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Cannabis Constituent May Be Key to Easing THC-Induced Anxiety
, new data from a small study suggested.
Participants who inhaled vaporized D-limonene and THC reported significantly greater decreases in anxiogenic effects than did people who received either component alone or a placebo. Reductions were greater as the dose of the D-limonene was increased.
Investigators noted that the findings could have implications for the use of medicinal or recreational cannabis, which has increased in recent years due to state legalization efforts.
“People use cannabis to help reduce anxiety, depression, and posttraumatic stress disorder, but since THC levels vary widely, if a person overshoots their tolerance of THC, cannabis can induce anxiety rather than relieve it,” senior investigator Ryan Vandrey, PhD, professor of psychiatry and behavioral sciences, Johns Hopkins School of Medicine, Baltimore, said in a news release.
“Our study demonstrates that D-limonene can modulate the effects of THC in a meaningful way and make THC more tolerable to people using it for both therapeutic and non-therapeutic purposes,” he added.
The study was published online in Drug and Alcohol Dependence.
Entourage Theory
Cannabis legalization has opened the door to an increased range of medicinal and nonmedicinal uses, but its benefits can be limited by the anxiety and panic some people experience with its use, investigators noted.
Many cannabis plants have been bred to contain higher concentrations of THC, with some dispensaries selling cannabis with more than 20%-30% THC. The plants often include cannabidiol, “minor” cannabinoids, and terpenes, such as D-limonene.
Prior studies pointed to THC as the cause of acute behavioral and psychoactive effects some cannabis users experience. However, a new, untested theory, the “cannabis entourage effect theory,” suggested other components in cannabis, including D-limonene, may contribute to the anxiogenic symptoms.
“We were motivated by scientific publications that hypothesized D-limonene can attenuate the acute anxiogenic effects of cannabis, but for which empirical data did not exist,” Dr. Vandrey said.
Investigators designed a small double-blind, within-subjects crossover study of 20 healthy adults (median age, 26 years; 50% men). About half of participants were Caucasian/non-Hispanic, 30% African American/non-Hispanic, 10% Caucasian/Hispanic, and 10% Asian/non-Hispanic.
All participants completed nine outpatient drug administration sessions, during which they inhaled vaporized D-limonene alone (1 or 5 mg), THC alone (15 or 30 mg), the same doses of THC and D-limonene together, or placebo.
Primary outcomes included subjective drug effects, measured with the Drug Effect Questionnaire (DEQ) and the 20-item state subscale of the State-Trait Anxiety Inventory (STAI-S). Investigators also measured cognitive/psychomotor performance with the Digit Symbol Substitution Task (DSST) and the Paced Serial Addition Task.
Vital signs such as heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), and plasma D-limonene and THC concentrations were also tracked.
Participants’ responses were measured at baseline and then an additional nine times after initial exposure over the course of each 6-hour test session. Blood and urine samples were collected from participants before, during, and after each session.
First Evidence
There were no significant differences in outcomes between the D-limonene alone and placebo groups.
Receipt of 15- and 30-mg doses of THC alone was associated with subjective reports of acute cannabis exposure, including cognitive and physiological effects.
A treatment effect was observed for “anxious/nervous” (P < .01), “paranoid” (P < .01), and “heart racing” (P < .0001).
In planned comparisons, ratings of anxiety-like subjective effects qualitatively decreased as D-limonene dose increased, and concurrent administration of 30-mg THC plus 15-mg D-limonene significantly reduced ratings of “anxious/nervous” and “paranoid” on the DEQ compared to 30 mg of THC alone (P < .05).
Findings were similar on the composite score of the STAI-S, and although planned comparisons did not reach the threshold for statistical significance, reductions in anxiety approached significance in the THC plus D-limonene group compared with the THC alone condition (P = .08). The combination group also reported significantly lower subjective ratings of unpleasant drug effects than the THC alone group (P = .03).
In particular, a main effect of treatment was found for the anxious/nervous category on the DEQ (P < .01), as well as the “paranoid” (P < .01) and heart racing (P < .0001) categories.
On the other hand, ratings of anxious/nervous and paranoid categories were significantly lower in the 30-mg THC plus 15-mg D-limonene vs the 30-mg THC alone condition (P < .05, for all).
As for cognition, following drug administration, a significant main effect of treatment was observed for the DSST (P < .05), but no significant differences between THC and THC plus D-limonene combination conditions or between D-limonene alone and placebo were detected.
There were no differences within each THC dose and between D-limonene alone versus placebo conditions. Moreover, there were no main effects of treatment found for SBP or DBP.
The combination condition produced significantly greater concentrations of THC than the THC alone condition (P < .05).
“This study provides the first evidence that there are chemical constituents found naturally in the cannabis plant that can reduce some of the adverse effects of using delta-9-THC,” Dr. Vandrey said.
Although the exact mechanism by which vaporized D-limonene counters the anxiogenic effects of THC is unclear, “our best guess is that D-limonene is producing an anxiolytic effect on its own that is not mediated by cannabinoid receptors,” Dr. Vandrey said.
Significant Impact
Commenting on the research, Joshua Lile, PhD, professor, Department of Behavioral Science, University of Kentucky College of Medicine, Lexington, noted that the study seems to be the first of its kind to study the influence of terpene on THC response.
The research “makes a significant impact on our field,” and is “among the few controlled clinical studies that have demonstrated interactions between THC and other cannabis constituents, supporting the validity of the ‘entourage’ effect,” said Dr. Lile, who was not involved with the current research.
“This work is particularly important, given the unfounded claims sometimes made by the cannabis industry regarding the effects of different cannabis products,” he added.
Also commenting on the study, Ziva Cooper, PhD, professor and director of the UCLA Center for Cannabis and Cannabinoids, University of California Los Angeles, said the findings “have direct implications for improving the safety of cannabis, whether it’s being used for medical or nonmedical purposes, especially in people and patients who do not have experience with cannabis, a group that is at high risk for experiencing anxiety after using cannabis.”
In addition, “an important aspect to this study is that the effects of limonene in reducing anxiety attributed to delta-9-THC were observed at higher concentrations (or doses) than those usually present in the plant,” Dr. Copper said. “This calls for further investigation into new cannabis formulations specifically designed to leverage the potential protective effects of the terpene.”
This research was supported by the National Institute on Drug Abuse. Dr. Vandrey served as a consultant or received honoraria from Mira1a Therapeutics, Inc.; Jazz Pharmaceuticals; Charlotte’s Web; Syqe Medical Ltd.; and WebMD. The other authors’ disclosures are listed on the original paper. Dr. Lile declared no relevant financial relationships. Dr. Cooper reported receiving study drug from Canopy Growth Corp and True Terpenes, study-related materials from Storz & Bickel, and research support from the National Institute on Drug Abuse, National Center for Complementary and Integrative Health, California Department of Cannabis Control, Center for Medicinal Cannabis Research, and California Highway Patrol.
A version of this article appeared on Medscape.com.
, new data from a small study suggested.
Participants who inhaled vaporized D-limonene and THC reported significantly greater decreases in anxiogenic effects than did people who received either component alone or a placebo. Reductions were greater as the dose of the D-limonene was increased.
Investigators noted that the findings could have implications for the use of medicinal or recreational cannabis, which has increased in recent years due to state legalization efforts.
“People use cannabis to help reduce anxiety, depression, and posttraumatic stress disorder, but since THC levels vary widely, if a person overshoots their tolerance of THC, cannabis can induce anxiety rather than relieve it,” senior investigator Ryan Vandrey, PhD, professor of psychiatry and behavioral sciences, Johns Hopkins School of Medicine, Baltimore, said in a news release.
“Our study demonstrates that D-limonene can modulate the effects of THC in a meaningful way and make THC more tolerable to people using it for both therapeutic and non-therapeutic purposes,” he added.
The study was published online in Drug and Alcohol Dependence.
Entourage Theory
Cannabis legalization has opened the door to an increased range of medicinal and nonmedicinal uses, but its benefits can be limited by the anxiety and panic some people experience with its use, investigators noted.
Many cannabis plants have been bred to contain higher concentrations of THC, with some dispensaries selling cannabis with more than 20%-30% THC. The plants often include cannabidiol, “minor” cannabinoids, and terpenes, such as D-limonene.
Prior studies pointed to THC as the cause of acute behavioral and psychoactive effects some cannabis users experience. However, a new, untested theory, the “cannabis entourage effect theory,” suggested other components in cannabis, including D-limonene, may contribute to the anxiogenic symptoms.
“We were motivated by scientific publications that hypothesized D-limonene can attenuate the acute anxiogenic effects of cannabis, but for which empirical data did not exist,” Dr. Vandrey said.
Investigators designed a small double-blind, within-subjects crossover study of 20 healthy adults (median age, 26 years; 50% men). About half of participants were Caucasian/non-Hispanic, 30% African American/non-Hispanic, 10% Caucasian/Hispanic, and 10% Asian/non-Hispanic.
All participants completed nine outpatient drug administration sessions, during which they inhaled vaporized D-limonene alone (1 or 5 mg), THC alone (15 or 30 mg), the same doses of THC and D-limonene together, or placebo.
Primary outcomes included subjective drug effects, measured with the Drug Effect Questionnaire (DEQ) and the 20-item state subscale of the State-Trait Anxiety Inventory (STAI-S). Investigators also measured cognitive/psychomotor performance with the Digit Symbol Substitution Task (DSST) and the Paced Serial Addition Task.
Vital signs such as heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), and plasma D-limonene and THC concentrations were also tracked.
Participants’ responses were measured at baseline and then an additional nine times after initial exposure over the course of each 6-hour test session. Blood and urine samples were collected from participants before, during, and after each session.
First Evidence
There were no significant differences in outcomes between the D-limonene alone and placebo groups.
Receipt of 15- and 30-mg doses of THC alone was associated with subjective reports of acute cannabis exposure, including cognitive and physiological effects.
A treatment effect was observed for “anxious/nervous” (P < .01), “paranoid” (P < .01), and “heart racing” (P < .0001).
In planned comparisons, ratings of anxiety-like subjective effects qualitatively decreased as D-limonene dose increased, and concurrent administration of 30-mg THC plus 15-mg D-limonene significantly reduced ratings of “anxious/nervous” and “paranoid” on the DEQ compared to 30 mg of THC alone (P < .05).
Findings were similar on the composite score of the STAI-S, and although planned comparisons did not reach the threshold for statistical significance, reductions in anxiety approached significance in the THC plus D-limonene group compared with the THC alone condition (P = .08). The combination group also reported significantly lower subjective ratings of unpleasant drug effects than the THC alone group (P = .03).
In particular, a main effect of treatment was found for the anxious/nervous category on the DEQ (P < .01), as well as the “paranoid” (P < .01) and heart racing (P < .0001) categories.
On the other hand, ratings of anxious/nervous and paranoid categories were significantly lower in the 30-mg THC plus 15-mg D-limonene vs the 30-mg THC alone condition (P < .05, for all).
As for cognition, following drug administration, a significant main effect of treatment was observed for the DSST (P < .05), but no significant differences between THC and THC plus D-limonene combination conditions or between D-limonene alone and placebo were detected.
There were no differences within each THC dose and between D-limonene alone versus placebo conditions. Moreover, there were no main effects of treatment found for SBP or DBP.
The combination condition produced significantly greater concentrations of THC than the THC alone condition (P < .05).
“This study provides the first evidence that there are chemical constituents found naturally in the cannabis plant that can reduce some of the adverse effects of using delta-9-THC,” Dr. Vandrey said.
Although the exact mechanism by which vaporized D-limonene counters the anxiogenic effects of THC is unclear, “our best guess is that D-limonene is producing an anxiolytic effect on its own that is not mediated by cannabinoid receptors,” Dr. Vandrey said.
Significant Impact
Commenting on the research, Joshua Lile, PhD, professor, Department of Behavioral Science, University of Kentucky College of Medicine, Lexington, noted that the study seems to be the first of its kind to study the influence of terpene on THC response.
The research “makes a significant impact on our field,” and is “among the few controlled clinical studies that have demonstrated interactions between THC and other cannabis constituents, supporting the validity of the ‘entourage’ effect,” said Dr. Lile, who was not involved with the current research.
“This work is particularly important, given the unfounded claims sometimes made by the cannabis industry regarding the effects of different cannabis products,” he added.
Also commenting on the study, Ziva Cooper, PhD, professor and director of the UCLA Center for Cannabis and Cannabinoids, University of California Los Angeles, said the findings “have direct implications for improving the safety of cannabis, whether it’s being used for medical or nonmedical purposes, especially in people and patients who do not have experience with cannabis, a group that is at high risk for experiencing anxiety after using cannabis.”
In addition, “an important aspect to this study is that the effects of limonene in reducing anxiety attributed to delta-9-THC were observed at higher concentrations (or doses) than those usually present in the plant,” Dr. Copper said. “This calls for further investigation into new cannabis formulations specifically designed to leverage the potential protective effects of the terpene.”
This research was supported by the National Institute on Drug Abuse. Dr. Vandrey served as a consultant or received honoraria from Mira1a Therapeutics, Inc.; Jazz Pharmaceuticals; Charlotte’s Web; Syqe Medical Ltd.; and WebMD. The other authors’ disclosures are listed on the original paper. Dr. Lile declared no relevant financial relationships. Dr. Cooper reported receiving study drug from Canopy Growth Corp and True Terpenes, study-related materials from Storz & Bickel, and research support from the National Institute on Drug Abuse, National Center for Complementary and Integrative Health, California Department of Cannabis Control, Center for Medicinal Cannabis Research, and California Highway Patrol.
A version of this article appeared on Medscape.com.
, new data from a small study suggested.
Participants who inhaled vaporized D-limonene and THC reported significantly greater decreases in anxiogenic effects than did people who received either component alone or a placebo. Reductions were greater as the dose of the D-limonene was increased.
Investigators noted that the findings could have implications for the use of medicinal or recreational cannabis, which has increased in recent years due to state legalization efforts.
“People use cannabis to help reduce anxiety, depression, and posttraumatic stress disorder, but since THC levels vary widely, if a person overshoots their tolerance of THC, cannabis can induce anxiety rather than relieve it,” senior investigator Ryan Vandrey, PhD, professor of psychiatry and behavioral sciences, Johns Hopkins School of Medicine, Baltimore, said in a news release.
“Our study demonstrates that D-limonene can modulate the effects of THC in a meaningful way and make THC more tolerable to people using it for both therapeutic and non-therapeutic purposes,” he added.
The study was published online in Drug and Alcohol Dependence.
Entourage Theory
Cannabis legalization has opened the door to an increased range of medicinal and nonmedicinal uses, but its benefits can be limited by the anxiety and panic some people experience with its use, investigators noted.
Many cannabis plants have been bred to contain higher concentrations of THC, with some dispensaries selling cannabis with more than 20%-30% THC. The plants often include cannabidiol, “minor” cannabinoids, and terpenes, such as D-limonene.
Prior studies pointed to THC as the cause of acute behavioral and psychoactive effects some cannabis users experience. However, a new, untested theory, the “cannabis entourage effect theory,” suggested other components in cannabis, including D-limonene, may contribute to the anxiogenic symptoms.
“We were motivated by scientific publications that hypothesized D-limonene can attenuate the acute anxiogenic effects of cannabis, but for which empirical data did not exist,” Dr. Vandrey said.
Investigators designed a small double-blind, within-subjects crossover study of 20 healthy adults (median age, 26 years; 50% men). About half of participants were Caucasian/non-Hispanic, 30% African American/non-Hispanic, 10% Caucasian/Hispanic, and 10% Asian/non-Hispanic.
All participants completed nine outpatient drug administration sessions, during which they inhaled vaporized D-limonene alone (1 or 5 mg), THC alone (15 or 30 mg), the same doses of THC and D-limonene together, or placebo.
Primary outcomes included subjective drug effects, measured with the Drug Effect Questionnaire (DEQ) and the 20-item state subscale of the State-Trait Anxiety Inventory (STAI-S). Investigators also measured cognitive/psychomotor performance with the Digit Symbol Substitution Task (DSST) and the Paced Serial Addition Task.
Vital signs such as heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), and plasma D-limonene and THC concentrations were also tracked.
Participants’ responses were measured at baseline and then an additional nine times after initial exposure over the course of each 6-hour test session. Blood and urine samples were collected from participants before, during, and after each session.
First Evidence
There were no significant differences in outcomes between the D-limonene alone and placebo groups.
Receipt of 15- and 30-mg doses of THC alone was associated with subjective reports of acute cannabis exposure, including cognitive and physiological effects.
A treatment effect was observed for “anxious/nervous” (P < .01), “paranoid” (P < .01), and “heart racing” (P < .0001).
In planned comparisons, ratings of anxiety-like subjective effects qualitatively decreased as D-limonene dose increased, and concurrent administration of 30-mg THC plus 15-mg D-limonene significantly reduced ratings of “anxious/nervous” and “paranoid” on the DEQ compared to 30 mg of THC alone (P < .05).
Findings were similar on the composite score of the STAI-S, and although planned comparisons did not reach the threshold for statistical significance, reductions in anxiety approached significance in the THC plus D-limonene group compared with the THC alone condition (P = .08). The combination group also reported significantly lower subjective ratings of unpleasant drug effects than the THC alone group (P = .03).
In particular, a main effect of treatment was found for the anxious/nervous category on the DEQ (P < .01), as well as the “paranoid” (P < .01) and heart racing (P < .0001) categories.
On the other hand, ratings of anxious/nervous and paranoid categories were significantly lower in the 30-mg THC plus 15-mg D-limonene vs the 30-mg THC alone condition (P < .05, for all).
As for cognition, following drug administration, a significant main effect of treatment was observed for the DSST (P < .05), but no significant differences between THC and THC plus D-limonene combination conditions or between D-limonene alone and placebo were detected.
There were no differences within each THC dose and between D-limonene alone versus placebo conditions. Moreover, there were no main effects of treatment found for SBP or DBP.
The combination condition produced significantly greater concentrations of THC than the THC alone condition (P < .05).
“This study provides the first evidence that there are chemical constituents found naturally in the cannabis plant that can reduce some of the adverse effects of using delta-9-THC,” Dr. Vandrey said.
Although the exact mechanism by which vaporized D-limonene counters the anxiogenic effects of THC is unclear, “our best guess is that D-limonene is producing an anxiolytic effect on its own that is not mediated by cannabinoid receptors,” Dr. Vandrey said.
Significant Impact
Commenting on the research, Joshua Lile, PhD, professor, Department of Behavioral Science, University of Kentucky College of Medicine, Lexington, noted that the study seems to be the first of its kind to study the influence of terpene on THC response.
The research “makes a significant impact on our field,” and is “among the few controlled clinical studies that have demonstrated interactions between THC and other cannabis constituents, supporting the validity of the ‘entourage’ effect,” said Dr. Lile, who was not involved with the current research.
“This work is particularly important, given the unfounded claims sometimes made by the cannabis industry regarding the effects of different cannabis products,” he added.
Also commenting on the study, Ziva Cooper, PhD, professor and director of the UCLA Center for Cannabis and Cannabinoids, University of California Los Angeles, said the findings “have direct implications for improving the safety of cannabis, whether it’s being used for medical or nonmedical purposes, especially in people and patients who do not have experience with cannabis, a group that is at high risk for experiencing anxiety after using cannabis.”
In addition, “an important aspect to this study is that the effects of limonene in reducing anxiety attributed to delta-9-THC were observed at higher concentrations (or doses) than those usually present in the plant,” Dr. Copper said. “This calls for further investigation into new cannabis formulations specifically designed to leverage the potential protective effects of the terpene.”
This research was supported by the National Institute on Drug Abuse. Dr. Vandrey served as a consultant or received honoraria from Mira1a Therapeutics, Inc.; Jazz Pharmaceuticals; Charlotte’s Web; Syqe Medical Ltd.; and WebMD. The other authors’ disclosures are listed on the original paper. Dr. Lile declared no relevant financial relationships. Dr. Cooper reported receiving study drug from Canopy Growth Corp and True Terpenes, study-related materials from Storz & Bickel, and research support from the National Institute on Drug Abuse, National Center for Complementary and Integrative Health, California Department of Cannabis Control, Center for Medicinal Cannabis Research, and California Highway Patrol.
A version of this article appeared on Medscape.com.
From Drug and Alcohol Dependence
Clozapine Underutilized in Black Patients With Schizophrenia
TOPLINE:
Black patients with schizophrenia are less likely to receive a clozapine prescription compared with White patients, a new study shows. The findings held even after the researchers controlled for demographic variables, social determinants of health, and care access patterns.
METHODOLOGY:
- The study drew on structured electronic health record data on 3160 adult patients with schizophrenia.
- The mean age at first recorded diagnosis was 39.5 years; 70% of participants were male, 53% Black, and 91% resided in an urban setting.
- The researchers used the social vulnerability index (SVI) to quantify social determinants of health.
- Descriptive data analysis, logistic regression, and sensitivity analysis were used to identify differences between those who received a clozapine prescription and those who were prescribed antipsychotic medications other than clozapine.
TAKEAWAY:
- Overall, 401 patients received a clozapine prescription, 51% of whom were White and 40% were Black.
- Moreover, 19% of all White patients in the study received clozapine vs 10% of Black patients.
- After the researchers controlled for demographic variables, SVI scores, and care patterns, White patients were significantly more likely to receive a clozapine prescription than Black patients (adjusted odds ratio [aOR], 1.71; P < .001).
- Factors that had a statistically significant influence on the likelihood of receiving a clozapine prescription were minority status and language (OR, 2.97; P < .007), treatment duration (OR, 1.36; P < .001), and socioeconomic status (OR, 0.27; P = .001).
IN PRACTICE:
“The reasons for the underprescription of clozapine among Black patients with schizophrenia are multifactorial and may include concerns about benign ethnic neutropenia, prescriber bias, prescribers’ anticipation of patients’ nonadherence to the treatment, and the notion that the medication is less effective for Black patients,” the authors wrote.
SOURCE:
Xiaoming Zeng, MD, PhD, professor of psychiatry, University of North Carolina, Chapel Hill, North Carolina, was the senior and corresponding on the study. It was published online on March 19 in Psychiatric Services.
LIMITATIONS:
Due to the study’s cross-sectional and single-site design, the findings may not be generalizable to other geographic areas or institutions. The study lacked information on substance use disorders, common health conditions, or other patient-level data. A question remains whether all patients who received clozapine actually had treatment-resistant schizophrenia because other research has shown that there is an overdiagnosis of schizophrenia among Black patients.
DISCLOSURES:
The study was supported by a grant from the Foundation of Hope. Dr. Zeng reported no relevant financial relationships. The other authors’ disclosures are listed on the original paper.
A version of this article appeared on Medscape.com.
TOPLINE:
Black patients with schizophrenia are less likely to receive a clozapine prescription compared with White patients, a new study shows. The findings held even after the researchers controlled for demographic variables, social determinants of health, and care access patterns.
METHODOLOGY:
- The study drew on structured electronic health record data on 3160 adult patients with schizophrenia.
- The mean age at first recorded diagnosis was 39.5 years; 70% of participants were male, 53% Black, and 91% resided in an urban setting.
- The researchers used the social vulnerability index (SVI) to quantify social determinants of health.
- Descriptive data analysis, logistic regression, and sensitivity analysis were used to identify differences between those who received a clozapine prescription and those who were prescribed antipsychotic medications other than clozapine.
TAKEAWAY:
- Overall, 401 patients received a clozapine prescription, 51% of whom were White and 40% were Black.
- Moreover, 19% of all White patients in the study received clozapine vs 10% of Black patients.
- After the researchers controlled for demographic variables, SVI scores, and care patterns, White patients were significantly more likely to receive a clozapine prescription than Black patients (adjusted odds ratio [aOR], 1.71; P < .001).
- Factors that had a statistically significant influence on the likelihood of receiving a clozapine prescription were minority status and language (OR, 2.97; P < .007), treatment duration (OR, 1.36; P < .001), and socioeconomic status (OR, 0.27; P = .001).
IN PRACTICE:
“The reasons for the underprescription of clozapine among Black patients with schizophrenia are multifactorial and may include concerns about benign ethnic neutropenia, prescriber bias, prescribers’ anticipation of patients’ nonadherence to the treatment, and the notion that the medication is less effective for Black patients,” the authors wrote.
SOURCE:
Xiaoming Zeng, MD, PhD, professor of psychiatry, University of North Carolina, Chapel Hill, North Carolina, was the senior and corresponding on the study. It was published online on March 19 in Psychiatric Services.
LIMITATIONS:
Due to the study’s cross-sectional and single-site design, the findings may not be generalizable to other geographic areas or institutions. The study lacked information on substance use disorders, common health conditions, or other patient-level data. A question remains whether all patients who received clozapine actually had treatment-resistant schizophrenia because other research has shown that there is an overdiagnosis of schizophrenia among Black patients.
DISCLOSURES:
The study was supported by a grant from the Foundation of Hope. Dr. Zeng reported no relevant financial relationships. The other authors’ disclosures are listed on the original paper.
A version of this article appeared on Medscape.com.
TOPLINE:
Black patients with schizophrenia are less likely to receive a clozapine prescription compared with White patients, a new study shows. The findings held even after the researchers controlled for demographic variables, social determinants of health, and care access patterns.
METHODOLOGY:
- The study drew on structured electronic health record data on 3160 adult patients with schizophrenia.
- The mean age at first recorded diagnosis was 39.5 years; 70% of participants were male, 53% Black, and 91% resided in an urban setting.
- The researchers used the social vulnerability index (SVI) to quantify social determinants of health.
- Descriptive data analysis, logistic regression, and sensitivity analysis were used to identify differences between those who received a clozapine prescription and those who were prescribed antipsychotic medications other than clozapine.
TAKEAWAY:
- Overall, 401 patients received a clozapine prescription, 51% of whom were White and 40% were Black.
- Moreover, 19% of all White patients in the study received clozapine vs 10% of Black patients.
- After the researchers controlled for demographic variables, SVI scores, and care patterns, White patients were significantly more likely to receive a clozapine prescription than Black patients (adjusted odds ratio [aOR], 1.71; P < .001).
- Factors that had a statistically significant influence on the likelihood of receiving a clozapine prescription were minority status and language (OR, 2.97; P < .007), treatment duration (OR, 1.36; P < .001), and socioeconomic status (OR, 0.27; P = .001).
IN PRACTICE:
“The reasons for the underprescription of clozapine among Black patients with schizophrenia are multifactorial and may include concerns about benign ethnic neutropenia, prescriber bias, prescribers’ anticipation of patients’ nonadherence to the treatment, and the notion that the medication is less effective for Black patients,” the authors wrote.
SOURCE:
Xiaoming Zeng, MD, PhD, professor of psychiatry, University of North Carolina, Chapel Hill, North Carolina, was the senior and corresponding on the study. It was published online on March 19 in Psychiatric Services.
LIMITATIONS:
Due to the study’s cross-sectional and single-site design, the findings may not be generalizable to other geographic areas or institutions. The study lacked information on substance use disorders, common health conditions, or other patient-level data. A question remains whether all patients who received clozapine actually had treatment-resistant schizophrenia because other research has shown that there is an overdiagnosis of schizophrenia among Black patients.
DISCLOSURES:
The study was supported by a grant from the Foundation of Hope. Dr. Zeng reported no relevant financial relationships. The other authors’ disclosures are listed on the original paper.
A version of this article appeared on Medscape.com.
Regular Exercise Linked to Better Sleep
TOPLINE:
Over time, exercising at least twice a week is associated with significantly fewer insomnia symptoms and better sleep duration, new research shows.
METHODOLOGY:
- The study included 4339 adults aged 39-67 years (48% men) from 21 centers in nine countries participating in the third follow-up to the European Community Respiratory Health Survey (ECRHS III).
- Participants responded to questions about physical activity, insomnia symptoms, sleep duration, and daytime sleepiness at 10-year follow-up.
- Being “physically active” was defined as exercising with a frequency of at least twice a week for ≥ 1 hour per week.
- The main outcome measures were insomnia, sleep time, and daytime sleepiness in relation to physical activity.
TAKEAWAY:
- From baseline to follow-up, 37% of participants were persistently inactive, 25% were persistently active, 20% became inactive, and 18% became active.
- After adjustment for age, sex, body mass index, smoking history, and study center, persistently active participants were less likely to report difficulties with sleep initiation (adjusted odds ratio [aOR], 0.60; 95% CI, 0.45-0.78), with short sleep duration of ≤ 6 hours/night (aOR, 0.71; 95% CI, 0.59-0.85) and long sleep of ≥ 9 hours/night (aOR, 0.53; 95% CI, 0.33-0.84), compared with persistently nonactive subjects.
- Daytime sleepiness and difficulties maintaining sleep were found to be unrelated to physical activity status.
IN PRACTICE:
“This study has a long follow-up period (10 years) and indicates strongly that consistency in physical activity might be an important factor in optimizing sleep duration and reducing the symptoms of insomnia,” the authors wrote.
SOURCE:
Erla Björnsdóttir, of the Department of Psychology, Reykjavik University, Reykjavik, Iceland, was the co-senior author and corresponding author of the study. It was published online on March 25 in BMJ Open.
LIMITATIONS:
It’s unclear whether individuals who were active at both timepoints had been continuously physically active throughout the study period or only at those two timepoints. Sleep variables were available only at follow-up and were all subjectively reported, meaning the associations between physical activity and sleep may not be longitudinal. Residual confounders (eg, mental health and musculoskeletal disorders or chronic pain) that can influence both sleep and exercise were not explored.
DISCLOSURES:
Financial support for ECRHS III was provided by the National Health and Medical Research Council (Australia); Antwerp South, Antwerp City: Research Foundation Flanders (Belgium); Estonian Ministry of Education (Estonia); and other international agencies. Additional sources of funding were listed on the original paper. The authors reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
TOPLINE:
Over time, exercising at least twice a week is associated with significantly fewer insomnia symptoms and better sleep duration, new research shows.
METHODOLOGY:
- The study included 4339 adults aged 39-67 years (48% men) from 21 centers in nine countries participating in the third follow-up to the European Community Respiratory Health Survey (ECRHS III).
- Participants responded to questions about physical activity, insomnia symptoms, sleep duration, and daytime sleepiness at 10-year follow-up.
- Being “physically active” was defined as exercising with a frequency of at least twice a week for ≥ 1 hour per week.
- The main outcome measures were insomnia, sleep time, and daytime sleepiness in relation to physical activity.
TAKEAWAY:
- From baseline to follow-up, 37% of participants were persistently inactive, 25% were persistently active, 20% became inactive, and 18% became active.
- After adjustment for age, sex, body mass index, smoking history, and study center, persistently active participants were less likely to report difficulties with sleep initiation (adjusted odds ratio [aOR], 0.60; 95% CI, 0.45-0.78), with short sleep duration of ≤ 6 hours/night (aOR, 0.71; 95% CI, 0.59-0.85) and long sleep of ≥ 9 hours/night (aOR, 0.53; 95% CI, 0.33-0.84), compared with persistently nonactive subjects.
- Daytime sleepiness and difficulties maintaining sleep were found to be unrelated to physical activity status.
IN PRACTICE:
“This study has a long follow-up period (10 years) and indicates strongly that consistency in physical activity might be an important factor in optimizing sleep duration and reducing the symptoms of insomnia,” the authors wrote.
SOURCE:
Erla Björnsdóttir, of the Department of Psychology, Reykjavik University, Reykjavik, Iceland, was the co-senior author and corresponding author of the study. It was published online on March 25 in BMJ Open.
LIMITATIONS:
It’s unclear whether individuals who were active at both timepoints had been continuously physically active throughout the study period or only at those two timepoints. Sleep variables were available only at follow-up and were all subjectively reported, meaning the associations between physical activity and sleep may not be longitudinal. Residual confounders (eg, mental health and musculoskeletal disorders or chronic pain) that can influence both sleep and exercise were not explored.
DISCLOSURES:
Financial support for ECRHS III was provided by the National Health and Medical Research Council (Australia); Antwerp South, Antwerp City: Research Foundation Flanders (Belgium); Estonian Ministry of Education (Estonia); and other international agencies. Additional sources of funding were listed on the original paper. The authors reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
TOPLINE:
Over time, exercising at least twice a week is associated with significantly fewer insomnia symptoms and better sleep duration, new research shows.
METHODOLOGY:
- The study included 4339 adults aged 39-67 years (48% men) from 21 centers in nine countries participating in the third follow-up to the European Community Respiratory Health Survey (ECRHS III).
- Participants responded to questions about physical activity, insomnia symptoms, sleep duration, and daytime sleepiness at 10-year follow-up.
- Being “physically active” was defined as exercising with a frequency of at least twice a week for ≥ 1 hour per week.
- The main outcome measures were insomnia, sleep time, and daytime sleepiness in relation to physical activity.
TAKEAWAY:
- From baseline to follow-up, 37% of participants were persistently inactive, 25% were persistently active, 20% became inactive, and 18% became active.
- After adjustment for age, sex, body mass index, smoking history, and study center, persistently active participants were less likely to report difficulties with sleep initiation (adjusted odds ratio [aOR], 0.60; 95% CI, 0.45-0.78), with short sleep duration of ≤ 6 hours/night (aOR, 0.71; 95% CI, 0.59-0.85) and long sleep of ≥ 9 hours/night (aOR, 0.53; 95% CI, 0.33-0.84), compared with persistently nonactive subjects.
- Daytime sleepiness and difficulties maintaining sleep were found to be unrelated to physical activity status.
IN PRACTICE:
“This study has a long follow-up period (10 years) and indicates strongly that consistency in physical activity might be an important factor in optimizing sleep duration and reducing the symptoms of insomnia,” the authors wrote.
SOURCE:
Erla Björnsdóttir, of the Department of Psychology, Reykjavik University, Reykjavik, Iceland, was the co-senior author and corresponding author of the study. It was published online on March 25 in BMJ Open.
LIMITATIONS:
It’s unclear whether individuals who were active at both timepoints had been continuously physically active throughout the study period or only at those two timepoints. Sleep variables were available only at follow-up and were all subjectively reported, meaning the associations between physical activity and sleep may not be longitudinal. Residual confounders (eg, mental health and musculoskeletal disorders or chronic pain) that can influence both sleep and exercise were not explored.
DISCLOSURES:
Financial support for ECRHS III was provided by the National Health and Medical Research Council (Australia); Antwerp South, Antwerp City: Research Foundation Flanders (Belgium); Estonian Ministry of Education (Estonia); and other international agencies. Additional sources of funding were listed on the original paper. The authors reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Erenumab Linked to Better Migraine Prevention
TOPLINE:
Earlier treatment with erenumab was associated with significantly better migraine prevention than that with nonspecific oral migraine preventive medications (OMPMs) in patients with resistant episodic migraine. Based on this research, the investigators suggest clinicians should start erenumab early and not prolong use of OMPMs.
METHODOLOGY:
- The 12-month prospective, international, multicenter, phase 4 randomized clinical APPRAISE trial included 621 adult patients (mean age, 41 years; 88% female) with a ≥ 12-month history of migraine and between 4 and 15 monthly migraine days (MMDs).
- Primary endpoint was the proportion of patients who completed 12 months of the initially assigned treatment and experiencing a reduction of ≥ 50% from baseline in MMDs at the end of the year.
- Secondary endpoints included cumulative mean change from baseline in MMDs during the treatment period and the proportion of responders (based on the Patients’ Global Impression of Change scale) at month 12 for patients taking the initially assigned treatment.
TAKEAWAY:
- At month 12, patients receiving erenumab were six times more likely to report a ≥ 50% reduction in MMDs than those receiving OMPMs (odds ratio [OR], 6.48; P < .001).
- Compared with OMPMs, treatment with erenumab yielded a higher responder rate at 1 year (76% vs 19%; OR, 13.75; P < .001) and a significantly greater reduction in cumulative average MMDs (−4.32 days vs −2.65 days; P < .001).
- Substantially, fewer patients in the erenumab vs the OMPM group switched medication (2% vs 35%) or discontinued treatment due to adverse events (3% vs 23%).
- Incidence of treatment-emergent adverse events was similar between the treatment arms (75% vs 76%) until the researchers adjusted for exposure to treatment, which revealed a roughly 30% lower exposure-adjusted rate (per 100 patient-years) in the erenumab group.
IN PRACTICE:
“Earlier initiation of erenumab may ultimately lead to fewer patients discontinuing or switching medication in a real-world clinical practice,” the authors wrote. In addition, the findings “lend further support to the recent guideline update issued by the European Headache Federation, in which CGRP-targeted mAbs are considered a first-line treatment option for patients with migraine who require preventive treatment.”
SOURCE:
Patricia Pozo-Rosich, MD, PhD, of the Headache and Neurological Pain Research Group, Vall d’Hebron Institute of Research, Department of Medicine, Universitat Autònoma de Barcelona, Spain, and the Headache Unit, Neurology Department, Vall d’Hebron University Hospital, Barcelona, Spain, was the lead and corresponding author of the study. It was published online in JAMA Neurology.
LIMITATIONS:
Only locally approved and marketed OMPMs at study onset were used as comparators. The open-label study design might have led to a placebo response, which could have played a role in the findings because erenumab can only be administered in a clinic and was administered subcutaneously.
DISCLOSURES:
This study was funded by Novartis Pharma AG, Basel, Switzerland. Dr. Pozo-Rosich reported receiving grants from AbbVie, Novartis, and Teva and personal fees from AbbVie, Eli Lilly, Lundbeck, Novartis, Pfizer, and Teva outside the submitted work. The other authors’ disclosures were listed on the original paper.
A version of this article first appeared on Medscape.com.
TOPLINE:
Earlier treatment with erenumab was associated with significantly better migraine prevention than that with nonspecific oral migraine preventive medications (OMPMs) in patients with resistant episodic migraine. Based on this research, the investigators suggest clinicians should start erenumab early and not prolong use of OMPMs.
METHODOLOGY:
- The 12-month prospective, international, multicenter, phase 4 randomized clinical APPRAISE trial included 621 adult patients (mean age, 41 years; 88% female) with a ≥ 12-month history of migraine and between 4 and 15 monthly migraine days (MMDs).
- Primary endpoint was the proportion of patients who completed 12 months of the initially assigned treatment and experiencing a reduction of ≥ 50% from baseline in MMDs at the end of the year.
- Secondary endpoints included cumulative mean change from baseline in MMDs during the treatment period and the proportion of responders (based on the Patients’ Global Impression of Change scale) at month 12 for patients taking the initially assigned treatment.
TAKEAWAY:
- At month 12, patients receiving erenumab were six times more likely to report a ≥ 50% reduction in MMDs than those receiving OMPMs (odds ratio [OR], 6.48; P < .001).
- Compared with OMPMs, treatment with erenumab yielded a higher responder rate at 1 year (76% vs 19%; OR, 13.75; P < .001) and a significantly greater reduction in cumulative average MMDs (−4.32 days vs −2.65 days; P < .001).
- Substantially, fewer patients in the erenumab vs the OMPM group switched medication (2% vs 35%) or discontinued treatment due to adverse events (3% vs 23%).
- Incidence of treatment-emergent adverse events was similar between the treatment arms (75% vs 76%) until the researchers adjusted for exposure to treatment, which revealed a roughly 30% lower exposure-adjusted rate (per 100 patient-years) in the erenumab group.
IN PRACTICE:
“Earlier initiation of erenumab may ultimately lead to fewer patients discontinuing or switching medication in a real-world clinical practice,” the authors wrote. In addition, the findings “lend further support to the recent guideline update issued by the European Headache Federation, in which CGRP-targeted mAbs are considered a first-line treatment option for patients with migraine who require preventive treatment.”
SOURCE:
Patricia Pozo-Rosich, MD, PhD, of the Headache and Neurological Pain Research Group, Vall d’Hebron Institute of Research, Department of Medicine, Universitat Autònoma de Barcelona, Spain, and the Headache Unit, Neurology Department, Vall d’Hebron University Hospital, Barcelona, Spain, was the lead and corresponding author of the study. It was published online in JAMA Neurology.
LIMITATIONS:
Only locally approved and marketed OMPMs at study onset were used as comparators. The open-label study design might have led to a placebo response, which could have played a role in the findings because erenumab can only be administered in a clinic and was administered subcutaneously.
DISCLOSURES:
This study was funded by Novartis Pharma AG, Basel, Switzerland. Dr. Pozo-Rosich reported receiving grants from AbbVie, Novartis, and Teva and personal fees from AbbVie, Eli Lilly, Lundbeck, Novartis, Pfizer, and Teva outside the submitted work. The other authors’ disclosures were listed on the original paper.
A version of this article first appeared on Medscape.com.
TOPLINE:
Earlier treatment with erenumab was associated with significantly better migraine prevention than that with nonspecific oral migraine preventive medications (OMPMs) in patients with resistant episodic migraine. Based on this research, the investigators suggest clinicians should start erenumab early and not prolong use of OMPMs.
METHODOLOGY:
- The 12-month prospective, international, multicenter, phase 4 randomized clinical APPRAISE trial included 621 adult patients (mean age, 41 years; 88% female) with a ≥ 12-month history of migraine and between 4 and 15 monthly migraine days (MMDs).
- Primary endpoint was the proportion of patients who completed 12 months of the initially assigned treatment and experiencing a reduction of ≥ 50% from baseline in MMDs at the end of the year.
- Secondary endpoints included cumulative mean change from baseline in MMDs during the treatment period and the proportion of responders (based on the Patients’ Global Impression of Change scale) at month 12 for patients taking the initially assigned treatment.
TAKEAWAY:
- At month 12, patients receiving erenumab were six times more likely to report a ≥ 50% reduction in MMDs than those receiving OMPMs (odds ratio [OR], 6.48; P < .001).
- Compared with OMPMs, treatment with erenumab yielded a higher responder rate at 1 year (76% vs 19%; OR, 13.75; P < .001) and a significantly greater reduction in cumulative average MMDs (−4.32 days vs −2.65 days; P < .001).
- Substantially, fewer patients in the erenumab vs the OMPM group switched medication (2% vs 35%) or discontinued treatment due to adverse events (3% vs 23%).
- Incidence of treatment-emergent adverse events was similar between the treatment arms (75% vs 76%) until the researchers adjusted for exposure to treatment, which revealed a roughly 30% lower exposure-adjusted rate (per 100 patient-years) in the erenumab group.
IN PRACTICE:
“Earlier initiation of erenumab may ultimately lead to fewer patients discontinuing or switching medication in a real-world clinical practice,” the authors wrote. In addition, the findings “lend further support to the recent guideline update issued by the European Headache Federation, in which CGRP-targeted mAbs are considered a first-line treatment option for patients with migraine who require preventive treatment.”
SOURCE:
Patricia Pozo-Rosich, MD, PhD, of the Headache and Neurological Pain Research Group, Vall d’Hebron Institute of Research, Department of Medicine, Universitat Autònoma de Barcelona, Spain, and the Headache Unit, Neurology Department, Vall d’Hebron University Hospital, Barcelona, Spain, was the lead and corresponding author of the study. It was published online in JAMA Neurology.
LIMITATIONS:
Only locally approved and marketed OMPMs at study onset were used as comparators. The open-label study design might have led to a placebo response, which could have played a role in the findings because erenumab can only be administered in a clinic and was administered subcutaneously.
DISCLOSURES:
This study was funded by Novartis Pharma AG, Basel, Switzerland. Dr. Pozo-Rosich reported receiving grants from AbbVie, Novartis, and Teva and personal fees from AbbVie, Eli Lilly, Lundbeck, Novartis, Pfizer, and Teva outside the submitted work. The other authors’ disclosures were listed on the original paper.
A version of this article first appeared on Medscape.com.
No Increased Stroke Risk After COVID-19 Bivalent Vaccine
TOPLINE:
, a new study of Medicare beneficiaries showed.
METHODOLOGY:
- The analysis included 5.4 million people age ≥ 65 years who received either the Pfizer-BioNTech COVID-19 bivalent vaccine or the Moderna bivalent vaccine, or the Pfizer vaccine and a high-dose or adjuvanted concomitant influenza vaccine (ie, administered on the same day).
- A total of 11,001 of the cohort experienced a stroke in the first 90 days after vaccination.
- The main outcome was stroke risk (nonhemorrhagic stroke, transient ischemic attack [TIA], or hemorrhagic stroke) during the 1- to 21-day or 22- to 42-day window after vaccination vs the 43- to 90-day control window.
- The mean age of participants was 74 years, and 56% were female.
TAKEAWAY:
- There was no statistically significant association with either brand of the COVID-19 bivalent vaccine or any of the stroke outcomes during the 1- to 21-day or 22- to 42-day risk window compared with the 43- to 90-day control window (incidence rate ratio [IRR] range, 0.72-1.12).
- Vaccination with COVID-19 bivalent vaccine plus a high-dose or adjuvanted influenza vaccine (n = 4596) was associated with a significantly greater risk for nonhemorrhagic stroke 22-42 days after vaccination with Pfizer-BioNTech (IRR, 1.20; risk difference/100,000 doses, 3.13) and an increase in TIA risk 1-21 days after vaccination with Moderna (IRR, 1.35; risk difference/100,000 doses, 3.33).
- There was a significant association between vaccination with a high-dose or adjuvanted influenza vaccine (n = 21,345) and nonhemorrhagic stroke 22-42 days after vaccination (IRR, 1.09; risk difference/100,000 doses, 1.65).
IN PRACTICE:
“The clinical significance of the risk of stroke after vaccination must be carefully considered together with the significant benefits of receiving an influenza vaccination,” the authors wrote. “Because the framework of the current self-controlled case series study does not compare the populations who were vaccinated vs those who were unvaccinated, it does not account for the reduced rate of severe influenza after vaccination. More studies are needed to better understand the association between high-dose or adjuvanted influenza vaccination and stroke.”
SOURCE:
Yun Lu, PhD, of the Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, was the lead and corresponding author of the study. It was published online on March 19 in JAMA.
LIMITATIONS:
Some stroke cases may have been missed or misclassified. The study included only vaccinated individuals — a population considered to have health-seeking behaviors — which may limit the generalizability of the findings. The study was conducted using COVID-19 bivalent vaccines, which are no longer available.
DISCLOSURES:
This work was funded by the US Food and Drug Administration through an interagency agreement with the Centers for Medicare & Medicaid Services. Dr. Lu reported no relevant financial relationships. The other authors’ disclosures are listed in the original paper.
A version of this article appeared on Medscape.com.
TOPLINE:
, a new study of Medicare beneficiaries showed.
METHODOLOGY:
- The analysis included 5.4 million people age ≥ 65 years who received either the Pfizer-BioNTech COVID-19 bivalent vaccine or the Moderna bivalent vaccine, or the Pfizer vaccine and a high-dose or adjuvanted concomitant influenza vaccine (ie, administered on the same day).
- A total of 11,001 of the cohort experienced a stroke in the first 90 days after vaccination.
- The main outcome was stroke risk (nonhemorrhagic stroke, transient ischemic attack [TIA], or hemorrhagic stroke) during the 1- to 21-day or 22- to 42-day window after vaccination vs the 43- to 90-day control window.
- The mean age of participants was 74 years, and 56% were female.
TAKEAWAY:
- There was no statistically significant association with either brand of the COVID-19 bivalent vaccine or any of the stroke outcomes during the 1- to 21-day or 22- to 42-day risk window compared with the 43- to 90-day control window (incidence rate ratio [IRR] range, 0.72-1.12).
- Vaccination with COVID-19 bivalent vaccine plus a high-dose or adjuvanted influenza vaccine (n = 4596) was associated with a significantly greater risk for nonhemorrhagic stroke 22-42 days after vaccination with Pfizer-BioNTech (IRR, 1.20; risk difference/100,000 doses, 3.13) and an increase in TIA risk 1-21 days after vaccination with Moderna (IRR, 1.35; risk difference/100,000 doses, 3.33).
- There was a significant association between vaccination with a high-dose or adjuvanted influenza vaccine (n = 21,345) and nonhemorrhagic stroke 22-42 days after vaccination (IRR, 1.09; risk difference/100,000 doses, 1.65).
IN PRACTICE:
“The clinical significance of the risk of stroke after vaccination must be carefully considered together with the significant benefits of receiving an influenza vaccination,” the authors wrote. “Because the framework of the current self-controlled case series study does not compare the populations who were vaccinated vs those who were unvaccinated, it does not account for the reduced rate of severe influenza after vaccination. More studies are needed to better understand the association between high-dose or adjuvanted influenza vaccination and stroke.”
SOURCE:
Yun Lu, PhD, of the Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, was the lead and corresponding author of the study. It was published online on March 19 in JAMA.
LIMITATIONS:
Some stroke cases may have been missed or misclassified. The study included only vaccinated individuals — a population considered to have health-seeking behaviors — which may limit the generalizability of the findings. The study was conducted using COVID-19 bivalent vaccines, which are no longer available.
DISCLOSURES:
This work was funded by the US Food and Drug Administration through an interagency agreement with the Centers for Medicare & Medicaid Services. Dr. Lu reported no relevant financial relationships. The other authors’ disclosures are listed in the original paper.
A version of this article appeared on Medscape.com.
TOPLINE:
, a new study of Medicare beneficiaries showed.
METHODOLOGY:
- The analysis included 5.4 million people age ≥ 65 years who received either the Pfizer-BioNTech COVID-19 bivalent vaccine or the Moderna bivalent vaccine, or the Pfizer vaccine and a high-dose or adjuvanted concomitant influenza vaccine (ie, administered on the same day).
- A total of 11,001 of the cohort experienced a stroke in the first 90 days after vaccination.
- The main outcome was stroke risk (nonhemorrhagic stroke, transient ischemic attack [TIA], or hemorrhagic stroke) during the 1- to 21-day or 22- to 42-day window after vaccination vs the 43- to 90-day control window.
- The mean age of participants was 74 years, and 56% were female.
TAKEAWAY:
- There was no statistically significant association with either brand of the COVID-19 bivalent vaccine or any of the stroke outcomes during the 1- to 21-day or 22- to 42-day risk window compared with the 43- to 90-day control window (incidence rate ratio [IRR] range, 0.72-1.12).
- Vaccination with COVID-19 bivalent vaccine plus a high-dose or adjuvanted influenza vaccine (n = 4596) was associated with a significantly greater risk for nonhemorrhagic stroke 22-42 days after vaccination with Pfizer-BioNTech (IRR, 1.20; risk difference/100,000 doses, 3.13) and an increase in TIA risk 1-21 days after vaccination with Moderna (IRR, 1.35; risk difference/100,000 doses, 3.33).
- There was a significant association between vaccination with a high-dose or adjuvanted influenza vaccine (n = 21,345) and nonhemorrhagic stroke 22-42 days after vaccination (IRR, 1.09; risk difference/100,000 doses, 1.65).
IN PRACTICE:
“The clinical significance of the risk of stroke after vaccination must be carefully considered together with the significant benefits of receiving an influenza vaccination,” the authors wrote. “Because the framework of the current self-controlled case series study does not compare the populations who were vaccinated vs those who were unvaccinated, it does not account for the reduced rate of severe influenza after vaccination. More studies are needed to better understand the association between high-dose or adjuvanted influenza vaccination and stroke.”
SOURCE:
Yun Lu, PhD, of the Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, was the lead and corresponding author of the study. It was published online on March 19 in JAMA.
LIMITATIONS:
Some stroke cases may have been missed or misclassified. The study included only vaccinated individuals — a population considered to have health-seeking behaviors — which may limit the generalizability of the findings. The study was conducted using COVID-19 bivalent vaccines, which are no longer available.
DISCLOSURES:
This work was funded by the US Food and Drug Administration through an interagency agreement with the Centers for Medicare & Medicaid Services. Dr. Lu reported no relevant financial relationships. The other authors’ disclosures are listed in the original paper.
A version of this article appeared on Medscape.com.
Hemorrhagic Stroke a Key Driver of Spike in US Stroke Rates
TOPLINE:
Age-standardized stroke rates decreased in the United States between 1990 and 2019, while absolute stroke incidence, prevalence, mortality, and disability-adjusted life years (DALYs) rates increased, a new study showed. Investigators noted the findings, which also show a significant increase in hemorrhagic stroke and an uptick in stroke among adults under 50 years in the South and Midwest, suggesting a significant shift in the US stroke burden.
METHODOLOGY:
- This in-depth, cross-sectional analysis of the 2019 Global Burden of Disease study included data on all-cause and ischemic strokes, intracerebral hemorrhages (ICHs), and subarachnoid hemorrhages (SAHs) between 1990 and 2019 in the United States.
- Researchers focused on both overall and age-standardized estimates, stroke incidence, prevalence, mortality, and DALYs per 100,000 people.
TAKEAWAY:
- In 2019, the United States recorded 7.09 million prevalent strokes, 83% of which were ischemic and 57% of which occurred in women.
- The absolute numbers of stroke cases, mortality, and DALYs increased from 1990 to 2019, but the age-standardized rates either declined or remained steady.
- Overall incidence increased by 40% for ICH, 51% for SAH, and 13% for , and stroke mortality increased by 56% for ICH, 72% for SAH, and 5.4% for ischemic stroke.
- Age-adjusted analyses showed the results were not uniform across all geographical areas, with older adults (ages, 50-74 years) experiencing decreased incidence in coastal areas and younger individuals (ages, 15-49 years) experiencing an uptick in the South and Midwest United States.
IN PRACTICE:
“As the country prepares for an imminent swell in the aging population, coupled with a noticeable plateau in advancements against stroke mortality, it becomes evident that future directions must focus on a multipronged strategy,” the authors wrote. “This involves both embracing precision medicine’s potential and fortifying widespread public health campaigns.”
SOURCE:
Kevin N. Sheth, MD, of the Yale Center for Brain and Mind Health, Yale School of Medicine, New Haven, Connecticut, was the senior and corresponding author of the study. It was published online in JAMA Neurology.
LIMITATIONS:
The accuracy of stroke ascertainment was limited by the data source, which may be prone to misclassification. The data lacked detailed information on race, ethnicity, and stroke characteristics other than stroke type.
DISCLOSURES:
This work was funded by the Bill and Melinda Gates Foundation, the American Heart Association Medical Student Research Fellowship, grants from the National Institutes of Health, the American Heart Association, the Yale Pepper Scholar Award, and the Neurocritical Care Society Research fellowship. Sheth reported receiving grants from the National Institutes of Health, American Heart Association, and Hyperfine; personal fees/monitoring board fees/equity from Astrocyte, CSL Behring, Zoll, Sense, Bexorg, Rhaeos, and Alva and having a patent for Alva licensed. The other authors’ disclosures are listed in the original paper.
A version of this article appeared on Medscape.com.
TOPLINE:
Age-standardized stroke rates decreased in the United States between 1990 and 2019, while absolute stroke incidence, prevalence, mortality, and disability-adjusted life years (DALYs) rates increased, a new study showed. Investigators noted the findings, which also show a significant increase in hemorrhagic stroke and an uptick in stroke among adults under 50 years in the South and Midwest, suggesting a significant shift in the US stroke burden.
METHODOLOGY:
- This in-depth, cross-sectional analysis of the 2019 Global Burden of Disease study included data on all-cause and ischemic strokes, intracerebral hemorrhages (ICHs), and subarachnoid hemorrhages (SAHs) between 1990 and 2019 in the United States.
- Researchers focused on both overall and age-standardized estimates, stroke incidence, prevalence, mortality, and DALYs per 100,000 people.
TAKEAWAY:
- In 2019, the United States recorded 7.09 million prevalent strokes, 83% of which were ischemic and 57% of which occurred in women.
- The absolute numbers of stroke cases, mortality, and DALYs increased from 1990 to 2019, but the age-standardized rates either declined or remained steady.
- Overall incidence increased by 40% for ICH, 51% for SAH, and 13% for , and stroke mortality increased by 56% for ICH, 72% for SAH, and 5.4% for ischemic stroke.
- Age-adjusted analyses showed the results were not uniform across all geographical areas, with older adults (ages, 50-74 years) experiencing decreased incidence in coastal areas and younger individuals (ages, 15-49 years) experiencing an uptick in the South and Midwest United States.
IN PRACTICE:
“As the country prepares for an imminent swell in the aging population, coupled with a noticeable plateau in advancements against stroke mortality, it becomes evident that future directions must focus on a multipronged strategy,” the authors wrote. “This involves both embracing precision medicine’s potential and fortifying widespread public health campaigns.”
SOURCE:
Kevin N. Sheth, MD, of the Yale Center for Brain and Mind Health, Yale School of Medicine, New Haven, Connecticut, was the senior and corresponding author of the study. It was published online in JAMA Neurology.
LIMITATIONS:
The accuracy of stroke ascertainment was limited by the data source, which may be prone to misclassification. The data lacked detailed information on race, ethnicity, and stroke characteristics other than stroke type.
DISCLOSURES:
This work was funded by the Bill and Melinda Gates Foundation, the American Heart Association Medical Student Research Fellowship, grants from the National Institutes of Health, the American Heart Association, the Yale Pepper Scholar Award, and the Neurocritical Care Society Research fellowship. Sheth reported receiving grants from the National Institutes of Health, American Heart Association, and Hyperfine; personal fees/monitoring board fees/equity from Astrocyte, CSL Behring, Zoll, Sense, Bexorg, Rhaeos, and Alva and having a patent for Alva licensed. The other authors’ disclosures are listed in the original paper.
A version of this article appeared on Medscape.com.
TOPLINE:
Age-standardized stroke rates decreased in the United States between 1990 and 2019, while absolute stroke incidence, prevalence, mortality, and disability-adjusted life years (DALYs) rates increased, a new study showed. Investigators noted the findings, which also show a significant increase in hemorrhagic stroke and an uptick in stroke among adults under 50 years in the South and Midwest, suggesting a significant shift in the US stroke burden.
METHODOLOGY:
- This in-depth, cross-sectional analysis of the 2019 Global Burden of Disease study included data on all-cause and ischemic strokes, intracerebral hemorrhages (ICHs), and subarachnoid hemorrhages (SAHs) between 1990 and 2019 in the United States.
- Researchers focused on both overall and age-standardized estimates, stroke incidence, prevalence, mortality, and DALYs per 100,000 people.
TAKEAWAY:
- In 2019, the United States recorded 7.09 million prevalent strokes, 83% of which were ischemic and 57% of which occurred in women.
- The absolute numbers of stroke cases, mortality, and DALYs increased from 1990 to 2019, but the age-standardized rates either declined or remained steady.
- Overall incidence increased by 40% for ICH, 51% for SAH, and 13% for , and stroke mortality increased by 56% for ICH, 72% for SAH, and 5.4% for ischemic stroke.
- Age-adjusted analyses showed the results were not uniform across all geographical areas, with older adults (ages, 50-74 years) experiencing decreased incidence in coastal areas and younger individuals (ages, 15-49 years) experiencing an uptick in the South and Midwest United States.
IN PRACTICE:
“As the country prepares for an imminent swell in the aging population, coupled with a noticeable plateau in advancements against stroke mortality, it becomes evident that future directions must focus on a multipronged strategy,” the authors wrote. “This involves both embracing precision medicine’s potential and fortifying widespread public health campaigns.”
SOURCE:
Kevin N. Sheth, MD, of the Yale Center for Brain and Mind Health, Yale School of Medicine, New Haven, Connecticut, was the senior and corresponding author of the study. It was published online in JAMA Neurology.
LIMITATIONS:
The accuracy of stroke ascertainment was limited by the data source, which may be prone to misclassification. The data lacked detailed information on race, ethnicity, and stroke characteristics other than stroke type.
DISCLOSURES:
This work was funded by the Bill and Melinda Gates Foundation, the American Heart Association Medical Student Research Fellowship, grants from the National Institutes of Health, the American Heart Association, the Yale Pepper Scholar Award, and the Neurocritical Care Society Research fellowship. Sheth reported receiving grants from the National Institutes of Health, American Heart Association, and Hyperfine; personal fees/monitoring board fees/equity from Astrocyte, CSL Behring, Zoll, Sense, Bexorg, Rhaeos, and Alva and having a patent for Alva licensed. The other authors’ disclosures are listed in the original paper.
A version of this article appeared on Medscape.com.
Statins Tied to Lower Mortality, Even With Comorbid Dementia
Use of statin drugs was associated with improved mortality in older nursing home residents, regardless of dementia status, a new study showed.
The study is among the first to explore whether statin use in older nursing home residents offers a mortality benefit, especially among individuals with dementia, a group largely excluded from earlier statin trials.
Investigators’ analysis of 4 years of data on nearly 300,000 nursing home residents revealed that statin use was associated with a 40% lower risk for all-cause mortality than statin nonuse in those without dementia and a 20% lower risk in those with dementia.
“These findings may provide evidence that supports the continued use of statins in older nursing home patients with multiple medical conditions,” wrote lead author Julie Lorraine O’Sullivan, PhD, of the Charité–Universitätsmedizin Berlin, Freie Universität Berlin, German Center for Mental Health, Berlin, and colleagues.
The study was published online on February 27 in Neurology.
Understudied Population
Statins are the first-line treatment for preventing atherosclerotic cardiovascular disease (ASCVD), but they are also known to carry risks to patients who are frail or care-dependent. Many prior clinical trials excluded older participants with multiple comorbidities, especially those with dementia. So, evidence regarding the drugs’ efficacy in this population was lacking.
Investigators retrospectively examined 5 years of claims data from a German health and long-term care insurance provider on 282,693 nursing home residents (mean age, 83 years) who had used statins consecutively for ≥ 6 months.
Researchers used propensity score matching in 96,162 individuals to adjust for potential imbalances in the distribution of covariates (eg, age, sex, atrial fibrillation, ASCVD, and other conditions, as well as medications) and to reduce bias. Cox regression models were similarly adjusted for these factors, as well as care level. Residents were followed for an average of 2 years.
There were 54,269 recorded deaths during the study period, with most patients requiring a high level of care and 65% with dementia.
Statin use was associated with lower all-cause mortality in residents with dementia (hazard ratio [HR], 0.80, P < .001) and those without dementia (HR, 0.73; P < .001) compared with nonusers. The benefits remained consistent even after excluding participants with a history of ASCVD and across subgroups stratified by age sex, care level, and dementia type.
Limitations included the potential for unknown confounders and a lack of information about previous statin use, smoking and sedentary behavior, and the cause of mortality.
“Although our findings suggest the benefits of statins ... it is vital to acknowledge the need for further research to understand the underlying mechanism and the need for replication of our results to understand the potential risks before making recommendations to clinicians and families regarding statin therapy,” investigators wrote.
‘First Step’
In an accompanying editorial, Ariela R. Orkaby, MD, MPH, assistant professor of medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, called the study a “first step” to a better understanding of statin use in an understudied population.
“These findings build on a limited body of observational evidence for statin use in high-risk older adults, which has generally demonstrated protective associations for statins and mortality, including those with dementia and frailty, although nursing home status has not been specifically explored,” Dr. Orkaby wrote.
Perhaps more important than gaining information about statins’ effect on mortality risk in older people with dementia may be a better understanding of how the drugs might improve quality of life by reducing the risk for stroke or other cardiovascular events.
“It may be time to reconsider the broad recommendations to avoid or deprescribe statins in nursing home residents and rather invest in high-quality evidence to guide the care of this vulnerable population. After all, a lack of evidence does not imply benefit or harm, rather a need for more data,” Dr. Orkaby added.
The research was funded by Stiftung Charité; Dr. O’Sullivan and coauthors reported no relevant financial relationships. Dr. Orkaby received funding from a VA CSR&D CDA-2 award.
A version of this article appeared on Medscape.com.
Use of statin drugs was associated with improved mortality in older nursing home residents, regardless of dementia status, a new study showed.
The study is among the first to explore whether statin use in older nursing home residents offers a mortality benefit, especially among individuals with dementia, a group largely excluded from earlier statin trials.
Investigators’ analysis of 4 years of data on nearly 300,000 nursing home residents revealed that statin use was associated with a 40% lower risk for all-cause mortality than statin nonuse in those without dementia and a 20% lower risk in those with dementia.
“These findings may provide evidence that supports the continued use of statins in older nursing home patients with multiple medical conditions,” wrote lead author Julie Lorraine O’Sullivan, PhD, of the Charité–Universitätsmedizin Berlin, Freie Universität Berlin, German Center for Mental Health, Berlin, and colleagues.
The study was published online on February 27 in Neurology.
Understudied Population
Statins are the first-line treatment for preventing atherosclerotic cardiovascular disease (ASCVD), but they are also known to carry risks to patients who are frail or care-dependent. Many prior clinical trials excluded older participants with multiple comorbidities, especially those with dementia. So, evidence regarding the drugs’ efficacy in this population was lacking.
Investigators retrospectively examined 5 years of claims data from a German health and long-term care insurance provider on 282,693 nursing home residents (mean age, 83 years) who had used statins consecutively for ≥ 6 months.
Researchers used propensity score matching in 96,162 individuals to adjust for potential imbalances in the distribution of covariates (eg, age, sex, atrial fibrillation, ASCVD, and other conditions, as well as medications) and to reduce bias. Cox regression models were similarly adjusted for these factors, as well as care level. Residents were followed for an average of 2 years.
There were 54,269 recorded deaths during the study period, with most patients requiring a high level of care and 65% with dementia.
Statin use was associated with lower all-cause mortality in residents with dementia (hazard ratio [HR], 0.80, P < .001) and those without dementia (HR, 0.73; P < .001) compared with nonusers. The benefits remained consistent even after excluding participants with a history of ASCVD and across subgroups stratified by age sex, care level, and dementia type.
Limitations included the potential for unknown confounders and a lack of information about previous statin use, smoking and sedentary behavior, and the cause of mortality.
“Although our findings suggest the benefits of statins ... it is vital to acknowledge the need for further research to understand the underlying mechanism and the need for replication of our results to understand the potential risks before making recommendations to clinicians and families regarding statin therapy,” investigators wrote.
‘First Step’
In an accompanying editorial, Ariela R. Orkaby, MD, MPH, assistant professor of medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, called the study a “first step” to a better understanding of statin use in an understudied population.
“These findings build on a limited body of observational evidence for statin use in high-risk older adults, which has generally demonstrated protective associations for statins and mortality, including those with dementia and frailty, although nursing home status has not been specifically explored,” Dr. Orkaby wrote.
Perhaps more important than gaining information about statins’ effect on mortality risk in older people with dementia may be a better understanding of how the drugs might improve quality of life by reducing the risk for stroke or other cardiovascular events.
“It may be time to reconsider the broad recommendations to avoid or deprescribe statins in nursing home residents and rather invest in high-quality evidence to guide the care of this vulnerable population. After all, a lack of evidence does not imply benefit or harm, rather a need for more data,” Dr. Orkaby added.
The research was funded by Stiftung Charité; Dr. O’Sullivan and coauthors reported no relevant financial relationships. Dr. Orkaby received funding from a VA CSR&D CDA-2 award.
A version of this article appeared on Medscape.com.
Use of statin drugs was associated with improved mortality in older nursing home residents, regardless of dementia status, a new study showed.
The study is among the first to explore whether statin use in older nursing home residents offers a mortality benefit, especially among individuals with dementia, a group largely excluded from earlier statin trials.
Investigators’ analysis of 4 years of data on nearly 300,000 nursing home residents revealed that statin use was associated with a 40% lower risk for all-cause mortality than statin nonuse in those without dementia and a 20% lower risk in those with dementia.
“These findings may provide evidence that supports the continued use of statins in older nursing home patients with multiple medical conditions,” wrote lead author Julie Lorraine O’Sullivan, PhD, of the Charité–Universitätsmedizin Berlin, Freie Universität Berlin, German Center for Mental Health, Berlin, and colleagues.
The study was published online on February 27 in Neurology.
Understudied Population
Statins are the first-line treatment for preventing atherosclerotic cardiovascular disease (ASCVD), but they are also known to carry risks to patients who are frail or care-dependent. Many prior clinical trials excluded older participants with multiple comorbidities, especially those with dementia. So, evidence regarding the drugs’ efficacy in this population was lacking.
Investigators retrospectively examined 5 years of claims data from a German health and long-term care insurance provider on 282,693 nursing home residents (mean age, 83 years) who had used statins consecutively for ≥ 6 months.
Researchers used propensity score matching in 96,162 individuals to adjust for potential imbalances in the distribution of covariates (eg, age, sex, atrial fibrillation, ASCVD, and other conditions, as well as medications) and to reduce bias. Cox regression models were similarly adjusted for these factors, as well as care level. Residents were followed for an average of 2 years.
There were 54,269 recorded deaths during the study period, with most patients requiring a high level of care and 65% with dementia.
Statin use was associated with lower all-cause mortality in residents with dementia (hazard ratio [HR], 0.80, P < .001) and those without dementia (HR, 0.73; P < .001) compared with nonusers. The benefits remained consistent even after excluding participants with a history of ASCVD and across subgroups stratified by age sex, care level, and dementia type.
Limitations included the potential for unknown confounders and a lack of information about previous statin use, smoking and sedentary behavior, and the cause of mortality.
“Although our findings suggest the benefits of statins ... it is vital to acknowledge the need for further research to understand the underlying mechanism and the need for replication of our results to understand the potential risks before making recommendations to clinicians and families regarding statin therapy,” investigators wrote.
‘First Step’
In an accompanying editorial, Ariela R. Orkaby, MD, MPH, assistant professor of medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, called the study a “first step” to a better understanding of statin use in an understudied population.
“These findings build on a limited body of observational evidence for statin use in high-risk older adults, which has generally demonstrated protective associations for statins and mortality, including those with dementia and frailty, although nursing home status has not been specifically explored,” Dr. Orkaby wrote.
Perhaps more important than gaining information about statins’ effect on mortality risk in older people with dementia may be a better understanding of how the drugs might improve quality of life by reducing the risk for stroke or other cardiovascular events.
“It may be time to reconsider the broad recommendations to avoid or deprescribe statins in nursing home residents and rather invest in high-quality evidence to guide the care of this vulnerable population. After all, a lack of evidence does not imply benefit or harm, rather a need for more data,” Dr. Orkaby added.
The research was funded by Stiftung Charité; Dr. O’Sullivan and coauthors reported no relevant financial relationships. Dr. Orkaby received funding from a VA CSR&D CDA-2 award.
A version of this article appeared on Medscape.com.
Glucose Level Fluctuations Affect Cognition in T1D
TOPLINE:
Naturally occurring glucose fluctuations affect cognitive function in people with type 1 diabetes, according to a new study. It matters less whether glucose is considerably higher or lower than the patient’s usual glucose level. Rather,
METHODOLOGY:
- The investigators used continuous glucose monitoring (CGM) digital sensors and smartphone-based cognitive tests (cognitive ecological momentary assessment [EMA]) to collect repeated, high-frequency glucose and cognitive data. Glucose data were collected every 5 minutes; cognitive data were collected three times daily for 15 days as participants went about their daily lives.
- The study included 200 participants (mean [standard deviation] age, 47.5 [15.6] years; 53.5% female; 86% White; mean A1c, 7.5 mmol/mol [1.3]).
- Using CGM and EMA, the researchers obtained “intensive” longitudinal measurements of glucose as well as cognition (processing speed and sustained attention).
- Hierarchical Bayesian modeling estimated dynamic, within-person associations between glucose and cognition, and data-driven lasso regression identified identify clinical characteristics that predicted differences from person to person in cognitive vulnerability to glucose fluctuations.
TAKEAWAY:
- Cognitive performance was reduced both at low and high glucose levels, “reflecting vulnerability to glucose fluctuations.”
- Large glucose fluctuations were associated with slower as well as less accurate processing speed, although slight glucose elevations (relative to the individual’s own means) were associated with faster processing speed, regardless of the absolute level (eg, euglycemic vs hyperglycemic) of those means.
- By contrast, glucose fluctuations were unrelated to sustained attention.
- The researchers identified seven clinical characteristics that predicted individual differences in cognitive vulnerability to glucose fluctuations: Older age, time in hypoglycemia, lifetime severe hypoglycemic events, microvascular complications, glucose variability, fatigue, and larger neck circumference.
IN PRACTICE:
“Our results demonstrate that people can differ a lot from one another in how their brains are impacted by glucose,” co-senior author Laura Germine, PhD, director of the Laboratory for Brain and Cognitive Health Technology, McLean Hospital, Boston, said in a news release. “We found that minimizing glucose fluctuations in daily life is important for optimizing processing speed, and this is especially true for people who are older or have other diabetes-related health conditions.”
SOURCE:
Zoë Hawks, PhD, research investigator, McLean Hospital, Boston, was the lead and corresponding author on the study. It was published online on March 18 in Digital Medicine.
LIMITATIONS:
The researchers required 24-hour access to a smartphone with reliable Internet access, which might have biased sampling toward people of higher economic status. Moreover, the present sample was predominantly White and non-Hispanic, so findings may not be generalizable to other populations.
DISCLOSURES:
The research was supported by grants from the National Institutes of Health, the Brain and Behavior Research Foundation, and the Alzheimer’s Association. Dr. Hawks received consulting fees from Blueprint Health. The other authors’ disclosures were listed in the original paper.
A version of this article appeared on Medscape.com.
TOPLINE:
Naturally occurring glucose fluctuations affect cognitive function in people with type 1 diabetes, according to a new study. It matters less whether glucose is considerably higher or lower than the patient’s usual glucose level. Rather,
METHODOLOGY:
- The investigators used continuous glucose monitoring (CGM) digital sensors and smartphone-based cognitive tests (cognitive ecological momentary assessment [EMA]) to collect repeated, high-frequency glucose and cognitive data. Glucose data were collected every 5 minutes; cognitive data were collected three times daily for 15 days as participants went about their daily lives.
- The study included 200 participants (mean [standard deviation] age, 47.5 [15.6] years; 53.5% female; 86% White; mean A1c, 7.5 mmol/mol [1.3]).
- Using CGM and EMA, the researchers obtained “intensive” longitudinal measurements of glucose as well as cognition (processing speed and sustained attention).
- Hierarchical Bayesian modeling estimated dynamic, within-person associations between glucose and cognition, and data-driven lasso regression identified identify clinical characteristics that predicted differences from person to person in cognitive vulnerability to glucose fluctuations.
TAKEAWAY:
- Cognitive performance was reduced both at low and high glucose levels, “reflecting vulnerability to glucose fluctuations.”
- Large glucose fluctuations were associated with slower as well as less accurate processing speed, although slight glucose elevations (relative to the individual’s own means) were associated with faster processing speed, regardless of the absolute level (eg, euglycemic vs hyperglycemic) of those means.
- By contrast, glucose fluctuations were unrelated to sustained attention.
- The researchers identified seven clinical characteristics that predicted individual differences in cognitive vulnerability to glucose fluctuations: Older age, time in hypoglycemia, lifetime severe hypoglycemic events, microvascular complications, glucose variability, fatigue, and larger neck circumference.
IN PRACTICE:
“Our results demonstrate that people can differ a lot from one another in how their brains are impacted by glucose,” co-senior author Laura Germine, PhD, director of the Laboratory for Brain and Cognitive Health Technology, McLean Hospital, Boston, said in a news release. “We found that minimizing glucose fluctuations in daily life is important for optimizing processing speed, and this is especially true for people who are older or have other diabetes-related health conditions.”
SOURCE:
Zoë Hawks, PhD, research investigator, McLean Hospital, Boston, was the lead and corresponding author on the study. It was published online on March 18 in Digital Medicine.
LIMITATIONS:
The researchers required 24-hour access to a smartphone with reliable Internet access, which might have biased sampling toward people of higher economic status. Moreover, the present sample was predominantly White and non-Hispanic, so findings may not be generalizable to other populations.
DISCLOSURES:
The research was supported by grants from the National Institutes of Health, the Brain and Behavior Research Foundation, and the Alzheimer’s Association. Dr. Hawks received consulting fees from Blueprint Health. The other authors’ disclosures were listed in the original paper.
A version of this article appeared on Medscape.com.
TOPLINE:
Naturally occurring glucose fluctuations affect cognitive function in people with type 1 diabetes, according to a new study. It matters less whether glucose is considerably higher or lower than the patient’s usual glucose level. Rather,
METHODOLOGY:
- The investigators used continuous glucose monitoring (CGM) digital sensors and smartphone-based cognitive tests (cognitive ecological momentary assessment [EMA]) to collect repeated, high-frequency glucose and cognitive data. Glucose data were collected every 5 minutes; cognitive data were collected three times daily for 15 days as participants went about their daily lives.
- The study included 200 participants (mean [standard deviation] age, 47.5 [15.6] years; 53.5% female; 86% White; mean A1c, 7.5 mmol/mol [1.3]).
- Using CGM and EMA, the researchers obtained “intensive” longitudinal measurements of glucose as well as cognition (processing speed and sustained attention).
- Hierarchical Bayesian modeling estimated dynamic, within-person associations between glucose and cognition, and data-driven lasso regression identified identify clinical characteristics that predicted differences from person to person in cognitive vulnerability to glucose fluctuations.
TAKEAWAY:
- Cognitive performance was reduced both at low and high glucose levels, “reflecting vulnerability to glucose fluctuations.”
- Large glucose fluctuations were associated with slower as well as less accurate processing speed, although slight glucose elevations (relative to the individual’s own means) were associated with faster processing speed, regardless of the absolute level (eg, euglycemic vs hyperglycemic) of those means.
- By contrast, glucose fluctuations were unrelated to sustained attention.
- The researchers identified seven clinical characteristics that predicted individual differences in cognitive vulnerability to glucose fluctuations: Older age, time in hypoglycemia, lifetime severe hypoglycemic events, microvascular complications, glucose variability, fatigue, and larger neck circumference.
IN PRACTICE:
“Our results demonstrate that people can differ a lot from one another in how their brains are impacted by glucose,” co-senior author Laura Germine, PhD, director of the Laboratory for Brain and Cognitive Health Technology, McLean Hospital, Boston, said in a news release. “We found that minimizing glucose fluctuations in daily life is important for optimizing processing speed, and this is especially true for people who are older or have other diabetes-related health conditions.”
SOURCE:
Zoë Hawks, PhD, research investigator, McLean Hospital, Boston, was the lead and corresponding author on the study. It was published online on March 18 in Digital Medicine.
LIMITATIONS:
The researchers required 24-hour access to a smartphone with reliable Internet access, which might have biased sampling toward people of higher economic status. Moreover, the present sample was predominantly White and non-Hispanic, so findings may not be generalizable to other populations.
DISCLOSURES:
The research was supported by grants from the National Institutes of Health, the Brain and Behavior Research Foundation, and the Alzheimer’s Association. Dr. Hawks received consulting fees from Blueprint Health. The other authors’ disclosures were listed in the original paper.
A version of this article appeared on Medscape.com.
Obstructive Sleep Apnea Linked to Higher Stroke Risk
TOPLINE:
Obstructive sleep apnea (OSA) is associated with a significantly higher risk for stroke — regardless of continuous positive airway pressure (CPAP) device use — but only in White individuals, new data suggested. The study also found that stroke risk among Black individuals with OSA was lower in those who used CPAP machines vs those who didn›t.
METHODOLOGY:
- Researchers used data on 22,192 people from the Reasons for Geographic and Racial Differences in Stroke study, a US population-based cohort of Black and White individuals with no history of stroke at baseline (mean age, 64 years; 38% Black individuals).
- 11% of overall participants had provider diagnosed OSA at baseline.
- Participants were followed for a mean of 12 years.
- Researchers adjusted for demographic, socioeconomic, and stroke risk factors.
TAKEAWAY:
- During the follow-up period, 969 participants (4.4%) experienced a stroke.
- After adjusting for confounders, having high OSA risk and diagnosed OSA were associated with higher risks for incident stroke in White individuals (adjusted hazard ratio [aHR], 1.22; 95% CI, 1.01-1.47 and aHR, 1.33; 95% CI, 1.04-1.70, respectively) but not in Black individuals.
- Snoring was not associated with incident stroke in either Black or White individuals.
- Snoring was not associated with incident stroke in either Black or White individuals.
IN PRACTICE:
“These results were not what we were expecting to find since Black people have been shown to have a higher risk of stroke and are more likely to have sleep apnea than White people,” lead author Rebecca Robbins, MMSc, PhD, of Brigham and Women’s Hospital in Boston, Massachusetts, said in a news release. “Since it has been shown that Black people have more severe sleep apnea than White people and take longer to be screened and treated than White people, it’s possible that using a CPAP machine provides a greater benefit on reducing stroke risk for Black people.”
SOURCE:
Robbins was the lead and corresponding author of the study. It was published online in Neurology.
LIMITATIONS:
The current study assessed only self-reported OSA symptoms, risk, diagnosis, and treatment and did not include data on the hours of CPAP usage at night, number of days of treatment, adherence during the follow-up period, and OSA severity.
DISCLOSURES:
The study was funded by the National Institute of Neurological Disorders and Stroke and the National Institute on Aging. Robbins received consulting income from Sonesta Hotels International, Oura Ring Ltd., Savoir Beds Ltd., Castle Hot Springs, and ByNacht GmbH. The other authors’ disclosures are listed in the original paper.
A version of this article appeared on Medscape.com.
TOPLINE:
Obstructive sleep apnea (OSA) is associated with a significantly higher risk for stroke — regardless of continuous positive airway pressure (CPAP) device use — but only in White individuals, new data suggested. The study also found that stroke risk among Black individuals with OSA was lower in those who used CPAP machines vs those who didn›t.
METHODOLOGY:
- Researchers used data on 22,192 people from the Reasons for Geographic and Racial Differences in Stroke study, a US population-based cohort of Black and White individuals with no history of stroke at baseline (mean age, 64 years; 38% Black individuals).
- 11% of overall participants had provider diagnosed OSA at baseline.
- Participants were followed for a mean of 12 years.
- Researchers adjusted for demographic, socioeconomic, and stroke risk factors.
TAKEAWAY:
- During the follow-up period, 969 participants (4.4%) experienced a stroke.
- After adjusting for confounders, having high OSA risk and diagnosed OSA were associated with higher risks for incident stroke in White individuals (adjusted hazard ratio [aHR], 1.22; 95% CI, 1.01-1.47 and aHR, 1.33; 95% CI, 1.04-1.70, respectively) but not in Black individuals.
- Snoring was not associated with incident stroke in either Black or White individuals.
- Snoring was not associated with incident stroke in either Black or White individuals.
IN PRACTICE:
“These results were not what we were expecting to find since Black people have been shown to have a higher risk of stroke and are more likely to have sleep apnea than White people,” lead author Rebecca Robbins, MMSc, PhD, of Brigham and Women’s Hospital in Boston, Massachusetts, said in a news release. “Since it has been shown that Black people have more severe sleep apnea than White people and take longer to be screened and treated than White people, it’s possible that using a CPAP machine provides a greater benefit on reducing stroke risk for Black people.”
SOURCE:
Robbins was the lead and corresponding author of the study. It was published online in Neurology.
LIMITATIONS:
The current study assessed only self-reported OSA symptoms, risk, diagnosis, and treatment and did not include data on the hours of CPAP usage at night, number of days of treatment, adherence during the follow-up period, and OSA severity.
DISCLOSURES:
The study was funded by the National Institute of Neurological Disorders and Stroke and the National Institute on Aging. Robbins received consulting income from Sonesta Hotels International, Oura Ring Ltd., Savoir Beds Ltd., Castle Hot Springs, and ByNacht GmbH. The other authors’ disclosures are listed in the original paper.
A version of this article appeared on Medscape.com.
TOPLINE:
Obstructive sleep apnea (OSA) is associated with a significantly higher risk for stroke — regardless of continuous positive airway pressure (CPAP) device use — but only in White individuals, new data suggested. The study also found that stroke risk among Black individuals with OSA was lower in those who used CPAP machines vs those who didn›t.
METHODOLOGY:
- Researchers used data on 22,192 people from the Reasons for Geographic and Racial Differences in Stroke study, a US population-based cohort of Black and White individuals with no history of stroke at baseline (mean age, 64 years; 38% Black individuals).
- 11% of overall participants had provider diagnosed OSA at baseline.
- Participants were followed for a mean of 12 years.
- Researchers adjusted for demographic, socioeconomic, and stroke risk factors.
TAKEAWAY:
- During the follow-up period, 969 participants (4.4%) experienced a stroke.
- After adjusting for confounders, having high OSA risk and diagnosed OSA were associated with higher risks for incident stroke in White individuals (adjusted hazard ratio [aHR], 1.22; 95% CI, 1.01-1.47 and aHR, 1.33; 95% CI, 1.04-1.70, respectively) but not in Black individuals.
- Snoring was not associated with incident stroke in either Black or White individuals.
- Snoring was not associated with incident stroke in either Black or White individuals.
IN PRACTICE:
“These results were not what we were expecting to find since Black people have been shown to have a higher risk of stroke and are more likely to have sleep apnea than White people,” lead author Rebecca Robbins, MMSc, PhD, of Brigham and Women’s Hospital in Boston, Massachusetts, said in a news release. “Since it has been shown that Black people have more severe sleep apnea than White people and take longer to be screened and treated than White people, it’s possible that using a CPAP machine provides a greater benefit on reducing stroke risk for Black people.”
SOURCE:
Robbins was the lead and corresponding author of the study. It was published online in Neurology.
LIMITATIONS:
The current study assessed only self-reported OSA symptoms, risk, diagnosis, and treatment and did not include data on the hours of CPAP usage at night, number of days of treatment, adherence during the follow-up period, and OSA severity.
DISCLOSURES:
The study was funded by the National Institute of Neurological Disorders and Stroke and the National Institute on Aging. Robbins received consulting income from Sonesta Hotels International, Oura Ring Ltd., Savoir Beds Ltd., Castle Hot Springs, and ByNacht GmbH. The other authors’ disclosures are listed in the original paper.
A version of this article appeared on Medscape.com.
New Data on Mild COVID’s Risk for Neurologic, Psychiatric Disorders
While severe COVID-19 is associated with a significantly higher risk for psychiatric and neurologic disorders a year after infection, mild does not carry the same risk, a new study shows.
However, less severe COVID-19 was not linked to a higher incidence of psychiatric diagnoses and was associated with only a slightly higher risk for neurologic disorders.
The new research challenges previous findings of long-term risk for psychiatric and neurologic disorders associated with SARS-CoV-2 in patients who had not been hospitalized for the condition.
“Our study does not support previous findings of substantial post-acute neurologic and psychiatric morbidities among the general population of SARS-CoV-2-infected individuals but does corroborate an elevated risk among the most severe cases with COVID-19,” the authors wrote.
The study was published online on February 21 in Neurology.
‘Alarming’ Findings
Previous studies have reported nervous system symptoms in patients who have experienced COVID-19, which may persist for several weeks or months after the acute phase, even in milder cases.
But these findings haven’t been consistent across all studies, and few studies have addressed the potential effect of different viral variants and vaccination status on post-acute psychiatric and neurologic morbidities.
“Our study was partly motivated by our strong research interest in the associations between infectious disease and later chronic disease and partly by international studies, such as those conducted in the US Veterans Health databases, that have suggested substantial risks of psychiatric and neurological conditions associated with infection,” senior author Anders Hviid, MSc, DrMedSci, head of the department and professor of pharmacoepidemiology, Statens Serum Institut, Copenhagen, Denmark, told this news organization.
Investigators drew on data from the Danish National Patient Registry to compare the risk for neurologic and psychiatric disorders during the 12 months after acute COVID-19 infection to risk among people who never tested positive.
They examined data on all recorded hospital contacts between January 2005 and January 2023 for a discharge diagnosis of at least one of 11 psychiatric illnesses or at least one of 30 neurologic disorders.
The researchers compared the incidence of each disorder within 1-12 months after infection with those of COVID-naive individuals and stratified analyses according to time since infection, vaccination status, variant period, age, sex, and infection severity.
The final study cohort included 1.8 million individuals who tested positive during the study period and 1.5 who didn’t. Three quarters of those who tested positive were infected primarily with the Omicron variant.
Hospitalized vs Nonhospitalized
Overall, individuals who tested positive had a 24% lower risk for psychiatric disorders during the post-acute period (incident rate ratio [IRR], 0.76; 95% CI, 0.74-0.78) compared with the control group, but a 5% higher risk for any neurologic disorder (IRR, 1.05; 95% CI, 1.04-1.07).
Age, sex, and variant had less influence on risk than infection severity, where the differences between hospitalized and nonhospitalized patients were significant.
Compared with COVID-negative individuals, the risk for any psychiatric disorder was double for hospitalized patients (IRR, 2.05; 95% CI, 1.78-2.37) but was 25% lower among nonhospitalized patients (IRR, 0.75; 95% CI, 0.73-0.77).
For neurologic disorders, the IRR for hospitalized patients was 2.44 (95% CI, 2.29-2.60) compared with COVID-negative individuals vs an IRR of only 1.02 (95% CI, 1.01-1.04) among nonhospitalized patients.
“In a general population, there was little support for clinically relevant post-acute risk increases of psychiatric and neurologic disorders associated with SARS-CoV-2 infection without hospitalization. This was particularly true for vaccinated individuals and for the more recent variants,” the authors wrote, adding that the only exception was for change in sense and smell.
‘Flaws’ in Previous Studies?
The findings in hospitalized patients were in line with previous findings, but those in nonhospitalized patients stand out, they added.
Previous studies were done predominantly in older males with comorbidities and those who were more socioeconomically disadvantaged, which could lead to a bias, Dr. Hviid said.
Those other studies “had a number of fundamental flaws that we do not believe our study has,” Dr. Hviid said. “Our study was conducted in the general population, with free and universal testing and healthcare.”
Researchers stress that sequelae after infection are predominantly associated with severe illness.
“Today, a healthy vaccinated adult having an asymptomatic or mild bout of COVID-19 with the current variants shouldn’t fear developing serious psychiatric or neurologic disorders in the months or years after infection.”
One limitation is that only hospital contacts were included, omitting possible diagnoses given outside hospital settings.
‘Extreme Caution’ Required
The link between COVID-19 and brain health is “complex,” and the new findings should be viewed cautiously, said Maxime Taquet, MRCPsych, PhD, National Institute for Health and Care Research clinical lecturer and specialty registrar in Psychiatry, Oxford Health NHS Foundation Trust, England, who commented on the findings.
Previous research by Dr. Taquet, who was not involved in the current study, found an increased risk for neurologic and psychiatric diagnoses during the first 6 months after COVID-19 diagnosis.
The current study “contributes to better understanding this link by providing data from another country with a different organization of healthcare provision than the US, where most of the existing data come from,” Dr. Taquet said.
However, “some observations — for example, that COVID-19 is associated with a 50% reduction in the risk of autism, a condition present from very early in life — call for extreme caution in the interpretation of the findings, as they suggest that residual bias has not been accounted for,” Dr. Taquet continued.
Authors of an accompanying editorial, Eric Chow, MD, MS, MPH, of the Division of Allergy and Infectious Diseases, University of Washington, School of Public Health, and Anita Chopra, MD, of the post-COVID Clinic, University of Washington, Seattle, called the study a “critical contribution to the published literature.”
The association of neurologic and psychiatric diagnoses with severe disease “is a reminder of the importance of risk reduction by combining vaccinations with improved indoor ventilation and masking,” they concluded.
The study was supported by a grant from the Independent Research Fund Denmark. Dr. Hviid and coauthors, Dr. Chopra, and Dr. Taquet reported no relevant financial relationships. Dr. Chow received a travel award from the Infectious Diseases Society of America to attend ID Week 2022.
A version of this article appeared on Medscape.com.
While severe COVID-19 is associated with a significantly higher risk for psychiatric and neurologic disorders a year after infection, mild does not carry the same risk, a new study shows.
However, less severe COVID-19 was not linked to a higher incidence of psychiatric diagnoses and was associated with only a slightly higher risk for neurologic disorders.
The new research challenges previous findings of long-term risk for psychiatric and neurologic disorders associated with SARS-CoV-2 in patients who had not been hospitalized for the condition.
“Our study does not support previous findings of substantial post-acute neurologic and psychiatric morbidities among the general population of SARS-CoV-2-infected individuals but does corroborate an elevated risk among the most severe cases with COVID-19,” the authors wrote.
The study was published online on February 21 in Neurology.
‘Alarming’ Findings
Previous studies have reported nervous system symptoms in patients who have experienced COVID-19, which may persist for several weeks or months after the acute phase, even in milder cases.
But these findings haven’t been consistent across all studies, and few studies have addressed the potential effect of different viral variants and vaccination status on post-acute psychiatric and neurologic morbidities.
“Our study was partly motivated by our strong research interest in the associations between infectious disease and later chronic disease and partly by international studies, such as those conducted in the US Veterans Health databases, that have suggested substantial risks of psychiatric and neurological conditions associated with infection,” senior author Anders Hviid, MSc, DrMedSci, head of the department and professor of pharmacoepidemiology, Statens Serum Institut, Copenhagen, Denmark, told this news organization.
Investigators drew on data from the Danish National Patient Registry to compare the risk for neurologic and psychiatric disorders during the 12 months after acute COVID-19 infection to risk among people who never tested positive.
They examined data on all recorded hospital contacts between January 2005 and January 2023 for a discharge diagnosis of at least one of 11 psychiatric illnesses or at least one of 30 neurologic disorders.
The researchers compared the incidence of each disorder within 1-12 months after infection with those of COVID-naive individuals and stratified analyses according to time since infection, vaccination status, variant period, age, sex, and infection severity.
The final study cohort included 1.8 million individuals who tested positive during the study period and 1.5 who didn’t. Three quarters of those who tested positive were infected primarily with the Omicron variant.
Hospitalized vs Nonhospitalized
Overall, individuals who tested positive had a 24% lower risk for psychiatric disorders during the post-acute period (incident rate ratio [IRR], 0.76; 95% CI, 0.74-0.78) compared with the control group, but a 5% higher risk for any neurologic disorder (IRR, 1.05; 95% CI, 1.04-1.07).
Age, sex, and variant had less influence on risk than infection severity, where the differences between hospitalized and nonhospitalized patients were significant.
Compared with COVID-negative individuals, the risk for any psychiatric disorder was double for hospitalized patients (IRR, 2.05; 95% CI, 1.78-2.37) but was 25% lower among nonhospitalized patients (IRR, 0.75; 95% CI, 0.73-0.77).
For neurologic disorders, the IRR for hospitalized patients was 2.44 (95% CI, 2.29-2.60) compared with COVID-negative individuals vs an IRR of only 1.02 (95% CI, 1.01-1.04) among nonhospitalized patients.
“In a general population, there was little support for clinically relevant post-acute risk increases of psychiatric and neurologic disorders associated with SARS-CoV-2 infection without hospitalization. This was particularly true for vaccinated individuals and for the more recent variants,” the authors wrote, adding that the only exception was for change in sense and smell.
‘Flaws’ in Previous Studies?
The findings in hospitalized patients were in line with previous findings, but those in nonhospitalized patients stand out, they added.
Previous studies were done predominantly in older males with comorbidities and those who were more socioeconomically disadvantaged, which could lead to a bias, Dr. Hviid said.
Those other studies “had a number of fundamental flaws that we do not believe our study has,” Dr. Hviid said. “Our study was conducted in the general population, with free and universal testing and healthcare.”
Researchers stress that sequelae after infection are predominantly associated with severe illness.
“Today, a healthy vaccinated adult having an asymptomatic or mild bout of COVID-19 with the current variants shouldn’t fear developing serious psychiatric or neurologic disorders in the months or years after infection.”
One limitation is that only hospital contacts were included, omitting possible diagnoses given outside hospital settings.
‘Extreme Caution’ Required
The link between COVID-19 and brain health is “complex,” and the new findings should be viewed cautiously, said Maxime Taquet, MRCPsych, PhD, National Institute for Health and Care Research clinical lecturer and specialty registrar in Psychiatry, Oxford Health NHS Foundation Trust, England, who commented on the findings.
Previous research by Dr. Taquet, who was not involved in the current study, found an increased risk for neurologic and psychiatric diagnoses during the first 6 months after COVID-19 diagnosis.
The current study “contributes to better understanding this link by providing data from another country with a different organization of healthcare provision than the US, where most of the existing data come from,” Dr. Taquet said.
However, “some observations — for example, that COVID-19 is associated with a 50% reduction in the risk of autism, a condition present from very early in life — call for extreme caution in the interpretation of the findings, as they suggest that residual bias has not been accounted for,” Dr. Taquet continued.
Authors of an accompanying editorial, Eric Chow, MD, MS, MPH, of the Division of Allergy and Infectious Diseases, University of Washington, School of Public Health, and Anita Chopra, MD, of the post-COVID Clinic, University of Washington, Seattle, called the study a “critical contribution to the published literature.”
The association of neurologic and psychiatric diagnoses with severe disease “is a reminder of the importance of risk reduction by combining vaccinations with improved indoor ventilation and masking,” they concluded.
The study was supported by a grant from the Independent Research Fund Denmark. Dr. Hviid and coauthors, Dr. Chopra, and Dr. Taquet reported no relevant financial relationships. Dr. Chow received a travel award from the Infectious Diseases Society of America to attend ID Week 2022.
A version of this article appeared on Medscape.com.
While severe COVID-19 is associated with a significantly higher risk for psychiatric and neurologic disorders a year after infection, mild does not carry the same risk, a new study shows.
However, less severe COVID-19 was not linked to a higher incidence of psychiatric diagnoses and was associated with only a slightly higher risk for neurologic disorders.
The new research challenges previous findings of long-term risk for psychiatric and neurologic disorders associated with SARS-CoV-2 in patients who had not been hospitalized for the condition.
“Our study does not support previous findings of substantial post-acute neurologic and psychiatric morbidities among the general population of SARS-CoV-2-infected individuals but does corroborate an elevated risk among the most severe cases with COVID-19,” the authors wrote.
The study was published online on February 21 in Neurology.
‘Alarming’ Findings
Previous studies have reported nervous system symptoms in patients who have experienced COVID-19, which may persist for several weeks or months after the acute phase, even in milder cases.
But these findings haven’t been consistent across all studies, and few studies have addressed the potential effect of different viral variants and vaccination status on post-acute psychiatric and neurologic morbidities.
“Our study was partly motivated by our strong research interest in the associations between infectious disease and later chronic disease and partly by international studies, such as those conducted in the US Veterans Health databases, that have suggested substantial risks of psychiatric and neurological conditions associated with infection,” senior author Anders Hviid, MSc, DrMedSci, head of the department and professor of pharmacoepidemiology, Statens Serum Institut, Copenhagen, Denmark, told this news organization.
Investigators drew on data from the Danish National Patient Registry to compare the risk for neurologic and psychiatric disorders during the 12 months after acute COVID-19 infection to risk among people who never tested positive.
They examined data on all recorded hospital contacts between January 2005 and January 2023 for a discharge diagnosis of at least one of 11 psychiatric illnesses or at least one of 30 neurologic disorders.
The researchers compared the incidence of each disorder within 1-12 months after infection with those of COVID-naive individuals and stratified analyses according to time since infection, vaccination status, variant period, age, sex, and infection severity.
The final study cohort included 1.8 million individuals who tested positive during the study period and 1.5 who didn’t. Three quarters of those who tested positive were infected primarily with the Omicron variant.
Hospitalized vs Nonhospitalized
Overall, individuals who tested positive had a 24% lower risk for psychiatric disorders during the post-acute period (incident rate ratio [IRR], 0.76; 95% CI, 0.74-0.78) compared with the control group, but a 5% higher risk for any neurologic disorder (IRR, 1.05; 95% CI, 1.04-1.07).
Age, sex, and variant had less influence on risk than infection severity, where the differences between hospitalized and nonhospitalized patients were significant.
Compared with COVID-negative individuals, the risk for any psychiatric disorder was double for hospitalized patients (IRR, 2.05; 95% CI, 1.78-2.37) but was 25% lower among nonhospitalized patients (IRR, 0.75; 95% CI, 0.73-0.77).
For neurologic disorders, the IRR for hospitalized patients was 2.44 (95% CI, 2.29-2.60) compared with COVID-negative individuals vs an IRR of only 1.02 (95% CI, 1.01-1.04) among nonhospitalized patients.
“In a general population, there was little support for clinically relevant post-acute risk increases of psychiatric and neurologic disorders associated with SARS-CoV-2 infection without hospitalization. This was particularly true for vaccinated individuals and for the more recent variants,” the authors wrote, adding that the only exception was for change in sense and smell.
‘Flaws’ in Previous Studies?
The findings in hospitalized patients were in line with previous findings, but those in nonhospitalized patients stand out, they added.
Previous studies were done predominantly in older males with comorbidities and those who were more socioeconomically disadvantaged, which could lead to a bias, Dr. Hviid said.
Those other studies “had a number of fundamental flaws that we do not believe our study has,” Dr. Hviid said. “Our study was conducted in the general population, with free and universal testing and healthcare.”
Researchers stress that sequelae after infection are predominantly associated with severe illness.
“Today, a healthy vaccinated adult having an asymptomatic or mild bout of COVID-19 with the current variants shouldn’t fear developing serious psychiatric or neurologic disorders in the months or years after infection.”
One limitation is that only hospital contacts were included, omitting possible diagnoses given outside hospital settings.
‘Extreme Caution’ Required
The link between COVID-19 and brain health is “complex,” and the new findings should be viewed cautiously, said Maxime Taquet, MRCPsych, PhD, National Institute for Health and Care Research clinical lecturer and specialty registrar in Psychiatry, Oxford Health NHS Foundation Trust, England, who commented on the findings.
Previous research by Dr. Taquet, who was not involved in the current study, found an increased risk for neurologic and psychiatric diagnoses during the first 6 months after COVID-19 diagnosis.
The current study “contributes to better understanding this link by providing data from another country with a different organization of healthcare provision than the US, where most of the existing data come from,” Dr. Taquet said.
However, “some observations — for example, that COVID-19 is associated with a 50% reduction in the risk of autism, a condition present from very early in life — call for extreme caution in the interpretation of the findings, as they suggest that residual bias has not been accounted for,” Dr. Taquet continued.
Authors of an accompanying editorial, Eric Chow, MD, MS, MPH, of the Division of Allergy and Infectious Diseases, University of Washington, School of Public Health, and Anita Chopra, MD, of the post-COVID Clinic, University of Washington, Seattle, called the study a “critical contribution to the published literature.”
The association of neurologic and psychiatric diagnoses with severe disease “is a reminder of the importance of risk reduction by combining vaccinations with improved indoor ventilation and masking,” they concluded.
The study was supported by a grant from the Independent Research Fund Denmark. Dr. Hviid and coauthors, Dr. Chopra, and Dr. Taquet reported no relevant financial relationships. Dr. Chow received a travel award from the Infectious Diseases Society of America to attend ID Week 2022.
A version of this article appeared on Medscape.com.