Megan Brooks

To address current gaps in expert guidance on newer nonstatin agents, the American College of Cardiology has issued an expert consensus decision pathway on the role of nonstatin therapies in LDL cholesterol lowering for risk reduction in atherosclerotic cardiovascular disease (ASCVD).

Since the publication of the most recent AHA/ACC cholesterol guidelines in 2018, a number of newer nonstatin medications have become available for management of lipid-associated risk, including bempedoic acid, inclisiran, evinacumab, and icosapent ethyl.

These medications were not addressed in the 2018 AHA/ACC Guideline on the Management of Blood Cholesterol.

The 53-page document – 2022 ACC Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk – was published online in the Journal of the American College of Cardiology.

The new expert consensus document provides guidance for clinicians until the next formal guidelines are produced, Donald Lloyd-Jones, MD, chair of the writing committee, told this news organization.

• In what patient populations should newer nonstatin therapies be considered?
• In what situations should newer nonstatin therapies be considered?
• If newer nonstatin therapies are to be added, which therapies should be considered and in what order to maximize patient benefit and preference?

The document provides algorithms that endorse the four evidence-based patient groups identified in the 2018 guidelines and assumes that the patient is currently taking or has attempted to take a statin, given that that is the most effective initial therapy, the writing group says.

“The algorithms have been streamlined for ease of use by clinicians to help them identify who may need adjunctive nonstatin medications, to provide thresholds for consideration of those medications, and to provide a prioritization of those medications based on the strength of available evidence of efficacy,” said Dr. Lloyd-Jones, chair of the department of preventive medicine at Northwestern University’s Feinberg School of Medicine, Chicago.

“We hope that these pathways will assist the decision-making process for clinicians and patients,” he added.

He also noted that statins remain the “most important first-line therapy for reducing ASCVD risk, because of their efficacy, safety, and low cost. However, for some patients, there are now options if statins do not fully achieve the goals for reducing ASCVD risk or if statins are not tolerated at effective doses.”

“The new expert consensus document highlights that higher-risk patients should be considered more often for adjunctive therapy and provides user-friendly decision pathways to assist in considering the reasonable choices available under different clinical scenarios,” Dr. Lloyd-Jones said.

The document has been endorsed by the National Lipid Association.

This research had no commercial funding. Dr. Lloyd-Jones has disclosed no relevant financial relationships.

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

To address current gaps in expert guidance on newer nonstatin agents, the American College of Cardiology has issued an expert consensus decision pathway on the role of nonstatin therapies in LDL cholesterol lowering for risk reduction in atherosclerotic cardiovascular disease (ASCVD).

Since the publication of the most recent AHA/ACC cholesterol guidelines in 2018, a number of newer nonstatin medications have become available for management of lipid-associated risk, including bempedoic acid, inclisiran, evinacumab, and icosapent ethyl.

These medications were not addressed in the 2018 AHA/ACC Guideline on the Management of Blood Cholesterol.

The 53-page document – 2022 ACC Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk – was published online in the Journal of the American College of Cardiology.

The new expert consensus document provides guidance for clinicians until the next formal guidelines are produced, Donald Lloyd-Jones, MD, chair of the writing committee, told this news organization.

• In what patient populations should newer nonstatin therapies be considered?
• In what situations should newer nonstatin therapies be considered?
• If newer nonstatin therapies are to be added, which therapies should be considered and in what order to maximize patient benefit and preference?

The document provides algorithms that endorse the four evidence-based patient groups identified in the 2018 guidelines and assumes that the patient is currently taking or has attempted to take a statin, given that that is the most effective initial therapy, the writing group says.

“The algorithms have been streamlined for ease of use by clinicians to help them identify who may need adjunctive nonstatin medications, to provide thresholds for consideration of those medications, and to provide a prioritization of those medications based on the strength of available evidence of efficacy,” said Dr. Lloyd-Jones, chair of the department of preventive medicine at Northwestern University’s Feinberg School of Medicine, Chicago.

“We hope that these pathways will assist the decision-making process for clinicians and patients,” he added.

He also noted that statins remain the “most important first-line therapy for reducing ASCVD risk, because of their efficacy, safety, and low cost. However, for some patients, there are now options if statins do not fully achieve the goals for reducing ASCVD risk or if statins are not tolerated at effective doses.”

“The new expert consensus document highlights that higher-risk patients should be considered more often for adjunctive therapy and provides user-friendly decision pathways to assist in considering the reasonable choices available under different clinical scenarios,” Dr. Lloyd-Jones said.

The document has been endorsed by the National Lipid Association.

This research had no commercial funding. Dr. Lloyd-Jones has disclosed no relevant financial relationships.

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

To address current gaps in expert guidance on newer nonstatin agents, the American College of Cardiology has issued an expert consensus decision pathway on the role of nonstatin therapies in LDL cholesterol lowering for risk reduction in atherosclerotic cardiovascular disease (ASCVD).

Since the publication of the most recent AHA/ACC cholesterol guidelines in 2018, a number of newer nonstatin medications have become available for management of lipid-associated risk, including bempedoic acid, inclisiran, evinacumab, and icosapent ethyl.

These medications were not addressed in the 2018 AHA/ACC Guideline on the Management of Blood Cholesterol.

The 53-page document – 2022 ACC Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk – was published online in the Journal of the American College of Cardiology.

The new expert consensus document provides guidance for clinicians until the next formal guidelines are produced, Donald Lloyd-Jones, MD, chair of the writing committee, told this news organization.

• In what patient populations should newer nonstatin therapies be considered?
• In what situations should newer nonstatin therapies be considered?
• If newer nonstatin therapies are to be added, which therapies should be considered and in what order to maximize patient benefit and preference?

The document provides algorithms that endorse the four evidence-based patient groups identified in the 2018 guidelines and assumes that the patient is currently taking or has attempted to take a statin, given that that is the most effective initial therapy, the writing group says.

“The algorithms have been streamlined for ease of use by clinicians to help them identify who may need adjunctive nonstatin medications, to provide thresholds for consideration of those medications, and to provide a prioritization of those medications based on the strength of available evidence of efficacy,” said Dr. Lloyd-Jones, chair of the department of preventive medicine at Northwestern University’s Feinberg School of Medicine, Chicago.

“We hope that these pathways will assist the decision-making process for clinicians and patients,” he added.

He also noted that statins remain the “most important first-line therapy for reducing ASCVD risk, because of their efficacy, safety, and low cost. However, for some patients, there are now options if statins do not fully achieve the goals for reducing ASCVD risk or if statins are not tolerated at effective doses.”

“The new expert consensus document highlights that higher-risk patients should be considered more often for adjunctive therapy and provides user-friendly decision pathways to assist in considering the reasonable choices available under different clinical scenarios,” Dr. Lloyd-Jones said.

The document has been endorsed by the National Lipid Association.

This research had no commercial funding. Dr. Lloyd-Jones has disclosed no relevant financial relationships.

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

Psilocybin paired with psychotherapy is associated with a robust and sustained decrease in drinking among adults with alcohol use disorder (AUD), new research suggests.

Results from the first randomized, placebo-controlled trial of psilocybin for alcohol dependence showed that during the 8 months after first treatment dose, participants who received psilocybin had less than half as many heavy drinking days as their counterparts who received placebo.

In addition, 7 months after the last dose of medication, twice as many psilocybin-treated patients as placebo-treated patients were abstinent.

The effects observed with psilocybin were “considerably larger” than those of currently approved treatments for AUD, senior investigator Michael Bogenschutz, MD, psychiatrist and director of the NYU Langone Center for Psychedelic Medicine, New York, said during an Aug. 24 press briefing.

If the findings hold up in future trials, psilocybin will be a “real breakthrough” in the treatment of the condition, Dr. Bogenschutz said.

The findings were published online in JAMA Psychiatry.

83% reduction in drinking days

The study included 93 adults (mean age, 46 years) with alcohol dependence who consumed an average of seven drinks on the days they drank and had had at least four heavy drinking days during the month prior to treatment.

Of the participants, 48 were randomly assigned to receive two doses of psilocybin, and 45 were assigned to receive an antihistamine (diphenhydramine) placebo. Study medication was administered during 2 day-long sessions at week 4 and week 8.

The participants also received 12 psychotherapy sessions over a 12-week period. All were assessed at intervals from the beginning of the study until 32 weeks after the first medication session.

The primary outcome was percentage of days in which the patient drank heavily during the 32-week period following first medication dose. Heavy drinking was defined as having five or more drinks in a day for a man and four or more drinks in a day for a woman.

The percentage of heavy drinking days during the 32-week period was 9.7% for the psilocybin group and 23.6% for the placebo group, for a mean difference of 13.9% (P = .01).

“Compared to their baseline before the study, after receiving medication, the psilocybin group decreased their heavy drinking days by 83%, while the placebo group reduced their heavy drinking by 51%,” Dr. Bogenschutz reported.

During the last month of follow-up, which was 7 months after the final dose of study medication, 48% of the psilocybin group were entirely abstinent vs. 24% of the placebo group.

“It is remarkable that the effects of psilocybin treatment persisted for 7 months after people received the last dose of medication. This suggests that psilocybin is treating the underlying disorder of alcohol addiction rather than merely treating symptoms,” Dr. Bogenschutz noted.

Total alcohol consumption and problems related to alcohol use were also significantly less in the psilocybin group.

‘Encouraged and hopeful’

Adverse events related to psilocybin were mostly mild, self-limiting, and consistent with other recent trials that evaluated the drug’s effects in various conditions.

However, the current investigators note that they implemented measures to ensure safety, including careful medical and psychiatric screening, therapy, and monitoring that was provided by well-trained therapists, including a licensed psychiatrist. In addition, medications were available to treat acute psychiatric reactions.

A cited limitation of the study was that blinding was not maintained because the average intensity of experience with psilocybin was high, whereas it was low with diphenhydramine.

This difference undermined the masking of treatment such that more than 90% of participants and therapists correctly guessed the treatment assignment.

Another limitation was that objective measures to validate self-reported drinking outcomes were available for only 54% of study participants.

Despite these limitations, the study builds on earlier work by the NYU team that showed that two doses of psilocybin taken over a period of 8 weeks significantly reduced alcohol use and cravings in patients with AUD.

“We’re very encouraged by these findings and hopeful about where they could lead. Personally, it’s been very meaningful and rewarding for me to do this work and inspiring to witness the remarkable recoveries that some of our participants have experienced,” Dr. Bogenschutz told briefing attendees.

Urgent need

The authors of an accompanying editorial note that novel medications for alcohol dependence are “sorely needed. Recent renewed interest in the potential of hallucinogens for treating psychiatric disorders, including AUD, represents a potential move in that direction.”

Henry Kranzler, MD, and Emily Hartwell, PhD, both with the Center for Studies of Addiction, University of Pennsylvania, Philadelphia, write that the new findings “underscore the potential of developing psilocybin as an addition to the alcohol treatment pharmacopeia.”

They question, however, the feasibility of using hallucinogens in routine clinical practice because intensive psychotherapy, such as that provided in this study, requires a significant investment of time and labor.

“Such concomitant therapy, if necessary to realize the therapeutic benefits of psilocybin for treating AUD, could limit its uptake by clinicians,” Dr. Kranzler and Dr. Hartwell write.

The study was funded by the Heffter Research Institute and by individual donations from Carey and Claudia Turnbull, Dr. Efrem Nulman, Rodrigo Niño, and Cody Swift. Dr. Bogenschutz reports having received research funds from and serving as a consultant to Mind Medicine, the Multidisciplinary Association for Psychedelic Studies, B. More, AJNA Labs, Beckley Psytech, Journey Colab, and Bright Minds Biosciences. Dr. Kranzler and Dr. Hartwell have reported no relevant financial relationships.

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

Psilocybin paired with psychotherapy is associated with a robust and sustained decrease in drinking among adults with alcohol use disorder (AUD), new research suggests.

Results from the first randomized, placebo-controlled trial of psilocybin for alcohol dependence showed that during the 8 months after first treatment dose, participants who received psilocybin had less than half as many heavy drinking days as their counterparts who received placebo.

In addition, 7 months after the last dose of medication, twice as many psilocybin-treated patients as placebo-treated patients were abstinent.

The effects observed with psilocybin were “considerably larger” than those of currently approved treatments for AUD, senior investigator Michael Bogenschutz, MD, psychiatrist and director of the NYU Langone Center for Psychedelic Medicine, New York, said during an Aug. 24 press briefing.

If the findings hold up in future trials, psilocybin will be a “real breakthrough” in the treatment of the condition, Dr. Bogenschutz said.

The findings were published online in JAMA Psychiatry.

83% reduction in drinking days

The study included 93 adults (mean age, 46 years) with alcohol dependence who consumed an average of seven drinks on the days they drank and had had at least four heavy drinking days during the month prior to treatment.

Of the participants, 48 were randomly assigned to receive two doses of psilocybin, and 45 were assigned to receive an antihistamine (diphenhydramine) placebo. Study medication was administered during 2 day-long sessions at week 4 and week 8.

The participants also received 12 psychotherapy sessions over a 12-week period. All were assessed at intervals from the beginning of the study until 32 weeks after the first medication session.

The primary outcome was percentage of days in which the patient drank heavily during the 32-week period following first medication dose. Heavy drinking was defined as having five or more drinks in a day for a man and four or more drinks in a day for a woman.

The percentage of heavy drinking days during the 32-week period was 9.7% for the psilocybin group and 23.6% for the placebo group, for a mean difference of 13.9% (P = .01).

“Compared to their baseline before the study, after receiving medication, the psilocybin group decreased their heavy drinking days by 83%, while the placebo group reduced their heavy drinking by 51%,” Dr. Bogenschutz reported.

During the last month of follow-up, which was 7 months after the final dose of study medication, 48% of the psilocybin group were entirely abstinent vs. 24% of the placebo group.

“It is remarkable that the effects of psilocybin treatment persisted for 7 months after people received the last dose of medication. This suggests that psilocybin is treating the underlying disorder of alcohol addiction rather than merely treating symptoms,” Dr. Bogenschutz noted.

Total alcohol consumption and problems related to alcohol use were also significantly less in the psilocybin group.

‘Encouraged and hopeful’

Adverse events related to psilocybin were mostly mild, self-limiting, and consistent with other recent trials that evaluated the drug’s effects in various conditions.

However, the current investigators note that they implemented measures to ensure safety, including careful medical and psychiatric screening, therapy, and monitoring that was provided by well-trained therapists, including a licensed psychiatrist. In addition, medications were available to treat acute psychiatric reactions.

A cited limitation of the study was that blinding was not maintained because the average intensity of experience with psilocybin was high, whereas it was low with diphenhydramine.

This difference undermined the masking of treatment such that more than 90% of participants and therapists correctly guessed the treatment assignment.

Another limitation was that objective measures to validate self-reported drinking outcomes were available for only 54% of study participants.

Despite these limitations, the study builds on earlier work by the NYU team that showed that two doses of psilocybin taken over a period of 8 weeks significantly reduced alcohol use and cravings in patients with AUD.

“We’re very encouraged by these findings and hopeful about where they could lead. Personally, it’s been very meaningful and rewarding for me to do this work and inspiring to witness the remarkable recoveries that some of our participants have experienced,” Dr. Bogenschutz told briefing attendees.

Urgent need

The authors of an accompanying editorial note that novel medications for alcohol dependence are “sorely needed. Recent renewed interest in the potential of hallucinogens for treating psychiatric disorders, including AUD, represents a potential move in that direction.”

Henry Kranzler, MD, and Emily Hartwell, PhD, both with the Center for Studies of Addiction, University of Pennsylvania, Philadelphia, write that the new findings “underscore the potential of developing psilocybin as an addition to the alcohol treatment pharmacopeia.”

They question, however, the feasibility of using hallucinogens in routine clinical practice because intensive psychotherapy, such as that provided in this study, requires a significant investment of time and labor.

“Such concomitant therapy, if necessary to realize the therapeutic benefits of psilocybin for treating AUD, could limit its uptake by clinicians,” Dr. Kranzler and Dr. Hartwell write.

The study was funded by the Heffter Research Institute and by individual donations from Carey and Claudia Turnbull, Dr. Efrem Nulman, Rodrigo Niño, and Cody Swift. Dr. Bogenschutz reports having received research funds from and serving as a consultant to Mind Medicine, the Multidisciplinary Association for Psychedelic Studies, B. More, AJNA Labs, Beckley Psytech, Journey Colab, and Bright Minds Biosciences. Dr. Kranzler and Dr. Hartwell have reported no relevant financial relationships.

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

Psilocybin paired with psychotherapy is associated with a robust and sustained decrease in drinking among adults with alcohol use disorder (AUD), new research suggests.

Results from the first randomized, placebo-controlled trial of psilocybin for alcohol dependence showed that during the 8 months after first treatment dose, participants who received psilocybin had less than half as many heavy drinking days as their counterparts who received placebo.

In addition, 7 months after the last dose of medication, twice as many psilocybin-treated patients as placebo-treated patients were abstinent.

The effects observed with psilocybin were “considerably larger” than those of currently approved treatments for AUD, senior investigator Michael Bogenschutz, MD, psychiatrist and director of the NYU Langone Center for Psychedelic Medicine, New York, said during an Aug. 24 press briefing.

If the findings hold up in future trials, psilocybin will be a “real breakthrough” in the treatment of the condition, Dr. Bogenschutz said.

The findings were published online in JAMA Psychiatry.

83% reduction in drinking days

The study included 93 adults (mean age, 46 years) with alcohol dependence who consumed an average of seven drinks on the days they drank and had had at least four heavy drinking days during the month prior to treatment.

Of the participants, 48 were randomly assigned to receive two doses of psilocybin, and 45 were assigned to receive an antihistamine (diphenhydramine) placebo. Study medication was administered during 2 day-long sessions at week 4 and week 8.

The participants also received 12 psychotherapy sessions over a 12-week period. All were assessed at intervals from the beginning of the study until 32 weeks after the first medication session.

The primary outcome was percentage of days in which the patient drank heavily during the 32-week period following first medication dose. Heavy drinking was defined as having five or more drinks in a day for a man and four or more drinks in a day for a woman.

The percentage of heavy drinking days during the 32-week period was 9.7% for the psilocybin group and 23.6% for the placebo group, for a mean difference of 13.9% (P = .01).

“Compared to their baseline before the study, after receiving medication, the psilocybin group decreased their heavy drinking days by 83%, while the placebo group reduced their heavy drinking by 51%,” Dr. Bogenschutz reported.

During the last month of follow-up, which was 7 months after the final dose of study medication, 48% of the psilocybin group were entirely abstinent vs. 24% of the placebo group.

“It is remarkable that the effects of psilocybin treatment persisted for 7 months after people received the last dose of medication. This suggests that psilocybin is treating the underlying disorder of alcohol addiction rather than merely treating symptoms,” Dr. Bogenschutz noted.

Total alcohol consumption and problems related to alcohol use were also significantly less in the psilocybin group.

‘Encouraged and hopeful’

Adverse events related to psilocybin were mostly mild, self-limiting, and consistent with other recent trials that evaluated the drug’s effects in various conditions.

However, the current investigators note that they implemented measures to ensure safety, including careful medical and psychiatric screening, therapy, and monitoring that was provided by well-trained therapists, including a licensed psychiatrist. In addition, medications were available to treat acute psychiatric reactions.

A cited limitation of the study was that blinding was not maintained because the average intensity of experience with psilocybin was high, whereas it was low with diphenhydramine.

This difference undermined the masking of treatment such that more than 90% of participants and therapists correctly guessed the treatment assignment.

Another limitation was that objective measures to validate self-reported drinking outcomes were available for only 54% of study participants.

Despite these limitations, the study builds on earlier work by the NYU team that showed that two doses of psilocybin taken over a period of 8 weeks significantly reduced alcohol use and cravings in patients with AUD.

“We’re very encouraged by these findings and hopeful about where they could lead. Personally, it’s been very meaningful and rewarding for me to do this work and inspiring to witness the remarkable recoveries that some of our participants have experienced,” Dr. Bogenschutz told briefing attendees.

Urgent need

The authors of an accompanying editorial note that novel medications for alcohol dependence are “sorely needed. Recent renewed interest in the potential of hallucinogens for treating psychiatric disorders, including AUD, represents a potential move in that direction.”

Henry Kranzler, MD, and Emily Hartwell, PhD, both with the Center for Studies of Addiction, University of Pennsylvania, Philadelphia, write that the new findings “underscore the potential of developing psilocybin as an addition to the alcohol treatment pharmacopeia.”

They question, however, the feasibility of using hallucinogens in routine clinical practice because intensive psychotherapy, such as that provided in this study, requires a significant investment of time and labor.

“Such concomitant therapy, if necessary to realize the therapeutic benefits of psilocybin for treating AUD, could limit its uptake by clinicians,” Dr. Kranzler and Dr. Hartwell write.

The study was funded by the Heffter Research Institute and by individual donations from Carey and Claudia Turnbull, Dr. Efrem Nulman, Rodrigo Niño, and Cody Swift. Dr. Bogenschutz reports having received research funds from and serving as a consultant to Mind Medicine, the Multidisciplinary Association for Psychedelic Studies, B. More, AJNA Labs, Beckley Psytech, Journey Colab, and Bright Minds Biosciences. Dr. Kranzler and Dr. Hartwell have reported no relevant financial relationships.

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

Two biomarkers present in blood measured on the day of traumatic brain injury (TBI) can accurately predict a patient’s risk for death or severe disability 6 months later, new research suggests.

In new data from the TRACK-TBI study group, high levels of glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) proteins found in glial cells and neurons, respectively, correlated with death and severe injury. Investigators note that measuring these biomarkers may give a more accurate assessment of a patient’s prognosis following TBI.

This study is the “first report of the accuracy of a blood test that can be obtained rapidly on the day of injury to predict neurological recovery at 6 months after injury,” lead author Frederick Korley, MD, PhD, associate professor of emergency medicine at the University of Michigan, Ann Arbor, said in a news release.

The findings were published online in the Lancet Neurology.
 

Added value

The researchers measured GFAP and UCH-L1 in blood samples taken from 1,696 patients with TBI on the day of their injury, and they assessed patient recovery 6 months later.

The markers were measured using the i-STAT TBI Plasma test (Abbott Labs). The test was approved in 2021 by the U.S. Food and Drug Administration to determine which patients with mild TBI should undergo computed tomography scans.

About two-thirds of the study population were men, and the average age was 39 years. All patients were evaluated at Level I trauma centers for injuries caused primarily by traffic accidents or falls.

Six months following injury, 7% of the patients had died and 14% had an unfavorable outcome, ranging from vegetative state to severe disability requiring daily support. In addition, 67% had incomplete recovery, ranging from moderate disabilities requiring assistance outside of the home to minor disabling neurological or psychological deficits.

Day-of-injury GFAP and UCH-L1 levels had a high probability of predicting death (87% for GFAP and 89% for UCH-L1) and severe disability (86% for both GFAP and UCH-L1) at 6 months, the investigators reported.

The biomarkers were less accurate in predicting incomplete recovery (62% for GFAP and 61% for UCH-L1).

The researchers also assessed the added value of combining the blood biomarkers to current TBI prognostic models that take into account variables such as age, motor score, pupil reactivity, and CT characteristics.

In patients with a Glasgow Coma Scale (GCS) score of 3-12, adding GFAP and UCH-L1 alone or combined to each of the three International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) models significantly increased their accuracy for predicting death (range, 90%-94%) and unfavorable outcome (range, 83%-89%).

In patients with milder TBI (GCS score, 13-15), adding GFAP and UCH-L1 to the UPFRONT prognostic model modestly increased accuracy for predicting incomplete recovery (69%).
 

‘Important’ findings

Commenting on the study, Cyrus A. Raji, MD, PhD, assistant professor of radiology and neurology, Washington University, St. Louis, said this “critical” study shows that these biomarkers can “predict key outcomes,” including mortality and severe disability. “Thus, in conjunction with clinical evaluations and related data such as neuroimaging, these tests may warrant translation to broader clinical practice, particularly in acute settings,” said Dr. Raji, who was not involved in the research.

Also weighing in, Heidi Fusco, MD, assistant director of the traumatic brain injury program at NYU Langone Rusk Rehabilitation, said the findings are “important.”

“Prognosis after brain injury often is based on the initial presentation, ongoing clinical exams, and neuroimaging; and the addition of biomarkers would contribute to creating a more objective prognostic model,” Dr. Fusco said.

She noted “it’s unclear” whether clinical hospital laboratories would be able to accommodate this type of laboratory drawing.

“It is imperative that clinicians still use the patient history [and] clinical and radiological exam when making clinical decisions for a patient and not just lab values. It would be best to incorporate the GFAP and UCH-L1 into a preexisting prognostic model,” Dr. Fusco said.

The study was funded by the U.S. National Institutes of Health, the National Institute of Neurologic Disorders and Stroke, the U.S. Department of Defense, One Mind, and U.S. Army Medical Research and Development Command. Dr. Korley reported having previously consulted for Abbott Laboratories and has received research funding from Abbott Laboratories, which makes the assays used in the study. Dr. Raji is a consultant for Brainreader ApS and Neurevolution. Dr. Fusco has reported no relevant financial relationships.

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

Two biomarkers present in blood measured on the day of traumatic brain injury (TBI) can accurately predict a patient’s risk for death or severe disability 6 months later, new research suggests.

In new data from the TRACK-TBI study group, high levels of glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) proteins found in glial cells and neurons, respectively, correlated with death and severe injury. Investigators note that measuring these biomarkers may give a more accurate assessment of a patient’s prognosis following TBI.

This study is the “first report of the accuracy of a blood test that can be obtained rapidly on the day of injury to predict neurological recovery at 6 months after injury,” lead author Frederick Korley, MD, PhD, associate professor of emergency medicine at the University of Michigan, Ann Arbor, said in a news release.

The findings were published online in the Lancet Neurology.
 

Added value

The researchers measured GFAP and UCH-L1 in blood samples taken from 1,696 patients with TBI on the day of their injury, and they assessed patient recovery 6 months later.

The markers were measured using the i-STAT TBI Plasma test (Abbott Labs). The test was approved in 2021 by the U.S. Food and Drug Administration to determine which patients with mild TBI should undergo computed tomography scans.

About two-thirds of the study population were men, and the average age was 39 years. All patients were evaluated at Level I trauma centers for injuries caused primarily by traffic accidents or falls.

Six months following injury, 7% of the patients had died and 14% had an unfavorable outcome, ranging from vegetative state to severe disability requiring daily support. In addition, 67% had incomplete recovery, ranging from moderate disabilities requiring assistance outside of the home to minor disabling neurological or psychological deficits.

Day-of-injury GFAP and UCH-L1 levels had a high probability of predicting death (87% for GFAP and 89% for UCH-L1) and severe disability (86% for both GFAP and UCH-L1) at 6 months, the investigators reported.

The biomarkers were less accurate in predicting incomplete recovery (62% for GFAP and 61% for UCH-L1).

The researchers also assessed the added value of combining the blood biomarkers to current TBI prognostic models that take into account variables such as age, motor score, pupil reactivity, and CT characteristics.

In patients with a Glasgow Coma Scale (GCS) score of 3-12, adding GFAP and UCH-L1 alone or combined to each of the three International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) models significantly increased their accuracy for predicting death (range, 90%-94%) and unfavorable outcome (range, 83%-89%).

In patients with milder TBI (GCS score, 13-15), adding GFAP and UCH-L1 to the UPFRONT prognostic model modestly increased accuracy for predicting incomplete recovery (69%).
 

‘Important’ findings

Commenting on the study, Cyrus A. Raji, MD, PhD, assistant professor of radiology and neurology, Washington University, St. Louis, said this “critical” study shows that these biomarkers can “predict key outcomes,” including mortality and severe disability. “Thus, in conjunction with clinical evaluations and related data such as neuroimaging, these tests may warrant translation to broader clinical practice, particularly in acute settings,” said Dr. Raji, who was not involved in the research.

Also weighing in, Heidi Fusco, MD, assistant director of the traumatic brain injury program at NYU Langone Rusk Rehabilitation, said the findings are “important.”

“Prognosis after brain injury often is based on the initial presentation, ongoing clinical exams, and neuroimaging; and the addition of biomarkers would contribute to creating a more objective prognostic model,” Dr. Fusco said.

She noted “it’s unclear” whether clinical hospital laboratories would be able to accommodate this type of laboratory drawing.

“It is imperative that clinicians still use the patient history [and] clinical and radiological exam when making clinical decisions for a patient and not just lab values. It would be best to incorporate the GFAP and UCH-L1 into a preexisting prognostic model,” Dr. Fusco said.

The study was funded by the U.S. National Institutes of Health, the National Institute of Neurologic Disorders and Stroke, the U.S. Department of Defense, One Mind, and U.S. Army Medical Research and Development Command. Dr. Korley reported having previously consulted for Abbott Laboratories and has received research funding from Abbott Laboratories, which makes the assays used in the study. Dr. Raji is a consultant for Brainreader ApS and Neurevolution. Dr. Fusco has reported no relevant financial relationships.

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

Two biomarkers present in blood measured on the day of traumatic brain injury (TBI) can accurately predict a patient’s risk for death or severe disability 6 months later, new research suggests.

In new data from the TRACK-TBI study group, high levels of glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) proteins found in glial cells and neurons, respectively, correlated with death and severe injury. Investigators note that measuring these biomarkers may give a more accurate assessment of a patient’s prognosis following TBI.

This study is the “first report of the accuracy of a blood test that can be obtained rapidly on the day of injury to predict neurological recovery at 6 months after injury,” lead author Frederick Korley, MD, PhD, associate professor of emergency medicine at the University of Michigan, Ann Arbor, said in a news release.

The findings were published online in the Lancet Neurology.
 

Added value

The researchers measured GFAP and UCH-L1 in blood samples taken from 1,696 patients with TBI on the day of their injury, and they assessed patient recovery 6 months later.

The markers were measured using the i-STAT TBI Plasma test (Abbott Labs). The test was approved in 2021 by the U.S. Food and Drug Administration to determine which patients with mild TBI should undergo computed tomography scans.

About two-thirds of the study population were men, and the average age was 39 years. All patients were evaluated at Level I trauma centers for injuries caused primarily by traffic accidents or falls.

Six months following injury, 7% of the patients had died and 14% had an unfavorable outcome, ranging from vegetative state to severe disability requiring daily support. In addition, 67% had incomplete recovery, ranging from moderate disabilities requiring assistance outside of the home to minor disabling neurological or psychological deficits.

Day-of-injury GFAP and UCH-L1 levels had a high probability of predicting death (87% for GFAP and 89% for UCH-L1) and severe disability (86% for both GFAP and UCH-L1) at 6 months, the investigators reported.

The biomarkers were less accurate in predicting incomplete recovery (62% for GFAP and 61% for UCH-L1).

The researchers also assessed the added value of combining the blood biomarkers to current TBI prognostic models that take into account variables such as age, motor score, pupil reactivity, and CT characteristics.

In patients with a Glasgow Coma Scale (GCS) score of 3-12, adding GFAP and UCH-L1 alone or combined to each of the three International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) models significantly increased their accuracy for predicting death (range, 90%-94%) and unfavorable outcome (range, 83%-89%).

In patients with milder TBI (GCS score, 13-15), adding GFAP and UCH-L1 to the UPFRONT prognostic model modestly increased accuracy for predicting incomplete recovery (69%).
 

‘Important’ findings

Commenting on the study, Cyrus A. Raji, MD, PhD, assistant professor of radiology and neurology, Washington University, St. Louis, said this “critical” study shows that these biomarkers can “predict key outcomes,” including mortality and severe disability. “Thus, in conjunction with clinical evaluations and related data such as neuroimaging, these tests may warrant translation to broader clinical practice, particularly in acute settings,” said Dr. Raji, who was not involved in the research.

Also weighing in, Heidi Fusco, MD, assistant director of the traumatic brain injury program at NYU Langone Rusk Rehabilitation, said the findings are “important.”

“Prognosis after brain injury often is based on the initial presentation, ongoing clinical exams, and neuroimaging; and the addition of biomarkers would contribute to creating a more objective prognostic model,” Dr. Fusco said.

She noted “it’s unclear” whether clinical hospital laboratories would be able to accommodate this type of laboratory drawing.

“It is imperative that clinicians still use the patient history [and] clinical and radiological exam when making clinical decisions for a patient and not just lab values. It would be best to incorporate the GFAP and UCH-L1 into a preexisting prognostic model,” Dr. Fusco said.

The study was funded by the U.S. National Institutes of Health, the National Institute of Neurologic Disorders and Stroke, the U.S. Department of Defense, One Mind, and U.S. Army Medical Research and Development Command. Dr. Korley reported having previously consulted for Abbott Laboratories and has received research funding from Abbott Laboratories, which makes the assays used in the study. Dr. Raji is a consultant for Brainreader ApS and Neurevolution. Dr. Fusco has reported no relevant financial relationships.

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

Use of the epidermal growth-factor receptor inhibitor erlotinib led to about a 30% reduction in duodenal polyp burden after 6 months of once-weekly treatment for patients with familial adenomatous polyposis (FAP) in a phase 2 clinical trial.

“If existing data are confirmed and extended through future research, this strategy has the potential for substantial impact on clinical practice by decreasing, delaying, or augmenting endoscopic and surgical interventions as the mainstay for duodenal cancer prevention in this high-risk patient population,” the study team says.

FAP is a rare genetic condition that markedly raises the risk for colorectal polyps and cancer.

“The biological pathway that leads to the development of polyps and colon cancer in patients with FAP is the same biological pathway as patients in the general population,” study investigator Niloy Jewel Samadder, MD, with the Mayo Clinic, Rochester, Minn., said in a news release.

“Our trial looked at opportunities to use chemoprevention agents in patients with FAP to inhibit the development of precancerous polyps in the small bowel and colorectum,” Dr. Samadder explains.

In an earlier study, the researchers found that the combination of the COX-2 inhibitor sulindac (150 mg twice daily) and erlotinib (75 mg daily) reduced duodenal polyp burden.

However, the dual-drug strategy was associated with a relatively high adverse event (AE) rate, which may limit use of the combination for chemoprevention, as reported previously.

This phase 2 study tested whether erlotinib’s AE profile would be improved with a once-weekly dosing schedule while still reducing polyp burden.

The study was first published online in the journal Gut.

In the single-arm, multicenter study, 46 adults with FAP (mean age, 44 years; 48% women) self-administered 350 mg of erlotinib by mouth one time per week for 6 months. All but four participants completed the 6-month study.

After 6 months of weekly erlotinib, duodenal polyp burden was significantly reduced, with a mean percent reduction of 29.6% (95% confidence interval: –39.6% to –19.7%; P < .0001).

The benefit was observed in patients with either Spigelman 2 or Spigelman 3 duodenal polyp burden.

“Though only 12% of patients noted a decrease in Spigelman stage from 3 to 2 associated with therapy, the majority of patients (86%) had stable disease while on treatment,” the study team reports.

GI polyp number (a secondary outcome) was also decreased after 6 months of treatment with erlotinib (median decrease of 30.8%; P = .0256).

While once-weekly erlotinib was “generally” well tolerated, grade 2 or 3 AEs were reported in 72% of patients; two suffered grade 3 toxicity. Nonetheless, the AE rate was significantly more than the expected null hypothesis rate of 50%, the study team states.

Four patients withdrew from the study because of drug-induced AEs, which included grade 3 rash acneiform, grade 2 infections (hand, foot, and mouth disease), grade 1 fatigue, and grade 1 rash acneiform. No grade 4 AEs were reported.

The most common AE was an erlotinib-induced acneiform-like rash, which occurred in 56.5% of study patients. The rash was managed with topical cortisone and/or clindamycin. Additional erlotinib-induced AEs included oral mucositis (6.5%), diarrhea (50%), and nausea (26.1%).

Summing up, Dr. Samadder and colleagues note that FAP “portends a heritable, systemic predisposition to cancer, and the ultimate goal of cancer preventive intervention is to interrupt the development of neoplasia, need for surgery, and ultimately death from cancer, with an acceptable AE profile.”

The findings from this phase 2 trial support further study of erlotinib as “an effective, acceptable cancer preventive agent for FAP-associated gastrointestinal polyposis,” they conclude.

The study was sponsored by the National Cancer Institute. Dr. Samadder is a consultant for Janssen Research and Development, Recursion Pharmaceuticals, and Cancer Prevention Pharmaceuticals.

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

Use of the epidermal growth-factor receptor inhibitor erlotinib led to about a 30% reduction in duodenal polyp burden after 6 months of once-weekly treatment for patients with familial adenomatous polyposis (FAP) in a phase 2 clinical trial.

“If existing data are confirmed and extended through future research, this strategy has the potential for substantial impact on clinical practice by decreasing, delaying, or augmenting endoscopic and surgical interventions as the mainstay for duodenal cancer prevention in this high-risk patient population,” the study team says.

FAP is a rare genetic condition that markedly raises the risk for colorectal polyps and cancer.

“The biological pathway that leads to the development of polyps and colon cancer in patients with FAP is the same biological pathway as patients in the general population,” study investigator Niloy Jewel Samadder, MD, with the Mayo Clinic, Rochester, Minn., said in a news release.

“Our trial looked at opportunities to use chemoprevention agents in patients with FAP to inhibit the development of precancerous polyps in the small bowel and colorectum,” Dr. Samadder explains.

In an earlier study, the researchers found that the combination of the COX-2 inhibitor sulindac (150 mg twice daily) and erlotinib (75 mg daily) reduced duodenal polyp burden.

However, the dual-drug strategy was associated with a relatively high adverse event (AE) rate, which may limit use of the combination for chemoprevention, as reported previously.

This phase 2 study tested whether erlotinib’s AE profile would be improved with a once-weekly dosing schedule while still reducing polyp burden.

The study was first published online in the journal Gut.

In the single-arm, multicenter study, 46 adults with FAP (mean age, 44 years; 48% women) self-administered 350 mg of erlotinib by mouth one time per week for 6 months. All but four participants completed the 6-month study.

After 6 months of weekly erlotinib, duodenal polyp burden was significantly reduced, with a mean percent reduction of 29.6% (95% confidence interval: –39.6% to –19.7%; P < .0001).

The benefit was observed in patients with either Spigelman 2 or Spigelman 3 duodenal polyp burden.

“Though only 12% of patients noted a decrease in Spigelman stage from 3 to 2 associated with therapy, the majority of patients (86%) had stable disease while on treatment,” the study team reports.

GI polyp number (a secondary outcome) was also decreased after 6 months of treatment with erlotinib (median decrease of 30.8%; P = .0256).

While once-weekly erlotinib was “generally” well tolerated, grade 2 or 3 AEs were reported in 72% of patients; two suffered grade 3 toxicity. Nonetheless, the AE rate was significantly more than the expected null hypothesis rate of 50%, the study team states.

Four patients withdrew from the study because of drug-induced AEs, which included grade 3 rash acneiform, grade 2 infections (hand, foot, and mouth disease), grade 1 fatigue, and grade 1 rash acneiform. No grade 4 AEs were reported.

The most common AE was an erlotinib-induced acneiform-like rash, which occurred in 56.5% of study patients. The rash was managed with topical cortisone and/or clindamycin. Additional erlotinib-induced AEs included oral mucositis (6.5%), diarrhea (50%), and nausea (26.1%).

Summing up, Dr. Samadder and colleagues note that FAP “portends a heritable, systemic predisposition to cancer, and the ultimate goal of cancer preventive intervention is to interrupt the development of neoplasia, need for surgery, and ultimately death from cancer, with an acceptable AE profile.”

The findings from this phase 2 trial support further study of erlotinib as “an effective, acceptable cancer preventive agent for FAP-associated gastrointestinal polyposis,” they conclude.

The study was sponsored by the National Cancer Institute. Dr. Samadder is a consultant for Janssen Research and Development, Recursion Pharmaceuticals, and Cancer Prevention Pharmaceuticals.

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

Use of the epidermal growth-factor receptor inhibitor erlotinib led to about a 30% reduction in duodenal polyp burden after 6 months of once-weekly treatment for patients with familial adenomatous polyposis (FAP) in a phase 2 clinical trial.

“If existing data are confirmed and extended through future research, this strategy has the potential for substantial impact on clinical practice by decreasing, delaying, or augmenting endoscopic and surgical interventions as the mainstay for duodenal cancer prevention in this high-risk patient population,” the study team says.

FAP is a rare genetic condition that markedly raises the risk for colorectal polyps and cancer.

“The biological pathway that leads to the development of polyps and colon cancer in patients with FAP is the same biological pathway as patients in the general population,” study investigator Niloy Jewel Samadder, MD, with the Mayo Clinic, Rochester, Minn., said in a news release.

“Our trial looked at opportunities to use chemoprevention agents in patients with FAP to inhibit the development of precancerous polyps in the small bowel and colorectum,” Dr. Samadder explains.

In an earlier study, the researchers found that the combination of the COX-2 inhibitor sulindac (150 mg twice daily) and erlotinib (75 mg daily) reduced duodenal polyp burden.

However, the dual-drug strategy was associated with a relatively high adverse event (AE) rate, which may limit use of the combination for chemoprevention, as reported previously.

This phase 2 study tested whether erlotinib’s AE profile would be improved with a once-weekly dosing schedule while still reducing polyp burden.

The study was first published online in the journal Gut.

In the single-arm, multicenter study, 46 adults with FAP (mean age, 44 years; 48% women) self-administered 350 mg of erlotinib by mouth one time per week for 6 months. All but four participants completed the 6-month study.

After 6 months of weekly erlotinib, duodenal polyp burden was significantly reduced, with a mean percent reduction of 29.6% (95% confidence interval: –39.6% to –19.7%; P < .0001).

The benefit was observed in patients with either Spigelman 2 or Spigelman 3 duodenal polyp burden.

“Though only 12% of patients noted a decrease in Spigelman stage from 3 to 2 associated with therapy, the majority of patients (86%) had stable disease while on treatment,” the study team reports.

GI polyp number (a secondary outcome) was also decreased after 6 months of treatment with erlotinib (median decrease of 30.8%; P = .0256).

While once-weekly erlotinib was “generally” well tolerated, grade 2 or 3 AEs were reported in 72% of patients; two suffered grade 3 toxicity. Nonetheless, the AE rate was significantly more than the expected null hypothesis rate of 50%, the study team states.

Four patients withdrew from the study because of drug-induced AEs, which included grade 3 rash acneiform, grade 2 infections (hand, foot, and mouth disease), grade 1 fatigue, and grade 1 rash acneiform. No grade 4 AEs were reported.

The most common AE was an erlotinib-induced acneiform-like rash, which occurred in 56.5% of study patients. The rash was managed with topical cortisone and/or clindamycin. Additional erlotinib-induced AEs included oral mucositis (6.5%), diarrhea (50%), and nausea (26.1%).

Summing up, Dr. Samadder and colleagues note that FAP “portends a heritable, systemic predisposition to cancer, and the ultimate goal of cancer preventive intervention is to interrupt the development of neoplasia, need for surgery, and ultimately death from cancer, with an acceptable AE profile.”

The findings from this phase 2 trial support further study of erlotinib as “an effective, acceptable cancer preventive agent for FAP-associated gastrointestinal polyposis,” they conclude.

The study was sponsored by the National Cancer Institute. Dr. Samadder is a consultant for Janssen Research and Development, Recursion Pharmaceuticals, and Cancer Prevention Pharmaceuticals.

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

More than half of patients with mild traumatic brain injury (TBI) and a negative head CT scan have not recovered completely 6 months after sustaining their injury, new data from the TRACK-TBI study shows.

“Seeing that more than half of the GCS [Glasgow Coma Score] 15, CT-negative TBI cohort in our study were not back to their preinjury baseline at 6 months was surprising and impacts the millions of Americans who suffer from concussions annually,” said lead author Debbie Madhok, MD, with department of emergency medicine, University of California, San Francisco.

“These results highlight the importance of improving care pathways for concussion, particularly from the emergency department,” Dr. Madhok said.

The findings were published online in JAMA Network Open.

The short- and long-term outcomes in the large group of patients who come into the ED with TBI, a GCS of 15, and without acute intracranial traumatic injury (defined as a negative head CT scan) remain poorly understood, the investigators noted. To investigate further, they evaluated outcomes at 2 weeks and 6 months in 991 of these patients (mean age, 38 years; 64% men) from the TRACK-TBI study.

Among the 751 (76%) participants followed up at 2 weeks after the injury, only 204 (27%) had functional recovery – with a Glasgow Outcome Scale-Extended (GOS-E) score of 8. The remaining 547 (73%) had incomplete recovery (GOS-E scores < 8).

Among the 659 patients (66%) followed up at 6 months after the injury, 287 (44%) had functional recovery and 372 (56%) had incomplete recovery.

Most patients who failed to recover completely reported they had not returned to their preinjury life (88%). They described trouble returning to social activities outside the home and disruptions in family relationships and friendships.

The researchers noted that the study population had a high rate of preinjury psychiatric comorbidities, and these patients were more likely to have incomplete recovery than those without psychiatric comorbidities. This aligns with results from previous studies, they added.

The investigators also noted that patients with mild TBI without acute intracranial trauma are typically managed by ED personnel.

“These findings highlight the importance of ED clinicians being aware of the risk of incomplete recovery for patients with a mild TBI (that is, GCS score of 15 and negative head CT scan) and providing accurate education and timely referral information before ED discharge,” they wrote.

The study was funded by grants from the National Foundation of Emergency Medicine, the National Institute of Neurological Disorders and Stroke, and the U.S. Department of Defense Traumatic Brain Injury Endpoints Development Initiative. Dr. Madhok has reported no relevant financial relationships.

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

More than half of patients with mild traumatic brain injury (TBI) and a negative head CT scan have not recovered completely 6 months after sustaining their injury, new data from the TRACK-TBI study shows.

“Seeing that more than half of the GCS [Glasgow Coma Score] 15, CT-negative TBI cohort in our study were not back to their preinjury baseline at 6 months was surprising and impacts the millions of Americans who suffer from concussions annually,” said lead author Debbie Madhok, MD, with department of emergency medicine, University of California, San Francisco.

“These results highlight the importance of improving care pathways for concussion, particularly from the emergency department,” Dr. Madhok said.

The findings were published online in JAMA Network Open.

The short- and long-term outcomes in the large group of patients who come into the ED with TBI, a GCS of 15, and without acute intracranial traumatic injury (defined as a negative head CT scan) remain poorly understood, the investigators noted. To investigate further, they evaluated outcomes at 2 weeks and 6 months in 991 of these patients (mean age, 38 years; 64% men) from the TRACK-TBI study.

Among the 751 (76%) participants followed up at 2 weeks after the injury, only 204 (27%) had functional recovery – with a Glasgow Outcome Scale-Extended (GOS-E) score of 8. The remaining 547 (73%) had incomplete recovery (GOS-E scores < 8).

Among the 659 patients (66%) followed up at 6 months after the injury, 287 (44%) had functional recovery and 372 (56%) had incomplete recovery.

Most patients who failed to recover completely reported they had not returned to their preinjury life (88%). They described trouble returning to social activities outside the home and disruptions in family relationships and friendships.

The researchers noted that the study population had a high rate of preinjury psychiatric comorbidities, and these patients were more likely to have incomplete recovery than those without psychiatric comorbidities. This aligns with results from previous studies, they added.

The investigators also noted that patients with mild TBI without acute intracranial trauma are typically managed by ED personnel.

“These findings highlight the importance of ED clinicians being aware of the risk of incomplete recovery for patients with a mild TBI (that is, GCS score of 15 and negative head CT scan) and providing accurate education and timely referral information before ED discharge,” they wrote.

The study was funded by grants from the National Foundation of Emergency Medicine, the National Institute of Neurological Disorders and Stroke, and the U.S. Department of Defense Traumatic Brain Injury Endpoints Development Initiative. Dr. Madhok has reported no relevant financial relationships.

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

More than half of patients with mild traumatic brain injury (TBI) and a negative head CT scan have not recovered completely 6 months after sustaining their injury, new data from the TRACK-TBI study shows.

“Seeing that more than half of the GCS [Glasgow Coma Score] 15, CT-negative TBI cohort in our study were not back to their preinjury baseline at 6 months was surprising and impacts the millions of Americans who suffer from concussions annually,” said lead author Debbie Madhok, MD, with department of emergency medicine, University of California, San Francisco.

“These results highlight the importance of improving care pathways for concussion, particularly from the emergency department,” Dr. Madhok said.

The findings were published online in JAMA Network Open.

The short- and long-term outcomes in the large group of patients who come into the ED with TBI, a GCS of 15, and without acute intracranial traumatic injury (defined as a negative head CT scan) remain poorly understood, the investigators noted. To investigate further, they evaluated outcomes at 2 weeks and 6 months in 991 of these patients (mean age, 38 years; 64% men) from the TRACK-TBI study.

Among the 751 (76%) participants followed up at 2 weeks after the injury, only 204 (27%) had functional recovery – with a Glasgow Outcome Scale-Extended (GOS-E) score of 8. The remaining 547 (73%) had incomplete recovery (GOS-E scores < 8).

Among the 659 patients (66%) followed up at 6 months after the injury, 287 (44%) had functional recovery and 372 (56%) had incomplete recovery.

Most patients who failed to recover completely reported they had not returned to their preinjury life (88%). They described trouble returning to social activities outside the home and disruptions in family relationships and friendships.

The researchers noted that the study population had a high rate of preinjury psychiatric comorbidities, and these patients were more likely to have incomplete recovery than those without psychiatric comorbidities. This aligns with results from previous studies, they added.

The investigators also noted that patients with mild TBI without acute intracranial trauma are typically managed by ED personnel.

“These findings highlight the importance of ED clinicians being aware of the risk of incomplete recovery for patients with a mild TBI (that is, GCS score of 15 and negative head CT scan) and providing accurate education and timely referral information before ED discharge,” they wrote.

The study was funded by grants from the National Foundation of Emergency Medicine, the National Institute of Neurological Disorders and Stroke, and the U.S. Department of Defense Traumatic Brain Injury Endpoints Development Initiative. Dr. Madhok has reported no relevant financial relationships.

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

New research suggests that regular physical activity can help lower the risk of COVID-19 infection and its severity, with a weekly tally of 150 minutes of moderate, or 75 minutes of vigorous, physical activity affording the best protection.

“Our findings highlight the protective effects of engaging in sufficient physical activity as a public health strategy, with potential benefits to reduce the risk of severe COVID-19,” say Antonio García-Hermoso, PhD, Public University of Navarra, Pamplona, Spain, and colleagues.

“Regular physical activity seemed to be related to a lower risk of COVID-19 infection, Dr. García-Hermoso said in an interview. “There is evidence that regular physical activity might contribute to a more effective immune response, providing enhanced protective immunity to infections, which could explain the relationship between exercise consistency with COVID-19 infection.”

Regular exercise may also help to boost the body’s anti-inflammatory responses, as well as cardiorespiratory and muscular fitness, all of which may explain its beneficial effects on COVID-19 severity, the researchers say.

The study was published online in the British Journal of Sports Medicine.
 

Strong protection from COVID?

A growing body of evidence suggests that increased physical activity may modulate the course of COVID-19 infection and reduce the risk of poor outcomes. The new analysis is the first to systematically evaluate and pool data on the effect of regular physical activity on COVID-19 outcomes.

The findings are based on data from 16 studies with over 1.8 million adults (53% women, mean age 53 years).

Individuals who included regular physical activity in their weekly routine had an 11% lower risk for infection with SARS-CoV-2 (hazard ratio, 0.89; 95% confidence interval, 0.84-0.95), compared with inactive peers.

The physically active adults also had a 36% (HR, 0.64; 95% CI, 0.54-0.76) lower risk of being hospitalized, a 44% (HR, 0.66; 95% CI, 0.58-0.77) lower risk for severe COVID-19 illness, and a 43% (HR, 0.57; 95% CI, 0.46-0.71) lower risk of dying from COVID-19 than their inactive peers.

The greatest protective effect occurs with achieving at least 500 metabolic equivalent of task (MET) minutes per week of physical activity – equivalent to 150 minutes of moderate-intensity or 75 min of vigorous-intensity physical activity per week – with no added benefit beyond this level.

The researchers caution that the analysis included observational studies, differing study designs, subjective assessments of physical activity levels, and concerned only the Beta and Delta variants of SARS-CoV-2, not Omicron.

Despite these limitations, the researchers say their findings “may help guide physicians and health care policymakers in making recommendations and developing guidelines with respect to the degree of physical activity that can help reduce the risk of infectivity, hospitalization, severity, and mortality of COVID-19 at both the individual and the population level, especially in high-risk patients.”
 

Helpful, but not a panacea

Reached for comment, Sean Heffron, MD, a preventive cardiologist and assistant professor of medicine at NYU Langone Health, New York, said the study “supports the well-established nonlinear association of increasing physical activity with adverse outcomes from a diverse array of diseases, including infectious diseases, such as COVID-19.”

The observation is not particularly surprising, he said.

“It is as I would suspect. They compiled data from a large number of studies published over the past several years that all had consistent findings,” Dr. Heffron said.

“The take-away from a public health standpoint is that being physically active improves health in myriad ways. That being said, it is not a panacea, so additional measures (masking, vaccinations, etc.) are important for everyone,” he said.

Also weighing in, Joseph Herrera, DO, chair of the department of rehabilitation for Mount Sinai Health System, New York, said, “If you are physically fit, your body is more resilient and better prepared to handle the stressors of COVID or any other disease process.”

For now, however, the question of whether physical fitness is actually protective against COVID remains unclear. “I’m just not sure right now,” Dr. Herrera said in an interview.

He said he has treated athletes in professional sports – including the National Football League and Major League Baseball – and some of them have had long COVID and have not returned to play. “These are athletes at the peak of fitness and their career.”

Nonetheless, Dr. Herrera said a good public health message in general is to stay fit or get fit.

“That’s something I preach all the time,” he told this news organization.

Dr. García-Hermoso agreed. “In contrast to the vast majority of drugs, exercise is free of adverse effects. It’s time to consider exercise as medicine. It’s never too late to start being physically active.”

The study had no specific funding. Dr. García-Hermoso, Dr. Heffron, and Dr. Herrera have reported no relevant financial relationships.

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

New research suggests that regular physical activity can help lower the risk of COVID-19 infection and its severity, with a weekly tally of 150 minutes of moderate, or 75 minutes of vigorous, physical activity affording the best protection.

“Our findings highlight the protective effects of engaging in sufficient physical activity as a public health strategy, with potential benefits to reduce the risk of severe COVID-19,” say Antonio García-Hermoso, PhD, Public University of Navarra, Pamplona, Spain, and colleagues.

“Regular physical activity seemed to be related to a lower risk of COVID-19 infection, Dr. García-Hermoso said in an interview. “There is evidence that regular physical activity might contribute to a more effective immune response, providing enhanced protective immunity to infections, which could explain the relationship between exercise consistency with COVID-19 infection.”

Regular exercise may also help to boost the body’s anti-inflammatory responses, as well as cardiorespiratory and muscular fitness, all of which may explain its beneficial effects on COVID-19 severity, the researchers say.

The study was published online in the British Journal of Sports Medicine.
 

Strong protection from COVID?

A growing body of evidence suggests that increased physical activity may modulate the course of COVID-19 infection and reduce the risk of poor outcomes. The new analysis is the first to systematically evaluate and pool data on the effect of regular physical activity on COVID-19 outcomes.

The findings are based on data from 16 studies with over 1.8 million adults (53% women, mean age 53 years).

Individuals who included regular physical activity in their weekly routine had an 11% lower risk for infection with SARS-CoV-2 (hazard ratio, 0.89; 95% confidence interval, 0.84-0.95), compared with inactive peers.

The physically active adults also had a 36% (HR, 0.64; 95% CI, 0.54-0.76) lower risk of being hospitalized, a 44% (HR, 0.66; 95% CI, 0.58-0.77) lower risk for severe COVID-19 illness, and a 43% (HR, 0.57; 95% CI, 0.46-0.71) lower risk of dying from COVID-19 than their inactive peers.

The greatest protective effect occurs with achieving at least 500 metabolic equivalent of task (MET) minutes per week of physical activity – equivalent to 150 minutes of moderate-intensity or 75 min of vigorous-intensity physical activity per week – with no added benefit beyond this level.

The researchers caution that the analysis included observational studies, differing study designs, subjective assessments of physical activity levels, and concerned only the Beta and Delta variants of SARS-CoV-2, not Omicron.

Despite these limitations, the researchers say their findings “may help guide physicians and health care policymakers in making recommendations and developing guidelines with respect to the degree of physical activity that can help reduce the risk of infectivity, hospitalization, severity, and mortality of COVID-19 at both the individual and the population level, especially in high-risk patients.”
 

Helpful, but not a panacea

Reached for comment, Sean Heffron, MD, a preventive cardiologist and assistant professor of medicine at NYU Langone Health, New York, said the study “supports the well-established nonlinear association of increasing physical activity with adverse outcomes from a diverse array of diseases, including infectious diseases, such as COVID-19.”

The observation is not particularly surprising, he said.

“It is as I would suspect. They compiled data from a large number of studies published over the past several years that all had consistent findings,” Dr. Heffron said.

“The take-away from a public health standpoint is that being physically active improves health in myriad ways. That being said, it is not a panacea, so additional measures (masking, vaccinations, etc.) are important for everyone,” he said.

Also weighing in, Joseph Herrera, DO, chair of the department of rehabilitation for Mount Sinai Health System, New York, said, “If you are physically fit, your body is more resilient and better prepared to handle the stressors of COVID or any other disease process.”

For now, however, the question of whether physical fitness is actually protective against COVID remains unclear. “I’m just not sure right now,” Dr. Herrera said in an interview.

He said he has treated athletes in professional sports – including the National Football League and Major League Baseball – and some of them have had long COVID and have not returned to play. “These are athletes at the peak of fitness and their career.”

Nonetheless, Dr. Herrera said a good public health message in general is to stay fit or get fit.

“That’s something I preach all the time,” he told this news organization.

Dr. García-Hermoso agreed. “In contrast to the vast majority of drugs, exercise is free of adverse effects. It’s time to consider exercise as medicine. It’s never too late to start being physically active.”

The study had no specific funding. Dr. García-Hermoso, Dr. Heffron, and Dr. Herrera have reported no relevant financial relationships.

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

New research suggests that regular physical activity can help lower the risk of COVID-19 infection and its severity, with a weekly tally of 150 minutes of moderate, or 75 minutes of vigorous, physical activity affording the best protection.

“Our findings highlight the protective effects of engaging in sufficient physical activity as a public health strategy, with potential benefits to reduce the risk of severe COVID-19,” say Antonio García-Hermoso, PhD, Public University of Navarra, Pamplona, Spain, and colleagues.

“Regular physical activity seemed to be related to a lower risk of COVID-19 infection, Dr. García-Hermoso said in an interview. “There is evidence that regular physical activity might contribute to a more effective immune response, providing enhanced protective immunity to infections, which could explain the relationship between exercise consistency with COVID-19 infection.”

Regular exercise may also help to boost the body’s anti-inflammatory responses, as well as cardiorespiratory and muscular fitness, all of which may explain its beneficial effects on COVID-19 severity, the researchers say.

The study was published online in the British Journal of Sports Medicine.
 

Strong protection from COVID?

A growing body of evidence suggests that increased physical activity may modulate the course of COVID-19 infection and reduce the risk of poor outcomes. The new analysis is the first to systematically evaluate and pool data on the effect of regular physical activity on COVID-19 outcomes.

The findings are based on data from 16 studies with over 1.8 million adults (53% women, mean age 53 years).

Individuals who included regular physical activity in their weekly routine had an 11% lower risk for infection with SARS-CoV-2 (hazard ratio, 0.89; 95% confidence interval, 0.84-0.95), compared with inactive peers.

The physically active adults also had a 36% (HR, 0.64; 95% CI, 0.54-0.76) lower risk of being hospitalized, a 44% (HR, 0.66; 95% CI, 0.58-0.77) lower risk for severe COVID-19 illness, and a 43% (HR, 0.57; 95% CI, 0.46-0.71) lower risk of dying from COVID-19 than their inactive peers.

The greatest protective effect occurs with achieving at least 500 metabolic equivalent of task (MET) minutes per week of physical activity – equivalent to 150 minutes of moderate-intensity or 75 min of vigorous-intensity physical activity per week – with no added benefit beyond this level.

The researchers caution that the analysis included observational studies, differing study designs, subjective assessments of physical activity levels, and concerned only the Beta and Delta variants of SARS-CoV-2, not Omicron.

Despite these limitations, the researchers say their findings “may help guide physicians and health care policymakers in making recommendations and developing guidelines with respect to the degree of physical activity that can help reduce the risk of infectivity, hospitalization, severity, and mortality of COVID-19 at both the individual and the population level, especially in high-risk patients.”
 

Helpful, but not a panacea

Reached for comment, Sean Heffron, MD, a preventive cardiologist and assistant professor of medicine at NYU Langone Health, New York, said the study “supports the well-established nonlinear association of increasing physical activity with adverse outcomes from a diverse array of diseases, including infectious diseases, such as COVID-19.”

The observation is not particularly surprising, he said.

“It is as I would suspect. They compiled data from a large number of studies published over the past several years that all had consistent findings,” Dr. Heffron said.

“The take-away from a public health standpoint is that being physically active improves health in myriad ways. That being said, it is not a panacea, so additional measures (masking, vaccinations, etc.) are important for everyone,” he said.

Also weighing in, Joseph Herrera, DO, chair of the department of rehabilitation for Mount Sinai Health System, New York, said, “If you are physically fit, your body is more resilient and better prepared to handle the stressors of COVID or any other disease process.”

For now, however, the question of whether physical fitness is actually protective against COVID remains unclear. “I’m just not sure right now,” Dr. Herrera said in an interview.

He said he has treated athletes in professional sports – including the National Football League and Major League Baseball – and some of them have had long COVID and have not returned to play. “These are athletes at the peak of fitness and their career.”

Nonetheless, Dr. Herrera said a good public health message in general is to stay fit or get fit.

“That’s something I preach all the time,” he told this news organization.

Dr. García-Hermoso agreed. “In contrast to the vast majority of drugs, exercise is free of adverse effects. It’s time to consider exercise as medicine. It’s never too late to start being physically active.”

The study had no specific funding. Dr. García-Hermoso, Dr. Heffron, and Dr. Herrera have reported no relevant financial relationships.

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

The Food and Drug Administration has approved Abbott Laboratories’ new Proclaim Plus spinal cord stimulation (SCS) system featuring FlexBurst360 therapy for the treatment of patients with chronic pain, the company announced Aug. 23.

The “next generation” of its proprietary BurstDR stimulation, FlexBurst360 therapy, provides pain coverage across up to six areas of the trunk and limbs, with programming that can be adjusted as a patient’s individual therapeutic needs evolve, the manufacturer noted.

“Using FlexBurst360 therapy on the Proclaim Plus system, physicians can identify the lowest effective dose of stimulation for each patient and adapt it based on evolving pain needs,” the company said in a news release.

The system also has therapy settings accessed with a mobile device.

Through their mobile devices, patients can access the manufacturer’s NeuroSphere Virtual Clinic, which allows them to communicate with their providers and receive remote adjustments to their therapeutic settings as needed.
 

Game changer?

The newly approved system has a battery life of up to 10 years, akin to the company’s Proclaim XR neurostimulation system for chronic pain. As reported at the time by this news organization, that system was approved by the FDA in 2019.

More than 50 million people in the United States experience chronic pain and most have pain in more than one area of the body. Steven Falowski, MD, with Argires Marotti Neurosurgical Associates of Lancaster, Pa., noted in the release that spinal cord stimulation has provided “tremendous relief” for patients with chronic pain.

Dr. Falowski added that “with its ability to mimic natural patterns found in the brain, the Abbott BurstDR platform has been a game changer” for these patients.

“However, despite the many benefits of BurstDR, such as being effective as a low-energy stimulation therapy, some patients continue to be burdened ... because of multiple painful areas and evolving pain,” he said.

“Now, with Proclaim Plus and FlexBurst360, an already established platform has been improved to treat more patients who suffer from pain across different body parts and changing pain over time,” said Dr. Falowski.

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

The Food and Drug Administration has approved Abbott Laboratories’ new Proclaim Plus spinal cord stimulation (SCS) system featuring FlexBurst360 therapy for the treatment of patients with chronic pain, the company announced Aug. 23.

The “next generation” of its proprietary BurstDR stimulation, FlexBurst360 therapy, provides pain coverage across up to six areas of the trunk and limbs, with programming that can be adjusted as a patient’s individual therapeutic needs evolve, the manufacturer noted.

“Using FlexBurst360 therapy on the Proclaim Plus system, physicians can identify the lowest effective dose of stimulation for each patient and adapt it based on evolving pain needs,” the company said in a news release.

The system also has therapy settings accessed with a mobile device.

Through their mobile devices, patients can access the manufacturer’s NeuroSphere Virtual Clinic, which allows them to communicate with their providers and receive remote adjustments to their therapeutic settings as needed.
 

Game changer?

The newly approved system has a battery life of up to 10 years, akin to the company’s Proclaim XR neurostimulation system for chronic pain. As reported at the time by this news organization, that system was approved by the FDA in 2019.

More than 50 million people in the United States experience chronic pain and most have pain in more than one area of the body. Steven Falowski, MD, with Argires Marotti Neurosurgical Associates of Lancaster, Pa., noted in the release that spinal cord stimulation has provided “tremendous relief” for patients with chronic pain.

Dr. Falowski added that “with its ability to mimic natural patterns found in the brain, the Abbott BurstDR platform has been a game changer” for these patients.

“However, despite the many benefits of BurstDR, such as being effective as a low-energy stimulation therapy, some patients continue to be burdened ... because of multiple painful areas and evolving pain,” he said.

“Now, with Proclaim Plus and FlexBurst360, an already established platform has been improved to treat more patients who suffer from pain across different body parts and changing pain over time,” said Dr. Falowski.

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

The Food and Drug Administration has approved Abbott Laboratories’ new Proclaim Plus spinal cord stimulation (SCS) system featuring FlexBurst360 therapy for the treatment of patients with chronic pain, the company announced Aug. 23.

The “next generation” of its proprietary BurstDR stimulation, FlexBurst360 therapy, provides pain coverage across up to six areas of the trunk and limbs, with programming that can be adjusted as a patient’s individual therapeutic needs evolve, the manufacturer noted.

“Using FlexBurst360 therapy on the Proclaim Plus system, physicians can identify the lowest effective dose of stimulation for each patient and adapt it based on evolving pain needs,” the company said in a news release.

The system also has therapy settings accessed with a mobile device.

Through their mobile devices, patients can access the manufacturer’s NeuroSphere Virtual Clinic, which allows them to communicate with their providers and receive remote adjustments to their therapeutic settings as needed.
 

Game changer?

The newly approved system has a battery life of up to 10 years, akin to the company’s Proclaim XR neurostimulation system for chronic pain. As reported at the time by this news organization, that system was approved by the FDA in 2019.

More than 50 million people in the United States experience chronic pain and most have pain in more than one area of the body. Steven Falowski, MD, with Argires Marotti Neurosurgical Associates of Lancaster, Pa., noted in the release that spinal cord stimulation has provided “tremendous relief” for patients with chronic pain.

Dr. Falowski added that “with its ability to mimic natural patterns found in the brain, the Abbott BurstDR platform has been a game changer” for these patients.

“However, despite the many benefits of BurstDR, such as being effective as a low-energy stimulation therapy, some patients continue to be burdened ... because of multiple painful areas and evolving pain,” he said.

“Now, with Proclaim Plus and FlexBurst360, an already established platform has been improved to treat more patients who suffer from pain across different body parts and changing pain over time,” said Dr. Falowski.

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

New research discounts the long-held notion that aspartame and other nonnutritive sweeteners (NNS) have no effect on the human body.

Researchers found that these sugar substitutes are not metabolically inert and can alter the gut microbiome in a way that can influence blood glucose levels.

The study was published online in the journal Cell.


 

Gut reaction?

Several years ago, a team led by Eran Elinav, MD, PhD, an immunologist and microbiome researcher at the Weizmann Institute of Science, Rehovot, Israel, observed that these sweeteners affect the microbiome of mice in ways that could affect glycemic responses.

They have now confirmed this observation in a randomized controlled trial with 120 healthy adults.

BigRedCurlyGuy/Thinkstock

Weighing the evidence

Several experts weighed in on the results in a statement from the U.K. nonprofit organization, Science Media Centre.

Duane Mellor, PhD, RD, RNutr, registered dietitian and senior teaching fellow, Aston University, Birmingham, England, notes that the study does not show a link between all NNS and higher blood glucose levels in the long term (only after a glucose tolerance test).

“It did suggest, though, that some individuals who do not normally consume sweeteners may not tolerate glucose as well after consuming six sachets of either saccharin or sucralose mixed with glucose per day,” Dr. Mellor says.

Kim Barrett, PhD, distinguished professor of physiology and membrane biology, University of California, Davis, concurs, saying “this well-designed study indicates the potential for NNS to have adverse effects in at least some individuals.”

The study also does not provide any information about how people who normally consume sweeteners or people with either type 1 or type 2 diabetes respond to NNS.

“Therefore, for some people, it is likely to be a better option and more sustainable approach to use sweeteners as a ‘stepping stone’ allowing them to reduce the amount of added sugar in foods and drinks, to reduce their sugar intake and still enjoy what they eat and drink, on the way to reducing both added sugar and sweeteners in their diet,” Dr. Mellor suggests.

Kevin McConway, PhD, with the Open University, Milton Keynes, England, said it’s “important to understand that the research is not saying that these sweeteners are worse for us, in heath terms, than sugar.

“But exactly what the health consequences of all this, if any, might be is a subject for future research,” Dr. McConway added.

Kathy Redfern, PhD, lecturer in human nutrition, University of Plymouth (England) agrees.

“We still have a lot to learn about the human microbiome, and although this study suggests two of the sweeteners tested in this study (sucralose and saccharin) significantly affected glucose tolerance, these deviations were small,” she says.

The International Sweeteners Association also weighs in, saying, “No conclusions about the effects of low/no calorie sweeteners on glucose control or overall health can be extrapolated from this study for the general population or for people who typically consume sweeteners, including people living with diabetes.”

They add “a recent review of the literature concluded that there is clear evidence that changes in the diet unrelated to low/no calorie sweeteners consumption are likely the major determinants of change in gut microbiota.”

Nevertheless, Dr. Redfern says the results “warrant further investigation to assess how small changes in glucose tolerance in response to NNS consumption may influence longer-term glucose tolerance and risk for metabolic complications, such as type 2 diabetes.”

The study had no specific funding. Dr. Elinav is a scientific founder of DayTwo and BiomX, a paid consultant to Hello Inside and Aposense, and a member of the scientific advisory board of Cell. Dr. Mellor has provided consultancy to the International Sweetener Agency and has worked on projects funded by the Food Standards Agency that investigated the health effects of aspartame. Dr. Barrett, Dr. McConway, and Dr. Redfern report no relevant financial relationships.

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

This article was updated 8/29/22.

New research discounts the long-held notion that aspartame and other nonnutritive sweeteners (NNS) have no effect on the human body.

Researchers found that these sugar substitutes are not metabolically inert and can alter the gut microbiome in a way that can influence blood glucose levels.

The study was published online in the journal Cell.


 

Gut reaction?

Several years ago, a team led by Eran Elinav, MD, PhD, an immunologist and microbiome researcher at the Weizmann Institute of Science, Rehovot, Israel, observed that these sweeteners affect the microbiome of mice in ways that could affect glycemic responses.

They have now confirmed this observation in a randomized controlled trial with 120 healthy adults.

BigRedCurlyGuy/Thinkstock

Weighing the evidence

Several experts weighed in on the results in a statement from the U.K. nonprofit organization, Science Media Centre.

Duane Mellor, PhD, RD, RNutr, registered dietitian and senior teaching fellow, Aston University, Birmingham, England, notes that the study does not show a link between all NNS and higher blood glucose levels in the long term (only after a glucose tolerance test).

“It did suggest, though, that some individuals who do not normally consume sweeteners may not tolerate glucose as well after consuming six sachets of either saccharin or sucralose mixed with glucose per day,” Dr. Mellor says.

Kim Barrett, PhD, distinguished professor of physiology and membrane biology, University of California, Davis, concurs, saying “this well-designed study indicates the potential for NNS to have adverse effects in at least some individuals.”

The study also does not provide any information about how people who normally consume sweeteners or people with either type 1 or type 2 diabetes respond to NNS.

“Therefore, for some people, it is likely to be a better option and more sustainable approach to use sweeteners as a ‘stepping stone’ allowing them to reduce the amount of added sugar in foods and drinks, to reduce their sugar intake and still enjoy what they eat and drink, on the way to reducing both added sugar and sweeteners in their diet,” Dr. Mellor suggests.

Kevin McConway, PhD, with the Open University, Milton Keynes, England, said it’s “important to understand that the research is not saying that these sweeteners are worse for us, in heath terms, than sugar.

“But exactly what the health consequences of all this, if any, might be is a subject for future research,” Dr. McConway added.

Kathy Redfern, PhD, lecturer in human nutrition, University of Plymouth (England) agrees.

“We still have a lot to learn about the human microbiome, and although this study suggests two of the sweeteners tested in this study (sucralose and saccharin) significantly affected glucose tolerance, these deviations were small,” she says.

The International Sweeteners Association also weighs in, saying, “No conclusions about the effects of low/no calorie sweeteners on glucose control or overall health can be extrapolated from this study for the general population or for people who typically consume sweeteners, including people living with diabetes.”

They add “a recent review of the literature concluded that there is clear evidence that changes in the diet unrelated to low/no calorie sweeteners consumption are likely the major determinants of change in gut microbiota.”

Nevertheless, Dr. Redfern says the results “warrant further investigation to assess how small changes in glucose tolerance in response to NNS consumption may influence longer-term glucose tolerance and risk for metabolic complications, such as type 2 diabetes.”

The study had no specific funding. Dr. Elinav is a scientific founder of DayTwo and BiomX, a paid consultant to Hello Inside and Aposense, and a member of the scientific advisory board of Cell. Dr. Mellor has provided consultancy to the International Sweetener Agency and has worked on projects funded by the Food Standards Agency that investigated the health effects of aspartame. Dr. Barrett, Dr. McConway, and Dr. Redfern report no relevant financial relationships.

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

This article was updated 8/29/22.

New research discounts the long-held notion that aspartame and other nonnutritive sweeteners (NNS) have no effect on the human body.

Researchers found that these sugar substitutes are not metabolically inert and can alter the gut microbiome in a way that can influence blood glucose levels.

The study was published online in the journal Cell.


 

Gut reaction?

Several years ago, a team led by Eran Elinav, MD, PhD, an immunologist and microbiome researcher at the Weizmann Institute of Science, Rehovot, Israel, observed that these sweeteners affect the microbiome of mice in ways that could affect glycemic responses.

They have now confirmed this observation in a randomized controlled trial with 120 healthy adults.

BigRedCurlyGuy/Thinkstock

Weighing the evidence

Several experts weighed in on the results in a statement from the U.K. nonprofit organization, Science Media Centre.

Duane Mellor, PhD, RD, RNutr, registered dietitian and senior teaching fellow, Aston University, Birmingham, England, notes that the study does not show a link between all NNS and higher blood glucose levels in the long term (only after a glucose tolerance test).

“It did suggest, though, that some individuals who do not normally consume sweeteners may not tolerate glucose as well after consuming six sachets of either saccharin or sucralose mixed with glucose per day,” Dr. Mellor says.

Kim Barrett, PhD, distinguished professor of physiology and membrane biology, University of California, Davis, concurs, saying “this well-designed study indicates the potential for NNS to have adverse effects in at least some individuals.”

The study also does not provide any information about how people who normally consume sweeteners or people with either type 1 or type 2 diabetes respond to NNS.

“Therefore, for some people, it is likely to be a better option and more sustainable approach to use sweeteners as a ‘stepping stone’ allowing them to reduce the amount of added sugar in foods and drinks, to reduce their sugar intake and still enjoy what they eat and drink, on the way to reducing both added sugar and sweeteners in their diet,” Dr. Mellor suggests.

Kevin McConway, PhD, with the Open University, Milton Keynes, England, said it’s “important to understand that the research is not saying that these sweeteners are worse for us, in heath terms, than sugar.

“But exactly what the health consequences of all this, if any, might be is a subject for future research,” Dr. McConway added.

Kathy Redfern, PhD, lecturer in human nutrition, University of Plymouth (England) agrees.

“We still have a lot to learn about the human microbiome, and although this study suggests two of the sweeteners tested in this study (sucralose and saccharin) significantly affected glucose tolerance, these deviations were small,” she says.

The International Sweeteners Association also weighs in, saying, “No conclusions about the effects of low/no calorie sweeteners on glucose control or overall health can be extrapolated from this study for the general population or for people who typically consume sweeteners, including people living with diabetes.”

They add “a recent review of the literature concluded that there is clear evidence that changes in the diet unrelated to low/no calorie sweeteners consumption are likely the major determinants of change in gut microbiota.”

Nevertheless, Dr. Redfern says the results “warrant further investigation to assess how small changes in glucose tolerance in response to NNS consumption may influence longer-term glucose tolerance and risk for metabolic complications, such as type 2 diabetes.”

The study had no specific funding. Dr. Elinav is a scientific founder of DayTwo and BiomX, a paid consultant to Hello Inside and Aposense, and a member of the scientific advisory board of Cell. Dr. Mellor has provided consultancy to the International Sweetener Agency and has worked on projects funded by the Food Standards Agency that investigated the health effects of aspartame. Dr. Barrett, Dr. McConway, and Dr. Redfern report no relevant financial relationships.

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

This article was updated 8/29/22.

The U.S. Food and Drug Administration has approved the first oral N-methyl D-aspartate (NMDA) receptor antagonist for the treatment of major depressive disorder (MDD) in adults, its manufacturer has announced.

Auvelity (Axsome Therapeutics) is a proprietary extended-release oral tablet containing dextromethorphan (45 mg) and bupropion (105 mg).

It is the “first and only rapid-acting oral medicine approved for the treatment of MDD with labeling of statistically significant antidepressant efficacy compared to placebo starting at one week,” the company said in a news release.

“The approval of Auvelity represents a milestone in depression treatment based on its novel oral NMDA antagonist mechanism, its rapid antidepressant efficacy demonstrated in controlled trials, and a relatively favorable safety profile,” Maurizio Fava, MD, psychiatrist-in-chief, Massachusetts General Hospital, Boston, added in the release. 
 

‘Milestone’ in depression treatment?

Dr. Fava noted that nearly two-thirds of patients treated with currently available antidepressants fail to respond adequately, and those who do may not achieve clinically meaningful responses for up to 6-8 weeks.

“Given the debilitating nature of depression, the efficacy of Auvelity observed at 1 week and sustained thereafter may have a significant impact on the current treatment paradigm for this condition,” he said.

The company noted the drug was studied in a comprehensive clinical program that included more than 1,100 patients with MDD.

The efficacy of the drug was demonstrated in the GEMINI placebo-controlled study – with confirmatory evidence provided by the ASCEND study, which  compared it with bupropion sustained-release tablets.

Axsome said it expects to launch the new oral medication in the fourth quarter of this year. It is not approved for use in children.

The full prescribing information and medication guide are available online.

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

The U.S. Food and Drug Administration has approved the first oral N-methyl D-aspartate (NMDA) receptor antagonist for the treatment of major depressive disorder (MDD) in adults, its manufacturer has announced.

Auvelity (Axsome Therapeutics) is a proprietary extended-release oral tablet containing dextromethorphan (45 mg) and bupropion (105 mg).

It is the “first and only rapid-acting oral medicine approved for the treatment of MDD with labeling of statistically significant antidepressant efficacy compared to placebo starting at one week,” the company said in a news release.

“The approval of Auvelity represents a milestone in depression treatment based on its novel oral NMDA antagonist mechanism, its rapid antidepressant efficacy demonstrated in controlled trials, and a relatively favorable safety profile,” Maurizio Fava, MD, psychiatrist-in-chief, Massachusetts General Hospital, Boston, added in the release. 
 

‘Milestone’ in depression treatment?

Dr. Fava noted that nearly two-thirds of patients treated with currently available antidepressants fail to respond adequately, and those who do may not achieve clinically meaningful responses for up to 6-8 weeks.

“Given the debilitating nature of depression, the efficacy of Auvelity observed at 1 week and sustained thereafter may have a significant impact on the current treatment paradigm for this condition,” he said.

The company noted the drug was studied in a comprehensive clinical program that included more than 1,100 patients with MDD.

The efficacy of the drug was demonstrated in the GEMINI placebo-controlled study – with confirmatory evidence provided by the ASCEND study, which  compared it with bupropion sustained-release tablets.

Axsome said it expects to launch the new oral medication in the fourth quarter of this year. It is not approved for use in children.

The full prescribing information and medication guide are available online.

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

The U.S. Food and Drug Administration has approved the first oral N-methyl D-aspartate (NMDA) receptor antagonist for the treatment of major depressive disorder (MDD) in adults, its manufacturer has announced.

Auvelity (Axsome Therapeutics) is a proprietary extended-release oral tablet containing dextromethorphan (45 mg) and bupropion (105 mg).

It is the “first and only rapid-acting oral medicine approved for the treatment of MDD with labeling of statistically significant antidepressant efficacy compared to placebo starting at one week,” the company said in a news release.

“The approval of Auvelity represents a milestone in depression treatment based on its novel oral NMDA antagonist mechanism, its rapid antidepressant efficacy demonstrated in controlled trials, and a relatively favorable safety profile,” Maurizio Fava, MD, psychiatrist-in-chief, Massachusetts General Hospital, Boston, added in the release. 
 

‘Milestone’ in depression treatment?

Dr. Fava noted that nearly two-thirds of patients treated with currently available antidepressants fail to respond adequately, and those who do may not achieve clinically meaningful responses for up to 6-8 weeks.

“Given the debilitating nature of depression, the efficacy of Auvelity observed at 1 week and sustained thereafter may have a significant impact on the current treatment paradigm for this condition,” he said.

The company noted the drug was studied in a comprehensive clinical program that included more than 1,100 patients with MDD.

The efficacy of the drug was demonstrated in the GEMINI placebo-controlled study – with confirmatory evidence provided by the ASCEND study, which  compared it with bupropion sustained-release tablets.

Axsome said it expects to launch the new oral medication in the fourth quarter of this year. It is not approved for use in children.

The full prescribing information and medication guide are available online.

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

Folic acid supplementation can improve histopathologic aspects of gastric precancerous conditions (GPC), including gastric mucosal atrophy and intestinal metaplasia, according to results of a meta-analysis of relevant research.

The results, say the authors, provide evidence for the potential clinical use of folic acid in the management of GPC.

“We believe doctors can try to use folic acid to halt or reverse progression of gastric precancerous conditions, thereby reducing the incidence rate of gastric cancer,” investigator Jinhao Zeng, PhD, with Hospital of Chengdu University of Traditional Chinese Medicine, said in an interview.

Dr. Zeng cautioned, however, that the number of relevant studies “remains relatively inadequate, and the results should be interpreted with caution.”

David Johnson, MD, professor of medicine and chief of gastroenterology at the Eastern Virginia School of Medicine, Norfolk, who wasn’t involved in the study, also urged caution in interpreting the results.

“Overall, folate supplementation is unlikely to be harmful, but these data should not be used as justification for risk reduction,” Dr. Johnson said in an interview.

The study was published online in BMC Gastroenterology.
 

Examining prevention, treatment effects

The study is believed to be the first meta-analysis to examine the effects of folic acid on prevention and treatment for patients with GPC. The analysis included 13 randomized controlled trials that had a total of 1,252 adults with GPC living in China.

A meta-analysis of five studies showed a statistically significant positive treatment effect of folic acid supplementation on gastric mucosal atrophy (relative risk, 1.61; 95% confidence interval 1.07 – 2.41), Dr. Zeng and colleagues reported.

A meta-analysis of two trials showed a statistically significant effect of folic acid on reversal of intestinal metaplasia (RR, 1.77; 95% CI, 1.32-2.37), they also found.

“Our study indicates that folic acid has a beneficial effect in the treatment of pathological changes of GPC when the dose was maintained at 20-30 mg/d and the duration of treatment was maintained at 3-6 months,” they wrote.

Folic acid supplementation did not appear to be effective for GPC symptom relief.

The authors said that, in a separate analysis, they confirmed that folic acid can inhibit development of gastric mucosal carcinogenesis by affecting the levels of gastrin and pepsinogen.
 

More study needed

Commenting on the study, Judith Kim, MD, division of gastroenterology and hepatology, New York University Langone Health, said prior studies have evaluated whether folic acid supplementation is associated with a lower risk of gastric cancer, but the results have been “mixed and inconclusive.”

“While there have been prior meta-analyses on folic acid and gastric cancer, this study is noteworthy, as it evaluated the impact of folic acid on precancerous lesions, for which there is no current treatment,” Dr. Kim said.

“Currently, there is no recommendation for folic acid supplementation for the treatment or prevention of GPC and gastric cancer,” Dr. Kim said. “There has been interest in folic acid as a chemopreventive agent, given its potential protective role against DNA damage, but randomized control trials have yet to confirm these benefits.”

The analysis by Dr. Zeng and colleagues “supports the need for larger randomized controlled trials to further study this association,” Dr. Kim said.

“Given the study’s small size and limitation to a Chinese population (who have a higher incidence of precancerous lesions and gastric cancer than the general US population), I would caution against folic acid use for the sole purpose of GPC prevention, as there could be negative side effects of supplementation,” she advised.

The study was supported by the National Natural Science Foundation of China, the Hospital of Chengdu University of Traditional Chinese Medicine, and Project of Sichuan Administration of Traditional Chinese Medicine. Dr. Zeng, Dr. Johnson, and Dr. Kim reported no relevant financial relationships.

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

Folic acid supplementation can improve histopathologic aspects of gastric precancerous conditions (GPC), including gastric mucosal atrophy and intestinal metaplasia, according to results of a meta-analysis of relevant research.

The results, say the authors, provide evidence for the potential clinical use of folic acid in the management of GPC.

“We believe doctors can try to use folic acid to halt or reverse progression of gastric precancerous conditions, thereby reducing the incidence rate of gastric cancer,” investigator Jinhao Zeng, PhD, with Hospital of Chengdu University of Traditional Chinese Medicine, said in an interview.

Dr. Zeng cautioned, however, that the number of relevant studies “remains relatively inadequate, and the results should be interpreted with caution.”

David Johnson, MD, professor of medicine and chief of gastroenterology at the Eastern Virginia School of Medicine, Norfolk, who wasn’t involved in the study, also urged caution in interpreting the results.

“Overall, folate supplementation is unlikely to be harmful, but these data should not be used as justification for risk reduction,” Dr. Johnson said in an interview.

The study was published online in BMC Gastroenterology.
 

Examining prevention, treatment effects

The study is believed to be the first meta-analysis to examine the effects of folic acid on prevention and treatment for patients with GPC. The analysis included 13 randomized controlled trials that had a total of 1,252 adults with GPC living in China.

A meta-analysis of five studies showed a statistically significant positive treatment effect of folic acid supplementation on gastric mucosal atrophy (relative risk, 1.61; 95% confidence interval 1.07 – 2.41), Dr. Zeng and colleagues reported.

A meta-analysis of two trials showed a statistically significant effect of folic acid on reversal of intestinal metaplasia (RR, 1.77; 95% CI, 1.32-2.37), they also found.

“Our study indicates that folic acid has a beneficial effect in the treatment of pathological changes of GPC when the dose was maintained at 20-30 mg/d and the duration of treatment was maintained at 3-6 months,” they wrote.

Folic acid supplementation did not appear to be effective for GPC symptom relief.

The authors said that, in a separate analysis, they confirmed that folic acid can inhibit development of gastric mucosal carcinogenesis by affecting the levels of gastrin and pepsinogen.
 

More study needed

Commenting on the study, Judith Kim, MD, division of gastroenterology and hepatology, New York University Langone Health, said prior studies have evaluated whether folic acid supplementation is associated with a lower risk of gastric cancer, but the results have been “mixed and inconclusive.”

“While there have been prior meta-analyses on folic acid and gastric cancer, this study is noteworthy, as it evaluated the impact of folic acid on precancerous lesions, for which there is no current treatment,” Dr. Kim said.

“Currently, there is no recommendation for folic acid supplementation for the treatment or prevention of GPC and gastric cancer,” Dr. Kim said. “There has been interest in folic acid as a chemopreventive agent, given its potential protective role against DNA damage, but randomized control trials have yet to confirm these benefits.”

The analysis by Dr. Zeng and colleagues “supports the need for larger randomized controlled trials to further study this association,” Dr. Kim said.

“Given the study’s small size and limitation to a Chinese population (who have a higher incidence of precancerous lesions and gastric cancer than the general US population), I would caution against folic acid use for the sole purpose of GPC prevention, as there could be negative side effects of supplementation,” she advised.

The study was supported by the National Natural Science Foundation of China, the Hospital of Chengdu University of Traditional Chinese Medicine, and Project of Sichuan Administration of Traditional Chinese Medicine. Dr. Zeng, Dr. Johnson, and Dr. Kim reported no relevant financial relationships.

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

Folic acid supplementation can improve histopathologic aspects of gastric precancerous conditions (GPC), including gastric mucosal atrophy and intestinal metaplasia, according to results of a meta-analysis of relevant research.

The results, say the authors, provide evidence for the potential clinical use of folic acid in the management of GPC.

“We believe doctors can try to use folic acid to halt or reverse progression of gastric precancerous conditions, thereby reducing the incidence rate of gastric cancer,” investigator Jinhao Zeng, PhD, with Hospital of Chengdu University of Traditional Chinese Medicine, said in an interview.

Dr. Zeng cautioned, however, that the number of relevant studies “remains relatively inadequate, and the results should be interpreted with caution.”

David Johnson, MD, professor of medicine and chief of gastroenterology at the Eastern Virginia School of Medicine, Norfolk, who wasn’t involved in the study, also urged caution in interpreting the results.

“Overall, folate supplementation is unlikely to be harmful, but these data should not be used as justification for risk reduction,” Dr. Johnson said in an interview.

The study was published online in BMC Gastroenterology.
 

Examining prevention, treatment effects

The study is believed to be the first meta-analysis to examine the effects of folic acid on prevention and treatment for patients with GPC. The analysis included 13 randomized controlled trials that had a total of 1,252 adults with GPC living in China.

A meta-analysis of five studies showed a statistically significant positive treatment effect of folic acid supplementation on gastric mucosal atrophy (relative risk, 1.61; 95% confidence interval 1.07 – 2.41), Dr. Zeng and colleagues reported.

A meta-analysis of two trials showed a statistically significant effect of folic acid on reversal of intestinal metaplasia (RR, 1.77; 95% CI, 1.32-2.37), they also found.

“Our study indicates that folic acid has a beneficial effect in the treatment of pathological changes of GPC when the dose was maintained at 20-30 mg/d and the duration of treatment was maintained at 3-6 months,” they wrote.

Folic acid supplementation did not appear to be effective for GPC symptom relief.

The authors said that, in a separate analysis, they confirmed that folic acid can inhibit development of gastric mucosal carcinogenesis by affecting the levels of gastrin and pepsinogen.
 

More study needed

Commenting on the study, Judith Kim, MD, division of gastroenterology and hepatology, New York University Langone Health, said prior studies have evaluated whether folic acid supplementation is associated with a lower risk of gastric cancer, but the results have been “mixed and inconclusive.”

“While there have been prior meta-analyses on folic acid and gastric cancer, this study is noteworthy, as it evaluated the impact of folic acid on precancerous lesions, for which there is no current treatment,” Dr. Kim said.

“Currently, there is no recommendation for folic acid supplementation for the treatment or prevention of GPC and gastric cancer,” Dr. Kim said. “There has been interest in folic acid as a chemopreventive agent, given its potential protective role against DNA damage, but randomized control trials have yet to confirm these benefits.”

The analysis by Dr. Zeng and colleagues “supports the need for larger randomized controlled trials to further study this association,” Dr. Kim said.

“Given the study’s small size and limitation to a Chinese population (who have a higher incidence of precancerous lesions and gastric cancer than the general US population), I would caution against folic acid use for the sole purpose of GPC prevention, as there could be negative side effects of supplementation,” she advised.

The study was supported by the National Natural Science Foundation of China, the Hospital of Chengdu University of Traditional Chinese Medicine, and Project of Sichuan Administration of Traditional Chinese Medicine. Dr. Zeng, Dr. Johnson, and Dr. Kim reported no relevant financial relationships.

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