Neurology Reviews

The World Health Organization and its partners recently released an ambitious plan, Defeating meningitis by 2030: A global road map. The goal is to reduce deaths and disabilities from bacterial meningitis, which kills about 250,000 people annually of the 1.2 million estimated to be infected.

This type of infection around the brain and spinal cord also causes long-term disabilities – deafness, learning problems, seizures, loss of limbs – in about one-quarter of survivors.

The leading causes of bacterial meningitis are Neisseria meningitidis (meningococcus), Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae, and group B streptococcus. As with malaria, about half of the cases are in children under age 5 years. The most severely affected area for both infections is sub-Saharan Africa.

The main goal of the roadmap is to reduce vaccine-preventable cases of bacterial meningitis by 50% and deaths by 70% by 2030. WHO’s partners included the Centers for Disease Control and Prevention, the London School of Hygiene and Tropical Medicine, Médecins Sans Frontières (Doctors Without Borders), the Meningitis Research Foundation, PATH, UNICEF, and numerous global consultants.

For primary prevention and epidemic control, a major goal is to achieve higher vaccine coverage. Another goal is developing and deploying rapid diagnostic tests to guide treatment and prevention activities and measure the impact of vaccination. The lack of laboratory capacity to confirm the bacteria is a significant challenge. Also, patients often receive antibiotics before appropriate tests are conducted, and lumbar punctures are frequently not done.

The commitment to this project emerged in 2017. It was followed by a baseline analysis in 2018 and a draft roadmap the following year. Consultations with experts and with more than 600 patient groups in more than 90 countries followed.

Prevention through greater vaccine uptake was the top priority. Vaccination is considered the first line of defense against antibiotic resistance among the targeted bacteria.

Another goal is to quantify the decrease in antibiotic use for invasive infections or prophylaxis and the subsequent reduction in antimicrobial resistance in relation to increased vaccination.

Surveillance is weak in many regions, limiting the ability to detect epidemics and to respond appropriately. Similarly, there are limited data on the burden of sequelae, such as deafness, on meningitis survivors.

There is an inadequate supply of affordable vaccines to respond to epidemics.  Currently, routine vaccination against Neisseria meningitidis is occurring in 18 of 26 countries in the meningitis belt. Epidemics of meningococcus occur every few years in the driest time of the year and abate with the rains. Epidemics of pneumococcal meningitis are much rarer but follow a similar pattern; they have also been associated with crowding and alcohol use.

Care for those affected by meningitis is another focus, as is affirming the right to prevention and care. There’s a need for earlier recognition of the complications of meningitis and an increase in efforts to treat those complications.

WHO’s final goal in its roadmap is to boost awareness of meningitis and make it a priority for policymakers. Similarly, there is a need to educate communities about the disease, including how to access vaccines. If someone becomes ill, they need to be aware of the symptoms, the need for early treatment, and what aftercare is available.

Marie-Pierre Préziosi, MD, the core secretariat of WHO’s Technical Taskforce, told this news organization that while the roadmap looks aspirational, “it is feasible … you have strategic goals – each has milestones with time limits and who will do it.”

Regarding vaccinations, Dr. Préziosi said that “the strategy was a victim of its success. The mass campaign knocked down transmission completely.” Some countries are now waiting for multivalent vaccines. She said that vaccine hesitancy is not a significant problem in Africa “because the disease is so feared.”

Major obstacles to implementing the roadmap include the complacency of public health leaders and the COVID-19 lockdowns, which decreased vaccination coverage rates. “The second thing is also sufficient funding to do the research and innovation so that we get the affordable tools that we need globally,” Dr. Préziosi said.

Marilyn Felkner, DrPH, School of Human Ecology, University of Texas at Austin, said in an interview, “It’s very cliché, but we have often said that communicable diseases do not respect political boundaries. So to expect a country to be able to control that by themselves is a false hope.”

Regarding the roadmap, Dr. Felkner said, “I think that organizing ideas and having them in writing is always a good first step. And it can help people move forward if they’re feeling overwhelmed ... Having a written plan can certainly provide that fundamental basis. So, the important thing is not to say, ‘Oh, we have this great plan done; hope somebody picks up the plan.’ There’s got to be some momentum behind it, and hopefully some funding.”

Dr. Préziosi and Dr. Felkner have disclosed no relevant financial relationships.

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

The World Health Organization and its partners recently released an ambitious plan, Defeating meningitis by 2030: A global road map. The goal is to reduce deaths and disabilities from bacterial meningitis, which kills about 250,000 people annually of the 1.2 million estimated to be infected.

This type of infection around the brain and spinal cord also causes long-term disabilities – deafness, learning problems, seizures, loss of limbs – in about one-quarter of survivors.

The leading causes of bacterial meningitis are Neisseria meningitidis (meningococcus), Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae, and group B streptococcus. As with malaria, about half of the cases are in children under age 5 years. The most severely affected area for both infections is sub-Saharan Africa.

The main goal of the roadmap is to reduce vaccine-preventable cases of bacterial meningitis by 50% and deaths by 70% by 2030. WHO’s partners included the Centers for Disease Control and Prevention, the London School of Hygiene and Tropical Medicine, Médecins Sans Frontières (Doctors Without Borders), the Meningitis Research Foundation, PATH, UNICEF, and numerous global consultants.

For primary prevention and epidemic control, a major goal is to achieve higher vaccine coverage. Another goal is developing and deploying rapid diagnostic tests to guide treatment and prevention activities and measure the impact of vaccination. The lack of laboratory capacity to confirm the bacteria is a significant challenge. Also, patients often receive antibiotics before appropriate tests are conducted, and lumbar punctures are frequently not done.

The commitment to this project emerged in 2017. It was followed by a baseline analysis in 2018 and a draft roadmap the following year. Consultations with experts and with more than 600 patient groups in more than 90 countries followed.

Prevention through greater vaccine uptake was the top priority. Vaccination is considered the first line of defense against antibiotic resistance among the targeted bacteria.

Another goal is to quantify the decrease in antibiotic use for invasive infections or prophylaxis and the subsequent reduction in antimicrobial resistance in relation to increased vaccination.

Surveillance is weak in many regions, limiting the ability to detect epidemics and to respond appropriately. Similarly, there are limited data on the burden of sequelae, such as deafness, on meningitis survivors.

There is an inadequate supply of affordable vaccines to respond to epidemics.  Currently, routine vaccination against Neisseria meningitidis is occurring in 18 of 26 countries in the meningitis belt. Epidemics of meningococcus occur every few years in the driest time of the year and abate with the rains. Epidemics of pneumococcal meningitis are much rarer but follow a similar pattern; they have also been associated with crowding and alcohol use.

Care for those affected by meningitis is another focus, as is affirming the right to prevention and care. There’s a need for earlier recognition of the complications of meningitis and an increase in efforts to treat those complications.

WHO’s final goal in its roadmap is to boost awareness of meningitis and make it a priority for policymakers. Similarly, there is a need to educate communities about the disease, including how to access vaccines. If someone becomes ill, they need to be aware of the symptoms, the need for early treatment, and what aftercare is available.

Marie-Pierre Préziosi, MD, the core secretariat of WHO’s Technical Taskforce, told this news organization that while the roadmap looks aspirational, “it is feasible … you have strategic goals – each has milestones with time limits and who will do it.”

Regarding vaccinations, Dr. Préziosi said that “the strategy was a victim of its success. The mass campaign knocked down transmission completely.” Some countries are now waiting for multivalent vaccines. She said that vaccine hesitancy is not a significant problem in Africa “because the disease is so feared.”

Major obstacles to implementing the roadmap include the complacency of public health leaders and the COVID-19 lockdowns, which decreased vaccination coverage rates. “The second thing is also sufficient funding to do the research and innovation so that we get the affordable tools that we need globally,” Dr. Préziosi said.

Marilyn Felkner, DrPH, School of Human Ecology, University of Texas at Austin, said in an interview, “It’s very cliché, but we have often said that communicable diseases do not respect political boundaries. So to expect a country to be able to control that by themselves is a false hope.”

Regarding the roadmap, Dr. Felkner said, “I think that organizing ideas and having them in writing is always a good first step. And it can help people move forward if they’re feeling overwhelmed ... Having a written plan can certainly provide that fundamental basis. So, the important thing is not to say, ‘Oh, we have this great plan done; hope somebody picks up the plan.’ There’s got to be some momentum behind it, and hopefully some funding.”

Dr. Préziosi and Dr. Felkner have disclosed no relevant financial relationships.

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

The World Health Organization and its partners recently released an ambitious plan, Defeating meningitis by 2030: A global road map. The goal is to reduce deaths and disabilities from bacterial meningitis, which kills about 250,000 people annually of the 1.2 million estimated to be infected.

This type of infection around the brain and spinal cord also causes long-term disabilities – deafness, learning problems, seizures, loss of limbs – in about one-quarter of survivors.

The leading causes of bacterial meningitis are Neisseria meningitidis (meningococcus), Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae, and group B streptococcus. As with malaria, about half of the cases are in children under age 5 years. The most severely affected area for both infections is sub-Saharan Africa.

The main goal of the roadmap is to reduce vaccine-preventable cases of bacterial meningitis by 50% and deaths by 70% by 2030. WHO’s partners included the Centers for Disease Control and Prevention, the London School of Hygiene and Tropical Medicine, Médecins Sans Frontières (Doctors Without Borders), the Meningitis Research Foundation, PATH, UNICEF, and numerous global consultants.

For primary prevention and epidemic control, a major goal is to achieve higher vaccine coverage. Another goal is developing and deploying rapid diagnostic tests to guide treatment and prevention activities and measure the impact of vaccination. The lack of laboratory capacity to confirm the bacteria is a significant challenge. Also, patients often receive antibiotics before appropriate tests are conducted, and lumbar punctures are frequently not done.

The commitment to this project emerged in 2017. It was followed by a baseline analysis in 2018 and a draft roadmap the following year. Consultations with experts and with more than 600 patient groups in more than 90 countries followed.

Prevention through greater vaccine uptake was the top priority. Vaccination is considered the first line of defense against antibiotic resistance among the targeted bacteria.

Another goal is to quantify the decrease in antibiotic use for invasive infections or prophylaxis and the subsequent reduction in antimicrobial resistance in relation to increased vaccination.

Surveillance is weak in many regions, limiting the ability to detect epidemics and to respond appropriately. Similarly, there are limited data on the burden of sequelae, such as deafness, on meningitis survivors.

There is an inadequate supply of affordable vaccines to respond to epidemics.  Currently, routine vaccination against Neisseria meningitidis is occurring in 18 of 26 countries in the meningitis belt. Epidemics of meningococcus occur every few years in the driest time of the year and abate with the rains. Epidemics of pneumococcal meningitis are much rarer but follow a similar pattern; they have also been associated with crowding and alcohol use.

Care for those affected by meningitis is another focus, as is affirming the right to prevention and care. There’s a need for earlier recognition of the complications of meningitis and an increase in efforts to treat those complications.

WHO’s final goal in its roadmap is to boost awareness of meningitis and make it a priority for policymakers. Similarly, there is a need to educate communities about the disease, including how to access vaccines. If someone becomes ill, they need to be aware of the symptoms, the need for early treatment, and what aftercare is available.

Marie-Pierre Préziosi, MD, the core secretariat of WHO’s Technical Taskforce, told this news organization that while the roadmap looks aspirational, “it is feasible … you have strategic goals – each has milestones with time limits and who will do it.”

Regarding vaccinations, Dr. Préziosi said that “the strategy was a victim of its success. The mass campaign knocked down transmission completely.” Some countries are now waiting for multivalent vaccines. She said that vaccine hesitancy is not a significant problem in Africa “because the disease is so feared.”

Major obstacles to implementing the roadmap include the complacency of public health leaders and the COVID-19 lockdowns, which decreased vaccination coverage rates. “The second thing is also sufficient funding to do the research and innovation so that we get the affordable tools that we need globally,” Dr. Préziosi said.

Marilyn Felkner, DrPH, School of Human Ecology, University of Texas at Austin, said in an interview, “It’s very cliché, but we have often said that communicable diseases do not respect political boundaries. So to expect a country to be able to control that by themselves is a false hope.”

Regarding the roadmap, Dr. Felkner said, “I think that organizing ideas and having them in writing is always a good first step. And it can help people move forward if they’re feeling overwhelmed ... Having a written plan can certainly provide that fundamental basis. So, the important thing is not to say, ‘Oh, we have this great plan done; hope somebody picks up the plan.’ There’s got to be some momentum behind it, and hopefully some funding.”

Dr. Préziosi and Dr. Felkner have disclosed no relevant financial relationships.

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

In frail elderly adults with COVID-19 infections, treatment with omega-3 fatty acids may improve lipid responses and decrease levels of proinflammatory lipid mediators, results of a small randomized controlled trial suggest.

Results of the study, which included 22 patients with multiple comorbidities, were presented at the European Geriatric Medicine Society annual congress, a hybrid live and online meeting.

The patients, who had a median age of 81 years, were randomized to receive an intravenous infusion of an omega-3 polyunsaturated fatty acid (PUFA) emulsion containing 10 g of fish oil per 100 mL or a saline placebo.

Those who received the intravenous infusion had significant decreases from baseline to end of treatment in the neutrophil-to-lymphocyte ratio (NLR), indicating marked reductions in systemic inflammation.

In contrast, patients randomized to a saline placebo had no significant improvements in NLR, Magnus Bäck, MD, PhD, from the Karolinska Institute in Stockholm reported at the meeting.

“Our lipidomic analysis also showed that omega-3 treatment skewed the lipid response, with reduced levels of proinflammatory lipid mediators, and increased levels of proresolving mediators,” according to a late-breaking abstract, which Dr. Bäck presented during the session.

Omega-3 treatment was not significantly associated with reduction in either C-reactive protein (CRP) or the proinflammatory cytokine interleukin-6, however.
 

‘Eicosanoid storm’

In a review article published in January 2021 in the open-access journal Frontiers in Physiology, Dr. Bäck and colleagues outlined the rationale for their randomized trial.

“Excessive inflammation has been reported in severe cases with respiratory failure and cardiovascular complications,” they wrote. “In addition to the release of cytokines, referred to as cytokine release syndrome or ‘cytokine storm,’ increased proinflammatory lipid mediators derived from the omega-6 polyunsaturated fatty acid (PUFA) arachidonic acid may cause an ‘eicosanoid storm,’ which contributes to the uncontrolled systemic inflammation.”

Omega-3 PUFA contains proresolving mediators that can limit inflammatory reactions, suggesting the possibility of an inflammation-resolving benefit in patients with COVID-19 without concerns about immunosuppression, the authors hypothesized.
 

Trial details

In the trial, COVID-Omega-F, they enrolled patients with a COVID-19 diagnosis requiring hospitalization. Patients with an allergy to fish oil or who had contraindications to intravenous PUFA administration (for example, risk for bleeding, shock, or emboli) were excluded.

Ten patients were randomly assigned to receive infusions of the omega-3 PUFA and 12 were assigned to receive infusions of the placebo, once daily for 5 days. The primary outcome measure was change in inflammatory biomarkers, including white blood cell counts, CRP, cytokines, and lipid mediators.

Baseline demographic and clinical characteristics were similar between the two study arms, with a median of about 7 days since the onset of symptoms, and 3.5 days since a diagnosis of COVID-19.

All patients had low lymphocyte responses reflected by a high NLR, a prognostic measure for worse outcomes in patients with COVID-19 infections, Dr. Bäck said.

Inflammation was moderate, with a CRP of 65 mg/L in the placebo group and 62 mg/L in the omega-3 group.

Seven patients in each study arm received concomitant corticoid treatment. Two patients in each arm died in hospital, but there were no serious treatment-related adverse events.
 

Inflammatory markers improve

As noted before, there was a significant decline in NLR from baseline among patients randomized to omega-3 (P = .02) but no corresponding decrease in patients assigned to placebo infusions.

“The significant decrease was largely driven by an increase in the lymphocyte count in the omega-3 treated group (P = .004), whereas lymphocytes did not significantly change,” Dr. Bäck said.

As expected, patients in the omega-3 group had pronounced increases in omega-3 fatty acids, including eicosapentaenoic acid and docosahexaenoic acid.

The metabolism of fatty acids also differed markedly between the groups, with a significant decrease in the omega-3 group but not the placebo group in proinflammatory mediators, and an increase in precursors to proresolving mediators, Dr. Bäck noted.
 

AFib concerns

In a question-and-answer part of the session, a physician who identified herself as “Senya from Russia” questioned the safety of omega-3 treatment in this population, “because recently there was a meta-analysis which showed that omega-3 fatty acids will increase the risk of atrial fibrillation in older adults especially.”

The systematic review and meta-analysis she referred to, published in Circulation and reported on by this news organization, showed that, among 81,210 patients with a mean age of 65 enrolled in seven randomized controlled trials, omega-3 fatty acid supplementation was associated with a 25% increase in risk for atrial fibrillation. This risk appeared to be higher in trials testing doses greater than 1 g/day, according to the paper.

“This was not monitored in this study,” Dr. Bäck replied. “It is true that the meta-analysis showed an increased incidence of atrial fibrillation, so it would be something to monitor in case this trial would be expanded to a larger population.”

The study was supported by the Karolinska Institute. Dr. Bäck disclosed no relevant financial relationships.

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

In frail elderly adults with COVID-19 infections, treatment with omega-3 fatty acids may improve lipid responses and decrease levels of proinflammatory lipid mediators, results of a small randomized controlled trial suggest.

Results of the study, which included 22 patients with multiple comorbidities, were presented at the European Geriatric Medicine Society annual congress, a hybrid live and online meeting.

The patients, who had a median age of 81 years, were randomized to receive an intravenous infusion of an omega-3 polyunsaturated fatty acid (PUFA) emulsion containing 10 g of fish oil per 100 mL or a saline placebo.

Those who received the intravenous infusion had significant decreases from baseline to end of treatment in the neutrophil-to-lymphocyte ratio (NLR), indicating marked reductions in systemic inflammation.

In contrast, patients randomized to a saline placebo had no significant improvements in NLR, Magnus Bäck, MD, PhD, from the Karolinska Institute in Stockholm reported at the meeting.

“Our lipidomic analysis also showed that omega-3 treatment skewed the lipid response, with reduced levels of proinflammatory lipid mediators, and increased levels of proresolving mediators,” according to a late-breaking abstract, which Dr. Bäck presented during the session.

Omega-3 treatment was not significantly associated with reduction in either C-reactive protein (CRP) or the proinflammatory cytokine interleukin-6, however.
 

‘Eicosanoid storm’

In a review article published in January 2021 in the open-access journal Frontiers in Physiology, Dr. Bäck and colleagues outlined the rationale for their randomized trial.

“Excessive inflammation has been reported in severe cases with respiratory failure and cardiovascular complications,” they wrote. “In addition to the release of cytokines, referred to as cytokine release syndrome or ‘cytokine storm,’ increased proinflammatory lipid mediators derived from the omega-6 polyunsaturated fatty acid (PUFA) arachidonic acid may cause an ‘eicosanoid storm,’ which contributes to the uncontrolled systemic inflammation.”

Omega-3 PUFA contains proresolving mediators that can limit inflammatory reactions, suggesting the possibility of an inflammation-resolving benefit in patients with COVID-19 without concerns about immunosuppression, the authors hypothesized.
 

Trial details

In the trial, COVID-Omega-F, they enrolled patients with a COVID-19 diagnosis requiring hospitalization. Patients with an allergy to fish oil or who had contraindications to intravenous PUFA administration (for example, risk for bleeding, shock, or emboli) were excluded.

Ten patients were randomly assigned to receive infusions of the omega-3 PUFA and 12 were assigned to receive infusions of the placebo, once daily for 5 days. The primary outcome measure was change in inflammatory biomarkers, including white blood cell counts, CRP, cytokines, and lipid mediators.

Baseline demographic and clinical characteristics were similar between the two study arms, with a median of about 7 days since the onset of symptoms, and 3.5 days since a diagnosis of COVID-19.

All patients had low lymphocyte responses reflected by a high NLR, a prognostic measure for worse outcomes in patients with COVID-19 infections, Dr. Bäck said.

Inflammation was moderate, with a CRP of 65 mg/L in the placebo group and 62 mg/L in the omega-3 group.

Seven patients in each study arm received concomitant corticoid treatment. Two patients in each arm died in hospital, but there were no serious treatment-related adverse events.
 

Inflammatory markers improve

As noted before, there was a significant decline in NLR from baseline among patients randomized to omega-3 (P = .02) but no corresponding decrease in patients assigned to placebo infusions.

“The significant decrease was largely driven by an increase in the lymphocyte count in the omega-3 treated group (P = .004), whereas lymphocytes did not significantly change,” Dr. Bäck said.

As expected, patients in the omega-3 group had pronounced increases in omega-3 fatty acids, including eicosapentaenoic acid and docosahexaenoic acid.

The metabolism of fatty acids also differed markedly between the groups, with a significant decrease in the omega-3 group but not the placebo group in proinflammatory mediators, and an increase in precursors to proresolving mediators, Dr. Bäck noted.
 

AFib concerns

In a question-and-answer part of the session, a physician who identified herself as “Senya from Russia” questioned the safety of omega-3 treatment in this population, “because recently there was a meta-analysis which showed that omega-3 fatty acids will increase the risk of atrial fibrillation in older adults especially.”

The systematic review and meta-analysis she referred to, published in Circulation and reported on by this news organization, showed that, among 81,210 patients with a mean age of 65 enrolled in seven randomized controlled trials, omega-3 fatty acid supplementation was associated with a 25% increase in risk for atrial fibrillation. This risk appeared to be higher in trials testing doses greater than 1 g/day, according to the paper.

“This was not monitored in this study,” Dr. Bäck replied. “It is true that the meta-analysis showed an increased incidence of atrial fibrillation, so it would be something to monitor in case this trial would be expanded to a larger population.”

The study was supported by the Karolinska Institute. Dr. Bäck disclosed no relevant financial relationships.

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

In frail elderly adults with COVID-19 infections, treatment with omega-3 fatty acids may improve lipid responses and decrease levels of proinflammatory lipid mediators, results of a small randomized controlled trial suggest.

Results of the study, which included 22 patients with multiple comorbidities, were presented at the European Geriatric Medicine Society annual congress, a hybrid live and online meeting.

The patients, who had a median age of 81 years, were randomized to receive an intravenous infusion of an omega-3 polyunsaturated fatty acid (PUFA) emulsion containing 10 g of fish oil per 100 mL or a saline placebo.

Those who received the intravenous infusion had significant decreases from baseline to end of treatment in the neutrophil-to-lymphocyte ratio (NLR), indicating marked reductions in systemic inflammation.

In contrast, patients randomized to a saline placebo had no significant improvements in NLR, Magnus Bäck, MD, PhD, from the Karolinska Institute in Stockholm reported at the meeting.

“Our lipidomic analysis also showed that omega-3 treatment skewed the lipid response, with reduced levels of proinflammatory lipid mediators, and increased levels of proresolving mediators,” according to a late-breaking abstract, which Dr. Bäck presented during the session.

Omega-3 treatment was not significantly associated with reduction in either C-reactive protein (CRP) or the proinflammatory cytokine interleukin-6, however.
 

‘Eicosanoid storm’

In a review article published in January 2021 in the open-access journal Frontiers in Physiology, Dr. Bäck and colleagues outlined the rationale for their randomized trial.

“Excessive inflammation has been reported in severe cases with respiratory failure and cardiovascular complications,” they wrote. “In addition to the release of cytokines, referred to as cytokine release syndrome or ‘cytokine storm,’ increased proinflammatory lipid mediators derived from the omega-6 polyunsaturated fatty acid (PUFA) arachidonic acid may cause an ‘eicosanoid storm,’ which contributes to the uncontrolled systemic inflammation.”

Omega-3 PUFA contains proresolving mediators that can limit inflammatory reactions, suggesting the possibility of an inflammation-resolving benefit in patients with COVID-19 without concerns about immunosuppression, the authors hypothesized.
 

Trial details

In the trial, COVID-Omega-F, they enrolled patients with a COVID-19 diagnosis requiring hospitalization. Patients with an allergy to fish oil or who had contraindications to intravenous PUFA administration (for example, risk for bleeding, shock, or emboli) were excluded.

Ten patients were randomly assigned to receive infusions of the omega-3 PUFA and 12 were assigned to receive infusions of the placebo, once daily for 5 days. The primary outcome measure was change in inflammatory biomarkers, including white blood cell counts, CRP, cytokines, and lipid mediators.

Baseline demographic and clinical characteristics were similar between the two study arms, with a median of about 7 days since the onset of symptoms, and 3.5 days since a diagnosis of COVID-19.

All patients had low lymphocyte responses reflected by a high NLR, a prognostic measure for worse outcomes in patients with COVID-19 infections, Dr. Bäck said.

Inflammation was moderate, with a CRP of 65 mg/L in the placebo group and 62 mg/L in the omega-3 group.

Seven patients in each study arm received concomitant corticoid treatment. Two patients in each arm died in hospital, but there were no serious treatment-related adverse events.
 

Inflammatory markers improve

As noted before, there was a significant decline in NLR from baseline among patients randomized to omega-3 (P = .02) but no corresponding decrease in patients assigned to placebo infusions.

“The significant decrease was largely driven by an increase in the lymphocyte count in the omega-3 treated group (P = .004), whereas lymphocytes did not significantly change,” Dr. Bäck said.

As expected, patients in the omega-3 group had pronounced increases in omega-3 fatty acids, including eicosapentaenoic acid and docosahexaenoic acid.

The metabolism of fatty acids also differed markedly between the groups, with a significant decrease in the omega-3 group but not the placebo group in proinflammatory mediators, and an increase in precursors to proresolving mediators, Dr. Bäck noted.
 

AFib concerns

In a question-and-answer part of the session, a physician who identified herself as “Senya from Russia” questioned the safety of omega-3 treatment in this population, “because recently there was a meta-analysis which showed that omega-3 fatty acids will increase the risk of atrial fibrillation in older adults especially.”

The systematic review and meta-analysis she referred to, published in Circulation and reported on by this news organization, showed that, among 81,210 patients with a mean age of 65 enrolled in seven randomized controlled trials, omega-3 fatty acid supplementation was associated with a 25% increase in risk for atrial fibrillation. This risk appeared to be higher in trials testing doses greater than 1 g/day, according to the paper.

“This was not monitored in this study,” Dr. Bäck replied. “It is true that the meta-analysis showed an increased incidence of atrial fibrillation, so it would be something to monitor in case this trial would be expanded to a larger population.”

The study was supported by the Karolinska Institute. Dr. Bäck disclosed no relevant financial relationships.

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

Armed with pediatric data from the COVID-19 pandemic, a team of researchers is suggesting that most cases of Guillain-Barré syndrome may not be connected to infectious disease, as is sometimes assumed.

While pediatric cases of various types of infections fell by 45%-95% during the early months of the pandemic, cases of acute inflammatory demyelinating polyneuropathy (AIDP), an inflammatory neuropathy belonging to the clinical spectrum of Guillain-Barré syndrome, only fell by about 32%-37%, a rate that’s similar to the 35.1% decline in overall hospital admissions over that time period, researchers found. There was also no apparent link between the appearance of COVID-19 and the number of reported AIDP cases.

“There was no clear association between respiratory or gastrointestinal infections and rates of AIDP. Further, we found that AIDP did not have the expected dramatic reduction when community-acquired infections decreased during the pandemic,” Children’s Hospital of Philadelphia neurologist Craig A. Press, MD, PhD, said in an interview.

Dr. Press and colleagues presented their findings in a poster at the 50th annual meeting of the Child Neurology Society.

According to Dr. Press, the cause of AIDP in most patients is unclear, although infections and vaccinations are often linked to cases. “However, the data supporting this link is often weak. Infections with Campylobacter jejuni [bacteria that causes food poisoning] are known to be associated with AIDP, while rates of AIDP in the general population and in those with influenza are similar.”

For the new multicenter, cross-sectional study, researchers tracked AIDP data from the 47 pediatric hospitals that provide statistics to the Pediatric Health Information System. They focused on the period from January 2017 to September 2020, which included the first months of the COVID-19 pandemic in the United States.

“Social distancing, masks, and increased hand hygiene decrease community-acquired infectious rates in a dramatic way,” Dr. Press said. “If these infections were causing AIDP, we hypothesized that the cases of AIDP would drop substantially as a result.”

But this didn’t appear to happen. Researchers found that the numbers of various types of infections declined from April to September 2020: Respiratory infections dipped by 73%-78%, gastrointestinal infections fell by 45%-61%, and influenza infections dipped by 88%-95%. But AIDP cases didn’t fall as precipitously. In fact, their levels were about the same as they were in April 2017, a month when rates of gastrointestinal, respiratory disease and influenza infections were at seasonally low – but not abnormal – ebbs.

“While we must be cautious interpreting the results,” Dr. Press said, “this makes the link between infections as the main driver of pediatric AIDP less likely.”

However, he said, “this study does not exclude the possibility that rare infections cause AIDP – the data supporting that some more rare infections like campylobacter have a connection to AIDP are more robust – or that common infections very rarely lead to AIDP. While we look for triggers causing inflammatory disorders, AIDP maybe an autoinflammatory disorder without a clear trigger.”

Going forward, Dr. Press said, “we hope to look at infectious data in a more granular way to identify if specific viral or bacterial infectious may be associated with this or other inflammatory disorders. We believe that the use of data like this and the natural experiment that COVID-19 provided may help us to explore the impact of infections on disorders thought to be postinfectious.”

No study funding is reported, and the authors report no relevant disclosures.
 

Armed with pediatric data from the COVID-19 pandemic, a team of researchers is suggesting that most cases of Guillain-Barré syndrome may not be connected to infectious disease, as is sometimes assumed.

While pediatric cases of various types of infections fell by 45%-95% during the early months of the pandemic, cases of acute inflammatory demyelinating polyneuropathy (AIDP), an inflammatory neuropathy belonging to the clinical spectrum of Guillain-Barré syndrome, only fell by about 32%-37%, a rate that’s similar to the 35.1% decline in overall hospital admissions over that time period, researchers found. There was also no apparent link between the appearance of COVID-19 and the number of reported AIDP cases.

“There was no clear association between respiratory or gastrointestinal infections and rates of AIDP. Further, we found that AIDP did not have the expected dramatic reduction when community-acquired infections decreased during the pandemic,” Children’s Hospital of Philadelphia neurologist Craig A. Press, MD, PhD, said in an interview.

Dr. Press and colleagues presented their findings in a poster at the 50th annual meeting of the Child Neurology Society.

According to Dr. Press, the cause of AIDP in most patients is unclear, although infections and vaccinations are often linked to cases. “However, the data supporting this link is often weak. Infections with Campylobacter jejuni [bacteria that causes food poisoning] are known to be associated with AIDP, while rates of AIDP in the general population and in those with influenza are similar.”

For the new multicenter, cross-sectional study, researchers tracked AIDP data from the 47 pediatric hospitals that provide statistics to the Pediatric Health Information System. They focused on the period from January 2017 to September 2020, which included the first months of the COVID-19 pandemic in the United States.

“Social distancing, masks, and increased hand hygiene decrease community-acquired infectious rates in a dramatic way,” Dr. Press said. “If these infections were causing AIDP, we hypothesized that the cases of AIDP would drop substantially as a result.”

But this didn’t appear to happen. Researchers found that the numbers of various types of infections declined from April to September 2020: Respiratory infections dipped by 73%-78%, gastrointestinal infections fell by 45%-61%, and influenza infections dipped by 88%-95%. But AIDP cases didn’t fall as precipitously. In fact, their levels were about the same as they were in April 2017, a month when rates of gastrointestinal, respiratory disease and influenza infections were at seasonally low – but not abnormal – ebbs.

“While we must be cautious interpreting the results,” Dr. Press said, “this makes the link between infections as the main driver of pediatric AIDP less likely.”

However, he said, “this study does not exclude the possibility that rare infections cause AIDP – the data supporting that some more rare infections like campylobacter have a connection to AIDP are more robust – or that common infections very rarely lead to AIDP. While we look for triggers causing inflammatory disorders, AIDP maybe an autoinflammatory disorder without a clear trigger.”

Going forward, Dr. Press said, “we hope to look at infectious data in a more granular way to identify if specific viral or bacterial infectious may be associated with this or other inflammatory disorders. We believe that the use of data like this and the natural experiment that COVID-19 provided may help us to explore the impact of infections on disorders thought to be postinfectious.”

No study funding is reported, and the authors report no relevant disclosures.
 

Armed with pediatric data from the COVID-19 pandemic, a team of researchers is suggesting that most cases of Guillain-Barré syndrome may not be connected to infectious disease, as is sometimes assumed.

While pediatric cases of various types of infections fell by 45%-95% during the early months of the pandemic, cases of acute inflammatory demyelinating polyneuropathy (AIDP), an inflammatory neuropathy belonging to the clinical spectrum of Guillain-Barré syndrome, only fell by about 32%-37%, a rate that’s similar to the 35.1% decline in overall hospital admissions over that time period, researchers found. There was also no apparent link between the appearance of COVID-19 and the number of reported AIDP cases.

“There was no clear association between respiratory or gastrointestinal infections and rates of AIDP. Further, we found that AIDP did not have the expected dramatic reduction when community-acquired infections decreased during the pandemic,” Children’s Hospital of Philadelphia neurologist Craig A. Press, MD, PhD, said in an interview.

Dr. Press and colleagues presented their findings in a poster at the 50th annual meeting of the Child Neurology Society.

According to Dr. Press, the cause of AIDP in most patients is unclear, although infections and vaccinations are often linked to cases. “However, the data supporting this link is often weak. Infections with Campylobacter jejuni [bacteria that causes food poisoning] are known to be associated with AIDP, while rates of AIDP in the general population and in those with influenza are similar.”

For the new multicenter, cross-sectional study, researchers tracked AIDP data from the 47 pediatric hospitals that provide statistics to the Pediatric Health Information System. They focused on the period from January 2017 to September 2020, which included the first months of the COVID-19 pandemic in the United States.

“Social distancing, masks, and increased hand hygiene decrease community-acquired infectious rates in a dramatic way,” Dr. Press said. “If these infections were causing AIDP, we hypothesized that the cases of AIDP would drop substantially as a result.”

But this didn’t appear to happen. Researchers found that the numbers of various types of infections declined from April to September 2020: Respiratory infections dipped by 73%-78%, gastrointestinal infections fell by 45%-61%, and influenza infections dipped by 88%-95%. But AIDP cases didn’t fall as precipitously. In fact, their levels were about the same as they were in April 2017, a month when rates of gastrointestinal, respiratory disease and influenza infections were at seasonally low – but not abnormal – ebbs.

“While we must be cautious interpreting the results,” Dr. Press said, “this makes the link between infections as the main driver of pediatric AIDP less likely.”

However, he said, “this study does not exclude the possibility that rare infections cause AIDP – the data supporting that some more rare infections like campylobacter have a connection to AIDP are more robust – or that common infections very rarely lead to AIDP. While we look for triggers causing inflammatory disorders, AIDP maybe an autoinflammatory disorder without a clear trigger.”

Going forward, Dr. Press said, “we hope to look at infectious data in a more granular way to identify if specific viral or bacterial infectious may be associated with this or other inflammatory disorders. We believe that the use of data like this and the natural experiment that COVID-19 provided may help us to explore the impact of infections on disorders thought to be postinfectious.”

No study funding is reported, and the authors report no relevant disclosures.
 

Children and young adults with epilepsy had fewer seizures after combination treatment with the drug Epidiolex, which contains the cannabidiol (CBD), and various doses of tetrahydrocannabinol (THC), the component of cannabis that makes people high in larger quantities, researchers reported.

“THC can contribute to seizure control and mitigation some of the side effects of CBD,” said study coauthor and Austin, Tex., child neurologist Karen Keough, MD, in an interview. Dr. Keough and colleagues presented their findings at the 50th annual meeting of the Child Neurology Society.

In a landmark move, the Food and Drug Administration approved Epidiolex in 2018 for the treatment of seizures in two rare forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome. The agency had never before approved a drug with a purified ingredient derived from marijuana.

CBD, the active ingredient in Epidiolex, is nonpsychoactive. The use in medicine of THC, the main driver of marijuana’s ability to make people stoned, is much more controversial.

Dr. Keough said she had treated 60-70 children with CBD, at the same strength as in Epidiolex (100 mg), and 5 mg of THC before the drug was approved. “I was seeing some very impressive results, and some became seizure free who’d always been refractory,” she said.

When the Epidiolex became available, she said, some patients transitioned to it and stopped taking THC. According to her, some patients fared well. But others immediately experienced worse seizures, she said, and some developed side effects to Epidiolex in the absence of THC, such as agitation and appetite suppression.
 

Combination therapy

For the new study, a retrospective, unblinded cohort analysis, Dr. Keough and colleagues tracked patients who received various doses of CBD, in some cases as Epidiolex, and various doses of THC prescribed by the Texas Original Compassionate Cultivation dispensary, where she serves as chief medical officer.

The initial number of patients was 212; 135 consented to review and 10 were excluded for various reasons leaving a total of 74 subjects in the study. The subjects, whose median age at the start of the study was 12 years (range, 2-25 years), were tracked from 2018 to2021. Just over half (55%) were male, and they remained on the regimen for a median of 805 days (range, 400-1,141).

Of the 74 subjects, 45.9% had a reduction of seizures of more than 75%, and 20.3% had a reduction of 50%-75%. Only 4.1% saw their seizures worsen.

The THC doses varied from none to more than 12 mg/day; CBD doses varied from none to more than 26 mg/kg per day. O the 74 patients, 18 saw their greatest seizure reduction from baseline when they received no THC; 12 saw their greatest seizure reduction from baseline when they received 0-2 mg/kg per day of CBD.
 

Still controversial

Did the patients get high? In some cases they did, Dr. Keough said. However, “a lot of these patients are either too young or too cognitively limited to describe whether they’re feeling intoxicated. That’s one of the many reasons why this is so controversial. You have to go into this with eyes wide open. We’re working in an environment with limited information as to what an intoxicating dose is for a small kid.”

However, she said, it seems clear that “THC can enhance the effect of CBD in children with epilepsy” and reduce CBD side effects. It’s not surprising that the substances work differently since they interact with brain cells in different ways, she said.

For neurologists, she said, “the challenge is to find a reliable source of THC that you can count on and verify so you aren’t overdosing the patients.”

University of Saskatchewan, Saskatoon, child neurologist and cannabinoid researcher Richard Huntsman, MD, who’s familiar with the study findings, said in an interview that they “provide another strong signal that the addition of THC provides benefit, at least in some patients.”

But it’s still unclear “why some children respond best in regards to seizure reduction and side effect profile with combination CBD:THC therapy, and others seemed to do better with CBD alone,” he said. Also unknown: “the ideal THC:CBD ratio that allows optimal seizure control while preventing the potential harmful effects of THC.”

As for the future, he said, “as we are just scratching the surface of our knowledge about the use of cannabis-based therapies in children with neurological disorders, I suspect that the use of these therapies will expand over time.”

No study funding is reported. Dr. Keough disclosed serving as chief medical officer of Texas Original Compassionate Cultivation. Dr. Huntsman disclosed serving as lead investigator of the Cannabidiol in Children with Refractory Epileptic Encephalopathy study and serving on the boards of the Cannabinoid Research Initiative of Saskatchewan (University of Saskatchewan) and Canadian Childhood Cannabinoid Clinical Trials Consortium. He is also cochair of Health Canada’s Scientific Advisory Committee on Cannabinoids for Health Purposes.
 

Children and young adults with epilepsy had fewer seizures after combination treatment with the drug Epidiolex, which contains the cannabidiol (CBD), and various doses of tetrahydrocannabinol (THC), the component of cannabis that makes people high in larger quantities, researchers reported.

“THC can contribute to seizure control and mitigation some of the side effects of CBD,” said study coauthor and Austin, Tex., child neurologist Karen Keough, MD, in an interview. Dr. Keough and colleagues presented their findings at the 50th annual meeting of the Child Neurology Society.

In a landmark move, the Food and Drug Administration approved Epidiolex in 2018 for the treatment of seizures in two rare forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome. The agency had never before approved a drug with a purified ingredient derived from marijuana.

CBD, the active ingredient in Epidiolex, is nonpsychoactive. The use in medicine of THC, the main driver of marijuana’s ability to make people stoned, is much more controversial.

Dr. Keough said she had treated 60-70 children with CBD, at the same strength as in Epidiolex (100 mg), and 5 mg of THC before the drug was approved. “I was seeing some very impressive results, and some became seizure free who’d always been refractory,” she said.

When the Epidiolex became available, she said, some patients transitioned to it and stopped taking THC. According to her, some patients fared well. But others immediately experienced worse seizures, she said, and some developed side effects to Epidiolex in the absence of THC, such as agitation and appetite suppression.
 

Combination therapy

For the new study, a retrospective, unblinded cohort analysis, Dr. Keough and colleagues tracked patients who received various doses of CBD, in some cases as Epidiolex, and various doses of THC prescribed by the Texas Original Compassionate Cultivation dispensary, where she serves as chief medical officer.

The initial number of patients was 212; 135 consented to review and 10 were excluded for various reasons leaving a total of 74 subjects in the study. The subjects, whose median age at the start of the study was 12 years (range, 2-25 years), were tracked from 2018 to2021. Just over half (55%) were male, and they remained on the regimen for a median of 805 days (range, 400-1,141).

Of the 74 subjects, 45.9% had a reduction of seizures of more than 75%, and 20.3% had a reduction of 50%-75%. Only 4.1% saw their seizures worsen.

The THC doses varied from none to more than 12 mg/day; CBD doses varied from none to more than 26 mg/kg per day. O the 74 patients, 18 saw their greatest seizure reduction from baseline when they received no THC; 12 saw their greatest seizure reduction from baseline when they received 0-2 mg/kg per day of CBD.
 

Still controversial

Did the patients get high? In some cases they did, Dr. Keough said. However, “a lot of these patients are either too young or too cognitively limited to describe whether they’re feeling intoxicated. That’s one of the many reasons why this is so controversial. You have to go into this with eyes wide open. We’re working in an environment with limited information as to what an intoxicating dose is for a small kid.”

However, she said, it seems clear that “THC can enhance the effect of CBD in children with epilepsy” and reduce CBD side effects. It’s not surprising that the substances work differently since they interact with brain cells in different ways, she said.

For neurologists, she said, “the challenge is to find a reliable source of THC that you can count on and verify so you aren’t overdosing the patients.”

University of Saskatchewan, Saskatoon, child neurologist and cannabinoid researcher Richard Huntsman, MD, who’s familiar with the study findings, said in an interview that they “provide another strong signal that the addition of THC provides benefit, at least in some patients.”

But it’s still unclear “why some children respond best in regards to seizure reduction and side effect profile with combination CBD:THC therapy, and others seemed to do better with CBD alone,” he said. Also unknown: “the ideal THC:CBD ratio that allows optimal seizure control while preventing the potential harmful effects of THC.”

As for the future, he said, “as we are just scratching the surface of our knowledge about the use of cannabis-based therapies in children with neurological disorders, I suspect that the use of these therapies will expand over time.”

No study funding is reported. Dr. Keough disclosed serving as chief medical officer of Texas Original Compassionate Cultivation. Dr. Huntsman disclosed serving as lead investigator of the Cannabidiol in Children with Refractory Epileptic Encephalopathy study and serving on the boards of the Cannabinoid Research Initiative of Saskatchewan (University of Saskatchewan) and Canadian Childhood Cannabinoid Clinical Trials Consortium. He is also cochair of Health Canada’s Scientific Advisory Committee on Cannabinoids for Health Purposes.
 

Children and young adults with epilepsy had fewer seizures after combination treatment with the drug Epidiolex, which contains the cannabidiol (CBD), and various doses of tetrahydrocannabinol (THC), the component of cannabis that makes people high in larger quantities, researchers reported.

“THC can contribute to seizure control and mitigation some of the side effects of CBD,” said study coauthor and Austin, Tex., child neurologist Karen Keough, MD, in an interview. Dr. Keough and colleagues presented their findings at the 50th annual meeting of the Child Neurology Society.

In a landmark move, the Food and Drug Administration approved Epidiolex in 2018 for the treatment of seizures in two rare forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome. The agency had never before approved a drug with a purified ingredient derived from marijuana.

CBD, the active ingredient in Epidiolex, is nonpsychoactive. The use in medicine of THC, the main driver of marijuana’s ability to make people stoned, is much more controversial.

Dr. Keough said she had treated 60-70 children with CBD, at the same strength as in Epidiolex (100 mg), and 5 mg of THC before the drug was approved. “I was seeing some very impressive results, and some became seizure free who’d always been refractory,” she said.

When the Epidiolex became available, she said, some patients transitioned to it and stopped taking THC. According to her, some patients fared well. But others immediately experienced worse seizures, she said, and some developed side effects to Epidiolex in the absence of THC, such as agitation and appetite suppression.
 

Combination therapy

For the new study, a retrospective, unblinded cohort analysis, Dr. Keough and colleagues tracked patients who received various doses of CBD, in some cases as Epidiolex, and various doses of THC prescribed by the Texas Original Compassionate Cultivation dispensary, where she serves as chief medical officer.

The initial number of patients was 212; 135 consented to review and 10 were excluded for various reasons leaving a total of 74 subjects in the study. The subjects, whose median age at the start of the study was 12 years (range, 2-25 years), were tracked from 2018 to2021. Just over half (55%) were male, and they remained on the regimen for a median of 805 days (range, 400-1,141).

Of the 74 subjects, 45.9% had a reduction of seizures of more than 75%, and 20.3% had a reduction of 50%-75%. Only 4.1% saw their seizures worsen.

The THC doses varied from none to more than 12 mg/day; CBD doses varied from none to more than 26 mg/kg per day. O the 74 patients, 18 saw their greatest seizure reduction from baseline when they received no THC; 12 saw their greatest seizure reduction from baseline when they received 0-2 mg/kg per day of CBD.
 

Still controversial

Did the patients get high? In some cases they did, Dr. Keough said. However, “a lot of these patients are either too young or too cognitively limited to describe whether they’re feeling intoxicated. That’s one of the many reasons why this is so controversial. You have to go into this with eyes wide open. We’re working in an environment with limited information as to what an intoxicating dose is for a small kid.”

However, she said, it seems clear that “THC can enhance the effect of CBD in children with epilepsy” and reduce CBD side effects. It’s not surprising that the substances work differently since they interact with brain cells in different ways, she said.

For neurologists, she said, “the challenge is to find a reliable source of THC that you can count on and verify so you aren’t overdosing the patients.”

University of Saskatchewan, Saskatoon, child neurologist and cannabinoid researcher Richard Huntsman, MD, who’s familiar with the study findings, said in an interview that they “provide another strong signal that the addition of THC provides benefit, at least in some patients.”

But it’s still unclear “why some children respond best in regards to seizure reduction and side effect profile with combination CBD:THC therapy, and others seemed to do better with CBD alone,” he said. Also unknown: “the ideal THC:CBD ratio that allows optimal seizure control while preventing the potential harmful effects of THC.”

As for the future, he said, “as we are just scratching the surface of our knowledge about the use of cannabis-based therapies in children with neurological disorders, I suspect that the use of these therapies will expand over time.”

No study funding is reported. Dr. Keough disclosed serving as chief medical officer of Texas Original Compassionate Cultivation. Dr. Huntsman disclosed serving as lead investigator of the Cannabidiol in Children with Refractory Epileptic Encephalopathy study and serving on the boards of the Cannabinoid Research Initiative of Saskatchewan (University of Saskatchewan) and Canadian Childhood Cannabinoid Clinical Trials Consortium. He is also cochair of Health Canada’s Scientific Advisory Committee on Cannabinoids for Health Purposes.
 

Sustained, intensive therapy with two antiglutamatergic drugs is superior to standard aggressive treatment for postanoxic super-refractory status epilepticus (SRSE), new research suggests.

In a retrospective cohort study of survivors of cardiac arrest with postanoxic sustained SRSE, resolution of the condition was achieved by 81% of those who received intensive treatment of ketamine plus perampanel, versus 41% of those who received standard care.

The novelty of the new treatment approach is the duration of therapy as well as the dual antiglutamate drugs, researchers note.

“So the logic is to continue treatment until resolution of refractory status epilepticus under continuous EEG [electroencephalographic] monitoring,” reported lead investigator Simone Beretta, MD, San Gerardo University Hospital, Monza, Italy.

Therapy was guided by data on brainstem reflexes, N20 cortical responses, neuronal serum enolase levels, and neuroimaging.

If all or most of these indicators are favorable, “we continue to treat without any time limit,” Dr. Beretta said. However, if the indicators become unfavorable, clinicians should consider lowering the intensity of care, he added.

The findings were presented at the 2021 World Congress of Neurology (WCN).
 

SUPER-CAT trial

In SRSE, epileptic seizures occur one after another without patients recovering consciousness in between. Standard aggressive therapy for the condition does not include antiglutamatergic drugs, the researchers noted.

In the Super-Refractory Status Epilepticus After Cardiac Arrest: Aggressive Treatment Guided by Multimodal Prognostic Indicators (SUPER-CAT) study, researchers assessed the combination of two such medications.

The first was the anti-NMDA receptor drug ketamine, which was given by intravenous bolus and then continuous infusion for 3 days guided by continuous EEG to reach a ketamine EEG pattern, as evidenced by alpha and beta waves. It was combined with the anti-AMPA receptor antiepileptic perampanel via nasogastric tube for 5 days, followed by slow tapering.

Dr. Beretta noted that in the ongoing TELSTAR trial, which involved a similar patient population, a different drug combination is being used. A major difference between the two trials is that in the TELSTAR trial, aggressive therapy continues for only 2 days if there is no response.

“In the SUPER-CAT study, we continue far beyond 2 days in the majority of patients,” he said. In addition, ketamine and perampanel were not assessed in TELSTAR.

In SUPER-CAT, 489 survivors of cardiac arrest were recruited over 10 years. Of these, 101 had refractory status epilepticus. After excluding those with more than two indicators of poor prognosis (n = 31) or whose status epilepticus resolved (n = 14), 56 patients were determined to have SRSE. All had experienced relapse after undergoing one cycle of anesthetic.

The 56 participants received one of three treatment regimens: double antiglutamate (DAG) therapy of ketamine and perampanel (n = 26), single antiglutamate therapy with either agent (n = 8), or aggressive nonantiglutamate (NAG) therapy with antiepilepsy drugs and anesthetics other than ketamine or perampanel (n = 22).

The single-antiglutamate group was not included in the analysis of patient outcomes.

The DAG and NAG groups were well balanced at baseline. There were no significant differences in median age (60 years vs. 66 years), gender, low cerebral blood flow, presence of bilateral pupillary or corneal reflexes, neuron-specific enolase levels, cortical N20 somatosenory evoked potentials, moderate to severe postanoxic brain injury, and hypothermia/targeted temperature management.
 

Primary outcome met

More patients in the DAG group (42%) had moderate to severe postanoxic brain injury than in the NAG group (28%). However, the difference was not statistically significant (P = .08), possibly because of the small sample sizes. The number of antiepileptic drugs and the number of cycles of anesthetics did not differ between the groups.

Results showed that efficacy and safety outcomes favored DAG therapy.

The primary efficacy outcome was resolution of status epilepticus within 3 days after initiation of treatments. Status epilepticus resolved for 21 of 26 patients in the DAG group (81%), versus 9 of 22 patients in the NAG group (41%; odds ratio, 6.06; 95% confidence interval, 1.66-22.12; P = .005).

For secondary efficacy outcomes, there was a trend in favor of DAG, but differences from the NAG group were not statistically significant. In the groups, 46% versus 32% awakened and responded to commands before discharge from the intensive care unit, and 32% versus 23% showed good neurologic outcome at 6 months.

The primary safety outcome of all-cause mortality risk in the ICU was 90% lower for patients treated with DAG than for those treated with NAG (15% vs. 64%; OR, 0.1; 95% CI, 0.02-0.41; P < .01). Dr. Beretta explained that the high mortality rate in the NAG group was presumably a result of unresolved status epilepticus.

The secondary safety outcome of a transitory rise of gamma-glutamyl transferase greater than three times the upper limit of normal in the DAG group was expected with high-dose perampanel, the investigators noted. This outcome occurred in 77% of the DAG group versus 27% of the NAG group (OR, 9.88; 95% CI, 2.4-32.9; P < .001).

There was no statistically significant difference in incidence of recurrent cardiac arrest during therapy. This occurred in one member of the DAG group and in none in the NAG group.

Dr. Beretta reported that their investigations are still in a retrospective phase, but the researchers plan to move the work into a prospective phase and possibly a randomized trial soon.
 

Fascinating, promising

Commenting on the findings, Jaysingh Singh, MD, co-director of the Epilepsy Surgery Center at the Ohio State University Wexner Medical Center, Columbus, said the study provides “fascinating, very helpful data” about a condition that has responded well to current treatment options.

He added that his center has used “the innovative treatments” discussed in the study for a few patients.

“More concrete evidence will push us to use it more uniformly across all our patient population [that] has refractory status. So I’m very optimistic, and the data were very promising,” said Dr. Singh, who was not involved with the research.

He cautioned that the study was retrospective, not randomized or controlled, and that it involved a small number of patients but said that the data were “heading in the right direction.”

Although resolution of status epilepticus was better among patients in the DAG group than in the NAG group, the awakenings and neurologic outcomes were “pretty much same as standard medical therapy, which we commonly give to our patients,” said Dr. Singh. “We see this phenomenon all the time in our patients.”

He noted that other factors can determine how patients respond, such as conditions of the heart or kidneys, the presence of sepsis, and multiorgan dysfunction. These factors were not controlled for in the study.

Nonetheless, he said the study achieved its primary endpoint of better resolution of status epilepticus “because that’s the first thing you want to see: whether the treatment is taking care of that.”

The study received no outside funding. Dr. Beretta and Dr. Singh have disclosed no relevant financial relationships.

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

Sustained, intensive therapy with two antiglutamatergic drugs is superior to standard aggressive treatment for postanoxic super-refractory status epilepticus (SRSE), new research suggests.

In a retrospective cohort study of survivors of cardiac arrest with postanoxic sustained SRSE, resolution of the condition was achieved by 81% of those who received intensive treatment of ketamine plus perampanel, versus 41% of those who received standard care.

The novelty of the new treatment approach is the duration of therapy as well as the dual antiglutamate drugs, researchers note.

“So the logic is to continue treatment until resolution of refractory status epilepticus under continuous EEG [electroencephalographic] monitoring,” reported lead investigator Simone Beretta, MD, San Gerardo University Hospital, Monza, Italy.

Therapy was guided by data on brainstem reflexes, N20 cortical responses, neuronal serum enolase levels, and neuroimaging.

If all or most of these indicators are favorable, “we continue to treat without any time limit,” Dr. Beretta said. However, if the indicators become unfavorable, clinicians should consider lowering the intensity of care, he added.

The findings were presented at the 2021 World Congress of Neurology (WCN).
 

SUPER-CAT trial

In SRSE, epileptic seizures occur one after another without patients recovering consciousness in between. Standard aggressive therapy for the condition does not include antiglutamatergic drugs, the researchers noted.

In the Super-Refractory Status Epilepticus After Cardiac Arrest: Aggressive Treatment Guided by Multimodal Prognostic Indicators (SUPER-CAT) study, researchers assessed the combination of two such medications.

The first was the anti-NMDA receptor drug ketamine, which was given by intravenous bolus and then continuous infusion for 3 days guided by continuous EEG to reach a ketamine EEG pattern, as evidenced by alpha and beta waves. It was combined with the anti-AMPA receptor antiepileptic perampanel via nasogastric tube for 5 days, followed by slow tapering.

Dr. Beretta noted that in the ongoing TELSTAR trial, which involved a similar patient population, a different drug combination is being used. A major difference between the two trials is that in the TELSTAR trial, aggressive therapy continues for only 2 days if there is no response.

“In the SUPER-CAT study, we continue far beyond 2 days in the majority of patients,” he said. In addition, ketamine and perampanel were not assessed in TELSTAR.

In SUPER-CAT, 489 survivors of cardiac arrest were recruited over 10 years. Of these, 101 had refractory status epilepticus. After excluding those with more than two indicators of poor prognosis (n = 31) or whose status epilepticus resolved (n = 14), 56 patients were determined to have SRSE. All had experienced relapse after undergoing one cycle of anesthetic.

The 56 participants received one of three treatment regimens: double antiglutamate (DAG) therapy of ketamine and perampanel (n = 26), single antiglutamate therapy with either agent (n = 8), or aggressive nonantiglutamate (NAG) therapy with antiepilepsy drugs and anesthetics other than ketamine or perampanel (n = 22).

The single-antiglutamate group was not included in the analysis of patient outcomes.

The DAG and NAG groups were well balanced at baseline. There were no significant differences in median age (60 years vs. 66 years), gender, low cerebral blood flow, presence of bilateral pupillary or corneal reflexes, neuron-specific enolase levels, cortical N20 somatosenory evoked potentials, moderate to severe postanoxic brain injury, and hypothermia/targeted temperature management.
 

Primary outcome met

More patients in the DAG group (42%) had moderate to severe postanoxic brain injury than in the NAG group (28%). However, the difference was not statistically significant (P = .08), possibly because of the small sample sizes. The number of antiepileptic drugs and the number of cycles of anesthetics did not differ between the groups.

Results showed that efficacy and safety outcomes favored DAG therapy.

The primary efficacy outcome was resolution of status epilepticus within 3 days after initiation of treatments. Status epilepticus resolved for 21 of 26 patients in the DAG group (81%), versus 9 of 22 patients in the NAG group (41%; odds ratio, 6.06; 95% confidence interval, 1.66-22.12; P = .005).

For secondary efficacy outcomes, there was a trend in favor of DAG, but differences from the NAG group were not statistically significant. In the groups, 46% versus 32% awakened and responded to commands before discharge from the intensive care unit, and 32% versus 23% showed good neurologic outcome at 6 months.

The primary safety outcome of all-cause mortality risk in the ICU was 90% lower for patients treated with DAG than for those treated with NAG (15% vs. 64%; OR, 0.1; 95% CI, 0.02-0.41; P < .01). Dr. Beretta explained that the high mortality rate in the NAG group was presumably a result of unresolved status epilepticus.

The secondary safety outcome of a transitory rise of gamma-glutamyl transferase greater than three times the upper limit of normal in the DAG group was expected with high-dose perampanel, the investigators noted. This outcome occurred in 77% of the DAG group versus 27% of the NAG group (OR, 9.88; 95% CI, 2.4-32.9; P < .001).

There was no statistically significant difference in incidence of recurrent cardiac arrest during therapy. This occurred in one member of the DAG group and in none in the NAG group.

Dr. Beretta reported that their investigations are still in a retrospective phase, but the researchers plan to move the work into a prospective phase and possibly a randomized trial soon.
 

Fascinating, promising

Commenting on the findings, Jaysingh Singh, MD, co-director of the Epilepsy Surgery Center at the Ohio State University Wexner Medical Center, Columbus, said the study provides “fascinating, very helpful data” about a condition that has responded well to current treatment options.

He added that his center has used “the innovative treatments” discussed in the study for a few patients.

“More concrete evidence will push us to use it more uniformly across all our patient population [that] has refractory status. So I’m very optimistic, and the data were very promising,” said Dr. Singh, who was not involved with the research.

He cautioned that the study was retrospective, not randomized or controlled, and that it involved a small number of patients but said that the data were “heading in the right direction.”

Although resolution of status epilepticus was better among patients in the DAG group than in the NAG group, the awakenings and neurologic outcomes were “pretty much same as standard medical therapy, which we commonly give to our patients,” said Dr. Singh. “We see this phenomenon all the time in our patients.”

He noted that other factors can determine how patients respond, such as conditions of the heart or kidneys, the presence of sepsis, and multiorgan dysfunction. These factors were not controlled for in the study.

Nonetheless, he said the study achieved its primary endpoint of better resolution of status epilepticus “because that’s the first thing you want to see: whether the treatment is taking care of that.”

The study received no outside funding. Dr. Beretta and Dr. Singh have disclosed no relevant financial relationships.

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

Sustained, intensive therapy with two antiglutamatergic drugs is superior to standard aggressive treatment for postanoxic super-refractory status epilepticus (SRSE), new research suggests.

In a retrospective cohort study of survivors of cardiac arrest with postanoxic sustained SRSE, resolution of the condition was achieved by 81% of those who received intensive treatment of ketamine plus perampanel, versus 41% of those who received standard care.

The novelty of the new treatment approach is the duration of therapy as well as the dual antiglutamate drugs, researchers note.

“So the logic is to continue treatment until resolution of refractory status epilepticus under continuous EEG [electroencephalographic] monitoring,” reported lead investigator Simone Beretta, MD, San Gerardo University Hospital, Monza, Italy.

Therapy was guided by data on brainstem reflexes, N20 cortical responses, neuronal serum enolase levels, and neuroimaging.

If all or most of these indicators are favorable, “we continue to treat without any time limit,” Dr. Beretta said. However, if the indicators become unfavorable, clinicians should consider lowering the intensity of care, he added.

The findings were presented at the 2021 World Congress of Neurology (WCN).
 

SUPER-CAT trial

In SRSE, epileptic seizures occur one after another without patients recovering consciousness in between. Standard aggressive therapy for the condition does not include antiglutamatergic drugs, the researchers noted.

In the Super-Refractory Status Epilepticus After Cardiac Arrest: Aggressive Treatment Guided by Multimodal Prognostic Indicators (SUPER-CAT) study, researchers assessed the combination of two such medications.

The first was the anti-NMDA receptor drug ketamine, which was given by intravenous bolus and then continuous infusion for 3 days guided by continuous EEG to reach a ketamine EEG pattern, as evidenced by alpha and beta waves. It was combined with the anti-AMPA receptor antiepileptic perampanel via nasogastric tube for 5 days, followed by slow tapering.

Dr. Beretta noted that in the ongoing TELSTAR trial, which involved a similar patient population, a different drug combination is being used. A major difference between the two trials is that in the TELSTAR trial, aggressive therapy continues for only 2 days if there is no response.

“In the SUPER-CAT study, we continue far beyond 2 days in the majority of patients,” he said. In addition, ketamine and perampanel were not assessed in TELSTAR.

In SUPER-CAT, 489 survivors of cardiac arrest were recruited over 10 years. Of these, 101 had refractory status epilepticus. After excluding those with more than two indicators of poor prognosis (n = 31) or whose status epilepticus resolved (n = 14), 56 patients were determined to have SRSE. All had experienced relapse after undergoing one cycle of anesthetic.

The 56 participants received one of three treatment regimens: double antiglutamate (DAG) therapy of ketamine and perampanel (n = 26), single antiglutamate therapy with either agent (n = 8), or aggressive nonantiglutamate (NAG) therapy with antiepilepsy drugs and anesthetics other than ketamine or perampanel (n = 22).

The single-antiglutamate group was not included in the analysis of patient outcomes.

The DAG and NAG groups were well balanced at baseline. There were no significant differences in median age (60 years vs. 66 years), gender, low cerebral blood flow, presence of bilateral pupillary or corneal reflexes, neuron-specific enolase levels, cortical N20 somatosenory evoked potentials, moderate to severe postanoxic brain injury, and hypothermia/targeted temperature management.
 

Primary outcome met

More patients in the DAG group (42%) had moderate to severe postanoxic brain injury than in the NAG group (28%). However, the difference was not statistically significant (P = .08), possibly because of the small sample sizes. The number of antiepileptic drugs and the number of cycles of anesthetics did not differ between the groups.

Results showed that efficacy and safety outcomes favored DAG therapy.

The primary efficacy outcome was resolution of status epilepticus within 3 days after initiation of treatments. Status epilepticus resolved for 21 of 26 patients in the DAG group (81%), versus 9 of 22 patients in the NAG group (41%; odds ratio, 6.06; 95% confidence interval, 1.66-22.12; P = .005).

For secondary efficacy outcomes, there was a trend in favor of DAG, but differences from the NAG group were not statistically significant. In the groups, 46% versus 32% awakened and responded to commands before discharge from the intensive care unit, and 32% versus 23% showed good neurologic outcome at 6 months.

The primary safety outcome of all-cause mortality risk in the ICU was 90% lower for patients treated with DAG than for those treated with NAG (15% vs. 64%; OR, 0.1; 95% CI, 0.02-0.41; P < .01). Dr. Beretta explained that the high mortality rate in the NAG group was presumably a result of unresolved status epilepticus.

The secondary safety outcome of a transitory rise of gamma-glutamyl transferase greater than three times the upper limit of normal in the DAG group was expected with high-dose perampanel, the investigators noted. This outcome occurred in 77% of the DAG group versus 27% of the NAG group (OR, 9.88; 95% CI, 2.4-32.9; P < .001).

There was no statistically significant difference in incidence of recurrent cardiac arrest during therapy. This occurred in one member of the DAG group and in none in the NAG group.

Dr. Beretta reported that their investigations are still in a retrospective phase, but the researchers plan to move the work into a prospective phase and possibly a randomized trial soon.
 

Fascinating, promising

Commenting on the findings, Jaysingh Singh, MD, co-director of the Epilepsy Surgery Center at the Ohio State University Wexner Medical Center, Columbus, said the study provides “fascinating, very helpful data” about a condition that has responded well to current treatment options.

He added that his center has used “the innovative treatments” discussed in the study for a few patients.

“More concrete evidence will push us to use it more uniformly across all our patient population [that] has refractory status. So I’m very optimistic, and the data were very promising,” said Dr. Singh, who was not involved with the research.

He cautioned that the study was retrospective, not randomized or controlled, and that it involved a small number of patients but said that the data were “heading in the right direction.”

Although resolution of status epilepticus was better among patients in the DAG group than in the NAG group, the awakenings and neurologic outcomes were “pretty much same as standard medical therapy, which we commonly give to our patients,” said Dr. Singh. “We see this phenomenon all the time in our patients.”

He noted that other factors can determine how patients respond, such as conditions of the heart or kidneys, the presence of sepsis, and multiorgan dysfunction. These factors were not controlled for in the study.

Nonetheless, he said the study achieved its primary endpoint of better resolution of status epilepticus “because that’s the first thing you want to see: whether the treatment is taking care of that.”

The study received no outside funding. Dr. Beretta and Dr. Singh have disclosed no relevant financial relationships.

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

Genetic testing in patients with epilepsy can yield useful information that informs treatment and improves seizure control and other outcomes, new research shows.

Results of a survey that included more than 400 patients showed that positive findings from genetic testing helped guide clinical management in 50% of cases and improved patient outcomes in 75%. In addition, the findings were applicable to both children and adults.

“Fifty percent of the time the physicians reported that, yes, receiving the genetic diagnosis did change how they managed the patients,” reported co-investigator Dianalee McKnight, PhD, director of medical affairs at Invitae, a medical genetic testing company headquartered in San Francisco. In 81.3% of cases, providers reported they changed clinical management within 3 months of receiving the genetic results, she added.

The findings were presented at the 2021 World Congress of Neurology (WCN).
 

Test results can be practice-changing

Nearly 50% of positive genetic test results in epilepsy patients can help guide clinical management, Dr. McKnight noted. However, information on how physicians use genetic information in decision-making has been limited, prompting her conduct the survey.

A total of 1,567 physicians with 3,572 patients who had a definitive diagnosis of epilepsy were contacted. A total of 170 (10.8%) clinicians provided completed and eligible surveys on 429 patients with epilepsy.

The patient cohort comprised mostly children, with nearly 50 adults, which Dr. McKnight said is typical of the population receiving genetic testing in clinical practice.

She reported that genetic testing results prompted clinicians to make medication changes about 50% of the time. Other changes included specialist referral or to a clinical trial, monitoring for other neurological disease, and recommendations for dietary change or for surgery.

Growing influence of genetic testing

Commenting on the findings, Jaysingh Singh, MD, co-director of the Epilepsy Surgery Center at the Ohio State University Wexner Medical Center in Columbus, noted that the study highlights the value of gene testing in improving outcomes in patients with epilepsy, particularly the pediatric population.

He said the findings make him optimistic about the potential of genetic testing in adult patients – with at least one caveat.

“The limitation is that if we do find some mutation, we don’t know what to do with that. That’s definitely one challenge. And we see that more often in the adult patient population,” said Dr. Singh, who was not involved with the research.

He noted that there is a small group of genetic mutations when, found in adults, may dramatically alter treatment.

For example, he noted that if there is a gene mutation related to mTOR pathways, that could provide a future target because there are already medications that target this pathway.

Genetic testing may also be useful in cases where patients have normal brain imaging and poor response to standard treatment or in cases where patients have congenital abnormalities such as intellectual impairment or facial dysmorphic features and a co-morbid seizure disorder, he said.

Dr. Singh noted that he has often found genetic testing impractical because “if I order DNA testing right now, it will take 4 months for me to get the results. I cannot wait 4 months for the results to come back” to adjust treatment.

Dr. McKnight is an employee of and a shareholder in Invitae, which funded the study. Dr. Singh has disclosed no relevant financial relationships.

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

Genetic testing in patients with epilepsy can yield useful information that informs treatment and improves seizure control and other outcomes, new research shows.

Results of a survey that included more than 400 patients showed that positive findings from genetic testing helped guide clinical management in 50% of cases and improved patient outcomes in 75%. In addition, the findings were applicable to both children and adults.

“Fifty percent of the time the physicians reported that, yes, receiving the genetic diagnosis did change how they managed the patients,” reported co-investigator Dianalee McKnight, PhD, director of medical affairs at Invitae, a medical genetic testing company headquartered in San Francisco. In 81.3% of cases, providers reported they changed clinical management within 3 months of receiving the genetic results, she added.

The findings were presented at the 2021 World Congress of Neurology (WCN).
 

Test results can be practice-changing

Nearly 50% of positive genetic test results in epilepsy patients can help guide clinical management, Dr. McKnight noted. However, information on how physicians use genetic information in decision-making has been limited, prompting her conduct the survey.

A total of 1,567 physicians with 3,572 patients who had a definitive diagnosis of epilepsy were contacted. A total of 170 (10.8%) clinicians provided completed and eligible surveys on 429 patients with epilepsy.

The patient cohort comprised mostly children, with nearly 50 adults, which Dr. McKnight said is typical of the population receiving genetic testing in clinical practice.

She reported that genetic testing results prompted clinicians to make medication changes about 50% of the time. Other changes included specialist referral or to a clinical trial, monitoring for other neurological disease, and recommendations for dietary change or for surgery.

Growing influence of genetic testing

Commenting on the findings, Jaysingh Singh, MD, co-director of the Epilepsy Surgery Center at the Ohio State University Wexner Medical Center in Columbus, noted that the study highlights the value of gene testing in improving outcomes in patients with epilepsy, particularly the pediatric population.

He said the findings make him optimistic about the potential of genetic testing in adult patients – with at least one caveat.

“The limitation is that if we do find some mutation, we don’t know what to do with that. That’s definitely one challenge. And we see that more often in the adult patient population,” said Dr. Singh, who was not involved with the research.

He noted that there is a small group of genetic mutations when, found in adults, may dramatically alter treatment.

For example, he noted that if there is a gene mutation related to mTOR pathways, that could provide a future target because there are already medications that target this pathway.

Genetic testing may also be useful in cases where patients have normal brain imaging and poor response to standard treatment or in cases where patients have congenital abnormalities such as intellectual impairment or facial dysmorphic features and a co-morbid seizure disorder, he said.

Dr. Singh noted that he has often found genetic testing impractical because “if I order DNA testing right now, it will take 4 months for me to get the results. I cannot wait 4 months for the results to come back” to adjust treatment.

Dr. McKnight is an employee of and a shareholder in Invitae, which funded the study. Dr. Singh has disclosed no relevant financial relationships.

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

Genetic testing in patients with epilepsy can yield useful information that informs treatment and improves seizure control and other outcomes, new research shows.

Results of a survey that included more than 400 patients showed that positive findings from genetic testing helped guide clinical management in 50% of cases and improved patient outcomes in 75%. In addition, the findings were applicable to both children and adults.

“Fifty percent of the time the physicians reported that, yes, receiving the genetic diagnosis did change how they managed the patients,” reported co-investigator Dianalee McKnight, PhD, director of medical affairs at Invitae, a medical genetic testing company headquartered in San Francisco. In 81.3% of cases, providers reported they changed clinical management within 3 months of receiving the genetic results, she added.

The findings were presented at the 2021 World Congress of Neurology (WCN).
 

Test results can be practice-changing

Nearly 50% of positive genetic test results in epilepsy patients can help guide clinical management, Dr. McKnight noted. However, information on how physicians use genetic information in decision-making has been limited, prompting her conduct the survey.

A total of 1,567 physicians with 3,572 patients who had a definitive diagnosis of epilepsy were contacted. A total of 170 (10.8%) clinicians provided completed and eligible surveys on 429 patients with epilepsy.

The patient cohort comprised mostly children, with nearly 50 adults, which Dr. McKnight said is typical of the population receiving genetic testing in clinical practice.

She reported that genetic testing results prompted clinicians to make medication changes about 50% of the time. Other changes included specialist referral or to a clinical trial, monitoring for other neurological disease, and recommendations for dietary change or for surgery.

Growing influence of genetic testing

Commenting on the findings, Jaysingh Singh, MD, co-director of the Epilepsy Surgery Center at the Ohio State University Wexner Medical Center in Columbus, noted that the study highlights the value of gene testing in improving outcomes in patients with epilepsy, particularly the pediatric population.

He said the findings make him optimistic about the potential of genetic testing in adult patients – with at least one caveat.

“The limitation is that if we do find some mutation, we don’t know what to do with that. That’s definitely one challenge. And we see that more often in the adult patient population,” said Dr. Singh, who was not involved with the research.

He noted that there is a small group of genetic mutations when, found in adults, may dramatically alter treatment.

For example, he noted that if there is a gene mutation related to mTOR pathways, that could provide a future target because there are already medications that target this pathway.

Genetic testing may also be useful in cases where patients have normal brain imaging and poor response to standard treatment or in cases where patients have congenital abnormalities such as intellectual impairment or facial dysmorphic features and a co-morbid seizure disorder, he said.

Dr. Singh noted that he has often found genetic testing impractical because “if I order DNA testing right now, it will take 4 months for me to get the results. I cannot wait 4 months for the results to come back” to adjust treatment.

Dr. McKnight is an employee of and a shareholder in Invitae, which funded the study. Dr. Singh has disclosed no relevant financial relationships.

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

Drugmaker Merck announced today that it submitted an application to the Food and Drug Administration for the emergency use authorization of molnupiravir, an experimental antiviral COVID-19 treatment.

If the FDA grants authorization, the drug would be the first oral antiviral treatment for COVID-19. The capsule, made by Merck and Ridgeback Biotherapeutics, is intended to treat mild to moderate COVID-19 in adults who are at risk of having severe COVID-19 or hospitalization.

“The extraordinary impact of this pandemic demands that we move with unprecedented urgency, and that is what our teams have done by submitting this application for molnupiravir to the FDA within 10 days of receiving the data,” Robert Davis, CEO and president of Merck, said in a statement. On Oct. 1, Merck and Ridgeback released interim data from its phase III clinical trial, which showed that molnupiravir reduced the risk of hospitalization or death by about 50%. About 7% of patients who received the drug were hospitalized within 30 days in the study, as compared with 14% of patients who took a placebo, the company said.

No deaths were reported in the group that received the drug, as compared with eight deaths in the group that received the placebo. None of the trial participants had been vaccinated.

“Medicines and vaccines are both essential to our collective efforts,” Mr. Davis said. “We look forward to working with the FDA on its review of our application, and to working with other regulatory agencies as we do everything we can to bring molnupiravir to patients around the world as quickly as possible.”

Merck has been producing molnupiravir in anticipation of the clinical trial results and FDA authorization. The company expects to produce 10 million courses of treatment by the end of the year, with more expected for 2022.

In June, Merck signed an agreement with the United States to supply 1.7 million courses of molnupiravir once the FDA authorizes the drug. The company has agreed to advance purchase agreements with other countries as well.

Earlier in the year, Merck also announced voluntary licensing agreements with several generics manufacturers in India to provide molnupiravir to more than 100 low- and middle-income countries after approval from local regulatory agencies.

Data from the company’s late-stage clinical trial has not yet been peer-reviewed or published.

Last week, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said the clinical trial results were “very encouraging” but noted that the FDA should closely scrutinize the drug, CNN reported.

“It is very important that this now must go through the usual process of careful examination of the data by the Food and Drug Administration, both for effectiveness but also for safety, because whenever you introduce a new compound, safety is very important,” Dr. Fauci said, adding that vaccines remain “our best tools against COVID-19.”


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

Drugmaker Merck announced today that it submitted an application to the Food and Drug Administration for the emergency use authorization of molnupiravir, an experimental antiviral COVID-19 treatment.

If the FDA grants authorization, the drug would be the first oral antiviral treatment for COVID-19. The capsule, made by Merck and Ridgeback Biotherapeutics, is intended to treat mild to moderate COVID-19 in adults who are at risk of having severe COVID-19 or hospitalization.

“The extraordinary impact of this pandemic demands that we move with unprecedented urgency, and that is what our teams have done by submitting this application for molnupiravir to the FDA within 10 days of receiving the data,” Robert Davis, CEO and president of Merck, said in a statement. On Oct. 1, Merck and Ridgeback released interim data from its phase III clinical trial, which showed that molnupiravir reduced the risk of hospitalization or death by about 50%. About 7% of patients who received the drug were hospitalized within 30 days in the study, as compared with 14% of patients who took a placebo, the company said.

No deaths were reported in the group that received the drug, as compared with eight deaths in the group that received the placebo. None of the trial participants had been vaccinated.

“Medicines and vaccines are both essential to our collective efforts,” Mr. Davis said. “We look forward to working with the FDA on its review of our application, and to working with other regulatory agencies as we do everything we can to bring molnupiravir to patients around the world as quickly as possible.”

Merck has been producing molnupiravir in anticipation of the clinical trial results and FDA authorization. The company expects to produce 10 million courses of treatment by the end of the year, with more expected for 2022.

In June, Merck signed an agreement with the United States to supply 1.7 million courses of molnupiravir once the FDA authorizes the drug. The company has agreed to advance purchase agreements with other countries as well.

Earlier in the year, Merck also announced voluntary licensing agreements with several generics manufacturers in India to provide molnupiravir to more than 100 low- and middle-income countries after approval from local regulatory agencies.

Data from the company’s late-stage clinical trial has not yet been peer-reviewed or published.

Last week, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said the clinical trial results were “very encouraging” but noted that the FDA should closely scrutinize the drug, CNN reported.

“It is very important that this now must go through the usual process of careful examination of the data by the Food and Drug Administration, both for effectiveness but also for safety, because whenever you introduce a new compound, safety is very important,” Dr. Fauci said, adding that vaccines remain “our best tools against COVID-19.”


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

Drugmaker Merck announced today that it submitted an application to the Food and Drug Administration for the emergency use authorization of molnupiravir, an experimental antiviral COVID-19 treatment.

If the FDA grants authorization, the drug would be the first oral antiviral treatment for COVID-19. The capsule, made by Merck and Ridgeback Biotherapeutics, is intended to treat mild to moderate COVID-19 in adults who are at risk of having severe COVID-19 or hospitalization.

“The extraordinary impact of this pandemic demands that we move with unprecedented urgency, and that is what our teams have done by submitting this application for molnupiravir to the FDA within 10 days of receiving the data,” Robert Davis, CEO and president of Merck, said in a statement. On Oct. 1, Merck and Ridgeback released interim data from its phase III clinical trial, which showed that molnupiravir reduced the risk of hospitalization or death by about 50%. About 7% of patients who received the drug were hospitalized within 30 days in the study, as compared with 14% of patients who took a placebo, the company said.

No deaths were reported in the group that received the drug, as compared with eight deaths in the group that received the placebo. None of the trial participants had been vaccinated.

“Medicines and vaccines are both essential to our collective efforts,” Mr. Davis said. “We look forward to working with the FDA on its review of our application, and to working with other regulatory agencies as we do everything we can to bring molnupiravir to patients around the world as quickly as possible.”

Merck has been producing molnupiravir in anticipation of the clinical trial results and FDA authorization. The company expects to produce 10 million courses of treatment by the end of the year, with more expected for 2022.

In June, Merck signed an agreement with the United States to supply 1.7 million courses of molnupiravir once the FDA authorizes the drug. The company has agreed to advance purchase agreements with other countries as well.

Earlier in the year, Merck also announced voluntary licensing agreements with several generics manufacturers in India to provide molnupiravir to more than 100 low- and middle-income countries after approval from local regulatory agencies.

Data from the company’s late-stage clinical trial has not yet been peer-reviewed or published.

Last week, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said the clinical trial results were “very encouraging” but noted that the FDA should closely scrutinize the drug, CNN reported.

“It is very important that this now must go through the usual process of careful examination of the data by the Food and Drug Administration, both for effectiveness but also for safety, because whenever you introduce a new compound, safety is very important,” Dr. Fauci said, adding that vaccines remain “our best tools against COVID-19.”


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

Psychological therapy that changes an individual’s beliefs about pain not only provides lasting chronic pain relief but also alters brain regions related to pain generation, new research shows.

In the first randomized controlled test of pain-reprocessing therapy (PRT), two-thirds of patients with chronic back pain (CBP) who received 4 weeks of PRT were pain free or nearly pain free afterward – and for most patients, relief was maintained for 1 year, the researchers found.

“Primary chronic back pain can be dramatically reduced or even eliminated by psychological treatment focused on changing how threatening we perceive the pain to be,” first author Yoni Ashar, PhD, department of psychiatry, Weill Cornell Medicine, New York, said in an interview.

“We were very surprised” by the impact, Dr. Ashar admitted, given that large reductions in pain have rarely been observed in studies that tested psychological therapies for chronic back pain.

The study was published online Sept. 29, 2021, in JAMA Psychiatry.
 

Rethinking pain

CBP is a leading cause of disability, and treatment is often ineffective. In about 85% of cases of primary CBP, a definitive cause of the pain can’t be identified. In these cases, fear, avoidance, and beliefs that pain indicates injury may contribute to ongoing CBP.

Thinkstock.com

PRT educates patients about the role of the brain in generating chronic pain; helps them reappraise their pain as they engage in movements that they had been afraid to undertake; and helps them address emotions that may exacerbate pain.

The study included 151 adults (54% women; mean age, 41 years) who had primary CBP of low to moderate severity (mean pain intensity, 4 of 10) for an average of 10 years.

A total of 50 participants were randomly allocated to undergo PRT (one telehealth session with a physician and eight PRT sessions over 4 weeks), 51 to receive placebo (subcutaneous saline injection in the back), and 50 to continue their routine, usual ongoing care.

Large group differences in pain were observed after treatment. The mean pain score was 1.18 in the PRT group, 2.84 in the placebo group, and 3.13 in the usual-care group. Hedges’ g was –1.14 for PRT versus placebo and –1.74 for PRT versus usual care (P < .001).

Two-thirds (66%) of adults in the PRT group were pain free or nearly pain free following treatment (pain-intensity score of 0 or 1 out of 10), compared with 20% of those in the placebo group and 10% of those who received usual care.

Treatment effects were maintained at 1-year follow-up. The mean pain score was 1.51 in the PRT group, 2.79 in the placebo group, and 3.00 in the usual-care group. Neither age nor sex moderated the effect of PRT on pain intensity.
 

Retraining the brain

The researchers said the effects of PRT on pain were mediated by lessening the belief that pain indicates tissue damage. Of note, PRT also reduced experimentally evoked back pain and spontaneous pain during functional MRI, with large effect sizes.

“The idea is that by thinking about the pain as safe rather than threatening, patients can alter the brain networks reinforcing the pain, and neutralize it,” Dr. Ashar said in a news release.

The authors noted that study participants were relatively well educated and active. The participants reported having longstanding low to moderate pain and disability at baseline.

The physician and therapists were experts in delivering PRT. Future studies should test generalizability to other patient populations, therapists, and treatment contexts.

“Our clinical experience shows that PRT is effective for other primary chronic pain conditions as well,” said Dr. Ashar, including primary knee pain and tension headache.
 

Restoring function

Commenting on the findings, Shaheen E. Lakhan, MD, PhD, neurologist and pain specialist in Newton, Mass., said he has long experience using psychological approaches to address pain, with good results.

“Imagine telling a person suffering from decades of chronic pain that your pain is all in your head. I’ve done that for years as a board-certified pain physician managing only the most severe and debilitating forms of pain. When used to ground brain retraining, I could ultimately restore function to people living with chronic pain,” Dr. Lakhan said.

“The statement is true – the brain ultimately processes signals from throughout the body, forms the perception of pain, and links it to emotional brain centers, among others. Pain is an important survival mechanism so that when your body is at threat of injury, you protect yourself from further damage and withdraw. The problem lies when pain outlasts its welcome and chronifies,” said Dr. Lakhan, senior vice president of research and development of Click Therapeutics in Boston.

The investigators in this study “eloquently prove” that with 4 weeks of PRT, patients can learn that chronic pain is largely a “brain-generated false alarm and that constantly affirming this truth can actually reduce or eliminate it,” Dr. Lakhan said.

“Further, the brain areas implicated with pain are calmed after going through the therapy to both resting pain and pain induced by extending the back,” he noted.

“Pain-reprocessing therapy can improve the lives of chronic [pain patients] who have low to moderate levels of pain and disability; however, much work needs to be done to make this scalable and universally available and covered by insurers as a treatment modality,” Dr. Lakhan added.

He cautioned that he has not seen therapies such as this work when there is significant depression, withdrawal, or lack of control over one’s situation such that one behaves in a helpless manner – “a terrible state of mind called learned helplessness.”

The study was funded by the National Institutes of Health, the National Center for Advancing Translational Sciences, the Radiological Society of North America, the German Research Foundation, the Psychophysiologic Disorders Association, the Foundation for the Study of the Therapeutic Encounter, and community donations. Dr. Ashar received grants from the National Institutes of Health during the conduct of the study and personal fees from UnitedHealth Group, Lin Health, Pain Reprocessing Therapy Center, and Mental Health Partners of Boulder County outside the submitted work. Dr. Lakhan disclosed no relevant financial relationships.

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

Psychological therapy that changes an individual’s beliefs about pain not only provides lasting chronic pain relief but also alters brain regions related to pain generation, new research shows.

In the first randomized controlled test of pain-reprocessing therapy (PRT), two-thirds of patients with chronic back pain (CBP) who received 4 weeks of PRT were pain free or nearly pain free afterward – and for most patients, relief was maintained for 1 year, the researchers found.

“Primary chronic back pain can be dramatically reduced or even eliminated by psychological treatment focused on changing how threatening we perceive the pain to be,” first author Yoni Ashar, PhD, department of psychiatry, Weill Cornell Medicine, New York, said in an interview.

“We were very surprised” by the impact, Dr. Ashar admitted, given that large reductions in pain have rarely been observed in studies that tested psychological therapies for chronic back pain.

The study was published online Sept. 29, 2021, in JAMA Psychiatry.
 

Rethinking pain

CBP is a leading cause of disability, and treatment is often ineffective. In about 85% of cases of primary CBP, a definitive cause of the pain can’t be identified. In these cases, fear, avoidance, and beliefs that pain indicates injury may contribute to ongoing CBP.

Thinkstock.com

PRT educates patients about the role of the brain in generating chronic pain; helps them reappraise their pain as they engage in movements that they had been afraid to undertake; and helps them address emotions that may exacerbate pain.

The study included 151 adults (54% women; mean age, 41 years) who had primary CBP of low to moderate severity (mean pain intensity, 4 of 10) for an average of 10 years.

A total of 50 participants were randomly allocated to undergo PRT (one telehealth session with a physician and eight PRT sessions over 4 weeks), 51 to receive placebo (subcutaneous saline injection in the back), and 50 to continue their routine, usual ongoing care.

Large group differences in pain were observed after treatment. The mean pain score was 1.18 in the PRT group, 2.84 in the placebo group, and 3.13 in the usual-care group. Hedges’ g was –1.14 for PRT versus placebo and –1.74 for PRT versus usual care (P < .001).

Two-thirds (66%) of adults in the PRT group were pain free or nearly pain free following treatment (pain-intensity score of 0 or 1 out of 10), compared with 20% of those in the placebo group and 10% of those who received usual care.

Treatment effects were maintained at 1-year follow-up. The mean pain score was 1.51 in the PRT group, 2.79 in the placebo group, and 3.00 in the usual-care group. Neither age nor sex moderated the effect of PRT on pain intensity.
 

Retraining the brain

The researchers said the effects of PRT on pain were mediated by lessening the belief that pain indicates tissue damage. Of note, PRT also reduced experimentally evoked back pain and spontaneous pain during functional MRI, with large effect sizes.

“The idea is that by thinking about the pain as safe rather than threatening, patients can alter the brain networks reinforcing the pain, and neutralize it,” Dr. Ashar said in a news release.

The authors noted that study participants were relatively well educated and active. The participants reported having longstanding low to moderate pain and disability at baseline.

The physician and therapists were experts in delivering PRT. Future studies should test generalizability to other patient populations, therapists, and treatment contexts.

“Our clinical experience shows that PRT is effective for other primary chronic pain conditions as well,” said Dr. Ashar, including primary knee pain and tension headache.
 

Restoring function

Commenting on the findings, Shaheen E. Lakhan, MD, PhD, neurologist and pain specialist in Newton, Mass., said he has long experience using psychological approaches to address pain, with good results.

“Imagine telling a person suffering from decades of chronic pain that your pain is all in your head. I’ve done that for years as a board-certified pain physician managing only the most severe and debilitating forms of pain. When used to ground brain retraining, I could ultimately restore function to people living with chronic pain,” Dr. Lakhan said.

“The statement is true – the brain ultimately processes signals from throughout the body, forms the perception of pain, and links it to emotional brain centers, among others. Pain is an important survival mechanism so that when your body is at threat of injury, you protect yourself from further damage and withdraw. The problem lies when pain outlasts its welcome and chronifies,” said Dr. Lakhan, senior vice president of research and development of Click Therapeutics in Boston.

The investigators in this study “eloquently prove” that with 4 weeks of PRT, patients can learn that chronic pain is largely a “brain-generated false alarm and that constantly affirming this truth can actually reduce or eliminate it,” Dr. Lakhan said.

“Further, the brain areas implicated with pain are calmed after going through the therapy to both resting pain and pain induced by extending the back,” he noted.

“Pain-reprocessing therapy can improve the lives of chronic [pain patients] who have low to moderate levels of pain and disability; however, much work needs to be done to make this scalable and universally available and covered by insurers as a treatment modality,” Dr. Lakhan added.

He cautioned that he has not seen therapies such as this work when there is significant depression, withdrawal, or lack of control over one’s situation such that one behaves in a helpless manner – “a terrible state of mind called learned helplessness.”

The study was funded by the National Institutes of Health, the National Center for Advancing Translational Sciences, the Radiological Society of North America, the German Research Foundation, the Psychophysiologic Disorders Association, the Foundation for the Study of the Therapeutic Encounter, and community donations. Dr. Ashar received grants from the National Institutes of Health during the conduct of the study and personal fees from UnitedHealth Group, Lin Health, Pain Reprocessing Therapy Center, and Mental Health Partners of Boulder County outside the submitted work. Dr. Lakhan disclosed no relevant financial relationships.

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

Psychological therapy that changes an individual’s beliefs about pain not only provides lasting chronic pain relief but also alters brain regions related to pain generation, new research shows.

In the first randomized controlled test of pain-reprocessing therapy (PRT), two-thirds of patients with chronic back pain (CBP) who received 4 weeks of PRT were pain free or nearly pain free afterward – and for most patients, relief was maintained for 1 year, the researchers found.

“Primary chronic back pain can be dramatically reduced or even eliminated by psychological treatment focused on changing how threatening we perceive the pain to be,” first author Yoni Ashar, PhD, department of psychiatry, Weill Cornell Medicine, New York, said in an interview.

“We were very surprised” by the impact, Dr. Ashar admitted, given that large reductions in pain have rarely been observed in studies that tested psychological therapies for chronic back pain.

The study was published online Sept. 29, 2021, in JAMA Psychiatry.
 

Rethinking pain

CBP is a leading cause of disability, and treatment is often ineffective. In about 85% of cases of primary CBP, a definitive cause of the pain can’t be identified. In these cases, fear, avoidance, and beliefs that pain indicates injury may contribute to ongoing CBP.

Thinkstock.com

PRT educates patients about the role of the brain in generating chronic pain; helps them reappraise their pain as they engage in movements that they had been afraid to undertake; and helps them address emotions that may exacerbate pain.

The study included 151 adults (54% women; mean age, 41 years) who had primary CBP of low to moderate severity (mean pain intensity, 4 of 10) for an average of 10 years.

A total of 50 participants were randomly allocated to undergo PRT (one telehealth session with a physician and eight PRT sessions over 4 weeks), 51 to receive placebo (subcutaneous saline injection in the back), and 50 to continue their routine, usual ongoing care.

Large group differences in pain were observed after treatment. The mean pain score was 1.18 in the PRT group, 2.84 in the placebo group, and 3.13 in the usual-care group. Hedges’ g was –1.14 for PRT versus placebo and –1.74 for PRT versus usual care (P < .001).

Two-thirds (66%) of adults in the PRT group were pain free or nearly pain free following treatment (pain-intensity score of 0 or 1 out of 10), compared with 20% of those in the placebo group and 10% of those who received usual care.

Treatment effects were maintained at 1-year follow-up. The mean pain score was 1.51 in the PRT group, 2.79 in the placebo group, and 3.00 in the usual-care group. Neither age nor sex moderated the effect of PRT on pain intensity.
 

Retraining the brain

The researchers said the effects of PRT on pain were mediated by lessening the belief that pain indicates tissue damage. Of note, PRT also reduced experimentally evoked back pain and spontaneous pain during functional MRI, with large effect sizes.

“The idea is that by thinking about the pain as safe rather than threatening, patients can alter the brain networks reinforcing the pain, and neutralize it,” Dr. Ashar said in a news release.

The authors noted that study participants were relatively well educated and active. The participants reported having longstanding low to moderate pain and disability at baseline.

The physician and therapists were experts in delivering PRT. Future studies should test generalizability to other patient populations, therapists, and treatment contexts.

“Our clinical experience shows that PRT is effective for other primary chronic pain conditions as well,” said Dr. Ashar, including primary knee pain and tension headache.
 

Restoring function

Commenting on the findings, Shaheen E. Lakhan, MD, PhD, neurologist and pain specialist in Newton, Mass., said he has long experience using psychological approaches to address pain, with good results.

“Imagine telling a person suffering from decades of chronic pain that your pain is all in your head. I’ve done that for years as a board-certified pain physician managing only the most severe and debilitating forms of pain. When used to ground brain retraining, I could ultimately restore function to people living with chronic pain,” Dr. Lakhan said.

“The statement is true – the brain ultimately processes signals from throughout the body, forms the perception of pain, and links it to emotional brain centers, among others. Pain is an important survival mechanism so that when your body is at threat of injury, you protect yourself from further damage and withdraw. The problem lies when pain outlasts its welcome and chronifies,” said Dr. Lakhan, senior vice president of research and development of Click Therapeutics in Boston.

The investigators in this study “eloquently prove” that with 4 weeks of PRT, patients can learn that chronic pain is largely a “brain-generated false alarm and that constantly affirming this truth can actually reduce or eliminate it,” Dr. Lakhan said.

“Further, the brain areas implicated with pain are calmed after going through the therapy to both resting pain and pain induced by extending the back,” he noted.

“Pain-reprocessing therapy can improve the lives of chronic [pain patients] who have low to moderate levels of pain and disability; however, much work needs to be done to make this scalable and universally available and covered by insurers as a treatment modality,” Dr. Lakhan added.

He cautioned that he has not seen therapies such as this work when there is significant depression, withdrawal, or lack of control over one’s situation such that one behaves in a helpless manner – “a terrible state of mind called learned helplessness.”

The study was funded by the National Institutes of Health, the National Center for Advancing Translational Sciences, the Radiological Society of North America, the German Research Foundation, the Psychophysiologic Disorders Association, the Foundation for the Study of the Therapeutic Encounter, and community donations. Dr. Ashar received grants from the National Institutes of Health during the conduct of the study and personal fees from UnitedHealth Group, Lin Health, Pain Reprocessing Therapy Center, and Mental Health Partners of Boulder County outside the submitted work. Dr. Lakhan disclosed no relevant financial relationships.

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

Anthem Blue Cross, the country’s second-biggest health insurance company, is behind on billions of dollars in payments owed to hospitals and doctors because of onerous new reimbursement rules, computer problems and mishandled claims, say hospital officials in multiple states.

Anthem, like other big insurers, is using the COVID-19 crisis as cover to institute “egregious” policies that harm patients and pinch hospital finances, said Molly Smith, group vice president at the American Hospital Association. “There’s this sense of ‘Everyone’s distracted. We can get this through.’ ”

Hospitals are also dealing with a spike in retroactive claims denials by UnitedHealthcare, the biggest health insurer, for ED care, the AHA said.

Disputes between insurers and hospitals are nothing new. But this fight sticks more patients in the middle, worried they’ll have to pay unresolved claims. Hospitals say it is hurting their finances as many cope with COVID surges – even after the industry has received tens of billions of dollars in emergency assistance from the federal government.

“We recognize there have been some challenges” to prompt payments caused by claims-processing changes and “a new set of dynamics” amid the pandemic, Anthem spokesperson Colin Manning said in an email. “We apologize for any delays or inconvenience this may have caused.”

Virginia law requires insurers to pay claims within 40 days. In a Sept. 24 letter to state insurance regulators, VCU Health, a system that operates a large teaching hospital in Richmond associated with Virginia Commonwealth University, said Anthem owes it $385 million. More than 40% of the claims are more than 90 days old, VCU said.

For all Virginia hospitals, Anthem’s late, unpaid claims amount to “hundreds of millions of dollars,” the Virginia Hospital and Healthcare Association said in a June 23 letter to state regulators.

Nationwide, the payment delays “are creating an untenable situation,” the American Hospital Association said in a Sept. 9 letter to Anthem CEO Gail Boudreaux. “Patients are facing greater hurdles to accessing care; clinicians are burning out on unnecessary administrative tasks; and the system is straining to finance the personnel and supplies” needed to fight Covid.

Complaints about Anthem extend “from sea to shining sea, from New Hampshire to California,” AHA CEO Rick Pollack told KHN.

Substantial payment delays can be seen on Anthem’s books. On June 30, 2019, before the pandemic, 43% of the insurer’s medical bills for that quarter were unpaid, according to regulatory filings. Two years later that figure had risen to 53% – a difference of $2.5 billion.

Anthem profits were $4.6 billion in 2020 and $3.5 billion in the first half of 2021.

Alexis Thurber, who lives near Seattle, was insured by Anthem when she got an $18,192 hospital bill in May for radiation therapy that doctors said was essential to treat her breast cancer.

The treatments were “experimental” and “not medically necessary,” Anthem said, according to Ms. Thurber. She spent much of the summer trying to get the insurer to pay up – placing two dozen phone calls, spending hours on hold, sending multiple emails and enduring unmeasurable stress and worry. It finally covered the claim months later.

“It’s so egregious. It’s a game they’re playing,” said Ms. Thurber, 51, whose cancer was diagnosed in November. “Trying to get true help was impossible.”

Privacy rules prevent Anthem from commenting on Ms. Thurber’s case, said Anthem spokesperson Colin Manning.

When insurers fail to promptly pay medical bills, patients are left in the lurch. They might first get a notice saying payment is pending or denied. A hospital might bill them for treatment they thought would be covered. Hospitals and doctors often sue patients whose insurance didn’t pay up.

Hospitals point to a variety of Anthem practices contributing to payment delays or denials, including new layers of document requirements, prior-authorization hurdles for routine procedures and requirements that doctors themselves – not support staffers – speak to insurance gatekeepers. “This requires providers to literally leave the patient[’s] bedside to get on the phone with Anthem,” AHA said in its letter.

Anthem often hinders coverage for outpatient surgery, specialty pharmacy and other services in health systems listed as in network, amounting to a “bait and switch” on Anthem members, AHA officials said.

“Demanding that patients be treated outside of the hospital setting, against the advice of the patient’s in-network treating physician, appears to be motivated by a desire to drive up Empire’s profits,” the Greater New York Hospital Association wrote in an April letter to Empire Blue Cross, which is owned by Anthem.

Anthem officials pushed back in a recent letter to the AHA, saying the insurer’s changing rules are intended partly to control excessive prices charged by hospitals for specialty drugs and nonemergency surgery, screening and diagnostic procedures.

Severe problems with Anthem’s new claims management system surfaced months ago and “persist without meaningful improvement,” AHA said in its letter.

Claims have gotten lost in Anthem’s computers, and in some cases VCU Health has had to print medical records and mail them to get paid, VCU said in its letter. The cash slowdown imposes “an unmanageable disruption that threatens to undermine our financial footing,” VCU said.

United denied $31,557 in claims for Emily Long’s care after she was struck in June by a motorcycle in New York City. She needed surgery to repair a fractured cheekbone. United said there was a lack of documentation for “medical necessity” – an “incredibly aggravating” response on top of the distress of the accident, Ms. Long said.

The Brooklyn hospital that treated Ms. Long was “paid appropriately under her plan and within the required time frame,” said United spokesperson Maria Gordon Shydlo. “The facility has the right to appeal the decision.”

United’s unpaid claims came to 54% as of June 30, about the same level as 2 years previously.

When Erin Conlisk initially had trouble gaining approval for a piece of medical equipment for her elderly father this summer, United employees told her the insurer’s entire prior-authorization database had gone down for weeks, said Ms. Conlisk, who lives in California.

“There was a brief issue with our prior-authorization process in mid-July, which was resolved quickly,” Gordon Shydlo said.

When asked by Wall Street analysts about the payment backups, Anthem executives said it partly reflects their decision to increase financial reserves amid the health crisis.

“Really a ton of uncertainty associated with this environment,” John Gallina, the company’s chief financial officer, said on a conference call in July. “We’ve tried to be extremely prudent and conservative in our approach.”

During the pandemic, hospitals have benefited from two extraordinary cash infusions. They and other medical providers have received more than $100 billion through the CARES Act of 2020 and the American Rescue Plan of 2021. Last year United, Anthem and other insurers accelerated billions in hospital reimbursements.

The federal payments enriched many of the biggest, wealthiest systems while poorer hospitals serving low-income patients and rural areas struggled.

Those are the systems most hurt now by insurer payment delays, hospital officials said. Federal relief funds “have been a lifeline, but they don’t make people whole in terms of the losses from increased expenses and lost revenue as a result of the COVID experience,” Mr. Pollack said.

Several health systems declined to comment about claims payment delays or didn’t respond to a reporter’s queries. Among individual hospitals “there is a deep fear of talking on the record about your largest business partner,” AHA’s Ms. Smith said.

Alexis Thurber worried she might have to pay her $18,192 radiation bill herself, and she’s not confident her Anthem policy will do a better job next time of covering the cost of her care.

“It makes me not want to go to the doctor anymore,” she said. “I’m scared to get another mammogram because you can’t rely on it.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Anthem Blue Cross, the country’s second-biggest health insurance company, is behind on billions of dollars in payments owed to hospitals and doctors because of onerous new reimbursement rules, computer problems and mishandled claims, say hospital officials in multiple states.

Anthem, like other big insurers, is using the COVID-19 crisis as cover to institute “egregious” policies that harm patients and pinch hospital finances, said Molly Smith, group vice president at the American Hospital Association. “There’s this sense of ‘Everyone’s distracted. We can get this through.’ ”

Hospitals are also dealing with a spike in retroactive claims denials by UnitedHealthcare, the biggest health insurer, for ED care, the AHA said.

Disputes between insurers and hospitals are nothing new. But this fight sticks more patients in the middle, worried they’ll have to pay unresolved claims. Hospitals say it is hurting their finances as many cope with COVID surges – even after the industry has received tens of billions of dollars in emergency assistance from the federal government.

“We recognize there have been some challenges” to prompt payments caused by claims-processing changes and “a new set of dynamics” amid the pandemic, Anthem spokesperson Colin Manning said in an email. “We apologize for any delays or inconvenience this may have caused.”

Virginia law requires insurers to pay claims within 40 days. In a Sept. 24 letter to state insurance regulators, VCU Health, a system that operates a large teaching hospital in Richmond associated with Virginia Commonwealth University, said Anthem owes it $385 million. More than 40% of the claims are more than 90 days old, VCU said.

For all Virginia hospitals, Anthem’s late, unpaid claims amount to “hundreds of millions of dollars,” the Virginia Hospital and Healthcare Association said in a June 23 letter to state regulators.

Nationwide, the payment delays “are creating an untenable situation,” the American Hospital Association said in a Sept. 9 letter to Anthem CEO Gail Boudreaux. “Patients are facing greater hurdles to accessing care; clinicians are burning out on unnecessary administrative tasks; and the system is straining to finance the personnel and supplies” needed to fight Covid.

Complaints about Anthem extend “from sea to shining sea, from New Hampshire to California,” AHA CEO Rick Pollack told KHN.

Substantial payment delays can be seen on Anthem’s books. On June 30, 2019, before the pandemic, 43% of the insurer’s medical bills for that quarter were unpaid, according to regulatory filings. Two years later that figure had risen to 53% – a difference of $2.5 billion.

Anthem profits were $4.6 billion in 2020 and $3.5 billion in the first half of 2021.

Alexis Thurber, who lives near Seattle, was insured by Anthem when she got an $18,192 hospital bill in May for radiation therapy that doctors said was essential to treat her breast cancer.

The treatments were “experimental” and “not medically necessary,” Anthem said, according to Ms. Thurber. She spent much of the summer trying to get the insurer to pay up – placing two dozen phone calls, spending hours on hold, sending multiple emails and enduring unmeasurable stress and worry. It finally covered the claim months later.

“It’s so egregious. It’s a game they’re playing,” said Ms. Thurber, 51, whose cancer was diagnosed in November. “Trying to get true help was impossible.”

Privacy rules prevent Anthem from commenting on Ms. Thurber’s case, said Anthem spokesperson Colin Manning.

When insurers fail to promptly pay medical bills, patients are left in the lurch. They might first get a notice saying payment is pending or denied. A hospital might bill them for treatment they thought would be covered. Hospitals and doctors often sue patients whose insurance didn’t pay up.

Hospitals point to a variety of Anthem practices contributing to payment delays or denials, including new layers of document requirements, prior-authorization hurdles for routine procedures and requirements that doctors themselves – not support staffers – speak to insurance gatekeepers. “This requires providers to literally leave the patient[’s] bedside to get on the phone with Anthem,” AHA said in its letter.

Anthem often hinders coverage for outpatient surgery, specialty pharmacy and other services in health systems listed as in network, amounting to a “bait and switch” on Anthem members, AHA officials said.

“Demanding that patients be treated outside of the hospital setting, against the advice of the patient’s in-network treating physician, appears to be motivated by a desire to drive up Empire’s profits,” the Greater New York Hospital Association wrote in an April letter to Empire Blue Cross, which is owned by Anthem.

Anthem officials pushed back in a recent letter to the AHA, saying the insurer’s changing rules are intended partly to control excessive prices charged by hospitals for specialty drugs and nonemergency surgery, screening and diagnostic procedures.

Severe problems with Anthem’s new claims management system surfaced months ago and “persist without meaningful improvement,” AHA said in its letter.

Claims have gotten lost in Anthem’s computers, and in some cases VCU Health has had to print medical records and mail them to get paid, VCU said in its letter. The cash slowdown imposes “an unmanageable disruption that threatens to undermine our financial footing,” VCU said.

United denied $31,557 in claims for Emily Long’s care after she was struck in June by a motorcycle in New York City. She needed surgery to repair a fractured cheekbone. United said there was a lack of documentation for “medical necessity” – an “incredibly aggravating” response on top of the distress of the accident, Ms. Long said.

The Brooklyn hospital that treated Ms. Long was “paid appropriately under her plan and within the required time frame,” said United spokesperson Maria Gordon Shydlo. “The facility has the right to appeal the decision.”

United’s unpaid claims came to 54% as of June 30, about the same level as 2 years previously.

When Erin Conlisk initially had trouble gaining approval for a piece of medical equipment for her elderly father this summer, United employees told her the insurer’s entire prior-authorization database had gone down for weeks, said Ms. Conlisk, who lives in California.

“There was a brief issue with our prior-authorization process in mid-July, which was resolved quickly,” Gordon Shydlo said.

When asked by Wall Street analysts about the payment backups, Anthem executives said it partly reflects their decision to increase financial reserves amid the health crisis.

“Really a ton of uncertainty associated with this environment,” John Gallina, the company’s chief financial officer, said on a conference call in July. “We’ve tried to be extremely prudent and conservative in our approach.”

During the pandemic, hospitals have benefited from two extraordinary cash infusions. They and other medical providers have received more than $100 billion through the CARES Act of 2020 and the American Rescue Plan of 2021. Last year United, Anthem and other insurers accelerated billions in hospital reimbursements.

The federal payments enriched many of the biggest, wealthiest systems while poorer hospitals serving low-income patients and rural areas struggled.

Those are the systems most hurt now by insurer payment delays, hospital officials said. Federal relief funds “have been a lifeline, but they don’t make people whole in terms of the losses from increased expenses and lost revenue as a result of the COVID experience,” Mr. Pollack said.

Several health systems declined to comment about claims payment delays or didn’t respond to a reporter’s queries. Among individual hospitals “there is a deep fear of talking on the record about your largest business partner,” AHA’s Ms. Smith said.

Alexis Thurber worried she might have to pay her $18,192 radiation bill herself, and she’s not confident her Anthem policy will do a better job next time of covering the cost of her care.

“It makes me not want to go to the doctor anymore,” she said. “I’m scared to get another mammogram because you can’t rely on it.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Anthem Blue Cross, the country’s second-biggest health insurance company, is behind on billions of dollars in payments owed to hospitals and doctors because of onerous new reimbursement rules, computer problems and mishandled claims, say hospital officials in multiple states.

Anthem, like other big insurers, is using the COVID-19 crisis as cover to institute “egregious” policies that harm patients and pinch hospital finances, said Molly Smith, group vice president at the American Hospital Association. “There’s this sense of ‘Everyone’s distracted. We can get this through.’ ”

Hospitals are also dealing with a spike in retroactive claims denials by UnitedHealthcare, the biggest health insurer, for ED care, the AHA said.

Disputes between insurers and hospitals are nothing new. But this fight sticks more patients in the middle, worried they’ll have to pay unresolved claims. Hospitals say it is hurting their finances as many cope with COVID surges – even after the industry has received tens of billions of dollars in emergency assistance from the federal government.

“We recognize there have been some challenges” to prompt payments caused by claims-processing changes and “a new set of dynamics” amid the pandemic, Anthem spokesperson Colin Manning said in an email. “We apologize for any delays or inconvenience this may have caused.”

Virginia law requires insurers to pay claims within 40 days. In a Sept. 24 letter to state insurance regulators, VCU Health, a system that operates a large teaching hospital in Richmond associated with Virginia Commonwealth University, said Anthem owes it $385 million. More than 40% of the claims are more than 90 days old, VCU said.

For all Virginia hospitals, Anthem’s late, unpaid claims amount to “hundreds of millions of dollars,” the Virginia Hospital and Healthcare Association said in a June 23 letter to state regulators.

Nationwide, the payment delays “are creating an untenable situation,” the American Hospital Association said in a Sept. 9 letter to Anthem CEO Gail Boudreaux. “Patients are facing greater hurdles to accessing care; clinicians are burning out on unnecessary administrative tasks; and the system is straining to finance the personnel and supplies” needed to fight Covid.

Complaints about Anthem extend “from sea to shining sea, from New Hampshire to California,” AHA CEO Rick Pollack told KHN.

Substantial payment delays can be seen on Anthem’s books. On June 30, 2019, before the pandemic, 43% of the insurer’s medical bills for that quarter were unpaid, according to regulatory filings. Two years later that figure had risen to 53% – a difference of $2.5 billion.

Anthem profits were $4.6 billion in 2020 and $3.5 billion in the first half of 2021.

Alexis Thurber, who lives near Seattle, was insured by Anthem when she got an $18,192 hospital bill in May for radiation therapy that doctors said was essential to treat her breast cancer.

The treatments were “experimental” and “not medically necessary,” Anthem said, according to Ms. Thurber. She spent much of the summer trying to get the insurer to pay up – placing two dozen phone calls, spending hours on hold, sending multiple emails and enduring unmeasurable stress and worry. It finally covered the claim months later.

“It’s so egregious. It’s a game they’re playing,” said Ms. Thurber, 51, whose cancer was diagnosed in November. “Trying to get true help was impossible.”

Privacy rules prevent Anthem from commenting on Ms. Thurber’s case, said Anthem spokesperson Colin Manning.

When insurers fail to promptly pay medical bills, patients are left in the lurch. They might first get a notice saying payment is pending or denied. A hospital might bill them for treatment they thought would be covered. Hospitals and doctors often sue patients whose insurance didn’t pay up.

Hospitals point to a variety of Anthem practices contributing to payment delays or denials, including new layers of document requirements, prior-authorization hurdles for routine procedures and requirements that doctors themselves – not support staffers – speak to insurance gatekeepers. “This requires providers to literally leave the patient[’s] bedside to get on the phone with Anthem,” AHA said in its letter.

Anthem often hinders coverage for outpatient surgery, specialty pharmacy and other services in health systems listed as in network, amounting to a “bait and switch” on Anthem members, AHA officials said.

“Demanding that patients be treated outside of the hospital setting, against the advice of the patient’s in-network treating physician, appears to be motivated by a desire to drive up Empire’s profits,” the Greater New York Hospital Association wrote in an April letter to Empire Blue Cross, which is owned by Anthem.

Anthem officials pushed back in a recent letter to the AHA, saying the insurer’s changing rules are intended partly to control excessive prices charged by hospitals for specialty drugs and nonemergency surgery, screening and diagnostic procedures.

Severe problems with Anthem’s new claims management system surfaced months ago and “persist without meaningful improvement,” AHA said in its letter.

Claims have gotten lost in Anthem’s computers, and in some cases VCU Health has had to print medical records and mail them to get paid, VCU said in its letter. The cash slowdown imposes “an unmanageable disruption that threatens to undermine our financial footing,” VCU said.

United denied $31,557 in claims for Emily Long’s care after she was struck in June by a motorcycle in New York City. She needed surgery to repair a fractured cheekbone. United said there was a lack of documentation for “medical necessity” – an “incredibly aggravating” response on top of the distress of the accident, Ms. Long said.

The Brooklyn hospital that treated Ms. Long was “paid appropriately under her plan and within the required time frame,” said United spokesperson Maria Gordon Shydlo. “The facility has the right to appeal the decision.”

United’s unpaid claims came to 54% as of June 30, about the same level as 2 years previously.

When Erin Conlisk initially had trouble gaining approval for a piece of medical equipment for her elderly father this summer, United employees told her the insurer’s entire prior-authorization database had gone down for weeks, said Ms. Conlisk, who lives in California.

“There was a brief issue with our prior-authorization process in mid-July, which was resolved quickly,” Gordon Shydlo said.

When asked by Wall Street analysts about the payment backups, Anthem executives said it partly reflects their decision to increase financial reserves amid the health crisis.

“Really a ton of uncertainty associated with this environment,” John Gallina, the company’s chief financial officer, said on a conference call in July. “We’ve tried to be extremely prudent and conservative in our approach.”

During the pandemic, hospitals have benefited from two extraordinary cash infusions. They and other medical providers have received more than $100 billion through the CARES Act of 2020 and the American Rescue Plan of 2021. Last year United, Anthem and other insurers accelerated billions in hospital reimbursements.

The federal payments enriched many of the biggest, wealthiest systems while poorer hospitals serving low-income patients and rural areas struggled.

Those are the systems most hurt now by insurer payment delays, hospital officials said. Federal relief funds “have been a lifeline, but they don’t make people whole in terms of the losses from increased expenses and lost revenue as a result of the COVID experience,” Mr. Pollack said.

Several health systems declined to comment about claims payment delays or didn’t respond to a reporter’s queries. Among individual hospitals “there is a deep fear of talking on the record about your largest business partner,” AHA’s Ms. Smith said.

Alexis Thurber worried she might have to pay her $18,192 radiation bill herself, and she’s not confident her Anthem policy will do a better job next time of covering the cost of her care.

“It makes me not want to go to the doctor anymore,” she said. “I’m scared to get another mammogram because you can’t rely on it.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Doctors removed a 4-inch piece of cement from a man’s heart, which had leaked into his body from a spinal surgery, according to a new report published in the New England Journal of Medicine.

The 56-year-old man, who was not identified in the report, went to the emergency room after experiencing 2 days of chest pain and shortness of breath. Imaging scans showed that the chest pain was caused by a foreign object, and he was rushed to surgery.

Surgeons then located and removed a thin, sharp, cylindrical piece of cement and repaired the damage to the patient’s heart. The cement had pierced the upper right chamber of his heart and his right lung, according to the report authors from the Yale University School of Medicine.

A week before, the man had undergone a spinal surgery known as kyphoplasty. The procedure treats spine injuries by injecting a special type of medical cement into damaged vertebrae, according to USA Today. The cement had leaked into the patient’s body, hardened, and traveled to his heart.

The man has now “nearly recovered” since the heart surgery and cement removal, which occurred about a month ago, the journal report stated. He experienced no additional complications.

Cement leakage after kyphoplasty can happen but is an extremely rare complication. Less than 2% of patients who undergo the procedure for osteoporosis or brittle bones have complications, according to patient information from the American Association of Neurological Surgeons.

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

Doctors removed a 4-inch piece of cement from a man’s heart, which had leaked into his body from a spinal surgery, according to a new report published in the New England Journal of Medicine.

The 56-year-old man, who was not identified in the report, went to the emergency room after experiencing 2 days of chest pain and shortness of breath. Imaging scans showed that the chest pain was caused by a foreign object, and he was rushed to surgery.

Surgeons then located and removed a thin, sharp, cylindrical piece of cement and repaired the damage to the patient’s heart. The cement had pierced the upper right chamber of his heart and his right lung, according to the report authors from the Yale University School of Medicine.

A week before, the man had undergone a spinal surgery known as kyphoplasty. The procedure treats spine injuries by injecting a special type of medical cement into damaged vertebrae, according to USA Today. The cement had leaked into the patient’s body, hardened, and traveled to his heart.

The man has now “nearly recovered” since the heart surgery and cement removal, which occurred about a month ago, the journal report stated. He experienced no additional complications.

Cement leakage after kyphoplasty can happen but is an extremely rare complication. Less than 2% of patients who undergo the procedure for osteoporosis or brittle bones have complications, according to patient information from the American Association of Neurological Surgeons.

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

Doctors removed a 4-inch piece of cement from a man’s heart, which had leaked into his body from a spinal surgery, according to a new report published in the New England Journal of Medicine.

The 56-year-old man, who was not identified in the report, went to the emergency room after experiencing 2 days of chest pain and shortness of breath. Imaging scans showed that the chest pain was caused by a foreign object, and he was rushed to surgery.

Surgeons then located and removed a thin, sharp, cylindrical piece of cement and repaired the damage to the patient’s heart. The cement had pierced the upper right chamber of his heart and his right lung, according to the report authors from the Yale University School of Medicine.

A week before, the man had undergone a spinal surgery known as kyphoplasty. The procedure treats spine injuries by injecting a special type of medical cement into damaged vertebrae, according to USA Today. The cement had leaked into the patient’s body, hardened, and traveled to his heart.

The man has now “nearly recovered” since the heart surgery and cement removal, which occurred about a month ago, the journal report stated. He experienced no additional complications.

Cement leakage after kyphoplasty can happen but is an extremely rare complication. Less than 2% of patients who undergo the procedure for osteoporosis or brittle bones have complications, according to patient information from the American Association of Neurological Surgeons.

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