User login
Single dose of psilocybin for major depression tied to short-term remission
, new research shows.
In the largest study of psilocybin for TRD to date, results of the phase 2b randomized, double-blind trial show participants in the 25-mg dose group experienced a significant reduction in depressive symptoms for at least 3 weeks vs. patients in the 10-mg or 1-mg group, which served as the control group.
Investigators found that 29% of participants who received the 25-mg dose were in remission 3 weeks after the treatment and 37% had at least a 50% drop in depression scores. However, at the 3-month mark, only 20% of those on the 25-mg dose experienced significant improvement.
The change from baseline to week 3 in the Montgomery–Åsberg Depression Rating Scale (MADRS) total score was significantly better with a 25-mg dose than with a 1-mg dose; there was no significant difference between the 10-mg dose and the 1-mg dose, the investigators reported.
The response rate was high for those receiving the 25-mg dose, lead investigator Guy Goodwin, MD, DPhil, told reporters attending a press briefing.
“It’s important to understand that response rates in these patients are usually somewhere between 10% and 20%, and we are seeing remission rates at three weeks of 30%,” he said.
Dr. Goodwin is chief medical officer of COMPASS Pathways, the company that funded the trial and created COMP360, the synthetic formulation of psilocybin used in the trial, and professor emeritus of psychiatry at the University of Oxford, England.
Based on the results of the trial it was announced that a phase 3 trial will launch in December.
The study was published online in the New England Journal of Medicine.
Further research planned
Psilocybin has been under investigation for TRD for some time, including one study that compared it with the antidepressant escitalopram (Lexapro) with promising results.
In the current study the researchers sought to find an acceptable, efficacious dose and the safety of a synthetic formulation of the drug administered in combination with psychological support.
The multicenter study was conducted at 22 sites in 10 countries and included 233 participants with TRD and evaluated the safety and efficacy of one of three doses. The study’s primary endpoint was change from baseline to 3 weeks in MADRS scores in patients with TRD. The scale runs from 0 to 60 with higher scores indicating more severe depression.
Participants were randomly assigned to receive 25 mg of psilocybin (n = 79), 10 mg (n = 75) or 1 mg (n = 79). Those taking medications discontinued them at least 2 weeks before the baseline visit. The mean MADRS score was 32 or 33 in each study group.
There was a 3- to 6-week run-up period to the study in which each participant met with a study therapist about three times to build trust and prepare for the psychedelic experience.
On the day of psilocybin administration, each participant listened to a tailored music playlist and wore eye shades while reclining in a comfortable chair to direct attention inwardly.
The psychotherapy sessions lasted 6-8 hours, and two therapists were always present. The following day, participants returned for an “integration” session with the therapists that was designed to help the participants explore insights from their session.
MADRS scores were measured at baseline, the day following psilocybin administration, and at weeks 1, 3, 6, 9, and 12.
Participants were asked to stay off standard antidepressant treatment during the first 3 weeks of the trial but could be restarted at any time if deemed necessary by a trial investigator.
Mean changes from baseline to week 3 in MADRS scores were −12.0 for 25-mg, −7.9 for 10-mg, and −5.4 for 1-mg groups. The difference between the 25-mg group and 1-mg group was −6.6 (95% confidence interval [CI], −10.2 to −2.9; P < .001 and between the 10-mg group and 1-mg group was −2.5 (95% CI, −6.2 to 1.2; P = .18).
The investigators reported that in the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results.
Up to 84% of those who received the 25-mg dosage reported adverse events, with the occurrence dropping slightly with each dosage group. The most frequent adverse events included headache, nausea, dizziness, and fatigue, and occurred only on administration day.
Among those who received the 25-mg dose of psilocybin, two participants reported suicidal thoughts during the 3 weeks following treatment, and 3 months post treatment, three patients exhibited suicidal behavior.
Dr. Goodwin noted that these participants had a prior history of suicidal behavior. Two participants in the 10-mg group also had suicidal thoughts. However, the investigators also noted that suicidal ideation, behavior, or self-injury occurred in all dose groups.
The researchers noted that longer and larger trials, including comparisons with existing depression treatments, are needed to determine the safety and efficacy of psilocybin for TRD.
Intriguing, sobering
In an accompanying editorial, Bertha Madras, PhD, McLean Hospital, Belmont, Mass., and Harvard Medical School, Boston, noted “the findings are both intriguing and sobering. The highest dose (25 mg), but not the intermediate dose (10 mg), resulted in significantly lower levels of depressive symptoms after 3 weeks than the lowest dose (1 mg, which served as a control), but the 37% incidence of response with the 25-mg dose was numerically lower than that in large trials of conventional antidepressants and less robust than in a trial showing similar efficacies of psilocybin and a selective serotonin reuptake inhibitor.”
Also sobering, she noted, were the high percentages of adverse events in the 25-mg group and suicidal ideation and behavior. Dr. Madras also wondered if “legalization and commercialization [of psychedelics] are allied with the medical movement, psychedelic shops and ‘clinics’ could proliferate even for vulnerable populations, and rigorously designed medical protocols will be compromised.
“Nevertheless,” she concluded, “it is provocative that these agents show some short-term benefit for depression in selected populations.”
Dr. Goodwin is CMO of Compass Pathways, which funded the study. He and several coauthors disclosed relationships with industry. Dr. Madras reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research shows.
In the largest study of psilocybin for TRD to date, results of the phase 2b randomized, double-blind trial show participants in the 25-mg dose group experienced a significant reduction in depressive symptoms for at least 3 weeks vs. patients in the 10-mg or 1-mg group, which served as the control group.
Investigators found that 29% of participants who received the 25-mg dose were in remission 3 weeks after the treatment and 37% had at least a 50% drop in depression scores. However, at the 3-month mark, only 20% of those on the 25-mg dose experienced significant improvement.
The change from baseline to week 3 in the Montgomery–Åsberg Depression Rating Scale (MADRS) total score was significantly better with a 25-mg dose than with a 1-mg dose; there was no significant difference between the 10-mg dose and the 1-mg dose, the investigators reported.
The response rate was high for those receiving the 25-mg dose, lead investigator Guy Goodwin, MD, DPhil, told reporters attending a press briefing.
“It’s important to understand that response rates in these patients are usually somewhere between 10% and 20%, and we are seeing remission rates at three weeks of 30%,” he said.
Dr. Goodwin is chief medical officer of COMPASS Pathways, the company that funded the trial and created COMP360, the synthetic formulation of psilocybin used in the trial, and professor emeritus of psychiatry at the University of Oxford, England.
Based on the results of the trial it was announced that a phase 3 trial will launch in December.
The study was published online in the New England Journal of Medicine.
Further research planned
Psilocybin has been under investigation for TRD for some time, including one study that compared it with the antidepressant escitalopram (Lexapro) with promising results.
In the current study the researchers sought to find an acceptable, efficacious dose and the safety of a synthetic formulation of the drug administered in combination with psychological support.
The multicenter study was conducted at 22 sites in 10 countries and included 233 participants with TRD and evaluated the safety and efficacy of one of three doses. The study’s primary endpoint was change from baseline to 3 weeks in MADRS scores in patients with TRD. The scale runs from 0 to 60 with higher scores indicating more severe depression.
Participants were randomly assigned to receive 25 mg of psilocybin (n = 79), 10 mg (n = 75) or 1 mg (n = 79). Those taking medications discontinued them at least 2 weeks before the baseline visit. The mean MADRS score was 32 or 33 in each study group.
There was a 3- to 6-week run-up period to the study in which each participant met with a study therapist about three times to build trust and prepare for the psychedelic experience.
On the day of psilocybin administration, each participant listened to a tailored music playlist and wore eye shades while reclining in a comfortable chair to direct attention inwardly.
The psychotherapy sessions lasted 6-8 hours, and two therapists were always present. The following day, participants returned for an “integration” session with the therapists that was designed to help the participants explore insights from their session.
MADRS scores were measured at baseline, the day following psilocybin administration, and at weeks 1, 3, 6, 9, and 12.
Participants were asked to stay off standard antidepressant treatment during the first 3 weeks of the trial but could be restarted at any time if deemed necessary by a trial investigator.
Mean changes from baseline to week 3 in MADRS scores were −12.0 for 25-mg, −7.9 for 10-mg, and −5.4 for 1-mg groups. The difference between the 25-mg group and 1-mg group was −6.6 (95% confidence interval [CI], −10.2 to −2.9; P < .001 and between the 10-mg group and 1-mg group was −2.5 (95% CI, −6.2 to 1.2; P = .18).
The investigators reported that in the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results.
Up to 84% of those who received the 25-mg dosage reported adverse events, with the occurrence dropping slightly with each dosage group. The most frequent adverse events included headache, nausea, dizziness, and fatigue, and occurred only on administration day.
Among those who received the 25-mg dose of psilocybin, two participants reported suicidal thoughts during the 3 weeks following treatment, and 3 months post treatment, three patients exhibited suicidal behavior.
Dr. Goodwin noted that these participants had a prior history of suicidal behavior. Two participants in the 10-mg group also had suicidal thoughts. However, the investigators also noted that suicidal ideation, behavior, or self-injury occurred in all dose groups.
The researchers noted that longer and larger trials, including comparisons with existing depression treatments, are needed to determine the safety and efficacy of psilocybin for TRD.
Intriguing, sobering
In an accompanying editorial, Bertha Madras, PhD, McLean Hospital, Belmont, Mass., and Harvard Medical School, Boston, noted “the findings are both intriguing and sobering. The highest dose (25 mg), but not the intermediate dose (10 mg), resulted in significantly lower levels of depressive symptoms after 3 weeks than the lowest dose (1 mg, which served as a control), but the 37% incidence of response with the 25-mg dose was numerically lower than that in large trials of conventional antidepressants and less robust than in a trial showing similar efficacies of psilocybin and a selective serotonin reuptake inhibitor.”
Also sobering, she noted, were the high percentages of adverse events in the 25-mg group and suicidal ideation and behavior. Dr. Madras also wondered if “legalization and commercialization [of psychedelics] are allied with the medical movement, psychedelic shops and ‘clinics’ could proliferate even for vulnerable populations, and rigorously designed medical protocols will be compromised.
“Nevertheless,” she concluded, “it is provocative that these agents show some short-term benefit for depression in selected populations.”
Dr. Goodwin is CMO of Compass Pathways, which funded the study. He and several coauthors disclosed relationships with industry. Dr. Madras reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research shows.
In the largest study of psilocybin for TRD to date, results of the phase 2b randomized, double-blind trial show participants in the 25-mg dose group experienced a significant reduction in depressive symptoms for at least 3 weeks vs. patients in the 10-mg or 1-mg group, which served as the control group.
Investigators found that 29% of participants who received the 25-mg dose were in remission 3 weeks after the treatment and 37% had at least a 50% drop in depression scores. However, at the 3-month mark, only 20% of those on the 25-mg dose experienced significant improvement.
The change from baseline to week 3 in the Montgomery–Åsberg Depression Rating Scale (MADRS) total score was significantly better with a 25-mg dose than with a 1-mg dose; there was no significant difference between the 10-mg dose and the 1-mg dose, the investigators reported.
The response rate was high for those receiving the 25-mg dose, lead investigator Guy Goodwin, MD, DPhil, told reporters attending a press briefing.
“It’s important to understand that response rates in these patients are usually somewhere between 10% and 20%, and we are seeing remission rates at three weeks of 30%,” he said.
Dr. Goodwin is chief medical officer of COMPASS Pathways, the company that funded the trial and created COMP360, the synthetic formulation of psilocybin used in the trial, and professor emeritus of psychiatry at the University of Oxford, England.
Based on the results of the trial it was announced that a phase 3 trial will launch in December.
The study was published online in the New England Journal of Medicine.
Further research planned
Psilocybin has been under investigation for TRD for some time, including one study that compared it with the antidepressant escitalopram (Lexapro) with promising results.
In the current study the researchers sought to find an acceptable, efficacious dose and the safety of a synthetic formulation of the drug administered in combination with psychological support.
The multicenter study was conducted at 22 sites in 10 countries and included 233 participants with TRD and evaluated the safety and efficacy of one of three doses. The study’s primary endpoint was change from baseline to 3 weeks in MADRS scores in patients with TRD. The scale runs from 0 to 60 with higher scores indicating more severe depression.
Participants were randomly assigned to receive 25 mg of psilocybin (n = 79), 10 mg (n = 75) or 1 mg (n = 79). Those taking medications discontinued them at least 2 weeks before the baseline visit. The mean MADRS score was 32 or 33 in each study group.
There was a 3- to 6-week run-up period to the study in which each participant met with a study therapist about three times to build trust and prepare for the psychedelic experience.
On the day of psilocybin administration, each participant listened to a tailored music playlist and wore eye shades while reclining in a comfortable chair to direct attention inwardly.
The psychotherapy sessions lasted 6-8 hours, and two therapists were always present. The following day, participants returned for an “integration” session with the therapists that was designed to help the participants explore insights from their session.
MADRS scores were measured at baseline, the day following psilocybin administration, and at weeks 1, 3, 6, 9, and 12.
Participants were asked to stay off standard antidepressant treatment during the first 3 weeks of the trial but could be restarted at any time if deemed necessary by a trial investigator.
Mean changes from baseline to week 3 in MADRS scores were −12.0 for 25-mg, −7.9 for 10-mg, and −5.4 for 1-mg groups. The difference between the 25-mg group and 1-mg group was −6.6 (95% confidence interval [CI], −10.2 to −2.9; P < .001 and between the 10-mg group and 1-mg group was −2.5 (95% CI, −6.2 to 1.2; P = .18).
The investigators reported that in the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results.
Up to 84% of those who received the 25-mg dosage reported adverse events, with the occurrence dropping slightly with each dosage group. The most frequent adverse events included headache, nausea, dizziness, and fatigue, and occurred only on administration day.
Among those who received the 25-mg dose of psilocybin, two participants reported suicidal thoughts during the 3 weeks following treatment, and 3 months post treatment, three patients exhibited suicidal behavior.
Dr. Goodwin noted that these participants had a prior history of suicidal behavior. Two participants in the 10-mg group also had suicidal thoughts. However, the investigators also noted that suicidal ideation, behavior, or self-injury occurred in all dose groups.
The researchers noted that longer and larger trials, including comparisons with existing depression treatments, are needed to determine the safety and efficacy of psilocybin for TRD.
Intriguing, sobering
In an accompanying editorial, Bertha Madras, PhD, McLean Hospital, Belmont, Mass., and Harvard Medical School, Boston, noted “the findings are both intriguing and sobering. The highest dose (25 mg), but not the intermediate dose (10 mg), resulted in significantly lower levels of depressive symptoms after 3 weeks than the lowest dose (1 mg, which served as a control), but the 37% incidence of response with the 25-mg dose was numerically lower than that in large trials of conventional antidepressants and less robust than in a trial showing similar efficacies of psilocybin and a selective serotonin reuptake inhibitor.”
Also sobering, she noted, were the high percentages of adverse events in the 25-mg group and suicidal ideation and behavior. Dr. Madras also wondered if “legalization and commercialization [of psychedelics] are allied with the medical movement, psychedelic shops and ‘clinics’ could proliferate even for vulnerable populations, and rigorously designed medical protocols will be compromised.
“Nevertheless,” she concluded, “it is provocative that these agents show some short-term benefit for depression in selected populations.”
Dr. Goodwin is CMO of Compass Pathways, which funded the study. He and several coauthors disclosed relationships with industry. Dr. Madras reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
STEP TEENS: Semaglutide ‘gives hope’ to adolescents with obesity
Attendees at ObesityWeek® 2022 listened with much excitement to the results of the STEP TEENS phase 3 trial of once-weekly subcutaneous semaglutide 2.4 mg (Wegovy) in adolescents aged 12 up to 18 years old with obesity.
When a session panel member said that clinical trials of weight-loss medications for adolescents with obesity should henceforth stop using placebo controls – implying that comparison with the once-weekly injection semaglutide would be more informative – the audience applauded.
The results were also simultaneously published in the New England Journal of Medicine to coincide with the presentation.
The research “gives hope” to adolescents with obesity, their parents, and their doctors, the trial’s principal investigator, Daniel Weghuber, MD, said in an interview.
“Many of them have been struggling for such a long time – both the parents and the kids themselves,” said Dr. Weghuber, from the department of pediatrics, Paracelsus Medical University, Salzburg, Austria.
“It’s not an issue of lack of willpower,” he stressed. “That’s a major misunderstanding.”
“This drug [semaglutide] seems to enable people who are living with obesity to adhere to the recommendations that they may have been following for years and years but were [still] not able to achieve their goal,” he said. It “enables people to achieve their goals.”
Asked about any potential negative impact on normal growth, Dr. Weghuber pointed out that the average weight of study participants was 107 kg (236 lb). “I’m really not afraid of a 15-year-old with 107 kg losing 10%, 15%, 20%” of their weight, he said. There was no indication of a problem regarding normal growth or development in the study.
, he summarized.
Senior study author, Silva Arslanian, MD, who holds the Richard L. Day Endowed Chair in Pediatrics at the University of Pittsburgh, agreed. “The results are amazing,” said Dr. Arslanian in a press release issued by the University of Pittsburgh. “For a person who is 5 foot, 5 inches tall and weighs 240 pounds, the average reduction in BMI equates to shedding about 40 pounds.”
‘Mind-blowing, awesome’ results
The session at ObesityWeek® 2022, the annual meeting of the Obesity Society, was chaired by Aaron S. Kelly, PhD, professor of pediatrics and codirector of the center for pediatric obesity medicine at the University of Minnesota, Minneapolis.
Dr. Kelly led the SCALE TEENS clinical trial of liraglutide (Saxenda), also a glucagon-like peptide (GLP-1) agonist like semaglutide, for adolescents aged 12 up to 18 years with obesity, which assigned 125 participants to the daily injectable liraglutide group and 126 to the placebo group. SCALE TEENS was presented and published in May 2020, leading to the approval of liraglutide for obesity in this age group, in December 2020.
Dr. Kelly called on two experts who were not involved in the research to offer their comments, starting with Claudia K. Fox, MD, MPH.
“These results are mind-blowing,” said Dr. Fox, who is associate professor of pediatrics and codirector of the center for pediatric obesity medicine at the University of Minnesota.
“We are getting close to bariatric surgery results” in these adolescent patients with obesity, added Dr. Fox, who is an American Board of Obesity Medicine diplomate. To have 40% of patients attain normal weight, “that’s massive” and “life-changing,” she said. And improvement in quality of life is what families care most about. “I am super excited,” she commented.
Next, Dr. Kelly called on Sarah C. Armstrong, MD, director of the Duke Children’s Healthy Lifestyles Program, Duke University, Durham, N.C.
Dr. Armstrong is a member of the executive committee for the American Academy of Pediatrics Section on Obesity and a coauthor of the upcoming clinical practice guidelines that are being published.
Looking at more than 16,000 abstracts at the meeting shows that “watchful waiting is not effective,” Dr. Armstrong said.
200 teens with obesity, only 1 with overweight
Obesity affects almost one in five children and adolescents worldwide. The chronic disease is linked with decreased life expectancy and higher risk of developing serious health problems such as type 2 diabetes, heart disease, nonalcoholic fatty liver disease, sleep apnea, and certain cancers. Teenagers with obesity are also more likely to have depression, anxiety, poor self-esteem, and other psychological issues.
STEP TEENS enrolled 201 adolescents aged 12 up to 18 years with obesity (body mass index [BMI] ≥ 95th percentile) or overweight (BMI ≥ 85th percentile) plus at least one weight-related comorbidity.
Only one recruited patient fit the latter category; the rest had obesity.
Most patients (62%) were female. They had a mean age of 15.4 years, a mean BMI of 37 kg/m2, and a mean waist circumference of 110 cm (43 inches).
Patients were randomized 2:1 to receive a once-weekly 2.4-mg subcutaneous injection of semaglutide or placebo for 68 weeks, plus lifestyle intervention.
Dr. Weghuber noted that 89.6% of patients in the semaglutide group completed treatment.
The primary endpoint, mean change in BMI from baseline to week 68, was −16.1% with semaglutide and +0.6% with placebo (estimated difference, −16.7 percentage points; P < .001).
A second confirmatory endpoint, at least 5% weight loss at week 68, was met by 73% of patients in the semaglutide group versus 18% of patients in the placebo group (P < .001).
Reductions in body weight and improvements in waist circumference, A1c, lipids (except HDL cholesterol), and the liver enzyme alanine aminotransferase were greater with semaglutide than placebo.
The Impact of Weight on Quality of Life – Kids (IWQOL-Kids) questionnaire total score as well as scores for body esteem, family relation, physical comfort, and social life were better in the semaglutide group.
However, the incidence of gastrointestinal adverse events was greater with semaglutide than placebo (62% versus 42%).
Five participants (4%) in the semaglutide group and none in the placebo group developed gallstones (cholelithiasis).
Serious adverse events were reported in 11% of patients in the semaglutide group and 9% of patients in the placebo group.
‘Big change’ coming in guidelines for obesity in teens
Commenting on the upcoming new recommendations for adolescents, Dr. Armstrong noted “there’s going to be a strong recommendation” for therapy in the new guidelines for pediatric obesity. “That’s a big change,” she said.
In the lively question-and-answer session that followed, a clinician wanted to know what explained the very high rate of study completion during the COVID-19 pandemic (when STEP TEENS was conducted). “What can we learn?” he asked.
“The bottom line is the relationship” and “close communication” between study investigators and patients, Dr. Weghuber replied.
“The fast track is likely to lead to approval in adolescents,” another member of the audience noted. He wanted to know if the company is planning a trial of semaglutide in younger children.
They are, Dr. Weghuber replied, and one with liraglutide is already underway.
The SCALE KIDS clinical trial of liraglutide is randomizing 78 participants aged 6 up to 12 years for 56 weeks of treatment and 26 weeks of follow-up, with an estimated primary completion date of July 7, 2023.
The last words went to Dr. Fox. The current results “are indeed very awesome,” she said, yet “thousands of providers are hesitant” to prescribe medications for adolescents with obesity.
The trial was funded by Novo Nordisk. Dr. Weghuber has reported being a consultant for Novo Nordisk and member of the Global Pediatric Obesity Expert Panel for the company. Disclosures for the other authors are listed with the article. Dr. Kelly has reported receiving donated drugs from AstraZeneca and travel support from Novo Nordisk and serving as an unpaid consultant for Novo Nordisk, Orexigen Therapeutics, VIVUS, and WW (formerly Weight Watchers).
A version of this article first appeared on Medscape.com.
Attendees at ObesityWeek® 2022 listened with much excitement to the results of the STEP TEENS phase 3 trial of once-weekly subcutaneous semaglutide 2.4 mg (Wegovy) in adolescents aged 12 up to 18 years old with obesity.
When a session panel member said that clinical trials of weight-loss medications for adolescents with obesity should henceforth stop using placebo controls – implying that comparison with the once-weekly injection semaglutide would be more informative – the audience applauded.
The results were also simultaneously published in the New England Journal of Medicine to coincide with the presentation.
The research “gives hope” to adolescents with obesity, their parents, and their doctors, the trial’s principal investigator, Daniel Weghuber, MD, said in an interview.
“Many of them have been struggling for such a long time – both the parents and the kids themselves,” said Dr. Weghuber, from the department of pediatrics, Paracelsus Medical University, Salzburg, Austria.
“It’s not an issue of lack of willpower,” he stressed. “That’s a major misunderstanding.”
“This drug [semaglutide] seems to enable people who are living with obesity to adhere to the recommendations that they may have been following for years and years but were [still] not able to achieve their goal,” he said. It “enables people to achieve their goals.”
Asked about any potential negative impact on normal growth, Dr. Weghuber pointed out that the average weight of study participants was 107 kg (236 lb). “I’m really not afraid of a 15-year-old with 107 kg losing 10%, 15%, 20%” of their weight, he said. There was no indication of a problem regarding normal growth or development in the study.
, he summarized.
Senior study author, Silva Arslanian, MD, who holds the Richard L. Day Endowed Chair in Pediatrics at the University of Pittsburgh, agreed. “The results are amazing,” said Dr. Arslanian in a press release issued by the University of Pittsburgh. “For a person who is 5 foot, 5 inches tall and weighs 240 pounds, the average reduction in BMI equates to shedding about 40 pounds.”
‘Mind-blowing, awesome’ results
The session at ObesityWeek® 2022, the annual meeting of the Obesity Society, was chaired by Aaron S. Kelly, PhD, professor of pediatrics and codirector of the center for pediatric obesity medicine at the University of Minnesota, Minneapolis.
Dr. Kelly led the SCALE TEENS clinical trial of liraglutide (Saxenda), also a glucagon-like peptide (GLP-1) agonist like semaglutide, for adolescents aged 12 up to 18 years with obesity, which assigned 125 participants to the daily injectable liraglutide group and 126 to the placebo group. SCALE TEENS was presented and published in May 2020, leading to the approval of liraglutide for obesity in this age group, in December 2020.
Dr. Kelly called on two experts who were not involved in the research to offer their comments, starting with Claudia K. Fox, MD, MPH.
“These results are mind-blowing,” said Dr. Fox, who is associate professor of pediatrics and codirector of the center for pediatric obesity medicine at the University of Minnesota.
“We are getting close to bariatric surgery results” in these adolescent patients with obesity, added Dr. Fox, who is an American Board of Obesity Medicine diplomate. To have 40% of patients attain normal weight, “that’s massive” and “life-changing,” she said. And improvement in quality of life is what families care most about. “I am super excited,” she commented.
Next, Dr. Kelly called on Sarah C. Armstrong, MD, director of the Duke Children’s Healthy Lifestyles Program, Duke University, Durham, N.C.
Dr. Armstrong is a member of the executive committee for the American Academy of Pediatrics Section on Obesity and a coauthor of the upcoming clinical practice guidelines that are being published.
Looking at more than 16,000 abstracts at the meeting shows that “watchful waiting is not effective,” Dr. Armstrong said.
200 teens with obesity, only 1 with overweight
Obesity affects almost one in five children and adolescents worldwide. The chronic disease is linked with decreased life expectancy and higher risk of developing serious health problems such as type 2 diabetes, heart disease, nonalcoholic fatty liver disease, sleep apnea, and certain cancers. Teenagers with obesity are also more likely to have depression, anxiety, poor self-esteem, and other psychological issues.
STEP TEENS enrolled 201 adolescents aged 12 up to 18 years with obesity (body mass index [BMI] ≥ 95th percentile) or overweight (BMI ≥ 85th percentile) plus at least one weight-related comorbidity.
Only one recruited patient fit the latter category; the rest had obesity.
Most patients (62%) were female. They had a mean age of 15.4 years, a mean BMI of 37 kg/m2, and a mean waist circumference of 110 cm (43 inches).
Patients were randomized 2:1 to receive a once-weekly 2.4-mg subcutaneous injection of semaglutide or placebo for 68 weeks, plus lifestyle intervention.
Dr. Weghuber noted that 89.6% of patients in the semaglutide group completed treatment.
The primary endpoint, mean change in BMI from baseline to week 68, was −16.1% with semaglutide and +0.6% with placebo (estimated difference, −16.7 percentage points; P < .001).
A second confirmatory endpoint, at least 5% weight loss at week 68, was met by 73% of patients in the semaglutide group versus 18% of patients in the placebo group (P < .001).
Reductions in body weight and improvements in waist circumference, A1c, lipids (except HDL cholesterol), and the liver enzyme alanine aminotransferase were greater with semaglutide than placebo.
The Impact of Weight on Quality of Life – Kids (IWQOL-Kids) questionnaire total score as well as scores for body esteem, family relation, physical comfort, and social life were better in the semaglutide group.
However, the incidence of gastrointestinal adverse events was greater with semaglutide than placebo (62% versus 42%).
Five participants (4%) in the semaglutide group and none in the placebo group developed gallstones (cholelithiasis).
Serious adverse events were reported in 11% of patients in the semaglutide group and 9% of patients in the placebo group.
‘Big change’ coming in guidelines for obesity in teens
Commenting on the upcoming new recommendations for adolescents, Dr. Armstrong noted “there’s going to be a strong recommendation” for therapy in the new guidelines for pediatric obesity. “That’s a big change,” she said.
In the lively question-and-answer session that followed, a clinician wanted to know what explained the very high rate of study completion during the COVID-19 pandemic (when STEP TEENS was conducted). “What can we learn?” he asked.
“The bottom line is the relationship” and “close communication” between study investigators and patients, Dr. Weghuber replied.
“The fast track is likely to lead to approval in adolescents,” another member of the audience noted. He wanted to know if the company is planning a trial of semaglutide in younger children.
They are, Dr. Weghuber replied, and one with liraglutide is already underway.
The SCALE KIDS clinical trial of liraglutide is randomizing 78 participants aged 6 up to 12 years for 56 weeks of treatment and 26 weeks of follow-up, with an estimated primary completion date of July 7, 2023.
The last words went to Dr. Fox. The current results “are indeed very awesome,” she said, yet “thousands of providers are hesitant” to prescribe medications for adolescents with obesity.
The trial was funded by Novo Nordisk. Dr. Weghuber has reported being a consultant for Novo Nordisk and member of the Global Pediatric Obesity Expert Panel for the company. Disclosures for the other authors are listed with the article. Dr. Kelly has reported receiving donated drugs from AstraZeneca and travel support from Novo Nordisk and serving as an unpaid consultant for Novo Nordisk, Orexigen Therapeutics, VIVUS, and WW (formerly Weight Watchers).
A version of this article first appeared on Medscape.com.
Attendees at ObesityWeek® 2022 listened with much excitement to the results of the STEP TEENS phase 3 trial of once-weekly subcutaneous semaglutide 2.4 mg (Wegovy) in adolescents aged 12 up to 18 years old with obesity.
When a session panel member said that clinical trials of weight-loss medications for adolescents with obesity should henceforth stop using placebo controls – implying that comparison with the once-weekly injection semaglutide would be more informative – the audience applauded.
The results were also simultaneously published in the New England Journal of Medicine to coincide with the presentation.
The research “gives hope” to adolescents with obesity, their parents, and their doctors, the trial’s principal investigator, Daniel Weghuber, MD, said in an interview.
“Many of them have been struggling for such a long time – both the parents and the kids themselves,” said Dr. Weghuber, from the department of pediatrics, Paracelsus Medical University, Salzburg, Austria.
“It’s not an issue of lack of willpower,” he stressed. “That’s a major misunderstanding.”
“This drug [semaglutide] seems to enable people who are living with obesity to adhere to the recommendations that they may have been following for years and years but were [still] not able to achieve their goal,” he said. It “enables people to achieve their goals.”
Asked about any potential negative impact on normal growth, Dr. Weghuber pointed out that the average weight of study participants was 107 kg (236 lb). “I’m really not afraid of a 15-year-old with 107 kg losing 10%, 15%, 20%” of their weight, he said. There was no indication of a problem regarding normal growth or development in the study.
, he summarized.
Senior study author, Silva Arslanian, MD, who holds the Richard L. Day Endowed Chair in Pediatrics at the University of Pittsburgh, agreed. “The results are amazing,” said Dr. Arslanian in a press release issued by the University of Pittsburgh. “For a person who is 5 foot, 5 inches tall and weighs 240 pounds, the average reduction in BMI equates to shedding about 40 pounds.”
‘Mind-blowing, awesome’ results
The session at ObesityWeek® 2022, the annual meeting of the Obesity Society, was chaired by Aaron S. Kelly, PhD, professor of pediatrics and codirector of the center for pediatric obesity medicine at the University of Minnesota, Minneapolis.
Dr. Kelly led the SCALE TEENS clinical trial of liraglutide (Saxenda), also a glucagon-like peptide (GLP-1) agonist like semaglutide, for adolescents aged 12 up to 18 years with obesity, which assigned 125 participants to the daily injectable liraglutide group and 126 to the placebo group. SCALE TEENS was presented and published in May 2020, leading to the approval of liraglutide for obesity in this age group, in December 2020.
Dr. Kelly called on two experts who were not involved in the research to offer their comments, starting with Claudia K. Fox, MD, MPH.
“These results are mind-blowing,” said Dr. Fox, who is associate professor of pediatrics and codirector of the center for pediatric obesity medicine at the University of Minnesota.
“We are getting close to bariatric surgery results” in these adolescent patients with obesity, added Dr. Fox, who is an American Board of Obesity Medicine diplomate. To have 40% of patients attain normal weight, “that’s massive” and “life-changing,” she said. And improvement in quality of life is what families care most about. “I am super excited,” she commented.
Next, Dr. Kelly called on Sarah C. Armstrong, MD, director of the Duke Children’s Healthy Lifestyles Program, Duke University, Durham, N.C.
Dr. Armstrong is a member of the executive committee for the American Academy of Pediatrics Section on Obesity and a coauthor of the upcoming clinical practice guidelines that are being published.
Looking at more than 16,000 abstracts at the meeting shows that “watchful waiting is not effective,” Dr. Armstrong said.
200 teens with obesity, only 1 with overweight
Obesity affects almost one in five children and adolescents worldwide. The chronic disease is linked with decreased life expectancy and higher risk of developing serious health problems such as type 2 diabetes, heart disease, nonalcoholic fatty liver disease, sleep apnea, and certain cancers. Teenagers with obesity are also more likely to have depression, anxiety, poor self-esteem, and other psychological issues.
STEP TEENS enrolled 201 adolescents aged 12 up to 18 years with obesity (body mass index [BMI] ≥ 95th percentile) or overweight (BMI ≥ 85th percentile) plus at least one weight-related comorbidity.
Only one recruited patient fit the latter category; the rest had obesity.
Most patients (62%) were female. They had a mean age of 15.4 years, a mean BMI of 37 kg/m2, and a mean waist circumference of 110 cm (43 inches).
Patients were randomized 2:1 to receive a once-weekly 2.4-mg subcutaneous injection of semaglutide or placebo for 68 weeks, plus lifestyle intervention.
Dr. Weghuber noted that 89.6% of patients in the semaglutide group completed treatment.
The primary endpoint, mean change in BMI from baseline to week 68, was −16.1% with semaglutide and +0.6% with placebo (estimated difference, −16.7 percentage points; P < .001).
A second confirmatory endpoint, at least 5% weight loss at week 68, was met by 73% of patients in the semaglutide group versus 18% of patients in the placebo group (P < .001).
Reductions in body weight and improvements in waist circumference, A1c, lipids (except HDL cholesterol), and the liver enzyme alanine aminotransferase were greater with semaglutide than placebo.
The Impact of Weight on Quality of Life – Kids (IWQOL-Kids) questionnaire total score as well as scores for body esteem, family relation, physical comfort, and social life were better in the semaglutide group.
However, the incidence of gastrointestinal adverse events was greater with semaglutide than placebo (62% versus 42%).
Five participants (4%) in the semaglutide group and none in the placebo group developed gallstones (cholelithiasis).
Serious adverse events were reported in 11% of patients in the semaglutide group and 9% of patients in the placebo group.
‘Big change’ coming in guidelines for obesity in teens
Commenting on the upcoming new recommendations for adolescents, Dr. Armstrong noted “there’s going to be a strong recommendation” for therapy in the new guidelines for pediatric obesity. “That’s a big change,” she said.
In the lively question-and-answer session that followed, a clinician wanted to know what explained the very high rate of study completion during the COVID-19 pandemic (when STEP TEENS was conducted). “What can we learn?” he asked.
“The bottom line is the relationship” and “close communication” between study investigators and patients, Dr. Weghuber replied.
“The fast track is likely to lead to approval in adolescents,” another member of the audience noted. He wanted to know if the company is planning a trial of semaglutide in younger children.
They are, Dr. Weghuber replied, and one with liraglutide is already underway.
The SCALE KIDS clinical trial of liraglutide is randomizing 78 participants aged 6 up to 12 years for 56 weeks of treatment and 26 weeks of follow-up, with an estimated primary completion date of July 7, 2023.
The last words went to Dr. Fox. The current results “are indeed very awesome,” she said, yet “thousands of providers are hesitant” to prescribe medications for adolescents with obesity.
The trial was funded by Novo Nordisk. Dr. Weghuber has reported being a consultant for Novo Nordisk and member of the Global Pediatric Obesity Expert Panel for the company. Disclosures for the other authors are listed with the article. Dr. Kelly has reported receiving donated drugs from AstraZeneca and travel support from Novo Nordisk and serving as an unpaid consultant for Novo Nordisk, Orexigen Therapeutics, VIVUS, and WW (formerly Weight Watchers).
A version of this article first appeared on Medscape.com.
FROM OBESITYWEEK® 2022
Fitness trackers: Useful in sleep medicine?
Who doesn’t love data, especially their own? With that thought in mind, over the years I have owned several activity trackers, including at least two Fitbits, and I frequently check my iPhone to see how far I’ve walked or how many steps I have taken. My most recent acquisition is an Oura (smart ring, third generation), which includes my first sleep tracker.
Sleep trackers are not unique to the Oura Ring; they are included on many of the newer activity trackers and smart watches, but the design and breakdown of daily sleep, activity, and readiness scores are hallmarks of Oura Rings.
The ring generates data for different phases of sleep, movements, oxygen saturation, disturbances in breathing, heart rate, and heart rate variability. I began to wonder how useful this information would be clinically and whether it might be helpful in either the diagnosis or treatment of sleep disorders.
David Neubauer, MD, is a psychiatrist at the Johns Hopkins Sleep Disorders Center. “Sleep tracking devices are more than just toys but less than medical devices. They do have clinical utility and might show findings that warrant further medical workup,” Dr. Neubauer said. “It is impressive that these devices estimate sleep as well as they do, but there is a problem with how they divide sleep stages that can lead people to believe their sleep is worse than it really is.”
For more than 50 years, he explained, sleep researchers and clinicians have categorized sleep as non–rapid eye movement (NREM) sleep stages 1-4 and REM sleep. More recently, sleep was reorganized to N1, N2, and N3 (which combines the older stages 3 and 4, representing “deep sleep” or “slow wave sleep”) and REM sleep. We normally spend more time in N2 than the other stages. However, the device companies often categorize their sleep estimates as “light sleep,” “deep sleep,” or “REM.” With “light sleep,” they are lumping together N1 and N2 sleep, and this is misleading, said Dr. Neubauer. “Understandably, people often think that there is something wrong if their tracker reports they are spending a lot of time in light sleep, when actually their sleep may be entirely normal.”
Sleep tracker validity
A study by Massimiliano de Zambotti, PhD, and colleagues, “The Sleep of the Ring: Comparison of the ŌURA Sleep Tracker Against Polysomnography”, looked at sleep patterns of 41 adolescents and young adults and concluded that the second-generation tracker was accurate in terms of total sleep but underestimated time spent in N3 stage sleep by approximately 20 minutes while overestimating time spent in REM sleep by 17 minutes. They concluded that the ring had potential to be clinically useful but that further studies and validation were needed.
A larger study of the newest, third-generation Oura tracker, conducted by Altini and Kinnunen at Oura Health, found that the added sensors with the newer-generation ring led to improved accuracy, but they noted that the study was done with a healthy population and might not generalize to clinical populations.
Fernando Goes, MD, and Matthew Reid, PhD, both at Johns Hopkins, are working on a multicenter study using the Oura Ring and the mindLAMP app to look at the impact of sleep on mood in people with mood disorders as well as healthy controls. Dr. Reid said that “validation of sleep stages takes a hit when the ring is used in people with insomnia. We find it useful for total sleep time, but when you look at sleep architecture, the concordance is only 60%. And oxygen saturation measures are less accurate in people with dark skin.”
Clinical uses for sleep trackers
More accurate information might prove reassuring to patients. Dr. Goes added, “One use, for example, might be to help patients to limit or come off of long-term hypnotics with a more benign intervention that incorporates passive monitoring such as that in the Oura Ring. Some patients worry excessively about not being able to sleep, and sleep monitoring data can be helpful to reduce some of these concerns so patients can focus on safer interventions, such as cognitive behavioral therapy for insomnia.” Dr. Reid believes that wearable trackers have potential usefulness in monitoring sleep in patients with insomnia. “In insomnia, sleep state misperception is common. They are hyper-aroused, and they perceive that they are awake when in fact they are sleeping.”
Dr. Goes mentioned another use for sleep trackers in clinical settings: “In our inpatient units, the nurses open the door to look in on patients every hour to monitor and document if they are sleeping. If they look in and the patient isn’t moving, they will ask the patient to raise their hand, which of course is not going to help someone to fall back asleep.” Wearable devices might provide data on sleep without the risk of waking patients every hour through the night.
Not medical devices
However, Dr. Neubauer emphasized that current sleep trackers are not medical devices, saying “they may be measuring the same parameters that are measured with medical devices, for example pulse oximetry or sleep states, but there’s no simple answer yet to the question of whether the devices provide reliable data for clinical decision-making.”
Dr. Neubauer is skeptical about the accuracy of some of the measures the device provides. “I would not use the information from a consumer device to rule out obstructive sleep apnea based on good oxygen saturation numbers. So much depends on the history – snoring, gasping awakenings, reports from bed partners, and daytime sleepiness. These devices do not measure respiratory effort or nasal airflow as sleep studies do. But big drops in oxygen saturation from a consumer device certainly warrant attention for further evaluation.” Dr. Neubauer also noted that the parameters on sleep trackers do not differentiate between central or obstructive sleep apnea and that insurers won’t pay for continuous positive airway pressure to treat sleep apnea without a sleep study.
I enjoy looking at the data, even knowing that they are not entirely accurate. and we may find more clinical uses for these devices. For now, I’m off to get more exercise, at the suggestion of my tracker!
Dinah Miller, MD, is assistant professor of psychiatry and behavioral sciences, Johns Hopkins Medicine, Baltimore.
A version of this article first appeared on Medscape.com.
Who doesn’t love data, especially their own? With that thought in mind, over the years I have owned several activity trackers, including at least two Fitbits, and I frequently check my iPhone to see how far I’ve walked or how many steps I have taken. My most recent acquisition is an Oura (smart ring, third generation), which includes my first sleep tracker.
Sleep trackers are not unique to the Oura Ring; they are included on many of the newer activity trackers and smart watches, but the design and breakdown of daily sleep, activity, and readiness scores are hallmarks of Oura Rings.
The ring generates data for different phases of sleep, movements, oxygen saturation, disturbances in breathing, heart rate, and heart rate variability. I began to wonder how useful this information would be clinically and whether it might be helpful in either the diagnosis or treatment of sleep disorders.
David Neubauer, MD, is a psychiatrist at the Johns Hopkins Sleep Disorders Center. “Sleep tracking devices are more than just toys but less than medical devices. They do have clinical utility and might show findings that warrant further medical workup,” Dr. Neubauer said. “It is impressive that these devices estimate sleep as well as they do, but there is a problem with how they divide sleep stages that can lead people to believe their sleep is worse than it really is.”
For more than 50 years, he explained, sleep researchers and clinicians have categorized sleep as non–rapid eye movement (NREM) sleep stages 1-4 and REM sleep. More recently, sleep was reorganized to N1, N2, and N3 (which combines the older stages 3 and 4, representing “deep sleep” or “slow wave sleep”) and REM sleep. We normally spend more time in N2 than the other stages. However, the device companies often categorize their sleep estimates as “light sleep,” “deep sleep,” or “REM.” With “light sleep,” they are lumping together N1 and N2 sleep, and this is misleading, said Dr. Neubauer. “Understandably, people often think that there is something wrong if their tracker reports they are spending a lot of time in light sleep, when actually their sleep may be entirely normal.”
Sleep tracker validity
A study by Massimiliano de Zambotti, PhD, and colleagues, “The Sleep of the Ring: Comparison of the ŌURA Sleep Tracker Against Polysomnography”, looked at sleep patterns of 41 adolescents and young adults and concluded that the second-generation tracker was accurate in terms of total sleep but underestimated time spent in N3 stage sleep by approximately 20 minutes while overestimating time spent in REM sleep by 17 minutes. They concluded that the ring had potential to be clinically useful but that further studies and validation were needed.
A larger study of the newest, third-generation Oura tracker, conducted by Altini and Kinnunen at Oura Health, found that the added sensors with the newer-generation ring led to improved accuracy, but they noted that the study was done with a healthy population and might not generalize to clinical populations.
Fernando Goes, MD, and Matthew Reid, PhD, both at Johns Hopkins, are working on a multicenter study using the Oura Ring and the mindLAMP app to look at the impact of sleep on mood in people with mood disorders as well as healthy controls. Dr. Reid said that “validation of sleep stages takes a hit when the ring is used in people with insomnia. We find it useful for total sleep time, but when you look at sleep architecture, the concordance is only 60%. And oxygen saturation measures are less accurate in people with dark skin.”
Clinical uses for sleep trackers
More accurate information might prove reassuring to patients. Dr. Goes added, “One use, for example, might be to help patients to limit or come off of long-term hypnotics with a more benign intervention that incorporates passive monitoring such as that in the Oura Ring. Some patients worry excessively about not being able to sleep, and sleep monitoring data can be helpful to reduce some of these concerns so patients can focus on safer interventions, such as cognitive behavioral therapy for insomnia.” Dr. Reid believes that wearable trackers have potential usefulness in monitoring sleep in patients with insomnia. “In insomnia, sleep state misperception is common. They are hyper-aroused, and they perceive that they are awake when in fact they are sleeping.”
Dr. Goes mentioned another use for sleep trackers in clinical settings: “In our inpatient units, the nurses open the door to look in on patients every hour to monitor and document if they are sleeping. If they look in and the patient isn’t moving, they will ask the patient to raise their hand, which of course is not going to help someone to fall back asleep.” Wearable devices might provide data on sleep without the risk of waking patients every hour through the night.
Not medical devices
However, Dr. Neubauer emphasized that current sleep trackers are not medical devices, saying “they may be measuring the same parameters that are measured with medical devices, for example pulse oximetry or sleep states, but there’s no simple answer yet to the question of whether the devices provide reliable data for clinical decision-making.”
Dr. Neubauer is skeptical about the accuracy of some of the measures the device provides. “I would not use the information from a consumer device to rule out obstructive sleep apnea based on good oxygen saturation numbers. So much depends on the history – snoring, gasping awakenings, reports from bed partners, and daytime sleepiness. These devices do not measure respiratory effort or nasal airflow as sleep studies do. But big drops in oxygen saturation from a consumer device certainly warrant attention for further evaluation.” Dr. Neubauer also noted that the parameters on sleep trackers do not differentiate between central or obstructive sleep apnea and that insurers won’t pay for continuous positive airway pressure to treat sleep apnea without a sleep study.
I enjoy looking at the data, even knowing that they are not entirely accurate. and we may find more clinical uses for these devices. For now, I’m off to get more exercise, at the suggestion of my tracker!
Dinah Miller, MD, is assistant professor of psychiatry and behavioral sciences, Johns Hopkins Medicine, Baltimore.
A version of this article first appeared on Medscape.com.
Who doesn’t love data, especially their own? With that thought in mind, over the years I have owned several activity trackers, including at least two Fitbits, and I frequently check my iPhone to see how far I’ve walked or how many steps I have taken. My most recent acquisition is an Oura (smart ring, third generation), which includes my first sleep tracker.
Sleep trackers are not unique to the Oura Ring; they are included on many of the newer activity trackers and smart watches, but the design and breakdown of daily sleep, activity, and readiness scores are hallmarks of Oura Rings.
The ring generates data for different phases of sleep, movements, oxygen saturation, disturbances in breathing, heart rate, and heart rate variability. I began to wonder how useful this information would be clinically and whether it might be helpful in either the diagnosis or treatment of sleep disorders.
David Neubauer, MD, is a psychiatrist at the Johns Hopkins Sleep Disorders Center. “Sleep tracking devices are more than just toys but less than medical devices. They do have clinical utility and might show findings that warrant further medical workup,” Dr. Neubauer said. “It is impressive that these devices estimate sleep as well as they do, but there is a problem with how they divide sleep stages that can lead people to believe their sleep is worse than it really is.”
For more than 50 years, he explained, sleep researchers and clinicians have categorized sleep as non–rapid eye movement (NREM) sleep stages 1-4 and REM sleep. More recently, sleep was reorganized to N1, N2, and N3 (which combines the older stages 3 and 4, representing “deep sleep” or “slow wave sleep”) and REM sleep. We normally spend more time in N2 than the other stages. However, the device companies often categorize their sleep estimates as “light sleep,” “deep sleep,” or “REM.” With “light sleep,” they are lumping together N1 and N2 sleep, and this is misleading, said Dr. Neubauer. “Understandably, people often think that there is something wrong if their tracker reports they are spending a lot of time in light sleep, when actually their sleep may be entirely normal.”
Sleep tracker validity
A study by Massimiliano de Zambotti, PhD, and colleagues, “The Sleep of the Ring: Comparison of the ŌURA Sleep Tracker Against Polysomnography”, looked at sleep patterns of 41 adolescents and young adults and concluded that the second-generation tracker was accurate in terms of total sleep but underestimated time spent in N3 stage sleep by approximately 20 minutes while overestimating time spent in REM sleep by 17 minutes. They concluded that the ring had potential to be clinically useful but that further studies and validation were needed.
A larger study of the newest, third-generation Oura tracker, conducted by Altini and Kinnunen at Oura Health, found that the added sensors with the newer-generation ring led to improved accuracy, but they noted that the study was done with a healthy population and might not generalize to clinical populations.
Fernando Goes, MD, and Matthew Reid, PhD, both at Johns Hopkins, are working on a multicenter study using the Oura Ring and the mindLAMP app to look at the impact of sleep on mood in people with mood disorders as well as healthy controls. Dr. Reid said that “validation of sleep stages takes a hit when the ring is used in people with insomnia. We find it useful for total sleep time, but when you look at sleep architecture, the concordance is only 60%. And oxygen saturation measures are less accurate in people with dark skin.”
Clinical uses for sleep trackers
More accurate information might prove reassuring to patients. Dr. Goes added, “One use, for example, might be to help patients to limit or come off of long-term hypnotics with a more benign intervention that incorporates passive monitoring such as that in the Oura Ring. Some patients worry excessively about not being able to sleep, and sleep monitoring data can be helpful to reduce some of these concerns so patients can focus on safer interventions, such as cognitive behavioral therapy for insomnia.” Dr. Reid believes that wearable trackers have potential usefulness in monitoring sleep in patients with insomnia. “In insomnia, sleep state misperception is common. They are hyper-aroused, and they perceive that they are awake when in fact they are sleeping.”
Dr. Goes mentioned another use for sleep trackers in clinical settings: “In our inpatient units, the nurses open the door to look in on patients every hour to monitor and document if they are sleeping. If they look in and the patient isn’t moving, they will ask the patient to raise their hand, which of course is not going to help someone to fall back asleep.” Wearable devices might provide data on sleep without the risk of waking patients every hour through the night.
Not medical devices
However, Dr. Neubauer emphasized that current sleep trackers are not medical devices, saying “they may be measuring the same parameters that are measured with medical devices, for example pulse oximetry or sleep states, but there’s no simple answer yet to the question of whether the devices provide reliable data for clinical decision-making.”
Dr. Neubauer is skeptical about the accuracy of some of the measures the device provides. “I would not use the information from a consumer device to rule out obstructive sleep apnea based on good oxygen saturation numbers. So much depends on the history – snoring, gasping awakenings, reports from bed partners, and daytime sleepiness. These devices do not measure respiratory effort or nasal airflow as sleep studies do. But big drops in oxygen saturation from a consumer device certainly warrant attention for further evaluation.” Dr. Neubauer also noted that the parameters on sleep trackers do not differentiate between central or obstructive sleep apnea and that insurers won’t pay for continuous positive airway pressure to treat sleep apnea without a sleep study.
I enjoy looking at the data, even knowing that they are not entirely accurate. and we may find more clinical uses for these devices. For now, I’m off to get more exercise, at the suggestion of my tracker!
Dinah Miller, MD, is assistant professor of psychiatry and behavioral sciences, Johns Hopkins Medicine, Baltimore.
A version of this article first appeared on Medscape.com.
Microplastics and health risks: What do we really know?
You eat a credit card’s worth of plastic in a week. That may bother you. But does it harm you?
The answer depends on who you ask. Awareness of microplastics in general is certainly increasing; the most recent news is the detection of microplastics in human breast milk. Other research has suggested that we may be consuming up to 5 grams of plastic each week from our food, water, and certain consumer products.
The World Health Organization has been releasing reports on microplastics and human health since 2019. Their most recent report was released in late August 2022.
“Although the limited data provide little evidence that nano- and microplastic particles have adverse effects in humans, there is increasing public awareness and an overwhelming consensus among all stakeholders that plastics do not belong in the environment, and measures should be taken to mitigate exposure,” the WHO said at the time.
The WHO can’t go beyond what the data shows, of course. If microplastics are wreaking long-term havoc in our bodies as we speak, science hasn’t connected the dots enough to definitively say “this is the problem.”
But some researchers are willing to speculate – and, at the very least, the risks are becoming impossible to ignore. Dick Vethaak, PhD, a microplastics researcher and emeritus professor of ecotoxicology at Vrije Universiteit, Amsterdam, is blunt, calling them “a plastic time bomb.”
The plastic problem
Every piece of plastic that has ever been created is still on our planet today, apart from what has been burned. Past estimates show we only recycle about 9% of all plastic, leaving 9 billion tons in our landfills, oceans, and ecosystems. For context, that amount is 1,500 times heavier than the Great Pyramid of Khufu.
New data is even more dire. A 2022 report from Greenpeace showed a 5% U.S. recycling rate in 2021, with a large portion of what consumers think of as “recycled” still winding up in garbage piles or bodies of water.
And this plastic doesn’t disappear. Instead, it breaks down into smaller and smaller pieces known as microplastics and nanoplastics.
Microplastics have been confirmed in human blood, lung tissue, colons, placentas, stool, and breast milk. But how they impact our health is still unknown.
To assess risk, we must ask: “How hazardous is the material?” said Flemming Cassee, PhD, professor of inhalation toxicology at Utrecht (the Netherlands) University and coauthor of the WHO’s recent microplastics report.
There are three potential hazards of microplastics: their physical presence in our bodies, what they’re made of, and what they carry. To determine the extent of these risks, we need to know how much we’re exposed to, said Dr. Cassee.
The first initiative to research the impact of microplastics on human health came from the European Union in 2018. Although microplastics were around before then, we were unable to detect them, said Dr. Cassee.
That’s the real problem: warned Dr. Vethaak.
What, exactly, are microplastics?
Microplastics are plastic particles between 5 mm and 100 nm in diameter, or the width of a pencil eraser and something 10 times thinner than a human hair. Anything smaller than that is known as a nanoplastic.
“Microplastics include a wide range of different materials, different sizes, different shapes, different densities, and different colors,” said Evangelos Danopoulos, PhD, a microplastics researcher at Hull York (England) Medical School.
“Primary” microplastics are manufactured to be small and used in things like cosmetics and paints. “Secondary” microplastics result from the breaking down of larger plastic materials, like water bottles and plastic bags.
Secondary microplastics are more diverse than primary microplastics and can take forms ranging from fibers shed from synthetic clothing (like polyester) to pieces of a plastic spoon left in our rivers, lakes, and oceans. Any plastic in the environment will eventually become a secondary microplastic as natural forces such as wind, water currents, and UV radiation break it down into smaller and smaller pieces.
Plastic is a diverse material. Heather Leslie, PhD, senior researcher in Vrije Universiteit’s department of environment and health, likens it to spaghetti with sauce. The noodles are the long polymer backbone that all plastic shares. The sauces are “the pigments, the antioxidants, the flame retardants, etc., that make it functional,” she said.
What makes microplastics dangerous?
There are more than 10,000 different chemicals, or “sauces,” used to alter a plastic’s physical characteristics – making it softer, more rigid, or more flexible, said Hanna Dusza, PhD, of the Institute for Risk Assessment Sciences at Utrecht University.
As plastics degrade and become microplastics, these chemicals likely remain. Recent research has shown that microplastics leach these chemicals locally in human tissues, or other areas of accumulation, said Dr. Dusza. Some 2,400 of the 10,000 chemical additives were classified as substances of potential concern, meeting the European Union’s criteria for persistence, bioaccumulation, or toxicity.
Many of these chemicals also act as endocrine-disrupting compounds, or toxicants that imitate hormones when they enter the body. Hormones are active at very low concentrations in your bloodstream, explained Dr. Leslie. To your body, some chemical additives in plastic resemble hormones, so the body responds.
“Sometimes even a low dose of some of these additives can cause unwanted effects,” said Dr. Leslie.
Bisphenol A (BPA), for example, is one of the more infamous endocrine disruptors. It is used as an additive to make plastics more rigid and can be found in any number of plastic products, though areas of concern have been plastic water bottles, baby bottles, and the protective coatings in canned foods.
BPA may mimic estrogen, the female sex hormone essential for reproduction, neurodevelopment, and bone density. In men, estrogen regulates sperm count, sex drive, and erectile function. BPA exposure has been linked with – but not proven to cause – multiple cancer types, ADHD, obesity, and low sperm count. Most everyone has some amount of BPA circulating within their blood, but microplastics may retain BPA as they degrade, potentially increasing our exposure, leading to its unwanted consequences, said Dr. Dusza.
And BPA is just one of those 2,400 substances of “potential concern.”
The inflammation problem
A potentially larger health issue emerges from our bodies yet again doing what they are supposed to do when encountering microplastics. Particles can trigger an immune response when they enter your bloodstream, explains Nienke Vrisekoop, PhD, assistant professor at UMC Utrecht.
White blood cells have no issue breaking down things like bacteria, but microplastics cannot be degraded. When a white blood cell engulfs a certain mass of microplastics – either many small particles or a singular large one – it dies, releasing its enzymes and causing local inflammation.
Meanwhile, the plastic particle remains. So more white blood cells attack.
“This triggers continual activation that can result in various adverse effects, including oxidative stress and the release of cytokines that trigger inflammatory reactions, said Dr. Vethaak.
And “chronic inflammation is the prelude to chronic diseases,” said Dr. Leslie. “Every chronic disease, like cancer, heart disease, and even neuropsychiatric diseases like Parkinson’s or major depression, begins with inflammation.”
Meanwhile, inhaling microplastic particles can lead to respiratory diseases and cancer.
“The smallest particles – less than one-tenth of a micrometer – penetrate deep into the lungs and even into the bloodstream, causing damage to the heart, blood vessels and brain,” said Dr. Vetaak. “The only direct evidence comes from workers in the textile and plastic industries that had been exposed to very high amounts of plastic fibrous dust.”
Microplastics as carriers
Microplastics can also pick up harmful substances and deliver them into your body.
“When they’re in an environment, they basically can suck up [chemicals] like a sponge,” said Dr. Dusza. “These chemicals are known environmental pollutants, like pesticides, fluorinated compounds, flame retardants, and so on.”
Once in the body, these chemicals can be released, potentially leading to cancer, chronic inflammation, or other unknown effects.
Particles can also act as a vector for microbes, bacteria, and viruses. A September 2022 study found that infectious viruses can survive for 3 days in fresh water by “hitchhiking” on microplastics. Their porous nature provides microbes with a perfect environment in which to live and reproduce, said Dr. Dusza. If you ingest the plastics, you ingest the microbes.
How to minimize exposure
There is no way to avoid microplastics. They’re in the air we breathe, the products we use, the water we drink, and the food we eat.
Dr. Danopoulos reviewed 72 studies to quantify our consumption of microplastics in drinking water, salt, and seafood.
“We are exposed to millions of microplastics every year, and I was only looking at three food sources, so there are really a lot more,” he said. “Once plastic waste is mismanaged and it enters the environment, there is very little we can do to extract it.”
That said, we can take steps to lower our exposure and keep the problem from getting worse.
Water filtration is one option, though it is not perfect. Research has shown that municipal water treatment can be effective. An October 2021 study found that two methods – electrocoagulation-electroflotation and membrane filtration – can be 100% effective in removing microplastics from treated water. The problem? Not all municipal water treatment uses these methods – and you would have to investigate to find out if your locality does.
As for at-home filtration methods, they can be effective but can also be dicey. Some consumer brands claim they remove microplastics, but how well depends on not just the type of filter but the size of the particles in the water. Meanwhile, how do you know if a filter is working on your water without testing it, something few people will do? Best not to take a brand’s claims on face-value, but look for independent testing on at-home brands.
A longer-term project: Reduce our risk by reusing and recycling plastic waste. Limiting our consumption of plastic, especially single use plastic, decreases the amount available to become micro- and nanoplastics.
We must all learn to not treat plastic as waste, but rather as a renewable material, said Dr. Cassee. But if that seems like a tall order, it’s because it is.
“You’re a human being and you have a voice and there are a lot of other humans out there with voices,” said Dr. Leslie.
“You sign a petition in your community. You talk about it with your friends at the pub. If you’re a teacher, you discuss it in your class. You call your elected representatives and tell them what you think and how you want them to vote on bills.”
When people start working together, you can really amplify that voice, said Dr. Leslie.
What’s the bottom line right now, today?
Numerous sources have declared microplastics do not impact human health. But that’s largely because no direct evidence of this exists yet.
Even the WHO in its report suggests that progress must happen if we’re to fully understand the scope of the problem.
“Strengthening of the evidence necessary for reliable characterization and quantification of the risks to human health posed by [nano- and microplastics] will require active participation by all stakeholders,” it said.
All researchers interviewed for this article agree we don’t have enough evidence to draw any definite conclusions. But “if you look at the wrong endpoints, things will look safe, until you look at the endpoint where it’s really causing the problem,” said Dr. Leslie.
We must research our blind spots and continually ask: Where could we be wrong?
“It is a problem; it’s not going to go away,” said Dr. Danopoulos. “It’s going to get worse, and will continue to get worse, not by something that we are doing now but by something we did 5 years ago.”
Perhaps the question to be asked, then, is the hardest to answer: Are we willing to wait for the science?
A version of this article first appeared on WebMD.com.
You eat a credit card’s worth of plastic in a week. That may bother you. But does it harm you?
The answer depends on who you ask. Awareness of microplastics in general is certainly increasing; the most recent news is the detection of microplastics in human breast milk. Other research has suggested that we may be consuming up to 5 grams of plastic each week from our food, water, and certain consumer products.
The World Health Organization has been releasing reports on microplastics and human health since 2019. Their most recent report was released in late August 2022.
“Although the limited data provide little evidence that nano- and microplastic particles have adverse effects in humans, there is increasing public awareness and an overwhelming consensus among all stakeholders that plastics do not belong in the environment, and measures should be taken to mitigate exposure,” the WHO said at the time.
The WHO can’t go beyond what the data shows, of course. If microplastics are wreaking long-term havoc in our bodies as we speak, science hasn’t connected the dots enough to definitively say “this is the problem.”
But some researchers are willing to speculate – and, at the very least, the risks are becoming impossible to ignore. Dick Vethaak, PhD, a microplastics researcher and emeritus professor of ecotoxicology at Vrije Universiteit, Amsterdam, is blunt, calling them “a plastic time bomb.”
The plastic problem
Every piece of plastic that has ever been created is still on our planet today, apart from what has been burned. Past estimates show we only recycle about 9% of all plastic, leaving 9 billion tons in our landfills, oceans, and ecosystems. For context, that amount is 1,500 times heavier than the Great Pyramid of Khufu.
New data is even more dire. A 2022 report from Greenpeace showed a 5% U.S. recycling rate in 2021, with a large portion of what consumers think of as “recycled” still winding up in garbage piles or bodies of water.
And this plastic doesn’t disappear. Instead, it breaks down into smaller and smaller pieces known as microplastics and nanoplastics.
Microplastics have been confirmed in human blood, lung tissue, colons, placentas, stool, and breast milk. But how they impact our health is still unknown.
To assess risk, we must ask: “How hazardous is the material?” said Flemming Cassee, PhD, professor of inhalation toxicology at Utrecht (the Netherlands) University and coauthor of the WHO’s recent microplastics report.
There are three potential hazards of microplastics: their physical presence in our bodies, what they’re made of, and what they carry. To determine the extent of these risks, we need to know how much we’re exposed to, said Dr. Cassee.
The first initiative to research the impact of microplastics on human health came from the European Union in 2018. Although microplastics were around before then, we were unable to detect them, said Dr. Cassee.
That’s the real problem: warned Dr. Vethaak.
What, exactly, are microplastics?
Microplastics are plastic particles between 5 mm and 100 nm in diameter, or the width of a pencil eraser and something 10 times thinner than a human hair. Anything smaller than that is known as a nanoplastic.
“Microplastics include a wide range of different materials, different sizes, different shapes, different densities, and different colors,” said Evangelos Danopoulos, PhD, a microplastics researcher at Hull York (England) Medical School.
“Primary” microplastics are manufactured to be small and used in things like cosmetics and paints. “Secondary” microplastics result from the breaking down of larger plastic materials, like water bottles and plastic bags.
Secondary microplastics are more diverse than primary microplastics and can take forms ranging from fibers shed from synthetic clothing (like polyester) to pieces of a plastic spoon left in our rivers, lakes, and oceans. Any plastic in the environment will eventually become a secondary microplastic as natural forces such as wind, water currents, and UV radiation break it down into smaller and smaller pieces.
Plastic is a diverse material. Heather Leslie, PhD, senior researcher in Vrije Universiteit’s department of environment and health, likens it to spaghetti with sauce. The noodles are the long polymer backbone that all plastic shares. The sauces are “the pigments, the antioxidants, the flame retardants, etc., that make it functional,” she said.
What makes microplastics dangerous?
There are more than 10,000 different chemicals, or “sauces,” used to alter a plastic’s physical characteristics – making it softer, more rigid, or more flexible, said Hanna Dusza, PhD, of the Institute for Risk Assessment Sciences at Utrecht University.
As plastics degrade and become microplastics, these chemicals likely remain. Recent research has shown that microplastics leach these chemicals locally in human tissues, or other areas of accumulation, said Dr. Dusza. Some 2,400 of the 10,000 chemical additives were classified as substances of potential concern, meeting the European Union’s criteria for persistence, bioaccumulation, or toxicity.
Many of these chemicals also act as endocrine-disrupting compounds, or toxicants that imitate hormones when they enter the body. Hormones are active at very low concentrations in your bloodstream, explained Dr. Leslie. To your body, some chemical additives in plastic resemble hormones, so the body responds.
“Sometimes even a low dose of some of these additives can cause unwanted effects,” said Dr. Leslie.
Bisphenol A (BPA), for example, is one of the more infamous endocrine disruptors. It is used as an additive to make plastics more rigid and can be found in any number of plastic products, though areas of concern have been plastic water bottles, baby bottles, and the protective coatings in canned foods.
BPA may mimic estrogen, the female sex hormone essential for reproduction, neurodevelopment, and bone density. In men, estrogen regulates sperm count, sex drive, and erectile function. BPA exposure has been linked with – but not proven to cause – multiple cancer types, ADHD, obesity, and low sperm count. Most everyone has some amount of BPA circulating within their blood, but microplastics may retain BPA as they degrade, potentially increasing our exposure, leading to its unwanted consequences, said Dr. Dusza.
And BPA is just one of those 2,400 substances of “potential concern.”
The inflammation problem
A potentially larger health issue emerges from our bodies yet again doing what they are supposed to do when encountering microplastics. Particles can trigger an immune response when they enter your bloodstream, explains Nienke Vrisekoop, PhD, assistant professor at UMC Utrecht.
White blood cells have no issue breaking down things like bacteria, but microplastics cannot be degraded. When a white blood cell engulfs a certain mass of microplastics – either many small particles or a singular large one – it dies, releasing its enzymes and causing local inflammation.
Meanwhile, the plastic particle remains. So more white blood cells attack.
“This triggers continual activation that can result in various adverse effects, including oxidative stress and the release of cytokines that trigger inflammatory reactions, said Dr. Vethaak.
And “chronic inflammation is the prelude to chronic diseases,” said Dr. Leslie. “Every chronic disease, like cancer, heart disease, and even neuropsychiatric diseases like Parkinson’s or major depression, begins with inflammation.”
Meanwhile, inhaling microplastic particles can lead to respiratory diseases and cancer.
“The smallest particles – less than one-tenth of a micrometer – penetrate deep into the lungs and even into the bloodstream, causing damage to the heart, blood vessels and brain,” said Dr. Vetaak. “The only direct evidence comes from workers in the textile and plastic industries that had been exposed to very high amounts of plastic fibrous dust.”
Microplastics as carriers
Microplastics can also pick up harmful substances and deliver them into your body.
“When they’re in an environment, they basically can suck up [chemicals] like a sponge,” said Dr. Dusza. “These chemicals are known environmental pollutants, like pesticides, fluorinated compounds, flame retardants, and so on.”
Once in the body, these chemicals can be released, potentially leading to cancer, chronic inflammation, or other unknown effects.
Particles can also act as a vector for microbes, bacteria, and viruses. A September 2022 study found that infectious viruses can survive for 3 days in fresh water by “hitchhiking” on microplastics. Their porous nature provides microbes with a perfect environment in which to live and reproduce, said Dr. Dusza. If you ingest the plastics, you ingest the microbes.
How to minimize exposure
There is no way to avoid microplastics. They’re in the air we breathe, the products we use, the water we drink, and the food we eat.
Dr. Danopoulos reviewed 72 studies to quantify our consumption of microplastics in drinking water, salt, and seafood.
“We are exposed to millions of microplastics every year, and I was only looking at three food sources, so there are really a lot more,” he said. “Once plastic waste is mismanaged and it enters the environment, there is very little we can do to extract it.”
That said, we can take steps to lower our exposure and keep the problem from getting worse.
Water filtration is one option, though it is not perfect. Research has shown that municipal water treatment can be effective. An October 2021 study found that two methods – electrocoagulation-electroflotation and membrane filtration – can be 100% effective in removing microplastics from treated water. The problem? Not all municipal water treatment uses these methods – and you would have to investigate to find out if your locality does.
As for at-home filtration methods, they can be effective but can also be dicey. Some consumer brands claim they remove microplastics, but how well depends on not just the type of filter but the size of the particles in the water. Meanwhile, how do you know if a filter is working on your water without testing it, something few people will do? Best not to take a brand’s claims on face-value, but look for independent testing on at-home brands.
A longer-term project: Reduce our risk by reusing and recycling plastic waste. Limiting our consumption of plastic, especially single use plastic, decreases the amount available to become micro- and nanoplastics.
We must all learn to not treat plastic as waste, but rather as a renewable material, said Dr. Cassee. But if that seems like a tall order, it’s because it is.
“You’re a human being and you have a voice and there are a lot of other humans out there with voices,” said Dr. Leslie.
“You sign a petition in your community. You talk about it with your friends at the pub. If you’re a teacher, you discuss it in your class. You call your elected representatives and tell them what you think and how you want them to vote on bills.”
When people start working together, you can really amplify that voice, said Dr. Leslie.
What’s the bottom line right now, today?
Numerous sources have declared microplastics do not impact human health. But that’s largely because no direct evidence of this exists yet.
Even the WHO in its report suggests that progress must happen if we’re to fully understand the scope of the problem.
“Strengthening of the evidence necessary for reliable characterization and quantification of the risks to human health posed by [nano- and microplastics] will require active participation by all stakeholders,” it said.
All researchers interviewed for this article agree we don’t have enough evidence to draw any definite conclusions. But “if you look at the wrong endpoints, things will look safe, until you look at the endpoint where it’s really causing the problem,” said Dr. Leslie.
We must research our blind spots and continually ask: Where could we be wrong?
“It is a problem; it’s not going to go away,” said Dr. Danopoulos. “It’s going to get worse, and will continue to get worse, not by something that we are doing now but by something we did 5 years ago.”
Perhaps the question to be asked, then, is the hardest to answer: Are we willing to wait for the science?
A version of this article first appeared on WebMD.com.
You eat a credit card’s worth of plastic in a week. That may bother you. But does it harm you?
The answer depends on who you ask. Awareness of microplastics in general is certainly increasing; the most recent news is the detection of microplastics in human breast milk. Other research has suggested that we may be consuming up to 5 grams of plastic each week from our food, water, and certain consumer products.
The World Health Organization has been releasing reports on microplastics and human health since 2019. Their most recent report was released in late August 2022.
“Although the limited data provide little evidence that nano- and microplastic particles have adverse effects in humans, there is increasing public awareness and an overwhelming consensus among all stakeholders that plastics do not belong in the environment, and measures should be taken to mitigate exposure,” the WHO said at the time.
The WHO can’t go beyond what the data shows, of course. If microplastics are wreaking long-term havoc in our bodies as we speak, science hasn’t connected the dots enough to definitively say “this is the problem.”
But some researchers are willing to speculate – and, at the very least, the risks are becoming impossible to ignore. Dick Vethaak, PhD, a microplastics researcher and emeritus professor of ecotoxicology at Vrije Universiteit, Amsterdam, is blunt, calling them “a plastic time bomb.”
The plastic problem
Every piece of plastic that has ever been created is still on our planet today, apart from what has been burned. Past estimates show we only recycle about 9% of all plastic, leaving 9 billion tons in our landfills, oceans, and ecosystems. For context, that amount is 1,500 times heavier than the Great Pyramid of Khufu.
New data is even more dire. A 2022 report from Greenpeace showed a 5% U.S. recycling rate in 2021, with a large portion of what consumers think of as “recycled” still winding up in garbage piles or bodies of water.
And this plastic doesn’t disappear. Instead, it breaks down into smaller and smaller pieces known as microplastics and nanoplastics.
Microplastics have been confirmed in human blood, lung tissue, colons, placentas, stool, and breast milk. But how they impact our health is still unknown.
To assess risk, we must ask: “How hazardous is the material?” said Flemming Cassee, PhD, professor of inhalation toxicology at Utrecht (the Netherlands) University and coauthor of the WHO’s recent microplastics report.
There are three potential hazards of microplastics: their physical presence in our bodies, what they’re made of, and what they carry. To determine the extent of these risks, we need to know how much we’re exposed to, said Dr. Cassee.
The first initiative to research the impact of microplastics on human health came from the European Union in 2018. Although microplastics were around before then, we were unable to detect them, said Dr. Cassee.
That’s the real problem: warned Dr. Vethaak.
What, exactly, are microplastics?
Microplastics are plastic particles between 5 mm and 100 nm in diameter, or the width of a pencil eraser and something 10 times thinner than a human hair. Anything smaller than that is known as a nanoplastic.
“Microplastics include a wide range of different materials, different sizes, different shapes, different densities, and different colors,” said Evangelos Danopoulos, PhD, a microplastics researcher at Hull York (England) Medical School.
“Primary” microplastics are manufactured to be small and used in things like cosmetics and paints. “Secondary” microplastics result from the breaking down of larger plastic materials, like water bottles and plastic bags.
Secondary microplastics are more diverse than primary microplastics and can take forms ranging from fibers shed from synthetic clothing (like polyester) to pieces of a plastic spoon left in our rivers, lakes, and oceans. Any plastic in the environment will eventually become a secondary microplastic as natural forces such as wind, water currents, and UV radiation break it down into smaller and smaller pieces.
Plastic is a diverse material. Heather Leslie, PhD, senior researcher in Vrije Universiteit’s department of environment and health, likens it to spaghetti with sauce. The noodles are the long polymer backbone that all plastic shares. The sauces are “the pigments, the antioxidants, the flame retardants, etc., that make it functional,” she said.
What makes microplastics dangerous?
There are more than 10,000 different chemicals, or “sauces,” used to alter a plastic’s physical characteristics – making it softer, more rigid, or more flexible, said Hanna Dusza, PhD, of the Institute for Risk Assessment Sciences at Utrecht University.
As plastics degrade and become microplastics, these chemicals likely remain. Recent research has shown that microplastics leach these chemicals locally in human tissues, or other areas of accumulation, said Dr. Dusza. Some 2,400 of the 10,000 chemical additives were classified as substances of potential concern, meeting the European Union’s criteria for persistence, bioaccumulation, or toxicity.
Many of these chemicals also act as endocrine-disrupting compounds, or toxicants that imitate hormones when they enter the body. Hormones are active at very low concentrations in your bloodstream, explained Dr. Leslie. To your body, some chemical additives in plastic resemble hormones, so the body responds.
“Sometimes even a low dose of some of these additives can cause unwanted effects,” said Dr. Leslie.
Bisphenol A (BPA), for example, is one of the more infamous endocrine disruptors. It is used as an additive to make plastics more rigid and can be found in any number of plastic products, though areas of concern have been plastic water bottles, baby bottles, and the protective coatings in canned foods.
BPA may mimic estrogen, the female sex hormone essential for reproduction, neurodevelopment, and bone density. In men, estrogen regulates sperm count, sex drive, and erectile function. BPA exposure has been linked with – but not proven to cause – multiple cancer types, ADHD, obesity, and low sperm count. Most everyone has some amount of BPA circulating within their blood, but microplastics may retain BPA as they degrade, potentially increasing our exposure, leading to its unwanted consequences, said Dr. Dusza.
And BPA is just one of those 2,400 substances of “potential concern.”
The inflammation problem
A potentially larger health issue emerges from our bodies yet again doing what they are supposed to do when encountering microplastics. Particles can trigger an immune response when they enter your bloodstream, explains Nienke Vrisekoop, PhD, assistant professor at UMC Utrecht.
White blood cells have no issue breaking down things like bacteria, but microplastics cannot be degraded. When a white blood cell engulfs a certain mass of microplastics – either many small particles or a singular large one – it dies, releasing its enzymes and causing local inflammation.
Meanwhile, the plastic particle remains. So more white blood cells attack.
“This triggers continual activation that can result in various adverse effects, including oxidative stress and the release of cytokines that trigger inflammatory reactions, said Dr. Vethaak.
And “chronic inflammation is the prelude to chronic diseases,” said Dr. Leslie. “Every chronic disease, like cancer, heart disease, and even neuropsychiatric diseases like Parkinson’s or major depression, begins with inflammation.”
Meanwhile, inhaling microplastic particles can lead to respiratory diseases and cancer.
“The smallest particles – less than one-tenth of a micrometer – penetrate deep into the lungs and even into the bloodstream, causing damage to the heart, blood vessels and brain,” said Dr. Vetaak. “The only direct evidence comes from workers in the textile and plastic industries that had been exposed to very high amounts of plastic fibrous dust.”
Microplastics as carriers
Microplastics can also pick up harmful substances and deliver them into your body.
“When they’re in an environment, they basically can suck up [chemicals] like a sponge,” said Dr. Dusza. “These chemicals are known environmental pollutants, like pesticides, fluorinated compounds, flame retardants, and so on.”
Once in the body, these chemicals can be released, potentially leading to cancer, chronic inflammation, or other unknown effects.
Particles can also act as a vector for microbes, bacteria, and viruses. A September 2022 study found that infectious viruses can survive for 3 days in fresh water by “hitchhiking” on microplastics. Their porous nature provides microbes with a perfect environment in which to live and reproduce, said Dr. Dusza. If you ingest the plastics, you ingest the microbes.
How to minimize exposure
There is no way to avoid microplastics. They’re in the air we breathe, the products we use, the water we drink, and the food we eat.
Dr. Danopoulos reviewed 72 studies to quantify our consumption of microplastics in drinking water, salt, and seafood.
“We are exposed to millions of microplastics every year, and I was only looking at three food sources, so there are really a lot more,” he said. “Once plastic waste is mismanaged and it enters the environment, there is very little we can do to extract it.”
That said, we can take steps to lower our exposure and keep the problem from getting worse.
Water filtration is one option, though it is not perfect. Research has shown that municipal water treatment can be effective. An October 2021 study found that two methods – electrocoagulation-electroflotation and membrane filtration – can be 100% effective in removing microplastics from treated water. The problem? Not all municipal water treatment uses these methods – and you would have to investigate to find out if your locality does.
As for at-home filtration methods, they can be effective but can also be dicey. Some consumer brands claim they remove microplastics, but how well depends on not just the type of filter but the size of the particles in the water. Meanwhile, how do you know if a filter is working on your water without testing it, something few people will do? Best not to take a brand’s claims on face-value, but look for independent testing on at-home brands.
A longer-term project: Reduce our risk by reusing and recycling plastic waste. Limiting our consumption of plastic, especially single use plastic, decreases the amount available to become micro- and nanoplastics.
We must all learn to not treat plastic as waste, but rather as a renewable material, said Dr. Cassee. But if that seems like a tall order, it’s because it is.
“You’re a human being and you have a voice and there are a lot of other humans out there with voices,” said Dr. Leslie.
“You sign a petition in your community. You talk about it with your friends at the pub. If you’re a teacher, you discuss it in your class. You call your elected representatives and tell them what you think and how you want them to vote on bills.”
When people start working together, you can really amplify that voice, said Dr. Leslie.
What’s the bottom line right now, today?
Numerous sources have declared microplastics do not impact human health. But that’s largely because no direct evidence of this exists yet.
Even the WHO in its report suggests that progress must happen if we’re to fully understand the scope of the problem.
“Strengthening of the evidence necessary for reliable characterization and quantification of the risks to human health posed by [nano- and microplastics] will require active participation by all stakeholders,” it said.
All researchers interviewed for this article agree we don’t have enough evidence to draw any definite conclusions. But “if you look at the wrong endpoints, things will look safe, until you look at the endpoint where it’s really causing the problem,” said Dr. Leslie.
We must research our blind spots and continually ask: Where could we be wrong?
“It is a problem; it’s not going to go away,” said Dr. Danopoulos. “It’s going to get worse, and will continue to get worse, not by something that we are doing now but by something we did 5 years ago.”
Perhaps the question to be asked, then, is the hardest to answer: Are we willing to wait for the science?
A version of this article first appeared on WebMD.com.
Black Veterans Less Likely to Get COVID-Specific Treatments at VAMCs
Black veterans hospitalized with COVID-19 were less likely to be treated with evidence-based treatments, in a study conducted in 130 US Department of Veterans Affairs (VA) medical centers between March 1, 2020, and February 28, 2022.
The study involved 12,135 Black veterans and 40,717 White veterans. Most patients hospitalized during period 1 (March-September 2020) were Black veterans and the proportion of White patients increased over time. The latter 3 periods, which included the Delta- and Omicron-predominant periods, saw the most admissions.
Controlling for the site of treatment, Black patients were equally likely to be admitted to the intensive care unit (40% vs 43%). However, they were less likely to receive steroids, remdesivir, or immunomodulatory drugs.
The researchers say their data confirm other findings from 41 US health care systems participating in the National Patient-Centered Clinical Research Network (PCORNet), which found lower use of monoclonal antibody treatment for COVID infection for patients who identified as Asian, Black, Hispanic, American Indian or Alaska Native, Native Hawaiian or other Pacific Islander, or multiple races.
The researchers did not observe consistent differences in clinical outcomes between Black and White patients. After adjusting for demographics, chronic health conditions, severity of acute illness, and receipt of COVID-19–specific treatments, there was no association of Black race with hospital mortality or 30-day readmission. Black and White patients had a similar burden of preexisting health conditions. Of 38,782 patients discharged, 14% were readmitted within 30 days; the median time to readmission for both groups was 9 days.
Differences in care were partially explained by within- and between-hospital differences, the researchers say. They also cite research that demonstrated a poorer quality of care for hospitals with higher monthly COVID-19 discharges and hospital size.
The study results contradict the assumptions that differences in inpatient treatment by race and ethnicity may be due to differences in clinical indications for medication use based on age and comorbidities, such as chronic kidney or liver disease, the researchers say. For one thing, the VA issued a systemwide COVID-19 response plan that included specific treatment guidelines and distribution plans. But they also point to recent reports that have suggested that occult hypoxemia not detected by pulse oximetry occurs “far more often in Black patients than White patients,” which could result in delayed or missed opportunities to treat patients with COVID-19.
Black veterans hospitalized with COVID-19 were less likely to be treated with evidence-based treatments, in a study conducted in 130 US Department of Veterans Affairs (VA) medical centers between March 1, 2020, and February 28, 2022.
The study involved 12,135 Black veterans and 40,717 White veterans. Most patients hospitalized during period 1 (March-September 2020) were Black veterans and the proportion of White patients increased over time. The latter 3 periods, which included the Delta- and Omicron-predominant periods, saw the most admissions.
Controlling for the site of treatment, Black patients were equally likely to be admitted to the intensive care unit (40% vs 43%). However, they were less likely to receive steroids, remdesivir, or immunomodulatory drugs.
The researchers say their data confirm other findings from 41 US health care systems participating in the National Patient-Centered Clinical Research Network (PCORNet), which found lower use of monoclonal antibody treatment for COVID infection for patients who identified as Asian, Black, Hispanic, American Indian or Alaska Native, Native Hawaiian or other Pacific Islander, or multiple races.
The researchers did not observe consistent differences in clinical outcomes between Black and White patients. After adjusting for demographics, chronic health conditions, severity of acute illness, and receipt of COVID-19–specific treatments, there was no association of Black race with hospital mortality or 30-day readmission. Black and White patients had a similar burden of preexisting health conditions. Of 38,782 patients discharged, 14% were readmitted within 30 days; the median time to readmission for both groups was 9 days.
Differences in care were partially explained by within- and between-hospital differences, the researchers say. They also cite research that demonstrated a poorer quality of care for hospitals with higher monthly COVID-19 discharges and hospital size.
The study results contradict the assumptions that differences in inpatient treatment by race and ethnicity may be due to differences in clinical indications for medication use based on age and comorbidities, such as chronic kidney or liver disease, the researchers say. For one thing, the VA issued a systemwide COVID-19 response plan that included specific treatment guidelines and distribution plans. But they also point to recent reports that have suggested that occult hypoxemia not detected by pulse oximetry occurs “far more often in Black patients than White patients,” which could result in delayed or missed opportunities to treat patients with COVID-19.
Black veterans hospitalized with COVID-19 were less likely to be treated with evidence-based treatments, in a study conducted in 130 US Department of Veterans Affairs (VA) medical centers between March 1, 2020, and February 28, 2022.
The study involved 12,135 Black veterans and 40,717 White veterans. Most patients hospitalized during period 1 (March-September 2020) were Black veterans and the proportion of White patients increased over time. The latter 3 periods, which included the Delta- and Omicron-predominant periods, saw the most admissions.
Controlling for the site of treatment, Black patients were equally likely to be admitted to the intensive care unit (40% vs 43%). However, they were less likely to receive steroids, remdesivir, or immunomodulatory drugs.
The researchers say their data confirm other findings from 41 US health care systems participating in the National Patient-Centered Clinical Research Network (PCORNet), which found lower use of monoclonal antibody treatment for COVID infection for patients who identified as Asian, Black, Hispanic, American Indian or Alaska Native, Native Hawaiian or other Pacific Islander, or multiple races.
The researchers did not observe consistent differences in clinical outcomes between Black and White patients. After adjusting for demographics, chronic health conditions, severity of acute illness, and receipt of COVID-19–specific treatments, there was no association of Black race with hospital mortality or 30-day readmission. Black and White patients had a similar burden of preexisting health conditions. Of 38,782 patients discharged, 14% were readmitted within 30 days; the median time to readmission for both groups was 9 days.
Differences in care were partially explained by within- and between-hospital differences, the researchers say. They also cite research that demonstrated a poorer quality of care for hospitals with higher monthly COVID-19 discharges and hospital size.
The study results contradict the assumptions that differences in inpatient treatment by race and ethnicity may be due to differences in clinical indications for medication use based on age and comorbidities, such as chronic kidney or liver disease, the researchers say. For one thing, the VA issued a systemwide COVID-19 response plan that included specific treatment guidelines and distribution plans. But they also point to recent reports that have suggested that occult hypoxemia not detected by pulse oximetry occurs “far more often in Black patients than White patients,” which could result in delayed or missed opportunities to treat patients with COVID-19.
Combo thrombolytic approach fails to reduce ICH in stroke
A study evaluating a new approach using a combination of two thrombolytics designed to reduce bleeding risk in patients with acute ischemic stroke has not shown any benefit on the primary outcome of all intracranial hemorrhage (ICH).
However, there were some encouraging findings including a trend towards a reduction in symptomatic ICH, researchers report, and the combination approach did not show any depletion of fibrinogen levels, which suggests a potential lower bleeding risk.
“Although the main results of this study are neutral, we are encouraged that the combination approach with a low dose of alteplase followed by the new mutant pro-urokinase product looked as effective as full-dose alteplase alone, and there were some promising signs signaling a potential lower bleeding risk,” senior investigator, Diederik Dippel, MD, Erasmus University Medical Center, Rotterdam, the Netherlands, told this news organization.
The DUMAS study (Dual Thrombolytic Therapy With Mutant Pro-Urokinase and Low Dose Alteplase for Ischemic Stroke) was presented at the World Stroke Congress in Singapore by study coauthor Nadinda van der Ende, MD, also from Erasmus University Medical Center.
She pointed out that thrombolysis with intravenous alteplase increases the likelihood of a good outcome in acute ischemic stroke but can cause symptomatic intracranial hemorrhage, which can be associated with death and major disability.
Mutant pro-urokinase is a new thrombolytic agent, in development by Thrombolytic Science, Cambridge, Mass., formed by changing one amino acid in pro-urokinase to make it more stable. It is more fibrin specific than alteplase and therefore believed to have a lower risk of intracranial hemorrhage.
Fibrin is formed as the last step in the clotting process, and the precursor of fibrin in the blood is fibrinogen, Dr. van der Ende noted. Alteplase depletes fibrinogen, contributing to its increased bleeding risk, but mutant pro-urokinase is not believed to affect fibrinogen.
“Mutant pro-urokinase does not bind to intact fibrin. It only binds to fibrin that has already been primed by alteplase,” she explained.
The hypothesis behind the current study is that giving a small dose of alteplase will break down fibrin in the clot enough to expose the binding sites for mutant pro-urokinase, which can then be given to continue to lyse the clot.
As alteplase has a short half-life, it disappears quickly, and new fibrin is not affected. As mutant pro-urokinase can only lyse fibrin that is primed with alteplase, new hemostatic clots should stay intact. Animal studies have shown less bleeding from distant sites with this approach, Dr. van der Ende said.
The primary analysis of the phase 2 DUMAS study included 238 patients with mild ischemic stroke (median National Institutes of Health Stroke Scale [NIHSS] score 3) who met the standard criteria for IV alteplase.
They were randomized to alteplase alone at the regular dose of 0.9 mg/kg (max 90 mg) with a 10% bolus and the remaining given over 60 minutes; or to a combination of a 5-mg bolus of IV alteplase followed by mutant pro-urokinase at a dose of 40 mg given over 60 minutes.
The primary outcome was the rate of all intracranial hemorrhage (symptomatic and asymptomatic) detected by neuroimaging.
This occurred in 14% of patients in the full-dose alteplase group vs. 13% of patients in the combined alteplase/mutant pro-urokinase group, a nonsignificant difference: adjusted odds ratio, 0.99 (95% confidence interval, 0.46-2.14).
Secondary outcomes showed no significant differences in NIHSS scores at 24 hours or 5-7 days; functional outcome as measured by a shift analysis of the Modified Rankin Scale (mRS); final infarct volume; or perfusion deficit.
However, blood fibrinogen levels were not depleted and significantly higher in the alteplase/mutant pro-urokinase group than in the full-dose alteplase alone group.
In terms of safety, symptomatic ICH occurred in three patients in the alteplase group (3%) and in none (0%) in the combined alteplase/mutant pro-urokinase group; death occurred in 4% vs. 2% patients respectively; and major extracranial hemorrhage occurred in 1% in both groups.
Dr. Van der Ende concluded that the study showed an overall low rate of ICH; a combination of alteplase and mutant pro-urokinase was not superior to alteplase alone in reducing ICH rates in this population of patients with minor stroke; and mutant pro-urokinase appeared to be safe and, unlike alteplase, did not show any reduction in fibrinogen levels.
“We think the lack of an effect on fibrinogen with this new combination of a small alteplase bolus followed by mutant pro-urokinase infusion is promising,” Dr. Dippel commented. “The fact that there was no symptomatic ICH with the combination treatment is also encouraging. Although the primary endpoint of this trial was neutral, we still believe this is a very interesting approach, with the potential for reduced bleeding, compared with alteplase alone, but we need larger numbers to see an effect on outcomes.”
Dr. Dippel also pointed out that the study included only patients with minor stroke who were not eligible for endovascular therapy, and these patients have a low risk of a poor outcome and a low bleeding risk.
They are hoping to do another study in patients with more severe stroke, who have a higher bleeding risk and would have more to gain from this combination approach.
Because many patients with severe stroke now have immediate thrombectomy if they present to a comprehensive stroke center, a trial in severe stroke patients would have to be done in primary stroke centers, so if the patents are referred to thrombectomy, the thrombolytic would have a chance to work, Dr. Dippel added.
Commenting on the study for this news organization, Stefan Kiechl, MD, Medical University of Innsbruck (Austria), who is cochair of the World Stroke Congress scientific committee, said, “Alteplase is not fibrin specific, and also causes a degeneration of fibrinogen, which results in ‘fibrinogen depletion coagulopathy.’ It is assumed that 20%-40% of intracerebral bleeding after thrombolysis with alteplase is caused by this problem. DUMAS tests the combination of a substantially reduced alteplase [5 mg] dose plus mutant pro-urokinase to avoid this problem.”
The new thrombolysis protocol, however, did not result in a lower bleeding risk, compared to the comparator alteplase,” he added. “The main limitation of this study is that mainly patients with minor strokes were included. Patients with moderate and severe strokes, who have a substantial risk of bleeding, were not adequately addressed.”
The DUMAS trial was funded by an unrestricted grant from Thrombolytic Science, paid to the institution. Dr. Van der Ende and Dr. Dippel report no relevant disclosures.
A version of this article first appeared on Medscape.com.
A study evaluating a new approach using a combination of two thrombolytics designed to reduce bleeding risk in patients with acute ischemic stroke has not shown any benefit on the primary outcome of all intracranial hemorrhage (ICH).
However, there were some encouraging findings including a trend towards a reduction in symptomatic ICH, researchers report, and the combination approach did not show any depletion of fibrinogen levels, which suggests a potential lower bleeding risk.
“Although the main results of this study are neutral, we are encouraged that the combination approach with a low dose of alteplase followed by the new mutant pro-urokinase product looked as effective as full-dose alteplase alone, and there were some promising signs signaling a potential lower bleeding risk,” senior investigator, Diederik Dippel, MD, Erasmus University Medical Center, Rotterdam, the Netherlands, told this news organization.
The DUMAS study (Dual Thrombolytic Therapy With Mutant Pro-Urokinase and Low Dose Alteplase for Ischemic Stroke) was presented at the World Stroke Congress in Singapore by study coauthor Nadinda van der Ende, MD, also from Erasmus University Medical Center.
She pointed out that thrombolysis with intravenous alteplase increases the likelihood of a good outcome in acute ischemic stroke but can cause symptomatic intracranial hemorrhage, which can be associated with death and major disability.
Mutant pro-urokinase is a new thrombolytic agent, in development by Thrombolytic Science, Cambridge, Mass., formed by changing one amino acid in pro-urokinase to make it more stable. It is more fibrin specific than alteplase and therefore believed to have a lower risk of intracranial hemorrhage.
Fibrin is formed as the last step in the clotting process, and the precursor of fibrin in the blood is fibrinogen, Dr. van der Ende noted. Alteplase depletes fibrinogen, contributing to its increased bleeding risk, but mutant pro-urokinase is not believed to affect fibrinogen.
“Mutant pro-urokinase does not bind to intact fibrin. It only binds to fibrin that has already been primed by alteplase,” she explained.
The hypothesis behind the current study is that giving a small dose of alteplase will break down fibrin in the clot enough to expose the binding sites for mutant pro-urokinase, which can then be given to continue to lyse the clot.
As alteplase has a short half-life, it disappears quickly, and new fibrin is not affected. As mutant pro-urokinase can only lyse fibrin that is primed with alteplase, new hemostatic clots should stay intact. Animal studies have shown less bleeding from distant sites with this approach, Dr. van der Ende said.
The primary analysis of the phase 2 DUMAS study included 238 patients with mild ischemic stroke (median National Institutes of Health Stroke Scale [NIHSS] score 3) who met the standard criteria for IV alteplase.
They were randomized to alteplase alone at the regular dose of 0.9 mg/kg (max 90 mg) with a 10% bolus and the remaining given over 60 minutes; or to a combination of a 5-mg bolus of IV alteplase followed by mutant pro-urokinase at a dose of 40 mg given over 60 minutes.
The primary outcome was the rate of all intracranial hemorrhage (symptomatic and asymptomatic) detected by neuroimaging.
This occurred in 14% of patients in the full-dose alteplase group vs. 13% of patients in the combined alteplase/mutant pro-urokinase group, a nonsignificant difference: adjusted odds ratio, 0.99 (95% confidence interval, 0.46-2.14).
Secondary outcomes showed no significant differences in NIHSS scores at 24 hours or 5-7 days; functional outcome as measured by a shift analysis of the Modified Rankin Scale (mRS); final infarct volume; or perfusion deficit.
However, blood fibrinogen levels were not depleted and significantly higher in the alteplase/mutant pro-urokinase group than in the full-dose alteplase alone group.
In terms of safety, symptomatic ICH occurred in three patients in the alteplase group (3%) and in none (0%) in the combined alteplase/mutant pro-urokinase group; death occurred in 4% vs. 2% patients respectively; and major extracranial hemorrhage occurred in 1% in both groups.
Dr. Van der Ende concluded that the study showed an overall low rate of ICH; a combination of alteplase and mutant pro-urokinase was not superior to alteplase alone in reducing ICH rates in this population of patients with minor stroke; and mutant pro-urokinase appeared to be safe and, unlike alteplase, did not show any reduction in fibrinogen levels.
“We think the lack of an effect on fibrinogen with this new combination of a small alteplase bolus followed by mutant pro-urokinase infusion is promising,” Dr. Dippel commented. “The fact that there was no symptomatic ICH with the combination treatment is also encouraging. Although the primary endpoint of this trial was neutral, we still believe this is a very interesting approach, with the potential for reduced bleeding, compared with alteplase alone, but we need larger numbers to see an effect on outcomes.”
Dr. Dippel also pointed out that the study included only patients with minor stroke who were not eligible for endovascular therapy, and these patients have a low risk of a poor outcome and a low bleeding risk.
They are hoping to do another study in patients with more severe stroke, who have a higher bleeding risk and would have more to gain from this combination approach.
Because many patients with severe stroke now have immediate thrombectomy if they present to a comprehensive stroke center, a trial in severe stroke patients would have to be done in primary stroke centers, so if the patents are referred to thrombectomy, the thrombolytic would have a chance to work, Dr. Dippel added.
Commenting on the study for this news organization, Stefan Kiechl, MD, Medical University of Innsbruck (Austria), who is cochair of the World Stroke Congress scientific committee, said, “Alteplase is not fibrin specific, and also causes a degeneration of fibrinogen, which results in ‘fibrinogen depletion coagulopathy.’ It is assumed that 20%-40% of intracerebral bleeding after thrombolysis with alteplase is caused by this problem. DUMAS tests the combination of a substantially reduced alteplase [5 mg] dose plus mutant pro-urokinase to avoid this problem.”
The new thrombolysis protocol, however, did not result in a lower bleeding risk, compared to the comparator alteplase,” he added. “The main limitation of this study is that mainly patients with minor strokes were included. Patients with moderate and severe strokes, who have a substantial risk of bleeding, were not adequately addressed.”
The DUMAS trial was funded by an unrestricted grant from Thrombolytic Science, paid to the institution. Dr. Van der Ende and Dr. Dippel report no relevant disclosures.
A version of this article first appeared on Medscape.com.
A study evaluating a new approach using a combination of two thrombolytics designed to reduce bleeding risk in patients with acute ischemic stroke has not shown any benefit on the primary outcome of all intracranial hemorrhage (ICH).
However, there were some encouraging findings including a trend towards a reduction in symptomatic ICH, researchers report, and the combination approach did not show any depletion of fibrinogen levels, which suggests a potential lower bleeding risk.
“Although the main results of this study are neutral, we are encouraged that the combination approach with a low dose of alteplase followed by the new mutant pro-urokinase product looked as effective as full-dose alteplase alone, and there were some promising signs signaling a potential lower bleeding risk,” senior investigator, Diederik Dippel, MD, Erasmus University Medical Center, Rotterdam, the Netherlands, told this news organization.
The DUMAS study (Dual Thrombolytic Therapy With Mutant Pro-Urokinase and Low Dose Alteplase for Ischemic Stroke) was presented at the World Stroke Congress in Singapore by study coauthor Nadinda van der Ende, MD, also from Erasmus University Medical Center.
She pointed out that thrombolysis with intravenous alteplase increases the likelihood of a good outcome in acute ischemic stroke but can cause symptomatic intracranial hemorrhage, which can be associated with death and major disability.
Mutant pro-urokinase is a new thrombolytic agent, in development by Thrombolytic Science, Cambridge, Mass., formed by changing one amino acid in pro-urokinase to make it more stable. It is more fibrin specific than alteplase and therefore believed to have a lower risk of intracranial hemorrhage.
Fibrin is formed as the last step in the clotting process, and the precursor of fibrin in the blood is fibrinogen, Dr. van der Ende noted. Alteplase depletes fibrinogen, contributing to its increased bleeding risk, but mutant pro-urokinase is not believed to affect fibrinogen.
“Mutant pro-urokinase does not bind to intact fibrin. It only binds to fibrin that has already been primed by alteplase,” she explained.
The hypothesis behind the current study is that giving a small dose of alteplase will break down fibrin in the clot enough to expose the binding sites for mutant pro-urokinase, which can then be given to continue to lyse the clot.
As alteplase has a short half-life, it disappears quickly, and new fibrin is not affected. As mutant pro-urokinase can only lyse fibrin that is primed with alteplase, new hemostatic clots should stay intact. Animal studies have shown less bleeding from distant sites with this approach, Dr. van der Ende said.
The primary analysis of the phase 2 DUMAS study included 238 patients with mild ischemic stroke (median National Institutes of Health Stroke Scale [NIHSS] score 3) who met the standard criteria for IV alteplase.
They were randomized to alteplase alone at the regular dose of 0.9 mg/kg (max 90 mg) with a 10% bolus and the remaining given over 60 minutes; or to a combination of a 5-mg bolus of IV alteplase followed by mutant pro-urokinase at a dose of 40 mg given over 60 minutes.
The primary outcome was the rate of all intracranial hemorrhage (symptomatic and asymptomatic) detected by neuroimaging.
This occurred in 14% of patients in the full-dose alteplase group vs. 13% of patients in the combined alteplase/mutant pro-urokinase group, a nonsignificant difference: adjusted odds ratio, 0.99 (95% confidence interval, 0.46-2.14).
Secondary outcomes showed no significant differences in NIHSS scores at 24 hours or 5-7 days; functional outcome as measured by a shift analysis of the Modified Rankin Scale (mRS); final infarct volume; or perfusion deficit.
However, blood fibrinogen levels were not depleted and significantly higher in the alteplase/mutant pro-urokinase group than in the full-dose alteplase alone group.
In terms of safety, symptomatic ICH occurred in three patients in the alteplase group (3%) and in none (0%) in the combined alteplase/mutant pro-urokinase group; death occurred in 4% vs. 2% patients respectively; and major extracranial hemorrhage occurred in 1% in both groups.
Dr. Van der Ende concluded that the study showed an overall low rate of ICH; a combination of alteplase and mutant pro-urokinase was not superior to alteplase alone in reducing ICH rates in this population of patients with minor stroke; and mutant pro-urokinase appeared to be safe and, unlike alteplase, did not show any reduction in fibrinogen levels.
“We think the lack of an effect on fibrinogen with this new combination of a small alteplase bolus followed by mutant pro-urokinase infusion is promising,” Dr. Dippel commented. “The fact that there was no symptomatic ICH with the combination treatment is also encouraging. Although the primary endpoint of this trial was neutral, we still believe this is a very interesting approach, with the potential for reduced bleeding, compared with alteplase alone, but we need larger numbers to see an effect on outcomes.”
Dr. Dippel also pointed out that the study included only patients with minor stroke who were not eligible for endovascular therapy, and these patients have a low risk of a poor outcome and a low bleeding risk.
They are hoping to do another study in patients with more severe stroke, who have a higher bleeding risk and would have more to gain from this combination approach.
Because many patients with severe stroke now have immediate thrombectomy if they present to a comprehensive stroke center, a trial in severe stroke patients would have to be done in primary stroke centers, so if the patents are referred to thrombectomy, the thrombolytic would have a chance to work, Dr. Dippel added.
Commenting on the study for this news organization, Stefan Kiechl, MD, Medical University of Innsbruck (Austria), who is cochair of the World Stroke Congress scientific committee, said, “Alteplase is not fibrin specific, and also causes a degeneration of fibrinogen, which results in ‘fibrinogen depletion coagulopathy.’ It is assumed that 20%-40% of intracerebral bleeding after thrombolysis with alteplase is caused by this problem. DUMAS tests the combination of a substantially reduced alteplase [5 mg] dose plus mutant pro-urokinase to avoid this problem.”
The new thrombolysis protocol, however, did not result in a lower bleeding risk, compared to the comparator alteplase,” he added. “The main limitation of this study is that mainly patients with minor strokes were included. Patients with moderate and severe strokes, who have a substantial risk of bleeding, were not adequately addressed.”
The DUMAS trial was funded by an unrestricted grant from Thrombolytic Science, paid to the institution. Dr. Van der Ende and Dr. Dippel report no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM WSC 2022
VA Delays EHR Rollout—Again
The US Department of Veterans Affairs (VA) is pushing further deployments of the system to June 2023 “to address challenges” and make sure it’s functioning optimally.
Among the challenges: Safety concerns “voluminous enough and prevalent enough” to prompt the VA to disclose to 41,500 veterans enrolled in Washington, Idaho, Oregon, Montana, and Ohio that their care “may have been impacted as a result of the system’s deployment as it is currently configured,” VA Undersecretary for Health Shereef Elnahal said in a news conference.
The plan was to launch in the first quarter of 2023 in Western Washington, Michigan, and Ohio. But in a recent release, the VA said an investigation had found several technical and system issues, such as latency and slowness, and problems with patient scheduling, referrals, medication management, and other types of medical orders. During this “assess and address” period, the VA says, it will correct outstanding issues—especially those that may have patient safety implications—before restarting deployments at other VA medical centers.
“Right now, the Oracle Cerner [EHR] system is not delivering for veterans or VA health care providers—and we are holding Oracle Cerner and ourselves accountable to get this right,” said VA Deputy Secretary Donald Remy, who has oversight over the EHR program. “We are delaying all future deployments of the new EHR while we fully assess performance and address every concern. Veterans and clinicians deserve a seamless, modernized health record system, and we will not rest until they get it.”
The modernized EHR, intended to replace the Veterans Health Information Systems and Technology Architecture (VistA), has been plagued by problems from the very first launch in October 2020 at Mann-Grandstaff VA Medical Center and associated clinics in the Northwest. Deputy Inspector David Case, of the Office of Inspector General (OIG), reported to the House Committee on Veterans’ Affairs on oversight between 2020 and July 2021. Among other things, the OIG identified problems with the infrastructure and with users’ experiences. Clinical and administrative staff at Mann-Grandstaff and a Columbus clinic shared their frustration with OIG personnel about the “significant system and process limitations that raised concerns about the continuity of and prompt access to quality patient care.”
For example, according to an OIG report from July 2022, the new EHR sent thousands of orders for medical care to an “undetectable location, or unknown queue” instead of the intended location. The mis-delivery caused 149 patient harm events.
On October 11, the VA confirmed to The Spokesman-Review, a Spokane-based newspaper, that a patient had died at the VA clinic in Columbus. The death was attributed to the patient not receiving medication due to incorrect information. The incident is being treated as a potential “sentinel event.”
Elnahal, who met with employees in September at the Columbus clinic where the Oracle Cerner system was launched in April, said he found that the highly complex system made it hard for clinicians to perform routine tasks, such as ordering tests or follow-up appointments. Delays in follow-ups—including a yearlong delay in treatment for a veteran ultimately diagnosed with terminal cancer—were the main cause of the cases of harm cited in the July OIG report.
The veterans who received the letter about the potential impact on their health care “got caught up in this phenomenon of commands not getting where they need to go,” Elnahal said in a news conference in September.
Senator Patty Murray (D-WA), a senior member of the Veterans Affairs Committee, has been consistently pressing the VA to do something about the EHR system’s flaws. “It’s painfully clear,” she said in a statement, “we need to stop this program until the VA can fix these serious issues before they hurt anyone else.”
After finding more than 200 orders in the unknown queue in May 2022, the OIG said, it “has concerns with the effectiveness of Cerner’s plan to mitigate the safety risk.” While executing its “assess and address” plan, the VA will continue to focus on the 5 facilities where the new system has been deployed. “Sometimes, you’re not presented with options to immediately resolve the safety concerns that are in front of you,” Elnahal told reporters. “It is simply the case that the best option in front of us to resolve these patient safety concerns is to work with Oracle Cerner over the next several months to resolve the Cerner system issues at the sites where it exists. We know that this is possible, because other health systems have gone through this journey before, and I think we can do it.”
Veterans who believe their care may have been affected can call a dedicated call center at 800.319.9446. A VA health care team will follow up within 5 days.
The US Department of Veterans Affairs (VA) is pushing further deployments of the system to June 2023 “to address challenges” and make sure it’s functioning optimally.
Among the challenges: Safety concerns “voluminous enough and prevalent enough” to prompt the VA to disclose to 41,500 veterans enrolled in Washington, Idaho, Oregon, Montana, and Ohio that their care “may have been impacted as a result of the system’s deployment as it is currently configured,” VA Undersecretary for Health Shereef Elnahal said in a news conference.
The plan was to launch in the first quarter of 2023 in Western Washington, Michigan, and Ohio. But in a recent release, the VA said an investigation had found several technical and system issues, such as latency and slowness, and problems with patient scheduling, referrals, medication management, and other types of medical orders. During this “assess and address” period, the VA says, it will correct outstanding issues—especially those that may have patient safety implications—before restarting deployments at other VA medical centers.
“Right now, the Oracle Cerner [EHR] system is not delivering for veterans or VA health care providers—and we are holding Oracle Cerner and ourselves accountable to get this right,” said VA Deputy Secretary Donald Remy, who has oversight over the EHR program. “We are delaying all future deployments of the new EHR while we fully assess performance and address every concern. Veterans and clinicians deserve a seamless, modernized health record system, and we will not rest until they get it.”
The modernized EHR, intended to replace the Veterans Health Information Systems and Technology Architecture (VistA), has been plagued by problems from the very first launch in October 2020 at Mann-Grandstaff VA Medical Center and associated clinics in the Northwest. Deputy Inspector David Case, of the Office of Inspector General (OIG), reported to the House Committee on Veterans’ Affairs on oversight between 2020 and July 2021. Among other things, the OIG identified problems with the infrastructure and with users’ experiences. Clinical and administrative staff at Mann-Grandstaff and a Columbus clinic shared their frustration with OIG personnel about the “significant system and process limitations that raised concerns about the continuity of and prompt access to quality patient care.”
For example, according to an OIG report from July 2022, the new EHR sent thousands of orders for medical care to an “undetectable location, or unknown queue” instead of the intended location. The mis-delivery caused 149 patient harm events.
On October 11, the VA confirmed to The Spokesman-Review, a Spokane-based newspaper, that a patient had died at the VA clinic in Columbus. The death was attributed to the patient not receiving medication due to incorrect information. The incident is being treated as a potential “sentinel event.”
Elnahal, who met with employees in September at the Columbus clinic where the Oracle Cerner system was launched in April, said he found that the highly complex system made it hard for clinicians to perform routine tasks, such as ordering tests or follow-up appointments. Delays in follow-ups—including a yearlong delay in treatment for a veteran ultimately diagnosed with terminal cancer—were the main cause of the cases of harm cited in the July OIG report.
The veterans who received the letter about the potential impact on their health care “got caught up in this phenomenon of commands not getting where they need to go,” Elnahal said in a news conference in September.
Senator Patty Murray (D-WA), a senior member of the Veterans Affairs Committee, has been consistently pressing the VA to do something about the EHR system’s flaws. “It’s painfully clear,” she said in a statement, “we need to stop this program until the VA can fix these serious issues before they hurt anyone else.”
After finding more than 200 orders in the unknown queue in May 2022, the OIG said, it “has concerns with the effectiveness of Cerner’s plan to mitigate the safety risk.” While executing its “assess and address” plan, the VA will continue to focus on the 5 facilities where the new system has been deployed. “Sometimes, you’re not presented with options to immediately resolve the safety concerns that are in front of you,” Elnahal told reporters. “It is simply the case that the best option in front of us to resolve these patient safety concerns is to work with Oracle Cerner over the next several months to resolve the Cerner system issues at the sites where it exists. We know that this is possible, because other health systems have gone through this journey before, and I think we can do it.”
Veterans who believe their care may have been affected can call a dedicated call center at 800.319.9446. A VA health care team will follow up within 5 days.
The US Department of Veterans Affairs (VA) is pushing further deployments of the system to June 2023 “to address challenges” and make sure it’s functioning optimally.
Among the challenges: Safety concerns “voluminous enough and prevalent enough” to prompt the VA to disclose to 41,500 veterans enrolled in Washington, Idaho, Oregon, Montana, and Ohio that their care “may have been impacted as a result of the system’s deployment as it is currently configured,” VA Undersecretary for Health Shereef Elnahal said in a news conference.
The plan was to launch in the first quarter of 2023 in Western Washington, Michigan, and Ohio. But in a recent release, the VA said an investigation had found several technical and system issues, such as latency and slowness, and problems with patient scheduling, referrals, medication management, and other types of medical orders. During this “assess and address” period, the VA says, it will correct outstanding issues—especially those that may have patient safety implications—before restarting deployments at other VA medical centers.
“Right now, the Oracle Cerner [EHR] system is not delivering for veterans or VA health care providers—and we are holding Oracle Cerner and ourselves accountable to get this right,” said VA Deputy Secretary Donald Remy, who has oversight over the EHR program. “We are delaying all future deployments of the new EHR while we fully assess performance and address every concern. Veterans and clinicians deserve a seamless, modernized health record system, and we will not rest until they get it.”
The modernized EHR, intended to replace the Veterans Health Information Systems and Technology Architecture (VistA), has been plagued by problems from the very first launch in October 2020 at Mann-Grandstaff VA Medical Center and associated clinics in the Northwest. Deputy Inspector David Case, of the Office of Inspector General (OIG), reported to the House Committee on Veterans’ Affairs on oversight between 2020 and July 2021. Among other things, the OIG identified problems with the infrastructure and with users’ experiences. Clinical and administrative staff at Mann-Grandstaff and a Columbus clinic shared their frustration with OIG personnel about the “significant system and process limitations that raised concerns about the continuity of and prompt access to quality patient care.”
For example, according to an OIG report from July 2022, the new EHR sent thousands of orders for medical care to an “undetectable location, or unknown queue” instead of the intended location. The mis-delivery caused 149 patient harm events.
On October 11, the VA confirmed to The Spokesman-Review, a Spokane-based newspaper, that a patient had died at the VA clinic in Columbus. The death was attributed to the patient not receiving medication due to incorrect information. The incident is being treated as a potential “sentinel event.”
Elnahal, who met with employees in September at the Columbus clinic where the Oracle Cerner system was launched in April, said he found that the highly complex system made it hard for clinicians to perform routine tasks, such as ordering tests or follow-up appointments. Delays in follow-ups—including a yearlong delay in treatment for a veteran ultimately diagnosed with terminal cancer—were the main cause of the cases of harm cited in the July OIG report.
The veterans who received the letter about the potential impact on their health care “got caught up in this phenomenon of commands not getting where they need to go,” Elnahal said in a news conference in September.
Senator Patty Murray (D-WA), a senior member of the Veterans Affairs Committee, has been consistently pressing the VA to do something about the EHR system’s flaws. “It’s painfully clear,” she said in a statement, “we need to stop this program until the VA can fix these serious issues before they hurt anyone else.”
After finding more than 200 orders in the unknown queue in May 2022, the OIG said, it “has concerns with the effectiveness of Cerner’s plan to mitigate the safety risk.” While executing its “assess and address” plan, the VA will continue to focus on the 5 facilities where the new system has been deployed. “Sometimes, you’re not presented with options to immediately resolve the safety concerns that are in front of you,” Elnahal told reporters. “It is simply the case that the best option in front of us to resolve these patient safety concerns is to work with Oracle Cerner over the next several months to resolve the Cerner system issues at the sites where it exists. We know that this is possible, because other health systems have gone through this journey before, and I think we can do it.”
Veterans who believe their care may have been affected can call a dedicated call center at 800.319.9446. A VA health care team will follow up within 5 days.
Uptake of high-sensitivity troponin assays lags in U.S. hospitals
Most hospitals in the United States have yet to transition from conventional to high-sensitivity cardiac troponin (hs-cTn) assays, despite their greater sensitivity for myocardial injury, a new National Cardiovascular Data Registry (NCDR) registry study indicates.
hs-cTn assays have been used in routine clinical practice in Europe, Canada, and Australia since 2010, but the first such assay did not gain approval in the United States until 2017. Although single-center studies have examined their efficacy and potential downstream consequences, few data exist on hs-cTn implementation nationally, explained study author Cian McCarthy, MB, BCh, BAO, Massachusetts General Hospital, Boston.
The results were published online in the Journal of the American College of Cardiology and will be presented Nov. 5 at the American Heart Association scientific sessions.
For the study, Dr. McCarthy and colleagues examined 550 hospitals participating in the NCDR Chest Pain-MI registry from January 2019 through September 2021.
Of the 251,000 patients included in the analysis (mean age, 64 years; 41.5% female), 155,049 had a non–ST-segment myocardial infarction (NSTEMI), 15,989 had unstable angina, and 79,962 had low-risk chest pain.
The hs-cTn assays included Roche Diagnostic’s Elecsys Gen5 STAT troponin T assay (23%); Abbott’s ARCHITECT STAT (17%); Beckman Coulter’s ACCESS (21%); and Siemens’ Atellica IM (18%), Dimension VISTA (14%), Dimension EXL (4%), and ADVIA Centaur (2%) troponin I assays.
During the study period, 11.5% of patients were evaluated with hs-cTn assays and the remainder were evaluated with conventional troponin assays. These patients were slightly older (65.0 vs. 64.0 years), more commonly White (83.1% vs. 79.9%), less likely to be of Hispanic or Latino ethnicity (8.9% vs. 10.0%), and less likely to be uninsured (6.8% vs. 8.3%; P for all < .001).
A slightly higher proportion of patients evaluated with hs-cTn assays were diagnosed with unstable angina (7.1% vs. 6.3%), a lower proportion with NSTEMI (61.1% vs. 61.9%), and a similar proportion with low-risk chest pain (31.8% vs. 31.9%) compared with those evaluated by conventional troponin assays.
Implementation, defined as at least 25% of patients evaluated by hs-cTn in each quarter, increased from 3.3% in the first quarter of 2019 to 32.6% in the third quarter of 2021 (P trend < .001).
Using higher implementation thresholds of at least 50% and 75% of patients evaluated by hs-cTn, the prevalence in 2021 was 28.9% and 24.7%, respectively.
“So still, the majority of the hospitals by the end of the third quarter 2021 were not using these assays,” Dr. McCarthy said.
Potential explanations for the slow uptake are that prospective comparative effectiveness trials of These assays have predominantly been in international populations and real-world data on U.S. implementation have been limited to integrated health networks at academic institutions.
Approval of several assays was also delayed and the study data cut off just before the October publication of the 2021 AHA/ACC Chest Pain guideline. “So, whether the chest pain guideline with the new class 1 recommendation for hs-cTn will lead to further uptake is something that will need to be looked at in the future,” he said.
Downstream testing
In adjusted analyses, hs-cTn use was associated with more echocardiography among patients with non-ST elevation–acute coronary syndrome (NSTE-ACS) (82.4% vs. 75.0%; odds ratio [OR], 1.43; 95% confidence interval [CI], 1.19-1.73), but not among those with low-risk chest pain (19.7% vs. 19.4%; OR, 0.93; 95% CI, 0.71-1.22) compared with conventional cTn assays.
Importantly, hs-cTn was not associated with a difference in stress testing or CT coronary angiography utilization.
Use of hs-cTn was associated with lower use of invasive coronary angiography among patients with low-risk chest pain (3.7% vs. 4.5%; OR, 0.73, 95% CI, 0.58-0.92) but similar use for NSTE-ACS (96.3% vs. 95.8%; OR, 0.99, 95% CI, 0.82-1.19).
Among patients with NSTE-ACS, there also was no difference in revascularization with percutaneous coronary intervention (PCI) (52.7% vs. 52.3%; OR, 0.99; 95% CI, 0.94-1.04) or coronary bypass graft surgery (9.4% vs. 9.1%; OR, 1.06; 95% CI, 0.94-1.18).
PCI (0.1% vs. 0.2%; P = .05) and bypass graft surgery (both 0.1%) were uncommon among patients with low-risk chest pain.
In-hospital mortality was similar among patients with low-risk chest pain evaluated using hs-cTn assays vs. conventional troponin assays (0% vs. 0.02%; P = .16) and among patients with NSTE-ACS (2.8% vs. 3.2%; OR, 0.98, 95% CI, 0.87-1.11).
Length of stay was slightly shorter with hs-cTn use for patients with low-risk chest pain (median, 5.8 vs. 6.2 hours; P < .001) and patients with NSTE-ACS (66.9 vs. 67.8 hours; P = .01).
“There was always a concern that maybe high-sensitivity cardiac troponin would dramatically increase testing and could even increase length of stay, but I think these data are reassuring, in that this study suggests high-sensitivity cardiac troponin is associated with a small reduction in length of stay and possibly more appropriate use of testing with echocardiography in STEMI and a reduction in invasive angiography in low-risk patients,” Dr. McCarthy said. “But the majority of hospitals haven’t implemented the assay.”
The authors pointed out that because registry entry of patients with low-risk chest pain and unstable angina is optional for participating sites, the percentage of patients with NSTEMI is higher than in typical chest pain analyses. This higher pretest probability for MI may thus affect post-test accuracy for a true positive result. “That stated, this is the exact scenario where higher sensitivity might be associated with favorable impact on utilization.”
Among other limitations: There was the potential for unmeasured confounders, the accuracy of diagnoses could not be confirmed, patients with type 2 MI were excluded from the registry, and post-discharge safety was not assessed.
“These data indicate further opportunities to more widely and effectively implement hs-cTn in the U.S. hospitals persist that could optimize care for patients with possible or definitive ACS,” Dr. McCarthy and colleagues concluded.
The study was funded by the American College of Cardiology’s National Cardiovascular Data Registry. Dr. McCarthy is supported by the National Heart, Lung, and Blood Institute and has received consulting income from Abbott Laboratories.
A version of this article first appeared on Medscape.com.
Most hospitals in the United States have yet to transition from conventional to high-sensitivity cardiac troponin (hs-cTn) assays, despite their greater sensitivity for myocardial injury, a new National Cardiovascular Data Registry (NCDR) registry study indicates.
hs-cTn assays have been used in routine clinical practice in Europe, Canada, and Australia since 2010, but the first such assay did not gain approval in the United States until 2017. Although single-center studies have examined their efficacy and potential downstream consequences, few data exist on hs-cTn implementation nationally, explained study author Cian McCarthy, MB, BCh, BAO, Massachusetts General Hospital, Boston.
The results were published online in the Journal of the American College of Cardiology and will be presented Nov. 5 at the American Heart Association scientific sessions.
For the study, Dr. McCarthy and colleagues examined 550 hospitals participating in the NCDR Chest Pain-MI registry from January 2019 through September 2021.
Of the 251,000 patients included in the analysis (mean age, 64 years; 41.5% female), 155,049 had a non–ST-segment myocardial infarction (NSTEMI), 15,989 had unstable angina, and 79,962 had low-risk chest pain.
The hs-cTn assays included Roche Diagnostic’s Elecsys Gen5 STAT troponin T assay (23%); Abbott’s ARCHITECT STAT (17%); Beckman Coulter’s ACCESS (21%); and Siemens’ Atellica IM (18%), Dimension VISTA (14%), Dimension EXL (4%), and ADVIA Centaur (2%) troponin I assays.
During the study period, 11.5% of patients were evaluated with hs-cTn assays and the remainder were evaluated with conventional troponin assays. These patients were slightly older (65.0 vs. 64.0 years), more commonly White (83.1% vs. 79.9%), less likely to be of Hispanic or Latino ethnicity (8.9% vs. 10.0%), and less likely to be uninsured (6.8% vs. 8.3%; P for all < .001).
A slightly higher proportion of patients evaluated with hs-cTn assays were diagnosed with unstable angina (7.1% vs. 6.3%), a lower proportion with NSTEMI (61.1% vs. 61.9%), and a similar proportion with low-risk chest pain (31.8% vs. 31.9%) compared with those evaluated by conventional troponin assays.
Implementation, defined as at least 25% of patients evaluated by hs-cTn in each quarter, increased from 3.3% in the first quarter of 2019 to 32.6% in the third quarter of 2021 (P trend < .001).
Using higher implementation thresholds of at least 50% and 75% of patients evaluated by hs-cTn, the prevalence in 2021 was 28.9% and 24.7%, respectively.
“So still, the majority of the hospitals by the end of the third quarter 2021 were not using these assays,” Dr. McCarthy said.
Potential explanations for the slow uptake are that prospective comparative effectiveness trials of These assays have predominantly been in international populations and real-world data on U.S. implementation have been limited to integrated health networks at academic institutions.
Approval of several assays was also delayed and the study data cut off just before the October publication of the 2021 AHA/ACC Chest Pain guideline. “So, whether the chest pain guideline with the new class 1 recommendation for hs-cTn will lead to further uptake is something that will need to be looked at in the future,” he said.
Downstream testing
In adjusted analyses, hs-cTn use was associated with more echocardiography among patients with non-ST elevation–acute coronary syndrome (NSTE-ACS) (82.4% vs. 75.0%; odds ratio [OR], 1.43; 95% confidence interval [CI], 1.19-1.73), but not among those with low-risk chest pain (19.7% vs. 19.4%; OR, 0.93; 95% CI, 0.71-1.22) compared with conventional cTn assays.
Importantly, hs-cTn was not associated with a difference in stress testing or CT coronary angiography utilization.
Use of hs-cTn was associated with lower use of invasive coronary angiography among patients with low-risk chest pain (3.7% vs. 4.5%; OR, 0.73, 95% CI, 0.58-0.92) but similar use for NSTE-ACS (96.3% vs. 95.8%; OR, 0.99, 95% CI, 0.82-1.19).
Among patients with NSTE-ACS, there also was no difference in revascularization with percutaneous coronary intervention (PCI) (52.7% vs. 52.3%; OR, 0.99; 95% CI, 0.94-1.04) or coronary bypass graft surgery (9.4% vs. 9.1%; OR, 1.06; 95% CI, 0.94-1.18).
PCI (0.1% vs. 0.2%; P = .05) and bypass graft surgery (both 0.1%) were uncommon among patients with low-risk chest pain.
In-hospital mortality was similar among patients with low-risk chest pain evaluated using hs-cTn assays vs. conventional troponin assays (0% vs. 0.02%; P = .16) and among patients with NSTE-ACS (2.8% vs. 3.2%; OR, 0.98, 95% CI, 0.87-1.11).
Length of stay was slightly shorter with hs-cTn use for patients with low-risk chest pain (median, 5.8 vs. 6.2 hours; P < .001) and patients with NSTE-ACS (66.9 vs. 67.8 hours; P = .01).
“There was always a concern that maybe high-sensitivity cardiac troponin would dramatically increase testing and could even increase length of stay, but I think these data are reassuring, in that this study suggests high-sensitivity cardiac troponin is associated with a small reduction in length of stay and possibly more appropriate use of testing with echocardiography in STEMI and a reduction in invasive angiography in low-risk patients,” Dr. McCarthy said. “But the majority of hospitals haven’t implemented the assay.”
The authors pointed out that because registry entry of patients with low-risk chest pain and unstable angina is optional for participating sites, the percentage of patients with NSTEMI is higher than in typical chest pain analyses. This higher pretest probability for MI may thus affect post-test accuracy for a true positive result. “That stated, this is the exact scenario where higher sensitivity might be associated with favorable impact on utilization.”
Among other limitations: There was the potential for unmeasured confounders, the accuracy of diagnoses could not be confirmed, patients with type 2 MI were excluded from the registry, and post-discharge safety was not assessed.
“These data indicate further opportunities to more widely and effectively implement hs-cTn in the U.S. hospitals persist that could optimize care for patients with possible or definitive ACS,” Dr. McCarthy and colleagues concluded.
The study was funded by the American College of Cardiology’s National Cardiovascular Data Registry. Dr. McCarthy is supported by the National Heart, Lung, and Blood Institute and has received consulting income from Abbott Laboratories.
A version of this article first appeared on Medscape.com.
Most hospitals in the United States have yet to transition from conventional to high-sensitivity cardiac troponin (hs-cTn) assays, despite their greater sensitivity for myocardial injury, a new National Cardiovascular Data Registry (NCDR) registry study indicates.
hs-cTn assays have been used in routine clinical practice in Europe, Canada, and Australia since 2010, but the first such assay did not gain approval in the United States until 2017. Although single-center studies have examined their efficacy and potential downstream consequences, few data exist on hs-cTn implementation nationally, explained study author Cian McCarthy, MB, BCh, BAO, Massachusetts General Hospital, Boston.
The results were published online in the Journal of the American College of Cardiology and will be presented Nov. 5 at the American Heart Association scientific sessions.
For the study, Dr. McCarthy and colleagues examined 550 hospitals participating in the NCDR Chest Pain-MI registry from January 2019 through September 2021.
Of the 251,000 patients included in the analysis (mean age, 64 years; 41.5% female), 155,049 had a non–ST-segment myocardial infarction (NSTEMI), 15,989 had unstable angina, and 79,962 had low-risk chest pain.
The hs-cTn assays included Roche Diagnostic’s Elecsys Gen5 STAT troponin T assay (23%); Abbott’s ARCHITECT STAT (17%); Beckman Coulter’s ACCESS (21%); and Siemens’ Atellica IM (18%), Dimension VISTA (14%), Dimension EXL (4%), and ADVIA Centaur (2%) troponin I assays.
During the study period, 11.5% of patients were evaluated with hs-cTn assays and the remainder were evaluated with conventional troponin assays. These patients were slightly older (65.0 vs. 64.0 years), more commonly White (83.1% vs. 79.9%), less likely to be of Hispanic or Latino ethnicity (8.9% vs. 10.0%), and less likely to be uninsured (6.8% vs. 8.3%; P for all < .001).
A slightly higher proportion of patients evaluated with hs-cTn assays were diagnosed with unstable angina (7.1% vs. 6.3%), a lower proportion with NSTEMI (61.1% vs. 61.9%), and a similar proportion with low-risk chest pain (31.8% vs. 31.9%) compared with those evaluated by conventional troponin assays.
Implementation, defined as at least 25% of patients evaluated by hs-cTn in each quarter, increased from 3.3% in the first quarter of 2019 to 32.6% in the third quarter of 2021 (P trend < .001).
Using higher implementation thresholds of at least 50% and 75% of patients evaluated by hs-cTn, the prevalence in 2021 was 28.9% and 24.7%, respectively.
“So still, the majority of the hospitals by the end of the third quarter 2021 were not using these assays,” Dr. McCarthy said.
Potential explanations for the slow uptake are that prospective comparative effectiveness trials of These assays have predominantly been in international populations and real-world data on U.S. implementation have been limited to integrated health networks at academic institutions.
Approval of several assays was also delayed and the study data cut off just before the October publication of the 2021 AHA/ACC Chest Pain guideline. “So, whether the chest pain guideline with the new class 1 recommendation for hs-cTn will lead to further uptake is something that will need to be looked at in the future,” he said.
Downstream testing
In adjusted analyses, hs-cTn use was associated with more echocardiography among patients with non-ST elevation–acute coronary syndrome (NSTE-ACS) (82.4% vs. 75.0%; odds ratio [OR], 1.43; 95% confidence interval [CI], 1.19-1.73), but not among those with low-risk chest pain (19.7% vs. 19.4%; OR, 0.93; 95% CI, 0.71-1.22) compared with conventional cTn assays.
Importantly, hs-cTn was not associated with a difference in stress testing or CT coronary angiography utilization.
Use of hs-cTn was associated with lower use of invasive coronary angiography among patients with low-risk chest pain (3.7% vs. 4.5%; OR, 0.73, 95% CI, 0.58-0.92) but similar use for NSTE-ACS (96.3% vs. 95.8%; OR, 0.99, 95% CI, 0.82-1.19).
Among patients with NSTE-ACS, there also was no difference in revascularization with percutaneous coronary intervention (PCI) (52.7% vs. 52.3%; OR, 0.99; 95% CI, 0.94-1.04) or coronary bypass graft surgery (9.4% vs. 9.1%; OR, 1.06; 95% CI, 0.94-1.18).
PCI (0.1% vs. 0.2%; P = .05) and bypass graft surgery (both 0.1%) were uncommon among patients with low-risk chest pain.
In-hospital mortality was similar among patients with low-risk chest pain evaluated using hs-cTn assays vs. conventional troponin assays (0% vs. 0.02%; P = .16) and among patients with NSTE-ACS (2.8% vs. 3.2%; OR, 0.98, 95% CI, 0.87-1.11).
Length of stay was slightly shorter with hs-cTn use for patients with low-risk chest pain (median, 5.8 vs. 6.2 hours; P < .001) and patients with NSTE-ACS (66.9 vs. 67.8 hours; P = .01).
“There was always a concern that maybe high-sensitivity cardiac troponin would dramatically increase testing and could even increase length of stay, but I think these data are reassuring, in that this study suggests high-sensitivity cardiac troponin is associated with a small reduction in length of stay and possibly more appropriate use of testing with echocardiography in STEMI and a reduction in invasive angiography in low-risk patients,” Dr. McCarthy said. “But the majority of hospitals haven’t implemented the assay.”
The authors pointed out that because registry entry of patients with low-risk chest pain and unstable angina is optional for participating sites, the percentage of patients with NSTEMI is higher than in typical chest pain analyses. This higher pretest probability for MI may thus affect post-test accuracy for a true positive result. “That stated, this is the exact scenario where higher sensitivity might be associated with favorable impact on utilization.”
Among other limitations: There was the potential for unmeasured confounders, the accuracy of diagnoses could not be confirmed, patients with type 2 MI were excluded from the registry, and post-discharge safety was not assessed.
“These data indicate further opportunities to more widely and effectively implement hs-cTn in the U.S. hospitals persist that could optimize care for patients with possible or definitive ACS,” Dr. McCarthy and colleagues concluded.
The study was funded by the American College of Cardiology’s National Cardiovascular Data Registry. Dr. McCarthy is supported by the National Heart, Lung, and Blood Institute and has received consulting income from Abbott Laboratories.
A version of this article first appeared on Medscape.com.
FROM AHA 2022
RSV vaccine given during pregnancy protects newborns: Pfizer
New trial data from drugmaker Pfizer shows promising results of a vaccine given to mothers during pregnancy that later protects infants in their first months from the worst effects of respiratory syncytial virus, or RSV.
Pfizer will apply for FDA approval by the end of the year, the company said in a statement Nov. 1.
Trial results are so promising that – after talking with government regulators – the company will stop enrolling new people in the study.
Specifically, the company reported that the vaccine prevented severe illness particularly well during the first 90 days of life, with measurable protection against severe illness continuing through 6 months of age. (That period is when infants are the most fragile if they get sick with RSV.)
RSV is a respiratory illness than can affect anyone, usually resulting in no symptoms or those similar to the common cold. But it can be particularly dangerous – and even deadly – for babies and for people over the age of 65. Pfizer and another drug company, GSK, are developing promising vaccines for older adults, the Washington Post reported.
RSV is the leading cause of hospitalization for infants, the Post noted.
The Pfizer study, called MATISSE, enrolled 7,400 pregnant women in 18 countries worldwide. Those who received the vaccine were given it during the late second to third trimester of pregnancy. Women in the study were monitored for safety through the rest of their pregnancy and 6 months after their children were born. Infants were monitored for at least 1 year for safety and effectiveness; more than half of them were monitored for 2 years.
The Pfizer vaccine works by passing maternal antibodies to the infant during pregnancy, the Post reported, noting that other vaccines transmitted via maternal immunization include those for influenza, diphtheria, tetanus, and pertussis.
Annually, RSV has a devastating impact on young children, hospitalizing tens of thousands and causing up to 300 deaths, data show.
For every 100 children who get RSV under 6 months of age, one or two of them may need to be hospitalized, according to the CDC. Those hospitalized infants may need oxygen, intubation, or even mechanical ventilation to help with breathing.
“Most improve with this type of supportive care and are discharged in a few days,” the CDC said.
“I think this is a big step for protecting babies against RSV and improving overall lung health,” vaccine researcher Barney Graham, PhD, told the Post. “Overall, it’s an exciting time for RSV. It’s also a troubling time, because you see how the patterns of infection have been changed by COVID, and we’re having an earlier, bigger season this year than we have for a couple of years – and it’s causing a lot of hospitalization and misery for people.”
As many as four RSV vaccines may have applications submitted to the FDA in 2022, according to CNN. Also in development is an antibody shot given to infants just after they are born, the news outlet reported.
Pfizer’s data, announced Tuesday, has not yet been published or peer-reviewed, but the company said it is seeking peer-reviewed publication.
“We are thrilled by these data, as this is the first-ever investigational vaccine shown to help protect newborns against severe RSV-related respiratory illness immediately at birth,” Annaliesa Anderson, PhD, Pfizer chief scientific officer for vaccine research & development, said in a statement. “We look forward to working with the FDA and other regulatory agencies to bring this vaccine candidate to expectant mothers to help protect their infants against severe RSV during their most vulnerable first six months of life, which has the highest burden of RSV illness in infants.”
A version of this article first appeared on WebMD.com.
New trial data from drugmaker Pfizer shows promising results of a vaccine given to mothers during pregnancy that later protects infants in their first months from the worst effects of respiratory syncytial virus, or RSV.
Pfizer will apply for FDA approval by the end of the year, the company said in a statement Nov. 1.
Trial results are so promising that – after talking with government regulators – the company will stop enrolling new people in the study.
Specifically, the company reported that the vaccine prevented severe illness particularly well during the first 90 days of life, with measurable protection against severe illness continuing through 6 months of age. (That period is when infants are the most fragile if they get sick with RSV.)
RSV is a respiratory illness than can affect anyone, usually resulting in no symptoms or those similar to the common cold. But it can be particularly dangerous – and even deadly – for babies and for people over the age of 65. Pfizer and another drug company, GSK, are developing promising vaccines for older adults, the Washington Post reported.
RSV is the leading cause of hospitalization for infants, the Post noted.
The Pfizer study, called MATISSE, enrolled 7,400 pregnant women in 18 countries worldwide. Those who received the vaccine were given it during the late second to third trimester of pregnancy. Women in the study were monitored for safety through the rest of their pregnancy and 6 months after their children were born. Infants were monitored for at least 1 year for safety and effectiveness; more than half of them were monitored for 2 years.
The Pfizer vaccine works by passing maternal antibodies to the infant during pregnancy, the Post reported, noting that other vaccines transmitted via maternal immunization include those for influenza, diphtheria, tetanus, and pertussis.
Annually, RSV has a devastating impact on young children, hospitalizing tens of thousands and causing up to 300 deaths, data show.
For every 100 children who get RSV under 6 months of age, one or two of them may need to be hospitalized, according to the CDC. Those hospitalized infants may need oxygen, intubation, or even mechanical ventilation to help with breathing.
“Most improve with this type of supportive care and are discharged in a few days,” the CDC said.
“I think this is a big step for protecting babies against RSV and improving overall lung health,” vaccine researcher Barney Graham, PhD, told the Post. “Overall, it’s an exciting time for RSV. It’s also a troubling time, because you see how the patterns of infection have been changed by COVID, and we’re having an earlier, bigger season this year than we have for a couple of years – and it’s causing a lot of hospitalization and misery for people.”
As many as four RSV vaccines may have applications submitted to the FDA in 2022, according to CNN. Also in development is an antibody shot given to infants just after they are born, the news outlet reported.
Pfizer’s data, announced Tuesday, has not yet been published or peer-reviewed, but the company said it is seeking peer-reviewed publication.
“We are thrilled by these data, as this is the first-ever investigational vaccine shown to help protect newborns against severe RSV-related respiratory illness immediately at birth,” Annaliesa Anderson, PhD, Pfizer chief scientific officer for vaccine research & development, said in a statement. “We look forward to working with the FDA and other regulatory agencies to bring this vaccine candidate to expectant mothers to help protect their infants against severe RSV during their most vulnerable first six months of life, which has the highest burden of RSV illness in infants.”
A version of this article first appeared on WebMD.com.
New trial data from drugmaker Pfizer shows promising results of a vaccine given to mothers during pregnancy that later protects infants in their first months from the worst effects of respiratory syncytial virus, or RSV.
Pfizer will apply for FDA approval by the end of the year, the company said in a statement Nov. 1.
Trial results are so promising that – after talking with government regulators – the company will stop enrolling new people in the study.
Specifically, the company reported that the vaccine prevented severe illness particularly well during the first 90 days of life, with measurable protection against severe illness continuing through 6 months of age. (That period is when infants are the most fragile if they get sick with RSV.)
RSV is a respiratory illness than can affect anyone, usually resulting in no symptoms or those similar to the common cold. But it can be particularly dangerous – and even deadly – for babies and for people over the age of 65. Pfizer and another drug company, GSK, are developing promising vaccines for older adults, the Washington Post reported.
RSV is the leading cause of hospitalization for infants, the Post noted.
The Pfizer study, called MATISSE, enrolled 7,400 pregnant women in 18 countries worldwide. Those who received the vaccine were given it during the late second to third trimester of pregnancy. Women in the study were monitored for safety through the rest of their pregnancy and 6 months after their children were born. Infants were monitored for at least 1 year for safety and effectiveness; more than half of them were monitored for 2 years.
The Pfizer vaccine works by passing maternal antibodies to the infant during pregnancy, the Post reported, noting that other vaccines transmitted via maternal immunization include those for influenza, diphtheria, tetanus, and pertussis.
Annually, RSV has a devastating impact on young children, hospitalizing tens of thousands and causing up to 300 deaths, data show.
For every 100 children who get RSV under 6 months of age, one or two of them may need to be hospitalized, according to the CDC. Those hospitalized infants may need oxygen, intubation, or even mechanical ventilation to help with breathing.
“Most improve with this type of supportive care and are discharged in a few days,” the CDC said.
“I think this is a big step for protecting babies against RSV and improving overall lung health,” vaccine researcher Barney Graham, PhD, told the Post. “Overall, it’s an exciting time for RSV. It’s also a troubling time, because you see how the patterns of infection have been changed by COVID, and we’re having an earlier, bigger season this year than we have for a couple of years – and it’s causing a lot of hospitalization and misery for people.”
As many as four RSV vaccines may have applications submitted to the FDA in 2022, according to CNN. Also in development is an antibody shot given to infants just after they are born, the news outlet reported.
Pfizer’s data, announced Tuesday, has not yet been published or peer-reviewed, but the company said it is seeking peer-reviewed publication.
“We are thrilled by these data, as this is the first-ever investigational vaccine shown to help protect newborns against severe RSV-related respiratory illness immediately at birth,” Annaliesa Anderson, PhD, Pfizer chief scientific officer for vaccine research & development, said in a statement. “We look forward to working with the FDA and other regulatory agencies to bring this vaccine candidate to expectant mothers to help protect their infants against severe RSV during their most vulnerable first six months of life, which has the highest burden of RSV illness in infants.”
A version of this article first appeared on WebMD.com.
Marital stress tied to worse outcome in young MI patients
Severe marital stress was associated with worse recovery after myocardial infarction in a large U.S. cohort of married/partnered patients aged 55 years or younger.
Compared with patients who reported no or mild marital stress a month after their MI, patients who reported severe marital stress had worse physical and mental health, worse generic and cardiovascular quality of life, more frequent angina symptoms, and a greater likelihood of having a hospital readmission a year later.
These findings held true after adjusting for gender, age, race/ethnicity, and baseline health status (model 1) and after further adjusting for education and income levels and employment and insurance status (model 2).
A greater percentage of women than men reported having severe marital stress (39% vs. 30%; P = .001).
Cenjing Zhu, MPhil, a PhD candidate at Yale University, New Haven, Conn., and colleagues will present this study at the American Heart Association scientific sessions.
The results show that “both patients and care providers should be aware that stress experienced in one’s everyday life, such as marital stress, can affect AMI [acute MI] recovery,” Ms. Zhu said in an email.
Health care providers should consider incorporating screening for everyday stress during follow-up patient visits to better spot people at high risk of a poor recovery and further hospitalizations, she added. When possible, they could guide patients to resources to help them manage and reduce their stress levels.
According to Ms. Zhu, the findings suggest that “managing personal stress may be as important as managing other clinical risk factors during the recovery process.”
This study in younger patients with MI “shows that high levels of marital stress impair heart attack recovery, and women have greater impairment in their heart attack recovery compared to men,” AHA spokesperson Nieca Goldberg, MD, who was not involved with this research, told this news organization.
The study shows that “clinicians have to incorporate mental health as part of their assessment of all patients,” said Dr. Goldberg, a clinical associate professor of medicine at New York University and medical director of Atria New York City.
“Our mental health impacts our physical health,” she noted. “Questions about marital stress should be included as part of an overall assessment of mental health. This means assessing all patients for stress, anxiety, and depression.”
Patients who are experiencing marital stress should share the information with their doctor and discuss ways to be referred to therapists and cardiac rehabilitation providers, she said. “My final thought is, women have often been told that their cardiac symptoms are due to stress by doctors. Now we know stress impacts physical health and [is] no longer an excuse but a contributing factor to our physical health.”
Does marital stress affect young MI recovery?
Previous literature has linked psychological stress with worse cardiovascular outcomes, Ms. Zhu noted.
However, little is known about the prognostic impact of marital stress on 1-year health outcomes for younger people who survive an MI.
To investigate this, the researchers analyzed data from participants in the Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) study.
The current study comprised 1,593 adults, including 1,020 female participants (64%), who were treated for MI at 103 hospitals in 30 U.S. states.
VIRGO enrolled participants in a 2:1 female-to-male ratio so as to enrich the inclusion of women, Ms. Zhu explained.
In the study, “partnered” participants were individuals who self-reported as “living as married/living with a partner.” There were 126 such patients (8%) in the current study.
The mean age of the patients was 47, and about 90% were 40-55 years old. Three quarters were White, 13% were Black, and 7% were Hispanic.
Marital stress was assessed on the basis of patients’ replies to 17 questions in the Stockholm Marital Stress Scale regarding the quality of their emotional and sexual relationships with their spouses/partners.
The researchers divided patients into three groups on the basis of their marital stress: mild or absent (lowest quartile), moderate (second quartile), and severe (upper two quartiles).
At 1 year after their MI, patients replied to questionnaires that assessed their health, quality of life, and depressive and angina symptoms. Hospital readmissions were determined on the basis of self-reports and medical records.
Compared to participants who reported no or mild marital stress, those who reported severe mental stress had significantly worse scores for physical and mental health and generic and cardiovascular quality of life, after adjusting for baseline health and demographics. They had worse scores for mental health and quality of life, after further adjusting for socioeconomic status.
In the fully adjusted model, patients who reported severe marital stress were significantly more likely to report more frequent chest pain/angina (odds ratio, 1.49; 95% confidence interval, 1.06-2.10; P = .023) and to have been readmitted to hospital for any cause (OR, 1.45; 95% CI, 1.04-2.00; P = .006), compared with the patients who reported no or mild marital stress.
Study limitations include the fact that the findings are based on self-reported questionnaire replies; they may not be generalizable to patients in other countries; and they do not extend beyond a period of 1 year.
The researchers call for further research “to understand this complex relationship and potential causal pathway associated with these findings.”
“Additional stressors beyond marital stress, such as financial strain or work stress, may also play a role in young adults’ recovery, and the interaction between these factors require further research,” Ms. Zhu noted in a press release from the AHA.
The study was funded by Canadian Institutes of Health Research. The VIRGO study was funded by the National Heart, Lung, and Blood Institute. Ms. Zhu and Dr. Goldberg have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Severe marital stress was associated with worse recovery after myocardial infarction in a large U.S. cohort of married/partnered patients aged 55 years or younger.
Compared with patients who reported no or mild marital stress a month after their MI, patients who reported severe marital stress had worse physical and mental health, worse generic and cardiovascular quality of life, more frequent angina symptoms, and a greater likelihood of having a hospital readmission a year later.
These findings held true after adjusting for gender, age, race/ethnicity, and baseline health status (model 1) and after further adjusting for education and income levels and employment and insurance status (model 2).
A greater percentage of women than men reported having severe marital stress (39% vs. 30%; P = .001).
Cenjing Zhu, MPhil, a PhD candidate at Yale University, New Haven, Conn., and colleagues will present this study at the American Heart Association scientific sessions.
The results show that “both patients and care providers should be aware that stress experienced in one’s everyday life, such as marital stress, can affect AMI [acute MI] recovery,” Ms. Zhu said in an email.
Health care providers should consider incorporating screening for everyday stress during follow-up patient visits to better spot people at high risk of a poor recovery and further hospitalizations, she added. When possible, they could guide patients to resources to help them manage and reduce their stress levels.
According to Ms. Zhu, the findings suggest that “managing personal stress may be as important as managing other clinical risk factors during the recovery process.”
This study in younger patients with MI “shows that high levels of marital stress impair heart attack recovery, and women have greater impairment in their heart attack recovery compared to men,” AHA spokesperson Nieca Goldberg, MD, who was not involved with this research, told this news organization.
The study shows that “clinicians have to incorporate mental health as part of their assessment of all patients,” said Dr. Goldberg, a clinical associate professor of medicine at New York University and medical director of Atria New York City.
“Our mental health impacts our physical health,” she noted. “Questions about marital stress should be included as part of an overall assessment of mental health. This means assessing all patients for stress, anxiety, and depression.”
Patients who are experiencing marital stress should share the information with their doctor and discuss ways to be referred to therapists and cardiac rehabilitation providers, she said. “My final thought is, women have often been told that their cardiac symptoms are due to stress by doctors. Now we know stress impacts physical health and [is] no longer an excuse but a contributing factor to our physical health.”
Does marital stress affect young MI recovery?
Previous literature has linked psychological stress with worse cardiovascular outcomes, Ms. Zhu noted.
However, little is known about the prognostic impact of marital stress on 1-year health outcomes for younger people who survive an MI.
To investigate this, the researchers analyzed data from participants in the Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) study.
The current study comprised 1,593 adults, including 1,020 female participants (64%), who were treated for MI at 103 hospitals in 30 U.S. states.
VIRGO enrolled participants in a 2:1 female-to-male ratio so as to enrich the inclusion of women, Ms. Zhu explained.
In the study, “partnered” participants were individuals who self-reported as “living as married/living with a partner.” There were 126 such patients (8%) in the current study.
The mean age of the patients was 47, and about 90% were 40-55 years old. Three quarters were White, 13% were Black, and 7% were Hispanic.
Marital stress was assessed on the basis of patients’ replies to 17 questions in the Stockholm Marital Stress Scale regarding the quality of their emotional and sexual relationships with their spouses/partners.
The researchers divided patients into three groups on the basis of their marital stress: mild or absent (lowest quartile), moderate (second quartile), and severe (upper two quartiles).
At 1 year after their MI, patients replied to questionnaires that assessed their health, quality of life, and depressive and angina symptoms. Hospital readmissions were determined on the basis of self-reports and medical records.
Compared to participants who reported no or mild marital stress, those who reported severe mental stress had significantly worse scores for physical and mental health and generic and cardiovascular quality of life, after adjusting for baseline health and demographics. They had worse scores for mental health and quality of life, after further adjusting for socioeconomic status.
In the fully adjusted model, patients who reported severe marital stress were significantly more likely to report more frequent chest pain/angina (odds ratio, 1.49; 95% confidence interval, 1.06-2.10; P = .023) and to have been readmitted to hospital for any cause (OR, 1.45; 95% CI, 1.04-2.00; P = .006), compared with the patients who reported no or mild marital stress.
Study limitations include the fact that the findings are based on self-reported questionnaire replies; they may not be generalizable to patients in other countries; and they do not extend beyond a period of 1 year.
The researchers call for further research “to understand this complex relationship and potential causal pathway associated with these findings.”
“Additional stressors beyond marital stress, such as financial strain or work stress, may also play a role in young adults’ recovery, and the interaction between these factors require further research,” Ms. Zhu noted in a press release from the AHA.
The study was funded by Canadian Institutes of Health Research. The VIRGO study was funded by the National Heart, Lung, and Blood Institute. Ms. Zhu and Dr. Goldberg have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Severe marital stress was associated with worse recovery after myocardial infarction in a large U.S. cohort of married/partnered patients aged 55 years or younger.
Compared with patients who reported no or mild marital stress a month after their MI, patients who reported severe marital stress had worse physical and mental health, worse generic and cardiovascular quality of life, more frequent angina symptoms, and a greater likelihood of having a hospital readmission a year later.
These findings held true after adjusting for gender, age, race/ethnicity, and baseline health status (model 1) and after further adjusting for education and income levels and employment and insurance status (model 2).
A greater percentage of women than men reported having severe marital stress (39% vs. 30%; P = .001).
Cenjing Zhu, MPhil, a PhD candidate at Yale University, New Haven, Conn., and colleagues will present this study at the American Heart Association scientific sessions.
The results show that “both patients and care providers should be aware that stress experienced in one’s everyday life, such as marital stress, can affect AMI [acute MI] recovery,” Ms. Zhu said in an email.
Health care providers should consider incorporating screening for everyday stress during follow-up patient visits to better spot people at high risk of a poor recovery and further hospitalizations, she added. When possible, they could guide patients to resources to help them manage and reduce their stress levels.
According to Ms. Zhu, the findings suggest that “managing personal stress may be as important as managing other clinical risk factors during the recovery process.”
This study in younger patients with MI “shows that high levels of marital stress impair heart attack recovery, and women have greater impairment in their heart attack recovery compared to men,” AHA spokesperson Nieca Goldberg, MD, who was not involved with this research, told this news organization.
The study shows that “clinicians have to incorporate mental health as part of their assessment of all patients,” said Dr. Goldberg, a clinical associate professor of medicine at New York University and medical director of Atria New York City.
“Our mental health impacts our physical health,” she noted. “Questions about marital stress should be included as part of an overall assessment of mental health. This means assessing all patients for stress, anxiety, and depression.”
Patients who are experiencing marital stress should share the information with their doctor and discuss ways to be referred to therapists and cardiac rehabilitation providers, she said. “My final thought is, women have often been told that their cardiac symptoms are due to stress by doctors. Now we know stress impacts physical health and [is] no longer an excuse but a contributing factor to our physical health.”
Does marital stress affect young MI recovery?
Previous literature has linked psychological stress with worse cardiovascular outcomes, Ms. Zhu noted.
However, little is known about the prognostic impact of marital stress on 1-year health outcomes for younger people who survive an MI.
To investigate this, the researchers analyzed data from participants in the Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) study.
The current study comprised 1,593 adults, including 1,020 female participants (64%), who were treated for MI at 103 hospitals in 30 U.S. states.
VIRGO enrolled participants in a 2:1 female-to-male ratio so as to enrich the inclusion of women, Ms. Zhu explained.
In the study, “partnered” participants were individuals who self-reported as “living as married/living with a partner.” There were 126 such patients (8%) in the current study.
The mean age of the patients was 47, and about 90% were 40-55 years old. Three quarters were White, 13% were Black, and 7% were Hispanic.
Marital stress was assessed on the basis of patients’ replies to 17 questions in the Stockholm Marital Stress Scale regarding the quality of their emotional and sexual relationships with their spouses/partners.
The researchers divided patients into three groups on the basis of their marital stress: mild or absent (lowest quartile), moderate (second quartile), and severe (upper two quartiles).
At 1 year after their MI, patients replied to questionnaires that assessed their health, quality of life, and depressive and angina symptoms. Hospital readmissions were determined on the basis of self-reports and medical records.
Compared to participants who reported no or mild marital stress, those who reported severe mental stress had significantly worse scores for physical and mental health and generic and cardiovascular quality of life, after adjusting for baseline health and demographics. They had worse scores for mental health and quality of life, after further adjusting for socioeconomic status.
In the fully adjusted model, patients who reported severe marital stress were significantly more likely to report more frequent chest pain/angina (odds ratio, 1.49; 95% confidence interval, 1.06-2.10; P = .023) and to have been readmitted to hospital for any cause (OR, 1.45; 95% CI, 1.04-2.00; P = .006), compared with the patients who reported no or mild marital stress.
Study limitations include the fact that the findings are based on self-reported questionnaire replies; they may not be generalizable to patients in other countries; and they do not extend beyond a period of 1 year.
The researchers call for further research “to understand this complex relationship and potential causal pathway associated with these findings.”
“Additional stressors beyond marital stress, such as financial strain or work stress, may also play a role in young adults’ recovery, and the interaction between these factors require further research,” Ms. Zhu noted in a press release from the AHA.
The study was funded by Canadian Institutes of Health Research. The VIRGO study was funded by the National Heart, Lung, and Blood Institute. Ms. Zhu and Dr. Goldberg have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AHA 2022