MDedge Psychiatry

The novel antipsychotic agent SEP-363856 (Sunovion Pharmaceuticals) has a significant and ongoing effect on negative symptoms in patients with schizophrenia, new research shows.

Results of a phase 2, placebo-controlled trial show SEP-363856 significantly decreased total scores on the Brief Negative Symptom Scale (BNSS), and lowered subscale scores for such symptoms as alogia and asociality, compared with placebo.

The active-treatment group also showed significantly lower scores on the negative subscale of the Positive and Negative Syndrome Scale (PANSS). During an open-label extension of the study, both BNSS total scores and PANSS negative symptom scores continued to decrease.

Overall, the results “provide further confirmation of the effectiveness of SEP-363856 in treating schizophrenia,” study investigator Kenneth Koblan, PhD, of Sunovion said in an interview.

He added that the compound also showed “a favorable safety and tolerability profile that is differentiated from first and second generation antipsychotics, and which is consistent with the absence of D2-receptor binding.”

The findings were presented at the 2021 annual congress of the Schizophrenia International Research Society.
 

FDA breakthrough designation

SEP-363856 has a completely different mechanism of action from currently available antipsychotics.

In May 2019, it was granted breakthrough therapy designation by the Food and Drug Administration as a novel treatment for patients with schizophrenia.

Phase 2 data published in the New England Journal of Medicine in 2020 showed it achieved significant and clinically meaningful improvements in PANSS total scores after 4 weeks in patients hospitalized with an acute exacerbation of schizophrenia. It also showed durable effects out to 26 weeks.

In the current analysis, the investigators focused on negative symptoms, both in the initial acute treatment phase and an open-label extension.

They analyzed data from the previous phase 2 trial using a validated Uncorrelated PANSS Score Matrix (UPSM) transformation of the PANSS to isolate the effects of the drug on apathy/avolition and deficit of expression. They also used the BNSS.

Patients aged 18-40 years with an acute exacerbation of schizophrenia were randomly assigned to receive either 50 mg or 75 mg of SEP-363856 per day (n = 120) or matching placebo (n = 125) for 4 weeks. Completers were eligible for enrollment in a 26-week phase 2 extension study of 25 mg, 50 mg, or 75 mg of SEP-363856 per day.

The mean age of the participants was 30 years, and 64% were men. The treatment groups were balanced in terms of demographics.

Significant improvement

The BNSS total score decreased significantly with SEP-363856 over placebo during the 4-week acute treatment period, at a mean reduction of 7.1 versus 2.7, or an effect size of 0.48 (P < .001).

Scores on the PANSS negative subscale also decreased significantly with the active drugs, with an effect size of 0.37 versus placebo (P < .05), as did scores on the UPSM apathy/avolition and deficit of expression subscales (effect size, 0.32; P < .05 for both).

In addition, there were significant reductions with SEP-363856 over placebo for the BNSS alogia, asociality, anhedonia, avolition, and blunted-affect subscales (P < .05 for all comparisons) but not for the distress subscale.

During the open-label extension, mean BNSS total scores continued to decrease for the SEP-363856 group, at an average reduction versus extension enrollment across the whole cohort of 11.3.

PANSS negative symptom scores also decreased by an average of 5.2 points, while UPSM apathy/volition scores decreased by 0.4 points on average. UPSM deficit expression scores decreased by 0.5 points.

When the researchers restricted the analysis to those who received SEP-363856 during the acute treatment phase and then continued using the drug during the open-label extension, they found BNSS total scores decreased by an additional 8 points.

Similarly, PANSS negative symptom scores decreased during the open-label extension by an average of 4 points. For UPSM apathy/avolition and deficit of expression, the additional decrease was 0.3 points on average.

In addition, an analysis of the drug’s safety and tolerability showed that, compared with the commonly prescribed antipsychotic lurasidone, it had a significantly lower risk of adverse effects. In addition, the drug was not associated with extrapyramidal symptoms and had no adverse cardiometabolic effects, Dr. Koblan reported.
 

Still in development

Commenting on the findings, René S. Kahn, MD, PhD, chair of the department of psychiatry, Icahn School of Medicine at Mount Sinai, New York, noted that, although the results showed that the drug had a “nice effect” on negative symptoms, it’s still in development.

Courtesy Mount Sinai Health System

Dr. Kahn, who was not involved in the research, said “we’ve all seen” drugs that were extremely promising in phase 2 trials that have then failed in phase 3 trials. “The proof of the pudding is phase 3, and we have to wait and see,” he added.

“Obviously I hope it’s going to work out, because we are in desperate need of new drugs, especially with a new mechanism of action and not ‘me too’ drugs. And this definitely not a ‘me too’ drug,” Dr. Kahn said. However, “we’ll have to wait.”

He noted that psychosis is often the primary focus of schizophrenia management. However, he added, cognitive and negative symptoms are also “very relevant” to the disorder.

“In fact, both of them may be more important in determining the long-term outcome of schizophrenia than psychosis, [and] most of the antipsychotics that we currently have are not very effective against negative symptoms,” he said.

“So it would really be a breakthrough if we have a drug that is really effective not only against positive psychotic symptoms, but also against negative and possibly cognitive, symptoms,” Dr. Kahn added.

Commenting on the drug’s safety, Dr. Kahn said there is a need for head-to-head studies of active drugs before any firm conclusions can be drawn.

However, he noted the exploratory analysis suggests it has a different side effect profile, compared with other medications on the market.

The study was supported by Sunovion Pharmaceuticals. Dr. Koblan and his coinvestigators are employees of Sunovion.

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

The novel antipsychotic agent SEP-363856 (Sunovion Pharmaceuticals) has a significant and ongoing effect on negative symptoms in patients with schizophrenia, new research shows.

Results of a phase 2, placebo-controlled trial show SEP-363856 significantly decreased total scores on the Brief Negative Symptom Scale (BNSS), and lowered subscale scores for such symptoms as alogia and asociality, compared with placebo.

The active-treatment group also showed significantly lower scores on the negative subscale of the Positive and Negative Syndrome Scale (PANSS). During an open-label extension of the study, both BNSS total scores and PANSS negative symptom scores continued to decrease.

Overall, the results “provide further confirmation of the effectiveness of SEP-363856 in treating schizophrenia,” study investigator Kenneth Koblan, PhD, of Sunovion said in an interview.

He added that the compound also showed “a favorable safety and tolerability profile that is differentiated from first and second generation antipsychotics, and which is consistent with the absence of D2-receptor binding.”

The findings were presented at the 2021 annual congress of the Schizophrenia International Research Society.
 

FDA breakthrough designation

SEP-363856 has a completely different mechanism of action from currently available antipsychotics.

In May 2019, it was granted breakthrough therapy designation by the Food and Drug Administration as a novel treatment for patients with schizophrenia.

Phase 2 data published in the New England Journal of Medicine in 2020 showed it achieved significant and clinically meaningful improvements in PANSS total scores after 4 weeks in patients hospitalized with an acute exacerbation of schizophrenia. It also showed durable effects out to 26 weeks.

In the current analysis, the investigators focused on negative symptoms, both in the initial acute treatment phase and an open-label extension.

They analyzed data from the previous phase 2 trial using a validated Uncorrelated PANSS Score Matrix (UPSM) transformation of the PANSS to isolate the effects of the drug on apathy/avolition and deficit of expression. They also used the BNSS.

Patients aged 18-40 years with an acute exacerbation of schizophrenia were randomly assigned to receive either 50 mg or 75 mg of SEP-363856 per day (n = 120) or matching placebo (n = 125) for 4 weeks. Completers were eligible for enrollment in a 26-week phase 2 extension study of 25 mg, 50 mg, or 75 mg of SEP-363856 per day.

The mean age of the participants was 30 years, and 64% were men. The treatment groups were balanced in terms of demographics.

Significant improvement

The BNSS total score decreased significantly with SEP-363856 over placebo during the 4-week acute treatment period, at a mean reduction of 7.1 versus 2.7, or an effect size of 0.48 (P < .001).

Scores on the PANSS negative subscale also decreased significantly with the active drugs, with an effect size of 0.37 versus placebo (P < .05), as did scores on the UPSM apathy/avolition and deficit of expression subscales (effect size, 0.32; P < .05 for both).

In addition, there were significant reductions with SEP-363856 over placebo for the BNSS alogia, asociality, anhedonia, avolition, and blunted-affect subscales (P < .05 for all comparisons) but not for the distress subscale.

During the open-label extension, mean BNSS total scores continued to decrease for the SEP-363856 group, at an average reduction versus extension enrollment across the whole cohort of 11.3.

PANSS negative symptom scores also decreased by an average of 5.2 points, while UPSM apathy/volition scores decreased by 0.4 points on average. UPSM deficit expression scores decreased by 0.5 points.

When the researchers restricted the analysis to those who received SEP-363856 during the acute treatment phase and then continued using the drug during the open-label extension, they found BNSS total scores decreased by an additional 8 points.

Similarly, PANSS negative symptom scores decreased during the open-label extension by an average of 4 points. For UPSM apathy/avolition and deficit of expression, the additional decrease was 0.3 points on average.

In addition, an analysis of the drug’s safety and tolerability showed that, compared with the commonly prescribed antipsychotic lurasidone, it had a significantly lower risk of adverse effects. In addition, the drug was not associated with extrapyramidal symptoms and had no adverse cardiometabolic effects, Dr. Koblan reported.
 

Still in development

Commenting on the findings, René S. Kahn, MD, PhD, chair of the department of psychiatry, Icahn School of Medicine at Mount Sinai, New York, noted that, although the results showed that the drug had a “nice effect” on negative symptoms, it’s still in development.

Courtesy Mount Sinai Health System

Dr. Kahn, who was not involved in the research, said “we’ve all seen” drugs that were extremely promising in phase 2 trials that have then failed in phase 3 trials. “The proof of the pudding is phase 3, and we have to wait and see,” he added.

“Obviously I hope it’s going to work out, because we are in desperate need of new drugs, especially with a new mechanism of action and not ‘me too’ drugs. And this definitely not a ‘me too’ drug,” Dr. Kahn said. However, “we’ll have to wait.”

He noted that psychosis is often the primary focus of schizophrenia management. However, he added, cognitive and negative symptoms are also “very relevant” to the disorder.

“In fact, both of them may be more important in determining the long-term outcome of schizophrenia than psychosis, [and] most of the antipsychotics that we currently have are not very effective against negative symptoms,” he said.

“So it would really be a breakthrough if we have a drug that is really effective not only against positive psychotic symptoms, but also against negative and possibly cognitive, symptoms,” Dr. Kahn added.

Commenting on the drug’s safety, Dr. Kahn said there is a need for head-to-head studies of active drugs before any firm conclusions can be drawn.

However, he noted the exploratory analysis suggests it has a different side effect profile, compared with other medications on the market.

The study was supported by Sunovion Pharmaceuticals. Dr. Koblan and his coinvestigators are employees of Sunovion.

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

The novel antipsychotic agent SEP-363856 (Sunovion Pharmaceuticals) has a significant and ongoing effect on negative symptoms in patients with schizophrenia, new research shows.

Results of a phase 2, placebo-controlled trial show SEP-363856 significantly decreased total scores on the Brief Negative Symptom Scale (BNSS), and lowered subscale scores for such symptoms as alogia and asociality, compared with placebo.

The active-treatment group also showed significantly lower scores on the negative subscale of the Positive and Negative Syndrome Scale (PANSS). During an open-label extension of the study, both BNSS total scores and PANSS negative symptom scores continued to decrease.

Overall, the results “provide further confirmation of the effectiveness of SEP-363856 in treating schizophrenia,” study investigator Kenneth Koblan, PhD, of Sunovion said in an interview.

He added that the compound also showed “a favorable safety and tolerability profile that is differentiated from first and second generation antipsychotics, and which is consistent with the absence of D2-receptor binding.”

The findings were presented at the 2021 annual congress of the Schizophrenia International Research Society.
 

FDA breakthrough designation

SEP-363856 has a completely different mechanism of action from currently available antipsychotics.

In May 2019, it was granted breakthrough therapy designation by the Food and Drug Administration as a novel treatment for patients with schizophrenia.

Phase 2 data published in the New England Journal of Medicine in 2020 showed it achieved significant and clinically meaningful improvements in PANSS total scores after 4 weeks in patients hospitalized with an acute exacerbation of schizophrenia. It also showed durable effects out to 26 weeks.

In the current analysis, the investigators focused on negative symptoms, both in the initial acute treatment phase and an open-label extension.

They analyzed data from the previous phase 2 trial using a validated Uncorrelated PANSS Score Matrix (UPSM) transformation of the PANSS to isolate the effects of the drug on apathy/avolition and deficit of expression. They also used the BNSS.

Patients aged 18-40 years with an acute exacerbation of schizophrenia were randomly assigned to receive either 50 mg or 75 mg of SEP-363856 per day (n = 120) or matching placebo (n = 125) for 4 weeks. Completers were eligible for enrollment in a 26-week phase 2 extension study of 25 mg, 50 mg, or 75 mg of SEP-363856 per day.

The mean age of the participants was 30 years, and 64% were men. The treatment groups were balanced in terms of demographics.

Significant improvement

The BNSS total score decreased significantly with SEP-363856 over placebo during the 4-week acute treatment period, at a mean reduction of 7.1 versus 2.7, or an effect size of 0.48 (P < .001).

Scores on the PANSS negative subscale also decreased significantly with the active drugs, with an effect size of 0.37 versus placebo (P < .05), as did scores on the UPSM apathy/avolition and deficit of expression subscales (effect size, 0.32; P < .05 for both).

In addition, there were significant reductions with SEP-363856 over placebo for the BNSS alogia, asociality, anhedonia, avolition, and blunted-affect subscales (P < .05 for all comparisons) but not for the distress subscale.

During the open-label extension, mean BNSS total scores continued to decrease for the SEP-363856 group, at an average reduction versus extension enrollment across the whole cohort of 11.3.

PANSS negative symptom scores also decreased by an average of 5.2 points, while UPSM apathy/volition scores decreased by 0.4 points on average. UPSM deficit expression scores decreased by 0.5 points.

When the researchers restricted the analysis to those who received SEP-363856 during the acute treatment phase and then continued using the drug during the open-label extension, they found BNSS total scores decreased by an additional 8 points.

Similarly, PANSS negative symptom scores decreased during the open-label extension by an average of 4 points. For UPSM apathy/avolition and deficit of expression, the additional decrease was 0.3 points on average.

In addition, an analysis of the drug’s safety and tolerability showed that, compared with the commonly prescribed antipsychotic lurasidone, it had a significantly lower risk of adverse effects. In addition, the drug was not associated with extrapyramidal symptoms and had no adverse cardiometabolic effects, Dr. Koblan reported.
 

Still in development

Commenting on the findings, René S. Kahn, MD, PhD, chair of the department of psychiatry, Icahn School of Medicine at Mount Sinai, New York, noted that, although the results showed that the drug had a “nice effect” on negative symptoms, it’s still in development.

Courtesy Mount Sinai Health System

Dr. Kahn, who was not involved in the research, said “we’ve all seen” drugs that were extremely promising in phase 2 trials that have then failed in phase 3 trials. “The proof of the pudding is phase 3, and we have to wait and see,” he added.

“Obviously I hope it’s going to work out, because we are in desperate need of new drugs, especially with a new mechanism of action and not ‘me too’ drugs. And this definitely not a ‘me too’ drug,” Dr. Kahn said. However, “we’ll have to wait.”

He noted that psychosis is often the primary focus of schizophrenia management. However, he added, cognitive and negative symptoms are also “very relevant” to the disorder.

“In fact, both of them may be more important in determining the long-term outcome of schizophrenia than psychosis, [and] most of the antipsychotics that we currently have are not very effective against negative symptoms,” he said.

“So it would really be a breakthrough if we have a drug that is really effective not only against positive psychotic symptoms, but also against negative and possibly cognitive, symptoms,” Dr. Kahn added.

Commenting on the drug’s safety, Dr. Kahn said there is a need for head-to-head studies of active drugs before any firm conclusions can be drawn.

However, he noted the exploratory analysis suggests it has a different side effect profile, compared with other medications on the market.

The study was supported by Sunovion Pharmaceuticals. Dr. Koblan and his coinvestigators are employees of Sunovion.

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

Accelerated brain aging among HIV-infected adults might be caused in part by altered deep sleep patterns, new research suggests.

Using a measure known as the brain age index (BAI) – a machine-learning model that measures deviations in brain activity during sleep relative to healthy individuals – investigators identified 34 sleep electroencephalogram features that were significantly altered by HIV infection. The most notable of these was the decline in slow-wave activity during non-REM sleep, which has been previously associated with MRI markers of brain aging in healthy adults.

“One of the functions of slow-wave sleep appears to be its association with the glymphatic system, which clears [metabolic] waste products and supports memory consolidation,” study coauthor Brandon Westover, MD, PhD, associate professor of neurology at Massachusetts General Hospital/Harvard Medical School, Boston, said in an interview. “It’s also believed to be associated with an accelerated risk for dementia and other cognitive issues.”

Previous work conducted at Johns Hopkins and other institutions confirm Dr. Westerson’s hypothesis. Charlene Gamaldo, MD, medical director of Johns Hopkins Sleep Disorders Center in Baltimore, pointed to other study findings in patients with neurodegenerative disease that have shown a link between predominant habitual sleep positions and dementia, potentially driven by inefficient glymphatic transport. Dr. Gamaldo was not involved in the current study.
 

Threefold acceleration vs. healthy volunteers

“We’ve been grappling with whether people with HIV on ART experience accelerated aging or accentuated aging,” coauthor Shibani Mukerji, MD, PhD, associate director of the neuroinfectious diseases unit at Massachusetts General, said in an interview. “We have yet to have biomarkers to address this question, and most of the tools are limited to invasive or expensive diagnostics. “In general, sleep and its influence on health have been understudied in the HIV population.”

To address this question, the researchers retrospectively examined a Massachusetts General Hospital database of diagnostic sleep study participants from 2008 to 2018, identifying 3,155 healthy, HIV-negative control subjects and 43 HIV-positive participants. Thirty-four (79%) of the HIV-positive participants were men, 30 (70%) were White, and 38 (93%) were virally suppressed at the time of their sleep study. Four patients were taking efavirenz, 13 were taking an integrase strand transfer inhibitor, and all were adherent to antiretroviral therapy (ART) at the time of their sleep study.

None of the HIV-positive participants had a history of secondary brain infection or brain tumor, although one patient had recovered fully from a previous HIV-associated encephalitis.

The study findings, which were published online March 30, 2021, in Sleep, first showed that HIV-positive participants had an average BAI of 3.19 years (standard error of the mean,1.43 years), compared with the control participants, who had an average BAI of –0.16 (SEM, 0.18 years).

These findings held after adjustment for potential confounders (age, sex, race, tobacco use disorder, and alcohol use disorder), yielding a total effect of HIV on BAI of 3.35 years (P < .01).

“Despite being well controlled on ART, HIV-positive individuals who had participated in the sleep studies still had elevated brain age,” said Dr. Westover. “We didn’t have enough information to determine the pathways by which HIV increases the BAI, but chronic inflammation appears to be an important factor.”

The findings also demonstrated that comorbidities accounted for roughly a quarter of the effect of HIV on BAI. However, the lack of statistical significance (in part because of the limited sample size) precluded the ability to determine if treating or preventing them might influence the degree to which HIV affects BAI and, in turn, cognitive decline.
 

HIV, sleep EEG, and brain aging

To estimate the effect of HIV on specific EEG features, the investigators again evaluated the total effect, this time replacing BAI with individual sleep EEG as the primary outcome. Among the 34 EEG features significantly altered by HIV, none were observed in the wake state and three were altered in REM (each associated with reduced delta band power). The rest were distributed in non-REM sleep, most notably in the deepest phase, corresponding to relative reductions in delta wave power.

The study findings build on the investigators’ previous research, which demonstrated an association between greater mean BAI and dementia, psychotic disorders, and anxiety/mood disorders in HIV-negative subjects, all of which correlated to attenuated slow-wave sleep.

More research is needed to determine if BAI, as it relates to sleep EEG, can effectively track the risk for cognitive decline among HIV-positive people, and if certain confounders might attenuate or accelerate this risk.

“While our team has not specifically looked at BAI, the findings in this study seem perfectly in line with what we have found with our own research,” Dr. Gamaldo said in an interview. “Not only have we observed a robust association between minimal cognitive deficits and patients’ sleep complaints (despite being virally controlled), but also, the potential value of measuring the architectural sleep features by ambulatory EEG to identify HIV patients’ vulnerability to cognitive decline.”

“BAI is a physiologic, easily repeatable measurement that can be used to track if an intervention is having a good effect,” Dr. Westover said.

Dr. Mukerji concurred, adding that “having a tool that can be used in resource-challenged settings and also be incorporated into longitudinal studies in a patient population with substantial age-related comorbidities, like HIV, would be really helpful.”

Dr. Westover and Dr. Mukerji disclosed no relevant financial relationships. Dr. Gamaldo is a consultant for Jazz Pharmaceuticals, and has received author royalties from UpToDate and honoraria from Medscape CME for content contribution.

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

Accelerated brain aging among HIV-infected adults might be caused in part by altered deep sleep patterns, new research suggests.

Using a measure known as the brain age index (BAI) – a machine-learning model that measures deviations in brain activity during sleep relative to healthy individuals – investigators identified 34 sleep electroencephalogram features that were significantly altered by HIV infection. The most notable of these was the decline in slow-wave activity during non-REM sleep, which has been previously associated with MRI markers of brain aging in healthy adults.

“One of the functions of slow-wave sleep appears to be its association with the glymphatic system, which clears [metabolic] waste products and supports memory consolidation,” study coauthor Brandon Westover, MD, PhD, associate professor of neurology at Massachusetts General Hospital/Harvard Medical School, Boston, said in an interview. “It’s also believed to be associated with an accelerated risk for dementia and other cognitive issues.”

Previous work conducted at Johns Hopkins and other institutions confirm Dr. Westerson’s hypothesis. Charlene Gamaldo, MD, medical director of Johns Hopkins Sleep Disorders Center in Baltimore, pointed to other study findings in patients with neurodegenerative disease that have shown a link between predominant habitual sleep positions and dementia, potentially driven by inefficient glymphatic transport. Dr. Gamaldo was not involved in the current study.
 

Threefold acceleration vs. healthy volunteers

“We’ve been grappling with whether people with HIV on ART experience accelerated aging or accentuated aging,” coauthor Shibani Mukerji, MD, PhD, associate director of the neuroinfectious diseases unit at Massachusetts General, said in an interview. “We have yet to have biomarkers to address this question, and most of the tools are limited to invasive or expensive diagnostics. “In general, sleep and its influence on health have been understudied in the HIV population.”

To address this question, the researchers retrospectively examined a Massachusetts General Hospital database of diagnostic sleep study participants from 2008 to 2018, identifying 3,155 healthy, HIV-negative control subjects and 43 HIV-positive participants. Thirty-four (79%) of the HIV-positive participants were men, 30 (70%) were White, and 38 (93%) were virally suppressed at the time of their sleep study. Four patients were taking efavirenz, 13 were taking an integrase strand transfer inhibitor, and all were adherent to antiretroviral therapy (ART) at the time of their sleep study.

None of the HIV-positive participants had a history of secondary brain infection or brain tumor, although one patient had recovered fully from a previous HIV-associated encephalitis.

The study findings, which were published online March 30, 2021, in Sleep, first showed that HIV-positive participants had an average BAI of 3.19 years (standard error of the mean,1.43 years), compared with the control participants, who had an average BAI of –0.16 (SEM, 0.18 years).

These findings held after adjustment for potential confounders (age, sex, race, tobacco use disorder, and alcohol use disorder), yielding a total effect of HIV on BAI of 3.35 years (P < .01).

“Despite being well controlled on ART, HIV-positive individuals who had participated in the sleep studies still had elevated brain age,” said Dr. Westover. “We didn’t have enough information to determine the pathways by which HIV increases the BAI, but chronic inflammation appears to be an important factor.”

The findings also demonstrated that comorbidities accounted for roughly a quarter of the effect of HIV on BAI. However, the lack of statistical significance (in part because of the limited sample size) precluded the ability to determine if treating or preventing them might influence the degree to which HIV affects BAI and, in turn, cognitive decline.
 

HIV, sleep EEG, and brain aging

To estimate the effect of HIV on specific EEG features, the investigators again evaluated the total effect, this time replacing BAI with individual sleep EEG as the primary outcome. Among the 34 EEG features significantly altered by HIV, none were observed in the wake state and three were altered in REM (each associated with reduced delta band power). The rest were distributed in non-REM sleep, most notably in the deepest phase, corresponding to relative reductions in delta wave power.

The study findings build on the investigators’ previous research, which demonstrated an association between greater mean BAI and dementia, psychotic disorders, and anxiety/mood disorders in HIV-negative subjects, all of which correlated to attenuated slow-wave sleep.

More research is needed to determine if BAI, as it relates to sleep EEG, can effectively track the risk for cognitive decline among HIV-positive people, and if certain confounders might attenuate or accelerate this risk.

“While our team has not specifically looked at BAI, the findings in this study seem perfectly in line with what we have found with our own research,” Dr. Gamaldo said in an interview. “Not only have we observed a robust association between minimal cognitive deficits and patients’ sleep complaints (despite being virally controlled), but also, the potential value of measuring the architectural sleep features by ambulatory EEG to identify HIV patients’ vulnerability to cognitive decline.”

“BAI is a physiologic, easily repeatable measurement that can be used to track if an intervention is having a good effect,” Dr. Westover said.

Dr. Mukerji concurred, adding that “having a tool that can be used in resource-challenged settings and also be incorporated into longitudinal studies in a patient population with substantial age-related comorbidities, like HIV, would be really helpful.”

Dr. Westover and Dr. Mukerji disclosed no relevant financial relationships. Dr. Gamaldo is a consultant for Jazz Pharmaceuticals, and has received author royalties from UpToDate and honoraria from Medscape CME for content contribution.

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

Accelerated brain aging among HIV-infected adults might be caused in part by altered deep sleep patterns, new research suggests.

Using a measure known as the brain age index (BAI) – a machine-learning model that measures deviations in brain activity during sleep relative to healthy individuals – investigators identified 34 sleep electroencephalogram features that were significantly altered by HIV infection. The most notable of these was the decline in slow-wave activity during non-REM sleep, which has been previously associated with MRI markers of brain aging in healthy adults.

“One of the functions of slow-wave sleep appears to be its association with the glymphatic system, which clears [metabolic] waste products and supports memory consolidation,” study coauthor Brandon Westover, MD, PhD, associate professor of neurology at Massachusetts General Hospital/Harvard Medical School, Boston, said in an interview. “It’s also believed to be associated with an accelerated risk for dementia and other cognitive issues.”

Previous work conducted at Johns Hopkins and other institutions confirm Dr. Westerson’s hypothesis. Charlene Gamaldo, MD, medical director of Johns Hopkins Sleep Disorders Center in Baltimore, pointed to other study findings in patients with neurodegenerative disease that have shown a link between predominant habitual sleep positions and dementia, potentially driven by inefficient glymphatic transport. Dr. Gamaldo was not involved in the current study.
 

Threefold acceleration vs. healthy volunteers

“We’ve been grappling with whether people with HIV on ART experience accelerated aging or accentuated aging,” coauthor Shibani Mukerji, MD, PhD, associate director of the neuroinfectious diseases unit at Massachusetts General, said in an interview. “We have yet to have biomarkers to address this question, and most of the tools are limited to invasive or expensive diagnostics. “In general, sleep and its influence on health have been understudied in the HIV population.”

To address this question, the researchers retrospectively examined a Massachusetts General Hospital database of diagnostic sleep study participants from 2008 to 2018, identifying 3,155 healthy, HIV-negative control subjects and 43 HIV-positive participants. Thirty-four (79%) of the HIV-positive participants were men, 30 (70%) were White, and 38 (93%) were virally suppressed at the time of their sleep study. Four patients were taking efavirenz, 13 were taking an integrase strand transfer inhibitor, and all were adherent to antiretroviral therapy (ART) at the time of their sleep study.

None of the HIV-positive participants had a history of secondary brain infection or brain tumor, although one patient had recovered fully from a previous HIV-associated encephalitis.

The study findings, which were published online March 30, 2021, in Sleep, first showed that HIV-positive participants had an average BAI of 3.19 years (standard error of the mean,1.43 years), compared with the control participants, who had an average BAI of –0.16 (SEM, 0.18 years).

These findings held after adjustment for potential confounders (age, sex, race, tobacco use disorder, and alcohol use disorder), yielding a total effect of HIV on BAI of 3.35 years (P < .01).

“Despite being well controlled on ART, HIV-positive individuals who had participated in the sleep studies still had elevated brain age,” said Dr. Westover. “We didn’t have enough information to determine the pathways by which HIV increases the BAI, but chronic inflammation appears to be an important factor.”

The findings also demonstrated that comorbidities accounted for roughly a quarter of the effect of HIV on BAI. However, the lack of statistical significance (in part because of the limited sample size) precluded the ability to determine if treating or preventing them might influence the degree to which HIV affects BAI and, in turn, cognitive decline.
 

HIV, sleep EEG, and brain aging

To estimate the effect of HIV on specific EEG features, the investigators again evaluated the total effect, this time replacing BAI with individual sleep EEG as the primary outcome. Among the 34 EEG features significantly altered by HIV, none were observed in the wake state and three were altered in REM (each associated with reduced delta band power). The rest were distributed in non-REM sleep, most notably in the deepest phase, corresponding to relative reductions in delta wave power.

The study findings build on the investigators’ previous research, which demonstrated an association between greater mean BAI and dementia, psychotic disorders, and anxiety/mood disorders in HIV-negative subjects, all of which correlated to attenuated slow-wave sleep.

More research is needed to determine if BAI, as it relates to sleep EEG, can effectively track the risk for cognitive decline among HIV-positive people, and if certain confounders might attenuate or accelerate this risk.

“While our team has not specifically looked at BAI, the findings in this study seem perfectly in line with what we have found with our own research,” Dr. Gamaldo said in an interview. “Not only have we observed a robust association between minimal cognitive deficits and patients’ sleep complaints (despite being virally controlled), but also, the potential value of measuring the architectural sleep features by ambulatory EEG to identify HIV patients’ vulnerability to cognitive decline.”

“BAI is a physiologic, easily repeatable measurement that can be used to track if an intervention is having a good effect,” Dr. Westover said.

Dr. Mukerji concurred, adding that “having a tool that can be used in resource-challenged settings and also be incorporated into longitudinal studies in a patient population with substantial age-related comorbidities, like HIV, would be really helpful.”

Dr. Westover and Dr. Mukerji disclosed no relevant financial relationships. Dr. Gamaldo is a consultant for Jazz Pharmaceuticals, and has received author royalties from UpToDate and honoraria from Medscape CME for content contribution.

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

Every psychiatrist knows that this past year has been a challenge. The COVID-19 pandemic altered our lives, practically overnight, in ways that most of us had never anticipated.

There were months of lockdown. A new work-from-home transition. Recommendations to distance and mask. The destruction and recreation of our social lives. And the end of some industries as we have known them.

Over a year later, many children are still in virtual school. This lifestyle and economic toll do not even begin to include the horror experienced by exhausted and distressed health care workers or by the many who have lost a loved one or survived a hospitalization. National and international anxiety are running high. More people are seeking mental health care, and many of the patients we were caring for prior to the pandemic have been distressed.

Rates of both depression and anxiety are up, and the fear has been that the isolation of lockdowns, with their emotional and economic toll, would also increase suicide rates. Despite the increase in psychiatric symptoms and general distress, initial studies in the United States have shown that overall suicide rates in the early months of the pandemic were lower than in prior years.

A study published in The Lancet looked at suicide data from around the world and compared expected suicides, based on data from past years, with observed suicides. The researchers restricted their analysis to the countries, and regions of countries, where real-time suicide data were available through internet searches. Their paper is based on findings from 21 countries, including 16 high-income countries and five upper-middle–income countries (from regions where data were available). The overall analysis showed a drop in suicides by 5% when looking at the first 4 months of the pandemic, defined as April 1, 2020, to July 31, 2020. There were statistically significant increases in suicide only in Vienna, Puerto Rico, and Japan.

Igor Galynker, MD, PhD, directs the Suicide Research and Prevention Lab and the Zirinsky Center for Bipolar Disorder at the Icahn School of Medicine at Mount Sinai. He was not surprised by these findings.

“This is an important study,” Dr. Galynker said. “When it was discovered that U.S. rates went down, it was ‘U.S. specific’ and it was confounded by the fact that there was a dramatic increase in opiate overdose deaths in the U.S., which are not reported as suicides. This study shows that the decrease is international and that the finding in the United States is not related to the spike in overdose deaths.”

The study authors postulated that the drop in suicide may be due to proactive protective measures that societies have put in place, such as improved mental health services and fiscal support to mitigate financial consequences of the pandemic. They explained that “communities might have actively tried to support at-risk individuals, people might have connected in new ways, and some relationships might have been strengthened by households spending more time with each other. For some people, everyday stresses might have been reduced during stay-at-home periods, and for others the collective feeling of ‘we’re all in this together’ might have been beneficial”.

Dr. Galynker noted that, in times of calamity, suicide rates historically go down. “Short-term disasters invoke a fight-or-flight response that mobilizes us and improves our functioning under stress. Those acute responses last 2-3 months and then chronic stress sets in.” He is concerned that there will be increases in suicide rates down the road.

It is possible that individuals who consider social gatherings to be stressful, or who are bullied at school, may have found some relief from social interactions and expectations during the lockdown. “Some people have discovered that they like their families!” Dr. Galynker said.

While suicide rates have gone down, that is not true for all population subsets, and the authors of the Lancet paper noted that they were unable to give breakdowns of rates for different demographics.

Paul Nestadt, MD, is codirector of the Johns Hopkins Anxiety Disorders Clinic and studies suicide, firearms, and opiates. He looked at suicides in Maryland during the first 2 months of the lockdown (March 5, 2020 to May 7, 2020) and found that, while rates were down among White Maryland residents, compared with prior years, they were increased among Black Maryland residents. Studies in Connecticut and Chicago yielded similar findings. These findings indicate that the overall trends may not reflect the impact on a specific subpopulation.

Dr. Nestadt talked about the disparities of suicide trends. “Communities hit harder by this pandemic in terms of sickness and death may experience more distress in ways that may come out as suicide in the context of other comorbid mood disorders. Also, in line with the idea of suicide as a marker of community- or population-level distress, there’s a general idea that having less of an economic cushion makes the pandemic more of a problem for some than for others. We know that suicide has been correlated to economic distress in general, and it makes sense that it would be community-specific where there is more economic duress.”

It has been a difficult year – not just for the United States, but for the entire world. One thing that may come of it is a unique opportunity to look at how stress and loss affect suicide rates, with the hope that preventive measures will follow.

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

Every psychiatrist knows that this past year has been a challenge. The COVID-19 pandemic altered our lives, practically overnight, in ways that most of us had never anticipated.

There were months of lockdown. A new work-from-home transition. Recommendations to distance and mask. The destruction and recreation of our social lives. And the end of some industries as we have known them.

Over a year later, many children are still in virtual school. This lifestyle and economic toll do not even begin to include the horror experienced by exhausted and distressed health care workers or by the many who have lost a loved one or survived a hospitalization. National and international anxiety are running high. More people are seeking mental health care, and many of the patients we were caring for prior to the pandemic have been distressed.

Rates of both depression and anxiety are up, and the fear has been that the isolation of lockdowns, with their emotional and economic toll, would also increase suicide rates. Despite the increase in psychiatric symptoms and general distress, initial studies in the United States have shown that overall suicide rates in the early months of the pandemic were lower than in prior years.

A study published in The Lancet looked at suicide data from around the world and compared expected suicides, based on data from past years, with observed suicides. The researchers restricted their analysis to the countries, and regions of countries, where real-time suicide data were available through internet searches. Their paper is based on findings from 21 countries, including 16 high-income countries and five upper-middle–income countries (from regions where data were available). The overall analysis showed a drop in suicides by 5% when looking at the first 4 months of the pandemic, defined as April 1, 2020, to July 31, 2020. There were statistically significant increases in suicide only in Vienna, Puerto Rico, and Japan.

Igor Galynker, MD, PhD, directs the Suicide Research and Prevention Lab and the Zirinsky Center for Bipolar Disorder at the Icahn School of Medicine at Mount Sinai. He was not surprised by these findings.

“This is an important study,” Dr. Galynker said. “When it was discovered that U.S. rates went down, it was ‘U.S. specific’ and it was confounded by the fact that there was a dramatic increase in opiate overdose deaths in the U.S., which are not reported as suicides. This study shows that the decrease is international and that the finding in the United States is not related to the spike in overdose deaths.”

The study authors postulated that the drop in suicide may be due to proactive protective measures that societies have put in place, such as improved mental health services and fiscal support to mitigate financial consequences of the pandemic. They explained that “communities might have actively tried to support at-risk individuals, people might have connected in new ways, and some relationships might have been strengthened by households spending more time with each other. For some people, everyday stresses might have been reduced during stay-at-home periods, and for others the collective feeling of ‘we’re all in this together’ might have been beneficial”.

Dr. Galynker noted that, in times of calamity, suicide rates historically go down. “Short-term disasters invoke a fight-or-flight response that mobilizes us and improves our functioning under stress. Those acute responses last 2-3 months and then chronic stress sets in.” He is concerned that there will be increases in suicide rates down the road.

It is possible that individuals who consider social gatherings to be stressful, or who are bullied at school, may have found some relief from social interactions and expectations during the lockdown. “Some people have discovered that they like their families!” Dr. Galynker said.

While suicide rates have gone down, that is not true for all population subsets, and the authors of the Lancet paper noted that they were unable to give breakdowns of rates for different demographics.

Paul Nestadt, MD, is codirector of the Johns Hopkins Anxiety Disorders Clinic and studies suicide, firearms, and opiates. He looked at suicides in Maryland during the first 2 months of the lockdown (March 5, 2020 to May 7, 2020) and found that, while rates were down among White Maryland residents, compared with prior years, they were increased among Black Maryland residents. Studies in Connecticut and Chicago yielded similar findings. These findings indicate that the overall trends may not reflect the impact on a specific subpopulation.

Dr. Nestadt talked about the disparities of suicide trends. “Communities hit harder by this pandemic in terms of sickness and death may experience more distress in ways that may come out as suicide in the context of other comorbid mood disorders. Also, in line with the idea of suicide as a marker of community- or population-level distress, there’s a general idea that having less of an economic cushion makes the pandemic more of a problem for some than for others. We know that suicide has been correlated to economic distress in general, and it makes sense that it would be community-specific where there is more economic duress.”

It has been a difficult year – not just for the United States, but for the entire world. One thing that may come of it is a unique opportunity to look at how stress and loss affect suicide rates, with the hope that preventive measures will follow.

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

Every psychiatrist knows that this past year has been a challenge. The COVID-19 pandemic altered our lives, practically overnight, in ways that most of us had never anticipated.

There were months of lockdown. A new work-from-home transition. Recommendations to distance and mask. The destruction and recreation of our social lives. And the end of some industries as we have known them.

Over a year later, many children are still in virtual school. This lifestyle and economic toll do not even begin to include the horror experienced by exhausted and distressed health care workers or by the many who have lost a loved one or survived a hospitalization. National and international anxiety are running high. More people are seeking mental health care, and many of the patients we were caring for prior to the pandemic have been distressed.

Rates of both depression and anxiety are up, and the fear has been that the isolation of lockdowns, with their emotional and economic toll, would also increase suicide rates. Despite the increase in psychiatric symptoms and general distress, initial studies in the United States have shown that overall suicide rates in the early months of the pandemic were lower than in prior years.

A study published in The Lancet looked at suicide data from around the world and compared expected suicides, based on data from past years, with observed suicides. The researchers restricted their analysis to the countries, and regions of countries, where real-time suicide data were available through internet searches. Their paper is based on findings from 21 countries, including 16 high-income countries and five upper-middle–income countries (from regions where data were available). The overall analysis showed a drop in suicides by 5% when looking at the first 4 months of the pandemic, defined as April 1, 2020, to July 31, 2020. There were statistically significant increases in suicide only in Vienna, Puerto Rico, and Japan.

Igor Galynker, MD, PhD, directs the Suicide Research and Prevention Lab and the Zirinsky Center for Bipolar Disorder at the Icahn School of Medicine at Mount Sinai. He was not surprised by these findings.

“This is an important study,” Dr. Galynker said. “When it was discovered that U.S. rates went down, it was ‘U.S. specific’ and it was confounded by the fact that there was a dramatic increase in opiate overdose deaths in the U.S., which are not reported as suicides. This study shows that the decrease is international and that the finding in the United States is not related to the spike in overdose deaths.”

The study authors postulated that the drop in suicide may be due to proactive protective measures that societies have put in place, such as improved mental health services and fiscal support to mitigate financial consequences of the pandemic. They explained that “communities might have actively tried to support at-risk individuals, people might have connected in new ways, and some relationships might have been strengthened by households spending more time with each other. For some people, everyday stresses might have been reduced during stay-at-home periods, and for others the collective feeling of ‘we’re all in this together’ might have been beneficial”.

Dr. Galynker noted that, in times of calamity, suicide rates historically go down. “Short-term disasters invoke a fight-or-flight response that mobilizes us and improves our functioning under stress. Those acute responses last 2-3 months and then chronic stress sets in.” He is concerned that there will be increases in suicide rates down the road.

It is possible that individuals who consider social gatherings to be stressful, or who are bullied at school, may have found some relief from social interactions and expectations during the lockdown. “Some people have discovered that they like their families!” Dr. Galynker said.

While suicide rates have gone down, that is not true for all population subsets, and the authors of the Lancet paper noted that they were unable to give breakdowns of rates for different demographics.

Paul Nestadt, MD, is codirector of the Johns Hopkins Anxiety Disorders Clinic and studies suicide, firearms, and opiates. He looked at suicides in Maryland during the first 2 months of the lockdown (March 5, 2020 to May 7, 2020) and found that, while rates were down among White Maryland residents, compared with prior years, they were increased among Black Maryland residents. Studies in Connecticut and Chicago yielded similar findings. These findings indicate that the overall trends may not reflect the impact on a specific subpopulation.

Dr. Nestadt talked about the disparities of suicide trends. “Communities hit harder by this pandemic in terms of sickness and death may experience more distress in ways that may come out as suicide in the context of other comorbid mood disorders. Also, in line with the idea of suicide as a marker of community- or population-level distress, there’s a general idea that having less of an economic cushion makes the pandemic more of a problem for some than for others. We know that suicide has been correlated to economic distress in general, and it makes sense that it would be community-specific where there is more economic duress.”

It has been a difficult year – not just for the United States, but for the entire world. One thing that may come of it is a unique opportunity to look at how stress and loss affect suicide rates, with the hope that preventive measures will follow.

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

I woke up from a nap on Tuesday, April 20, to a barrage of text messages and social media alerts about the Derek Chauvin verdict. Messages varied in content, from “let’s celebrate,” to “just so exciting,” to “finally.” As I took in the sentiments of others, I could barely sense what, if any, sentiments I had of my own.

There I sat, a Black DEI [diversity, equity, and inclusion] consultant who calls herself a “psychiatrist-activist,” but slept through the landmark court decision for policing African Americans and felt almost nothing about it.

However, I did have feelings about other matters such as the slide decks due for my client, sending reassuring text messages about the hospitalization of a friend’s child, and the 2 weeks of patient notes on my to-do list. So why did I feel emotionally flatlined about an issue that should stimulate the opposite – emotional intensity?

The answer to “why” could be attributed to a number of psychological buzz words like trauma, grief, desensitization, dissociation, numbness, or my new favorite term, languishing.

Despite the applicability of any of the above, I think my emotional flattening has more to do with the fact that in addition to the guilty verdict, I also woke up to news that 16-year-old Ma’Khia Bryant had been shot by a police officer in Columbus, Ohio.

I asked myself: How can anyone find time to grieve, nevertheless celebrate when (young) Black people continue to be killed by the police?

While it hurts to see individuals who look like me being shot by police, or even emboldened citizens, my hurt likely pales in comparison to someone who grew up surrounded by police gun violence. I grew up solidly middle class, lived in a house at the end of a cul-de-sac in a semi-gated community, and have many years ahead of me to reach my earning potential as a physician in one of the most liberal cities in the nation. While I have the skin color that puts me at risk of being shot by police due to racism, I am in a cushy position compared to other Black people who live in cities or neighborhoods with more police shootings.

Given this line of thinking, it seems clearer to me why I do not feel like celebrating, but instead, feel grateful to be alive. Not only do I feel grateful to be alive, but alive with the emotional stamina to help White people understand their contributions to the widespread oppression that keeps our society rooted in white supremacy.

This brings me to my point of what I want people, especially physicians, to know about the guilty verdict of Derek Chauvin: Some of us cannot really celebrate until there is actual police reform. This is not to say that anyone is wrong to celebrate, as long as there is an understanding that a landmark court decision can represent a drop in the bucket for Black and Brown people who risk being shot by the police while unarmed just for being Black or Brown.

Meanwhile, White men like Kyle Rittenhouse who are peaceably arrested after shooting a man with a semi-automatic weapon receive donations from a Virginia police lieutenant; a policeman who, in a possible world, could one day pull me over while driving through Virginia given its proximity to Washington D.C., where I currently live.

Black and Brown people cannot fully celebrate until there is actual police reform, and reform across American institutions like the health care system. Celebration comes when the leaders who run schools, hospitals, and courtrooms look more like the numbers actually reflected in U.S. racial demographics and look less like Derek Chauvin.

Until there are more doctors who look like the racial breakdown of the nation, Black and Brown patients can never fully trust their primary care doctors, orthopedic surgeons, and psychiatrists who are White. While this reality may sound harsh, it is the reality for many of us who are dealing with trauma, grief, desensitization, dissociation, emotional numbness, or languishment resulting from racist experiences.

People of color cannot and will not stop protesting in the streets, being the one who always brings up race in the meeting, or disagreeing that the new changes are “not enough” until there is actual anti-racist institutional reform. More importantly, the efforts of people of color can be made more powerful working collectively with White allies.

But we need White allies who recognize their tendency to perceive “progress” in racial equality. We need White allies who recognize that despite the passage of the Civil Rights Act, the two-time election of a Black president, and the guilty verdict of Derek Chauvin, there is still so much work to do.
 

Dr. Cyrus is assistant professor in the department of psychiatry at Johns Hopkins University, Baltimore. She reports no relevant financial relationships.

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

I woke up from a nap on Tuesday, April 20, to a barrage of text messages and social media alerts about the Derek Chauvin verdict. Messages varied in content, from “let’s celebrate,” to “just so exciting,” to “finally.” As I took in the sentiments of others, I could barely sense what, if any, sentiments I had of my own.

There I sat, a Black DEI [diversity, equity, and inclusion] consultant who calls herself a “psychiatrist-activist,” but slept through the landmark court decision for policing African Americans and felt almost nothing about it.

However, I did have feelings about other matters such as the slide decks due for my client, sending reassuring text messages about the hospitalization of a friend’s child, and the 2 weeks of patient notes on my to-do list. So why did I feel emotionally flatlined about an issue that should stimulate the opposite – emotional intensity?

The answer to “why” could be attributed to a number of psychological buzz words like trauma, grief, desensitization, dissociation, numbness, or my new favorite term, languishing.

Despite the applicability of any of the above, I think my emotional flattening has more to do with the fact that in addition to the guilty verdict, I also woke up to news that 16-year-old Ma’Khia Bryant had been shot by a police officer in Columbus, Ohio.

I asked myself: How can anyone find time to grieve, nevertheless celebrate when (young) Black people continue to be killed by the police?

While it hurts to see individuals who look like me being shot by police, or even emboldened citizens, my hurt likely pales in comparison to someone who grew up surrounded by police gun violence. I grew up solidly middle class, lived in a house at the end of a cul-de-sac in a semi-gated community, and have many years ahead of me to reach my earning potential as a physician in one of the most liberal cities in the nation. While I have the skin color that puts me at risk of being shot by police due to racism, I am in a cushy position compared to other Black people who live in cities or neighborhoods with more police shootings.

Given this line of thinking, it seems clearer to me why I do not feel like celebrating, but instead, feel grateful to be alive. Not only do I feel grateful to be alive, but alive with the emotional stamina to help White people understand their contributions to the widespread oppression that keeps our society rooted in white supremacy.

This brings me to my point of what I want people, especially physicians, to know about the guilty verdict of Derek Chauvin: Some of us cannot really celebrate until there is actual police reform. This is not to say that anyone is wrong to celebrate, as long as there is an understanding that a landmark court decision can represent a drop in the bucket for Black and Brown people who risk being shot by the police while unarmed just for being Black or Brown.

Meanwhile, White men like Kyle Rittenhouse who are peaceably arrested after shooting a man with a semi-automatic weapon receive donations from a Virginia police lieutenant; a policeman who, in a possible world, could one day pull me over while driving through Virginia given its proximity to Washington D.C., where I currently live.

Black and Brown people cannot fully celebrate until there is actual police reform, and reform across American institutions like the health care system. Celebration comes when the leaders who run schools, hospitals, and courtrooms look more like the numbers actually reflected in U.S. racial demographics and look less like Derek Chauvin.

Until there are more doctors who look like the racial breakdown of the nation, Black and Brown patients can never fully trust their primary care doctors, orthopedic surgeons, and psychiatrists who are White. While this reality may sound harsh, it is the reality for many of us who are dealing with trauma, grief, desensitization, dissociation, emotional numbness, or languishment resulting from racist experiences.

People of color cannot and will not stop protesting in the streets, being the one who always brings up race in the meeting, or disagreeing that the new changes are “not enough” until there is actual anti-racist institutional reform. More importantly, the efforts of people of color can be made more powerful working collectively with White allies.

But we need White allies who recognize their tendency to perceive “progress” in racial equality. We need White allies who recognize that despite the passage of the Civil Rights Act, the two-time election of a Black president, and the guilty verdict of Derek Chauvin, there is still so much work to do.
 

Dr. Cyrus is assistant professor in the department of psychiatry at Johns Hopkins University, Baltimore. She reports no relevant financial relationships.

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

I woke up from a nap on Tuesday, April 20, to a barrage of text messages and social media alerts about the Derek Chauvin verdict. Messages varied in content, from “let’s celebrate,” to “just so exciting,” to “finally.” As I took in the sentiments of others, I could barely sense what, if any, sentiments I had of my own.

There I sat, a Black DEI [diversity, equity, and inclusion] consultant who calls herself a “psychiatrist-activist,” but slept through the landmark court decision for policing African Americans and felt almost nothing about it.

However, I did have feelings about other matters such as the slide decks due for my client, sending reassuring text messages about the hospitalization of a friend’s child, and the 2 weeks of patient notes on my to-do list. So why did I feel emotionally flatlined about an issue that should stimulate the opposite – emotional intensity?

The answer to “why” could be attributed to a number of psychological buzz words like trauma, grief, desensitization, dissociation, numbness, or my new favorite term, languishing.

Despite the applicability of any of the above, I think my emotional flattening has more to do with the fact that in addition to the guilty verdict, I also woke up to news that 16-year-old Ma’Khia Bryant had been shot by a police officer in Columbus, Ohio.

I asked myself: How can anyone find time to grieve, nevertheless celebrate when (young) Black people continue to be killed by the police?

While it hurts to see individuals who look like me being shot by police, or even emboldened citizens, my hurt likely pales in comparison to someone who grew up surrounded by police gun violence. I grew up solidly middle class, lived in a house at the end of a cul-de-sac in a semi-gated community, and have many years ahead of me to reach my earning potential as a physician in one of the most liberal cities in the nation. While I have the skin color that puts me at risk of being shot by police due to racism, I am in a cushy position compared to other Black people who live in cities or neighborhoods with more police shootings.

Given this line of thinking, it seems clearer to me why I do not feel like celebrating, but instead, feel grateful to be alive. Not only do I feel grateful to be alive, but alive with the emotional stamina to help White people understand their contributions to the widespread oppression that keeps our society rooted in white supremacy.

This brings me to my point of what I want people, especially physicians, to know about the guilty verdict of Derek Chauvin: Some of us cannot really celebrate until there is actual police reform. This is not to say that anyone is wrong to celebrate, as long as there is an understanding that a landmark court decision can represent a drop in the bucket for Black and Brown people who risk being shot by the police while unarmed just for being Black or Brown.

Meanwhile, White men like Kyle Rittenhouse who are peaceably arrested after shooting a man with a semi-automatic weapon receive donations from a Virginia police lieutenant; a policeman who, in a possible world, could one day pull me over while driving through Virginia given its proximity to Washington D.C., where I currently live.

Black and Brown people cannot fully celebrate until there is actual police reform, and reform across American institutions like the health care system. Celebration comes when the leaders who run schools, hospitals, and courtrooms look more like the numbers actually reflected in U.S. racial demographics and look less like Derek Chauvin.

Until there are more doctors who look like the racial breakdown of the nation, Black and Brown patients can never fully trust their primary care doctors, orthopedic surgeons, and psychiatrists who are White. While this reality may sound harsh, it is the reality for many of us who are dealing with trauma, grief, desensitization, dissociation, emotional numbness, or languishment resulting from racist experiences.

People of color cannot and will not stop protesting in the streets, being the one who always brings up race in the meeting, or disagreeing that the new changes are “not enough” until there is actual anti-racist institutional reform. More importantly, the efforts of people of color can be made more powerful working collectively with White allies.

But we need White allies who recognize their tendency to perceive “progress” in racial equality. We need White allies who recognize that despite the passage of the Civil Rights Act, the two-time election of a Black president, and the guilty verdict of Derek Chauvin, there is still so much work to do.
 

Dr. Cyrus is assistant professor in the department of psychiatry at Johns Hopkins University, Baltimore. She reports no relevant financial relationships.

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

Pfizer CEO Albert Bourla, DVM, PhD, says an oral drug the company is developing to treat COVID-19 symptoms could be available to the public by the end of the year.

“If all goes well, and we implement the same speed that we are, and if regulators do the same, and they are, I hope that (it will be available) by the end of the year,” Dr. Bourla said on CNBC’s Squawk Box.

So far, the only antiviral drug authorized for use with COVID-19 is remdesivir, which is produced by Gilead Sciences and must be administered by injection in a health care setting.

An oral drug like the one Pfizer is developing could be taken at home and might keep people out of the hospital.

“Particular attention is on the oral because it provides several advantages,” Dr. Bourla said. “One of them is that you don’t need to go to the hospital to get the treatment, which is the case with all the injectables so far. You could get it at home, and that could be a game-changer.”

The drug might be effective against the emerging variants, he said. Pfizer is also working on an injectable antiviral drug.

Pfizer, with its European partner BioNTech, developed the first coronavirus vaccine authorized for use in the United States and Europe. The Pfizer pill under development would not be a vaccine to protect people from the virus but a drug to treat people who catch the virus.

The company announced in late March that it was starting clinical trials on the oral drug.

In a news release, the company said the oral drug would work by blocking protease, a critical enzyme that the virus needs to replicate. Protease inhibitors are used in medicines to treat HIV and hepatitis C.

A coronavirus vaccine that could be taken as a pill may enter clinical trials in the second quarter of 2021. The oral vaccine is being developed by Oravax Medical, a new joint venture of the Israeli-American company Oramed and the Indian company Premas Biotech. So far, all coronavirus vaccines are injectable.

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

Pfizer CEO Albert Bourla, DVM, PhD, says an oral drug the company is developing to treat COVID-19 symptoms could be available to the public by the end of the year.

“If all goes well, and we implement the same speed that we are, and if regulators do the same, and they are, I hope that (it will be available) by the end of the year,” Dr. Bourla said on CNBC’s Squawk Box.

So far, the only antiviral drug authorized for use with COVID-19 is remdesivir, which is produced by Gilead Sciences and must be administered by injection in a health care setting.

An oral drug like the one Pfizer is developing could be taken at home and might keep people out of the hospital.

“Particular attention is on the oral because it provides several advantages,” Dr. Bourla said. “One of them is that you don’t need to go to the hospital to get the treatment, which is the case with all the injectables so far. You could get it at home, and that could be a game-changer.”

The drug might be effective against the emerging variants, he said. Pfizer is also working on an injectable antiviral drug.

Pfizer, with its European partner BioNTech, developed the first coronavirus vaccine authorized for use in the United States and Europe. The Pfizer pill under development would not be a vaccine to protect people from the virus but a drug to treat people who catch the virus.

The company announced in late March that it was starting clinical trials on the oral drug.

In a news release, the company said the oral drug would work by blocking protease, a critical enzyme that the virus needs to replicate. Protease inhibitors are used in medicines to treat HIV and hepatitis C.

A coronavirus vaccine that could be taken as a pill may enter clinical trials in the second quarter of 2021. The oral vaccine is being developed by Oravax Medical, a new joint venture of the Israeli-American company Oramed and the Indian company Premas Biotech. So far, all coronavirus vaccines are injectable.

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

Pfizer CEO Albert Bourla, DVM, PhD, says an oral drug the company is developing to treat COVID-19 symptoms could be available to the public by the end of the year.

“If all goes well, and we implement the same speed that we are, and if regulators do the same, and they are, I hope that (it will be available) by the end of the year,” Dr. Bourla said on CNBC’s Squawk Box.

So far, the only antiviral drug authorized for use with COVID-19 is remdesivir, which is produced by Gilead Sciences and must be administered by injection in a health care setting.

An oral drug like the one Pfizer is developing could be taken at home and might keep people out of the hospital.

“Particular attention is on the oral because it provides several advantages,” Dr. Bourla said. “One of them is that you don’t need to go to the hospital to get the treatment, which is the case with all the injectables so far. You could get it at home, and that could be a game-changer.”

The drug might be effective against the emerging variants, he said. Pfizer is also working on an injectable antiviral drug.

Pfizer, with its European partner BioNTech, developed the first coronavirus vaccine authorized for use in the United States and Europe. The Pfizer pill under development would not be a vaccine to protect people from the virus but a drug to treat people who catch the virus.

The company announced in late March that it was starting clinical trials on the oral drug.

In a news release, the company said the oral drug would work by blocking protease, a critical enzyme that the virus needs to replicate. Protease inhibitors are used in medicines to treat HIV and hepatitis C.

A coronavirus vaccine that could be taken as a pill may enter clinical trials in the second quarter of 2021. The oral vaccine is being developed by Oravax Medical, a new joint venture of the Israeli-American company Oramed and the Indian company Premas Biotech. So far, all coronavirus vaccines are injectable.

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

People with psoriasis have a higher risk of infection with COVID-19 than the general population, but some systemic treatments appear to lower risk in patients, compared with those on topical therapy, a new study finds.

“Our study results suggest that psoriasis is an independent risk factor for COVID-19 illness,” study coauthor Jeffrey Liu, a medical student at the University of Southern California, Los Angeles, said in an interview after he presented the findings at the American Academy of Dermatology Virtual Meeting Experience. “And our findings are consistent with the hypothesis that certain systemic agents may confer a protective effect against COVID-19 illness.”

Mr. Liu and coinvestigators used a Symphony Health dataset to analyze the health records of 167,027 U.S. patients diagnosed with psoriasis and a control group of 1,002,162 patients. The participants, all at least 20 years old, had been treated for psoriasis or psoriatic arthritis from May 2019 through Jan. 1, 2020, and were tracked until Nov. 11, 2020.

The ages and races of peoples in the two groups were roughly similar. Overall, 55% were women and 75% were White, and their average age was 58 years. Type 2 diabetes was more common in the psoriasis group than the control group (23% vs. 16%), as was obesity (27% vs. 15%). Of the patients with psoriasis, 60% were on topical treatments, 19% were on oral therapies, and 22% were on biologic therapy, with only a few taking both oral and biologic therapies.

After adjustment for age and gender, patients with psoriasis were 33% more likely than the control group to develop COVID-19 (adjusted incidence rate ratio, 1.33; 95% confidence interval, 1.23-1.38; P < .0001).

In a separate analysis, the gap persisted after adjustment for demographics and comorbidities: Patients with psoriasis had a higher rate of COVID-19 infection vs. controls (adjusted odds ratio, 1.18; 95% CI, 1.13-1.23; P < .0001). Among all patients, non-White race, older age, and comorbidities were all linked to higher risk of COVID-19 (all P < .0001).

Psoriasis might make patients more vulnerable to COVID-19 because the presence of up-regulated genes in psoriatic skin “may lead to systemic hyperinflammation and sensitization of patients with psoriasis to proinflammatory cytokine storm,” Mr. Liu said. This, in turn, may trigger more severe symptomatic disease that requires medical treatment, he said.

Reduced risk, compared with topical therapies

After adjustment for age and gender, those treated with TNF-alpha inhibitors, methotrexate, and apremilast (Otezla) all had statistically lower risks of COVID-19 vs. those on topical therapy (aIRR, 0.82; 95% CI, 0.69-0.95; P < .0029 for TNF-alpha inhibitors; aIRR, 0.75; 95% CI, 0.67-0.86; P < .0001 for methotrexate; and aIRR, 0.69; 95% CI, 0.55-0.85; P < .0006 for apremilast).

Reduced risk held true for those in the separate analysis after adjustment for comorbidities and demographics (respectively, aOR, 0.87; 95% CI, 0.77-1.00; P < .0469; aOR, 0.81; 95% CI, 0.71-0.92; P < .0011; and aOR, 0.70; 95% CI, 0.57-0.87; P < .0014).

Apremilast and methotrexate may boost protection against COVID-19 by inhibiting the body’s production of cytokines, Mr. Liu said.

One message of the study is that “dermatologists should not be scared of prescribing biologics or oral therapies for psoriasis,” the study’s lead author Jashin J. Wu, MD, of the Dermatology Research and Education Foundation in Irvine, Calif., said in an interview.

However, the results on the effects of systemic therapies were not all positive. Interleukin (IL)–17 inhibitors were an outlier: After adjustment for age and gender, patients treated with this class of drugs were 36% more likely to develop COVID-19 than those on oral agents (aIRR, 1.36; 95% CI, 1.13-1.63; P < .0009).

Among patients on biologics, those taking IL-17 inhibitors had the highest risk of COVID-19, Mr. Liu said. “The risk was higher in this class regardless of reference group – general population, the topical cohort, and the oral cohort,” he said. “This may relate to the observation that this biologic class exerts more broad immunosuppressive effects on antiviral host immunity. Notably, large meta-estimates of pivotal trials have observed increased risk of respiratory tract infections for patients on IL-17 inhibitors.”

In an interview, Erica Dommasch, MD, MPH, of the department of dermatology at Beth Israel Deaconess Medical Center, Boston, cautioned that “the data from this study is very hard to interpret.”

It’s likely that some patients with psoriasis on systemic medications “may have been the most careful about limiting exposures,” she said. “Thus, it’s hard to account for behavioral changes in individuals that may have led to the decreased incidence in psoriasis in patients on systemic agents versus topical therapy alone.”

Patients with psoriasis may also be tested more often for COVID-19, and unmeasured comorbidities like chronic kidney disease may play a role too, she said. Still, she added, “it’s reassuring that the authors did not find an increased rate of COVID among psoriasis patients on systemic agents versus topicals alone.” And she agreed with Dr. Wu about the importance of treating psoriasis with therapy beyond topical treatments during the pandemic: “Providers should feel comfortable prescribing systemic medications to psoriasis patients when otherwise appropriate.”

As for the next steps, Dr. Wu said, “we will be exploring more about the prognosis of COVID-19 infection in psoriasis patients. In addition, we will be exploring the relationship of COVID-19 infection with other inflammatory skin diseases, such as atopic dermatitis.”

No study funding is reported. Dr. Wu discloses investigator, consultant, or speaker relationships with AbbVie, Almirall, Amgen, Arcutis, Aristea Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Dr. Reddy’s Laboratories, Eli Lilly, Galderma, Janssen, LEO Pharma, Mindera, Novartis, Regeneron, Sanofi Genzyme, Solius, Sun Pharmaceutical, UCB, Valeant Pharmaceuticals North America, and Zerigo Health. Mr. Liu and Dr. Dommasch have no disclosures.

People with psoriasis have a higher risk of infection with COVID-19 than the general population, but some systemic treatments appear to lower risk in patients, compared with those on topical therapy, a new study finds.

“Our study results suggest that psoriasis is an independent risk factor for COVID-19 illness,” study coauthor Jeffrey Liu, a medical student at the University of Southern California, Los Angeles, said in an interview after he presented the findings at the American Academy of Dermatology Virtual Meeting Experience. “And our findings are consistent with the hypothesis that certain systemic agents may confer a protective effect against COVID-19 illness.”

Mr. Liu and coinvestigators used a Symphony Health dataset to analyze the health records of 167,027 U.S. patients diagnosed with psoriasis and a control group of 1,002,162 patients. The participants, all at least 20 years old, had been treated for psoriasis or psoriatic arthritis from May 2019 through Jan. 1, 2020, and were tracked until Nov. 11, 2020.

The ages and races of peoples in the two groups were roughly similar. Overall, 55% were women and 75% were White, and their average age was 58 years. Type 2 diabetes was more common in the psoriasis group than the control group (23% vs. 16%), as was obesity (27% vs. 15%). Of the patients with psoriasis, 60% were on topical treatments, 19% were on oral therapies, and 22% were on biologic therapy, with only a few taking both oral and biologic therapies.

After adjustment for age and gender, patients with psoriasis were 33% more likely than the control group to develop COVID-19 (adjusted incidence rate ratio, 1.33; 95% confidence interval, 1.23-1.38; P < .0001).

In a separate analysis, the gap persisted after adjustment for demographics and comorbidities: Patients with psoriasis had a higher rate of COVID-19 infection vs. controls (adjusted odds ratio, 1.18; 95% CI, 1.13-1.23; P < .0001). Among all patients, non-White race, older age, and comorbidities were all linked to higher risk of COVID-19 (all P < .0001).

Psoriasis might make patients more vulnerable to COVID-19 because the presence of up-regulated genes in psoriatic skin “may lead to systemic hyperinflammation and sensitization of patients with psoriasis to proinflammatory cytokine storm,” Mr. Liu said. This, in turn, may trigger more severe symptomatic disease that requires medical treatment, he said.

Reduced risk, compared with topical therapies

After adjustment for age and gender, those treated with TNF-alpha inhibitors, methotrexate, and apremilast (Otezla) all had statistically lower risks of COVID-19 vs. those on topical therapy (aIRR, 0.82; 95% CI, 0.69-0.95; P < .0029 for TNF-alpha inhibitors; aIRR, 0.75; 95% CI, 0.67-0.86; P < .0001 for methotrexate; and aIRR, 0.69; 95% CI, 0.55-0.85; P < .0006 for apremilast).

Reduced risk held true for those in the separate analysis after adjustment for comorbidities and demographics (respectively, aOR, 0.87; 95% CI, 0.77-1.00; P < .0469; aOR, 0.81; 95% CI, 0.71-0.92; P < .0011; and aOR, 0.70; 95% CI, 0.57-0.87; P < .0014).

Apremilast and methotrexate may boost protection against COVID-19 by inhibiting the body’s production of cytokines, Mr. Liu said.

One message of the study is that “dermatologists should not be scared of prescribing biologics or oral therapies for psoriasis,” the study’s lead author Jashin J. Wu, MD, of the Dermatology Research and Education Foundation in Irvine, Calif., said in an interview.

However, the results on the effects of systemic therapies were not all positive. Interleukin (IL)–17 inhibitors were an outlier: After adjustment for age and gender, patients treated with this class of drugs were 36% more likely to develop COVID-19 than those on oral agents (aIRR, 1.36; 95% CI, 1.13-1.63; P < .0009).

Among patients on biologics, those taking IL-17 inhibitors had the highest risk of COVID-19, Mr. Liu said. “The risk was higher in this class regardless of reference group – general population, the topical cohort, and the oral cohort,” he said. “This may relate to the observation that this biologic class exerts more broad immunosuppressive effects on antiviral host immunity. Notably, large meta-estimates of pivotal trials have observed increased risk of respiratory tract infections for patients on IL-17 inhibitors.”

In an interview, Erica Dommasch, MD, MPH, of the department of dermatology at Beth Israel Deaconess Medical Center, Boston, cautioned that “the data from this study is very hard to interpret.”

It’s likely that some patients with psoriasis on systemic medications “may have been the most careful about limiting exposures,” she said. “Thus, it’s hard to account for behavioral changes in individuals that may have led to the decreased incidence in psoriasis in patients on systemic agents versus topical therapy alone.”

Patients with psoriasis may also be tested more often for COVID-19, and unmeasured comorbidities like chronic kidney disease may play a role too, she said. Still, she added, “it’s reassuring that the authors did not find an increased rate of COVID among psoriasis patients on systemic agents versus topicals alone.” And she agreed with Dr. Wu about the importance of treating psoriasis with therapy beyond topical treatments during the pandemic: “Providers should feel comfortable prescribing systemic medications to psoriasis patients when otherwise appropriate.”

As for the next steps, Dr. Wu said, “we will be exploring more about the prognosis of COVID-19 infection in psoriasis patients. In addition, we will be exploring the relationship of COVID-19 infection with other inflammatory skin diseases, such as atopic dermatitis.”

No study funding is reported. Dr. Wu discloses investigator, consultant, or speaker relationships with AbbVie, Almirall, Amgen, Arcutis, Aristea Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Dr. Reddy’s Laboratories, Eli Lilly, Galderma, Janssen, LEO Pharma, Mindera, Novartis, Regeneron, Sanofi Genzyme, Solius, Sun Pharmaceutical, UCB, Valeant Pharmaceuticals North America, and Zerigo Health. Mr. Liu and Dr. Dommasch have no disclosures.

People with psoriasis have a higher risk of infection with COVID-19 than the general population, but some systemic treatments appear to lower risk in patients, compared with those on topical therapy, a new study finds.

“Our study results suggest that psoriasis is an independent risk factor for COVID-19 illness,” study coauthor Jeffrey Liu, a medical student at the University of Southern California, Los Angeles, said in an interview after he presented the findings at the American Academy of Dermatology Virtual Meeting Experience. “And our findings are consistent with the hypothesis that certain systemic agents may confer a protective effect against COVID-19 illness.”

Mr. Liu and coinvestigators used a Symphony Health dataset to analyze the health records of 167,027 U.S. patients diagnosed with psoriasis and a control group of 1,002,162 patients. The participants, all at least 20 years old, had been treated for psoriasis or psoriatic arthritis from May 2019 through Jan. 1, 2020, and were tracked until Nov. 11, 2020.

The ages and races of peoples in the two groups were roughly similar. Overall, 55% were women and 75% were White, and their average age was 58 years. Type 2 diabetes was more common in the psoriasis group than the control group (23% vs. 16%), as was obesity (27% vs. 15%). Of the patients with psoriasis, 60% were on topical treatments, 19% were on oral therapies, and 22% were on biologic therapy, with only a few taking both oral and biologic therapies.

After adjustment for age and gender, patients with psoriasis were 33% more likely than the control group to develop COVID-19 (adjusted incidence rate ratio, 1.33; 95% confidence interval, 1.23-1.38; P < .0001).

In a separate analysis, the gap persisted after adjustment for demographics and comorbidities: Patients with psoriasis had a higher rate of COVID-19 infection vs. controls (adjusted odds ratio, 1.18; 95% CI, 1.13-1.23; P < .0001). Among all patients, non-White race, older age, and comorbidities were all linked to higher risk of COVID-19 (all P < .0001).

Psoriasis might make patients more vulnerable to COVID-19 because the presence of up-regulated genes in psoriatic skin “may lead to systemic hyperinflammation and sensitization of patients with psoriasis to proinflammatory cytokine storm,” Mr. Liu said. This, in turn, may trigger more severe symptomatic disease that requires medical treatment, he said.

Reduced risk, compared with topical therapies

After adjustment for age and gender, those treated with TNF-alpha inhibitors, methotrexate, and apremilast (Otezla) all had statistically lower risks of COVID-19 vs. those on topical therapy (aIRR, 0.82; 95% CI, 0.69-0.95; P < .0029 for TNF-alpha inhibitors; aIRR, 0.75; 95% CI, 0.67-0.86; P < .0001 for methotrexate; and aIRR, 0.69; 95% CI, 0.55-0.85; P < .0006 for apremilast).

Reduced risk held true for those in the separate analysis after adjustment for comorbidities and demographics (respectively, aOR, 0.87; 95% CI, 0.77-1.00; P < .0469; aOR, 0.81; 95% CI, 0.71-0.92; P < .0011; and aOR, 0.70; 95% CI, 0.57-0.87; P < .0014).

Apremilast and methotrexate may boost protection against COVID-19 by inhibiting the body’s production of cytokines, Mr. Liu said.

One message of the study is that “dermatologists should not be scared of prescribing biologics or oral therapies for psoriasis,” the study’s lead author Jashin J. Wu, MD, of the Dermatology Research and Education Foundation in Irvine, Calif., said in an interview.

However, the results on the effects of systemic therapies were not all positive. Interleukin (IL)–17 inhibitors were an outlier: After adjustment for age and gender, patients treated with this class of drugs were 36% more likely to develop COVID-19 than those on oral agents (aIRR, 1.36; 95% CI, 1.13-1.63; P < .0009).

Among patients on biologics, those taking IL-17 inhibitors had the highest risk of COVID-19, Mr. Liu said. “The risk was higher in this class regardless of reference group – general population, the topical cohort, and the oral cohort,” he said. “This may relate to the observation that this biologic class exerts more broad immunosuppressive effects on antiviral host immunity. Notably, large meta-estimates of pivotal trials have observed increased risk of respiratory tract infections for patients on IL-17 inhibitors.”

In an interview, Erica Dommasch, MD, MPH, of the department of dermatology at Beth Israel Deaconess Medical Center, Boston, cautioned that “the data from this study is very hard to interpret.”

It’s likely that some patients with psoriasis on systemic medications “may have been the most careful about limiting exposures,” she said. “Thus, it’s hard to account for behavioral changes in individuals that may have led to the decreased incidence in psoriasis in patients on systemic agents versus topical therapy alone.”

Patients with psoriasis may also be tested more often for COVID-19, and unmeasured comorbidities like chronic kidney disease may play a role too, she said. Still, she added, “it’s reassuring that the authors did not find an increased rate of COVID among psoriasis patients on systemic agents versus topicals alone.” And she agreed with Dr. Wu about the importance of treating psoriasis with therapy beyond topical treatments during the pandemic: “Providers should feel comfortable prescribing systemic medications to psoriasis patients when otherwise appropriate.”

As for the next steps, Dr. Wu said, “we will be exploring more about the prognosis of COVID-19 infection in psoriasis patients. In addition, we will be exploring the relationship of COVID-19 infection with other inflammatory skin diseases, such as atopic dermatitis.”

No study funding is reported. Dr. Wu discloses investigator, consultant, or speaker relationships with AbbVie, Almirall, Amgen, Arcutis, Aristea Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Dr. Reddy’s Laboratories, Eli Lilly, Galderma, Janssen, LEO Pharma, Mindera, Novartis, Regeneron, Sanofi Genzyme, Solius, Sun Pharmaceutical, UCB, Valeant Pharmaceuticals North America, and Zerigo Health. Mr. Liu and Dr. Dommasch have no disclosures.

After hinting that new guidelines on outdoor mask-wearing were coming, the Centers for Disease Control and Prevention on April 27 officially gave a green light to fully vaccinated people gathering outside in uncrowded activities without the masks that have become so common during the COVID-19 pandemic.

It is a minor – but still significant – step toward the end of pandemic restrictions.

“Over the past year, we have spent a lot of time telling Americans what they cannot do, what they should not do,” CDC director Rochelle Walensky, MD, MPH, said at a White House press briefing. “Today, I’m going to tell you some of the things you can do if you are fully vaccinated.”

President Joe Biden affirmed the new guidelines at a press conference soon after the CDC briefing ended.

“Starting today, if you are fully vaccinated and you’re outdoors and not in a big crowd, you no longer need to wear a mask,” he said, adding “the bottom line is clear: If you’re vaccinated, you can do more things, more safely, both outdoors as well as indoors.”

President Biden emphasized the role science played in the decision, saying “The CDC is able to make this announcement because our scientists are convinced by the data that the odds of getting or giving the virus to others is very, very low if you’ve both been fully vaccinated and are out in the open air.”

President Biden also said these new guidelines should be an incentive for more people to get vaccinated. “This is another great reason to go get vaccinated now. Now,” he said.

The CDC has long advised that outdoor activities are safer than indoor activities.

“Most of transmission is happening indoors rather than outdoors. Less than 10% of documented transmissions in many studies have occurred outdoors,” said Dr. Walensky. “We also know there’s almost a 20-fold increased risk of transmission in the indoor setting, than the outdoor setting.”

Dr. Walensky said the lower risks outdoors, combined with growing vaccination coverage and falling COVID cases around the country, motivated the change.

The new guidelines come as the share of people in the United States who are vaccinated is growing. About 37% of all eligible Americans are fully vaccinated, according to the CDC. Nearly 54% have had at least one dose.

The new guidelines say unvaccinated people should continue to wear masks outdoors when gathering with others or dining at an outdoor restaurant.

And vaccinated people should continue to wear masks outdoors in crowded settings where social distancing might not always be possible, like a concert or sporting event. People are considered fully vaccinated when they are 2 weeks past their last shot

The CDC guidelines say people who live in the same house don’t need to wear masks if they’re exercising or hanging out together outdoors.

You also don’t need a mask if you’re attending a small, outdoor gathering with fully vaccinated family and friends, whether you’re vaccinated or not.

The new guidelines also say it’s OK for fully vaccinated people to take their masks off outdoors when gathering in a small group of vaccinated and unvaccinated people, but suggest that unvaccinated people should still wear a mask.



Reporter Marcia Frellick contributed to this report.

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

After hinting that new guidelines on outdoor mask-wearing were coming, the Centers for Disease Control and Prevention on April 27 officially gave a green light to fully vaccinated people gathering outside in uncrowded activities without the masks that have become so common during the COVID-19 pandemic.

It is a minor – but still significant – step toward the end of pandemic restrictions.

“Over the past year, we have spent a lot of time telling Americans what they cannot do, what they should not do,” CDC director Rochelle Walensky, MD, MPH, said at a White House press briefing. “Today, I’m going to tell you some of the things you can do if you are fully vaccinated.”

President Joe Biden affirmed the new guidelines at a press conference soon after the CDC briefing ended.

“Starting today, if you are fully vaccinated and you’re outdoors and not in a big crowd, you no longer need to wear a mask,” he said, adding “the bottom line is clear: If you’re vaccinated, you can do more things, more safely, both outdoors as well as indoors.”

President Biden emphasized the role science played in the decision, saying “The CDC is able to make this announcement because our scientists are convinced by the data that the odds of getting or giving the virus to others is very, very low if you’ve both been fully vaccinated and are out in the open air.”

President Biden also said these new guidelines should be an incentive for more people to get vaccinated. “This is another great reason to go get vaccinated now. Now,” he said.

The CDC has long advised that outdoor activities are safer than indoor activities.

“Most of transmission is happening indoors rather than outdoors. Less than 10% of documented transmissions in many studies have occurred outdoors,” said Dr. Walensky. “We also know there’s almost a 20-fold increased risk of transmission in the indoor setting, than the outdoor setting.”

Dr. Walensky said the lower risks outdoors, combined with growing vaccination coverage and falling COVID cases around the country, motivated the change.

The new guidelines come as the share of people in the United States who are vaccinated is growing. About 37% of all eligible Americans are fully vaccinated, according to the CDC. Nearly 54% have had at least one dose.

The new guidelines say unvaccinated people should continue to wear masks outdoors when gathering with others or dining at an outdoor restaurant.

And vaccinated people should continue to wear masks outdoors in crowded settings where social distancing might not always be possible, like a concert or sporting event. People are considered fully vaccinated when they are 2 weeks past their last shot

The CDC guidelines say people who live in the same house don’t need to wear masks if they’re exercising or hanging out together outdoors.

You also don’t need a mask if you’re attending a small, outdoor gathering with fully vaccinated family and friends, whether you’re vaccinated or not.

The new guidelines also say it’s OK for fully vaccinated people to take their masks off outdoors when gathering in a small group of vaccinated and unvaccinated people, but suggest that unvaccinated people should still wear a mask.



Reporter Marcia Frellick contributed to this report.

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

After hinting that new guidelines on outdoor mask-wearing were coming, the Centers for Disease Control and Prevention on April 27 officially gave a green light to fully vaccinated people gathering outside in uncrowded activities without the masks that have become so common during the COVID-19 pandemic.

It is a minor – but still significant – step toward the end of pandemic restrictions.

“Over the past year, we have spent a lot of time telling Americans what they cannot do, what they should not do,” CDC director Rochelle Walensky, MD, MPH, said at a White House press briefing. “Today, I’m going to tell you some of the things you can do if you are fully vaccinated.”

President Joe Biden affirmed the new guidelines at a press conference soon after the CDC briefing ended.

“Starting today, if you are fully vaccinated and you’re outdoors and not in a big crowd, you no longer need to wear a mask,” he said, adding “the bottom line is clear: If you’re vaccinated, you can do more things, more safely, both outdoors as well as indoors.”

President Biden emphasized the role science played in the decision, saying “The CDC is able to make this announcement because our scientists are convinced by the data that the odds of getting or giving the virus to others is very, very low if you’ve both been fully vaccinated and are out in the open air.”

President Biden also said these new guidelines should be an incentive for more people to get vaccinated. “This is another great reason to go get vaccinated now. Now,” he said.

The CDC has long advised that outdoor activities are safer than indoor activities.

“Most of transmission is happening indoors rather than outdoors. Less than 10% of documented transmissions in many studies have occurred outdoors,” said Dr. Walensky. “We also know there’s almost a 20-fold increased risk of transmission in the indoor setting, than the outdoor setting.”

Dr. Walensky said the lower risks outdoors, combined with growing vaccination coverage and falling COVID cases around the country, motivated the change.

The new guidelines come as the share of people in the United States who are vaccinated is growing. About 37% of all eligible Americans are fully vaccinated, according to the CDC. Nearly 54% have had at least one dose.

The new guidelines say unvaccinated people should continue to wear masks outdoors when gathering with others or dining at an outdoor restaurant.

And vaccinated people should continue to wear masks outdoors in crowded settings where social distancing might not always be possible, like a concert or sporting event. People are considered fully vaccinated when they are 2 weeks past their last shot

The CDC guidelines say people who live in the same house don’t need to wear masks if they’re exercising or hanging out together outdoors.

You also don’t need a mask if you’re attending a small, outdoor gathering with fully vaccinated family and friends, whether you’re vaccinated or not.

The new guidelines also say it’s OK for fully vaccinated people to take their masks off outdoors when gathering in a small group of vaccinated and unvaccinated people, but suggest that unvaccinated people should still wear a mask.



Reporter Marcia Frellick contributed to this report.

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

People with clinically diagnosed depression and anxiety may be prone to developing Alzheimer’s disease at a younger age than other people, and those with a history of posttraumatic stress disorder may be prone to Alzheimer’s disease onset even earlier in life, according to findings from a review of 1,500 patients with Alzheimer’s disease from a single-center population.

“Could psychosis symptoms be the proverbial canary in a coal mine?” Emily Eijansantos, a medical student at the University of California, San Francisco, said in reporting results of the chart review at the 2021 annual meeting of the American Academy of Neurology. “Previously in this cohort it was found that neurodevelopmental factors as well as chronic insults such as autoimmunity and seizure were also associated with an early age of onset in Alzheimer’s disease.”

The link between depression and autoimmunity, and anxiety and seizure “beg more questions about underlying pathophysiology,” she said. The study included 750 patients with early-onset Alzheimer’s disease and a similar number of late-onset patients from the UCSF Memory and Aging Center.
 

An inverse correlation between psychiatric disorders and age of Alzheimer’s onset

In the total study population, 43.5% (n = 652) had a previous diagnosis of depression and 32.3% (n = 485) had been diagnosed with anxiety. That, Ms. Eijansantos said, falls into similar ranges that other studies have reported.

“When we look at individual psychiatric disorders, we find that those with depression, anxiety, or PTSD are younger on average,” she said. “Patients with depression and anxiety are more [likely] female and have less vascular risk factors, and we observed an association between depression and autoimmunity, anxiety, and seizures.”

Specifically, patients with a history of depression were 2.2 years younger, on average, at the age of onset than patients without such history (P = .01); those with anxiety were 3 years younger on average (P = .01); and those with PTSD were 6.8 years younger on average, although only 1% (n = 15) of study subjects had PTSD, making for a small sample to study. These age-of-onset disparities didn’t appear among patients with previously diagnosed bipolar disorder (BPD) or schizophrenia.

Ms. Eijansantos noted that there were no differences in education attained or apolipoprotein-E gene status between the patients with and without a history of psychosis, and, within the subgroups of individual psychiatric disorders, there were no differences between patients with past and current or formal and informal diagnoses.

“When we split the cohort into quintiles based on age of Alzheimer’s disease onset, we find an inverse correlation between the amount of depression, anxiety, and PTSD endorsed and their ages of onset,” Ms. Eijansantos said. For example, the youngest quintile had a greater than 50% rate of depression while the oldest quintile had a depression rate around 36%. A similar spread was found with anxiety: a rate around 46% in the youngest quantile versus around 25% in the oldest, whereas rates of PTSD, BPD, and schizophrenia were similar across the five age-of-onset groups.

Patients with a history of multiple psychiatric disorders had an even younger age of onset. “We see that those with two psychiatric disorder are younger than those with one, and those with three psychiatric disorders are younger still,” Ms. Eijansantos said. “And we find that the Alzheimer’s disease age-at-onset reduction doubles with each additional psychiatric disorder.” Multiple disorders also adversely impacted survival, she said.

Because they found no difference between patients with past versus active symptoms and informal versus formal diagnosis, Ms. Eijansantos explained that they further studied the National Alzheimer’s Coordinating Center cohort of 8,267 patients with Alzheimer’s disease and found a similar relationship between psychiatric history and age of onset among patients with depression or anxiety or both. This cohort also documented symptom severity, she noted. “So when we look at depression and anxiety we find similar reductions in the Alzheimer’s disease age of onset with each increasing degree of symptom severity,” she said.

“Does this mean that psychiatric disease is a risk factor for Alzheimr’s disease?” Ms. Eijansantos said. “We can’t answer that with this study because it was only designed to see if the psychiatric factors modulate the age of onset in those that have Alzheimer’s disease, but taken together we believe that these results fit the framework that there are pathophysiological and profound differences between earlier and later presentations of Alzheimer’s disease.”

She pointed to reports that early-onset Alzheimer’s disease is associated with more aggressive tau pathology and that depression is associated with tau. However, the evidence supporting a link between amyloid and psychiatric disease is less certain, she said.
 

Preliminary and speculative findings

Senior study author Zachary Miller, MD, an assistant professor in the UCSF Memory and Aging Center, explained the significance of the study findings of potential links between depression and autoimmunity, and anxiety and seizure. “There may be distinct underlying pathophysiological mechanisms in patients with Alzheimer’s disease who have symptoms of depression versus anxiety,” he said, acknowledging the findings “are quite preliminary and our interpretations quite speculative.”

The findings raise the question that the symptomatic presentation of greater amounts of depression in early-onset Alzheimer’s disease may be moderated by an underlying neuroinflammatory insult, he said. “If so, depression symptomatology could then be seen as a possible clinical marker of this inflammatory response and possibly be used in testing clinical endpoints for future intervention trials,” Dr. Miller said. “Similarly, if neuronal hyperexcitability in Alzheimer’s disease manifests itself as either seizure and/or anxiety, this would have significant impact for therapeutic monitoring and treatment.”

He said a multicenter study of Alzheimer’s disease cohorts would validate the findings. “At the same time, we are also interested in looking deeper into these findings, investigating the potential cognitive and neuroanatomical correlates associated with these conditions,” Dr. Miller said.

Clinical phenotyping may provide more insight into the relationship between psychosis and age of Alzheimer’s disease onset, said Vijay K. Ramanan, MD, PhD, an assistant professor of neurology at Mayo Clinic in Rochester, Minn.

People with clinically diagnosed depression and anxiety may be prone to developing Alzheimer’s disease at a younger age than other people, and those with a history of posttraumatic stress disorder may be prone to Alzheimer’s disease onset even earlier in life, according to findings from a review of 1,500 patients with Alzheimer’s disease from a single-center population.

“Could psychosis symptoms be the proverbial canary in a coal mine?” Emily Eijansantos, a medical student at the University of California, San Francisco, said in reporting results of the chart review at the 2021 annual meeting of the American Academy of Neurology. “Previously in this cohort it was found that neurodevelopmental factors as well as chronic insults such as autoimmunity and seizure were also associated with an early age of onset in Alzheimer’s disease.”

The link between depression and autoimmunity, and anxiety and seizure “beg more questions about underlying pathophysiology,” she said. The study included 750 patients with early-onset Alzheimer’s disease and a similar number of late-onset patients from the UCSF Memory and Aging Center.
 

An inverse correlation between psychiatric disorders and age of Alzheimer’s onset

In the total study population, 43.5% (n = 652) had a previous diagnosis of depression and 32.3% (n = 485) had been diagnosed with anxiety. That, Ms. Eijansantos said, falls into similar ranges that other studies have reported.

“When we look at individual psychiatric disorders, we find that those with depression, anxiety, or PTSD are younger on average,” she said. “Patients with depression and anxiety are more [likely] female and have less vascular risk factors, and we observed an association between depression and autoimmunity, anxiety, and seizures.”

Specifically, patients with a history of depression were 2.2 years younger, on average, at the age of onset than patients without such history (P = .01); those with anxiety were 3 years younger on average (P = .01); and those with PTSD were 6.8 years younger on average, although only 1% (n = 15) of study subjects had PTSD, making for a small sample to study. These age-of-onset disparities didn’t appear among patients with previously diagnosed bipolar disorder (BPD) or schizophrenia.

Ms. Eijansantos noted that there were no differences in education attained or apolipoprotein-E gene status between the patients with and without a history of psychosis, and, within the subgroups of individual psychiatric disorders, there were no differences between patients with past and current or formal and informal diagnoses.

“When we split the cohort into quintiles based on age of Alzheimer’s disease onset, we find an inverse correlation between the amount of depression, anxiety, and PTSD endorsed and their ages of onset,” Ms. Eijansantos said. For example, the youngest quintile had a greater than 50% rate of depression while the oldest quintile had a depression rate around 36%. A similar spread was found with anxiety: a rate around 46% in the youngest quantile versus around 25% in the oldest, whereas rates of PTSD, BPD, and schizophrenia were similar across the five age-of-onset groups.

Patients with a history of multiple psychiatric disorders had an even younger age of onset. “We see that those with two psychiatric disorder are younger than those with one, and those with three psychiatric disorders are younger still,” Ms. Eijansantos said. “And we find that the Alzheimer’s disease age-at-onset reduction doubles with each additional psychiatric disorder.” Multiple disorders also adversely impacted survival, she said.

Because they found no difference between patients with past versus active symptoms and informal versus formal diagnosis, Ms. Eijansantos explained that they further studied the National Alzheimer’s Coordinating Center cohort of 8,267 patients with Alzheimer’s disease and found a similar relationship between psychiatric history and age of onset among patients with depression or anxiety or both. This cohort also documented symptom severity, she noted. “So when we look at depression and anxiety we find similar reductions in the Alzheimer’s disease age of onset with each increasing degree of symptom severity,” she said.

“Does this mean that psychiatric disease is a risk factor for Alzheimr’s disease?” Ms. Eijansantos said. “We can’t answer that with this study because it was only designed to see if the psychiatric factors modulate the age of onset in those that have Alzheimer’s disease, but taken together we believe that these results fit the framework that there are pathophysiological and profound differences between earlier and later presentations of Alzheimer’s disease.”

She pointed to reports that early-onset Alzheimer’s disease is associated with more aggressive tau pathology and that depression is associated with tau. However, the evidence supporting a link between amyloid and psychiatric disease is less certain, she said.
 

Preliminary and speculative findings

Senior study author Zachary Miller, MD, an assistant professor in the UCSF Memory and Aging Center, explained the significance of the study findings of potential links between depression and autoimmunity, and anxiety and seizure. “There may be distinct underlying pathophysiological mechanisms in patients with Alzheimer’s disease who have symptoms of depression versus anxiety,” he said, acknowledging the findings “are quite preliminary and our interpretations quite speculative.”

The findings raise the question that the symptomatic presentation of greater amounts of depression in early-onset Alzheimer’s disease may be moderated by an underlying neuroinflammatory insult, he said. “If so, depression symptomatology could then be seen as a possible clinical marker of this inflammatory response and possibly be used in testing clinical endpoints for future intervention trials,” Dr. Miller said. “Similarly, if neuronal hyperexcitability in Alzheimer’s disease manifests itself as either seizure and/or anxiety, this would have significant impact for therapeutic monitoring and treatment.”

He said a multicenter study of Alzheimer’s disease cohorts would validate the findings. “At the same time, we are also interested in looking deeper into these findings, investigating the potential cognitive and neuroanatomical correlates associated with these conditions,” Dr. Miller said.

Clinical phenotyping may provide more insight into the relationship between psychosis and age of Alzheimer’s disease onset, said Vijay K. Ramanan, MD, PhD, an assistant professor of neurology at Mayo Clinic in Rochester, Minn.

People with clinically diagnosed depression and anxiety may be prone to developing Alzheimer’s disease at a younger age than other people, and those with a history of posttraumatic stress disorder may be prone to Alzheimer’s disease onset even earlier in life, according to findings from a review of 1,500 patients with Alzheimer’s disease from a single-center population.

“Could psychosis symptoms be the proverbial canary in a coal mine?” Emily Eijansantos, a medical student at the University of California, San Francisco, said in reporting results of the chart review at the 2021 annual meeting of the American Academy of Neurology. “Previously in this cohort it was found that neurodevelopmental factors as well as chronic insults such as autoimmunity and seizure were also associated with an early age of onset in Alzheimer’s disease.”

The link between depression and autoimmunity, and anxiety and seizure “beg more questions about underlying pathophysiology,” she said. The study included 750 patients with early-onset Alzheimer’s disease and a similar number of late-onset patients from the UCSF Memory and Aging Center.
 

An inverse correlation between psychiatric disorders and age of Alzheimer’s onset

In the total study population, 43.5% (n = 652) had a previous diagnosis of depression and 32.3% (n = 485) had been diagnosed with anxiety. That, Ms. Eijansantos said, falls into similar ranges that other studies have reported.

“When we look at individual psychiatric disorders, we find that those with depression, anxiety, or PTSD are younger on average,” she said. “Patients with depression and anxiety are more [likely] female and have less vascular risk factors, and we observed an association between depression and autoimmunity, anxiety, and seizures.”

Specifically, patients with a history of depression were 2.2 years younger, on average, at the age of onset than patients without such history (P = .01); those with anxiety were 3 years younger on average (P = .01); and those with PTSD were 6.8 years younger on average, although only 1% (n = 15) of study subjects had PTSD, making for a small sample to study. These age-of-onset disparities didn’t appear among patients with previously diagnosed bipolar disorder (BPD) or schizophrenia.

Ms. Eijansantos noted that there were no differences in education attained or apolipoprotein-E gene status between the patients with and without a history of psychosis, and, within the subgroups of individual psychiatric disorders, there were no differences between patients with past and current or formal and informal diagnoses.

“When we split the cohort into quintiles based on age of Alzheimer’s disease onset, we find an inverse correlation between the amount of depression, anxiety, and PTSD endorsed and their ages of onset,” Ms. Eijansantos said. For example, the youngest quintile had a greater than 50% rate of depression while the oldest quintile had a depression rate around 36%. A similar spread was found with anxiety: a rate around 46% in the youngest quantile versus around 25% in the oldest, whereas rates of PTSD, BPD, and schizophrenia were similar across the five age-of-onset groups.

Patients with a history of multiple psychiatric disorders had an even younger age of onset. “We see that those with two psychiatric disorder are younger than those with one, and those with three psychiatric disorders are younger still,” Ms. Eijansantos said. “And we find that the Alzheimer’s disease age-at-onset reduction doubles with each additional psychiatric disorder.” Multiple disorders also adversely impacted survival, she said.

Because they found no difference between patients with past versus active symptoms and informal versus formal diagnosis, Ms. Eijansantos explained that they further studied the National Alzheimer’s Coordinating Center cohort of 8,267 patients with Alzheimer’s disease and found a similar relationship between psychiatric history and age of onset among patients with depression or anxiety or both. This cohort also documented symptom severity, she noted. “So when we look at depression and anxiety we find similar reductions in the Alzheimer’s disease age of onset with each increasing degree of symptom severity,” she said.

“Does this mean that psychiatric disease is a risk factor for Alzheimr’s disease?” Ms. Eijansantos said. “We can’t answer that with this study because it was only designed to see if the psychiatric factors modulate the age of onset in those that have Alzheimer’s disease, but taken together we believe that these results fit the framework that there are pathophysiological and profound differences between earlier and later presentations of Alzheimer’s disease.”

She pointed to reports that early-onset Alzheimer’s disease is associated with more aggressive tau pathology and that depression is associated with tau. However, the evidence supporting a link between amyloid and psychiatric disease is less certain, she said.
 

Preliminary and speculative findings

Senior study author Zachary Miller, MD, an assistant professor in the UCSF Memory and Aging Center, explained the significance of the study findings of potential links between depression and autoimmunity, and anxiety and seizure. “There may be distinct underlying pathophysiological mechanisms in patients with Alzheimer’s disease who have symptoms of depression versus anxiety,” he said, acknowledging the findings “are quite preliminary and our interpretations quite speculative.”

The findings raise the question that the symptomatic presentation of greater amounts of depression in early-onset Alzheimer’s disease may be moderated by an underlying neuroinflammatory insult, he said. “If so, depression symptomatology could then be seen as a possible clinical marker of this inflammatory response and possibly be used in testing clinical endpoints for future intervention trials,” Dr. Miller said. “Similarly, if neuronal hyperexcitability in Alzheimer’s disease manifests itself as either seizure and/or anxiety, this would have significant impact for therapeutic monitoring and treatment.”

He said a multicenter study of Alzheimer’s disease cohorts would validate the findings. “At the same time, we are also interested in looking deeper into these findings, investigating the potential cognitive and neuroanatomical correlates associated with these conditions,” Dr. Miller said.

Clinical phenotyping may provide more insight into the relationship between psychosis and age of Alzheimer’s disease onset, said Vijay K. Ramanan, MD, PhD, an assistant professor of neurology at Mayo Clinic in Rochester, Minn.

COVID-19 is linked to novel seizures and subsequent adverse outcomes, including death, in patients without a previous history of epilepsy, new research shows. In a retrospective study of more than 900 patients admitted to the hospital with COVID-19, those without a known history of epilepsy had three times greater odds of experiencing novel seizures than those with a known history of epilepsy.

In addition, among patients with new-onset seizures, hospital stays were about 15 days longer – and mortality rates were significantly higher.

“We’re finding that there are many neurological consequences that can happen with COVID-19 infections, and it’s important for clinicians to keep that in mind as they monitor people long term,” said study investigator Neeraj Singh, MD, neurologist and epileptologist with Northwell Health System, Great Neck, New York.

Dr. Singh noted that although seizures “might not be the most common thing we see in people with COVID-19, they seem to be new seizures and not just a seizure we knew would happen in someone with epilepsy.”

“So there’s definitely a need now for more prospective research and following people over time to fully understand all the different things that might be newly a problem for them in the long term,” he added.

Dr. Singh and Hardik Bhaskar, an undergraduate student at Hunter College, New York, presented the study findings at the American Academy of Neurology’s 2021 annual meeting.
 

Largest sample to date

“This study explores the relationship between the incidences of COVID-19 infections and [novel] epileptic seizures in the largest sample to date in a single New York–based hospital system,” the investigators noted. Novel seizures included both new-onset and breakthrough seizures.

Dr. Singh told meeting attendees that the “early epicenter” of the COVID pandemic was in New York and occurred from Feb. 29, 2020 to June 1, 2020. Patients with COVID-19 “had multiple neurological sequelae, including seizures, strokes, and encephalopathy,” he said.

However, the effects of COVID-19 on individuals with epilepsy “remain unclear,” Dr. Singh said.

For their study, the researchers assessed 917 patients in 13 New York City metropolitan hospitals. All participants had received a confirmed positive test result on PCR for COVID and had received an antiepileptic medication upon admission. The patients were admitted between Feb. 14 and June 14, 2020.

For the study, the patients were first divided into two groups: those with a history of epilepsy (n = 451), and those without such a history (n = 466).

The first group was further divided on the basis of those who presented with breakthrough seizures and those who presented without them. The second group was further divided on the basis of those who presented with new-onset seizures and those who presented without them.
 

Significant adverse outcomes

Results showed that 27% of the patients without a history of epilepsy experienced a novel/new-onset seizure and that 11% of the patients with a history of epilepsy experienced a novel/breakthrough seizure (odds ratio, 3.15; P < .0001).

In addition, participants with new-onset seizures had a longer stay in the hospital (mean, 26.9 days) than the subgroup with a history of epilepsy and no breakthrough seizures (10.9 days) and the subgroup with a history of epilepsy who did experience breakthrough seizures (12.8 days; P < .0001 for both comparisons).

In the group of patients with a history of epilepsy, there were no significant differences in lengths of stay between those with and those without breakthrough seizures (P = .68).

Although mortality rates did not differ significantly between the full group with a history of epilepsy versus the full group without epilepsy (23% vs. 25%; OR, 0.9), the mortality rate was significantly higher among patients who experienced novel seizures than among those who did not experience such seizures (29% vs. 23%; OR, 1.4; P = .045).

Mr. Bhaskar noted that there are “many hypotheses for the mechanism by which COVID-19 might cause seizures.” Those mechanisms include proinflammatory cytokine storms, which may increase the rate of apoptosis, neuronal necrosis, and glutamate concentrations and may disrupt the blood-brain barrier. Another hypothesis is that SARS-CoV-2 infection may lead to hypoxia and abnormal coagulation, resulting in stroke and a subsequent increase in the risk for seizures.

Interestingly, “the presence of antiepileptic medications in patients with epilepsy may confer a protective effect against breakthrough seizures,” Dr. Singh said. “However, some subclinical seizures may be misdiagnosed as encephalopathy when patients present with COVID-19 infections.”

He added that further research is needed into the mechanisms linking these infections and new-onset seizures and to “identify subclinical seizures in encephalopathic patients.”

Asked during the question-and-answer session whether the investigators had assessed differences by demographics, such as age or sex, Dr. Singh said, “We have not subdivided them that way yet,” but he said he would like to do so in the future. He also plans to look further into which specific medications were used by the participants.

The investigators have reported no relevant financial relationships.

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

COVID-19 is linked to novel seizures and subsequent adverse outcomes, including death, in patients without a previous history of epilepsy, new research shows. In a retrospective study of more than 900 patients admitted to the hospital with COVID-19, those without a known history of epilepsy had three times greater odds of experiencing novel seizures than those with a known history of epilepsy.

In addition, among patients with new-onset seizures, hospital stays were about 15 days longer – and mortality rates were significantly higher.

“We’re finding that there are many neurological consequences that can happen with COVID-19 infections, and it’s important for clinicians to keep that in mind as they monitor people long term,” said study investigator Neeraj Singh, MD, neurologist and epileptologist with Northwell Health System, Great Neck, New York.

Dr. Singh noted that although seizures “might not be the most common thing we see in people with COVID-19, they seem to be new seizures and not just a seizure we knew would happen in someone with epilepsy.”

“So there’s definitely a need now for more prospective research and following people over time to fully understand all the different things that might be newly a problem for them in the long term,” he added.

Dr. Singh and Hardik Bhaskar, an undergraduate student at Hunter College, New York, presented the study findings at the American Academy of Neurology’s 2021 annual meeting.
 

Largest sample to date

“This study explores the relationship between the incidences of COVID-19 infections and [novel] epileptic seizures in the largest sample to date in a single New York–based hospital system,” the investigators noted. Novel seizures included both new-onset and breakthrough seizures.

Dr. Singh told meeting attendees that the “early epicenter” of the COVID pandemic was in New York and occurred from Feb. 29, 2020 to June 1, 2020. Patients with COVID-19 “had multiple neurological sequelae, including seizures, strokes, and encephalopathy,” he said.

However, the effects of COVID-19 on individuals with epilepsy “remain unclear,” Dr. Singh said.

For their study, the researchers assessed 917 patients in 13 New York City metropolitan hospitals. All participants had received a confirmed positive test result on PCR for COVID and had received an antiepileptic medication upon admission. The patients were admitted between Feb. 14 and June 14, 2020.

For the study, the patients were first divided into two groups: those with a history of epilepsy (n = 451), and those without such a history (n = 466).

The first group was further divided on the basis of those who presented with breakthrough seizures and those who presented without them. The second group was further divided on the basis of those who presented with new-onset seizures and those who presented without them.
 

Significant adverse outcomes

Results showed that 27% of the patients without a history of epilepsy experienced a novel/new-onset seizure and that 11% of the patients with a history of epilepsy experienced a novel/breakthrough seizure (odds ratio, 3.15; P < .0001).

In addition, participants with new-onset seizures had a longer stay in the hospital (mean, 26.9 days) than the subgroup with a history of epilepsy and no breakthrough seizures (10.9 days) and the subgroup with a history of epilepsy who did experience breakthrough seizures (12.8 days; P < .0001 for both comparisons).

In the group of patients with a history of epilepsy, there were no significant differences in lengths of stay between those with and those without breakthrough seizures (P = .68).

Although mortality rates did not differ significantly between the full group with a history of epilepsy versus the full group without epilepsy (23% vs. 25%; OR, 0.9), the mortality rate was significantly higher among patients who experienced novel seizures than among those who did not experience such seizures (29% vs. 23%; OR, 1.4; P = .045).

Mr. Bhaskar noted that there are “many hypotheses for the mechanism by which COVID-19 might cause seizures.” Those mechanisms include proinflammatory cytokine storms, which may increase the rate of apoptosis, neuronal necrosis, and glutamate concentrations and may disrupt the blood-brain barrier. Another hypothesis is that SARS-CoV-2 infection may lead to hypoxia and abnormal coagulation, resulting in stroke and a subsequent increase in the risk for seizures.

Interestingly, “the presence of antiepileptic medications in patients with epilepsy may confer a protective effect against breakthrough seizures,” Dr. Singh said. “However, some subclinical seizures may be misdiagnosed as encephalopathy when patients present with COVID-19 infections.”

He added that further research is needed into the mechanisms linking these infections and new-onset seizures and to “identify subclinical seizures in encephalopathic patients.”

Asked during the question-and-answer session whether the investigators had assessed differences by demographics, such as age or sex, Dr. Singh said, “We have not subdivided them that way yet,” but he said he would like to do so in the future. He also plans to look further into which specific medications were used by the participants.

The investigators have reported no relevant financial relationships.

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

COVID-19 is linked to novel seizures and subsequent adverse outcomes, including death, in patients without a previous history of epilepsy, new research shows. In a retrospective study of more than 900 patients admitted to the hospital with COVID-19, those without a known history of epilepsy had three times greater odds of experiencing novel seizures than those with a known history of epilepsy.

In addition, among patients with new-onset seizures, hospital stays were about 15 days longer – and mortality rates were significantly higher.

“We’re finding that there are many neurological consequences that can happen with COVID-19 infections, and it’s important for clinicians to keep that in mind as they monitor people long term,” said study investigator Neeraj Singh, MD, neurologist and epileptologist with Northwell Health System, Great Neck, New York.

Dr. Singh noted that although seizures “might not be the most common thing we see in people with COVID-19, they seem to be new seizures and not just a seizure we knew would happen in someone with epilepsy.”

“So there’s definitely a need now for more prospective research and following people over time to fully understand all the different things that might be newly a problem for them in the long term,” he added.

Dr. Singh and Hardik Bhaskar, an undergraduate student at Hunter College, New York, presented the study findings at the American Academy of Neurology’s 2021 annual meeting.
 

Largest sample to date

“This study explores the relationship between the incidences of COVID-19 infections and [novel] epileptic seizures in the largest sample to date in a single New York–based hospital system,” the investigators noted. Novel seizures included both new-onset and breakthrough seizures.

Dr. Singh told meeting attendees that the “early epicenter” of the COVID pandemic was in New York and occurred from Feb. 29, 2020 to June 1, 2020. Patients with COVID-19 “had multiple neurological sequelae, including seizures, strokes, and encephalopathy,” he said.

However, the effects of COVID-19 on individuals with epilepsy “remain unclear,” Dr. Singh said.

For their study, the researchers assessed 917 patients in 13 New York City metropolitan hospitals. All participants had received a confirmed positive test result on PCR for COVID and had received an antiepileptic medication upon admission. The patients were admitted between Feb. 14 and June 14, 2020.

For the study, the patients were first divided into two groups: those with a history of epilepsy (n = 451), and those without such a history (n = 466).

The first group was further divided on the basis of those who presented with breakthrough seizures and those who presented without them. The second group was further divided on the basis of those who presented with new-onset seizures and those who presented without them.
 

Significant adverse outcomes

Results showed that 27% of the patients without a history of epilepsy experienced a novel/new-onset seizure and that 11% of the patients with a history of epilepsy experienced a novel/breakthrough seizure (odds ratio, 3.15; P < .0001).

In addition, participants with new-onset seizures had a longer stay in the hospital (mean, 26.9 days) than the subgroup with a history of epilepsy and no breakthrough seizures (10.9 days) and the subgroup with a history of epilepsy who did experience breakthrough seizures (12.8 days; P < .0001 for both comparisons).

In the group of patients with a history of epilepsy, there were no significant differences in lengths of stay between those with and those without breakthrough seizures (P = .68).

Although mortality rates did not differ significantly between the full group with a history of epilepsy versus the full group without epilepsy (23% vs. 25%; OR, 0.9), the mortality rate was significantly higher among patients who experienced novel seizures than among those who did not experience such seizures (29% vs. 23%; OR, 1.4; P = .045).

Mr. Bhaskar noted that there are “many hypotheses for the mechanism by which COVID-19 might cause seizures.” Those mechanisms include proinflammatory cytokine storms, which may increase the rate of apoptosis, neuronal necrosis, and glutamate concentrations and may disrupt the blood-brain barrier. Another hypothesis is that SARS-CoV-2 infection may lead to hypoxia and abnormal coagulation, resulting in stroke and a subsequent increase in the risk for seizures.

Interestingly, “the presence of antiepileptic medications in patients with epilepsy may confer a protective effect against breakthrough seizures,” Dr. Singh said. “However, some subclinical seizures may be misdiagnosed as encephalopathy when patients present with COVID-19 infections.”

He added that further research is needed into the mechanisms linking these infections and new-onset seizures and to “identify subclinical seizures in encephalopathic patients.”

Asked during the question-and-answer session whether the investigators had assessed differences by demographics, such as age or sex, Dr. Singh said, “We have not subdivided them that way yet,” but he said he would like to do so in the future. He also plans to look further into which specific medications were used by the participants.

The investigators have reported no relevant financial relationships.

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

Use of the Johnson & Johnson COVID-19 vaccine should resume in the United States for all adults, the Food and Drug Administration and Centers for Disease Contol and Prevention said April 23, although health care providers should warn patients of the risk of developing the rare and serious blood clots that caused the agencies to pause the vaccine’s distribution earlier this month.

Johnson &amp; Johnson

Use of the Johnson & Johnson COVID-19 vaccine should resume in the United States for all adults, the Food and Drug Administration and Centers for Disease Contol and Prevention said April 23, although health care providers should warn patients of the risk of developing the rare and serious blood clots that caused the agencies to pause the vaccine’s distribution earlier this month.

Johnson &amp; Johnson

Use of the Johnson & Johnson COVID-19 vaccine should resume in the United States for all adults, the Food and Drug Administration and Centers for Disease Contol and Prevention said April 23, although health care providers should warn patients of the risk of developing the rare and serious blood clots that caused the agencies to pause the vaccine’s distribution earlier this month.

Johnson &amp; Johnson