A novel, once-nightly formulation of sodium oxybate is safe and effective for treating both subjective and objective symptoms of narcolepsy, new research suggests. Top-line results from the phase 3 REST-ON trial released earlier this year showed that the agent known as FT218 (Avadel Pharmaceuticals) met all three of its coprimary efficacy endpoints at all three doses assessed (6 g, 7.5 g, and 9 g). Patients receiving the drug showed significantly greater improvements on the Maintenance of Wakefulness Test (MWT), the Clinical Global Impression of Improvement (CGI-I), and mean weekly attacks of cataplexy, compared with those who received placebo.

The new analyses, which focused on key secondary outcomes, showed that all three doses of the novel agent were associated with significant improvements in sleep quality, refreshing nature of sleep, sleep paralysis, disturbed nocturnal sleep, and scores on the Epworth Sleepiness Scale (ESS).

Principal investigator Michael J. Thorpy, MD, director of the Sleep-Wake Disorders Center at the Montefiore Medical Center, New York, said in a news release that the results represent “the promise of a potential new treatment strategy for physicians and patients.”

“I am particularly impressed by the consistency of results as early as 3 weeks with only a 6-g dose,” he added.

Dr. Thorpy, who is also a professor of neurology at the Albert Einstein College of Medicine, noted that the new formulation will be more convenient for patients. “The advantage of this medication is its once-nightly formulation, so patients don’t need to awaken during the night and can actually have a better night’s sleep,” he said.

Dr. Thorpy presented the study findings at the 2021 annual meeting of the American Academy of Neurology.

FT218 is currently under review by the U.S. Food and Drug Administration, which has set Oct. 15 as the Prescription Drug User Fee Act target date.

Forced awakening

Sodium oxybate was first approved by the FDA in 2002 to treat cataplexy in adults with narcolepsy and was expanded in 2005 to also treat excessive daytime sleepiness (EDS). That formulation is indicated for twice-nightly administration, with the second dose taken 2.5-4 hours after the first.

“The need for forced awakening to take the second dose ... may result in noncompliance, which may lead to reduced efficacy and/or mistimed doses,” the investigators noted.

FT218 is a modified-release version of sodium oxybate. A single 6-g dose of the investigational agent “has shown bioequivalent exposure to twice-nightly immediate-release [sodium oxybate] given as two 3-g doses,” wrote the researchers.

It also currently has Orphan Drug Designation from the FDA for the treatment of narcolepsy.

The randomized, double-blind, placebo-controlled, multicenter REST-ON study was conducted from November 2016 to March 2020 and included patients 16 years or older who had narcolepsy type 1 or type 2.

Patients received the active treatment (n = 107; mean age, 30.9 years; 64.5% women) or placebo (n = 105; mean age, 31.6 years; 71.4% women) according to a four-period forced uptitration dosing schedule of 4.5 g for 1 week, 6 g for 2 weeks, 7.5 g for 5 weeks, and 9 g for 5 weeks.

Secondary outcome measures included the ESS, sleep quality/refreshing nature of sleep on a visual analog scale, sleep paralysis and hypnagogic hallucinations on a sleep symptoms diary, disturbed nocturnal sleep on polysomnographic measures, and number of arousals as defined per the American Academy of Sleep Medicine Score Manual.

Reports of adverse events (AEs) were collected from time of informed consent until 7 days after the last dose received.

Improvement across doses

Results showed that, compared with placebo, improvement in disturbed nocturnal sleep from baseline was significantly greater for the active treatment at 6 g at week 3 (mean between-group difference, –11; P < .001), at 7.5 g at week 8 (mean difference, –17.7; P < .001), and at 9 g at week 13 (mean difference, –22.6; P < .001).

The mean difference between the three doses and placebo for reduction in number of arousals was –11.3 (P < .05), –19.4 (P < .001), and –23.7 (P < .001), respectively. And the 6 g at week 3, 7.5 g at week 8, and 9 g at week 13 doses showed significant (P < .001) improvements versus placebo on the ESS (mean difference, –2.1, –3.2, and –3.9, respectively).

All three doses also showed significant improvement in sleep quality and refreshing nature of sleep (P < .001 for all comparisons), as well as improvement of sleep paralysis (P = .04, P = .02, and P = .04, respectively).

There were no significant differences between FT218 and placebo for improvement in hypnagogic hallucinations. Dr. Thorpy noted that the number of patients with baseline hallucinations “was relatively small,” which may have led to this finding. “Had there been a much larger population with hallucinations, I suspect that we would have seen a statistically significant improvement there as well,” he said.

Generally well tolerated

The investigators noted that FT218 was “generally well tolerated, and the most common adverse reactions were well-known and established sodium oxybate adverse reactions.”

Treatment-related AEs that occurred in more than 2% of the patients receiving FT218 included nausea, dizziness, enuresis, headache, decreased appetite, and vomiting.

Seven serious AEs were reported, including five in those assigned to the active treatment. This included one case each of diabetes inadequate control, paresthesia, perirectal abscess, hypertension, and suicidal ideation. Only the case of suicidal ideation was considered to be a treatment-related AE.

The investigators noted that, although they have not yet delved into subgroup analysis to look for differences among sex, age, or race, they plan to do so in the future.

Overall, the results indicate that “FT218 is an effective agent not only for the major symptoms of sleepiness and cataplexy, but also the quality of sleep at night,” said Dr. Thorpy.

Asked whether he thinks the FDA will approve the drug, he said that it should be “straightforward” because it’s just a different formulation of an already-approved agent. “I very much expect there will not be any problems in this medication being approved,” Dr. Thorpy said.

Benefits ‘sleep architecture’

Commenting on the findings, Logan Schneider, MD, codirector of the Stanford/VA Alzheimer’s Center and clinical assistant professor at the Stanford Sleep Center, Redwood City, Calif., said that the investigators’ focus on these secondary outcomes “was really worthwhile.”

Dr. Schneider, who was not involved in the research, noted that, because the study only included patients with narcolepsy, the results can’t be extrapolated to groups who have other sleep disorders.

Still, “it is worthwhile now to expand beyond the two primary symptoms that are, in my consideration, life threatening: daytime sleepiness and cataplexy. We should also address more of the quality of life and other aspects of narcolepsy, including disturbed nocturnal sleep and sleep quality issues related to that,” he said.

“Being able to address those aspects and say, ‘I have a therapy that clearly helps the multidimensionality of our patients’ is very vindicating,” Dr. Schneider noted.

He was also impressed with the various measures the researchers used, rather than relying just on patient reports, “which are subject to recollection difficulties. This was a nice way to quantify possibly as a diagnostic marker the underlying disruption of sleep, as well as a possible treatment marker to show how well a therapy works.”

“It actually shows a beneficial effect on sleep architecture,” Dr. Schneider said.

The study was funded by Avadel Pharmaceuticals. Dr. Thorpy is a consultant/advisory board member for Avadel, Axsome, Balance Therapeutics, Eisai, Harmony Biosciences, Jazz Pharmaceuticals, NLS Pharmaceuticals, Suven Life Sciences, and Takeda Pharmaceutical. Dr. Schneider reports being an adviser and/or on the speakers’ bureau for similar drugs by Jazz Pharmaceuticals and Harmony Biosciences.

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

A novel, once-nightly formulation of sodium oxybate is safe and effective for treating both subjective and objective symptoms of narcolepsy, new research suggests. Top-line results from the phase 3 REST-ON trial released earlier this year showed that the agent known as FT218 (Avadel Pharmaceuticals) met all three of its coprimary efficacy endpoints at all three doses assessed (6 g, 7.5 g, and 9 g). Patients receiving the drug showed significantly greater improvements on the Maintenance of Wakefulness Test (MWT), the Clinical Global Impression of Improvement (CGI-I), and mean weekly attacks of cataplexy, compared with those who received placebo.

The new analyses, which focused on key secondary outcomes, showed that all three doses of the novel agent were associated with significant improvements in sleep quality, refreshing nature of sleep, sleep paralysis, disturbed nocturnal sleep, and scores on the Epworth Sleepiness Scale (ESS).

Principal investigator Michael J. Thorpy, MD, director of the Sleep-Wake Disorders Center at the Montefiore Medical Center, New York, said in a news release that the results represent “the promise of a potential new treatment strategy for physicians and patients.”

“I am particularly impressed by the consistency of results as early as 3 weeks with only a 6-g dose,” he added.

Dr. Thorpy, who is also a professor of neurology at the Albert Einstein College of Medicine, noted that the new formulation will be more convenient for patients. “The advantage of this medication is its once-nightly formulation, so patients don’t need to awaken during the night and can actually have a better night’s sleep,” he said.

Dr. Thorpy presented the study findings at the 2021 annual meeting of the American Academy of Neurology.

FT218 is currently under review by the U.S. Food and Drug Administration, which has set Oct. 15 as the Prescription Drug User Fee Act target date.

Forced awakening

Sodium oxybate was first approved by the FDA in 2002 to treat cataplexy in adults with narcolepsy and was expanded in 2005 to also treat excessive daytime sleepiness (EDS). That formulation is indicated for twice-nightly administration, with the second dose taken 2.5-4 hours after the first.

“The need for forced awakening to take the second dose ... may result in noncompliance, which may lead to reduced efficacy and/or mistimed doses,” the investigators noted.

FT218 is a modified-release version of sodium oxybate. A single 6-g dose of the investigational agent “has shown bioequivalent exposure to twice-nightly immediate-release [sodium oxybate] given as two 3-g doses,” wrote the researchers.

It also currently has Orphan Drug Designation from the FDA for the treatment of narcolepsy.

The randomized, double-blind, placebo-controlled, multicenter REST-ON study was conducted from November 2016 to March 2020 and included patients 16 years or older who had narcolepsy type 1 or type 2.

Patients received the active treatment (n = 107; mean age, 30.9 years; 64.5% women) or placebo (n = 105; mean age, 31.6 years; 71.4% women) according to a four-period forced uptitration dosing schedule of 4.5 g for 1 week, 6 g for 2 weeks, 7.5 g for 5 weeks, and 9 g for 5 weeks.

Secondary outcome measures included the ESS, sleep quality/refreshing nature of sleep on a visual analog scale, sleep paralysis and hypnagogic hallucinations on a sleep symptoms diary, disturbed nocturnal sleep on polysomnographic measures, and number of arousals as defined per the American Academy of Sleep Medicine Score Manual.

Reports of adverse events (AEs) were collected from time of informed consent until 7 days after the last dose received.

Improvement across doses

Results showed that, compared with placebo, improvement in disturbed nocturnal sleep from baseline was significantly greater for the active treatment at 6 g at week 3 (mean between-group difference, –11; P < .001), at 7.5 g at week 8 (mean difference, –17.7; P < .001), and at 9 g at week 13 (mean difference, –22.6; P < .001).

The mean difference between the three doses and placebo for reduction in number of arousals was –11.3 (P < .05), –19.4 (P < .001), and –23.7 (P < .001), respectively. And the 6 g at week 3, 7.5 g at week 8, and 9 g at week 13 doses showed significant (P < .001) improvements versus placebo on the ESS (mean difference, –2.1, –3.2, and –3.9, respectively).

All three doses also showed significant improvement in sleep quality and refreshing nature of sleep (P < .001 for all comparisons), as well as improvement of sleep paralysis (P = .04, P = .02, and P = .04, respectively).

There were no significant differences between FT218 and placebo for improvement in hypnagogic hallucinations. Dr. Thorpy noted that the number of patients with baseline hallucinations “was relatively small,” which may have led to this finding. “Had there been a much larger population with hallucinations, I suspect that we would have seen a statistically significant improvement there as well,” he said.

Generally well tolerated

The investigators noted that FT218 was “generally well tolerated, and the most common adverse reactions were well-known and established sodium oxybate adverse reactions.”

Treatment-related AEs that occurred in more than 2% of the patients receiving FT218 included nausea, dizziness, enuresis, headache, decreased appetite, and vomiting.

Seven serious AEs were reported, including five in those assigned to the active treatment. This included one case each of diabetes inadequate control, paresthesia, perirectal abscess, hypertension, and suicidal ideation. Only the case of suicidal ideation was considered to be a treatment-related AE.

The investigators noted that, although they have not yet delved into subgroup analysis to look for differences among sex, age, or race, they plan to do so in the future.

Overall, the results indicate that “FT218 is an effective agent not only for the major symptoms of sleepiness and cataplexy, but also the quality of sleep at night,” said Dr. Thorpy.

Asked whether he thinks the FDA will approve the drug, he said that it should be “straightforward” because it’s just a different formulation of an already-approved agent. “I very much expect there will not be any problems in this medication being approved,” Dr. Thorpy said.

Benefits ‘sleep architecture’

Commenting on the findings, Logan Schneider, MD, codirector of the Stanford/VA Alzheimer’s Center and clinical assistant professor at the Stanford Sleep Center, Redwood City, Calif., said that the investigators’ focus on these secondary outcomes “was really worthwhile.”

Dr. Schneider, who was not involved in the research, noted that, because the study only included patients with narcolepsy, the results can’t be extrapolated to groups who have other sleep disorders.

Still, “it is worthwhile now to expand beyond the two primary symptoms that are, in my consideration, life threatening: daytime sleepiness and cataplexy. We should also address more of the quality of life and other aspects of narcolepsy, including disturbed nocturnal sleep and sleep quality issues related to that,” he said.

“Being able to address those aspects and say, ‘I have a therapy that clearly helps the multidimensionality of our patients’ is very vindicating,” Dr. Schneider noted.

He was also impressed with the various measures the researchers used, rather than relying just on patient reports, “which are subject to recollection difficulties. This was a nice way to quantify possibly as a diagnostic marker the underlying disruption of sleep, as well as a possible treatment marker to show how well a therapy works.”

“It actually shows a beneficial effect on sleep architecture,” Dr. Schneider said.

The study was funded by Avadel Pharmaceuticals. Dr. Thorpy is a consultant/advisory board member for Avadel, Axsome, Balance Therapeutics, Eisai, Harmony Biosciences, Jazz Pharmaceuticals, NLS Pharmaceuticals, Suven Life Sciences, and Takeda Pharmaceutical. Dr. Schneider reports being an adviser and/or on the speakers’ bureau for similar drugs by Jazz Pharmaceuticals and Harmony Biosciences.

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

A novel, once-nightly formulation of sodium oxybate is safe and effective for treating both subjective and objective symptoms of narcolepsy, new research suggests. Top-line results from the phase 3 REST-ON trial released earlier this year showed that the agent known as FT218 (Avadel Pharmaceuticals) met all three of its coprimary efficacy endpoints at all three doses assessed (6 g, 7.5 g, and 9 g). Patients receiving the drug showed significantly greater improvements on the Maintenance of Wakefulness Test (MWT), the Clinical Global Impression of Improvement (CGI-I), and mean weekly attacks of cataplexy, compared with those who received placebo.

The new analyses, which focused on key secondary outcomes, showed that all three doses of the novel agent were associated with significant improvements in sleep quality, refreshing nature of sleep, sleep paralysis, disturbed nocturnal sleep, and scores on the Epworth Sleepiness Scale (ESS).

Principal investigator Michael J. Thorpy, MD, director of the Sleep-Wake Disorders Center at the Montefiore Medical Center, New York, said in a news release that the results represent “the promise of a potential new treatment strategy for physicians and patients.”

“I am particularly impressed by the consistency of results as early as 3 weeks with only a 6-g dose,” he added.

Dr. Thorpy, who is also a professor of neurology at the Albert Einstein College of Medicine, noted that the new formulation will be more convenient for patients. “The advantage of this medication is its once-nightly formulation, so patients don’t need to awaken during the night and can actually have a better night’s sleep,” he said.

Dr. Thorpy presented the study findings at the 2021 annual meeting of the American Academy of Neurology.

FT218 is currently under review by the U.S. Food and Drug Administration, which has set Oct. 15 as the Prescription Drug User Fee Act target date.

Forced awakening

Sodium oxybate was first approved by the FDA in 2002 to treat cataplexy in adults with narcolepsy and was expanded in 2005 to also treat excessive daytime sleepiness (EDS). That formulation is indicated for twice-nightly administration, with the second dose taken 2.5-4 hours after the first.

“The need for forced awakening to take the second dose ... may result in noncompliance, which may lead to reduced efficacy and/or mistimed doses,” the investigators noted.

FT218 is a modified-release version of sodium oxybate. A single 6-g dose of the investigational agent “has shown bioequivalent exposure to twice-nightly immediate-release [sodium oxybate] given as two 3-g doses,” wrote the researchers.

It also currently has Orphan Drug Designation from the FDA for the treatment of narcolepsy.

The randomized, double-blind, placebo-controlled, multicenter REST-ON study was conducted from November 2016 to March 2020 and included patients 16 years or older who had narcolepsy type 1 or type 2.

Patients received the active treatment (n = 107; mean age, 30.9 years; 64.5% women) or placebo (n = 105; mean age, 31.6 years; 71.4% women) according to a four-period forced uptitration dosing schedule of 4.5 g for 1 week, 6 g for 2 weeks, 7.5 g for 5 weeks, and 9 g for 5 weeks.

Secondary outcome measures included the ESS, sleep quality/refreshing nature of sleep on a visual analog scale, sleep paralysis and hypnagogic hallucinations on a sleep symptoms diary, disturbed nocturnal sleep on polysomnographic measures, and number of arousals as defined per the American Academy of Sleep Medicine Score Manual.

Reports of adverse events (AEs) were collected from time of informed consent until 7 days after the last dose received.

Improvement across doses

Results showed that, compared with placebo, improvement in disturbed nocturnal sleep from baseline was significantly greater for the active treatment at 6 g at week 3 (mean between-group difference, –11; P < .001), at 7.5 g at week 8 (mean difference, –17.7; P < .001), and at 9 g at week 13 (mean difference, –22.6; P < .001).

The mean difference between the three doses and placebo for reduction in number of arousals was –11.3 (P < .05), –19.4 (P < .001), and –23.7 (P < .001), respectively. And the 6 g at week 3, 7.5 g at week 8, and 9 g at week 13 doses showed significant (P < .001) improvements versus placebo on the ESS (mean difference, –2.1, –3.2, and –3.9, respectively).

All three doses also showed significant improvement in sleep quality and refreshing nature of sleep (P < .001 for all comparisons), as well as improvement of sleep paralysis (P = .04, P = .02, and P = .04, respectively).

There were no significant differences between FT218 and placebo for improvement in hypnagogic hallucinations. Dr. Thorpy noted that the number of patients with baseline hallucinations “was relatively small,” which may have led to this finding. “Had there been a much larger population with hallucinations, I suspect that we would have seen a statistically significant improvement there as well,” he said.

Generally well tolerated

The investigators noted that FT218 was “generally well tolerated, and the most common adverse reactions were well-known and established sodium oxybate adverse reactions.”

Treatment-related AEs that occurred in more than 2% of the patients receiving FT218 included nausea, dizziness, enuresis, headache, decreased appetite, and vomiting.

Seven serious AEs were reported, including five in those assigned to the active treatment. This included one case each of diabetes inadequate control, paresthesia, perirectal abscess, hypertension, and suicidal ideation. Only the case of suicidal ideation was considered to be a treatment-related AE.

The investigators noted that, although they have not yet delved into subgroup analysis to look for differences among sex, age, or race, they plan to do so in the future.

Overall, the results indicate that “FT218 is an effective agent not only for the major symptoms of sleepiness and cataplexy, but also the quality of sleep at night,” said Dr. Thorpy.

Asked whether he thinks the FDA will approve the drug, he said that it should be “straightforward” because it’s just a different formulation of an already-approved agent. “I very much expect there will not be any problems in this medication being approved,” Dr. Thorpy said.

Benefits ‘sleep architecture’

Commenting on the findings, Logan Schneider, MD, codirector of the Stanford/VA Alzheimer’s Center and clinical assistant professor at the Stanford Sleep Center, Redwood City, Calif., said that the investigators’ focus on these secondary outcomes “was really worthwhile.”

Dr. Schneider, who was not involved in the research, noted that, because the study only included patients with narcolepsy, the results can’t be extrapolated to groups who have other sleep disorders.

Still, “it is worthwhile now to expand beyond the two primary symptoms that are, in my consideration, life threatening: daytime sleepiness and cataplexy. We should also address more of the quality of life and other aspects of narcolepsy, including disturbed nocturnal sleep and sleep quality issues related to that,” he said.

“Being able to address those aspects and say, ‘I have a therapy that clearly helps the multidimensionality of our patients’ is very vindicating,” Dr. Schneider noted.

He was also impressed with the various measures the researchers used, rather than relying just on patient reports, “which are subject to recollection difficulties. This was a nice way to quantify possibly as a diagnostic marker the underlying disruption of sleep, as well as a possible treatment marker to show how well a therapy works.”

“It actually shows a beneficial effect on sleep architecture,” Dr. Schneider said.

The study was funded by Avadel Pharmaceuticals. Dr. Thorpy is a consultant/advisory board member for Avadel, Axsome, Balance Therapeutics, Eisai, Harmony Biosciences, Jazz Pharmaceuticals, NLS Pharmaceuticals, Suven Life Sciences, and Takeda Pharmaceutical. Dr. Schneider reports being an adviser and/or on the speakers’ bureau for similar drugs by Jazz Pharmaceuticals and Harmony Biosciences.

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

Motor problems in children may be a harbinger of serious mental illness, new research suggests.

Investigators found that motor abnormalities were twice as common among those who develop psychosis or depression, compared with their counterparts in the general population, suggesting that these abnormalities may help predict vulnerability and provide an opportunity for early intervention.

“We have learned there are motor signs that are measurable in adolescence [that are] more prevalent in these disorders,” said lead investigator Katherine S. F. Damme, PhD, adolescent development and preventive treatment program (ADAPT), Northwestern University, Chicago. 

A core symptom

There has been a lot of interest in the pathophysiology of psychosis and in detecting it early, said Dr. Damme. “It has devastating effects, and early intervention is of great importance,” she added.

However, previous research has typically focused on affect or cognition, rather than on motor signs, despite the fact that motor signs are a “core symptom of both psychosis and depression.”

The prevalence and presentation of motor signs in adolescence, which is a “critical time for identifying these risk markers” because of their proximity to the onset of psychosis, has been understudied, Dr. Damme said.

For their study, the investigators gathered motor function data from the Adolescent Brain Cognitive Development Study (ABCD), which included 10,835 children aged 9-11 years with broad demographic diversity from 21 sites across the United States.

Overall, 27.6% of the children were reported to have least one motor sign; approximately 3% were reported to have two or more motor signs.

The most common of these was dyscoordination, which was endorsed by 19.3% of participants. In addition, 8.8% were reported to have had experienced developmental motor delays, 1.5% had psychomotor agitation, and 0.3% had psychomotor retardation.

The investigators determined that 4.6% of participants met criteria for depression, 2.6% for a psychosis, and 1.8% for comorbid psychosis and depression.

Motor signs were much more common among children with depression, psychosis, or both than among those who did not have these conditions; 45.8% reported having at least one motor sign.

Developmental motor delays and dyscoordination occurred at about the same rate in both patients with depression and those with psychosis. Rates were higher among patients with both of these conditions than among those with either condition alone.

In contrast, psychomotor agitation was more common among patients with depression alone and among those with comorbid depression and psychosis than among patients with psychosis alone. The rate of psychomotor retardation was increased among patients with psychosis alone but was less common among patients with comorbidity than in the healthy control group.

Familial vulnerability

The investigators also assessed participants who had not been diagnosed with a mental illness but who had a family history of depression only (28.9%), a relative with psychosis-like experiences (0.6%), or a family history of both depression and psychosis experiences (1.8%).

Although the effect size was smaller, there was a higher rate of motor signs among participants with a family history of these conditions, Dr. Damme said. “Again, we see that it’s elevated across developmental motor delays and at a similar rate in people who have depression and psychosis.”

In addition, psychomotor agitation was linked to depression with psychosis and depression without it.

Sensorimotor connectivity network data for the cohort indicated there was no main effect of diagnosis on corticostriatal connectivity.

However, more depressive symptoms were related to less connectivity (P = .024). There was a similar finding for psychotic-like experiences. The total number of such experiences related to lower connectivity (P < .001).

During the postpresentation discussion, Ian Kelleher, MD, PhD, honorary clinical lecturer in psychiatry at the Royal College of Surgeons in Ireland, Dublin, said he was “surprised” by the finding that the rate of psychomotor retardation was lower among participants with psychosis and depression.

Dr. Damme noted that some of the motor sign item ratings came by way of a child interview and that some of these item ratings came from the adults in the children’s lives.

She added that she was not entirely sure whether asking an 8- to 11-year-old in a clinical interview whether they are experiencing motor signs “might be the best way to get at motor slowing.”

Subtle features

Commenting on the findings in an interview, Peter F. Liddle, MD, PhD, professor of psychiatry, at the University of Nottingham (England), noted that the “features we’re talking about are pretty subtle.

“What I’ve been wondering about for some time is whether we should be getting video recordings and using machine learning approaches to teach a computer to recognize normal movements vs abnormal movements, and particularly facial expression,” said Dr. Liddle, who was not involved with the research.

He called the current study “interesting” but noted several factors that affect the potential utility of the findings in predicting outcomes.

First, they “may not be very good for distinguishing schizophrenia from mood disorders; but if the question is simply determining which young person might go on to develop a significant mental disorder, then it may be useful,” Dr. Liddle said.

He endorsed the investigators’ conclusion that motor abnormalities may be a transdiagnostic marker. Beyond that, they may be “more useful as a predictor of the likely long-term severity, but that’s my own hypothesis based on my work,” he added.

Another question concerns the sensitivity of motor abnormalities as a predictive marker. With the rate of the abnormalities identified in those who developed psychosis and depression about double the rate in the overall population, “it sounds like those assessors were fairly sensitive. … but not all that specific,” said Dr. Liddle.

A third issue relates to treatment. “By the time people get sent to a psychiatrist for assessment for possible impending psychotic illness, they’ve often already had medication,” typically an antidepressant or antipsychotic.

“It’s very well established that dopamine-blocking antipsychotics produce hypokinesia and also dyskinesia,” which could then become a confounding factor, Dr. Liddle said.

The study was funded by grants from the National Institute of Mental Health. The study authors and Dr. Liddle have disclosed no relevant financial relationships.

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

Motor problems in children may be a harbinger of serious mental illness, new research suggests.

Investigators found that motor abnormalities were twice as common among those who develop psychosis or depression, compared with their counterparts in the general population, suggesting that these abnormalities may help predict vulnerability and provide an opportunity for early intervention.

“We have learned there are motor signs that are measurable in adolescence [that are] more prevalent in these disorders,” said lead investigator Katherine S. F. Damme, PhD, adolescent development and preventive treatment program (ADAPT), Northwestern University, Chicago. 

A core symptom

There has been a lot of interest in the pathophysiology of psychosis and in detecting it early, said Dr. Damme. “It has devastating effects, and early intervention is of great importance,” she added.

However, previous research has typically focused on affect or cognition, rather than on motor signs, despite the fact that motor signs are a “core symptom of both psychosis and depression.”

The prevalence and presentation of motor signs in adolescence, which is a “critical time for identifying these risk markers” because of their proximity to the onset of psychosis, has been understudied, Dr. Damme said.

For their study, the investigators gathered motor function data from the Adolescent Brain Cognitive Development Study (ABCD), which included 10,835 children aged 9-11 years with broad demographic diversity from 21 sites across the United States.

Overall, 27.6% of the children were reported to have least one motor sign; approximately 3% were reported to have two or more motor signs.

The most common of these was dyscoordination, which was endorsed by 19.3% of participants. In addition, 8.8% were reported to have had experienced developmental motor delays, 1.5% had psychomotor agitation, and 0.3% had psychomotor retardation.

The investigators determined that 4.6% of participants met criteria for depression, 2.6% for a psychosis, and 1.8% for comorbid psychosis and depression.

Motor signs were much more common among children with depression, psychosis, or both than among those who did not have these conditions; 45.8% reported having at least one motor sign.

Developmental motor delays and dyscoordination occurred at about the same rate in both patients with depression and those with psychosis. Rates were higher among patients with both of these conditions than among those with either condition alone.

In contrast, psychomotor agitation was more common among patients with depression alone and among those with comorbid depression and psychosis than among patients with psychosis alone. The rate of psychomotor retardation was increased among patients with psychosis alone but was less common among patients with comorbidity than in the healthy control group.

Familial vulnerability

The investigators also assessed participants who had not been diagnosed with a mental illness but who had a family history of depression only (28.9%), a relative with psychosis-like experiences (0.6%), or a family history of both depression and psychosis experiences (1.8%).

Although the effect size was smaller, there was a higher rate of motor signs among participants with a family history of these conditions, Dr. Damme said. “Again, we see that it’s elevated across developmental motor delays and at a similar rate in people who have depression and psychosis.”

In addition, psychomotor agitation was linked to depression with psychosis and depression without it.

Sensorimotor connectivity network data for the cohort indicated there was no main effect of diagnosis on corticostriatal connectivity.

However, more depressive symptoms were related to less connectivity (P = .024). There was a similar finding for psychotic-like experiences. The total number of such experiences related to lower connectivity (P < .001).

During the postpresentation discussion, Ian Kelleher, MD, PhD, honorary clinical lecturer in psychiatry at the Royal College of Surgeons in Ireland, Dublin, said he was “surprised” by the finding that the rate of psychomotor retardation was lower among participants with psychosis and depression.

Dr. Damme noted that some of the motor sign item ratings came by way of a child interview and that some of these item ratings came from the adults in the children’s lives.

She added that she was not entirely sure whether asking an 8- to 11-year-old in a clinical interview whether they are experiencing motor signs “might be the best way to get at motor slowing.”

Subtle features

Commenting on the findings in an interview, Peter F. Liddle, MD, PhD, professor of psychiatry, at the University of Nottingham (England), noted that the “features we’re talking about are pretty subtle.

“What I’ve been wondering about for some time is whether we should be getting video recordings and using machine learning approaches to teach a computer to recognize normal movements vs abnormal movements, and particularly facial expression,” said Dr. Liddle, who was not involved with the research.

He called the current study “interesting” but noted several factors that affect the potential utility of the findings in predicting outcomes.

First, they “may not be very good for distinguishing schizophrenia from mood disorders; but if the question is simply determining which young person might go on to develop a significant mental disorder, then it may be useful,” Dr. Liddle said.

He endorsed the investigators’ conclusion that motor abnormalities may be a transdiagnostic marker. Beyond that, they may be “more useful as a predictor of the likely long-term severity, but that’s my own hypothesis based on my work,” he added.

Another question concerns the sensitivity of motor abnormalities as a predictive marker. With the rate of the abnormalities identified in those who developed psychosis and depression about double the rate in the overall population, “it sounds like those assessors were fairly sensitive. … but not all that specific,” said Dr. Liddle.

A third issue relates to treatment. “By the time people get sent to a psychiatrist for assessment for possible impending psychotic illness, they’ve often already had medication,” typically an antidepressant or antipsychotic.

“It’s very well established that dopamine-blocking antipsychotics produce hypokinesia and also dyskinesia,” which could then become a confounding factor, Dr. Liddle said.

The study was funded by grants from the National Institute of Mental Health. The study authors and Dr. Liddle have disclosed no relevant financial relationships.

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

Motor problems in children may be a harbinger of serious mental illness, new research suggests.

Investigators found that motor abnormalities were twice as common among those who develop psychosis or depression, compared with their counterparts in the general population, suggesting that these abnormalities may help predict vulnerability and provide an opportunity for early intervention.

“We have learned there are motor signs that are measurable in adolescence [that are] more prevalent in these disorders,” said lead investigator Katherine S. F. Damme, PhD, adolescent development and preventive treatment program (ADAPT), Northwestern University, Chicago. 

A core symptom

There has been a lot of interest in the pathophysiology of psychosis and in detecting it early, said Dr. Damme. “It has devastating effects, and early intervention is of great importance,” she added.

However, previous research has typically focused on affect or cognition, rather than on motor signs, despite the fact that motor signs are a “core symptom of both psychosis and depression.”

The prevalence and presentation of motor signs in adolescence, which is a “critical time for identifying these risk markers” because of their proximity to the onset of psychosis, has been understudied, Dr. Damme said.

For their study, the investigators gathered motor function data from the Adolescent Brain Cognitive Development Study (ABCD), which included 10,835 children aged 9-11 years with broad demographic diversity from 21 sites across the United States.

Overall, 27.6% of the children were reported to have least one motor sign; approximately 3% were reported to have two or more motor signs.

The most common of these was dyscoordination, which was endorsed by 19.3% of participants. In addition, 8.8% were reported to have had experienced developmental motor delays, 1.5% had psychomotor agitation, and 0.3% had psychomotor retardation.

The investigators determined that 4.6% of participants met criteria for depression, 2.6% for a psychosis, and 1.8% for comorbid psychosis and depression.

Motor signs were much more common among children with depression, psychosis, or both than among those who did not have these conditions; 45.8% reported having at least one motor sign.

Developmental motor delays and dyscoordination occurred at about the same rate in both patients with depression and those with psychosis. Rates were higher among patients with both of these conditions than among those with either condition alone.

In contrast, psychomotor agitation was more common among patients with depression alone and among those with comorbid depression and psychosis than among patients with psychosis alone. The rate of psychomotor retardation was increased among patients with psychosis alone but was less common among patients with comorbidity than in the healthy control group.

Familial vulnerability

The investigators also assessed participants who had not been diagnosed with a mental illness but who had a family history of depression only (28.9%), a relative with psychosis-like experiences (0.6%), or a family history of both depression and psychosis experiences (1.8%).

Although the effect size was smaller, there was a higher rate of motor signs among participants with a family history of these conditions, Dr. Damme said. “Again, we see that it’s elevated across developmental motor delays and at a similar rate in people who have depression and psychosis.”

In addition, psychomotor agitation was linked to depression with psychosis and depression without it.

Sensorimotor connectivity network data for the cohort indicated there was no main effect of diagnosis on corticostriatal connectivity.

However, more depressive symptoms were related to less connectivity (P = .024). There was a similar finding for psychotic-like experiences. The total number of such experiences related to lower connectivity (P < .001).

During the postpresentation discussion, Ian Kelleher, MD, PhD, honorary clinical lecturer in psychiatry at the Royal College of Surgeons in Ireland, Dublin, said he was “surprised” by the finding that the rate of psychomotor retardation was lower among participants with psychosis and depression.

Dr. Damme noted that some of the motor sign item ratings came by way of a child interview and that some of these item ratings came from the adults in the children’s lives.

She added that she was not entirely sure whether asking an 8- to 11-year-old in a clinical interview whether they are experiencing motor signs “might be the best way to get at motor slowing.”

Subtle features

Commenting on the findings in an interview, Peter F. Liddle, MD, PhD, professor of psychiatry, at the University of Nottingham (England), noted that the “features we’re talking about are pretty subtle.

“What I’ve been wondering about for some time is whether we should be getting video recordings and using machine learning approaches to teach a computer to recognize normal movements vs abnormal movements, and particularly facial expression,” said Dr. Liddle, who was not involved with the research.

He called the current study “interesting” but noted several factors that affect the potential utility of the findings in predicting outcomes.

First, they “may not be very good for distinguishing schizophrenia from mood disorders; but if the question is simply determining which young person might go on to develop a significant mental disorder, then it may be useful,” Dr. Liddle said.

He endorsed the investigators’ conclusion that motor abnormalities may be a transdiagnostic marker. Beyond that, they may be “more useful as a predictor of the likely long-term severity, but that’s my own hypothesis based on my work,” he added.

Another question concerns the sensitivity of motor abnormalities as a predictive marker. With the rate of the abnormalities identified in those who developed psychosis and depression about double the rate in the overall population, “it sounds like those assessors were fairly sensitive. … but not all that specific,” said Dr. Liddle.

A third issue relates to treatment. “By the time people get sent to a psychiatrist for assessment for possible impending psychotic illness, they’ve often already had medication,” typically an antidepressant or antipsychotic.

“It’s very well established that dopamine-blocking antipsychotics produce hypokinesia and also dyskinesia,” which could then become a confounding factor, Dr. Liddle said.

The study was funded by grants from the National Institute of Mental Health. The study authors and Dr. Liddle have disclosed no relevant financial relationships.

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

Social and economic disparities are linked to an increased risk for psychosis in Black and Latino communities, new research shows.

Results of a literature review of social and economic disparities in mental illness suggest that “structural racism” contributes to social and environmental conditions that affect psychosis risk.

“Black and Latino people suffer disproportionately from psychosis risk factors, at the neighborhood level and at the individual level, in large part as a result of structural racism,” study investigator Deidre M. Anglin, PhD, associate professor, department of psychology, City College of New York (N.Y.), told reporters attending a press briefing.

The social environment, which, for minorities, involves disadvantage and discrimination, may account for this increased psychosis risk, perhaps even more so than genetics, she said. Structural racism “is a critical public health threat,” Dr. Anglin added.

The findings were presented at the virtual American Psychiatric Association annual meeting and were simultaneously published online May 3 in The American Journal of Psychiatry.
 

Perpetual disadvantage

Dr. Anglin and colleagues examined U.S.-based evidence connecting characteristics of social environments with outcomes across the psychosis continuum – from psychotic experiences to schizophrenia.

Citing numerous studies, the researchers highlighted three key areas that reflect social and environmental conditions that may affect psychosis risk, and that disproportionately affect minorities. These were neighborhood factors, trauma in a U.S. context, and racial disparities during the prenatal and perinatal periods.

The data that were related to neighborhoods revealed “just how much racism has historically structured U.S. neighborhoods in ways that generationally perpetuate disadvantage for racially minoritized communities,” said Dr. Anglin.

“This happens through inequitable access to resources, such as health care, clean air, education, [and] employment, but also in terms of disproportionate exposure to environmental toxins and stressors,” she said.

These neighborhood factors are associated with cumulative stress that may be linked to heightened risk for psychosis, the investigators noted.

U.S. studies show that rates of adverse childhood experiences, such as abuse and emotional and physical neglect, are higher among racial and ethnic minorities.

Police victimization and gun violence disproportionately affect racial minorities and create what the investigators call “a unique type of collective trauma” in the United States. They note that Black men have a 1 in 1,000 chance of being victims of lethal force by police over their lifetimes. By comparison, White men have a 39 in 100,000 chance.

One study of a diverse sample from four large U.S. urban centers showed that those who self-reported different types of police victimization were more likely to report psychotic experiences. Another study showed that greater exposure to gun violence fatalities, regardless of police involvement, was positively associated with psychotic experiences.
 

Obstetric complications

A variety of obstetric complications, including infection, maternal inflammation, and stress, have been associated with increased risk for psychotic disorders in U.S. samples.

“What we saw emerge from the literature is that Black women in the U.S. are at substantially increased risk for many of these obstetrical complications compared to White women, and this is not necessarily explained by socioeconomic status,” said Dr. Anglin.

Neighborhood- and individual-level factors appear to affect the disparity in these outcomes. A recent study revealed that exposure to environmental contaminants such as air pollution is associated with higher rates of preterm birth and low birth weight differentially in Black mothers compared with other mothers, “possibly as a result of an interaction between prenatal stress and contaminants,” the investigators noted.

Research also indicates that Black women are more likely to have lower levels of cortisol during the second trimester of pregnancy compared with women of other racial and ethnic groups. Cortisol is essential for fetal growth. Evidence links lower cortisol levels in later stages of pregnancy with decreased fetal growth in individuals who develop schizophrenia.

Black women have higher levels of certain stress biomarkers, including inflammatory C-reactive protein and adrenocorticotropic hormone, in mid- to late pregnancy, compared with White women of the same socioeconomic status.

Such findings “highlight a complex picture” involving maternal cortisol levels and other stress biomarkers, “potentially leading to poor birth outcomes and subsequent risk for psychotic disorders in adulthood,” the investigators noted.

The researchers call for the dismantling of structural racism and the social policies and norms it shapes. They also recommend changes in health care policy and in the approach to early intervention for psychosis among Black and other racially-minoritized groups.

“Altogether, the current evidence suggests the need to identify, address, and tackle the social determinants deeply ingrained in U.S. society, in tandem with empowering the most marginalized communities,” the researchers wrote.

“We recommend that the field of psychiatry devote considerably more effort to addressing structural racism and social determinants of psychosis in funding priorities, training, and intervention development,” they added.

Dr. Anglin suggests that mental health providers use what she called a “cultural formulation interview” that takes a person’s environmental and social context into consideration. Studies show that incorporating this into clinical practice helps reduce misdiagnosis of mental illness in Black populations, she said.
 

Call to action

Commenting on the findings in an interview, Ned H. Kalin, MD, editor of The American Journal of Psychiatry and professor and chair of the department of psychiatry, University of Wisconsin, Madison, said the study was well done and serves as a “call to action” to address the impact of structural racism on mental health issues and psychiatric diseases.

The article highlights the need for “collecting better data” on structural racism, said Dr. Kalin. “We know it’s a big issue, but we can’t even quantitate it, so we need some fundamental measures to use as a benchmark as we move forward, as we try to make change.”

He noted that racism “is so embedded in one’s experience and in our society that we sort of don’t even think about it as a trauma.”

In psychiatry, for example, trauma is often thought of as a loss or a traumatic event. “We don’t typically think of trauma as an experience that pervades one’s entire life,” but that needs to change, he said. “At the individual level and in the doctor’s office, being sensitive to and aware of these issues is absolutely critical.”

Dr. Anglin and Dr. Kalin have disclosed no relevant financial relationships.

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

Social and economic disparities are linked to an increased risk for psychosis in Black and Latino communities, new research shows.

Results of a literature review of social and economic disparities in mental illness suggest that “structural racism” contributes to social and environmental conditions that affect psychosis risk.

“Black and Latino people suffer disproportionately from psychosis risk factors, at the neighborhood level and at the individual level, in large part as a result of structural racism,” study investigator Deidre M. Anglin, PhD, associate professor, department of psychology, City College of New York (N.Y.), told reporters attending a press briefing.

The social environment, which, for minorities, involves disadvantage and discrimination, may account for this increased psychosis risk, perhaps even more so than genetics, she said. Structural racism “is a critical public health threat,” Dr. Anglin added.

The findings were presented at the virtual American Psychiatric Association annual meeting and were simultaneously published online May 3 in The American Journal of Psychiatry.
 

Perpetual disadvantage

Dr. Anglin and colleagues examined U.S.-based evidence connecting characteristics of social environments with outcomes across the psychosis continuum – from psychotic experiences to schizophrenia.

Citing numerous studies, the researchers highlighted three key areas that reflect social and environmental conditions that may affect psychosis risk, and that disproportionately affect minorities. These were neighborhood factors, trauma in a U.S. context, and racial disparities during the prenatal and perinatal periods.

The data that were related to neighborhoods revealed “just how much racism has historically structured U.S. neighborhoods in ways that generationally perpetuate disadvantage for racially minoritized communities,” said Dr. Anglin.

“This happens through inequitable access to resources, such as health care, clean air, education, [and] employment, but also in terms of disproportionate exposure to environmental toxins and stressors,” she said.

These neighborhood factors are associated with cumulative stress that may be linked to heightened risk for psychosis, the investigators noted.

U.S. studies show that rates of adverse childhood experiences, such as abuse and emotional and physical neglect, are higher among racial and ethnic minorities.

Police victimization and gun violence disproportionately affect racial minorities and create what the investigators call “a unique type of collective trauma” in the United States. They note that Black men have a 1 in 1,000 chance of being victims of lethal force by police over their lifetimes. By comparison, White men have a 39 in 100,000 chance.

One study of a diverse sample from four large U.S. urban centers showed that those who self-reported different types of police victimization were more likely to report psychotic experiences. Another study showed that greater exposure to gun violence fatalities, regardless of police involvement, was positively associated with psychotic experiences.
 

Obstetric complications

A variety of obstetric complications, including infection, maternal inflammation, and stress, have been associated with increased risk for psychotic disorders in U.S. samples.

“What we saw emerge from the literature is that Black women in the U.S. are at substantially increased risk for many of these obstetrical complications compared to White women, and this is not necessarily explained by socioeconomic status,” said Dr. Anglin.

Neighborhood- and individual-level factors appear to affect the disparity in these outcomes. A recent study revealed that exposure to environmental contaminants such as air pollution is associated with higher rates of preterm birth and low birth weight differentially in Black mothers compared with other mothers, “possibly as a result of an interaction between prenatal stress and contaminants,” the investigators noted.

Research also indicates that Black women are more likely to have lower levels of cortisol during the second trimester of pregnancy compared with women of other racial and ethnic groups. Cortisol is essential for fetal growth. Evidence links lower cortisol levels in later stages of pregnancy with decreased fetal growth in individuals who develop schizophrenia.

Black women have higher levels of certain stress biomarkers, including inflammatory C-reactive protein and adrenocorticotropic hormone, in mid- to late pregnancy, compared with White women of the same socioeconomic status.

Such findings “highlight a complex picture” involving maternal cortisol levels and other stress biomarkers, “potentially leading to poor birth outcomes and subsequent risk for psychotic disorders in adulthood,” the investigators noted.

The researchers call for the dismantling of structural racism and the social policies and norms it shapes. They also recommend changes in health care policy and in the approach to early intervention for psychosis among Black and other racially-minoritized groups.

“Altogether, the current evidence suggests the need to identify, address, and tackle the social determinants deeply ingrained in U.S. society, in tandem with empowering the most marginalized communities,” the researchers wrote.

“We recommend that the field of psychiatry devote considerably more effort to addressing structural racism and social determinants of psychosis in funding priorities, training, and intervention development,” they added.

Dr. Anglin suggests that mental health providers use what she called a “cultural formulation interview” that takes a person’s environmental and social context into consideration. Studies show that incorporating this into clinical practice helps reduce misdiagnosis of mental illness in Black populations, she said.
 

Call to action

Commenting on the findings in an interview, Ned H. Kalin, MD, editor of The American Journal of Psychiatry and professor and chair of the department of psychiatry, University of Wisconsin, Madison, said the study was well done and serves as a “call to action” to address the impact of structural racism on mental health issues and psychiatric diseases.

The article highlights the need for “collecting better data” on structural racism, said Dr. Kalin. “We know it’s a big issue, but we can’t even quantitate it, so we need some fundamental measures to use as a benchmark as we move forward, as we try to make change.”

He noted that racism “is so embedded in one’s experience and in our society that we sort of don’t even think about it as a trauma.”

In psychiatry, for example, trauma is often thought of as a loss or a traumatic event. “We don’t typically think of trauma as an experience that pervades one’s entire life,” but that needs to change, he said. “At the individual level and in the doctor’s office, being sensitive to and aware of these issues is absolutely critical.”

Dr. Anglin and Dr. Kalin have disclosed no relevant financial relationships.

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

Social and economic disparities are linked to an increased risk for psychosis in Black and Latino communities, new research shows.

Results of a literature review of social and economic disparities in mental illness suggest that “structural racism” contributes to social and environmental conditions that affect psychosis risk.

“Black and Latino people suffer disproportionately from psychosis risk factors, at the neighborhood level and at the individual level, in large part as a result of structural racism,” study investigator Deidre M. Anglin, PhD, associate professor, department of psychology, City College of New York (N.Y.), told reporters attending a press briefing.

The social environment, which, for minorities, involves disadvantage and discrimination, may account for this increased psychosis risk, perhaps even more so than genetics, she said. Structural racism “is a critical public health threat,” Dr. Anglin added.

The findings were presented at the virtual American Psychiatric Association annual meeting and were simultaneously published online May 3 in The American Journal of Psychiatry.
 

Perpetual disadvantage

Dr. Anglin and colleagues examined U.S.-based evidence connecting characteristics of social environments with outcomes across the psychosis continuum – from psychotic experiences to schizophrenia.

Citing numerous studies, the researchers highlighted three key areas that reflect social and environmental conditions that may affect psychosis risk, and that disproportionately affect minorities. These were neighborhood factors, trauma in a U.S. context, and racial disparities during the prenatal and perinatal periods.

The data that were related to neighborhoods revealed “just how much racism has historically structured U.S. neighborhoods in ways that generationally perpetuate disadvantage for racially minoritized communities,” said Dr. Anglin.

“This happens through inequitable access to resources, such as health care, clean air, education, [and] employment, but also in terms of disproportionate exposure to environmental toxins and stressors,” she said.

These neighborhood factors are associated with cumulative stress that may be linked to heightened risk for psychosis, the investigators noted.

U.S. studies show that rates of adverse childhood experiences, such as abuse and emotional and physical neglect, are higher among racial and ethnic minorities.

Police victimization and gun violence disproportionately affect racial minorities and create what the investigators call “a unique type of collective trauma” in the United States. They note that Black men have a 1 in 1,000 chance of being victims of lethal force by police over their lifetimes. By comparison, White men have a 39 in 100,000 chance.

One study of a diverse sample from four large U.S. urban centers showed that those who self-reported different types of police victimization were more likely to report psychotic experiences. Another study showed that greater exposure to gun violence fatalities, regardless of police involvement, was positively associated with psychotic experiences.
 

Obstetric complications

A variety of obstetric complications, including infection, maternal inflammation, and stress, have been associated with increased risk for psychotic disorders in U.S. samples.

“What we saw emerge from the literature is that Black women in the U.S. are at substantially increased risk for many of these obstetrical complications compared to White women, and this is not necessarily explained by socioeconomic status,” said Dr. Anglin.

Neighborhood- and individual-level factors appear to affect the disparity in these outcomes. A recent study revealed that exposure to environmental contaminants such as air pollution is associated with higher rates of preterm birth and low birth weight differentially in Black mothers compared with other mothers, “possibly as a result of an interaction between prenatal stress and contaminants,” the investigators noted.

Research also indicates that Black women are more likely to have lower levels of cortisol during the second trimester of pregnancy compared with women of other racial and ethnic groups. Cortisol is essential for fetal growth. Evidence links lower cortisol levels in later stages of pregnancy with decreased fetal growth in individuals who develop schizophrenia.

Black women have higher levels of certain stress biomarkers, including inflammatory C-reactive protein and adrenocorticotropic hormone, in mid- to late pregnancy, compared with White women of the same socioeconomic status.

Such findings “highlight a complex picture” involving maternal cortisol levels and other stress biomarkers, “potentially leading to poor birth outcomes and subsequent risk for psychotic disorders in adulthood,” the investigators noted.

The researchers call for the dismantling of structural racism and the social policies and norms it shapes. They also recommend changes in health care policy and in the approach to early intervention for psychosis among Black and other racially-minoritized groups.

“Altogether, the current evidence suggests the need to identify, address, and tackle the social determinants deeply ingrained in U.S. society, in tandem with empowering the most marginalized communities,” the researchers wrote.

“We recommend that the field of psychiatry devote considerably more effort to addressing structural racism and social determinants of psychosis in funding priorities, training, and intervention development,” they added.

Dr. Anglin suggests that mental health providers use what she called a “cultural formulation interview” that takes a person’s environmental and social context into consideration. Studies show that incorporating this into clinical practice helps reduce misdiagnosis of mental illness in Black populations, she said.
 

Call to action

Commenting on the findings in an interview, Ned H. Kalin, MD, editor of The American Journal of Psychiatry and professor and chair of the department of psychiatry, University of Wisconsin, Madison, said the study was well done and serves as a “call to action” to address the impact of structural racism on mental health issues and psychiatric diseases.

The article highlights the need for “collecting better data” on structural racism, said Dr. Kalin. “We know it’s a big issue, but we can’t even quantitate it, so we need some fundamental measures to use as a benchmark as we move forward, as we try to make change.”

He noted that racism “is so embedded in one’s experience and in our society that we sort of don’t even think about it as a trauma.”

In psychiatry, for example, trauma is often thought of as a loss or a traumatic event. “We don’t typically think of trauma as an experience that pervades one’s entire life,” but that needs to change, he said. “At the individual level and in the doctor’s office, being sensitive to and aware of these issues is absolutely critical.”

Dr. Anglin and Dr. Kalin have disclosed no relevant financial relationships.

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

Editor in Chief of this news organization Eric Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and professor of molecular medicine, has been closely following COVID-19 data since the pandemic began. He spoke with writer Miriam E. Tucker about the latest on SARS-CoV-2 variants and their impact on vaccine efficacy. The conversation serves as a follow-up to his April 13, 2021, New York Times opinion piece, in which he advised readers that “all variants are innocent until proven guilty.”

You have expressed overall confidence in the efficacy of the vaccines thus far despite the emergence of variants, with some caveats. How do you see the current situation?

The Centers for Disease Control and Prevention has designated five “variants of concern,” but only three of them are real concerns – B.1.1.7, first detected in the United Kingdom; P.1, in Brazil and Japan; and B.1.351, in South Africa. Yet, all three are susceptible to our current vaccines.

The U.K. B.1.1.7 is the worst variant of all because it’s hypertransmissible, so I call it a “superspreader strain.” It also causes more severe illness independent of the spread, so it’s a double whammy. It’s clear that it also causes more deaths. The only arguable point is whether it’s 30% or 50% more deaths, but regardless, it’s more lethal and more transmissible.

The B.1.1.7 is going to be the dominant strain worldwide. It could develop new mutations within it that could come back to haunt us. We must keep watch.

But for now, it’s fully responsive to all the vaccines, which is great because if we didn’t have them, we wouldn’t have gotten through this U.S. pandemic like we have, and neither would Israel and the United Kingdom and other countries that have been able to get out of the crisis. We met the enemy and put it in check.

As for the South Africa variant of concern, B.1.351, we just got some encouraging news showing that it›s very responsive to the Pfizer/BioNTech mRNA vaccine in large numbers of people. The study was conducted in Qatar following that country’s mass immunization campaign in which a total of 385,853 people had received at least one vaccine dose and 265,410 had completed the two doses as of March 31, 2021.

At 2 weeks past the second dose, the vaccine was 75% effective at preventing any documented infection with the B.1.351 variant and 89.5% effective against B.1.1.7. The vaccine’s effectiveness against severe, critical, or fatal COVID-19 was greater than 97.4% for all circulating strains in Qatar, where B.1.1.7 and B.1.351 are most prominent.

We also know that B.1.351 is very responsive to the Johnson & Johnson vaccine and the Novavax [vaccine in development] to a lesser degree. It is the most immune-evading variant we’ve seen thus far, with the highest likelihood of providing some vaccine resistance, yet not enough to interfere with vaccination campaigns. So that’s great news.

The caveats here are that you definitely need two doses of the mRNA vaccines to combat the B.1.351 variant. Also, the AstraZeneca vaccine failed to prevent it in South Africa. However, that study was hard to judge because it was underpowered for number of people with mild infections. So, it didn’t look as if it had any efficacy, but maybe it would if tested in a real trial.

The P.1 (Brazil) variant is the second-highest concern after B.1.1.7 because it’s the only one in the United States that’s still headed up. It seems to be competing a bit with B.1.1.7 here. We know it was associated with the crisis in Brazil, in Chile, and some other South American countries. It has some immune escape, but not as bad as B.1.351. It also appears to have somewhat greater transmissibility but not as much as B.1.1.7.

With P.1, we just don’t know enough yet. It was difficult to assess in Brazil because they were in the midst of a catastrophe – like India is now – and you don’t know how much of it is dragged by the catastrophe vs driving it.

We have to respond to P.1 carefully. There are some good data that it does respond to the Chinese vaccine Sinovac and the AstraZeneca vaccine, and it appears to respond to the others as well, based on serum studies. So it doesn’t look like vaccines will be the worry with this variant. Rather, it could be competing with B.1.1.7 and could lead to breakthrough infections in vaccinated people or reinfections in unvaccinated people who had COVID-19. We need several more weeks to sort it out.

Although the B.1.427 and B.1.429 variants initially seen in California remain on the CDC’s concern list, I’m not worried about them.
 

You mentioned the current COVID-19 crisis in India, where a new variant has been described as a “double mutant,” but on Twitter you called it a “scariant.” Why?

First of all, the B.1.617 variant isn’t a double mutant. It has 15 mutations. It’s a stupid term, focusing on two mutations which largely have been put aside as to concern. One of them is the L452R, which is the same as one of the California variants, and that hasn’t proved to be particularly serious or concerning. The other is the 484Q, and it’s not clear whether that has any function.

The B.1.617 is not the driver of the catastrophe in India. It may be contributing a small amount, but it has been overhyped as the double mutant that’s causing it all. Adding to that are what I call “scariant” headlines here in the United States when a few cases of that variant have been seen.

I coined the term scariant in early February because it was a pretty clear trend. People don’t know what variants are. They know a little bit about mutations but not variants, and they’re scared. A few variants are concerning, but we keep learning more and more things to decrease the concern. That’s why I wrote the New York Times op-ed, to try to provide some reassurance, since there’s such paranoia.
 

Do you think booster vaccinations will be necessary? If so, will those be of the original vaccines or new ones that incorporate the variants?

As we go forward, there’s still potential for new variants that we haven’t seen yet that combine the worst of all features – transmissibility and immune evasion – especially since we have a world where COVID-19 is unchecked. So, we’re not out of it yet, but at least for the moment, we have vaccines that are capable of protecting against all variants.

In most people, the immune response against SARS-CoV-2 is very durable and strong and may well last for years. With the most closely related SARS-CoV-1, people still had immune responses up to 18 years later. However, some people will have less robust vaccine responses, including the elderly and the immunocompromised. If they don’t have great responses to the vaccine to start with, over time they’re likely to become more vulnerable, especially if they’re exposed to the variants with some degree of immune evasion.

I think we need to study these individuals post vaccination. A lot of people fit into those categories, including seniors, people being treated for cancer or autoimmune conditions, or post organ transplant. We could set up a prospective study to see whether they develop symptomatic COVID-19 and if so, from what – the original strain, B.1.1.7, or the newer variants.

That’s where I think booster shots may be needed. They may not be necessary across the board, but perhaps just in these special subgroups.

All of the current vaccines can be tweaked to include new variants, but the need for that is uncertain as of now. Moderna is working on a so-called bivalent vaccine that includes the original SARS-CoV-2 strain plus the B.1.351 variant, but it isn’t clear that that’s going to be necessary.

Currently, at least 200 COVID-19 vaccines are in development. There will be vaccines you can inhale, room temperature mRNA vaccines, and potentially even oral vaccines.

In the near future, Novavax is close, and there will likely be a two-dose Johnson & Johnson version that has the same potency as the mRNA vaccines. There are a lot of moving parts here.

There may be a step down in efficacy from mRNA to the others, though, and that shouldn’t be discounted. All of the available vaccines so far protect very well against severe disease and death, but some are less effective against mild to moderate infections, which may then lead to long COVID. We don’t yet know whether those who get mild infection post vaccination can still get long COVID.
 

What do you think it will take to achieve herd immunity?

I prefer the term “containment.” It’s quantitative. If you get to an infection rate of less than 1 in 100,000 people, as they’ve done in Israel, with 0.8 per 100,000, then you have the virus in check, and there will be very little spread when it’s at that controlled rate, with no outbreaks. The United States is currently at about 15 per 100,000. California is at 4. That still has to get lower.

It will be a challenge to get to President Biden’s goal of having 70% of U.S. adults given at least one dose by July 4. We’re now at about 57%. To get that next 13% of adults is going to take an all-out effort: mobile units, going to homes, making it ultraconvenient, education for people with safety concerns, incentivization, and days off.

We also need to get employers, universities, and health systems to get to the mandatory level. We haven’t done that yet. Some universities have mandated it for students, faculty, and staff. We need it in more health care systems. Right now, we only have a couple. We mandate flu shots, and flu is nothing, compared with COVID-19. And the COVID-19 vaccine is far more efficacious – flu shots are 40% efficacious, while these are 95%. COVID-19 is a tenfold more lethal and serious disease, and much more spreadable.

People are using the lack of full licensure by the Food and Drug Administration – as opposed to emergency use authorization – as an excuse not to get vaccinated. A biologics license application takes time to approve. Meanwhile, we have hundreds of millions of doses that have been well tolerated and incredibly effective.

Another aspect to consider regarding containment is that about 110 million Americans have already had COVID-19, even though only about 30 million cases have been confirmed. Most of these people have immune protection, although it’s not as good as if they have one vaccine dose. But they have enough protection to be part of the story here of the wall against COVID-19 and will help us get through this.

That’s a silver lining of having an unchecked epidemic for the entire year of 2020. The good part is that’s helping to get us to achieve an incredible level of containment when we haven’t even been close. Right now, we’re as good as the country has been in the pandemic, but we still have a long gap to get down to that 1 per 100,000. That’s what we should be working toward, and we can get there.

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

Editor in Chief of this news organization Eric Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and professor of molecular medicine, has been closely following COVID-19 data since the pandemic began. He spoke with writer Miriam E. Tucker about the latest on SARS-CoV-2 variants and their impact on vaccine efficacy. The conversation serves as a follow-up to his April 13, 2021, New York Times opinion piece, in which he advised readers that “all variants are innocent until proven guilty.”

You have expressed overall confidence in the efficacy of the vaccines thus far despite the emergence of variants, with some caveats. How do you see the current situation?

The Centers for Disease Control and Prevention has designated five “variants of concern,” but only three of them are real concerns – B.1.1.7, first detected in the United Kingdom; P.1, in Brazil and Japan; and B.1.351, in South Africa. Yet, all three are susceptible to our current vaccines.

The U.K. B.1.1.7 is the worst variant of all because it’s hypertransmissible, so I call it a “superspreader strain.” It also causes more severe illness independent of the spread, so it’s a double whammy. It’s clear that it also causes more deaths. The only arguable point is whether it’s 30% or 50% more deaths, but regardless, it’s more lethal and more transmissible.

The B.1.1.7 is going to be the dominant strain worldwide. It could develop new mutations within it that could come back to haunt us. We must keep watch.

But for now, it’s fully responsive to all the vaccines, which is great because if we didn’t have them, we wouldn’t have gotten through this U.S. pandemic like we have, and neither would Israel and the United Kingdom and other countries that have been able to get out of the crisis. We met the enemy and put it in check.

As for the South Africa variant of concern, B.1.351, we just got some encouraging news showing that it›s very responsive to the Pfizer/BioNTech mRNA vaccine in large numbers of people. The study was conducted in Qatar following that country’s mass immunization campaign in which a total of 385,853 people had received at least one vaccine dose and 265,410 had completed the two doses as of March 31, 2021.

At 2 weeks past the second dose, the vaccine was 75% effective at preventing any documented infection with the B.1.351 variant and 89.5% effective against B.1.1.7. The vaccine’s effectiveness against severe, critical, or fatal COVID-19 was greater than 97.4% for all circulating strains in Qatar, where B.1.1.7 and B.1.351 are most prominent.

We also know that B.1.351 is very responsive to the Johnson & Johnson vaccine and the Novavax [vaccine in development] to a lesser degree. It is the most immune-evading variant we’ve seen thus far, with the highest likelihood of providing some vaccine resistance, yet not enough to interfere with vaccination campaigns. So that’s great news.

The caveats here are that you definitely need two doses of the mRNA vaccines to combat the B.1.351 variant. Also, the AstraZeneca vaccine failed to prevent it in South Africa. However, that study was hard to judge because it was underpowered for number of people with mild infections. So, it didn’t look as if it had any efficacy, but maybe it would if tested in a real trial.

The P.1 (Brazil) variant is the second-highest concern after B.1.1.7 because it’s the only one in the United States that’s still headed up. It seems to be competing a bit with B.1.1.7 here. We know it was associated with the crisis in Brazil, in Chile, and some other South American countries. It has some immune escape, but not as bad as B.1.351. It also appears to have somewhat greater transmissibility but not as much as B.1.1.7.

With P.1, we just don’t know enough yet. It was difficult to assess in Brazil because they were in the midst of a catastrophe – like India is now – and you don’t know how much of it is dragged by the catastrophe vs driving it.

We have to respond to P.1 carefully. There are some good data that it does respond to the Chinese vaccine Sinovac and the AstraZeneca vaccine, and it appears to respond to the others as well, based on serum studies. So it doesn’t look like vaccines will be the worry with this variant. Rather, it could be competing with B.1.1.7 and could lead to breakthrough infections in vaccinated people or reinfections in unvaccinated people who had COVID-19. We need several more weeks to sort it out.

Although the B.1.427 and B.1.429 variants initially seen in California remain on the CDC’s concern list, I’m not worried about them.
 

You mentioned the current COVID-19 crisis in India, where a new variant has been described as a “double mutant,” but on Twitter you called it a “scariant.” Why?

First of all, the B.1.617 variant isn’t a double mutant. It has 15 mutations. It’s a stupid term, focusing on two mutations which largely have been put aside as to concern. One of them is the L452R, which is the same as one of the California variants, and that hasn’t proved to be particularly serious or concerning. The other is the 484Q, and it’s not clear whether that has any function.

The B.1.617 is not the driver of the catastrophe in India. It may be contributing a small amount, but it has been overhyped as the double mutant that’s causing it all. Adding to that are what I call “scariant” headlines here in the United States when a few cases of that variant have been seen.

I coined the term scariant in early February because it was a pretty clear trend. People don’t know what variants are. They know a little bit about mutations but not variants, and they’re scared. A few variants are concerning, but we keep learning more and more things to decrease the concern. That’s why I wrote the New York Times op-ed, to try to provide some reassurance, since there’s such paranoia.
 

Do you think booster vaccinations will be necessary? If so, will those be of the original vaccines or new ones that incorporate the variants?

As we go forward, there’s still potential for new variants that we haven’t seen yet that combine the worst of all features – transmissibility and immune evasion – especially since we have a world where COVID-19 is unchecked. So, we’re not out of it yet, but at least for the moment, we have vaccines that are capable of protecting against all variants.

In most people, the immune response against SARS-CoV-2 is very durable and strong and may well last for years. With the most closely related SARS-CoV-1, people still had immune responses up to 18 years later. However, some people will have less robust vaccine responses, including the elderly and the immunocompromised. If they don’t have great responses to the vaccine to start with, over time they’re likely to become more vulnerable, especially if they’re exposed to the variants with some degree of immune evasion.

I think we need to study these individuals post vaccination. A lot of people fit into those categories, including seniors, people being treated for cancer or autoimmune conditions, or post organ transplant. We could set up a prospective study to see whether they develop symptomatic COVID-19 and if so, from what – the original strain, B.1.1.7, or the newer variants.

That’s where I think booster shots may be needed. They may not be necessary across the board, but perhaps just in these special subgroups.

All of the current vaccines can be tweaked to include new variants, but the need for that is uncertain as of now. Moderna is working on a so-called bivalent vaccine that includes the original SARS-CoV-2 strain plus the B.1.351 variant, but it isn’t clear that that’s going to be necessary.

Currently, at least 200 COVID-19 vaccines are in development. There will be vaccines you can inhale, room temperature mRNA vaccines, and potentially even oral vaccines.

In the near future, Novavax is close, and there will likely be a two-dose Johnson & Johnson version that has the same potency as the mRNA vaccines. There are a lot of moving parts here.

There may be a step down in efficacy from mRNA to the others, though, and that shouldn’t be discounted. All of the available vaccines so far protect very well against severe disease and death, but some are less effective against mild to moderate infections, which may then lead to long COVID. We don’t yet know whether those who get mild infection post vaccination can still get long COVID.
 

What do you think it will take to achieve herd immunity?

I prefer the term “containment.” It’s quantitative. If you get to an infection rate of less than 1 in 100,000 people, as they’ve done in Israel, with 0.8 per 100,000, then you have the virus in check, and there will be very little spread when it’s at that controlled rate, with no outbreaks. The United States is currently at about 15 per 100,000. California is at 4. That still has to get lower.

It will be a challenge to get to President Biden’s goal of having 70% of U.S. adults given at least one dose by July 4. We’re now at about 57%. To get that next 13% of adults is going to take an all-out effort: mobile units, going to homes, making it ultraconvenient, education for people with safety concerns, incentivization, and days off.

We also need to get employers, universities, and health systems to get to the mandatory level. We haven’t done that yet. Some universities have mandated it for students, faculty, and staff. We need it in more health care systems. Right now, we only have a couple. We mandate flu shots, and flu is nothing, compared with COVID-19. And the COVID-19 vaccine is far more efficacious – flu shots are 40% efficacious, while these are 95%. COVID-19 is a tenfold more lethal and serious disease, and much more spreadable.

People are using the lack of full licensure by the Food and Drug Administration – as opposed to emergency use authorization – as an excuse not to get vaccinated. A biologics license application takes time to approve. Meanwhile, we have hundreds of millions of doses that have been well tolerated and incredibly effective.

Another aspect to consider regarding containment is that about 110 million Americans have already had COVID-19, even though only about 30 million cases have been confirmed. Most of these people have immune protection, although it’s not as good as if they have one vaccine dose. But they have enough protection to be part of the story here of the wall against COVID-19 and will help us get through this.

That’s a silver lining of having an unchecked epidemic for the entire year of 2020. The good part is that’s helping to get us to achieve an incredible level of containment when we haven’t even been close. Right now, we’re as good as the country has been in the pandemic, but we still have a long gap to get down to that 1 per 100,000. That’s what we should be working toward, and we can get there.

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

Editor in Chief of this news organization Eric Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and professor of molecular medicine, has been closely following COVID-19 data since the pandemic began. He spoke with writer Miriam E. Tucker about the latest on SARS-CoV-2 variants and their impact on vaccine efficacy. The conversation serves as a follow-up to his April 13, 2021, New York Times opinion piece, in which he advised readers that “all variants are innocent until proven guilty.”

You have expressed overall confidence in the efficacy of the vaccines thus far despite the emergence of variants, with some caveats. How do you see the current situation?

The Centers for Disease Control and Prevention has designated five “variants of concern,” but only three of them are real concerns – B.1.1.7, first detected in the United Kingdom; P.1, in Brazil and Japan; and B.1.351, in South Africa. Yet, all three are susceptible to our current vaccines.

The U.K. B.1.1.7 is the worst variant of all because it’s hypertransmissible, so I call it a “superspreader strain.” It also causes more severe illness independent of the spread, so it’s a double whammy. It’s clear that it also causes more deaths. The only arguable point is whether it’s 30% or 50% more deaths, but regardless, it’s more lethal and more transmissible.

The B.1.1.7 is going to be the dominant strain worldwide. It could develop new mutations within it that could come back to haunt us. We must keep watch.

But for now, it’s fully responsive to all the vaccines, which is great because if we didn’t have them, we wouldn’t have gotten through this U.S. pandemic like we have, and neither would Israel and the United Kingdom and other countries that have been able to get out of the crisis. We met the enemy and put it in check.

As for the South Africa variant of concern, B.1.351, we just got some encouraging news showing that it›s very responsive to the Pfizer/BioNTech mRNA vaccine in large numbers of people. The study was conducted in Qatar following that country’s mass immunization campaign in which a total of 385,853 people had received at least one vaccine dose and 265,410 had completed the two doses as of March 31, 2021.

At 2 weeks past the second dose, the vaccine was 75% effective at preventing any documented infection with the B.1.351 variant and 89.5% effective against B.1.1.7. The vaccine’s effectiveness against severe, critical, or fatal COVID-19 was greater than 97.4% for all circulating strains in Qatar, where B.1.1.7 and B.1.351 are most prominent.

We also know that B.1.351 is very responsive to the Johnson & Johnson vaccine and the Novavax [vaccine in development] to a lesser degree. It is the most immune-evading variant we’ve seen thus far, with the highest likelihood of providing some vaccine resistance, yet not enough to interfere with vaccination campaigns. So that’s great news.

The caveats here are that you definitely need two doses of the mRNA vaccines to combat the B.1.351 variant. Also, the AstraZeneca vaccine failed to prevent it in South Africa. However, that study was hard to judge because it was underpowered for number of people with mild infections. So, it didn’t look as if it had any efficacy, but maybe it would if tested in a real trial.

The P.1 (Brazil) variant is the second-highest concern after B.1.1.7 because it’s the only one in the United States that’s still headed up. It seems to be competing a bit with B.1.1.7 here. We know it was associated with the crisis in Brazil, in Chile, and some other South American countries. It has some immune escape, but not as bad as B.1.351. It also appears to have somewhat greater transmissibility but not as much as B.1.1.7.

With P.1, we just don’t know enough yet. It was difficult to assess in Brazil because they were in the midst of a catastrophe – like India is now – and you don’t know how much of it is dragged by the catastrophe vs driving it.

We have to respond to P.1 carefully. There are some good data that it does respond to the Chinese vaccine Sinovac and the AstraZeneca vaccine, and it appears to respond to the others as well, based on serum studies. So it doesn’t look like vaccines will be the worry with this variant. Rather, it could be competing with B.1.1.7 and could lead to breakthrough infections in vaccinated people or reinfections in unvaccinated people who had COVID-19. We need several more weeks to sort it out.

Although the B.1.427 and B.1.429 variants initially seen in California remain on the CDC’s concern list, I’m not worried about them.
 

You mentioned the current COVID-19 crisis in India, where a new variant has been described as a “double mutant,” but on Twitter you called it a “scariant.” Why?

First of all, the B.1.617 variant isn’t a double mutant. It has 15 mutations. It’s a stupid term, focusing on two mutations which largely have been put aside as to concern. One of them is the L452R, which is the same as one of the California variants, and that hasn’t proved to be particularly serious or concerning. The other is the 484Q, and it’s not clear whether that has any function.

The B.1.617 is not the driver of the catastrophe in India. It may be contributing a small amount, but it has been overhyped as the double mutant that’s causing it all. Adding to that are what I call “scariant” headlines here in the United States when a few cases of that variant have been seen.

I coined the term scariant in early February because it was a pretty clear trend. People don’t know what variants are. They know a little bit about mutations but not variants, and they’re scared. A few variants are concerning, but we keep learning more and more things to decrease the concern. That’s why I wrote the New York Times op-ed, to try to provide some reassurance, since there’s such paranoia.
 

Do you think booster vaccinations will be necessary? If so, will those be of the original vaccines or new ones that incorporate the variants?

As we go forward, there’s still potential for new variants that we haven’t seen yet that combine the worst of all features – transmissibility and immune evasion – especially since we have a world where COVID-19 is unchecked. So, we’re not out of it yet, but at least for the moment, we have vaccines that are capable of protecting against all variants.

In most people, the immune response against SARS-CoV-2 is very durable and strong and may well last for years. With the most closely related SARS-CoV-1, people still had immune responses up to 18 years later. However, some people will have less robust vaccine responses, including the elderly and the immunocompromised. If they don’t have great responses to the vaccine to start with, over time they’re likely to become more vulnerable, especially if they’re exposed to the variants with some degree of immune evasion.

I think we need to study these individuals post vaccination. A lot of people fit into those categories, including seniors, people being treated for cancer or autoimmune conditions, or post organ transplant. We could set up a prospective study to see whether they develop symptomatic COVID-19 and if so, from what – the original strain, B.1.1.7, or the newer variants.

That’s where I think booster shots may be needed. They may not be necessary across the board, but perhaps just in these special subgroups.

All of the current vaccines can be tweaked to include new variants, but the need for that is uncertain as of now. Moderna is working on a so-called bivalent vaccine that includes the original SARS-CoV-2 strain plus the B.1.351 variant, but it isn’t clear that that’s going to be necessary.

Currently, at least 200 COVID-19 vaccines are in development. There will be vaccines you can inhale, room temperature mRNA vaccines, and potentially even oral vaccines.

In the near future, Novavax is close, and there will likely be a two-dose Johnson & Johnson version that has the same potency as the mRNA vaccines. There are a lot of moving parts here.

There may be a step down in efficacy from mRNA to the others, though, and that shouldn’t be discounted. All of the available vaccines so far protect very well against severe disease and death, but some are less effective against mild to moderate infections, which may then lead to long COVID. We don’t yet know whether those who get mild infection post vaccination can still get long COVID.
 

What do you think it will take to achieve herd immunity?

I prefer the term “containment.” It’s quantitative. If you get to an infection rate of less than 1 in 100,000 people, as they’ve done in Israel, with 0.8 per 100,000, then you have the virus in check, and there will be very little spread when it’s at that controlled rate, with no outbreaks. The United States is currently at about 15 per 100,000. California is at 4. That still has to get lower.

It will be a challenge to get to President Biden’s goal of having 70% of U.S. adults given at least one dose by July 4. We’re now at about 57%. To get that next 13% of adults is going to take an all-out effort: mobile units, going to homes, making it ultraconvenient, education for people with safety concerns, incentivization, and days off.

We also need to get employers, universities, and health systems to get to the mandatory level. We haven’t done that yet. Some universities have mandated it for students, faculty, and staff. We need it in more health care systems. Right now, we only have a couple. We mandate flu shots, and flu is nothing, compared with COVID-19. And the COVID-19 vaccine is far more efficacious – flu shots are 40% efficacious, while these are 95%. COVID-19 is a tenfold more lethal and serious disease, and much more spreadable.

People are using the lack of full licensure by the Food and Drug Administration – as opposed to emergency use authorization – as an excuse not to get vaccinated. A biologics license application takes time to approve. Meanwhile, we have hundreds of millions of doses that have been well tolerated and incredibly effective.

Another aspect to consider regarding containment is that about 110 million Americans have already had COVID-19, even though only about 30 million cases have been confirmed. Most of these people have immune protection, although it’s not as good as if they have one vaccine dose. But they have enough protection to be part of the story here of the wall against COVID-19 and will help us get through this.

That’s a silver lining of having an unchecked epidemic for the entire year of 2020. The good part is that’s helping to get us to achieve an incredible level of containment when we haven’t even been close. Right now, we’re as good as the country has been in the pandemic, but we still have a long gap to get down to that 1 per 100,000. That’s what we should be working toward, and we can get there.

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

Patients who suffer a stroke during hospitalization for infective endocarditis (IE) after transcatheter aortic valve replacement (TAVR) have a dismal prognosis, with more than half dying during the index hospitalization and two-thirds within the first year, a new study shows.

The study – the first to evaluate stroke as an IE-related complication following TAVR in a large multicenter cohort – is published in the May 11 issue of the Journal of the American College of Cardiology.

The authors, led by David del Val, MD, Quebec Heart & Lung Institute, Quebec City, explain that IE after TAVR is a rare but serious complication associated with a high mortality rate. Neurologic events, especially stroke, remain one of the most common and potentially disabling IE-related complications, but until now, no study has attempted to evaluate the predictors of stroke and outcomes in patients with IE following TAVR.

For the current study, the authors analyzed data from the Infectious Endocarditis after TAVR International Registry, including 569 patients who developed definite IE following TAVR from 59 centers in 11 countries.

Patients who experienced a stroke during IE admission were compared with patients who did not have a stroke.

Results showed that 57 patients (10%) had a stroke during IE hospitalization, with no differences in the causative microorganism between groups. Stroke patients had higher rates of acute renal failure, systemic embolization, and persistent bacteremia.

Factors associated with a higher risk for stroke during the index IE hospitalization included stroke before IE, moderate or higher residual aortic regurgitation after TAVR, balloon-expandable valves, IE within 30 days after TAVR, and vegetation size greater than 8 mm.

The stroke rate was 3.1% in patients with none of these risk factors; 6.1% with one risk factor; 13.1% with two risk factors; 28.9% with three risk factors, and 60% with four risk factors.

“The presence of such factors (particularly in combination) may be considered for determining an earlier and more aggressive (medical or surgical) treatment in these patients,” the researchers say.

IE patients with stroke had higher rates of in-hospital mortality (54.4% vs. 28.7%) and overall mortality at 1 year (66.3% vs. 45.6%).

Surgery rates were low (25%) even in the presence of stroke and failed to improve outcomes in this population.

Noting that consensus guidelines for managing patients with IE recommend surgery along with antibiotic treatment for patients developing systemic embolism, particularly stroke, the researchers say their findings suggest that such surgery recommendations may not be extrapolated to TAVR-IE patients, and specific guidelines are warranted for this particular population.

Furthermore, the possibility of early surgery in those patients with factors increasing the risk for stroke should be evaluated in future studies.

The authors note that TAVR has revolutionized the treatment of aortic stenosis and is currently moving toward less complex and younger patients with lower surgical risk. Despite the relatively low incidence of IE after TAVR, the number of procedures is expected to grow exponentially, increasing the number of patients at risk of developing this life-threatening complication. Therefore, detailed knowledge of this disease and its complications is essential to improve outcomes.

They point out that the 10% rate of stroke found in this study is substantially lower, compared with the largest surgical prosthetic-valve infective endocarditis registries, but they suggest that the unique clinical profile of TAVR patients may lead to an underdiagnosis of stroke, with a high proportion of elderly patients who more frequently present with nonspecific symptoms.

They conclude that “IE post-TAVR is associated with a poor prognosis with high in-hospital and late mortality rates. Our study reveals that patients with IE after TAVR complicated by stroke showed an even worse prognosis.”

“The progressive implementation of advanced imaging modalities for early IE diagnosis, especially nuclear imaging, may translate into a better prognosis in coming years. Close attention should be paid to early recognition of stroke-associated factors to improve clinical outcomes,” they add.

In an accompanying editorial, Vuyisile Nkomo, MD, Daniel DeSimone, MD, and William Miranda, MD, Mayo Clinic, Rochester, Minn., say the current study “highlights the devastating consequences of IE after TAVR and the even worse consequences when IE was associated with stroke.”

This points to the critical importance of efforts to prevent IE with appropriate antibiotic prophylaxis and addressing potential sources of infection (for example, dental screening) before invasive cardiac procedures.

“Patient education is critical in regard to recognizing early signs and symptoms of IE. In particular, patients must be informed to obtain blood cultures with any episode of fever, as identification of bacteremia is critical in the diagnosis of IE,” the editorialists comment.  

Endocarditis should also be suspected in afebrile patients with increasing transcatheter heart valve gradients or new or worsening regurgitation, they state.

Multimodality imaging is important for the early diagnosis of IE to facilitate prompt antibiotic treatment and potentially decrease the risk for IE complications, especially systemic embolization, they add.

“Despite the unequivocal advances in the safety and periprocedural complications of TAVR, IE with and without stroke in this TAVR population remains a dreadful complication,” they conclude.

Dr. Del Val was supported by a research grant from the Fundación Alfonso Martin Escudero. The editorialists have disclosed no relevant financial relationships.

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

Patients who suffer a stroke during hospitalization for infective endocarditis (IE) after transcatheter aortic valve replacement (TAVR) have a dismal prognosis, with more than half dying during the index hospitalization and two-thirds within the first year, a new study shows.

The study – the first to evaluate stroke as an IE-related complication following TAVR in a large multicenter cohort – is published in the May 11 issue of the Journal of the American College of Cardiology.

The authors, led by David del Val, MD, Quebec Heart & Lung Institute, Quebec City, explain that IE after TAVR is a rare but serious complication associated with a high mortality rate. Neurologic events, especially stroke, remain one of the most common and potentially disabling IE-related complications, but until now, no study has attempted to evaluate the predictors of stroke and outcomes in patients with IE following TAVR.

For the current study, the authors analyzed data from the Infectious Endocarditis after TAVR International Registry, including 569 patients who developed definite IE following TAVR from 59 centers in 11 countries.

Patients who experienced a stroke during IE admission were compared with patients who did not have a stroke.

Results showed that 57 patients (10%) had a stroke during IE hospitalization, with no differences in the causative microorganism between groups. Stroke patients had higher rates of acute renal failure, systemic embolization, and persistent bacteremia.

Factors associated with a higher risk for stroke during the index IE hospitalization included stroke before IE, moderate or higher residual aortic regurgitation after TAVR, balloon-expandable valves, IE within 30 days after TAVR, and vegetation size greater than 8 mm.

The stroke rate was 3.1% in patients with none of these risk factors; 6.1% with one risk factor; 13.1% with two risk factors; 28.9% with three risk factors, and 60% with four risk factors.

“The presence of such factors (particularly in combination) may be considered for determining an earlier and more aggressive (medical or surgical) treatment in these patients,” the researchers say.

IE patients with stroke had higher rates of in-hospital mortality (54.4% vs. 28.7%) and overall mortality at 1 year (66.3% vs. 45.6%).

Surgery rates were low (25%) even in the presence of stroke and failed to improve outcomes in this population.

Noting that consensus guidelines for managing patients with IE recommend surgery along with antibiotic treatment for patients developing systemic embolism, particularly stroke, the researchers say their findings suggest that such surgery recommendations may not be extrapolated to TAVR-IE patients, and specific guidelines are warranted for this particular population.

Furthermore, the possibility of early surgery in those patients with factors increasing the risk for stroke should be evaluated in future studies.

The authors note that TAVR has revolutionized the treatment of aortic stenosis and is currently moving toward less complex and younger patients with lower surgical risk. Despite the relatively low incidence of IE after TAVR, the number of procedures is expected to grow exponentially, increasing the number of patients at risk of developing this life-threatening complication. Therefore, detailed knowledge of this disease and its complications is essential to improve outcomes.

They point out that the 10% rate of stroke found in this study is substantially lower, compared with the largest surgical prosthetic-valve infective endocarditis registries, but they suggest that the unique clinical profile of TAVR patients may lead to an underdiagnosis of stroke, with a high proportion of elderly patients who more frequently present with nonspecific symptoms.

They conclude that “IE post-TAVR is associated with a poor prognosis with high in-hospital and late mortality rates. Our study reveals that patients with IE after TAVR complicated by stroke showed an even worse prognosis.”

“The progressive implementation of advanced imaging modalities for early IE diagnosis, especially nuclear imaging, may translate into a better prognosis in coming years. Close attention should be paid to early recognition of stroke-associated factors to improve clinical outcomes,” they add.

In an accompanying editorial, Vuyisile Nkomo, MD, Daniel DeSimone, MD, and William Miranda, MD, Mayo Clinic, Rochester, Minn., say the current study “highlights the devastating consequences of IE after TAVR and the even worse consequences when IE was associated with stroke.”

This points to the critical importance of efforts to prevent IE with appropriate antibiotic prophylaxis and addressing potential sources of infection (for example, dental screening) before invasive cardiac procedures.

“Patient education is critical in regard to recognizing early signs and symptoms of IE. In particular, patients must be informed to obtain blood cultures with any episode of fever, as identification of bacteremia is critical in the diagnosis of IE,” the editorialists comment.  

Endocarditis should also be suspected in afebrile patients with increasing transcatheter heart valve gradients or new or worsening regurgitation, they state.

Multimodality imaging is important for the early diagnosis of IE to facilitate prompt antibiotic treatment and potentially decrease the risk for IE complications, especially systemic embolization, they add.

“Despite the unequivocal advances in the safety and periprocedural complications of TAVR, IE with and without stroke in this TAVR population remains a dreadful complication,” they conclude.

Dr. Del Val was supported by a research grant from the Fundación Alfonso Martin Escudero. The editorialists have disclosed no relevant financial relationships.

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

Patients who suffer a stroke during hospitalization for infective endocarditis (IE) after transcatheter aortic valve replacement (TAVR) have a dismal prognosis, with more than half dying during the index hospitalization and two-thirds within the first year, a new study shows.

The study – the first to evaluate stroke as an IE-related complication following TAVR in a large multicenter cohort – is published in the May 11 issue of the Journal of the American College of Cardiology.

The authors, led by David del Val, MD, Quebec Heart & Lung Institute, Quebec City, explain that IE after TAVR is a rare but serious complication associated with a high mortality rate. Neurologic events, especially stroke, remain one of the most common and potentially disabling IE-related complications, but until now, no study has attempted to evaluate the predictors of stroke and outcomes in patients with IE following TAVR.

For the current study, the authors analyzed data from the Infectious Endocarditis after TAVR International Registry, including 569 patients who developed definite IE following TAVR from 59 centers in 11 countries.

Patients who experienced a stroke during IE admission were compared with patients who did not have a stroke.

Results showed that 57 patients (10%) had a stroke during IE hospitalization, with no differences in the causative microorganism between groups. Stroke patients had higher rates of acute renal failure, systemic embolization, and persistent bacteremia.

Factors associated with a higher risk for stroke during the index IE hospitalization included stroke before IE, moderate or higher residual aortic regurgitation after TAVR, balloon-expandable valves, IE within 30 days after TAVR, and vegetation size greater than 8 mm.

The stroke rate was 3.1% in patients with none of these risk factors; 6.1% with one risk factor; 13.1% with two risk factors; 28.9% with three risk factors, and 60% with four risk factors.

“The presence of such factors (particularly in combination) may be considered for determining an earlier and more aggressive (medical or surgical) treatment in these patients,” the researchers say.

IE patients with stroke had higher rates of in-hospital mortality (54.4% vs. 28.7%) and overall mortality at 1 year (66.3% vs. 45.6%).

Surgery rates were low (25%) even in the presence of stroke and failed to improve outcomes in this population.

Noting that consensus guidelines for managing patients with IE recommend surgery along with antibiotic treatment for patients developing systemic embolism, particularly stroke, the researchers say their findings suggest that such surgery recommendations may not be extrapolated to TAVR-IE patients, and specific guidelines are warranted for this particular population.

Furthermore, the possibility of early surgery in those patients with factors increasing the risk for stroke should be evaluated in future studies.

The authors note that TAVR has revolutionized the treatment of aortic stenosis and is currently moving toward less complex and younger patients with lower surgical risk. Despite the relatively low incidence of IE after TAVR, the number of procedures is expected to grow exponentially, increasing the number of patients at risk of developing this life-threatening complication. Therefore, detailed knowledge of this disease and its complications is essential to improve outcomes.

They point out that the 10% rate of stroke found in this study is substantially lower, compared with the largest surgical prosthetic-valve infective endocarditis registries, but they suggest that the unique clinical profile of TAVR patients may lead to an underdiagnosis of stroke, with a high proportion of elderly patients who more frequently present with nonspecific symptoms.

They conclude that “IE post-TAVR is associated with a poor prognosis with high in-hospital and late mortality rates. Our study reveals that patients with IE after TAVR complicated by stroke showed an even worse prognosis.”

“The progressive implementation of advanced imaging modalities for early IE diagnosis, especially nuclear imaging, may translate into a better prognosis in coming years. Close attention should be paid to early recognition of stroke-associated factors to improve clinical outcomes,” they add.

In an accompanying editorial, Vuyisile Nkomo, MD, Daniel DeSimone, MD, and William Miranda, MD, Mayo Clinic, Rochester, Minn., say the current study “highlights the devastating consequences of IE after TAVR and the even worse consequences when IE was associated with stroke.”

This points to the critical importance of efforts to prevent IE with appropriate antibiotic prophylaxis and addressing potential sources of infection (for example, dental screening) before invasive cardiac procedures.

“Patient education is critical in regard to recognizing early signs and symptoms of IE. In particular, patients must be informed to obtain blood cultures with any episode of fever, as identification of bacteremia is critical in the diagnosis of IE,” the editorialists comment.  

Endocarditis should also be suspected in afebrile patients with increasing transcatheter heart valve gradients or new or worsening regurgitation, they state.

Multimodality imaging is important for the early diagnosis of IE to facilitate prompt antibiotic treatment and potentially decrease the risk for IE complications, especially systemic embolization, they add.

“Despite the unequivocal advances in the safety and periprocedural complications of TAVR, IE with and without stroke in this TAVR population remains a dreadful complication,” they conclude.

Dr. Del Val was supported by a research grant from the Fundación Alfonso Martin Escudero. The editorialists have disclosed no relevant financial relationships.

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

One of the newest trends in pulmonary embolism management is treatment of cancer associated venous thromboembolism (VTE) which encompasses deep vein thrombosis (DVT) and PE. Following the clinical management of cancer-associated venous thromboembolism in the hospital, direct oral anticoagulant therapy at discharge is your starting point, except in cases of intact luminal cancers, Scott Kaatz, DO, MSc, FACP, SFHM, said during SHM Converge, the annual conference of the Society of Hospital Medicine.

Dr. Kaatz, of the division of hospital medicine at Henry Ford Hospital, Detroit, based his remarks on emerging recommendations from leading medical societies on the topic, as well as a one-page algorithm from the Anticoagulation Forum that can be accessed at https://acforum-excellence.org/Resource-Center/resource_files/1638-2020-11-30-121425.pdf.

For the short-term treatment of VTE (3-6 months) for patients with active cancer, the American Society of Hematology guideline panel suggests direct oral anticoagulants, such as apixaban, edoxaban, or rivaroxaban, over low-molecular-weight heparin (LMWH) – a conditional recommendation based on low certainty in the evidence of effects.

Dr. Kaatz also discussed the latest recommendations regarding length of VTE treatment. After completion of primary treatment for patients with DVT and/or PE provoked by a chronic risk factor such as a surgery, pregnancy, or having a leg in a cast, the ASH guideline panel suggests indefinite antithrombotic therapy over stopping anticoagulation. “On the other hand, patients with DVT and/or PE provoked by a transient factor typically do not require antithrombotic therapy after completion of primary treatment,” said Dr. Kaatz, who is also a clinical professor of medicine at Wayne State University, Detroit.

After completion of primary treatment for patients with unprovoked DVT and/or PE, the ASH guideline panel suggests indefinite antithrombotic therapy over stopping anticoagulation. “The recommendation does not apply to patients who have a high risk for bleeding complications,” he noted.

Transient or reversible risk factors should be also considered in length of VTE treatment. For example, according to guidelines from the European Society of Cardiology, the estimated risk for long-term VTE recurrence is high (defined as greater than 8% per year) for patients with active cancer, for patients with one or more previous episodes of VTE in the absence of a major transient or reversible factor, and for those with antiphospholipid antibody syndrome.

Dr. Kaatz also highlighted recommendations for the acute treatment of intermediate risk, or submassive PE. The ESC guidelines state that if anticoagulation is initiated parenterally, LMWH or fondaparinux is recommended over unfractionated heparin (UFH) for most patients. “The reason for that is, one drug-use evaluation study found that, after 24 hours using UFH, only about 24% of patients had reached their therapeutic goal,” Dr. Kaatz said. Guidelines for intermediate risk patients from ASH recommend anticoagulation as your starting point, while thrombolysis is reasonable to consider for submassive PE and low risk for bleeding in selected younger patients or for patients at high risk for decompensation because of concomitant cardiopulmonary disease. “The bleeding rates get much higher in patients over age 65,” he said.

Another resource Dr. Kaatz mentioned is the Pulmonary Embolism Response Team (PERT) Consortium, which was developed after initial efforts of a multidisciplinary team of physicians at Massachusetts General Hospital. The first PERT sought to coordinate and expedite the treatment of pulmonary embolus with a team of physicians from a variety of specialties. In 2019 the PERT Consortium published guidelines on the diagnosis, treatment, and follow-up of acute PE. “It includes detailed algorithms that are a little different from the ASH and ESC guidelines,” Dr. Kaatz said.

Dr. Kaatz disclosed that he is a consultant for Janssen, Pfizer, Portola/Alexion, Bristol-Myers Squibb, Novartis, and CSL Behring. He has also received research funding from Janssen, Bristol-Myers Squibb, and Osmosis. He also holds board positions with the AC Forum and the National Blood Clot Alliance Medical and Scientific Advisory Board.


 

One of the newest trends in pulmonary embolism management is treatment of cancer associated venous thromboembolism (VTE) which encompasses deep vein thrombosis (DVT) and PE. Following the clinical management of cancer-associated venous thromboembolism in the hospital, direct oral anticoagulant therapy at discharge is your starting point, except in cases of intact luminal cancers, Scott Kaatz, DO, MSc, FACP, SFHM, said during SHM Converge, the annual conference of the Society of Hospital Medicine.

Dr. Kaatz, of the division of hospital medicine at Henry Ford Hospital, Detroit, based his remarks on emerging recommendations from leading medical societies on the topic, as well as a one-page algorithm from the Anticoagulation Forum that can be accessed at https://acforum-excellence.org/Resource-Center/resource_files/1638-2020-11-30-121425.pdf.

For the short-term treatment of VTE (3-6 months) for patients with active cancer, the American Society of Hematology guideline panel suggests direct oral anticoagulants, such as apixaban, edoxaban, or rivaroxaban, over low-molecular-weight heparin (LMWH) – a conditional recommendation based on low certainty in the evidence of effects.

Dr. Kaatz also discussed the latest recommendations regarding length of VTE treatment. After completion of primary treatment for patients with DVT and/or PE provoked by a chronic risk factor such as a surgery, pregnancy, or having a leg in a cast, the ASH guideline panel suggests indefinite antithrombotic therapy over stopping anticoagulation. “On the other hand, patients with DVT and/or PE provoked by a transient factor typically do not require antithrombotic therapy after completion of primary treatment,” said Dr. Kaatz, who is also a clinical professor of medicine at Wayne State University, Detroit.

After completion of primary treatment for patients with unprovoked DVT and/or PE, the ASH guideline panel suggests indefinite antithrombotic therapy over stopping anticoagulation. “The recommendation does not apply to patients who have a high risk for bleeding complications,” he noted.

Transient or reversible risk factors should be also considered in length of VTE treatment. For example, according to guidelines from the European Society of Cardiology, the estimated risk for long-term VTE recurrence is high (defined as greater than 8% per year) for patients with active cancer, for patients with one or more previous episodes of VTE in the absence of a major transient or reversible factor, and for those with antiphospholipid antibody syndrome.

Dr. Kaatz also highlighted recommendations for the acute treatment of intermediate risk, or submassive PE. The ESC guidelines state that if anticoagulation is initiated parenterally, LMWH or fondaparinux is recommended over unfractionated heparin (UFH) for most patients. “The reason for that is, one drug-use evaluation study found that, after 24 hours using UFH, only about 24% of patients had reached their therapeutic goal,” Dr. Kaatz said. Guidelines for intermediate risk patients from ASH recommend anticoagulation as your starting point, while thrombolysis is reasonable to consider for submassive PE and low risk for bleeding in selected younger patients or for patients at high risk for decompensation because of concomitant cardiopulmonary disease. “The bleeding rates get much higher in patients over age 65,” he said.

Another resource Dr. Kaatz mentioned is the Pulmonary Embolism Response Team (PERT) Consortium, which was developed after initial efforts of a multidisciplinary team of physicians at Massachusetts General Hospital. The first PERT sought to coordinate and expedite the treatment of pulmonary embolus with a team of physicians from a variety of specialties. In 2019 the PERT Consortium published guidelines on the diagnosis, treatment, and follow-up of acute PE. “It includes detailed algorithms that are a little different from the ASH and ESC guidelines,” Dr. Kaatz said.

Dr. Kaatz disclosed that he is a consultant for Janssen, Pfizer, Portola/Alexion, Bristol-Myers Squibb, Novartis, and CSL Behring. He has also received research funding from Janssen, Bristol-Myers Squibb, and Osmosis. He also holds board positions with the AC Forum and the National Blood Clot Alliance Medical and Scientific Advisory Board.


 

One of the newest trends in pulmonary embolism management is treatment of cancer associated venous thromboembolism (VTE) which encompasses deep vein thrombosis (DVT) and PE. Following the clinical management of cancer-associated venous thromboembolism in the hospital, direct oral anticoagulant therapy at discharge is your starting point, except in cases of intact luminal cancers, Scott Kaatz, DO, MSc, FACP, SFHM, said during SHM Converge, the annual conference of the Society of Hospital Medicine.

Dr. Kaatz, of the division of hospital medicine at Henry Ford Hospital, Detroit, based his remarks on emerging recommendations from leading medical societies on the topic, as well as a one-page algorithm from the Anticoagulation Forum that can be accessed at https://acforum-excellence.org/Resource-Center/resource_files/1638-2020-11-30-121425.pdf.

For the short-term treatment of VTE (3-6 months) for patients with active cancer, the American Society of Hematology guideline panel suggests direct oral anticoagulants, such as apixaban, edoxaban, or rivaroxaban, over low-molecular-weight heparin (LMWH) – a conditional recommendation based on low certainty in the evidence of effects.

Dr. Kaatz also discussed the latest recommendations regarding length of VTE treatment. After completion of primary treatment for patients with DVT and/or PE provoked by a chronic risk factor such as a surgery, pregnancy, or having a leg in a cast, the ASH guideline panel suggests indefinite antithrombotic therapy over stopping anticoagulation. “On the other hand, patients with DVT and/or PE provoked by a transient factor typically do not require antithrombotic therapy after completion of primary treatment,” said Dr. Kaatz, who is also a clinical professor of medicine at Wayne State University, Detroit.

After completion of primary treatment for patients with unprovoked DVT and/or PE, the ASH guideline panel suggests indefinite antithrombotic therapy over stopping anticoagulation. “The recommendation does not apply to patients who have a high risk for bleeding complications,” he noted.

Transient or reversible risk factors should be also considered in length of VTE treatment. For example, according to guidelines from the European Society of Cardiology, the estimated risk for long-term VTE recurrence is high (defined as greater than 8% per year) for patients with active cancer, for patients with one or more previous episodes of VTE in the absence of a major transient or reversible factor, and for those with antiphospholipid antibody syndrome.

Dr. Kaatz also highlighted recommendations for the acute treatment of intermediate risk, or submassive PE. The ESC guidelines state that if anticoagulation is initiated parenterally, LMWH or fondaparinux is recommended over unfractionated heparin (UFH) for most patients. “The reason for that is, one drug-use evaluation study found that, after 24 hours using UFH, only about 24% of patients had reached their therapeutic goal,” Dr. Kaatz said. Guidelines for intermediate risk patients from ASH recommend anticoagulation as your starting point, while thrombolysis is reasonable to consider for submassive PE and low risk for bleeding in selected younger patients or for patients at high risk for decompensation because of concomitant cardiopulmonary disease. “The bleeding rates get much higher in patients over age 65,” he said.

Another resource Dr. Kaatz mentioned is the Pulmonary Embolism Response Team (PERT) Consortium, which was developed after initial efforts of a multidisciplinary team of physicians at Massachusetts General Hospital. The first PERT sought to coordinate and expedite the treatment of pulmonary embolus with a team of physicians from a variety of specialties. In 2019 the PERT Consortium published guidelines on the diagnosis, treatment, and follow-up of acute PE. “It includes detailed algorithms that are a little different from the ASH and ESC guidelines,” Dr. Kaatz said.

Dr. Kaatz disclosed that he is a consultant for Janssen, Pfizer, Portola/Alexion, Bristol-Myers Squibb, Novartis, and CSL Behring. He has also received research funding from Janssen, Bristol-Myers Squibb, and Osmosis. He also holds board positions with the AC Forum and the National Blood Clot Alliance Medical and Scientific Advisory Board.


 

FDA guidance for power morcellation

“The FDA has granted marketing authorization for one containment system and continues to encourage innovation in this area” said the report. Olympus’ Pneumoliner is the only FDA cleared containment device to provide a laparoscopic option for appropriately identified patients undergoing myomectomy and hysterectomy. The containment system is sold with Olympus’ PK Morcellator, but the company says that it has made the Pneumoliner available to physicians choosing an alternate to the PK Morcellator, provided that there is device compatibility. The Pneumoliner “reduces the spread of benign tissue into the abdominal cavity, in which pathologies, like fibroids, may regrow when tissue or cells are inadvertently left behind,” according to Olympus.

For more information, visit : https://medical.olympusamerica.com/products/contained-tissue-extraction-system

Vaginal odor elimination gel

The gel is sold in 7 single-day applications, with a single tube used per day at bedtime to eliminate unwanted odor. To maintain freshness and comfort, a single tube of Relactagel can be used for 2 to 3 days after a woman’s menstrual cycle, says Kora Healthcare. The company warns that mild irritation can occur with product use during fungal infections or when small tears are present in the vaginal tissue and that use should be discontinued if irritation occurs. In addition, if trying to become pregnant Relatagel should not be used, advises Kora Healthcare, although the gel is not a contraceptive.

For more information, visit: https://www.relactagel.com/.

Intrauterine electrosurgery system

For more information, visit: https://medical.olympusamerica.com/

FDA guidance for power morcellation

“The FDA has granted marketing authorization for one containment system and continues to encourage innovation in this area” said the report. Olympus’ Pneumoliner is the only FDA cleared containment device to provide a laparoscopic option for appropriately identified patients undergoing myomectomy and hysterectomy. The containment system is sold with Olympus’ PK Morcellator, but the company says that it has made the Pneumoliner available to physicians choosing an alternate to the PK Morcellator, provided that there is device compatibility. The Pneumoliner “reduces the spread of benign tissue into the abdominal cavity, in which pathologies, like fibroids, may regrow when tissue or cells are inadvertently left behind,” according to Olympus.

For more information, visit : https://medical.olympusamerica.com/products/contained-tissue-extraction-system

Vaginal odor elimination gel

The gel is sold in 7 single-day applications, with a single tube used per day at bedtime to eliminate unwanted odor. To maintain freshness and comfort, a single tube of Relactagel can be used for 2 to 3 days after a woman’s menstrual cycle, says Kora Healthcare. The company warns that mild irritation can occur with product use during fungal infections or when small tears are present in the vaginal tissue and that use should be discontinued if irritation occurs. In addition, if trying to become pregnant Relatagel should not be used, advises Kora Healthcare, although the gel is not a contraceptive.

For more information, visit: https://www.relactagel.com/.

Intrauterine electrosurgery system

For more information, visit: https://medical.olympusamerica.com/

FDA guidance for power morcellation

“The FDA has granted marketing authorization for one containment system and continues to encourage innovation in this area” said the report. Olympus’ Pneumoliner is the only FDA cleared containment device to provide a laparoscopic option for appropriately identified patients undergoing myomectomy and hysterectomy. The containment system is sold with Olympus’ PK Morcellator, but the company says that it has made the Pneumoliner available to physicians choosing an alternate to the PK Morcellator, provided that there is device compatibility. The Pneumoliner “reduces the spread of benign tissue into the abdominal cavity, in which pathologies, like fibroids, may regrow when tissue or cells are inadvertently left behind,” according to Olympus.

For more information, visit : https://medical.olympusamerica.com/products/contained-tissue-extraction-system

Vaginal odor elimination gel

The gel is sold in 7 single-day applications, with a single tube used per day at bedtime to eliminate unwanted odor. To maintain freshness and comfort, a single tube of Relactagel can be used for 2 to 3 days after a woman’s menstrual cycle, says Kora Healthcare. The company warns that mild irritation can occur with product use during fungal infections or when small tears are present in the vaginal tissue and that use should be discontinued if irritation occurs. In addition, if trying to become pregnant Relatagel should not be used, advises Kora Healthcare, although the gel is not a contraceptive.

For more information, visit: https://www.relactagel.com/.

Intrauterine electrosurgery system

For more information, visit: https://medical.olympusamerica.com/

Clinicians’ well-being is a “crisis” of grave import to the public health and a top issue that he hopes to get more squarely on the public radar screen, Surgeon General Vivek Murthy, MD, MBA, said May 6 in a “fireside chat” with SHM president Danielle Scheurer, MD, MSRC, SFHM, at SHM Converge, the annual conference of the Society of Hospital Medicine.

“This is a crisis that I don’t know that the country recognizes is fully important,” Dr. Murthy said. “I don’t think that most people in the public recognize just how extraordinarily difficult it is, for many clinicians, to come to practice. And if the clinicians continue to burn out at the rate that they are – in addition to the humanitarian crisis of people who are struggling that we should all feel concern about – it will impact care in a profound way.” He said part of his plan is a “national agenda” for clinician well-being, with a clear pathway for creating an environment more conducive to providing quality patient care.

Dr. Scheurer said that this was “welcome news and wonderful to hear.”

“Fortunately or unfortunately, now I do think it’s more in the front seat,” she said, adding that “this notion of ‘heal thyself,’ we know doesn’t work and these are really systemic ailments that we all have to tackle together.”

Dr. Murthy, a hospitalist by training, recently began his second term as Surgeon General, having served under President Obama and appointed to the post again by President Biden. This second appointment is different in the knowledge he has about the job from the start, in the enormity of the public health challenges posed by the COVID-19 pandemic, and in the political tenor of the country.

He said one of his main priorities is to “recenter our public health response” with scientists and public health leaders regaining their proper role.

“Have them be the voices that are actually speaking directly to the public, not in a way that’s biased by the politics or by politicians, but it’s really guided again by the science and substance of what we know needs to happen,” he said.

The response to COVID goes beyond continuing an aggressive vaccination and testing campaign, he said. The pandemic has given rise to worse mental health issues such as depression and anxiety, substance use disorders, and delays in care for other medical conditions for fear of infection – and these are all priorities, Dr. Murthy said.

One “silver lining” of the pandemic is the expansion of telehealth, but this needs refining and persistence to make it work optimally for all patients, he said.

“We have to ensure that that expansion continues and that it’s even – meaning that there are so many parts of the country where broadband access is a challenge for patients, so they don’t have the benefits of telemedicine,” he said. “We also need to ensure that these systems are integrated across our current systems, across hospitals so that we’re not creating more work for clinicians when it comes to utilizing this technology to reach their patients.”

Clinicians – typically viewed as coming to Capitol Hill only to push for higher payment or changes to medical liability laws – need to use their trusted voices to raise the profile of preventive care and identifying and fixing social barriers related to health, such as transportation issues and unsafe neighborhoods, Dr. Murthy said.

“No one really celebrates the heart attack that was prevented or the asthma that was prevented – we celebrate the illness that took place and was cured,” he said. “We know as clinicians that if you really want to reduce human suffering that you have to focus on the prevention side of the house, and I think that unless our colleagues in medicine and in public health come together and advocate for greater investments in prevention, or a national agenda around prevention, my worry is that it won’t naturally develop.”

On vaccine hesitancy, Dr. Murthy said that the United States needs to work more in increasing confidence that the vaccines will work, and in access to vaccines, but, mostly, in motivation.

“What we’ve learned is that ultimately trusted voices are what make all the difference when it comes to vaccination,” he said. “It’s one of these large, people-powered movements that we have to build in our community.”

Dr. Scheurer noted that, with hospitalists in 90% of U.S. hospitals, they can play a big role. “If we can all do our part then we’ll at least take the ball further down the field.”

Dr. Murthy added that, since residency, when he cared for young cancer patients near his own age, he has focused on “finding meaning now” in his work and life. The pandemic has reinforced this, and he doesn’t necessarily want life to go back to exactly how it was before the pandemic.

“Many of us are thinking – ‘Is there actually a better way for us to live our lives and design our workdays and our choices other than what we were doing prepandemic? Can we center our lives more around the people we love and care about, can we design our work to accommodate our family as opposed to the other way around, to always make our families accommodate our work?’ – These are the kinds of choices that we have to make as a society.”

Clinicians’ well-being is a “crisis” of grave import to the public health and a top issue that he hopes to get more squarely on the public radar screen, Surgeon General Vivek Murthy, MD, MBA, said May 6 in a “fireside chat” with SHM president Danielle Scheurer, MD, MSRC, SFHM, at SHM Converge, the annual conference of the Society of Hospital Medicine.

“This is a crisis that I don’t know that the country recognizes is fully important,” Dr. Murthy said. “I don’t think that most people in the public recognize just how extraordinarily difficult it is, for many clinicians, to come to practice. And if the clinicians continue to burn out at the rate that they are – in addition to the humanitarian crisis of people who are struggling that we should all feel concern about – it will impact care in a profound way.” He said part of his plan is a “national agenda” for clinician well-being, with a clear pathway for creating an environment more conducive to providing quality patient care.

Dr. Scheurer said that this was “welcome news and wonderful to hear.”

“Fortunately or unfortunately, now I do think it’s more in the front seat,” she said, adding that “this notion of ‘heal thyself,’ we know doesn’t work and these are really systemic ailments that we all have to tackle together.”

Dr. Murthy, a hospitalist by training, recently began his second term as Surgeon General, having served under President Obama and appointed to the post again by President Biden. This second appointment is different in the knowledge he has about the job from the start, in the enormity of the public health challenges posed by the COVID-19 pandemic, and in the political tenor of the country.

He said one of his main priorities is to “recenter our public health response” with scientists and public health leaders regaining their proper role.

“Have them be the voices that are actually speaking directly to the public, not in a way that’s biased by the politics or by politicians, but it’s really guided again by the science and substance of what we know needs to happen,” he said.

The response to COVID goes beyond continuing an aggressive vaccination and testing campaign, he said. The pandemic has given rise to worse mental health issues such as depression and anxiety, substance use disorders, and delays in care for other medical conditions for fear of infection – and these are all priorities, Dr. Murthy said.

One “silver lining” of the pandemic is the expansion of telehealth, but this needs refining and persistence to make it work optimally for all patients, he said.

“We have to ensure that that expansion continues and that it’s even – meaning that there are so many parts of the country where broadband access is a challenge for patients, so they don’t have the benefits of telemedicine,” he said. “We also need to ensure that these systems are integrated across our current systems, across hospitals so that we’re not creating more work for clinicians when it comes to utilizing this technology to reach their patients.”

Clinicians – typically viewed as coming to Capitol Hill only to push for higher payment or changes to medical liability laws – need to use their trusted voices to raise the profile of preventive care and identifying and fixing social barriers related to health, such as transportation issues and unsafe neighborhoods, Dr. Murthy said.

“No one really celebrates the heart attack that was prevented or the asthma that was prevented – we celebrate the illness that took place and was cured,” he said. “We know as clinicians that if you really want to reduce human suffering that you have to focus on the prevention side of the house, and I think that unless our colleagues in medicine and in public health come together and advocate for greater investments in prevention, or a national agenda around prevention, my worry is that it won’t naturally develop.”

On vaccine hesitancy, Dr. Murthy said that the United States needs to work more in increasing confidence that the vaccines will work, and in access to vaccines, but, mostly, in motivation.

“What we’ve learned is that ultimately trusted voices are what make all the difference when it comes to vaccination,” he said. “It’s one of these large, people-powered movements that we have to build in our community.”

Dr. Scheurer noted that, with hospitalists in 90% of U.S. hospitals, they can play a big role. “If we can all do our part then we’ll at least take the ball further down the field.”

Dr. Murthy added that, since residency, when he cared for young cancer patients near his own age, he has focused on “finding meaning now” in his work and life. The pandemic has reinforced this, and he doesn’t necessarily want life to go back to exactly how it was before the pandemic.

“Many of us are thinking – ‘Is there actually a better way for us to live our lives and design our workdays and our choices other than what we were doing prepandemic? Can we center our lives more around the people we love and care about, can we design our work to accommodate our family as opposed to the other way around, to always make our families accommodate our work?’ – These are the kinds of choices that we have to make as a society.”

Clinicians’ well-being is a “crisis” of grave import to the public health and a top issue that he hopes to get more squarely on the public radar screen, Surgeon General Vivek Murthy, MD, MBA, said May 6 in a “fireside chat” with SHM president Danielle Scheurer, MD, MSRC, SFHM, at SHM Converge, the annual conference of the Society of Hospital Medicine.

“This is a crisis that I don’t know that the country recognizes is fully important,” Dr. Murthy said. “I don’t think that most people in the public recognize just how extraordinarily difficult it is, for many clinicians, to come to practice. And if the clinicians continue to burn out at the rate that they are – in addition to the humanitarian crisis of people who are struggling that we should all feel concern about – it will impact care in a profound way.” He said part of his plan is a “national agenda” for clinician well-being, with a clear pathway for creating an environment more conducive to providing quality patient care.

Dr. Scheurer said that this was “welcome news and wonderful to hear.”

“Fortunately or unfortunately, now I do think it’s more in the front seat,” she said, adding that “this notion of ‘heal thyself,’ we know doesn’t work and these are really systemic ailments that we all have to tackle together.”

Dr. Murthy, a hospitalist by training, recently began his second term as Surgeon General, having served under President Obama and appointed to the post again by President Biden. This second appointment is different in the knowledge he has about the job from the start, in the enormity of the public health challenges posed by the COVID-19 pandemic, and in the political tenor of the country.

He said one of his main priorities is to “recenter our public health response” with scientists and public health leaders regaining their proper role.

“Have them be the voices that are actually speaking directly to the public, not in a way that’s biased by the politics or by politicians, but it’s really guided again by the science and substance of what we know needs to happen,” he said.

The response to COVID goes beyond continuing an aggressive vaccination and testing campaign, he said. The pandemic has given rise to worse mental health issues such as depression and anxiety, substance use disorders, and delays in care for other medical conditions for fear of infection – and these are all priorities, Dr. Murthy said.

One “silver lining” of the pandemic is the expansion of telehealth, but this needs refining and persistence to make it work optimally for all patients, he said.

“We have to ensure that that expansion continues and that it’s even – meaning that there are so many parts of the country where broadband access is a challenge for patients, so they don’t have the benefits of telemedicine,” he said. “We also need to ensure that these systems are integrated across our current systems, across hospitals so that we’re not creating more work for clinicians when it comes to utilizing this technology to reach their patients.”

Clinicians – typically viewed as coming to Capitol Hill only to push for higher payment or changes to medical liability laws – need to use their trusted voices to raise the profile of preventive care and identifying and fixing social barriers related to health, such as transportation issues and unsafe neighborhoods, Dr. Murthy said.

“No one really celebrates the heart attack that was prevented or the asthma that was prevented – we celebrate the illness that took place and was cured,” he said. “We know as clinicians that if you really want to reduce human suffering that you have to focus on the prevention side of the house, and I think that unless our colleagues in medicine and in public health come together and advocate for greater investments in prevention, or a national agenda around prevention, my worry is that it won’t naturally develop.”

On vaccine hesitancy, Dr. Murthy said that the United States needs to work more in increasing confidence that the vaccines will work, and in access to vaccines, but, mostly, in motivation.

“What we’ve learned is that ultimately trusted voices are what make all the difference when it comes to vaccination,” he said. “It’s one of these large, people-powered movements that we have to build in our community.”

Dr. Scheurer noted that, with hospitalists in 90% of U.S. hospitals, they can play a big role. “If we can all do our part then we’ll at least take the ball further down the field.”

Dr. Murthy added that, since residency, when he cared for young cancer patients near his own age, he has focused on “finding meaning now” in his work and life. The pandemic has reinforced this, and he doesn’t necessarily want life to go back to exactly how it was before the pandemic.

“Many of us are thinking – ‘Is there actually a better way for us to live our lives and design our workdays and our choices other than what we were doing prepandemic? Can we center our lives more around the people we love and care about, can we design our work to accommodate our family as opposed to the other way around, to always make our families accommodate our work?’ – These are the kinds of choices that we have to make as a society.”

The first clinical trial of fecal microbiota transplantation in patients with psoriatic arthritis has found the procedure to be as safe as a sham procedure, but it didn’t show any effectiveness in decreasing PsA symptoms over 6 months, a team of researchers in Denmark reported in Annals of the Rheumatic Diseases (2021 Apr 29. 10.1136/annrheumdis-2020-219511).

ChrisChrisW/Getty Images

Nonetheless, the investigators said the trial indicates fecal microbiota transplantation (FMT) is worthy of further study.

“Overall, we think that the results are very interesting and that the feasibility and safety aspects as well as the clinical results of the trial may encourage more research into the potential of FMT in the treatment of inflammatory arthritis and may help guide the direction of future trials within the field,” lead author Maja S. Kragsnaes, MD, PhD, and principal investigator Torkell Ellingsen, MD, PhD, of Odense (Denmark) University Hospital said together in an interview.

“The most important findings from this trial is that FMT appears to be safe in patients with PsA and that the patients find the treatment acceptable, and it supports future research into the therapeutic potential of FMT in PsA,” they said.

The study evaluated 6-month outcomes of 31 patients randomized to the FMT and sham groups. FMT patients were three times more likely to experience treatment failure – defined by the need for treatment intensification – with failure rates of 60% versus 20% in the sham group.

As a secondary endpoint, the study used 6-month change in the Health Assessment Questionnaire Disability Index (HAQ-DI) and 20% improvement in American College of Rheumatology criteria (ACR20). The sham group demonstrated a greater decrease in HAQ-DI, indicating better physical function (–0.30 vs. –0.07; P = .031). The proportion of ACR20 responders was similar between both groups: 47% for the FMT patients (7 of 15) and 53% for sham (8 of 15).

The study included adults aged 18-75 years with active peripheral disease, defined as three or more swollen joints, who’d been taking at least15 mg methotrexate a week for at least 3 months before enrolling in the study, with a washout period of 12 weeks (26 weeks for those on biologic agents). Four healthy donors provided the stool transplants.

In the study, Dr. Kragsnaes and Dr. Ellingsen acknowledged that FMT has been shown to be safe for Clostridioides difficile infection or inflammatory bowel disease when “thoroughly screened stool” is used. “Hence,” they wrote, “our findings add to the growing body of evidence suggesting a gut-joint axis in the pathogenesis of PsA.”

Factors that may influence the effectiveness of FMT in PsA merit further investigation, Dr. Kragsnaes and Dr. Ellingsen said. “From FMT trials in patients with active ulcerative colitis, higher dose and repeated administration appear to be effective and safe in inducing remission,” they said in their joint statement, pointing to research from China.

“Moreover,” they added, “successes of FMT in inflammatory bowel disease appear to have been driven by ‘superdonors’ characterized by the presence or absence of specific bacteria species.”

They said will continue to investigate the effectiveness of FMT in immune-mediated diseases, including how to characterize superdonors.

“We will conduct new randomized trials using different FMT strategies – by changing the type of administration form, dose, and treatment frequency – to explore whether microbial dysbiosis or specific bacteria are common or decisive mediators of disease activity in inflammatory diseases and whether this proposed relation can be modified without exacerbating the disease,” Dr. Kragsnaes and Dr. Ellingsen said.

Dr. Kragsnaes and Dr. Ellingsen had no relevant financial relationships to disclose.

The first clinical trial of fecal microbiota transplantation in patients with psoriatic arthritis has found the procedure to be as safe as a sham procedure, but it didn’t show any effectiveness in decreasing PsA symptoms over 6 months, a team of researchers in Denmark reported in Annals of the Rheumatic Diseases (2021 Apr 29. 10.1136/annrheumdis-2020-219511).

ChrisChrisW/Getty Images

Nonetheless, the investigators said the trial indicates fecal microbiota transplantation (FMT) is worthy of further study.

“Overall, we think that the results are very interesting and that the feasibility and safety aspects as well as the clinical results of the trial may encourage more research into the potential of FMT in the treatment of inflammatory arthritis and may help guide the direction of future trials within the field,” lead author Maja S. Kragsnaes, MD, PhD, and principal investigator Torkell Ellingsen, MD, PhD, of Odense (Denmark) University Hospital said together in an interview.

“The most important findings from this trial is that FMT appears to be safe in patients with PsA and that the patients find the treatment acceptable, and it supports future research into the therapeutic potential of FMT in PsA,” they said.

The study evaluated 6-month outcomes of 31 patients randomized to the FMT and sham groups. FMT patients were three times more likely to experience treatment failure – defined by the need for treatment intensification – with failure rates of 60% versus 20% in the sham group.

As a secondary endpoint, the study used 6-month change in the Health Assessment Questionnaire Disability Index (HAQ-DI) and 20% improvement in American College of Rheumatology criteria (ACR20). The sham group demonstrated a greater decrease in HAQ-DI, indicating better physical function (–0.30 vs. –0.07; P = .031). The proportion of ACR20 responders was similar between both groups: 47% for the FMT patients (7 of 15) and 53% for sham (8 of 15).

The study included adults aged 18-75 years with active peripheral disease, defined as three or more swollen joints, who’d been taking at least15 mg methotrexate a week for at least 3 months before enrolling in the study, with a washout period of 12 weeks (26 weeks for those on biologic agents). Four healthy donors provided the stool transplants.

In the study, Dr. Kragsnaes and Dr. Ellingsen acknowledged that FMT has been shown to be safe for Clostridioides difficile infection or inflammatory bowel disease when “thoroughly screened stool” is used. “Hence,” they wrote, “our findings add to the growing body of evidence suggesting a gut-joint axis in the pathogenesis of PsA.”

Factors that may influence the effectiveness of FMT in PsA merit further investigation, Dr. Kragsnaes and Dr. Ellingsen said. “From FMT trials in patients with active ulcerative colitis, higher dose and repeated administration appear to be effective and safe in inducing remission,” they said in their joint statement, pointing to research from China.

“Moreover,” they added, “successes of FMT in inflammatory bowel disease appear to have been driven by ‘superdonors’ characterized by the presence or absence of specific bacteria species.”

They said will continue to investigate the effectiveness of FMT in immune-mediated diseases, including how to characterize superdonors.

“We will conduct new randomized trials using different FMT strategies – by changing the type of administration form, dose, and treatment frequency – to explore whether microbial dysbiosis or specific bacteria are common or decisive mediators of disease activity in inflammatory diseases and whether this proposed relation can be modified without exacerbating the disease,” Dr. Kragsnaes and Dr. Ellingsen said.

Dr. Kragsnaes and Dr. Ellingsen had no relevant financial relationships to disclose.

The first clinical trial of fecal microbiota transplantation in patients with psoriatic arthritis has found the procedure to be as safe as a sham procedure, but it didn’t show any effectiveness in decreasing PsA symptoms over 6 months, a team of researchers in Denmark reported in Annals of the Rheumatic Diseases (2021 Apr 29. 10.1136/annrheumdis-2020-219511).

ChrisChrisW/Getty Images

Nonetheless, the investigators said the trial indicates fecal microbiota transplantation (FMT) is worthy of further study.

“Overall, we think that the results are very interesting and that the feasibility and safety aspects as well as the clinical results of the trial may encourage more research into the potential of FMT in the treatment of inflammatory arthritis and may help guide the direction of future trials within the field,” lead author Maja S. Kragsnaes, MD, PhD, and principal investigator Torkell Ellingsen, MD, PhD, of Odense (Denmark) University Hospital said together in an interview.

“The most important findings from this trial is that FMT appears to be safe in patients with PsA and that the patients find the treatment acceptable, and it supports future research into the therapeutic potential of FMT in PsA,” they said.

The study evaluated 6-month outcomes of 31 patients randomized to the FMT and sham groups. FMT patients were three times more likely to experience treatment failure – defined by the need for treatment intensification – with failure rates of 60% versus 20% in the sham group.

As a secondary endpoint, the study used 6-month change in the Health Assessment Questionnaire Disability Index (HAQ-DI) and 20% improvement in American College of Rheumatology criteria (ACR20). The sham group demonstrated a greater decrease in HAQ-DI, indicating better physical function (–0.30 vs. –0.07; P = .031). The proportion of ACR20 responders was similar between both groups: 47% for the FMT patients (7 of 15) and 53% for sham (8 of 15).

The study included adults aged 18-75 years with active peripheral disease, defined as three or more swollen joints, who’d been taking at least15 mg methotrexate a week for at least 3 months before enrolling in the study, with a washout period of 12 weeks (26 weeks for those on biologic agents). Four healthy donors provided the stool transplants.

In the study, Dr. Kragsnaes and Dr. Ellingsen acknowledged that FMT has been shown to be safe for Clostridioides difficile infection or inflammatory bowel disease when “thoroughly screened stool” is used. “Hence,” they wrote, “our findings add to the growing body of evidence suggesting a gut-joint axis in the pathogenesis of PsA.”

Factors that may influence the effectiveness of FMT in PsA merit further investigation, Dr. Kragsnaes and Dr. Ellingsen said. “From FMT trials in patients with active ulcerative colitis, higher dose and repeated administration appear to be effective and safe in inducing remission,” they said in their joint statement, pointing to research from China.

“Moreover,” they added, “successes of FMT in inflammatory bowel disease appear to have been driven by ‘superdonors’ characterized by the presence or absence of specific bacteria species.”

They said will continue to investigate the effectiveness of FMT in immune-mediated diseases, including how to characterize superdonors.

“We will conduct new randomized trials using different FMT strategies – by changing the type of administration form, dose, and treatment frequency – to explore whether microbial dysbiosis or specific bacteria are common or decisive mediators of disease activity in inflammatory diseases and whether this proposed relation can be modified without exacerbating the disease,” Dr. Kragsnaes and Dr. Ellingsen said.

Dr. Kragsnaes and Dr. Ellingsen had no relevant financial relationships to disclose.

Genital skin exams in girls must be conducted with special care and alertness for signs of abuse, a dermatologist told colleagues at the American Academy of Dermatology Virtual Meeting Experience.

“One in four adult women report being childhood victims of sexual abuse, which is just a staggering number. This is an opportunity for us to identify these patients early and give them the terminology to be able to report what is happening to them,” said pediatric dermatologist Kalyani Marathe, MD, MPH, director of the division of dermatology at Cincinnati Children’s Hospital. “We also have the chance to give them a sense of agency over their bodies.”

Dr. Marathe offered the following recommendations when performing a genital skin exam:

• Make sure a “chaperone” is present. “Chaperones are a must when you’re examining children and teens,” she said. “Ask whom they prefer. For prepubertal children, you’re going to usually use the parent who’s there with them. If the parent is their father, they might ask him to step behind the curtain, in which case you can bring over your nurse or medical assistant.” Teens may ask either parent to step out of the room, she said. In that case, a nurse, medical assistant, resident, or trainee can fill in. “If you have male residents or trainees with you and the patient really does not want to be examined by a male, honor their request. Do not force them.”
• Explain why the exam is being performed. Make sure the patient understands why she is being seen, Dr. Marathe advised. For example, say something like “your pediatrician told us that you have an itchy area” or “your mom told us that there’s some loss of color in that area, that you’re having a problem there.” She added that it’s helpful to explain the type of doctor you are, with a comment such as the following: “We’re examining you because we’re doctors who specialize in skin. ... We want to help you feel better and make sure that your skin heals and is healthy.”
• Ask both the child and the parent for permission to perform the exam. While this may seem trivial, “it’s very, very important in setting the right tone for the encounter,” she said. “If the child says yes, we turn to the mom and say: ‘Mom, is it okay for us to do this exam today?’ You can see visible relief on the part of the parent, and as the parent relaxes, the child relaxes. Just saying those few things really makes the encounter so much smoother.” However, “if they say no, you have to honor the response. ... You say: ‘Okay, we’re not going to do the exam today,” and see the patient in a few weeks. If it’s urgent, an exam under anesthesia may be an option, she added.
• Talk to the child about the terms they use for private parts. It can be helpful to ask: “Do you have any terms for your private area?” According to Dr. Marathe, “this is a good chance to educate them on the terms vulva and vagina since they may be using other terminology. Making sure that they have the correct terms will actually help patients identify and report abuse earlier.” Dr. Marathe recalled that a colleague had a patient who’d been calling her private area “pound cake” and had been “reporting to her teacher that someone had been touching her ‘pound cake.’ Her teacher did not know what she meant by that, and this led to a great delay in her childhood abuse being reported.”
• Talk about what will happen during the exam. “I like to show them any instruments that we’re going to be using,” Dr. Marathe said. “If we’re using a flashlight, for example, I like to show them a picture [of a flashlight] or show them that flashlight. If we’re using a camera to do digital photography, show them that. If we’re going to be using a Q-tip or a swab to demonstrate anything or to take a culture, I like to show them that beforehand to make sure that they know what we’re doing.” In regard to photography, “make sure the parent and child know where the photos are going to go, who’s going to see them, what are they going to be used for. If they’re going to be used for educational purposes, make sure they have given explicit permission for that and they know they’ll be deidentified.”
• Make it clear that the exam won’t be painful. It’s important to put both the patient and the parent at ease on this front, Dr. Marathe said. “A lot of parents are concerned that we’re going to do a speculum exam in their prepubertal child. So make sure that it’s clarified ahead of time that we’re not going to be doing a speculum exam.”

Commenting on this topic, Tor Shwayder, MD, a pediatric dermatologist at Henry Ford Health System, Detroit, urged colleagues to take action if they feel suspicious about a possible sign of child abuse, even if they’re far from certain that anything is wrong. “Don’t ignore those feelings in the back of the brain,” he said in an interview.

Most states have child-abuse hotlines for medical professionals, and major hospitals will have child-abuse teams, Dr. Shwayder said. He urged dermatologists to take advantage of these resources when appropriate. “The professionals on the other side of the 800 number or at the hospital will help you. You don’t have to decide immediately whether this is child abuse. You just need to have a suspicion.”

Dr. Marathe and Dr. Shwayder report no disclosures.

Genital skin exams in girls must be conducted with special care and alertness for signs of abuse, a dermatologist told colleagues at the American Academy of Dermatology Virtual Meeting Experience.

“One in four adult women report being childhood victims of sexual abuse, which is just a staggering number. This is an opportunity for us to identify these patients early and give them the terminology to be able to report what is happening to them,” said pediatric dermatologist Kalyani Marathe, MD, MPH, director of the division of dermatology at Cincinnati Children’s Hospital. “We also have the chance to give them a sense of agency over their bodies.”

Dr. Marathe offered the following recommendations when performing a genital skin exam:

• Make sure a “chaperone” is present. “Chaperones are a must when you’re examining children and teens,” she said. “Ask whom they prefer. For prepubertal children, you’re going to usually use the parent who’s there with them. If the parent is their father, they might ask him to step behind the curtain, in which case you can bring over your nurse or medical assistant.” Teens may ask either parent to step out of the room, she said. In that case, a nurse, medical assistant, resident, or trainee can fill in. “If you have male residents or trainees with you and the patient really does not want to be examined by a male, honor their request. Do not force them.”
• Explain why the exam is being performed. Make sure the patient understands why she is being seen, Dr. Marathe advised. For example, say something like “your pediatrician told us that you have an itchy area” or “your mom told us that there’s some loss of color in that area, that you’re having a problem there.” She added that it’s helpful to explain the type of doctor you are, with a comment such as the following: “We’re examining you because we’re doctors who specialize in skin. ... We want to help you feel better and make sure that your skin heals and is healthy.”
• Ask both the child and the parent for permission to perform the exam. While this may seem trivial, “it’s very, very important in setting the right tone for the encounter,” she said. “If the child says yes, we turn to the mom and say: ‘Mom, is it okay for us to do this exam today?’ You can see visible relief on the part of the parent, and as the parent relaxes, the child relaxes. Just saying those few things really makes the encounter so much smoother.” However, “if they say no, you have to honor the response. ... You say: ‘Okay, we’re not going to do the exam today,” and see the patient in a few weeks. If it’s urgent, an exam under anesthesia may be an option, she added.
• Talk to the child about the terms they use for private parts. It can be helpful to ask: “Do you have any terms for your private area?” According to Dr. Marathe, “this is a good chance to educate them on the terms vulva and vagina since they may be using other terminology. Making sure that they have the correct terms will actually help patients identify and report abuse earlier.” Dr. Marathe recalled that a colleague had a patient who’d been calling her private area “pound cake” and had been “reporting to her teacher that someone had been touching her ‘pound cake.’ Her teacher did not know what she meant by that, and this led to a great delay in her childhood abuse being reported.”
• Talk about what will happen during the exam. “I like to show them any instruments that we’re going to be using,” Dr. Marathe said. “If we’re using a flashlight, for example, I like to show them a picture [of a flashlight] or show them that flashlight. If we’re using a camera to do digital photography, show them that. If we’re going to be using a Q-tip or a swab to demonstrate anything or to take a culture, I like to show them that beforehand to make sure that they know what we’re doing.” In regard to photography, “make sure the parent and child know where the photos are going to go, who’s going to see them, what are they going to be used for. If they’re going to be used for educational purposes, make sure they have given explicit permission for that and they know they’ll be deidentified.”
• Make it clear that the exam won’t be painful. It’s important to put both the patient and the parent at ease on this front, Dr. Marathe said. “A lot of parents are concerned that we’re going to do a speculum exam in their prepubertal child. So make sure that it’s clarified ahead of time that we’re not going to be doing a speculum exam.”

Commenting on this topic, Tor Shwayder, MD, a pediatric dermatologist at Henry Ford Health System, Detroit, urged colleagues to take action if they feel suspicious about a possible sign of child abuse, even if they’re far from certain that anything is wrong. “Don’t ignore those feelings in the back of the brain,” he said in an interview.

Most states have child-abuse hotlines for medical professionals, and major hospitals will have child-abuse teams, Dr. Shwayder said. He urged dermatologists to take advantage of these resources when appropriate. “The professionals on the other side of the 800 number or at the hospital will help you. You don’t have to decide immediately whether this is child abuse. You just need to have a suspicion.”

Dr. Marathe and Dr. Shwayder report no disclosures.

Genital skin exams in girls must be conducted with special care and alertness for signs of abuse, a dermatologist told colleagues at the American Academy of Dermatology Virtual Meeting Experience.

“One in four adult women report being childhood victims of sexual abuse, which is just a staggering number. This is an opportunity for us to identify these patients early and give them the terminology to be able to report what is happening to them,” said pediatric dermatologist Kalyani Marathe, MD, MPH, director of the division of dermatology at Cincinnati Children’s Hospital. “We also have the chance to give them a sense of agency over their bodies.”

Dr. Marathe offered the following recommendations when performing a genital skin exam:

• Make sure a “chaperone” is present. “Chaperones are a must when you’re examining children and teens,” she said. “Ask whom they prefer. For prepubertal children, you’re going to usually use the parent who’s there with them. If the parent is their father, they might ask him to step behind the curtain, in which case you can bring over your nurse or medical assistant.” Teens may ask either parent to step out of the room, she said. In that case, a nurse, medical assistant, resident, or trainee can fill in. “If you have male residents or trainees with you and the patient really does not want to be examined by a male, honor their request. Do not force them.”
• Explain why the exam is being performed. Make sure the patient understands why she is being seen, Dr. Marathe advised. For example, say something like “your pediatrician told us that you have an itchy area” or “your mom told us that there’s some loss of color in that area, that you’re having a problem there.” She added that it’s helpful to explain the type of doctor you are, with a comment such as the following: “We’re examining you because we’re doctors who specialize in skin. ... We want to help you feel better and make sure that your skin heals and is healthy.”
• Ask both the child and the parent for permission to perform the exam. While this may seem trivial, “it’s very, very important in setting the right tone for the encounter,” she said. “If the child says yes, we turn to the mom and say: ‘Mom, is it okay for us to do this exam today?’ You can see visible relief on the part of the parent, and as the parent relaxes, the child relaxes. Just saying those few things really makes the encounter so much smoother.” However, “if they say no, you have to honor the response. ... You say: ‘Okay, we’re not going to do the exam today,” and see the patient in a few weeks. If it’s urgent, an exam under anesthesia may be an option, she added.
• Talk to the child about the terms they use for private parts. It can be helpful to ask: “Do you have any terms for your private area?” According to Dr. Marathe, “this is a good chance to educate them on the terms vulva and vagina since they may be using other terminology. Making sure that they have the correct terms will actually help patients identify and report abuse earlier.” Dr. Marathe recalled that a colleague had a patient who’d been calling her private area “pound cake” and had been “reporting to her teacher that someone had been touching her ‘pound cake.’ Her teacher did not know what she meant by that, and this led to a great delay in her childhood abuse being reported.”
• Talk about what will happen during the exam. “I like to show them any instruments that we’re going to be using,” Dr. Marathe said. “If we’re using a flashlight, for example, I like to show them a picture [of a flashlight] or show them that flashlight. If we’re using a camera to do digital photography, show them that. If we’re going to be using a Q-tip or a swab to demonstrate anything or to take a culture, I like to show them that beforehand to make sure that they know what we’re doing.” In regard to photography, “make sure the parent and child know where the photos are going to go, who’s going to see them, what are they going to be used for. If they’re going to be used for educational purposes, make sure they have given explicit permission for that and they know they’ll be deidentified.”
• Make it clear that the exam won’t be painful. It’s important to put both the patient and the parent at ease on this front, Dr. Marathe said. “A lot of parents are concerned that we’re going to do a speculum exam in their prepubertal child. So make sure that it’s clarified ahead of time that we’re not going to be doing a speculum exam.”

Commenting on this topic, Tor Shwayder, MD, a pediatric dermatologist at Henry Ford Health System, Detroit, urged colleagues to take action if they feel suspicious about a possible sign of child abuse, even if they’re far from certain that anything is wrong. “Don’t ignore those feelings in the back of the brain,” he said in an interview.

Most states have child-abuse hotlines for medical professionals, and major hospitals will have child-abuse teams, Dr. Shwayder said. He urged dermatologists to take advantage of these resources when appropriate. “The professionals on the other side of the 800 number or at the hospital will help you. You don’t have to decide immediately whether this is child abuse. You just need to have a suspicion.”

Dr. Marathe and Dr. Shwayder report no disclosures.