Federal Practitioner

The U.S. Food and Drug Administration has approved the anti–amyloid-beta protofibril antibody lecanemab (Leqembi, Eisai) for the treatment of early Alzheimer’s disease.

Like its controversial cousin aducanumab (Aduhelm, Biogen/Eisai), lecanemab was approved under the FDA’s accelerated approval pathway, which can be used to fast-track a drug that provides a meaningful therapeutic advantage over existing treatments for a serious or life-threatening illness.

Unlike aducanumab, however, there was no formal FDA advisory committee meeting on lecanemab prior to approval.

“Alzheimer’s disease immeasurably incapacitates the lives of those who suffer from it and has devastating effects on their loved ones,” Billy Dunn, MD, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a press release.

“This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease,” Dr. Dunn added.

Eisai has reported that lecanemab will cost $26,500 a year.

Modest benefit, adverse events

The FDA noted, “The labeling states that treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was studied in clinical trials.”

The agency approved the treatment on the basis of findings from the CLARITY AD trial, which showed modest cognitive benefit for patients with early AD – but at a cost of increased risk for amyloid-related edema and effusions.

The trial enrolled 1,795 adults with mild cognitive impairment or early Alzheimer’s disease in whom amyloid pathology in the brain had been confirmed. Treatment consisted of lecanemab 10 mg/kg biweekly or matching placebo.

After 18 months of treatment, lecanemab slowed cognitive decline by 27%, compared with placebo, as measured by the Clinical Dementia Rating–Sum of Boxes (CDR-SB). This was an absolute difference of 0.45 points (change from baseline, 1.21 for lecanemab vs. 1.66 with placebo; P < .001).

While the results are “welcome news,” a 0.45-point difference on the CDR-SB might not be clinically meaningful, authors of a recent editorial in The Lancet cautioned.

Amyloid-related imaging abnormalities that manifest as edema or microhemorrhages also occurred in one in five patients taking lecanemab.

In addition, a newly published case report in The New England Journal of Medicine describes a patient with Alzheimer’s disease who was taking lecanemab and who died after experiencing numerous intracerebral hemorrhages during treatment with tissue plasminogen activator (tPA) for acute ischemic stroke.

“The findings raise the possibility of cerebral hemorrhages and necrotizing vasculopathy associated with tPA infusion in a patient with cerebrovascular amyloid who had received lecanemab,” the authors wrote.
 

Alzheimer’s Association reaction

Still, in anticipation of accelerated approval of lecanemab and the antiamyloid drug donanemab (Eli Lilly), which the FDA has also fast-tracked, the Alzheimer’s Association filed a formal request last month with the Centers for Medicare & Medicaid Services asking that it provide full and unrestricted coverage for FDA-approved Alzheimer’s disease treatments.

In a letter addressed to CMS administrator Chiquita Brooks-LaSure, the association asked the agency to remove the requirements for “coverage with evidence development” in its national coverage determination for FDA-approved antiamyloid monoclonal antibodies.

“Each day matters when it comes to slowing the progression of this disease,” Joanne Pike, DrPH, president and CEO for the Alzheimer’s Association, noted in a news release at the time.

“The current CMS policy to severely limit access to these treatments eliminates people’s options, is resulting in continued irreversible disease progression, and contributes to greater health inequities. That’s not acceptable,” Dr. Pike added.

After news of today’s approval was released, Dr. Pike noted in a new release, “The Alzheimer’s Association welcomes and celebrates this action by the FDA. We now have a second approved treatment that changes the course of Alzheimer’s disease in a meaningful way for people in the early stages of the disease.”

Maria C. Carrillo, PhD, chief science officer at the Alzheimer’s Association, called today’s approval “a milestone achievement.”

“The progress we’ve seen in not only this class of treatments but also in the diversification of treatment types and targets over the past few years is exciting and provides real hope to those impacted by this devastating disease,” Dr. Carrillo said.
 

Critical issues

Commenting on the approval, Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School, Boston, and chief medical officer at Linus Health, said FDA approval of lecanemab and its adoption in the clinic represent a “very exciting development and prospect; but arguably some critical issues need to be considered.”

He noted that the health care system “is not currently prepared to cope with the challenges and demands of lecanemab,” as well as future pharmacologic agents.

“First, we need better workflows to identify suitable patients who can most benefit from this treatment,” said Dr. Pascual-Leone. He added that beyond identification of cognitive difficulties, amyloid status will need to be determined.

“Presently, this requires expensive and invasive tests,” such as positron-emission tomography scans or lumbar punctures for cerebrospinal fluid analysis. However, these are not fully covered by insurance companies and would be challenging to fully scale, he noted.

“In addition to screening, health systems will need to resolve the logistics challenges around the administration of lecanemab with twice-monthly infusions and the need for careful longitudinal evaluations for potential side effects,” said Dr. Pascual-Leone.

“While lecanemab may represent the first disease-modifying therapy widely available for early Alzheimer’s disease, the likely more promising approach is the addition of other therapies to lecanemab as part of a multi-intervention strategy combining pharmacologic and nonpharmacologic interventions,” he added.

Dr. Pascual-Leone has served as a paid member on scientific advisory boards for Neuroelectrics, Magstim, TetraNeuron, Skin2Neuron, MedRhythms, and Hearts Radiant and is a cofounder of TI Solutions and Linus Health.

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

This article was updated 1/9/23.

The U.S. Food and Drug Administration has approved the anti–amyloid-beta protofibril antibody lecanemab (Leqembi, Eisai) for the treatment of early Alzheimer’s disease.

Like its controversial cousin aducanumab (Aduhelm, Biogen/Eisai), lecanemab was approved under the FDA’s accelerated approval pathway, which can be used to fast-track a drug that provides a meaningful therapeutic advantage over existing treatments for a serious or life-threatening illness.

Unlike aducanumab, however, there was no formal FDA advisory committee meeting on lecanemab prior to approval.

“Alzheimer’s disease immeasurably incapacitates the lives of those who suffer from it and has devastating effects on their loved ones,” Billy Dunn, MD, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a press release.

“This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease,” Dr. Dunn added.

Eisai has reported that lecanemab will cost $26,500 a year.

Modest benefit, adverse events

The FDA noted, “The labeling states that treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was studied in clinical trials.”

The agency approved the treatment on the basis of findings from the CLARITY AD trial, which showed modest cognitive benefit for patients with early AD – but at a cost of increased risk for amyloid-related edema and effusions.

The trial enrolled 1,795 adults with mild cognitive impairment or early Alzheimer’s disease in whom amyloid pathology in the brain had been confirmed. Treatment consisted of lecanemab 10 mg/kg biweekly or matching placebo.

After 18 months of treatment, lecanemab slowed cognitive decline by 27%, compared with placebo, as measured by the Clinical Dementia Rating–Sum of Boxes (CDR-SB). This was an absolute difference of 0.45 points (change from baseline, 1.21 for lecanemab vs. 1.66 with placebo; P < .001).

While the results are “welcome news,” a 0.45-point difference on the CDR-SB might not be clinically meaningful, authors of a recent editorial in The Lancet cautioned.

Amyloid-related imaging abnormalities that manifest as edema or microhemorrhages also occurred in one in five patients taking lecanemab.

In addition, a newly published case report in The New England Journal of Medicine describes a patient with Alzheimer’s disease who was taking lecanemab and who died after experiencing numerous intracerebral hemorrhages during treatment with tissue plasminogen activator (tPA) for acute ischemic stroke.

“The findings raise the possibility of cerebral hemorrhages and necrotizing vasculopathy associated with tPA infusion in a patient with cerebrovascular amyloid who had received lecanemab,” the authors wrote.
 

Alzheimer’s Association reaction

Still, in anticipation of accelerated approval of lecanemab and the antiamyloid drug donanemab (Eli Lilly), which the FDA has also fast-tracked, the Alzheimer’s Association filed a formal request last month with the Centers for Medicare & Medicaid Services asking that it provide full and unrestricted coverage for FDA-approved Alzheimer’s disease treatments.

In a letter addressed to CMS administrator Chiquita Brooks-LaSure, the association asked the agency to remove the requirements for “coverage with evidence development” in its national coverage determination for FDA-approved antiamyloid monoclonal antibodies.

“Each day matters when it comes to slowing the progression of this disease,” Joanne Pike, DrPH, president and CEO for the Alzheimer’s Association, noted in a news release at the time.

“The current CMS policy to severely limit access to these treatments eliminates people’s options, is resulting in continued irreversible disease progression, and contributes to greater health inequities. That’s not acceptable,” Dr. Pike added.

After news of today’s approval was released, Dr. Pike noted in a new release, “The Alzheimer’s Association welcomes and celebrates this action by the FDA. We now have a second approved treatment that changes the course of Alzheimer’s disease in a meaningful way for people in the early stages of the disease.”

Maria C. Carrillo, PhD, chief science officer at the Alzheimer’s Association, called today’s approval “a milestone achievement.”

“The progress we’ve seen in not only this class of treatments but also in the diversification of treatment types and targets over the past few years is exciting and provides real hope to those impacted by this devastating disease,” Dr. Carrillo said.
 

Critical issues

Commenting on the approval, Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School, Boston, and chief medical officer at Linus Health, said FDA approval of lecanemab and its adoption in the clinic represent a “very exciting development and prospect; but arguably some critical issues need to be considered.”

He noted that the health care system “is not currently prepared to cope with the challenges and demands of lecanemab,” as well as future pharmacologic agents.

“First, we need better workflows to identify suitable patients who can most benefit from this treatment,” said Dr. Pascual-Leone. He added that beyond identification of cognitive difficulties, amyloid status will need to be determined.

“Presently, this requires expensive and invasive tests,” such as positron-emission tomography scans or lumbar punctures for cerebrospinal fluid analysis. However, these are not fully covered by insurance companies and would be challenging to fully scale, he noted.

“In addition to screening, health systems will need to resolve the logistics challenges around the administration of lecanemab with twice-monthly infusions and the need for careful longitudinal evaluations for potential side effects,” said Dr. Pascual-Leone.

“While lecanemab may represent the first disease-modifying therapy widely available for early Alzheimer’s disease, the likely more promising approach is the addition of other therapies to lecanemab as part of a multi-intervention strategy combining pharmacologic and nonpharmacologic interventions,” he added.

Dr. Pascual-Leone has served as a paid member on scientific advisory boards for Neuroelectrics, Magstim, TetraNeuron, Skin2Neuron, MedRhythms, and Hearts Radiant and is a cofounder of TI Solutions and Linus Health.

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

This article was updated 1/9/23.

The U.S. Food and Drug Administration has approved the anti–amyloid-beta protofibril antibody lecanemab (Leqembi, Eisai) for the treatment of early Alzheimer’s disease.

Like its controversial cousin aducanumab (Aduhelm, Biogen/Eisai), lecanemab was approved under the FDA’s accelerated approval pathway, which can be used to fast-track a drug that provides a meaningful therapeutic advantage over existing treatments for a serious or life-threatening illness.

Unlike aducanumab, however, there was no formal FDA advisory committee meeting on lecanemab prior to approval.

“Alzheimer’s disease immeasurably incapacitates the lives of those who suffer from it and has devastating effects on their loved ones,” Billy Dunn, MD, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a press release.

“This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease,” Dr. Dunn added.

Eisai has reported that lecanemab will cost $26,500 a year.

Modest benefit, adverse events

The FDA noted, “The labeling states that treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was studied in clinical trials.”

The agency approved the treatment on the basis of findings from the CLARITY AD trial, which showed modest cognitive benefit for patients with early AD – but at a cost of increased risk for amyloid-related edema and effusions.

The trial enrolled 1,795 adults with mild cognitive impairment or early Alzheimer’s disease in whom amyloid pathology in the brain had been confirmed. Treatment consisted of lecanemab 10 mg/kg biweekly or matching placebo.

After 18 months of treatment, lecanemab slowed cognitive decline by 27%, compared with placebo, as measured by the Clinical Dementia Rating–Sum of Boxes (CDR-SB). This was an absolute difference of 0.45 points (change from baseline, 1.21 for lecanemab vs. 1.66 with placebo; P < .001).

While the results are “welcome news,” a 0.45-point difference on the CDR-SB might not be clinically meaningful, authors of a recent editorial in The Lancet cautioned.

Amyloid-related imaging abnormalities that manifest as edema or microhemorrhages also occurred in one in five patients taking lecanemab.

In addition, a newly published case report in The New England Journal of Medicine describes a patient with Alzheimer’s disease who was taking lecanemab and who died after experiencing numerous intracerebral hemorrhages during treatment with tissue plasminogen activator (tPA) for acute ischemic stroke.

“The findings raise the possibility of cerebral hemorrhages and necrotizing vasculopathy associated with tPA infusion in a patient with cerebrovascular amyloid who had received lecanemab,” the authors wrote.
 

Alzheimer’s Association reaction

Still, in anticipation of accelerated approval of lecanemab and the antiamyloid drug donanemab (Eli Lilly), which the FDA has also fast-tracked, the Alzheimer’s Association filed a formal request last month with the Centers for Medicare & Medicaid Services asking that it provide full and unrestricted coverage for FDA-approved Alzheimer’s disease treatments.

In a letter addressed to CMS administrator Chiquita Brooks-LaSure, the association asked the agency to remove the requirements for “coverage with evidence development” in its national coverage determination for FDA-approved antiamyloid monoclonal antibodies.

“Each day matters when it comes to slowing the progression of this disease,” Joanne Pike, DrPH, president and CEO for the Alzheimer’s Association, noted in a news release at the time.

“The current CMS policy to severely limit access to these treatments eliminates people’s options, is resulting in continued irreversible disease progression, and contributes to greater health inequities. That’s not acceptable,” Dr. Pike added.

After news of today’s approval was released, Dr. Pike noted in a new release, “The Alzheimer’s Association welcomes and celebrates this action by the FDA. We now have a second approved treatment that changes the course of Alzheimer’s disease in a meaningful way for people in the early stages of the disease.”

Maria C. Carrillo, PhD, chief science officer at the Alzheimer’s Association, called today’s approval “a milestone achievement.”

“The progress we’ve seen in not only this class of treatments but also in the diversification of treatment types and targets over the past few years is exciting and provides real hope to those impacted by this devastating disease,” Dr. Carrillo said.
 

Critical issues

Commenting on the approval, Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School, Boston, and chief medical officer at Linus Health, said FDA approval of lecanemab and its adoption in the clinic represent a “very exciting development and prospect; but arguably some critical issues need to be considered.”

He noted that the health care system “is not currently prepared to cope with the challenges and demands of lecanemab,” as well as future pharmacologic agents.

“First, we need better workflows to identify suitable patients who can most benefit from this treatment,” said Dr. Pascual-Leone. He added that beyond identification of cognitive difficulties, amyloid status will need to be determined.

“Presently, this requires expensive and invasive tests,” such as positron-emission tomography scans or lumbar punctures for cerebrospinal fluid analysis. However, these are not fully covered by insurance companies and would be challenging to fully scale, he noted.

“In addition to screening, health systems will need to resolve the logistics challenges around the administration of lecanemab with twice-monthly infusions and the need for careful longitudinal evaluations for potential side effects,” said Dr. Pascual-Leone.

“While lecanemab may represent the first disease-modifying therapy widely available for early Alzheimer’s disease, the likely more promising approach is the addition of other therapies to lecanemab as part of a multi-intervention strategy combining pharmacologic and nonpharmacologic interventions,” he added.

Dr. Pascual-Leone has served as a paid member on scientific advisory boards for Neuroelectrics, Magstim, TetraNeuron, Skin2Neuron, MedRhythms, and Hearts Radiant and is a cofounder of TI Solutions and Linus Health.

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

This article was updated 1/9/23.

The administration of IV ketamine over the course of 2 months can improve treatment resistant depression (TRD) and executive function in older adults, findings from a new pilot study suggest.

Results showed nearly 50% of participants responded to ketamine and 25% achieved complete remission from TRD, as measured by scores on the Montgomery-Asberg Depression Rating Scale (MADRS).

“Our pilot study suggests that IV ketamine is well-tolerated, safe, and associated with improvement in late-life TRD,” co-investigator Marie Anne Gebara, MD, assistant professor of psychiatry at the University of Pittsburgh, told this news organization.

Dr. Gebara pointed out the treatment “may not be appropriate for all patients with TRD,” such as those with a history of psychotic symptoms or uncontrolled hypertension; but “it appears to be a promising option.”

The findings were published online in the American Journal of Geriatric Psychiatry.
 

Lack of data in seniors

Although ketamine has been shown in prior research to rapidly reduce suicidal ideation in adults, there has been a lack of data on its efficacy and safety in older adults, the current investigators note.

“Almost 50% of older adults suffering from depression have TRD, which is a leading cause of disability, excess mortality from suicide, and dementia,” Dr. Gebara said.

She added that after two failed trials of antidepressants, “older adults have few evidence-based choices: aripiprazole or bupropion augmentation, transcranial magnetic stimulation, or electroconvulsive therapy. Novel treatments with rapid benefit are needed as long-term outcomes are poor and recurrence rates are high.”

Dr. Gebara and colleagues at five sites (Columbia University, New York State Psychiatric Institute, University of Toronto, University of Pittsburgh, and Washington University in St. Louis) each enrolled five participants aged 60 and older into the pilot study between October 2020 and November 2021, for a total of 25 participants (mean age, 71 years).

Each participant was recruited from patient registries or referred by behavioral health or primary care providers and diagnosed with TRD, which was defined as an episode of major depressive disorder without psychotic features that persisted despite two or more trials of antidepressants including at least one evidence-based second-line treatment.

Participants had to take an oral antidepressant dosage for at least 1 month prior to the start of the IV ketamine infusions, and continue their antidepressant for the length of the trial.

They received IV ketamine twice weekly for 4 weeks. The dosage was weight-dependent.

At the end of the 4 weeks, participants who achieved a MADRS total score of less than 10 or had a 30% or greater reduction from their baseline MADRS score entered another 4-week phase of the trial. This phase consisted of once-weekly administration of IV ketamine.
 

Larger plans

Results showed 15 of the 25 participants (60%) experienced a 30% or higher reduction in MADRS scores in the first phase of the study. The mean change in MADRS total score from the beginning to the end of the first phase was a decrease of 9.4 points (P < .01).

At the end of the continuation phase, half (48%) met criteria for response and 27% met criteria for remission.

After ketamine administration, the researchers also found an improvement in Fluid Cognition Composite Score (Cohen’s d value = .61), indicating a medium to large effect size, and in three measures of executive function.

Overall, adverse events were rare and did not keep patients from participating in the study, the investigators note. Five of the 25 participants reported infusion-induced hypertension that was transient.

Study limitations cited include the small sample size and the absence of randomization and placebo control or comparison treatment.

“We were very pleased with these findings because they establish the safety of this novel intervention in older adults,” Dr. Gebara said.

“After establishing safety and tolerability, we can plan for larger, randomized controlled trials that will allow us to determine the effectiveness of IV ketamine for older adults with TRD,” she added.
 

Multiple mechanisms

In a comment, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University and director of the Yale Depression Research Program, New Haven, Conn., noted multiple mechanisms likely contribute to the antidepressant effects of ketamine.

Dr. Sanacora has independently researched the effects of ketamine but was not involved with the current study.

“Much of the work to date has focused on the drug’s proximal effects on the glutamatergic neurotransmitter system and the resulting enhancement of adaptive neuroplasticity in several brain regions,” he said.

“However, there is also evidence to suggest other neurotransmitter systems and possibly even neuroinflammatory regulators are also contributing to the effect,” Dr. Sanacora added.

He noted that these mechanisms are also likely amplified by the “hope, optimism, expectations, and improved medical management overall that are known to be associated with treatments that require close monitoring and follow-up with health care providers.”

Dr. Gebara noted that “internal/department funds at each site” were used to support the study. She also reported receiving support from Otsuka US. Disclosures for the other investigators are listed in the original article. Dr. Sanacora has reported having “no major direct conflicts” with the study.

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

The administration of IV ketamine over the course of 2 months can improve treatment resistant depression (TRD) and executive function in older adults, findings from a new pilot study suggest.

Results showed nearly 50% of participants responded to ketamine and 25% achieved complete remission from TRD, as measured by scores on the Montgomery-Asberg Depression Rating Scale (MADRS).

“Our pilot study suggests that IV ketamine is well-tolerated, safe, and associated with improvement in late-life TRD,” co-investigator Marie Anne Gebara, MD, assistant professor of psychiatry at the University of Pittsburgh, told this news organization.

Dr. Gebara pointed out the treatment “may not be appropriate for all patients with TRD,” such as those with a history of psychotic symptoms or uncontrolled hypertension; but “it appears to be a promising option.”

The findings were published online in the American Journal of Geriatric Psychiatry.
 

Lack of data in seniors

Although ketamine has been shown in prior research to rapidly reduce suicidal ideation in adults, there has been a lack of data on its efficacy and safety in older adults, the current investigators note.

“Almost 50% of older adults suffering from depression have TRD, which is a leading cause of disability, excess mortality from suicide, and dementia,” Dr. Gebara said.

She added that after two failed trials of antidepressants, “older adults have few evidence-based choices: aripiprazole or bupropion augmentation, transcranial magnetic stimulation, or electroconvulsive therapy. Novel treatments with rapid benefit are needed as long-term outcomes are poor and recurrence rates are high.”

Dr. Gebara and colleagues at five sites (Columbia University, New York State Psychiatric Institute, University of Toronto, University of Pittsburgh, and Washington University in St. Louis) each enrolled five participants aged 60 and older into the pilot study between October 2020 and November 2021, for a total of 25 participants (mean age, 71 years).

Each participant was recruited from patient registries or referred by behavioral health or primary care providers and diagnosed with TRD, which was defined as an episode of major depressive disorder without psychotic features that persisted despite two or more trials of antidepressants including at least one evidence-based second-line treatment.

Participants had to take an oral antidepressant dosage for at least 1 month prior to the start of the IV ketamine infusions, and continue their antidepressant for the length of the trial.

They received IV ketamine twice weekly for 4 weeks. The dosage was weight-dependent.

At the end of the 4 weeks, participants who achieved a MADRS total score of less than 10 or had a 30% or greater reduction from their baseline MADRS score entered another 4-week phase of the trial. This phase consisted of once-weekly administration of IV ketamine.
 

Larger plans

Results showed 15 of the 25 participants (60%) experienced a 30% or higher reduction in MADRS scores in the first phase of the study. The mean change in MADRS total score from the beginning to the end of the first phase was a decrease of 9.4 points (P < .01).

At the end of the continuation phase, half (48%) met criteria for response and 27% met criteria for remission.

After ketamine administration, the researchers also found an improvement in Fluid Cognition Composite Score (Cohen’s d value = .61), indicating a medium to large effect size, and in three measures of executive function.

Overall, adverse events were rare and did not keep patients from participating in the study, the investigators note. Five of the 25 participants reported infusion-induced hypertension that was transient.

Study limitations cited include the small sample size and the absence of randomization and placebo control or comparison treatment.

“We were very pleased with these findings because they establish the safety of this novel intervention in older adults,” Dr. Gebara said.

“After establishing safety and tolerability, we can plan for larger, randomized controlled trials that will allow us to determine the effectiveness of IV ketamine for older adults with TRD,” she added.
 

Multiple mechanisms

In a comment, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University and director of the Yale Depression Research Program, New Haven, Conn., noted multiple mechanisms likely contribute to the antidepressant effects of ketamine.

Dr. Sanacora has independently researched the effects of ketamine but was not involved with the current study.

“Much of the work to date has focused on the drug’s proximal effects on the glutamatergic neurotransmitter system and the resulting enhancement of adaptive neuroplasticity in several brain regions,” he said.

“However, there is also evidence to suggest other neurotransmitter systems and possibly even neuroinflammatory regulators are also contributing to the effect,” Dr. Sanacora added.

He noted that these mechanisms are also likely amplified by the “hope, optimism, expectations, and improved medical management overall that are known to be associated with treatments that require close monitoring and follow-up with health care providers.”

Dr. Gebara noted that “internal/department funds at each site” were used to support the study. She also reported receiving support from Otsuka US. Disclosures for the other investigators are listed in the original article. Dr. Sanacora has reported having “no major direct conflicts” with the study.

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

The administration of IV ketamine over the course of 2 months can improve treatment resistant depression (TRD) and executive function in older adults, findings from a new pilot study suggest.

Results showed nearly 50% of participants responded to ketamine and 25% achieved complete remission from TRD, as measured by scores on the Montgomery-Asberg Depression Rating Scale (MADRS).

“Our pilot study suggests that IV ketamine is well-tolerated, safe, and associated with improvement in late-life TRD,” co-investigator Marie Anne Gebara, MD, assistant professor of psychiatry at the University of Pittsburgh, told this news organization.

Dr. Gebara pointed out the treatment “may not be appropriate for all patients with TRD,” such as those with a history of psychotic symptoms or uncontrolled hypertension; but “it appears to be a promising option.”

The findings were published online in the American Journal of Geriatric Psychiatry.
 

Lack of data in seniors

Although ketamine has been shown in prior research to rapidly reduce suicidal ideation in adults, there has been a lack of data on its efficacy and safety in older adults, the current investigators note.

“Almost 50% of older adults suffering from depression have TRD, which is a leading cause of disability, excess mortality from suicide, and dementia,” Dr. Gebara said.

She added that after two failed trials of antidepressants, “older adults have few evidence-based choices: aripiprazole or bupropion augmentation, transcranial magnetic stimulation, or electroconvulsive therapy. Novel treatments with rapid benefit are needed as long-term outcomes are poor and recurrence rates are high.”

Dr. Gebara and colleagues at five sites (Columbia University, New York State Psychiatric Institute, University of Toronto, University of Pittsburgh, and Washington University in St. Louis) each enrolled five participants aged 60 and older into the pilot study between October 2020 and November 2021, for a total of 25 participants (mean age, 71 years).

Each participant was recruited from patient registries or referred by behavioral health or primary care providers and diagnosed with TRD, which was defined as an episode of major depressive disorder without psychotic features that persisted despite two or more trials of antidepressants including at least one evidence-based second-line treatment.

Participants had to take an oral antidepressant dosage for at least 1 month prior to the start of the IV ketamine infusions, and continue their antidepressant for the length of the trial.

They received IV ketamine twice weekly for 4 weeks. The dosage was weight-dependent.

At the end of the 4 weeks, participants who achieved a MADRS total score of less than 10 or had a 30% or greater reduction from their baseline MADRS score entered another 4-week phase of the trial. This phase consisted of once-weekly administration of IV ketamine.
 

Larger plans

Results showed 15 of the 25 participants (60%) experienced a 30% or higher reduction in MADRS scores in the first phase of the study. The mean change in MADRS total score from the beginning to the end of the first phase was a decrease of 9.4 points (P < .01).

At the end of the continuation phase, half (48%) met criteria for response and 27% met criteria for remission.

After ketamine administration, the researchers also found an improvement in Fluid Cognition Composite Score (Cohen’s d value = .61), indicating a medium to large effect size, and in three measures of executive function.

Overall, adverse events were rare and did not keep patients from participating in the study, the investigators note. Five of the 25 participants reported infusion-induced hypertension that was transient.

Study limitations cited include the small sample size and the absence of randomization and placebo control or comparison treatment.

“We were very pleased with these findings because they establish the safety of this novel intervention in older adults,” Dr. Gebara said.

“After establishing safety and tolerability, we can plan for larger, randomized controlled trials that will allow us to determine the effectiveness of IV ketamine for older adults with TRD,” she added.
 

Multiple mechanisms

In a comment, Gerard Sanacora, MD, PhD, professor of psychiatry at Yale University and director of the Yale Depression Research Program, New Haven, Conn., noted multiple mechanisms likely contribute to the antidepressant effects of ketamine.

Dr. Sanacora has independently researched the effects of ketamine but was not involved with the current study.

“Much of the work to date has focused on the drug’s proximal effects on the glutamatergic neurotransmitter system and the resulting enhancement of adaptive neuroplasticity in several brain regions,” he said.

“However, there is also evidence to suggest other neurotransmitter systems and possibly even neuroinflammatory regulators are also contributing to the effect,” Dr. Sanacora added.

He noted that these mechanisms are also likely amplified by the “hope, optimism, expectations, and improved medical management overall that are known to be associated with treatments that require close monitoring and follow-up with health care providers.”

Dr. Gebara noted that “internal/department funds at each site” were used to support the study. She also reported receiving support from Otsuka US. Disclosures for the other investigators are listed in the original article. Dr. Sanacora has reported having “no major direct conflicts” with the study.

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

The obvious first statement is that it’s neither wise nor appropriate to speculate on the specifics of Damar Hamlin’s cardiac event during a football game on Jan. 2 (including the possibility of commotio cordis) or his ongoing care. The public nature of his collapse induces intense curiosity but people with illness deserve privacy. Privacy in health care is in short supply. I disagree strongly with those who say his doctors ought to be giving public updates. That’s up to the family.

But there are important general concepts to consider about this incident. These include ...

Cardiac arrest can happen to anyone

People with structural heart disease or other chronic illnesses have a higher risk of arrhythmia, but the notion that athletes are immune from cardiac arrest is wrong. This sentence almost seems too obvious to write, but to this day, I hear clinicians express surprise that an athletic person has heart disease.

Survival turns on rapid and effective intervention

In the old days of electrophysiology, we used to test implantable cardioverter-defibrillators during an implant procedure by inducing ventricular fibrillation (VF) and watching the device convert it. Thankfully, trials have shown that this is no longer necessary for most implants.

When you induce VF In the EP lab, you learn quickly that a) it causes loss of consciousness in a matter of seconds, b) rapid defibrillation restores consciousness, often without the patients knowing or remembering they passed out, and c) the failure of the shock to terminate VF results in deterioration in a matter of 1-2 minutes. Even 1 minute in VF feels so long.

Need is an appropriate word in VF treatment

Clinicians often use the verb need. As in, this patient needs this pill or this procedure. It’s rarely appropriate.

But in the case of treating VF, patients truly need rapid defibrillation. Survival of out-of-hospital cardiac arrest is low because there just aren’t enough automated external defibrillators (AEDs) or people trained to use them. A study of patients who had out-of-hospital cardiac arrest in Denmark found that 30-day survival almost doubled (28.8% vs. 16.4%), when the nearest AED was accessible.

Bystanders must act

The public messages are simple: If a person loses consciousness in front of you, and is not breathing normally, assume it is a cardiac arrest, call 911 to get professional help, and start hands-only chest compressions. Don’t spend time checking for a pulse or trying to wake the person. If this is not a cardiac arrest, they will soon tell you to stop compressing their chest. Seconds matter.

Chest compressions are important but what is really needed is defibrillation. A crucial step in CPR is to send someone to get an AED and get the pads attached. If this is a shockable rhythm, deliver the shock. Hamlin’s collapse emphasizes the importance of the AED; without it, his survival to the hospital would have been unlikely.

Widespread preparticipation screening of young athletes remains a bad idea

Whenever cardiac arrest occurs in an athlete, in such a public way, people think about prevention. Surely it is better to prevent such an event than react to it, goes the thinking. The argument against this idea has four prongs:

The incidence of cardiac disease in a young athlete is extremely low, which sets up a situation where most “positive” tests are false positive. A false positive screening ECG or echocardiogram can create harm in multiple ways. One is the risk from downstream procedures, but worse is the inappropriate disqualification from sport. Healthwise, few harms could be greater than creating long-term fear of exercise in someone.

There is also the problem of false-negative screening tests. An ECG may be normal in the setting of hypertrophic cardiomyopathy. And a normal echocardiogram does not exclude arrhythmogenic right ventricular cardiomyopathy or other genetic causes of cardiac arrest. In a 2018 study from a major sports cardiology center in London, 6 of the 8 sudden cardiac deaths in their series were in athletes who had no detectable abnormalities on screening.

Even when disease is found, it’s not clear that prohibiting participation in sports prevents sudden death. Many previous class III recommendations against participation in sport now carry class II – may be considered – designations.

Finally, screening for any disease loses value as treatments improve. Public education regarding rapid intervention with CPR and AED use is the best treatment option. A great example is the case of Christian Erikson, a Danish soccer player who suffered cardiac arrest during a match at the European Championships in 2021 and was rapidly defibrillated on the field. Therapy was so effective that he was conscious and able to wave to fans on his way out of the stadium. He has now returned to elite competition.

Proponents of screening might oppose my take by saying that National Football League players are intensely screened. But this is different from widespread screening of high school and college athletes. It might sound harsh to say, but professional teams have dualities of interests in the health of their athletes given the million-dollar contracts.

What’s more, professional teams can afford to hire expert cardiologists to perform the testing. This would likely reduce the rate of false-positive findings, compared with screening in the community setting. I often have young people referred to me because of asymptomatic bradycardia found during athletic screening – an obviously normal finding.

Conclusions

As long as there are sports, there will be athletes who suffer cardiac arrest.

We can both hope for Hamlin’s full recovery and learn lessons to help reduce the rate of death from out-of-hospital cardiac arrest. This mostly involves education on how to help fellow humans and a public health commitment to access to AEDs.

John Mandrola, MD, practices cardiac electrophysiology in Louisville, Ky. and is a writer and podcaster for Medscape. He has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

The obvious first statement is that it’s neither wise nor appropriate to speculate on the specifics of Damar Hamlin’s cardiac event during a football game on Jan. 2 (including the possibility of commotio cordis) or his ongoing care. The public nature of his collapse induces intense curiosity but people with illness deserve privacy. Privacy in health care is in short supply. I disagree strongly with those who say his doctors ought to be giving public updates. That’s up to the family.

But there are important general concepts to consider about this incident. These include ...

Cardiac arrest can happen to anyone

People with structural heart disease or other chronic illnesses have a higher risk of arrhythmia, but the notion that athletes are immune from cardiac arrest is wrong. This sentence almost seems too obvious to write, but to this day, I hear clinicians express surprise that an athletic person has heart disease.

Survival turns on rapid and effective intervention

In the old days of electrophysiology, we used to test implantable cardioverter-defibrillators during an implant procedure by inducing ventricular fibrillation (VF) and watching the device convert it. Thankfully, trials have shown that this is no longer necessary for most implants.

When you induce VF In the EP lab, you learn quickly that a) it causes loss of consciousness in a matter of seconds, b) rapid defibrillation restores consciousness, often without the patients knowing or remembering they passed out, and c) the failure of the shock to terminate VF results in deterioration in a matter of 1-2 minutes. Even 1 minute in VF feels so long.

Need is an appropriate word in VF treatment

Clinicians often use the verb need. As in, this patient needs this pill or this procedure. It’s rarely appropriate.

But in the case of treating VF, patients truly need rapid defibrillation. Survival of out-of-hospital cardiac arrest is low because there just aren’t enough automated external defibrillators (AEDs) or people trained to use them. A study of patients who had out-of-hospital cardiac arrest in Denmark found that 30-day survival almost doubled (28.8% vs. 16.4%), when the nearest AED was accessible.

Bystanders must act

The public messages are simple: If a person loses consciousness in front of you, and is not breathing normally, assume it is a cardiac arrest, call 911 to get professional help, and start hands-only chest compressions. Don’t spend time checking for a pulse or trying to wake the person. If this is not a cardiac arrest, they will soon tell you to stop compressing their chest. Seconds matter.

Chest compressions are important but what is really needed is defibrillation. A crucial step in CPR is to send someone to get an AED and get the pads attached. If this is a shockable rhythm, deliver the shock. Hamlin’s collapse emphasizes the importance of the AED; without it, his survival to the hospital would have been unlikely.

Widespread preparticipation screening of young athletes remains a bad idea

Whenever cardiac arrest occurs in an athlete, in such a public way, people think about prevention. Surely it is better to prevent such an event than react to it, goes the thinking. The argument against this idea has four prongs:

The incidence of cardiac disease in a young athlete is extremely low, which sets up a situation where most “positive” tests are false positive. A false positive screening ECG or echocardiogram can create harm in multiple ways. One is the risk from downstream procedures, but worse is the inappropriate disqualification from sport. Healthwise, few harms could be greater than creating long-term fear of exercise in someone.

There is also the problem of false-negative screening tests. An ECG may be normal in the setting of hypertrophic cardiomyopathy. And a normal echocardiogram does not exclude arrhythmogenic right ventricular cardiomyopathy or other genetic causes of cardiac arrest. In a 2018 study from a major sports cardiology center in London, 6 of the 8 sudden cardiac deaths in their series were in athletes who had no detectable abnormalities on screening.

Even when disease is found, it’s not clear that prohibiting participation in sports prevents sudden death. Many previous class III recommendations against participation in sport now carry class II – may be considered – designations.

Finally, screening for any disease loses value as treatments improve. Public education regarding rapid intervention with CPR and AED use is the best treatment option. A great example is the case of Christian Erikson, a Danish soccer player who suffered cardiac arrest during a match at the European Championships in 2021 and was rapidly defibrillated on the field. Therapy was so effective that he was conscious and able to wave to fans on his way out of the stadium. He has now returned to elite competition.

Proponents of screening might oppose my take by saying that National Football League players are intensely screened. But this is different from widespread screening of high school and college athletes. It might sound harsh to say, but professional teams have dualities of interests in the health of their athletes given the million-dollar contracts.

What’s more, professional teams can afford to hire expert cardiologists to perform the testing. This would likely reduce the rate of false-positive findings, compared with screening in the community setting. I often have young people referred to me because of asymptomatic bradycardia found during athletic screening – an obviously normal finding.

Conclusions

As long as there are sports, there will be athletes who suffer cardiac arrest.

We can both hope for Hamlin’s full recovery and learn lessons to help reduce the rate of death from out-of-hospital cardiac arrest. This mostly involves education on how to help fellow humans and a public health commitment to access to AEDs.

John Mandrola, MD, practices cardiac electrophysiology in Louisville, Ky. and is a writer and podcaster for Medscape. He has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

The obvious first statement is that it’s neither wise nor appropriate to speculate on the specifics of Damar Hamlin’s cardiac event during a football game on Jan. 2 (including the possibility of commotio cordis) or his ongoing care. The public nature of his collapse induces intense curiosity but people with illness deserve privacy. Privacy in health care is in short supply. I disagree strongly with those who say his doctors ought to be giving public updates. That’s up to the family.

But there are important general concepts to consider about this incident. These include ...

Cardiac arrest can happen to anyone

People with structural heart disease or other chronic illnesses have a higher risk of arrhythmia, but the notion that athletes are immune from cardiac arrest is wrong. This sentence almost seems too obvious to write, but to this day, I hear clinicians express surprise that an athletic person has heart disease.

Survival turns on rapid and effective intervention

In the old days of electrophysiology, we used to test implantable cardioverter-defibrillators during an implant procedure by inducing ventricular fibrillation (VF) and watching the device convert it. Thankfully, trials have shown that this is no longer necessary for most implants.

When you induce VF In the EP lab, you learn quickly that a) it causes loss of consciousness in a matter of seconds, b) rapid defibrillation restores consciousness, often without the patients knowing or remembering they passed out, and c) the failure of the shock to terminate VF results in deterioration in a matter of 1-2 minutes. Even 1 minute in VF feels so long.

Need is an appropriate word in VF treatment

Clinicians often use the verb need. As in, this patient needs this pill or this procedure. It’s rarely appropriate.

But in the case of treating VF, patients truly need rapid defibrillation. Survival of out-of-hospital cardiac arrest is low because there just aren’t enough automated external defibrillators (AEDs) or people trained to use them. A study of patients who had out-of-hospital cardiac arrest in Denmark found that 30-day survival almost doubled (28.8% vs. 16.4%), when the nearest AED was accessible.

Bystanders must act

The public messages are simple: If a person loses consciousness in front of you, and is not breathing normally, assume it is a cardiac arrest, call 911 to get professional help, and start hands-only chest compressions. Don’t spend time checking for a pulse or trying to wake the person. If this is not a cardiac arrest, they will soon tell you to stop compressing their chest. Seconds matter.

Chest compressions are important but what is really needed is defibrillation. A crucial step in CPR is to send someone to get an AED and get the pads attached. If this is a shockable rhythm, deliver the shock. Hamlin’s collapse emphasizes the importance of the AED; without it, his survival to the hospital would have been unlikely.

Widespread preparticipation screening of young athletes remains a bad idea

Whenever cardiac arrest occurs in an athlete, in such a public way, people think about prevention. Surely it is better to prevent such an event than react to it, goes the thinking. The argument against this idea has four prongs:

The incidence of cardiac disease in a young athlete is extremely low, which sets up a situation where most “positive” tests are false positive. A false positive screening ECG or echocardiogram can create harm in multiple ways. One is the risk from downstream procedures, but worse is the inappropriate disqualification from sport. Healthwise, few harms could be greater than creating long-term fear of exercise in someone.

There is also the problem of false-negative screening tests. An ECG may be normal in the setting of hypertrophic cardiomyopathy. And a normal echocardiogram does not exclude arrhythmogenic right ventricular cardiomyopathy or other genetic causes of cardiac arrest. In a 2018 study from a major sports cardiology center in London, 6 of the 8 sudden cardiac deaths in their series were in athletes who had no detectable abnormalities on screening.

Even when disease is found, it’s not clear that prohibiting participation in sports prevents sudden death. Many previous class III recommendations against participation in sport now carry class II – may be considered – designations.

Finally, screening for any disease loses value as treatments improve. Public education regarding rapid intervention with CPR and AED use is the best treatment option. A great example is the case of Christian Erikson, a Danish soccer player who suffered cardiac arrest during a match at the European Championships in 2021 and was rapidly defibrillated on the field. Therapy was so effective that he was conscious and able to wave to fans on his way out of the stadium. He has now returned to elite competition.

Proponents of screening might oppose my take by saying that National Football League players are intensely screened. But this is different from widespread screening of high school and college athletes. It might sound harsh to say, but professional teams have dualities of interests in the health of their athletes given the million-dollar contracts.

What’s more, professional teams can afford to hire expert cardiologists to perform the testing. This would likely reduce the rate of false-positive findings, compared with screening in the community setting. I often have young people referred to me because of asymptomatic bradycardia found during athletic screening – an obviously normal finding.

Conclusions

As long as there are sports, there will be athletes who suffer cardiac arrest.

We can both hope for Hamlin’s full recovery and learn lessons to help reduce the rate of death from out-of-hospital cardiac arrest. This mostly involves education on how to help fellow humans and a public health commitment to access to AEDs.

John Mandrola, MD, practices cardiac electrophysiology in Louisville, Ky. and is a writer and podcaster for Medscape. He has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

High-dose vitamin D led to improvement of toxic erythema of chemotherapy (TEC) within 1 to 4 days in a retrospective case series of six patients seen on an inpatient dermatology consultative service.

Currently, chemotherapy cessation, delay, or dose modification are the “only reliable methods of resolving TEC,” and supportive agents such as topical corticosteroids, topical keratolytics, and pain control are associated with variable and “relatively slow improvement involving 2 to 4 weeks of recovery after chemotherapy interruption,” Cuong V. Nguyen, MD, of the department of dermatology at Northwestern University, Chicago, and colleagues, wrote in a research letter.

Onset of TEC in the six patients occurred a mean of 8.5 days after chemotherapy. Vitamin D – 50,000 IU for one patient and 100,000 IU for the others – was administered a mean of 4.3 days from rash onset and again in 7 days. Triamcinolone, 0.1%, or clobetasol, 0.05%, ointments were also prescribed.

All patients experienced symptomatic improvement in pain, pruritus, or swelling within a day of the first vitamin D treatment, and improvement in redness within 1 to 4 days, the authors said. The second treatment was administered for residual symptoms.

Adam Friedman, MD, professor and chair of dermatology and director of the supportive oncodermatology clinic at George Washington University, Washington, said that supporting patients through the “expected, disabling and often treatment-limiting side effects of oncologic therapies” is an area that is “in its infancy” and is characterized by limited evidence-based approaches.

“Creativity is therefore a must,” he said, commenting on the research letter. “Practice starts with anecdote, and this is certainly an exciting finding ... I look forward to trialing this with our patients at GW.”

Five of the six patients had a hematologic condition that required induction chemotherapy before hematopoietic stem cell transplant, and one was receiving regorafenib for treatment of glioblastoma multiforme. Diagnosis of TEC was established by clinical presentation, and five of the six patients underwent a biopsy. Biopsy findings were consistent with a TEC diagnosis in three patients, and showed nonspecific perivascular dermatitis in two, the investigators reported.

Further research is needed to determine optimal dosing, “delineate safety concerns and potential role in cancer treatment, and establish whether a durable response in patients with continuous chemotherapy, such as in an outpatient setting, is possible,” they said.

Dr. Nguyen and his coauthors reported no conflict of interest disclosures.

High-dose vitamin D led to improvement of toxic erythema of chemotherapy (TEC) within 1 to 4 days in a retrospective case series of six patients seen on an inpatient dermatology consultative service.

Currently, chemotherapy cessation, delay, or dose modification are the “only reliable methods of resolving TEC,” and supportive agents such as topical corticosteroids, topical keratolytics, and pain control are associated with variable and “relatively slow improvement involving 2 to 4 weeks of recovery after chemotherapy interruption,” Cuong V. Nguyen, MD, of the department of dermatology at Northwestern University, Chicago, and colleagues, wrote in a research letter.

Onset of TEC in the six patients occurred a mean of 8.5 days after chemotherapy. Vitamin D – 50,000 IU for one patient and 100,000 IU for the others – was administered a mean of 4.3 days from rash onset and again in 7 days. Triamcinolone, 0.1%, or clobetasol, 0.05%, ointments were also prescribed.

All patients experienced symptomatic improvement in pain, pruritus, or swelling within a day of the first vitamin D treatment, and improvement in redness within 1 to 4 days, the authors said. The second treatment was administered for residual symptoms.

Adam Friedman, MD, professor and chair of dermatology and director of the supportive oncodermatology clinic at George Washington University, Washington, said that supporting patients through the “expected, disabling and often treatment-limiting side effects of oncologic therapies” is an area that is “in its infancy” and is characterized by limited evidence-based approaches.

“Creativity is therefore a must,” he said, commenting on the research letter. “Practice starts with anecdote, and this is certainly an exciting finding ... I look forward to trialing this with our patients at GW.”

Five of the six patients had a hematologic condition that required induction chemotherapy before hematopoietic stem cell transplant, and one was receiving regorafenib for treatment of glioblastoma multiforme. Diagnosis of TEC was established by clinical presentation, and five of the six patients underwent a biopsy. Biopsy findings were consistent with a TEC diagnosis in three patients, and showed nonspecific perivascular dermatitis in two, the investigators reported.

Further research is needed to determine optimal dosing, “delineate safety concerns and potential role in cancer treatment, and establish whether a durable response in patients with continuous chemotherapy, such as in an outpatient setting, is possible,” they said.

Dr. Nguyen and his coauthors reported no conflict of interest disclosures.

High-dose vitamin D led to improvement of toxic erythema of chemotherapy (TEC) within 1 to 4 days in a retrospective case series of six patients seen on an inpatient dermatology consultative service.

Currently, chemotherapy cessation, delay, or dose modification are the “only reliable methods of resolving TEC,” and supportive agents such as topical corticosteroids, topical keratolytics, and pain control are associated with variable and “relatively slow improvement involving 2 to 4 weeks of recovery after chemotherapy interruption,” Cuong V. Nguyen, MD, of the department of dermatology at Northwestern University, Chicago, and colleagues, wrote in a research letter.

Onset of TEC in the six patients occurred a mean of 8.5 days after chemotherapy. Vitamin D – 50,000 IU for one patient and 100,000 IU for the others – was administered a mean of 4.3 days from rash onset and again in 7 days. Triamcinolone, 0.1%, or clobetasol, 0.05%, ointments were also prescribed.

All patients experienced symptomatic improvement in pain, pruritus, or swelling within a day of the first vitamin D treatment, and improvement in redness within 1 to 4 days, the authors said. The second treatment was administered for residual symptoms.

Adam Friedman, MD, professor and chair of dermatology and director of the supportive oncodermatology clinic at George Washington University, Washington, said that supporting patients through the “expected, disabling and often treatment-limiting side effects of oncologic therapies” is an area that is “in its infancy” and is characterized by limited evidence-based approaches.

“Creativity is therefore a must,” he said, commenting on the research letter. “Practice starts with anecdote, and this is certainly an exciting finding ... I look forward to trialing this with our patients at GW.”

Five of the six patients had a hematologic condition that required induction chemotherapy before hematopoietic stem cell transplant, and one was receiving regorafenib for treatment of glioblastoma multiforme. Diagnosis of TEC was established by clinical presentation, and five of the six patients underwent a biopsy. Biopsy findings were consistent with a TEC diagnosis in three patients, and showed nonspecific perivascular dermatitis in two, the investigators reported.

Further research is needed to determine optimal dosing, “delineate safety concerns and potential role in cancer treatment, and establish whether a durable response in patients with continuous chemotherapy, such as in an outpatient setting, is possible,” they said.

Dr. Nguyen and his coauthors reported no conflict of interest disclosures.

Could gut health be behind a person’s motivation – or lack thereof – to exercise?

Researchers at the University of Pennsylvania, Philadelphia recently explored this topic when they wanted to find out why some lab mice seem to love their exercise wheel, while others mostly ignore it.

To start, the researchers used a machine-learning algorithm to look for biological traits that could explain the differences in activity levels among mice. And what they found surprised them: Genetics seemed to have little to do with it, but differences in gut bacteria appeared to matter more. A handful of studies backed that up: Thriving gut microbiomes have been linked with optimal muscle function in mice.

Sure enough, when the researchers dosed mice with broad-spectrum antibiotics, killing off their gut bacteria, the distance the rodents were able to run dropped by half. But off the antibiotics, the mice mostly regained their previous performance levels.

The findings, published in the journal Nature, suggest that the gut microbiome may help regulate the desire to exercise. 

If confirmed in humans, this hypothesis could help explain why so many Americans fail to get the recommended amount of physical activity. Some may blame lack of time, energy, or interest. But perhaps the reason could come down to the trillions of microbes living in their gut. 

This line of research could also lead to microbiome-based ways to get sedentary people off the couch or optimize athletic performance.  

But how could one’s microbiome impact the motivation to move? To find the answer, the researchers zeroed in on the brain. 
 

The gut-brain connection

After treating the mice with antibiotics, the researchers sequenced RNA in the rodents’ striatum (the part of the brain responsible for motivation). They found reduced gene expression in the cells’ dopamine receptors – which release the neurochemical dopamine, making one feel like they’ve accomplished something good. In other words: Mice treated with antibiotics were getting less of a dopamine hit after their run. 

“Only when we started focusing on the brain did we understand that the microbiome’s effect on exercise capacity was mediated by the central and peripheral nervous systems,” said study author Christoph Thaiss, PhD, a microbiologist at the University of Pennsylvania. “This realization completely changed the trajectory of the project.”

To find out how, exactly, bacteria in the colon were signaling the brain, the researchers performed a series of experiments over several years. They identified two types of bacteria, Eubacterium rectale and Coprococcus eutactus. These strains produce compounds called fatty acid amides that interact with endocannabinoid receptors in the gut. 

Those endocannabinoid receptors signal the brain to cut back its production of monoamine oxidase, the compound that breaks down dopamine. With less of this dopamine-clearing compound in the brain, more dopamine could build up after a long run, making the mice feel good and eager to hit the exercise wheel again soon. 

This gut-brain pathway “may have evolved to couple the initiation of prolonged physical activity to the nutritional status of the gastrointestinal tract,” Dr. Thaiss said. Gut bacteria monitor what’s in your colon and tell your brain whether you have enough food to fuel a workout. 

The colon, or gut, hosts trillions of microbes with potentially hundreds of different bacteria strains. These strains are determined by the food we eat and the environment we occupy.

“The genetic impact on the microbiome is rather minor,” Dr. Thaiss said, “but lifestyle factors strongly impact the composition of the gut microbiome.”

He hopes to develop nutritional interventions to encourage the growth of the motivating types of bacteria, the kind that make a person want to go for a 5-mile run.
 

What’s next?  

Moving forward,  the researchers need to find out whether the gut affects motivation in humans, too. To do that, they’re analyzing the gut microbiomes of people with varying levels of exercise motivation. 

“With enough samples, we could potentially correlate species of microbiota that exist in exercise-motivated individuals,” said study coauthor Nicholas Betley, PhD, a biologist at the University of Pennsylvania. 

Variations in the gut microbiome could help explain the “runner’s high” that some people have in a long-distance race. The research could also help promote weight training or sports participation. 

“Imagine if a sports team could optimally motivate the athletes on the team to exercise,” said Dr. Betley. The lab is investigating the microbiome’s impact on high-intensity interval training.

Signals from the gut to the brain could be affecting body processes in other ways too, the researchers speculated. 

“There are so many possibilities for how these signals may change physiology and impact health,” Dr. Betley said. “A new set of studies may well establish a whole new branch of exercise physiology.”

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

Could gut health be behind a person’s motivation – or lack thereof – to exercise?

Researchers at the University of Pennsylvania, Philadelphia recently explored this topic when they wanted to find out why some lab mice seem to love their exercise wheel, while others mostly ignore it.

To start, the researchers used a machine-learning algorithm to look for biological traits that could explain the differences in activity levels among mice. And what they found surprised them: Genetics seemed to have little to do with it, but differences in gut bacteria appeared to matter more. A handful of studies backed that up: Thriving gut microbiomes have been linked with optimal muscle function in mice.

Sure enough, when the researchers dosed mice with broad-spectrum antibiotics, killing off their gut bacteria, the distance the rodents were able to run dropped by half. But off the antibiotics, the mice mostly regained their previous performance levels.

The findings, published in the journal Nature, suggest that the gut microbiome may help regulate the desire to exercise. 

If confirmed in humans, this hypothesis could help explain why so many Americans fail to get the recommended amount of physical activity. Some may blame lack of time, energy, or interest. But perhaps the reason could come down to the trillions of microbes living in their gut. 

This line of research could also lead to microbiome-based ways to get sedentary people off the couch or optimize athletic performance.  

But how could one’s microbiome impact the motivation to move? To find the answer, the researchers zeroed in on the brain. 
 

The gut-brain connection

After treating the mice with antibiotics, the researchers sequenced RNA in the rodents’ striatum (the part of the brain responsible for motivation). They found reduced gene expression in the cells’ dopamine receptors – which release the neurochemical dopamine, making one feel like they’ve accomplished something good. In other words: Mice treated with antibiotics were getting less of a dopamine hit after their run. 

“Only when we started focusing on the brain did we understand that the microbiome’s effect on exercise capacity was mediated by the central and peripheral nervous systems,” said study author Christoph Thaiss, PhD, a microbiologist at the University of Pennsylvania. “This realization completely changed the trajectory of the project.”

To find out how, exactly, bacteria in the colon were signaling the brain, the researchers performed a series of experiments over several years. They identified two types of bacteria, Eubacterium rectale and Coprococcus eutactus. These strains produce compounds called fatty acid amides that interact with endocannabinoid receptors in the gut. 

Those endocannabinoid receptors signal the brain to cut back its production of monoamine oxidase, the compound that breaks down dopamine. With less of this dopamine-clearing compound in the brain, more dopamine could build up after a long run, making the mice feel good and eager to hit the exercise wheel again soon. 

This gut-brain pathway “may have evolved to couple the initiation of prolonged physical activity to the nutritional status of the gastrointestinal tract,” Dr. Thaiss said. Gut bacteria monitor what’s in your colon and tell your brain whether you have enough food to fuel a workout. 

The colon, or gut, hosts trillions of microbes with potentially hundreds of different bacteria strains. These strains are determined by the food we eat and the environment we occupy.

“The genetic impact on the microbiome is rather minor,” Dr. Thaiss said, “but lifestyle factors strongly impact the composition of the gut microbiome.”

He hopes to develop nutritional interventions to encourage the growth of the motivating types of bacteria, the kind that make a person want to go for a 5-mile run.
 

What’s next?  

Moving forward,  the researchers need to find out whether the gut affects motivation in humans, too. To do that, they’re analyzing the gut microbiomes of people with varying levels of exercise motivation. 

“With enough samples, we could potentially correlate species of microbiota that exist in exercise-motivated individuals,” said study coauthor Nicholas Betley, PhD, a biologist at the University of Pennsylvania. 

Variations in the gut microbiome could help explain the “runner’s high” that some people have in a long-distance race. The research could also help promote weight training or sports participation. 

“Imagine if a sports team could optimally motivate the athletes on the team to exercise,” said Dr. Betley. The lab is investigating the microbiome’s impact on high-intensity interval training.

Signals from the gut to the brain could be affecting body processes in other ways too, the researchers speculated. 

“There are so many possibilities for how these signals may change physiology and impact health,” Dr. Betley said. “A new set of studies may well establish a whole new branch of exercise physiology.”

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

Could gut health be behind a person’s motivation – or lack thereof – to exercise?

Researchers at the University of Pennsylvania, Philadelphia recently explored this topic when they wanted to find out why some lab mice seem to love their exercise wheel, while others mostly ignore it.

To start, the researchers used a machine-learning algorithm to look for biological traits that could explain the differences in activity levels among mice. And what they found surprised them: Genetics seemed to have little to do with it, but differences in gut bacteria appeared to matter more. A handful of studies backed that up: Thriving gut microbiomes have been linked with optimal muscle function in mice.

Sure enough, when the researchers dosed mice with broad-spectrum antibiotics, killing off their gut bacteria, the distance the rodents were able to run dropped by half. But off the antibiotics, the mice mostly regained their previous performance levels.

The findings, published in the journal Nature, suggest that the gut microbiome may help regulate the desire to exercise. 

If confirmed in humans, this hypothesis could help explain why so many Americans fail to get the recommended amount of physical activity. Some may blame lack of time, energy, or interest. But perhaps the reason could come down to the trillions of microbes living in their gut. 

This line of research could also lead to microbiome-based ways to get sedentary people off the couch or optimize athletic performance.  

But how could one’s microbiome impact the motivation to move? To find the answer, the researchers zeroed in on the brain. 
 

The gut-brain connection

After treating the mice with antibiotics, the researchers sequenced RNA in the rodents’ striatum (the part of the brain responsible for motivation). They found reduced gene expression in the cells’ dopamine receptors – which release the neurochemical dopamine, making one feel like they’ve accomplished something good. In other words: Mice treated with antibiotics were getting less of a dopamine hit after their run. 

“Only when we started focusing on the brain did we understand that the microbiome’s effect on exercise capacity was mediated by the central and peripheral nervous systems,” said study author Christoph Thaiss, PhD, a microbiologist at the University of Pennsylvania. “This realization completely changed the trajectory of the project.”

To find out how, exactly, bacteria in the colon were signaling the brain, the researchers performed a series of experiments over several years. They identified two types of bacteria, Eubacterium rectale and Coprococcus eutactus. These strains produce compounds called fatty acid amides that interact with endocannabinoid receptors in the gut. 

Those endocannabinoid receptors signal the brain to cut back its production of monoamine oxidase, the compound that breaks down dopamine. With less of this dopamine-clearing compound in the brain, more dopamine could build up after a long run, making the mice feel good and eager to hit the exercise wheel again soon. 

This gut-brain pathway “may have evolved to couple the initiation of prolonged physical activity to the nutritional status of the gastrointestinal tract,” Dr. Thaiss said. Gut bacteria monitor what’s in your colon and tell your brain whether you have enough food to fuel a workout. 

The colon, or gut, hosts trillions of microbes with potentially hundreds of different bacteria strains. These strains are determined by the food we eat and the environment we occupy.

“The genetic impact on the microbiome is rather minor,” Dr. Thaiss said, “but lifestyle factors strongly impact the composition of the gut microbiome.”

He hopes to develop nutritional interventions to encourage the growth of the motivating types of bacteria, the kind that make a person want to go for a 5-mile run.
 

What’s next?  

Moving forward,  the researchers need to find out whether the gut affects motivation in humans, too. To do that, they’re analyzing the gut microbiomes of people with varying levels of exercise motivation. 

“With enough samples, we could potentially correlate species of microbiota that exist in exercise-motivated individuals,” said study coauthor Nicholas Betley, PhD, a biologist at the University of Pennsylvania. 

Variations in the gut microbiome could help explain the “runner’s high” that some people have in a long-distance race. The research could also help promote weight training or sports participation. 

“Imagine if a sports team could optimally motivate the athletes on the team to exercise,” said Dr. Betley. The lab is investigating the microbiome’s impact on high-intensity interval training.

Signals from the gut to the brain could be affecting body processes in other ways too, the researchers speculated. 

“There are so many possibilities for how these signals may change physiology and impact health,” Dr. Betley said. “A new set of studies may well establish a whole new branch of exercise physiology.”

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

Changes regarding smoking, drinking, body weight, and physical activity may alter the risk for colorectal cancer (CRC), the results of a study on a large European cohort suggest.

“This is a clear message that practicing clinicians and gastroenterologists could give to their patients and to CRC screening participants to improve CRC prevention,” write Edoardo Botteri, PhD, Cancer Registry of Norway, Oslo, and colleagues in an article published in the American Journal of Gastroenterology.

Previous studies have shown a correlation between cancer in general and unhealthy lifestyle factors. They have also shown an association between weight gain and an increased risk for CRC and a reduced risk with smoking cessation. But Dr. Botteri and colleagues could not find any published research on the association of other lifestyle factors and the risk for CRC specifically, they write.

To help fill this gap, they followed 295,865 people who participated in the European Prospective Investigation into Cancer (EPIC) for a median of 7.8 years. The participants were mostly aged from 35 to 70 years and lived in Denmark, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom.

The researchers calculated a healthy lifestyle index (HLI) score on the basis of smoking status, alcohol consumption, body mass index, and physical activity. The median time between baseline and the follow-up questionnaire was 5.7 years.

They awarded points as indicated in the following table.

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

Changes regarding smoking, drinking, body weight, and physical activity may alter the risk for colorectal cancer (CRC), the results of a study on a large European cohort suggest.

“This is a clear message that practicing clinicians and gastroenterologists could give to their patients and to CRC screening participants to improve CRC prevention,” write Edoardo Botteri, PhD, Cancer Registry of Norway, Oslo, and colleagues in an article published in the American Journal of Gastroenterology.

Previous studies have shown a correlation between cancer in general and unhealthy lifestyle factors. They have also shown an association between weight gain and an increased risk for CRC and a reduced risk with smoking cessation. But Dr. Botteri and colleagues could not find any published research on the association of other lifestyle factors and the risk for CRC specifically, they write.

To help fill this gap, they followed 295,865 people who participated in the European Prospective Investigation into Cancer (EPIC) for a median of 7.8 years. The participants were mostly aged from 35 to 70 years and lived in Denmark, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom.

The researchers calculated a healthy lifestyle index (HLI) score on the basis of smoking status, alcohol consumption, body mass index, and physical activity. The median time between baseline and the follow-up questionnaire was 5.7 years.

They awarded points as indicated in the following table.

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

Changes regarding smoking, drinking, body weight, and physical activity may alter the risk for colorectal cancer (CRC), the results of a study on a large European cohort suggest.

“This is a clear message that practicing clinicians and gastroenterologists could give to their patients and to CRC screening participants to improve CRC prevention,” write Edoardo Botteri, PhD, Cancer Registry of Norway, Oslo, and colleagues in an article published in the American Journal of Gastroenterology.

Previous studies have shown a correlation between cancer in general and unhealthy lifestyle factors. They have also shown an association between weight gain and an increased risk for CRC and a reduced risk with smoking cessation. But Dr. Botteri and colleagues could not find any published research on the association of other lifestyle factors and the risk for CRC specifically, they write.

To help fill this gap, they followed 295,865 people who participated in the European Prospective Investigation into Cancer (EPIC) for a median of 7.8 years. The participants were mostly aged from 35 to 70 years and lived in Denmark, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom.

The researchers calculated a healthy lifestyle index (HLI) score on the basis of smoking status, alcohol consumption, body mass index, and physical activity. The median time between baseline and the follow-up questionnaire was 5.7 years.

They awarded points as indicated in the following table.

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

With no proven treatments for long COVID, millions of Americans struggling with debilitating symptoms may be wondering whether it’s worth it to try something they’ve never considered before: a clinical trial. 

Dozens of clinical trials nationwide are already underway or starting soon, many of which are aided by $1.5 billion in funding from the National Institutes of Health to help identify new treatments for common symptoms like brain fog, fatigue, sleep disturbances, and a hard time breathing. But it may take years for these trials to prove which drugs, devices, and behavioral therapies are safe and effective. 

“We’re not in warp speed,” said Kanecia Zimmerman, MD, a principal investigator at the Duke Clinical Research Institute in Durham, N.C., who is overseeing long COVID trials for the NIH. Operation Warp Speed – the 2020-2021 federal effort to get COVID vaccines designed, tested, authorized and distributed – benefited from existing scientific knowledge about other coronaviruses and about vaccines in general. But there’s no similar foundation of scientific knowledge about long COVID. 

“We are in a place of not really knowing anything,” Dr. Zimmerman said.

But some glimmers of hope are emerging. A Veterans Affairs study recently found the antiviral Paxlovid might help prevent long COVID. A small case study at Yale found the ADHD drug guanfacine may ease brain fog from long COVID. And preliminary results from an NIH-funded study suggest COVID vaccines might help children with a rare but serious inflammatory condition known as multisystem inflammatory syndrome (MIS-C). 

More results are expected very soon from the trial for kids with MIS-C, which can strike suddenly long after a COVID infection clears up. While the exact causes aren’t yet clear, MIS-C can cause dangerous inflammation in the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal system. 

Because the virus often triggered a delayed response of MIS-C in kids who had few if any symptoms of acute COVID-19, scientists wondered whether children infected with the virus might respond to a vaccine dose to prevent MIS-C from developing, Gary Gibbons, MD, director of the National Heart, Lung, and Blood Institute, said during a Dec. 9 presentation at the NIH. It’s not yet clear if vaccination helps, but it doesn’t harm the children, Dr. Gibbons said. 

“Indeed, the studies suggest with some relief that yes, these children could be vaccinated safely,” he said. 

Several new trials are also testing Paxlovid against long COVID, including one late-stage study that may have results in about a year. 

“We already know that Paxlovid reduces the risk of developing long COVID, but it would be a game changer if it can improve long COVID symptoms as well,” said Surendra Barshikar, MD, an associate professor and medical director of the COVID Recover program at the University of Texas Southwestern Medical Center, Dallas. 

In other studies, researchers are looking at a wide variety of previously approved and experimental drugs and devices. For example, scientists in New York are testing the mood stabilizer lithium to treat brain fog and fatigue. And researchers in Illinois are investigating efgartigimod, a drug approved for the rare muscle-weakening autoimmune disorder myasthenia gravis, to see if it helps ease a long COVID complication known as POTS that can cause a sudden rapid heart rate and chronic fatigue. 

“The good news is that enrollment will proceed quickly, given the vast number of patients,” said Kristin Englund, MD, director of the reCOVer Center of Excellence at the Cleveland Clinic. 

This is all encouraging because roughly one in five American adults who have acute COVID infections develop persistent symptoms of long COVID, also known as post–acute sequelae of SARS-CoV-2 (PASC). And many of these long COVID patients have complex, overlapping clusters of symptoms that make traditional treatment approaches largely ineffective against this new, formidable disease. 

But not every patient living with long COVID will qualify for trials or find it easy to take part even if they do. Patients should consider how severe their symptoms are, the potential risks of any experimental treatments, and the many challenges they may have with getting to and from clinical trial sites that are largely concentrated around major cities and might be far from home. 

While this holds true for any type of trial, it’s essential for long COVID patients, who may have fatigue, muscle weakness, and other symptoms that make distance an impossible factor to ignore, said Aaron Friedberg, MD, clinical colead of the post–COVID-19 recovery program at the Ohio State University Wexner Medical Center, Columbus. 

“I think it is a personal decision, since the fatigue and pain that patients with PASC can experience can make it very challenging to travel long distances,” Dr. Friedberg said. “I would recommend calling or messaging ahead to find out exactly what type of travel might be required because there may be steps that can be completed by email or video, which could make it easier to participate, and some trials may be entirely remote.”

Even when patients feel up to the travel, they still might not be a good fit for a clinical trial. Scientists often look for people who didn’t have pre-existing health problems before they got long COVID, Dr. Barshikar noted. Patients taking medications may also be unable to participate in drug trials, particularly for experimental treatments because of concerns about unknown side effects from drug interactions. 

When clinical trials do seem like a good option, patients may want to consider seeking treatment at an academic medical center that is already doing long COVID research, particularly if their symptoms are too complex or severe to manage only through their primary care provider, said Jonathan Whiteson, MD, who helped draft long COVID treatment guidelines for the American Academy of Physical Medicine and Rehabilitation. He also serves as codirector of the New York University Langone Health post–COVID care program.

Many health care professionals on the front lines treating long COVID patients are optimistic that the sheer number of trials and the vast number of patients taking part should ultimately produce some better treatment options than people have right now. It’s just not going to happen overnight. 

“I suspect that while we will see some new treatments coming in the next 1-2 years, it may be several years before targets can be identified and full trials conducted to see results,” Dr. Friedberg said. “Getting good data takes time.”

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

With no proven treatments for long COVID, millions of Americans struggling with debilitating symptoms may be wondering whether it’s worth it to try something they’ve never considered before: a clinical trial. 

Dozens of clinical trials nationwide are already underway or starting soon, many of which are aided by $1.5 billion in funding from the National Institutes of Health to help identify new treatments for common symptoms like brain fog, fatigue, sleep disturbances, and a hard time breathing. But it may take years for these trials to prove which drugs, devices, and behavioral therapies are safe and effective. 

“We’re not in warp speed,” said Kanecia Zimmerman, MD, a principal investigator at the Duke Clinical Research Institute in Durham, N.C., who is overseeing long COVID trials for the NIH. Operation Warp Speed – the 2020-2021 federal effort to get COVID vaccines designed, tested, authorized and distributed – benefited from existing scientific knowledge about other coronaviruses and about vaccines in general. But there’s no similar foundation of scientific knowledge about long COVID. 

“We are in a place of not really knowing anything,” Dr. Zimmerman said.

But some glimmers of hope are emerging. A Veterans Affairs study recently found the antiviral Paxlovid might help prevent long COVID. A small case study at Yale found the ADHD drug guanfacine may ease brain fog from long COVID. And preliminary results from an NIH-funded study suggest COVID vaccines might help children with a rare but serious inflammatory condition known as multisystem inflammatory syndrome (MIS-C). 

More results are expected very soon from the trial for kids with MIS-C, which can strike suddenly long after a COVID infection clears up. While the exact causes aren’t yet clear, MIS-C can cause dangerous inflammation in the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal system. 

Because the virus often triggered a delayed response of MIS-C in kids who had few if any symptoms of acute COVID-19, scientists wondered whether children infected with the virus might respond to a vaccine dose to prevent MIS-C from developing, Gary Gibbons, MD, director of the National Heart, Lung, and Blood Institute, said during a Dec. 9 presentation at the NIH. It’s not yet clear if vaccination helps, but it doesn’t harm the children, Dr. Gibbons said. 

“Indeed, the studies suggest with some relief that yes, these children could be vaccinated safely,” he said. 

Several new trials are also testing Paxlovid against long COVID, including one late-stage study that may have results in about a year. 

“We already know that Paxlovid reduces the risk of developing long COVID, but it would be a game changer if it can improve long COVID symptoms as well,” said Surendra Barshikar, MD, an associate professor and medical director of the COVID Recover program at the University of Texas Southwestern Medical Center, Dallas. 

In other studies, researchers are looking at a wide variety of previously approved and experimental drugs and devices. For example, scientists in New York are testing the mood stabilizer lithium to treat brain fog and fatigue. And researchers in Illinois are investigating efgartigimod, a drug approved for the rare muscle-weakening autoimmune disorder myasthenia gravis, to see if it helps ease a long COVID complication known as POTS that can cause a sudden rapid heart rate and chronic fatigue. 

“The good news is that enrollment will proceed quickly, given the vast number of patients,” said Kristin Englund, MD, director of the reCOVer Center of Excellence at the Cleveland Clinic. 

This is all encouraging because roughly one in five American adults who have acute COVID infections develop persistent symptoms of long COVID, also known as post–acute sequelae of SARS-CoV-2 (PASC). And many of these long COVID patients have complex, overlapping clusters of symptoms that make traditional treatment approaches largely ineffective against this new, formidable disease. 

But not every patient living with long COVID will qualify for trials or find it easy to take part even if they do. Patients should consider how severe their symptoms are, the potential risks of any experimental treatments, and the many challenges they may have with getting to and from clinical trial sites that are largely concentrated around major cities and might be far from home. 

While this holds true for any type of trial, it’s essential for long COVID patients, who may have fatigue, muscle weakness, and other symptoms that make distance an impossible factor to ignore, said Aaron Friedberg, MD, clinical colead of the post–COVID-19 recovery program at the Ohio State University Wexner Medical Center, Columbus. 

“I think it is a personal decision, since the fatigue and pain that patients with PASC can experience can make it very challenging to travel long distances,” Dr. Friedberg said. “I would recommend calling or messaging ahead to find out exactly what type of travel might be required because there may be steps that can be completed by email or video, which could make it easier to participate, and some trials may be entirely remote.”

Even when patients feel up to the travel, they still might not be a good fit for a clinical trial. Scientists often look for people who didn’t have pre-existing health problems before they got long COVID, Dr. Barshikar noted. Patients taking medications may also be unable to participate in drug trials, particularly for experimental treatments because of concerns about unknown side effects from drug interactions. 

When clinical trials do seem like a good option, patients may want to consider seeking treatment at an academic medical center that is already doing long COVID research, particularly if their symptoms are too complex or severe to manage only through their primary care provider, said Jonathan Whiteson, MD, who helped draft long COVID treatment guidelines for the American Academy of Physical Medicine and Rehabilitation. He also serves as codirector of the New York University Langone Health post–COVID care program.

Many health care professionals on the front lines treating long COVID patients are optimistic that the sheer number of trials and the vast number of patients taking part should ultimately produce some better treatment options than people have right now. It’s just not going to happen overnight. 

“I suspect that while we will see some new treatments coming in the next 1-2 years, it may be several years before targets can be identified and full trials conducted to see results,” Dr. Friedberg said. “Getting good data takes time.”

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

With no proven treatments for long COVID, millions of Americans struggling with debilitating symptoms may be wondering whether it’s worth it to try something they’ve never considered before: a clinical trial. 

Dozens of clinical trials nationwide are already underway or starting soon, many of which are aided by $1.5 billion in funding from the National Institutes of Health to help identify new treatments for common symptoms like brain fog, fatigue, sleep disturbances, and a hard time breathing. But it may take years for these trials to prove which drugs, devices, and behavioral therapies are safe and effective. 

“We’re not in warp speed,” said Kanecia Zimmerman, MD, a principal investigator at the Duke Clinical Research Institute in Durham, N.C., who is overseeing long COVID trials for the NIH. Operation Warp Speed – the 2020-2021 federal effort to get COVID vaccines designed, tested, authorized and distributed – benefited from existing scientific knowledge about other coronaviruses and about vaccines in general. But there’s no similar foundation of scientific knowledge about long COVID. 

“We are in a place of not really knowing anything,” Dr. Zimmerman said.

But some glimmers of hope are emerging. A Veterans Affairs study recently found the antiviral Paxlovid might help prevent long COVID. A small case study at Yale found the ADHD drug guanfacine may ease brain fog from long COVID. And preliminary results from an NIH-funded study suggest COVID vaccines might help children with a rare but serious inflammatory condition known as multisystem inflammatory syndrome (MIS-C). 

More results are expected very soon from the trial for kids with MIS-C, which can strike suddenly long after a COVID infection clears up. While the exact causes aren’t yet clear, MIS-C can cause dangerous inflammation in the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal system. 

Because the virus often triggered a delayed response of MIS-C in kids who had few if any symptoms of acute COVID-19, scientists wondered whether children infected with the virus might respond to a vaccine dose to prevent MIS-C from developing, Gary Gibbons, MD, director of the National Heart, Lung, and Blood Institute, said during a Dec. 9 presentation at the NIH. It’s not yet clear if vaccination helps, but it doesn’t harm the children, Dr. Gibbons said. 

“Indeed, the studies suggest with some relief that yes, these children could be vaccinated safely,” he said. 

Several new trials are also testing Paxlovid against long COVID, including one late-stage study that may have results in about a year. 

“We already know that Paxlovid reduces the risk of developing long COVID, but it would be a game changer if it can improve long COVID symptoms as well,” said Surendra Barshikar, MD, an associate professor and medical director of the COVID Recover program at the University of Texas Southwestern Medical Center, Dallas. 

In other studies, researchers are looking at a wide variety of previously approved and experimental drugs and devices. For example, scientists in New York are testing the mood stabilizer lithium to treat brain fog and fatigue. And researchers in Illinois are investigating efgartigimod, a drug approved for the rare muscle-weakening autoimmune disorder myasthenia gravis, to see if it helps ease a long COVID complication known as POTS that can cause a sudden rapid heart rate and chronic fatigue. 

“The good news is that enrollment will proceed quickly, given the vast number of patients,” said Kristin Englund, MD, director of the reCOVer Center of Excellence at the Cleveland Clinic. 

This is all encouraging because roughly one in five American adults who have acute COVID infections develop persistent symptoms of long COVID, also known as post–acute sequelae of SARS-CoV-2 (PASC). And many of these long COVID patients have complex, overlapping clusters of symptoms that make traditional treatment approaches largely ineffective against this new, formidable disease. 

But not every patient living with long COVID will qualify for trials or find it easy to take part even if they do. Patients should consider how severe their symptoms are, the potential risks of any experimental treatments, and the many challenges they may have with getting to and from clinical trial sites that are largely concentrated around major cities and might be far from home. 

While this holds true for any type of trial, it’s essential for long COVID patients, who may have fatigue, muscle weakness, and other symptoms that make distance an impossible factor to ignore, said Aaron Friedberg, MD, clinical colead of the post–COVID-19 recovery program at the Ohio State University Wexner Medical Center, Columbus. 

“I think it is a personal decision, since the fatigue and pain that patients with PASC can experience can make it very challenging to travel long distances,” Dr. Friedberg said. “I would recommend calling or messaging ahead to find out exactly what type of travel might be required because there may be steps that can be completed by email or video, which could make it easier to participate, and some trials may be entirely remote.”

Even when patients feel up to the travel, they still might not be a good fit for a clinical trial. Scientists often look for people who didn’t have pre-existing health problems before they got long COVID, Dr. Barshikar noted. Patients taking medications may also be unable to participate in drug trials, particularly for experimental treatments because of concerns about unknown side effects from drug interactions. 

When clinical trials do seem like a good option, patients may want to consider seeking treatment at an academic medical center that is already doing long COVID research, particularly if their symptoms are too complex or severe to manage only through their primary care provider, said Jonathan Whiteson, MD, who helped draft long COVID treatment guidelines for the American Academy of Physical Medicine and Rehabilitation. He also serves as codirector of the New York University Langone Health post–COVID care program.

Many health care professionals on the front lines treating long COVID patients are optimistic that the sheer number of trials and the vast number of patients taking part should ultimately produce some better treatment options than people have right now. It’s just not going to happen overnight. 

“I suspect that while we will see some new treatments coming in the next 1-2 years, it may be several years before targets can be identified and full trials conducted to see results,” Dr. Friedberg said. “Getting good data takes time.”

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

We wish you a merry Christmas and a happy heart failure

Does anyone really like it when places of business send out cards or messages for the holidays? A card from a truly small family business is one thing, but when you start getting emails from multibillion dollar corporations, it feels a bit dishonest. And that’s not even mentioning the potential blowback when things go wrong.

Petr Kratochvil

Now, you may wonder how a company could possibly mess up something so simple. “We wish you a merry Christmas and a happy New Year.” Not that difficult. Unless you’re Askern Medical Practice in Doncaster, England. Instead of expressing a simple expression of joy for the holiday season, Askern informed all 8,000 of its patients that they had aggressive lung cancer with metastases and they needed to fill out a DS1500 form, which entitles terminal patients to certain benefits.

It only took an hour for Askern to recognize its mistake and send a second text apologizing and adding in the appropriate season’s greetings, but obviously the damage was done. Presumably patients who were last at the doctor to have their cold treated were able to shrug off the text, or simply didn’t see it before the correction came through, but obviously many patients had concerns directly related to cancer and panicked. They called in but were by and large unable to reach anyone at the practice. Some patients close by even went to center itself to clear things up.

One patient, Mr. Carl Chegwin, raised an excellent point about the debacle: “What if that message was meant for someone, and then they are told it’s a Christmas message, then again told, ‘Oh no, that was actually meant for you?’ ” The old double backtrack into yes, you actually do have cancer has got to be a candidate for worst Christmas gift of all. Yes, even worse than socks.
 

Genes know it: You are when you eat

There’s been a lot of recent research on intermittent fasting and what it can and can’t do for one’s health. Much of it has focused on participants’ metabolic rates, but a study just published in Cell Metabolism shows how time-restricted feeding (TRF) has an impact on gene expression, the process through which genes are activated and respond to their environment by creating proteins.

Salk Institute

The research conducted by Satchidananda Panda, PhD, of the Salk Institute and his team involved two groups of mice, one with free access to food and the other with a daily 9-hour feeding window. Analysis of tissue samples collected from 22 organ groups revealed that nearly 80% of mouse genes responded to TRF. Interestingly, 40% of the genes in the hypothalamus, adrenal gland, and pancreas, which handle hormone regulation, were affected, suggesting that TRF could potentially aid in diabetes and stress disorder management, the investigators said in a written statement.

The researchers also found that TRF aligned the circadian rhythms of multiple organs of the body, which brings sleep into the picture. “Time-restricted eating synchronized the circadian rhythms to have two major waves: one during fasting, and another just after eating. We suspect this allows the body to coordinate different processes,” said Dr. Panda, whose previous research looked at TRF in firefighters, who typically work on shift schedules.

Time-restricted eating, it appears, affects gene expression throughout the body and allows interconnected organ systems to work smoothly. It’s not just about eating. Go figure.
 

This group practice reduced stress for everyone

It’s been awhile since we checked in on the good folks at Maharishi International University in Fairfield, Iowa – fictional home of the Fighting Transcendentalists [MAHARISHI RULES!] – but we just have to mention their long-term effort to reduce the national stress.

Goodboy Picture Company/E+/Getty Images

Way back in the year 2000, a group from MIU began practicing transcendental meditation. The size of the group increased over the next few years and eventually reached 1,725 in 2006. That number is important because it represents the square root of 1% of the U.S. population. When that “transition threshold was achieved,” the university explained in a written statement, “all stress indicators immediately started decreasing.”

By stress indicators they mean the U.S. stress index, the mean of eight variables – murder, rape, assault, robbery, infant mortality, drug deaths, vehicle fatalities, and child deaths by injuries – that the study investigators used to track the effectiveness of the meditation program, they said in the World Journal of Social Science.

After 2011, “when the size of the group size began to decline the rate of decrease in stress slowed and then it reversed and began to increase,” MIU reported.

Coauthor Dr. Kenneth Cavanaugh of MIU explained the process: “This study used state-of-the-art methods of time series regression analysis for eliminating potential alternative explanations due to intrinsic preexisting trends and fluctuations in the data. We carefully studied potential alternative explanations in terms of changes in economic conditions, political leadership, population demographics, and policing strategies. None of these factors could account for the results.”

Since we here at LOTME are serious professional journalists, the use of quotes means we are not making this up. Here’s one more thing in quotes: “A grant for 75 million dollars from the Howard and Alice Settle Foundation provided stipends for participants to be in the group and provided funding to bring several hundred visiting [meditation] experts from India to further augment the MIU group.”

Who needs to make up stuff? Not us.

We wish you a merry Christmas and a happy heart failure

Does anyone really like it when places of business send out cards or messages for the holidays? A card from a truly small family business is one thing, but when you start getting emails from multibillion dollar corporations, it feels a bit dishonest. And that’s not even mentioning the potential blowback when things go wrong.

Petr Kratochvil

Now, you may wonder how a company could possibly mess up something so simple. “We wish you a merry Christmas and a happy New Year.” Not that difficult. Unless you’re Askern Medical Practice in Doncaster, England. Instead of expressing a simple expression of joy for the holiday season, Askern informed all 8,000 of its patients that they had aggressive lung cancer with metastases and they needed to fill out a DS1500 form, which entitles terminal patients to certain benefits.

It only took an hour for Askern to recognize its mistake and send a second text apologizing and adding in the appropriate season’s greetings, but obviously the damage was done. Presumably patients who were last at the doctor to have their cold treated were able to shrug off the text, or simply didn’t see it before the correction came through, but obviously many patients had concerns directly related to cancer and panicked. They called in but were by and large unable to reach anyone at the practice. Some patients close by even went to center itself to clear things up.

One patient, Mr. Carl Chegwin, raised an excellent point about the debacle: “What if that message was meant for someone, and then they are told it’s a Christmas message, then again told, ‘Oh no, that was actually meant for you?’ ” The old double backtrack into yes, you actually do have cancer has got to be a candidate for worst Christmas gift of all. Yes, even worse than socks.
 

Genes know it: You are when you eat

There’s been a lot of recent research on intermittent fasting and what it can and can’t do for one’s health. Much of it has focused on participants’ metabolic rates, but a study just published in Cell Metabolism shows how time-restricted feeding (TRF) has an impact on gene expression, the process through which genes are activated and respond to their environment by creating proteins.

Salk Institute

The research conducted by Satchidananda Panda, PhD, of the Salk Institute and his team involved two groups of mice, one with free access to food and the other with a daily 9-hour feeding window. Analysis of tissue samples collected from 22 organ groups revealed that nearly 80% of mouse genes responded to TRF. Interestingly, 40% of the genes in the hypothalamus, adrenal gland, and pancreas, which handle hormone regulation, were affected, suggesting that TRF could potentially aid in diabetes and stress disorder management, the investigators said in a written statement.

The researchers also found that TRF aligned the circadian rhythms of multiple organs of the body, which brings sleep into the picture. “Time-restricted eating synchronized the circadian rhythms to have two major waves: one during fasting, and another just after eating. We suspect this allows the body to coordinate different processes,” said Dr. Panda, whose previous research looked at TRF in firefighters, who typically work on shift schedules.

Time-restricted eating, it appears, affects gene expression throughout the body and allows interconnected organ systems to work smoothly. It’s not just about eating. Go figure.
 

This group practice reduced stress for everyone

It’s been awhile since we checked in on the good folks at Maharishi International University in Fairfield, Iowa – fictional home of the Fighting Transcendentalists [MAHARISHI RULES!] – but we just have to mention their long-term effort to reduce the national stress.

Goodboy Picture Company/E+/Getty Images

Way back in the year 2000, a group from MIU began practicing transcendental meditation. The size of the group increased over the next few years and eventually reached 1,725 in 2006. That number is important because it represents the square root of 1% of the U.S. population. When that “transition threshold was achieved,” the university explained in a written statement, “all stress indicators immediately started decreasing.”

By stress indicators they mean the U.S. stress index, the mean of eight variables – murder, rape, assault, robbery, infant mortality, drug deaths, vehicle fatalities, and child deaths by injuries – that the study investigators used to track the effectiveness of the meditation program, they said in the World Journal of Social Science.

After 2011, “when the size of the group size began to decline the rate of decrease in stress slowed and then it reversed and began to increase,” MIU reported.

Coauthor Dr. Kenneth Cavanaugh of MIU explained the process: “This study used state-of-the-art methods of time series regression analysis for eliminating potential alternative explanations due to intrinsic preexisting trends and fluctuations in the data. We carefully studied potential alternative explanations in terms of changes in economic conditions, political leadership, population demographics, and policing strategies. None of these factors could account for the results.”

Since we here at LOTME are serious professional journalists, the use of quotes means we are not making this up. Here’s one more thing in quotes: “A grant for 75 million dollars from the Howard and Alice Settle Foundation provided stipends for participants to be in the group and provided funding to bring several hundred visiting [meditation] experts from India to further augment the MIU group.”

Who needs to make up stuff? Not us.

We wish you a merry Christmas and a happy heart failure

Does anyone really like it when places of business send out cards or messages for the holidays? A card from a truly small family business is one thing, but when you start getting emails from multibillion dollar corporations, it feels a bit dishonest. And that’s not even mentioning the potential blowback when things go wrong.

Petr Kratochvil

Now, you may wonder how a company could possibly mess up something so simple. “We wish you a merry Christmas and a happy New Year.” Not that difficult. Unless you’re Askern Medical Practice in Doncaster, England. Instead of expressing a simple expression of joy for the holiday season, Askern informed all 8,000 of its patients that they had aggressive lung cancer with metastases and they needed to fill out a DS1500 form, which entitles terminal patients to certain benefits.

It only took an hour for Askern to recognize its mistake and send a second text apologizing and adding in the appropriate season’s greetings, but obviously the damage was done. Presumably patients who were last at the doctor to have their cold treated were able to shrug off the text, or simply didn’t see it before the correction came through, but obviously many patients had concerns directly related to cancer and panicked. They called in but were by and large unable to reach anyone at the practice. Some patients close by even went to center itself to clear things up.

One patient, Mr. Carl Chegwin, raised an excellent point about the debacle: “What if that message was meant for someone, and then they are told it’s a Christmas message, then again told, ‘Oh no, that was actually meant for you?’ ” The old double backtrack into yes, you actually do have cancer has got to be a candidate for worst Christmas gift of all. Yes, even worse than socks.
 

Genes know it: You are when you eat

There’s been a lot of recent research on intermittent fasting and what it can and can’t do for one’s health. Much of it has focused on participants’ metabolic rates, but a study just published in Cell Metabolism shows how time-restricted feeding (TRF) has an impact on gene expression, the process through which genes are activated and respond to their environment by creating proteins.

Salk Institute

The research conducted by Satchidananda Panda, PhD, of the Salk Institute and his team involved two groups of mice, one with free access to food and the other with a daily 9-hour feeding window. Analysis of tissue samples collected from 22 organ groups revealed that nearly 80% of mouse genes responded to TRF. Interestingly, 40% of the genes in the hypothalamus, adrenal gland, and pancreas, which handle hormone regulation, were affected, suggesting that TRF could potentially aid in diabetes and stress disorder management, the investigators said in a written statement.

The researchers also found that TRF aligned the circadian rhythms of multiple organs of the body, which brings sleep into the picture. “Time-restricted eating synchronized the circadian rhythms to have two major waves: one during fasting, and another just after eating. We suspect this allows the body to coordinate different processes,” said Dr. Panda, whose previous research looked at TRF in firefighters, who typically work on shift schedules.

Time-restricted eating, it appears, affects gene expression throughout the body and allows interconnected organ systems to work smoothly. It’s not just about eating. Go figure.
 

This group practice reduced stress for everyone

It’s been awhile since we checked in on the good folks at Maharishi International University in Fairfield, Iowa – fictional home of the Fighting Transcendentalists [MAHARISHI RULES!] – but we just have to mention their long-term effort to reduce the national stress.

Goodboy Picture Company/E+/Getty Images

Way back in the year 2000, a group from MIU began practicing transcendental meditation. The size of the group increased over the next few years and eventually reached 1,725 in 2006. That number is important because it represents the square root of 1% of the U.S. population. When that “transition threshold was achieved,” the university explained in a written statement, “all stress indicators immediately started decreasing.”

By stress indicators they mean the U.S. stress index, the mean of eight variables – murder, rape, assault, robbery, infant mortality, drug deaths, vehicle fatalities, and child deaths by injuries – that the study investigators used to track the effectiveness of the meditation program, they said in the World Journal of Social Science.

After 2011, “when the size of the group size began to decline the rate of decrease in stress slowed and then it reversed and began to increase,” MIU reported.

Coauthor Dr. Kenneth Cavanaugh of MIU explained the process: “This study used state-of-the-art methods of time series regression analysis for eliminating potential alternative explanations due to intrinsic preexisting trends and fluctuations in the data. We carefully studied potential alternative explanations in terms of changes in economic conditions, political leadership, population demographics, and policing strategies. None of these factors could account for the results.”

Since we here at LOTME are serious professional journalists, the use of quotes means we are not making this up. Here’s one more thing in quotes: “A grant for 75 million dollars from the Howard and Alice Settle Foundation provided stipends for participants to be in the group and provided funding to bring several hundred visiting [meditation] experts from India to further augment the MIU group.”

Who needs to make up stuff? Not us.