factors that have an array of effects on the brain, pancreas, heart, liver, and muscles. Moreover, it has plasticity, with the ability to change, constantly adjusting our metabolism as nutrient supply and demand changes, she continued.

Obesity leads to a decline in this plasticity, leading to fibrosis and inflammation and other problems. These changes can further impair the function of adipose tissue, leading to metabolic disease. But the central role of adipose tissue, and its dynamic nature, presents an opportunity for treatment, Dr. Apovian said, during her talk.
 

Hints to why obesity has become more common

More than 42% of the U.S. population – “unbelievably,” Dr. Apovian said – is obese, meaning they have a BMI over 30, according to the Centers for Disease Control and Prevention. That’s up by about 25% since 1960, although calories eaten hasn’t increased, and physical activity has increased somewhat, she said.

The root cause is still a bit of a mystery, but according to “good hints and clues” from animal models that are starting to be translated to the study of human obesity, “it has to do with epigenetics and how our brains and our bodies are perceiving the environment,” she noted, during her presentation.

“Our genes haven’t changed. Our environment has changed,” she said.

The industrialization of the food supply, the use of pesticides and preservatives, the dawn of fast food have all combined, most likely, to do “a number on our bodies,” Dr. Apovian said.

But not all hope is lost thanks to new research, Dr. Apovian suggested.
 

New treatments show promise for helping patients’ obesity

New research that has increased Dr. Apovian’s understanding of the sophisticated role of adipose tissue may be helpful for treating patients with obesity, offering more targets for intervention, she told the audience.

Some treatment avenues already identified have started producing results, Dr. Apovian noted.

Gastric bypass surgery typically leads to a loss of 25% of body weight, but is often shunned by patients, she said. “With such a great surgical procedure, we still only do 256,000 procedures and we have millions of Americans with a BMI over 30.”

Weight control with obsessive dieting, meal-planning and calorie-counting, “can be done, but it’s really hard,” Dr. Apovian noted.

More appealing therapies targeting hormones and appetite suppression have produced impressive results. Recently approved semaglutide produced 14% weight loss, compared with about 2% for placebo, she said.

Results just released for tirzepatide, a dual agonist of gut hormones GLP-1 and GIP, show a 22% total weight loss, compared with about 2% for placebo, with about 56% of patients losing more than 20% of their body weight, Dr. Apovian said.

Referencing studies finding that several hormones are altered during weight loss, she predicted that targeting multiple hormones with drug treatment will also be necessary for best results.

But, she noted, “we’re treating obesity now with one- or two-drug combos.”
 

Medication costs are too high for many patients

Isis Smith, MD, an internist at University Medical Center in New Orleans, said in an interview that the cost of the most effective medications – which are not covered by Medicaid – means that many of her patients don’t have access to these treatments.

“We’re talking about $1,000 a month. And so there is no way they can afford [them]. I can prescribe phentermine [but] unless a patient has another indication, Medicaid will not pay for it,” she explained.

“I love hearing about all of the new developments. ... It’s interesting to hear, but we need to get insurance to pay so that I can actually prescribe,” Dr. Smith noted.

Dr. Apovian reports financial relationships with Xeno Biosciences, Cowen, Allergan, Novo Nordisk, Abbott Nutrition, and other companies.

CHICAGO – Recent research has changed at least one physician’s understanding of obesity and boosted her hope for fighting it.

Caroline Apovian, MD, codirector of the Center for Weight Management and Wellness at Brigham and Women’s Hospital, described some of the new insights about obesity she has gained during her talk at the annual meeting of the American College of Physicians.

“When I was a medical student a while back, I learned that fat tissue just sat there and stored fat,” she said. “Now we know it’s an endocrine organ.”

This tissue secretes hormones, such as leptin, and other factors that have an array of effects on the brain, pancreas, heart, liver, and muscles. Moreover, it has plasticity, with the ability to change, constantly adjusting our metabolism as nutrient supply and demand changes, she continued.

Obesity leads to a decline in this plasticity, leading to fibrosis and inflammation and other problems. These changes can further impair the function of adipose tissue, leading to metabolic disease. But the central role of adipose tissue, and its dynamic nature, presents an opportunity for treatment, Dr. Apovian said, during her talk.
 

Hints to why obesity has become more common

More than 42% of the U.S. population – “unbelievably,” Dr. Apovian said – is obese, meaning they have a BMI over 30, according to the Centers for Disease Control and Prevention. That’s up by about 25% since 1960, although calories eaten hasn’t increased, and physical activity has increased somewhat, she said.

The root cause is still a bit of a mystery, but according to “good hints and clues” from animal models that are starting to be translated to the study of human obesity, “it has to do with epigenetics and how our brains and our bodies are perceiving the environment,” she noted, during her presentation.

“Our genes haven’t changed. Our environment has changed,” she said.

The industrialization of the food supply, the use of pesticides and preservatives, the dawn of fast food have all combined, most likely, to do “a number on our bodies,” Dr. Apovian said.

But not all hope is lost thanks to new research, Dr. Apovian suggested.
 

New treatments show promise for helping patients’ obesity

New research that has increased Dr. Apovian’s understanding of the sophisticated role of adipose tissue may be helpful for treating patients with obesity, offering more targets for intervention, she told the audience.

Some treatment avenues already identified have started producing results, Dr. Apovian noted.

Gastric bypass surgery typically leads to a loss of 25% of body weight, but is often shunned by patients, she said. “With such a great surgical procedure, we still only do 256,000 procedures and we have millions of Americans with a BMI over 30.”

Weight control with obsessive dieting, meal-planning and calorie-counting, “can be done, but it’s really hard,” Dr. Apovian noted.

More appealing therapies targeting hormones and appetite suppression have produced impressive results. Recently approved semaglutide produced 14% weight loss, compared with about 2% for placebo, she said.

Results just released for tirzepatide, a dual agonist of gut hormones GLP-1 and GIP, show a 22% total weight loss, compared with about 2% for placebo, with about 56% of patients losing more than 20% of their body weight, Dr. Apovian said.

Referencing studies finding that several hormones are altered during weight loss, she predicted that targeting multiple hormones with drug treatment will also be necessary for best results.

But, she noted, “we’re treating obesity now with one- or two-drug combos.”
 

Medication costs are too high for many patients

Isis Smith, MD, an internist at University Medical Center in New Orleans, said in an interview that the cost of the most effective medications – which are not covered by Medicaid – means that many of her patients don’t have access to these treatments.

“We’re talking about $1,000 a month. And so there is no way they can afford [them]. I can prescribe phentermine [but] unless a patient has another indication, Medicaid will not pay for it,” she explained.

“I love hearing about all of the new developments. ... It’s interesting to hear, but we need to get insurance to pay so that I can actually prescribe,” Dr. Smith noted.

Dr. Apovian reports financial relationships with Xeno Biosciences, Cowen, Allergan, Novo Nordisk, Abbott Nutrition, and other companies.

Elevated concentrations of carbon monoxide (CO) due to air pollution increases the risk of epileptic seizures, a unique new study suggests.

The link between daily outdoor CO exposure and seizure risk was particularly evident for subclinical seizures – those in patients with abnormal electroencephalography (EEG) signals but no clinical symptoms.

“Our findings suggest that people with epilepsy should avoid high CO exposure to reduce potential seizure risk,” said study investigator Zhuying Chen, PhD candidate, department of biomedical engineering, University of Melbourne.

The study was published online in Epilepsia.
 

Pollution’s impact on brain health

Emerging evidence indicates air pollution affects brain health and may increase the risk of hospitalization or outpatient visits for epilepsy. However, little is known about the effect of pollution on the occurrence of epileptic seizures.

The study used two independent long-term seizure datasets – the NeuroVista (NV) study and the Seer App seizure diary (SD). In the NeuroVista study, researchers recorded continuous intracranial iEEG from patients with refractory focal epilepsy who had been implanted with a personal seizure advisory device that wirelessly recorded seizures on an external device.

The SD dataset included diaries documenting self-reported seizures, seizure cycles, and medication adherence.

Researchers collected data on hourly concentrations of outdoor CO, nitrogen dioxide (NO₂), particulate matter of 10 μm or less in diameter (PM₁₀), ozone (O₃), and sulfur dioxide (SO₂). The levels were measured at air quality monitoring stations in Australia.

Investigators aggregated hourly observations into daily mean data. All daily concentrations of CO and SO₂ and at least 95% of daily concentrations of NO₂, O₃, and PM₁₀ were within Australian air quality standards, said Mr. Chen.

The study included 49 participants, with epilepsy data on 15 patients in the NeuroVista study and on 34 from the SD dataset.

Overall, 6,692 epileptic seizures on 3,639 seizure days were recorded during 23,349 follow-up days from 2010 to 2012 (NV dataset) and 2018 to 2021 (SD dataset).

The investigators found a significant positive association between CO concentrations and epileptic seizure risks. The relative risk (RR) was 1.04 (95% confidence interval, 1.01–1.07; P < .01) for an interquartile range (IQR) increase of CO (0.13 parts per million).
 

Sex differences

There were no significant relationships for the other four air pollutants. However, Mr. Chen noted that Australia has very low air pollution levels; most usually are within World Health Organization air quality guidelines.

“Our findings may not be generalized to other countries with high air pollution levels,” said Mr. Chen. He noted that the relatively small number of patients in the study may limit the statistical power to detect some associations.

The study showed that females had a significantly increased risk of epileptic seizures when exposed to elevated CO (RR, 1.05; 95% CI, 1.01–1.08; P < .05) and NO₂ (RR, 1.09; 95% CI, 1.01–1.16; P < .05) concentrations. There were no significant associations in males for any air pollutants.

Differences in outdoor activities and behaviors such as smoking and exercise may lead to variations in environmental exposure and help explain the sex differences, said Mr. Chen. These differences may also be due to the study’s limited sample size.

Analyzing the two datasets separately, the researchers found there was a significant association between CO concentration and epileptic seizure risk in the NV dataset (RR, 1.10; 95% CI, 1.03–1.17; P < .01).

There were no significant associations in the SD dataset for any air pollutants. This may be because only clinical seizures – those associated with evident symptoms – are self-reported, said Mr. Chen. He also noted that seizure diaries may be unreliable.

In the NV dataset, the epileptic seizure risk was significantly increased when only subclinical seizures were considered (RR, 1.20; 95% CI, 1.12–1.28; P < .001) for an IQR increase of CO concentration.

The risk was significantly decreased by 13% for subclinical seizures with an IQR increase of PM₁₀ and by 9% for subclinical seizures with an IQR increase of SO₂ concentrations.

These negative associations should be interpreted with caution, inasmuch as the associations were not robust in subsequent subgroup and sensitivity analyses, said Mr. Chen.

There were no significant associations when considering clinical seizures for any air pollutants.

The positive association for subclinical but not clinical seizures suggests that low-level CO exposure may not be strong enough to directly trigger clinical seizures, said Mr. Chen.

Although previous research has demonstrated adverse neurologic effects of exposure to air pollutants, most studies were based on hospital databases or registers. Thus, they may have missed seizures that did not lead to hospital admission.
 

Unclear mechanism

The exact mechanisms linking air pollution to seizures are unclear but probably involve the synergistic interaction of multiple pathways, said Mr. Chen. “Air pollution may affect brain metabolism, alter the immune response of the brain, and induce oxidative stress and neuroinflammation, causing the brain to be more susceptible to seizures,” he noted.

This is the first study to investigate seizure rates through intracranial EEG signals and self-reported seizure diaries. It’s also the first to look into the impact of pollutants at low concentration levels on subclinical seizures.

However, the study has some limitations. Self-reported seizures in the SD dataset might underestimate the influence of air pollution on seizures. The study used postal codes as proxies for exposure to pollution, which could introduce measurement errors and underestimate associations.

In addition, Mr. Chen noted that seizures from the NeuroVista dataset were recorded from patients with drug-resistant focal epilepsy. “Whether our findings can be generalized to other epilepsy types needs further investigation.”

The study could have important clinical and public health implications. For example, said Mr. Chen, it’s possible that seizure risk could be reduced through behavioral interventions, such as avoiding being outside or using an air filtration system when pollutant levels are high.

“Clinicians could counsel their patients to avoid the potential risk of high carbon monoxide exposure,” he said.

CO exposure could be a new factor for seizure risk forecasting, which could reduce the uncertainty of seizures and help guide epilepsy management, Mr. Chen added.

The study was supported by the Melbourne Monash Consciousness Research Seed Funding and an Australian National Health and Medical Research Council Ideas grant. Mr. Chen has disclosed no relevant financial relationships.

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

Elevated concentrations of carbon monoxide (CO) due to air pollution increases the risk of epileptic seizures, a unique new study suggests.

The link between daily outdoor CO exposure and seizure risk was particularly evident for subclinical seizures – those in patients with abnormal electroencephalography (EEG) signals but no clinical symptoms.

“Our findings suggest that people with epilepsy should avoid high CO exposure to reduce potential seizure risk,” said study investigator Zhuying Chen, PhD candidate, department of biomedical engineering, University of Melbourne.

The study was published online in Epilepsia.
 

Pollution’s impact on brain health

Emerging evidence indicates air pollution affects brain health and may increase the risk of hospitalization or outpatient visits for epilepsy. However, little is known about the effect of pollution on the occurrence of epileptic seizures.

The study used two independent long-term seizure datasets – the NeuroVista (NV) study and the Seer App seizure diary (SD). In the NeuroVista study, researchers recorded continuous intracranial iEEG from patients with refractory focal epilepsy who had been implanted with a personal seizure advisory device that wirelessly recorded seizures on an external device.

The SD dataset included diaries documenting self-reported seizures, seizure cycles, and medication adherence.

Researchers collected data on hourly concentrations of outdoor CO, nitrogen dioxide (NO₂), particulate matter of 10 μm or less in diameter (PM₁₀), ozone (O₃), and sulfur dioxide (SO₂). The levels were measured at air quality monitoring stations in Australia.

Investigators aggregated hourly observations into daily mean data. All daily concentrations of CO and SO₂ and at least 95% of daily concentrations of NO₂, O₃, and PM₁₀ were within Australian air quality standards, said Mr. Chen.

The study included 49 participants, with epilepsy data on 15 patients in the NeuroVista study and on 34 from the SD dataset.

Overall, 6,692 epileptic seizures on 3,639 seizure days were recorded during 23,349 follow-up days from 2010 to 2012 (NV dataset) and 2018 to 2021 (SD dataset).

The investigators found a significant positive association between CO concentrations and epileptic seizure risks. The relative risk (RR) was 1.04 (95% confidence interval, 1.01–1.07; P < .01) for an interquartile range (IQR) increase of CO (0.13 parts per million).
 

Sex differences

There were no significant relationships for the other four air pollutants. However, Mr. Chen noted that Australia has very low air pollution levels; most usually are within World Health Organization air quality guidelines.

“Our findings may not be generalized to other countries with high air pollution levels,” said Mr. Chen. He noted that the relatively small number of patients in the study may limit the statistical power to detect some associations.

The study showed that females had a significantly increased risk of epileptic seizures when exposed to elevated CO (RR, 1.05; 95% CI, 1.01–1.08; P < .05) and NO₂ (RR, 1.09; 95% CI, 1.01–1.16; P < .05) concentrations. There were no significant associations in males for any air pollutants.

Differences in outdoor activities and behaviors such as smoking and exercise may lead to variations in environmental exposure and help explain the sex differences, said Mr. Chen. These differences may also be due to the study’s limited sample size.

Analyzing the two datasets separately, the researchers found there was a significant association between CO concentration and epileptic seizure risk in the NV dataset (RR, 1.10; 95% CI, 1.03–1.17; P < .01).

There were no significant associations in the SD dataset for any air pollutants. This may be because only clinical seizures – those associated with evident symptoms – are self-reported, said Mr. Chen. He also noted that seizure diaries may be unreliable.

In the NV dataset, the epileptic seizure risk was significantly increased when only subclinical seizures were considered (RR, 1.20; 95% CI, 1.12–1.28; P < .001) for an IQR increase of CO concentration.

The risk was significantly decreased by 13% for subclinical seizures with an IQR increase of PM₁₀ and by 9% for subclinical seizures with an IQR increase of SO₂ concentrations.

These negative associations should be interpreted with caution, inasmuch as the associations were not robust in subsequent subgroup and sensitivity analyses, said Mr. Chen.

There were no significant associations when considering clinical seizures for any air pollutants.

The positive association for subclinical but not clinical seizures suggests that low-level CO exposure may not be strong enough to directly trigger clinical seizures, said Mr. Chen.

Although previous research has demonstrated adverse neurologic effects of exposure to air pollutants, most studies were based on hospital databases or registers. Thus, they may have missed seizures that did not lead to hospital admission.
 

Unclear mechanism

The exact mechanisms linking air pollution to seizures are unclear but probably involve the synergistic interaction of multiple pathways, said Mr. Chen. “Air pollution may affect brain metabolism, alter the immune response of the brain, and induce oxidative stress and neuroinflammation, causing the brain to be more susceptible to seizures,” he noted.

This is the first study to investigate seizure rates through intracranial EEG signals and self-reported seizure diaries. It’s also the first to look into the impact of pollutants at low concentration levels on subclinical seizures.

However, the study has some limitations. Self-reported seizures in the SD dataset might underestimate the influence of air pollution on seizures. The study used postal codes as proxies for exposure to pollution, which could introduce measurement errors and underestimate associations.

In addition, Mr. Chen noted that seizures from the NeuroVista dataset were recorded from patients with drug-resistant focal epilepsy. “Whether our findings can be generalized to other epilepsy types needs further investigation.”

The study could have important clinical and public health implications. For example, said Mr. Chen, it’s possible that seizure risk could be reduced through behavioral interventions, such as avoiding being outside or using an air filtration system when pollutant levels are high.

“Clinicians could counsel their patients to avoid the potential risk of high carbon monoxide exposure,” he said.

CO exposure could be a new factor for seizure risk forecasting, which could reduce the uncertainty of seizures and help guide epilepsy management, Mr. Chen added.

The study was supported by the Melbourne Monash Consciousness Research Seed Funding and an Australian National Health and Medical Research Council Ideas grant. Mr. Chen has disclosed no relevant financial relationships.

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

Elevated concentrations of carbon monoxide (CO) due to air pollution increases the risk of epileptic seizures, a unique new study suggests.

The link between daily outdoor CO exposure and seizure risk was particularly evident for subclinical seizures – those in patients with abnormal electroencephalography (EEG) signals but no clinical symptoms.

“Our findings suggest that people with epilepsy should avoid high CO exposure to reduce potential seizure risk,” said study investigator Zhuying Chen, PhD candidate, department of biomedical engineering, University of Melbourne.

The study was published online in Epilepsia.
 

Pollution’s impact on brain health

Emerging evidence indicates air pollution affects brain health and may increase the risk of hospitalization or outpatient visits for epilepsy. However, little is known about the effect of pollution on the occurrence of epileptic seizures.

The study used two independent long-term seizure datasets – the NeuroVista (NV) study and the Seer App seizure diary (SD). In the NeuroVista study, researchers recorded continuous intracranial iEEG from patients with refractory focal epilepsy who had been implanted with a personal seizure advisory device that wirelessly recorded seizures on an external device.

The SD dataset included diaries documenting self-reported seizures, seizure cycles, and medication adherence.

Researchers collected data on hourly concentrations of outdoor CO, nitrogen dioxide (NO₂), particulate matter of 10 μm or less in diameter (PM₁₀), ozone (O₃), and sulfur dioxide (SO₂). The levels were measured at air quality monitoring stations in Australia.

Investigators aggregated hourly observations into daily mean data. All daily concentrations of CO and SO₂ and at least 95% of daily concentrations of NO₂, O₃, and PM₁₀ were within Australian air quality standards, said Mr. Chen.

The study included 49 participants, with epilepsy data on 15 patients in the NeuroVista study and on 34 from the SD dataset.

Overall, 6,692 epileptic seizures on 3,639 seizure days were recorded during 23,349 follow-up days from 2010 to 2012 (NV dataset) and 2018 to 2021 (SD dataset).

The investigators found a significant positive association between CO concentrations and epileptic seizure risks. The relative risk (RR) was 1.04 (95% confidence interval, 1.01–1.07; P < .01) for an interquartile range (IQR) increase of CO (0.13 parts per million).
 

Sex differences

There were no significant relationships for the other four air pollutants. However, Mr. Chen noted that Australia has very low air pollution levels; most usually are within World Health Organization air quality guidelines.

“Our findings may not be generalized to other countries with high air pollution levels,” said Mr. Chen. He noted that the relatively small number of patients in the study may limit the statistical power to detect some associations.

The study showed that females had a significantly increased risk of epileptic seizures when exposed to elevated CO (RR, 1.05; 95% CI, 1.01–1.08; P < .05) and NO₂ (RR, 1.09; 95% CI, 1.01–1.16; P < .05) concentrations. There were no significant associations in males for any air pollutants.

Differences in outdoor activities and behaviors such as smoking and exercise may lead to variations in environmental exposure and help explain the sex differences, said Mr. Chen. These differences may also be due to the study’s limited sample size.

Analyzing the two datasets separately, the researchers found there was a significant association between CO concentration and epileptic seizure risk in the NV dataset (RR, 1.10; 95% CI, 1.03–1.17; P < .01).

There were no significant associations in the SD dataset for any air pollutants. This may be because only clinical seizures – those associated with evident symptoms – are self-reported, said Mr. Chen. He also noted that seizure diaries may be unreliable.

In the NV dataset, the epileptic seizure risk was significantly increased when only subclinical seizures were considered (RR, 1.20; 95% CI, 1.12–1.28; P < .001) for an IQR increase of CO concentration.

The risk was significantly decreased by 13% for subclinical seizures with an IQR increase of PM₁₀ and by 9% for subclinical seizures with an IQR increase of SO₂ concentrations.

These negative associations should be interpreted with caution, inasmuch as the associations were not robust in subsequent subgroup and sensitivity analyses, said Mr. Chen.

There were no significant associations when considering clinical seizures for any air pollutants.

The positive association for subclinical but not clinical seizures suggests that low-level CO exposure may not be strong enough to directly trigger clinical seizures, said Mr. Chen.

Although previous research has demonstrated adverse neurologic effects of exposure to air pollutants, most studies were based on hospital databases or registers. Thus, they may have missed seizures that did not lead to hospital admission.
 

Unclear mechanism

The exact mechanisms linking air pollution to seizures are unclear but probably involve the synergistic interaction of multiple pathways, said Mr. Chen. “Air pollution may affect brain metabolism, alter the immune response of the brain, and induce oxidative stress and neuroinflammation, causing the brain to be more susceptible to seizures,” he noted.

This is the first study to investigate seizure rates through intracranial EEG signals and self-reported seizure diaries. It’s also the first to look into the impact of pollutants at low concentration levels on subclinical seizures.

However, the study has some limitations. Self-reported seizures in the SD dataset might underestimate the influence of air pollution on seizures. The study used postal codes as proxies for exposure to pollution, which could introduce measurement errors and underestimate associations.

In addition, Mr. Chen noted that seizures from the NeuroVista dataset were recorded from patients with drug-resistant focal epilepsy. “Whether our findings can be generalized to other epilepsy types needs further investigation.”

The study could have important clinical and public health implications. For example, said Mr. Chen, it’s possible that seizure risk could be reduced through behavioral interventions, such as avoiding being outside or using an air filtration system when pollutant levels are high.

“Clinicians could counsel their patients to avoid the potential risk of high carbon monoxide exposure,” he said.

CO exposure could be a new factor for seizure risk forecasting, which could reduce the uncertainty of seizures and help guide epilepsy management, Mr. Chen added.

The study was supported by the Melbourne Monash Consciousness Research Seed Funding and an Australian National Health and Medical Research Council Ideas grant. Mr. Chen has disclosed no relevant financial relationships.

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