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Drug combo slows functional decline in ALS
, according to results of the phase 2/3 CENTAUR study.
Patients with a fast-progressing form of ALS who were treated with AMX0035 “retained higher levels of physical function over 6 months compared with those who received placebo,” reported principal investigator Sabrina Paganoni, MD, PhD, of the Sean M. Healey and AMG Center for ALS at Massachusetts General Hospital, Boston.
“This is very hopeful news for people affected by ALS, especially because we were able to see a treatment effect in a relatively short period of time,” Dr. Paganoni said.
The study was published online Sept. 3 in the New England Journal of Medicine.
In this study, AMX0035 demonstrated a “clinically meaningful benefit and a favorable safety profile for people living with ALS,” Josh Cohen, co-CEO, chairman, and cofounder at Amylyx, said in a news release. The company is “working collaboratively and expeditiously with agencies worldwide to bring this potential new treatment option forward.”
“The data ... makes a clear and compelling case that AMX0035 should be made available to people with ALS as soon as possible,” Calaneet Balas, president and CEO of The ALS Association, said in the release.
The CENTAUR trial
Sodium phenylbutyrate and taurursodiol have been found to reduce neuronal death in experimental models. AMX0035 combines 3 g sodium phenylbutyrate and 1 g of taurursodiol.
The CENTAUR trial tested AMX0035 against placebo in 137 ALS patients with symptom onset within the prior 18 months, with 89 patients in the AMX0035 group and 48 in the placebo group. AMX0035 or matching placebo were administered once daily for 3 weeks and then twice daily for a planned duration of 24 weeks.
In a modified intention-to-treat analysis, the mean rate of change in the Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised (ALSFRS-R) score was −1.24 points per month with AMX0035 and −1.66 points per month with placebo (difference, 0.42 points per month; 95% CI, 0.03 - 0.81; P = .03). After 24 weeks, patients treated with AMX0035 scored on average 2.32 points higher on the ALSFRS-R than their peers on placebo group (P = .03).
“The score, consisting of four subdomains, showed a change that was most prominent for the fine-motor subscale and less apparent for the other subscales,” the investigators said.
Treatment with AMX0035 led to slowing of disease progression in a population in which many participants were receiving riluzole (Tiglutik), edaravone (Radicava) or both, they pointed out.
The secondary outcomes were rate of decline in isometric muscle strength and breathing function; change in plasma phosphorylated axonal neurofilament H subunit (pNF-H) levels; and the time to composite events of death, tracheostomy, permanent ventilation, and hospitalization. These outcomes did not differ significantly between the two groups.
Open-label extension ongoing
AMX0035 was generally well tolerated. Nearly all patients in both groups had one or more adverse events. Events occurring at 2% or greater frequency in the AMX0035 group were primarily gastrointestinal (diarrhea, nausea, salivary hypersecretion, and abdominal discomfort). Serious adverse events were more common in the placebo group (19% vs. 12%). The incidence of respiratory serious adverse events was 8% in the placebo group and 3% in the AMX0035 group.
More patients on active treatment than placebo (19% vs. 8%) stopped the trial regimen early owing to adverse events. The most common adverse events leading to discontinuation of the trial regimen were diarrhea and respiratory failure.
The trial was “too short for us to detect an effect on survival,” Dr. Paganoni said in an interview. Most of the participants who completed the trial elected to enroll in an open-label extension study and receive AMX0035 long-term. “This is important because it will teach us about the impact of AMX0035 on survival,” said Dr. Paganoni.
Interim data from the ongoing open-label extension study are being submitted to a peer-reviewed journal shortly and will be published in the coming months.
A cause for hope
“There has been understandable frustration with the slow pace of development of therapy for ALS,” Michael Benatar, MD, PhD, University of Miami, and Michael McDermott, PhD, University of Rochester (N.Y.), said in an accompanying editorial.
“Despite dozens of trials, few pharmacologic agents have emerged that affect functional decline or survival – and all only modestly so. Although the effects of sodium phenylbutyrate–taurursodiol are similarly modest, the incremental gains that they provide in the battle against ALS are a cause for hope,” they wrote.
They caution, however, that this study was enriched for patients with more rapidly progressive disease, which “raises questions about generalizability to the broader population of patients with ALS.
“Although the patients who were enrolled in the trial may not be biologically different from the broader population of patients with ALS, the magnitude of therapeutic effect may be smaller in the latter,” Dr. Benatar and Dr. McDermott noted.
They said that in light of “residual questions about efficacy and the ability of patients to continue taking the drug,” they agree with the authors’ conclusion that “longer and larger trials are needed to evaluate the efficacy and safety of sodium phenylbutyrate–taurursodiol in persons with ALS.”
Given these “tantalizing preliminary data,” Dr. Benatar and Dr. McDermott said they look forward to “a confirmatory phase 3 trial.”
The study was supported by Amylyx Pharmaceuticals, the ALS Finding a Cure Foundation, and the ALS Association. Dr. Paganoni has received grants from Revalesio, Ra Pharma, Biohaven, Clene, and Prilenia. A complete list of disclosures for authors and editorialists is available with the original article.
A version of this article originally appeared on Medscape.com.
, according to results of the phase 2/3 CENTAUR study.
Patients with a fast-progressing form of ALS who were treated with AMX0035 “retained higher levels of physical function over 6 months compared with those who received placebo,” reported principal investigator Sabrina Paganoni, MD, PhD, of the Sean M. Healey and AMG Center for ALS at Massachusetts General Hospital, Boston.
“This is very hopeful news for people affected by ALS, especially because we were able to see a treatment effect in a relatively short period of time,” Dr. Paganoni said.
The study was published online Sept. 3 in the New England Journal of Medicine.
In this study, AMX0035 demonstrated a “clinically meaningful benefit and a favorable safety profile for people living with ALS,” Josh Cohen, co-CEO, chairman, and cofounder at Amylyx, said in a news release. The company is “working collaboratively and expeditiously with agencies worldwide to bring this potential new treatment option forward.”
“The data ... makes a clear and compelling case that AMX0035 should be made available to people with ALS as soon as possible,” Calaneet Balas, president and CEO of The ALS Association, said in the release.
The CENTAUR trial
Sodium phenylbutyrate and taurursodiol have been found to reduce neuronal death in experimental models. AMX0035 combines 3 g sodium phenylbutyrate and 1 g of taurursodiol.
The CENTAUR trial tested AMX0035 against placebo in 137 ALS patients with symptom onset within the prior 18 months, with 89 patients in the AMX0035 group and 48 in the placebo group. AMX0035 or matching placebo were administered once daily for 3 weeks and then twice daily for a planned duration of 24 weeks.
In a modified intention-to-treat analysis, the mean rate of change in the Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised (ALSFRS-R) score was −1.24 points per month with AMX0035 and −1.66 points per month with placebo (difference, 0.42 points per month; 95% CI, 0.03 - 0.81; P = .03). After 24 weeks, patients treated with AMX0035 scored on average 2.32 points higher on the ALSFRS-R than their peers on placebo group (P = .03).
“The score, consisting of four subdomains, showed a change that was most prominent for the fine-motor subscale and less apparent for the other subscales,” the investigators said.
Treatment with AMX0035 led to slowing of disease progression in a population in which many participants were receiving riluzole (Tiglutik), edaravone (Radicava) or both, they pointed out.
The secondary outcomes were rate of decline in isometric muscle strength and breathing function; change in plasma phosphorylated axonal neurofilament H subunit (pNF-H) levels; and the time to composite events of death, tracheostomy, permanent ventilation, and hospitalization. These outcomes did not differ significantly between the two groups.
Open-label extension ongoing
AMX0035 was generally well tolerated. Nearly all patients in both groups had one or more adverse events. Events occurring at 2% or greater frequency in the AMX0035 group were primarily gastrointestinal (diarrhea, nausea, salivary hypersecretion, and abdominal discomfort). Serious adverse events were more common in the placebo group (19% vs. 12%). The incidence of respiratory serious adverse events was 8% in the placebo group and 3% in the AMX0035 group.
More patients on active treatment than placebo (19% vs. 8%) stopped the trial regimen early owing to adverse events. The most common adverse events leading to discontinuation of the trial regimen were diarrhea and respiratory failure.
The trial was “too short for us to detect an effect on survival,” Dr. Paganoni said in an interview. Most of the participants who completed the trial elected to enroll in an open-label extension study and receive AMX0035 long-term. “This is important because it will teach us about the impact of AMX0035 on survival,” said Dr. Paganoni.
Interim data from the ongoing open-label extension study are being submitted to a peer-reviewed journal shortly and will be published in the coming months.
A cause for hope
“There has been understandable frustration with the slow pace of development of therapy for ALS,” Michael Benatar, MD, PhD, University of Miami, and Michael McDermott, PhD, University of Rochester (N.Y.), said in an accompanying editorial.
“Despite dozens of trials, few pharmacologic agents have emerged that affect functional decline or survival – and all only modestly so. Although the effects of sodium phenylbutyrate–taurursodiol are similarly modest, the incremental gains that they provide in the battle against ALS are a cause for hope,” they wrote.
They caution, however, that this study was enriched for patients with more rapidly progressive disease, which “raises questions about generalizability to the broader population of patients with ALS.
“Although the patients who were enrolled in the trial may not be biologically different from the broader population of patients with ALS, the magnitude of therapeutic effect may be smaller in the latter,” Dr. Benatar and Dr. McDermott noted.
They said that in light of “residual questions about efficacy and the ability of patients to continue taking the drug,” they agree with the authors’ conclusion that “longer and larger trials are needed to evaluate the efficacy and safety of sodium phenylbutyrate–taurursodiol in persons with ALS.”
Given these “tantalizing preliminary data,” Dr. Benatar and Dr. McDermott said they look forward to “a confirmatory phase 3 trial.”
The study was supported by Amylyx Pharmaceuticals, the ALS Finding a Cure Foundation, and the ALS Association. Dr. Paganoni has received grants from Revalesio, Ra Pharma, Biohaven, Clene, and Prilenia. A complete list of disclosures for authors and editorialists is available with the original article.
A version of this article originally appeared on Medscape.com.
, according to results of the phase 2/3 CENTAUR study.
Patients with a fast-progressing form of ALS who were treated with AMX0035 “retained higher levels of physical function over 6 months compared with those who received placebo,” reported principal investigator Sabrina Paganoni, MD, PhD, of the Sean M. Healey and AMG Center for ALS at Massachusetts General Hospital, Boston.
“This is very hopeful news for people affected by ALS, especially because we were able to see a treatment effect in a relatively short period of time,” Dr. Paganoni said.
The study was published online Sept. 3 in the New England Journal of Medicine.
In this study, AMX0035 demonstrated a “clinically meaningful benefit and a favorable safety profile for people living with ALS,” Josh Cohen, co-CEO, chairman, and cofounder at Amylyx, said in a news release. The company is “working collaboratively and expeditiously with agencies worldwide to bring this potential new treatment option forward.”
“The data ... makes a clear and compelling case that AMX0035 should be made available to people with ALS as soon as possible,” Calaneet Balas, president and CEO of The ALS Association, said in the release.
The CENTAUR trial
Sodium phenylbutyrate and taurursodiol have been found to reduce neuronal death in experimental models. AMX0035 combines 3 g sodium phenylbutyrate and 1 g of taurursodiol.
The CENTAUR trial tested AMX0035 against placebo in 137 ALS patients with symptom onset within the prior 18 months, with 89 patients in the AMX0035 group and 48 in the placebo group. AMX0035 or matching placebo were administered once daily for 3 weeks and then twice daily for a planned duration of 24 weeks.
In a modified intention-to-treat analysis, the mean rate of change in the Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised (ALSFRS-R) score was −1.24 points per month with AMX0035 and −1.66 points per month with placebo (difference, 0.42 points per month; 95% CI, 0.03 - 0.81; P = .03). After 24 weeks, patients treated with AMX0035 scored on average 2.32 points higher on the ALSFRS-R than their peers on placebo group (P = .03).
“The score, consisting of four subdomains, showed a change that was most prominent for the fine-motor subscale and less apparent for the other subscales,” the investigators said.
Treatment with AMX0035 led to slowing of disease progression in a population in which many participants were receiving riluzole (Tiglutik), edaravone (Radicava) or both, they pointed out.
The secondary outcomes were rate of decline in isometric muscle strength and breathing function; change in plasma phosphorylated axonal neurofilament H subunit (pNF-H) levels; and the time to composite events of death, tracheostomy, permanent ventilation, and hospitalization. These outcomes did not differ significantly between the two groups.
Open-label extension ongoing
AMX0035 was generally well tolerated. Nearly all patients in both groups had one or more adverse events. Events occurring at 2% or greater frequency in the AMX0035 group were primarily gastrointestinal (diarrhea, nausea, salivary hypersecretion, and abdominal discomfort). Serious adverse events were more common in the placebo group (19% vs. 12%). The incidence of respiratory serious adverse events was 8% in the placebo group and 3% in the AMX0035 group.
More patients on active treatment than placebo (19% vs. 8%) stopped the trial regimen early owing to adverse events. The most common adverse events leading to discontinuation of the trial regimen were diarrhea and respiratory failure.
The trial was “too short for us to detect an effect on survival,” Dr. Paganoni said in an interview. Most of the participants who completed the trial elected to enroll in an open-label extension study and receive AMX0035 long-term. “This is important because it will teach us about the impact of AMX0035 on survival,” said Dr. Paganoni.
Interim data from the ongoing open-label extension study are being submitted to a peer-reviewed journal shortly and will be published in the coming months.
A cause for hope
“There has been understandable frustration with the slow pace of development of therapy for ALS,” Michael Benatar, MD, PhD, University of Miami, and Michael McDermott, PhD, University of Rochester (N.Y.), said in an accompanying editorial.
“Despite dozens of trials, few pharmacologic agents have emerged that affect functional decline or survival – and all only modestly so. Although the effects of sodium phenylbutyrate–taurursodiol are similarly modest, the incremental gains that they provide in the battle against ALS are a cause for hope,” they wrote.
They caution, however, that this study was enriched for patients with more rapidly progressive disease, which “raises questions about generalizability to the broader population of patients with ALS.
“Although the patients who were enrolled in the trial may not be biologically different from the broader population of patients with ALS, the magnitude of therapeutic effect may be smaller in the latter,” Dr. Benatar and Dr. McDermott noted.
They said that in light of “residual questions about efficacy and the ability of patients to continue taking the drug,” they agree with the authors’ conclusion that “longer and larger trials are needed to evaluate the efficacy and safety of sodium phenylbutyrate–taurursodiol in persons with ALS.”
Given these “tantalizing preliminary data,” Dr. Benatar and Dr. McDermott said they look forward to “a confirmatory phase 3 trial.”
The study was supported by Amylyx Pharmaceuticals, the ALS Finding a Cure Foundation, and the ALS Association. Dr. Paganoni has received grants from Revalesio, Ra Pharma, Biohaven, Clene, and Prilenia. A complete list of disclosures for authors and editorialists is available with the original article.
A version of this article originally appeared on Medscape.com.
From New England Journal of Medicine
‘No mobile phone’ phobia tied to sleep problems in college students
In a study of more than 300 college students, nearly 9 in 10 (89%) were classified as having moderate to severe nomophobia. Greater levels of nomophobia were significantly linked to daytime sleepiness and more behaviors associated with poor sleep hygiene.
“My undergraduate research team came up with the idea for this study,” said study investigator Jennifer Peszka, PhD, professor of psychology at Hendrix College, Conway, Ark. She explained that her students had been looking at the impact of technology use in the 2 hours before bed, and hypothesized that ‘cell phone addiction’ might play a role in sleep problems.
Incidentally, “that group of students were all pretty high on nomophobia themselves so they were really interested in the outcome,” Dr. Peszka said.
The study findings were presented at the virtual annual meeting of the Associated Professional Sleep Societies.
A likely suspect
The study involved 327 undergraduates (mean age, 19.7 years) recruited from introductory psychology courses and campus newsletters. They completed several questionnaires, including the Nomophobia Questionnaire, the Epworth Sleepiness Scale, and the Sleep Hygiene Index.
Nomophobia was prevalent, with mild, moderate, and severe nomophobia reported by 10%, 83%, and 7% of students, respectively. Only one student reported no nomophobia at all. Dr. Peszka said the fact that 89% of students had moderate or severe nomophobia is “concerning,” given a 2012 study suggesting that 77% of 18- to 24-year-olds had nomophobia. This phobia “very well may be on a rapid rise,” she lamented.
Greater severity of nomophobia was significantly correlated with greater sleepiness measured by both the Epworth Sleepiness Scale (P < .05) and the Associated Features of Poor Sleep Hygiene daytime sleepiness item (P < .05). More severe nomophobia was also related to decreased motivation (a commonly reported symptom of insufficient sleep) and with more maladaptive sleep hygiene behaviors (including using technology during sleep time, long daytime naps, inconsistent wake and bed times, using bed for nonsleep purposes, uncomfortable bed, and bedtime cognitive rumination).
Prior research has shown that smartphones may lead to compulsive “checking” habits, compulsive usage, increased distress, and potentially addictive behaviors. Active phone use at bedtime has also been implicated in disrupted sleep. Nomophobia is likely to be an important consideration when treating sleep disorders and/or making any sleep hygiene recommendations, Dr. Peszka said.
Proliferation of ‘night owls’
Reached for comment, Rajkumar (Raj) Dasgupta, MD, University of Southern California, Los Angeles, said this is a “very timely study with COVID-19. Right now, more than ever, technology is a double-edged sword. I’m a father of three kids and, for now, technology is the only way some kids are going to be socializing and learning.”
Yet a foundation of good sleep hygiene is keeping a nightly sleep routine, said Dr. Dasgupta, who was not involved in the study. “Right now, it seems like all my sleep patients are becoming night owls and sleep time is becoming more and more delayed because there is so much news to keep up with. Also, you may be stressed at night and you may not have the motivation to wake up early in the morning.”
He said it is important to counsel patients to “put technology away at night. That goes for kids and adults.”
Support for the study was provided by Hendrix College Charles Brewer Fund for Psychology. Dr. Peszka and Dr. Dasgupta disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
In a study of more than 300 college students, nearly 9 in 10 (89%) were classified as having moderate to severe nomophobia. Greater levels of nomophobia were significantly linked to daytime sleepiness and more behaviors associated with poor sleep hygiene.
“My undergraduate research team came up with the idea for this study,” said study investigator Jennifer Peszka, PhD, professor of psychology at Hendrix College, Conway, Ark. She explained that her students had been looking at the impact of technology use in the 2 hours before bed, and hypothesized that ‘cell phone addiction’ might play a role in sleep problems.
Incidentally, “that group of students were all pretty high on nomophobia themselves so they were really interested in the outcome,” Dr. Peszka said.
The study findings were presented at the virtual annual meeting of the Associated Professional Sleep Societies.
A likely suspect
The study involved 327 undergraduates (mean age, 19.7 years) recruited from introductory psychology courses and campus newsletters. They completed several questionnaires, including the Nomophobia Questionnaire, the Epworth Sleepiness Scale, and the Sleep Hygiene Index.
Nomophobia was prevalent, with mild, moderate, and severe nomophobia reported by 10%, 83%, and 7% of students, respectively. Only one student reported no nomophobia at all. Dr. Peszka said the fact that 89% of students had moderate or severe nomophobia is “concerning,” given a 2012 study suggesting that 77% of 18- to 24-year-olds had nomophobia. This phobia “very well may be on a rapid rise,” she lamented.
Greater severity of nomophobia was significantly correlated with greater sleepiness measured by both the Epworth Sleepiness Scale (P < .05) and the Associated Features of Poor Sleep Hygiene daytime sleepiness item (P < .05). More severe nomophobia was also related to decreased motivation (a commonly reported symptom of insufficient sleep) and with more maladaptive sleep hygiene behaviors (including using technology during sleep time, long daytime naps, inconsistent wake and bed times, using bed for nonsleep purposes, uncomfortable bed, and bedtime cognitive rumination).
Prior research has shown that smartphones may lead to compulsive “checking” habits, compulsive usage, increased distress, and potentially addictive behaviors. Active phone use at bedtime has also been implicated in disrupted sleep. Nomophobia is likely to be an important consideration when treating sleep disorders and/or making any sleep hygiene recommendations, Dr. Peszka said.
Proliferation of ‘night owls’
Reached for comment, Rajkumar (Raj) Dasgupta, MD, University of Southern California, Los Angeles, said this is a “very timely study with COVID-19. Right now, more than ever, technology is a double-edged sword. I’m a father of three kids and, for now, technology is the only way some kids are going to be socializing and learning.”
Yet a foundation of good sleep hygiene is keeping a nightly sleep routine, said Dr. Dasgupta, who was not involved in the study. “Right now, it seems like all my sleep patients are becoming night owls and sleep time is becoming more and more delayed because there is so much news to keep up with. Also, you may be stressed at night and you may not have the motivation to wake up early in the morning.”
He said it is important to counsel patients to “put technology away at night. That goes for kids and adults.”
Support for the study was provided by Hendrix College Charles Brewer Fund for Psychology. Dr. Peszka and Dr. Dasgupta disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
In a study of more than 300 college students, nearly 9 in 10 (89%) were classified as having moderate to severe nomophobia. Greater levels of nomophobia were significantly linked to daytime sleepiness and more behaviors associated with poor sleep hygiene.
“My undergraduate research team came up with the idea for this study,” said study investigator Jennifer Peszka, PhD, professor of psychology at Hendrix College, Conway, Ark. She explained that her students had been looking at the impact of technology use in the 2 hours before bed, and hypothesized that ‘cell phone addiction’ might play a role in sleep problems.
Incidentally, “that group of students were all pretty high on nomophobia themselves so they were really interested in the outcome,” Dr. Peszka said.
The study findings were presented at the virtual annual meeting of the Associated Professional Sleep Societies.
A likely suspect
The study involved 327 undergraduates (mean age, 19.7 years) recruited from introductory psychology courses and campus newsletters. They completed several questionnaires, including the Nomophobia Questionnaire, the Epworth Sleepiness Scale, and the Sleep Hygiene Index.
Nomophobia was prevalent, with mild, moderate, and severe nomophobia reported by 10%, 83%, and 7% of students, respectively. Only one student reported no nomophobia at all. Dr. Peszka said the fact that 89% of students had moderate or severe nomophobia is “concerning,” given a 2012 study suggesting that 77% of 18- to 24-year-olds had nomophobia. This phobia “very well may be on a rapid rise,” she lamented.
Greater severity of nomophobia was significantly correlated with greater sleepiness measured by both the Epworth Sleepiness Scale (P < .05) and the Associated Features of Poor Sleep Hygiene daytime sleepiness item (P < .05). More severe nomophobia was also related to decreased motivation (a commonly reported symptom of insufficient sleep) and with more maladaptive sleep hygiene behaviors (including using technology during sleep time, long daytime naps, inconsistent wake and bed times, using bed for nonsleep purposes, uncomfortable bed, and bedtime cognitive rumination).
Prior research has shown that smartphones may lead to compulsive “checking” habits, compulsive usage, increased distress, and potentially addictive behaviors. Active phone use at bedtime has also been implicated in disrupted sleep. Nomophobia is likely to be an important consideration when treating sleep disorders and/or making any sleep hygiene recommendations, Dr. Peszka said.
Proliferation of ‘night owls’
Reached for comment, Rajkumar (Raj) Dasgupta, MD, University of Southern California, Los Angeles, said this is a “very timely study with COVID-19. Right now, more than ever, technology is a double-edged sword. I’m a father of three kids and, for now, technology is the only way some kids are going to be socializing and learning.”
Yet a foundation of good sleep hygiene is keeping a nightly sleep routine, said Dr. Dasgupta, who was not involved in the study. “Right now, it seems like all my sleep patients are becoming night owls and sleep time is becoming more and more delayed because there is so much news to keep up with. Also, you may be stressed at night and you may not have the motivation to wake up early in the morning.”
He said it is important to counsel patients to “put technology away at night. That goes for kids and adults.”
Support for the study was provided by Hendrix College Charles Brewer Fund for Psychology. Dr. Peszka and Dr. Dasgupta disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM SLEEP 2020
Experts advocate for the elimination of daylight savings time
In the interest of public health and safety, – a recommendation that has garnered strong support from multiple medical and other high-profile organizations.
“Permanent, year-round standard time is the best choice to most closely match our circadian sleep-wake cycle,” M. Adeel Rishi, MD, lead author of the AASM position statement, said in a news release. “Daylight saving time results in more darkness in the morning and more light in the evening, disrupting the body’s natural rhythm,” said Dr. Rishi, of the department of pulmonology, critical care, and sleep medicine, Mayo Clinic, Eau Claire, Wis., and vice chair of the AASM Public Safety Committee.
The position statement was published Aug. 26 in the Journal of Clinical Sleep Medicine to coincide with the virtual annual meeting of the Associated Professional Sleep Societies .
Significant health risks
In the United States, the annual “spring forward” to daylight saving time and “fall back” to standard time is required by law, although under the statute some exceptions are permitted.
There has been intense debate over the last several years about transitioning between standard and daylight saving time. The AASM says there is “an abundance of evidence” to indicate that quick transition from standard time to daylight saving time incurs significant public health and safety risks, including increased risk of heart attack, stroke, mood disorders, and car crashes.
“Although chronic effects of remaining in daylight saving time year-round have not been well-studied, daylight saving time is less aligned with human circadian biology – which, because of the impacts of the delayed natural light/dark cycle on human activity, could result in circadian misalignment, which has been associated in some studies with increased cardiovascular disease risk, metabolic syndrome and other health risks,” the authors wrote.
A recent study also showed an increase in medical errors in the week after switching to daylight saving time.
“Because the adoption of permanent standard time would be beneficial for public health and safety, the AASM will be advocating at the federal level for this legislative change,” said AASM President Kannan Ramar, MBBS, MD, with the Mayo Clinic in Rochester, Minn.
It seems that many Americans are in favor of the change. In July, an AASM survey of roughly 2,000 U.S. adults showed that two-thirds support doing away with the seasonal time change. Only 11% opposed it. In addition, the academy’s 2019 survey showed more than half of adults feel extremely, or somewhat, tired after the springing ahead to daylight saving time.
Strong support
The position statement has been endorsed by 19 organizations, including the American Academy of Cardiovascular Sleep Medicine, American College of Chest Physicians (CHEST), American College of Occupational and Environmental Medicine, National PTA, National Safety Council, Society of Anesthesia and Sleep Medicine, and the Society of Behavioral Sleep Medicine.
Weighing in on the issue, Saul Rothenberg, PhD, from the Sleep Center at Greenwich Hospital, Conn., said the literature on daylight saving time has grown over the past 20 years. He said he was ”humbled” by the research that shows that a “relatively small” misalignment of biological and social clocks has a measurable impact on human health and behavior.
“Because misalignment is associated with negative health and performance outcomes, keeping one set of hours year-round is promoted to minimize misalignment and associated consequences,” he added.
In light of this research, the recommendation to dispense with daylight saving time seems “quite reasonable” from a public health perspective. “I am left with a strengthened view on the importance of regular adequate sleep as a way to enhance health, performance, and quality of life,” he added.
This research had no commercial funding. Dr. Rishi and Dr. Rothenberg have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
In the interest of public health and safety, – a recommendation that has garnered strong support from multiple medical and other high-profile organizations.
“Permanent, year-round standard time is the best choice to most closely match our circadian sleep-wake cycle,” M. Adeel Rishi, MD, lead author of the AASM position statement, said in a news release. “Daylight saving time results in more darkness in the morning and more light in the evening, disrupting the body’s natural rhythm,” said Dr. Rishi, of the department of pulmonology, critical care, and sleep medicine, Mayo Clinic, Eau Claire, Wis., and vice chair of the AASM Public Safety Committee.
The position statement was published Aug. 26 in the Journal of Clinical Sleep Medicine to coincide with the virtual annual meeting of the Associated Professional Sleep Societies .
Significant health risks
In the United States, the annual “spring forward” to daylight saving time and “fall back” to standard time is required by law, although under the statute some exceptions are permitted.
There has been intense debate over the last several years about transitioning between standard and daylight saving time. The AASM says there is “an abundance of evidence” to indicate that quick transition from standard time to daylight saving time incurs significant public health and safety risks, including increased risk of heart attack, stroke, mood disorders, and car crashes.
“Although chronic effects of remaining in daylight saving time year-round have not been well-studied, daylight saving time is less aligned with human circadian biology – which, because of the impacts of the delayed natural light/dark cycle on human activity, could result in circadian misalignment, which has been associated in some studies with increased cardiovascular disease risk, metabolic syndrome and other health risks,” the authors wrote.
A recent study also showed an increase in medical errors in the week after switching to daylight saving time.
“Because the adoption of permanent standard time would be beneficial for public health and safety, the AASM will be advocating at the federal level for this legislative change,” said AASM President Kannan Ramar, MBBS, MD, with the Mayo Clinic in Rochester, Minn.
It seems that many Americans are in favor of the change. In July, an AASM survey of roughly 2,000 U.S. adults showed that two-thirds support doing away with the seasonal time change. Only 11% opposed it. In addition, the academy’s 2019 survey showed more than half of adults feel extremely, or somewhat, tired after the springing ahead to daylight saving time.
Strong support
The position statement has been endorsed by 19 organizations, including the American Academy of Cardiovascular Sleep Medicine, American College of Chest Physicians (CHEST), American College of Occupational and Environmental Medicine, National PTA, National Safety Council, Society of Anesthesia and Sleep Medicine, and the Society of Behavioral Sleep Medicine.
Weighing in on the issue, Saul Rothenberg, PhD, from the Sleep Center at Greenwich Hospital, Conn., said the literature on daylight saving time has grown over the past 20 years. He said he was ”humbled” by the research that shows that a “relatively small” misalignment of biological and social clocks has a measurable impact on human health and behavior.
“Because misalignment is associated with negative health and performance outcomes, keeping one set of hours year-round is promoted to minimize misalignment and associated consequences,” he added.
In light of this research, the recommendation to dispense with daylight saving time seems “quite reasonable” from a public health perspective. “I am left with a strengthened view on the importance of regular adequate sleep as a way to enhance health, performance, and quality of life,” he added.
This research had no commercial funding. Dr. Rishi and Dr. Rothenberg have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
In the interest of public health and safety, – a recommendation that has garnered strong support from multiple medical and other high-profile organizations.
“Permanent, year-round standard time is the best choice to most closely match our circadian sleep-wake cycle,” M. Adeel Rishi, MD, lead author of the AASM position statement, said in a news release. “Daylight saving time results in more darkness in the morning and more light in the evening, disrupting the body’s natural rhythm,” said Dr. Rishi, of the department of pulmonology, critical care, and sleep medicine, Mayo Clinic, Eau Claire, Wis., and vice chair of the AASM Public Safety Committee.
The position statement was published Aug. 26 in the Journal of Clinical Sleep Medicine to coincide with the virtual annual meeting of the Associated Professional Sleep Societies .
Significant health risks
In the United States, the annual “spring forward” to daylight saving time and “fall back” to standard time is required by law, although under the statute some exceptions are permitted.
There has been intense debate over the last several years about transitioning between standard and daylight saving time. The AASM says there is “an abundance of evidence” to indicate that quick transition from standard time to daylight saving time incurs significant public health and safety risks, including increased risk of heart attack, stroke, mood disorders, and car crashes.
“Although chronic effects of remaining in daylight saving time year-round have not been well-studied, daylight saving time is less aligned with human circadian biology – which, because of the impacts of the delayed natural light/dark cycle on human activity, could result in circadian misalignment, which has been associated in some studies with increased cardiovascular disease risk, metabolic syndrome and other health risks,” the authors wrote.
A recent study also showed an increase in medical errors in the week after switching to daylight saving time.
“Because the adoption of permanent standard time would be beneficial for public health and safety, the AASM will be advocating at the federal level for this legislative change,” said AASM President Kannan Ramar, MBBS, MD, with the Mayo Clinic in Rochester, Minn.
It seems that many Americans are in favor of the change. In July, an AASM survey of roughly 2,000 U.S. adults showed that two-thirds support doing away with the seasonal time change. Only 11% opposed it. In addition, the academy’s 2019 survey showed more than half of adults feel extremely, or somewhat, tired after the springing ahead to daylight saving time.
Strong support
The position statement has been endorsed by 19 organizations, including the American Academy of Cardiovascular Sleep Medicine, American College of Chest Physicians (CHEST), American College of Occupational and Environmental Medicine, National PTA, National Safety Council, Society of Anesthesia and Sleep Medicine, and the Society of Behavioral Sleep Medicine.
Weighing in on the issue, Saul Rothenberg, PhD, from the Sleep Center at Greenwich Hospital, Conn., said the literature on daylight saving time has grown over the past 20 years. He said he was ”humbled” by the research that shows that a “relatively small” misalignment of biological and social clocks has a measurable impact on human health and behavior.
“Because misalignment is associated with negative health and performance outcomes, keeping one set of hours year-round is promoted to minimize misalignment and associated consequences,” he added.
In light of this research, the recommendation to dispense with daylight saving time seems “quite reasonable” from a public health perspective. “I am left with a strengthened view on the importance of regular adequate sleep as a way to enhance health, performance, and quality of life,” he added.
This research had no commercial funding. Dr. Rishi and Dr. Rothenberg have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM SLEEP 2020
Blood biomarkers could help predict when athletes recover from concussions
, according to a new study of collegiate athletes and recovery time. “Although preliminary, the current results highlight the potential role of biomarkers in tracking neuronal recovery, which may be associated with duration of [return to sport],” wrote Cassandra L. Pattinson, PhD, of the University of Queensland, Brisbane, Australia, and the National Institutes of Health, Bethesda, Md., along with coauthors. The study was published in JAMA Network Open.
To determine if three specific blood biomarkers – total tau protein, glial fibrillary acidic protein (GFAP), and neurofilament light chain protein (NfL) – can help predict when athletes should return from sports-related concussions, a multicenter, prospective diagnostic study was launched and led by the Advanced Research Core (ARC) of the Concussion Assessment, Research, and Education (CARE) Consortium. The consortium is a joint effort of the National Collegiate Athletics Association (NCAA) and the U.S. Department of Defense.
From among the CARE ARC database, researchers evaluated 127 eligible student athletes who had experienced a sports-related concussion, underwent clinical testing and blood collection before and after their injuries, and returned to their sports. Their average age was 18.9 years old, 76% were men, and 65% were White. Biomarker levels were measured from nonfasting blood samples via ultrasensitive single molecule array technology. As current NCAA guidelines indicate that most athletes will be asymptomatic roughly 2 weeks after a concussion, the study used 14 days as a cutoff period.
Among the 127 athletes, the median return-to-sport time was 14 days; 65 returned to their sports in less than 14 days while 62 returned to their sports in 14 days or more. According to the study’s linear mixed models, athletes with a return-to-sport time of 14 days or longer had significantly higher total tau levels at 24-48 hours post injury (mean difference –0.51 pg/mL, 95% confidence interval, –0.88 to –0.14; P = .008) and when symptoms had resolved (mean difference –0.71 pg/mL, 95% CI, –1.09 to –0.34; P < .001) compared with athletes with a return-to-sport time of less than 14 days. Athletes who returned in 14 days or more also had comparatively lower levels of GFAP postinjury than did those who returned in under 14 days (4.39 pg/mL versus 4.72 pg/mL; P = .04).
Preliminary steps toward an appropriate point-of-care test
“This particular study is one of several emerging studies on what these biomarkers look like,” Brian W. Hainline, MD, chief medical officer of the NCAA, said in an interview. “It’s all still very preliminary – you couldn’t make policy changes based on what we have – but the data is accumulating. Ultimately, we should be able to perform a multivariate analysis of all the different objective biomarkers, looking at repetitive head impact exposure, looking at imaging, looking at these blood-based biomarkers. Then you can say, ‘OK, what can we do? Can we actually predict recovery, who is likely or less likely to do well?’ ”
“It’s not realistic to be taking blood samples all the time,” said Dr. Hainline, who was not involved in the study. “Another goal, once we know which biomarkers are valuable, is to convert to a point-of-care test. You get a finger prick or even a salivary test and we get the result immediately; that’s the direction that all of this is heading. But first, we have to lay out the groundwork. We envision a day, in the not too distant future, where we can get this information much more quickly.”
The authors acknowledged their study’s limitations, including an inability to standardize the time of biomarker collection and the fact that they analyzed a “relatively small number of athletes” who met their specific criteria. That said, they emphasized that their work is based on “the largest prospective sample of sports-related concussions in athletes to date” and that they “anticipate that we will be able to continue to gather a more representative sample” in the future to better generalize to the larger collegiate community.
The study was supported by the Grand Alliance Concussion Assessment, Research, and Education Consortium, which was funded in part by the NCAA and the Department of Defense. The authors disclosed receiving grants and travel reimbursements from – or working as advisers or consultants for – various organizations, college programs, and sports leagues.
SOURCE: Pattinson CL, et al. JAMA Netw Open. 2020 Aug 27. doi: 10.1001/jamanetworkopen.2020.13191.
, according to a new study of collegiate athletes and recovery time. “Although preliminary, the current results highlight the potential role of biomarkers in tracking neuronal recovery, which may be associated with duration of [return to sport],” wrote Cassandra L. Pattinson, PhD, of the University of Queensland, Brisbane, Australia, and the National Institutes of Health, Bethesda, Md., along with coauthors. The study was published in JAMA Network Open.
To determine if three specific blood biomarkers – total tau protein, glial fibrillary acidic protein (GFAP), and neurofilament light chain protein (NfL) – can help predict when athletes should return from sports-related concussions, a multicenter, prospective diagnostic study was launched and led by the Advanced Research Core (ARC) of the Concussion Assessment, Research, and Education (CARE) Consortium. The consortium is a joint effort of the National Collegiate Athletics Association (NCAA) and the U.S. Department of Defense.
From among the CARE ARC database, researchers evaluated 127 eligible student athletes who had experienced a sports-related concussion, underwent clinical testing and blood collection before and after their injuries, and returned to their sports. Their average age was 18.9 years old, 76% were men, and 65% were White. Biomarker levels were measured from nonfasting blood samples via ultrasensitive single molecule array technology. As current NCAA guidelines indicate that most athletes will be asymptomatic roughly 2 weeks after a concussion, the study used 14 days as a cutoff period.
Among the 127 athletes, the median return-to-sport time was 14 days; 65 returned to their sports in less than 14 days while 62 returned to their sports in 14 days or more. According to the study’s linear mixed models, athletes with a return-to-sport time of 14 days or longer had significantly higher total tau levels at 24-48 hours post injury (mean difference –0.51 pg/mL, 95% confidence interval, –0.88 to –0.14; P = .008) and when symptoms had resolved (mean difference –0.71 pg/mL, 95% CI, –1.09 to –0.34; P < .001) compared with athletes with a return-to-sport time of less than 14 days. Athletes who returned in 14 days or more also had comparatively lower levels of GFAP postinjury than did those who returned in under 14 days (4.39 pg/mL versus 4.72 pg/mL; P = .04).
Preliminary steps toward an appropriate point-of-care test
“This particular study is one of several emerging studies on what these biomarkers look like,” Brian W. Hainline, MD, chief medical officer of the NCAA, said in an interview. “It’s all still very preliminary – you couldn’t make policy changes based on what we have – but the data is accumulating. Ultimately, we should be able to perform a multivariate analysis of all the different objective biomarkers, looking at repetitive head impact exposure, looking at imaging, looking at these blood-based biomarkers. Then you can say, ‘OK, what can we do? Can we actually predict recovery, who is likely or less likely to do well?’ ”
“It’s not realistic to be taking blood samples all the time,” said Dr. Hainline, who was not involved in the study. “Another goal, once we know which biomarkers are valuable, is to convert to a point-of-care test. You get a finger prick or even a salivary test and we get the result immediately; that’s the direction that all of this is heading. But first, we have to lay out the groundwork. We envision a day, in the not too distant future, where we can get this information much more quickly.”
The authors acknowledged their study’s limitations, including an inability to standardize the time of biomarker collection and the fact that they analyzed a “relatively small number of athletes” who met their specific criteria. That said, they emphasized that their work is based on “the largest prospective sample of sports-related concussions in athletes to date” and that they “anticipate that we will be able to continue to gather a more representative sample” in the future to better generalize to the larger collegiate community.
The study was supported by the Grand Alliance Concussion Assessment, Research, and Education Consortium, which was funded in part by the NCAA and the Department of Defense. The authors disclosed receiving grants and travel reimbursements from – or working as advisers or consultants for – various organizations, college programs, and sports leagues.
SOURCE: Pattinson CL, et al. JAMA Netw Open. 2020 Aug 27. doi: 10.1001/jamanetworkopen.2020.13191.
, according to a new study of collegiate athletes and recovery time. “Although preliminary, the current results highlight the potential role of biomarkers in tracking neuronal recovery, which may be associated with duration of [return to sport],” wrote Cassandra L. Pattinson, PhD, of the University of Queensland, Brisbane, Australia, and the National Institutes of Health, Bethesda, Md., along with coauthors. The study was published in JAMA Network Open.
To determine if three specific blood biomarkers – total tau protein, glial fibrillary acidic protein (GFAP), and neurofilament light chain protein (NfL) – can help predict when athletes should return from sports-related concussions, a multicenter, prospective diagnostic study was launched and led by the Advanced Research Core (ARC) of the Concussion Assessment, Research, and Education (CARE) Consortium. The consortium is a joint effort of the National Collegiate Athletics Association (NCAA) and the U.S. Department of Defense.
From among the CARE ARC database, researchers evaluated 127 eligible student athletes who had experienced a sports-related concussion, underwent clinical testing and blood collection before and after their injuries, and returned to their sports. Their average age was 18.9 years old, 76% were men, and 65% were White. Biomarker levels were measured from nonfasting blood samples via ultrasensitive single molecule array technology. As current NCAA guidelines indicate that most athletes will be asymptomatic roughly 2 weeks after a concussion, the study used 14 days as a cutoff period.
Among the 127 athletes, the median return-to-sport time was 14 days; 65 returned to their sports in less than 14 days while 62 returned to their sports in 14 days or more. According to the study’s linear mixed models, athletes with a return-to-sport time of 14 days or longer had significantly higher total tau levels at 24-48 hours post injury (mean difference –0.51 pg/mL, 95% confidence interval, –0.88 to –0.14; P = .008) and when symptoms had resolved (mean difference –0.71 pg/mL, 95% CI, –1.09 to –0.34; P < .001) compared with athletes with a return-to-sport time of less than 14 days. Athletes who returned in 14 days or more also had comparatively lower levels of GFAP postinjury than did those who returned in under 14 days (4.39 pg/mL versus 4.72 pg/mL; P = .04).
Preliminary steps toward an appropriate point-of-care test
“This particular study is one of several emerging studies on what these biomarkers look like,” Brian W. Hainline, MD, chief medical officer of the NCAA, said in an interview. “It’s all still very preliminary – you couldn’t make policy changes based on what we have – but the data is accumulating. Ultimately, we should be able to perform a multivariate analysis of all the different objective biomarkers, looking at repetitive head impact exposure, looking at imaging, looking at these blood-based biomarkers. Then you can say, ‘OK, what can we do? Can we actually predict recovery, who is likely or less likely to do well?’ ”
“It’s not realistic to be taking blood samples all the time,” said Dr. Hainline, who was not involved in the study. “Another goal, once we know which biomarkers are valuable, is to convert to a point-of-care test. You get a finger prick or even a salivary test and we get the result immediately; that’s the direction that all of this is heading. But first, we have to lay out the groundwork. We envision a day, in the not too distant future, where we can get this information much more quickly.”
The authors acknowledged their study’s limitations, including an inability to standardize the time of biomarker collection and the fact that they analyzed a “relatively small number of athletes” who met their specific criteria. That said, they emphasized that their work is based on “the largest prospective sample of sports-related concussions in athletes to date” and that they “anticipate that we will be able to continue to gather a more representative sample” in the future to better generalize to the larger collegiate community.
The study was supported by the Grand Alliance Concussion Assessment, Research, and Education Consortium, which was funded in part by the NCAA and the Department of Defense. The authors disclosed receiving grants and travel reimbursements from – or working as advisers or consultants for – various organizations, college programs, and sports leagues.
SOURCE: Pattinson CL, et al. JAMA Netw Open. 2020 Aug 27. doi: 10.1001/jamanetworkopen.2020.13191.
FROM JAMA NETWORK OPEN
SSRIs risky after intracerebral hemorrhage
SSRIs effectively treat depression following intracerebral hemorrhage (ICH) but also increase risk for recurrent hemorrhagic stroke, particularly in patients at high risk for repeat ICH, new research indicates.
“Clinicians must exercise judgment when weighing the use of SSRIs for ICH survivors in the high risk category – especially those with multiple ICH events,” study investigator Alessandro Biffi, MD, director, Aging and Brain Health Research (ABHR) Group, Departments of Neurology and Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, told Medscape Medical News.
The study was published online August 31 in JAMA Neurology.
Risks and benefits
Depression is common following stroke. SSRIs are generally considered first-line treatment for post-stroke depression but are associated with increased risk for first ICH, most likely owing to their antithrombotic effects. Less is known about SSRI use and recurrent ICH risk.
To investigate, Biffi and colleagues followed 1,279 adults (mean age, 71.3 years) for a median of 53.2 months (4.5 years) following primary ICH; 602 were women, 1049 were White, 89 Black, 77 Hispanic, and 64 were other race/ethnicity.
During follow-up, 128 adults suffered recurrent ICH (annual rate, 4.2%) and 766 (60%) were diagnosed with depression.
(subhazard ratio, 1.53; 95% CI, 1.12-2.09; P = .009).
However, SSRI use was also an independent risk factor for recurrent ICH (SHR, 1.31; 95% CI, 1.08-1.59; P = .006).
High SSRI dose was associated with higher ICH recurrence risk (SHR, 1.61; 95% CI, 1.15-2.25), with a larger effect size (comparison P = .02) than low SSRI dose (SHR, 1.25; 95% CI, 1.01-1.55), but there was no difference in depression remission comparing low vs. high SSRI dose.
Among individuals at high risk for recurrent ICH, SSRI use was associated with further increased risk for ICH recurrence (SHR, 1.79; 95% CI, 1.22 - 2.64) compared with all other survivors of ICH (SHR, 1.20; 95% CI, 1.01-1.42; P = .008 for comparison of effect sizes).
These higher-risk subgroups included carriers of the APOE e2/e4 alleles, patients with lobar ICH, patients with prior ICH, and minority participants.
“Our analyses identified patients for whom the risks are higher, and therefore additional thought is warranted. This approach may in the future lead to personalized/precision medicine approaches to determining whether these patients should receive SSRIs or not,” said Biffi.
Experts weigh in
Commenting on the research for Medscape Medical News, Daniel G. Hackam, MD, division of clinical pharmacology, Western University, London, Ont., said the study is “an important contribution to the literature, as there are to date no data on the risk of ICH in prior ICH survivors in relation to SSRI exposure.”
“The bottom line is that I would be very cautious about initiating SSRIs in patients with a history of ICH,” said Hackam, who was not involved with the study.
“There are other nonserotonergic antidepressants that could be used instead, which do not inhibit platelet function. There was still a risk even in the lower-risk ICH survivors. ICH is a highly recurrent disease. We already avoid antiplatelets, anticoagulants, and high dose statins in these patients. I would add SSRI’s to that list, based on this study,” said Hackam.
Also weighing in, Amytis Towfighi, MD, associate professor of neurology, University of Southern California, Los Angeles, said this study addresses a “common clinical dilemma: how to manage depression among individuals with ICH, given the high risk of recurrent ICH among ICH survivors and potential for SSRIs to increase that risk. This scenario is common, and a source of debate for practicing clinicians.”
“The authors conducted an elegant study,” said Towfighi, by considering sociodemographic, historical, imaging, and genetic factors.
“One must interpret this study with caution as it is a single-center cohort study. However, it provides the most rigorous information to date regarding the associations between SSRI use and recurrent ICH,” she told Medscape Medical News.
The study was supported by the National Institutes of Health. Biffi, Hackam, and Towfighi have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
SSRIs effectively treat depression following intracerebral hemorrhage (ICH) but also increase risk for recurrent hemorrhagic stroke, particularly in patients at high risk for repeat ICH, new research indicates.
“Clinicians must exercise judgment when weighing the use of SSRIs for ICH survivors in the high risk category – especially those with multiple ICH events,” study investigator Alessandro Biffi, MD, director, Aging and Brain Health Research (ABHR) Group, Departments of Neurology and Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, told Medscape Medical News.
The study was published online August 31 in JAMA Neurology.
Risks and benefits
Depression is common following stroke. SSRIs are generally considered first-line treatment for post-stroke depression but are associated with increased risk for first ICH, most likely owing to their antithrombotic effects. Less is known about SSRI use and recurrent ICH risk.
To investigate, Biffi and colleagues followed 1,279 adults (mean age, 71.3 years) for a median of 53.2 months (4.5 years) following primary ICH; 602 were women, 1049 were White, 89 Black, 77 Hispanic, and 64 were other race/ethnicity.
During follow-up, 128 adults suffered recurrent ICH (annual rate, 4.2%) and 766 (60%) were diagnosed with depression.
(subhazard ratio, 1.53; 95% CI, 1.12-2.09; P = .009).
However, SSRI use was also an independent risk factor for recurrent ICH (SHR, 1.31; 95% CI, 1.08-1.59; P = .006).
High SSRI dose was associated with higher ICH recurrence risk (SHR, 1.61; 95% CI, 1.15-2.25), with a larger effect size (comparison P = .02) than low SSRI dose (SHR, 1.25; 95% CI, 1.01-1.55), but there was no difference in depression remission comparing low vs. high SSRI dose.
Among individuals at high risk for recurrent ICH, SSRI use was associated with further increased risk for ICH recurrence (SHR, 1.79; 95% CI, 1.22 - 2.64) compared with all other survivors of ICH (SHR, 1.20; 95% CI, 1.01-1.42; P = .008 for comparison of effect sizes).
These higher-risk subgroups included carriers of the APOE e2/e4 alleles, patients with lobar ICH, patients with prior ICH, and minority participants.
“Our analyses identified patients for whom the risks are higher, and therefore additional thought is warranted. This approach may in the future lead to personalized/precision medicine approaches to determining whether these patients should receive SSRIs or not,” said Biffi.
Experts weigh in
Commenting on the research for Medscape Medical News, Daniel G. Hackam, MD, division of clinical pharmacology, Western University, London, Ont., said the study is “an important contribution to the literature, as there are to date no data on the risk of ICH in prior ICH survivors in relation to SSRI exposure.”
“The bottom line is that I would be very cautious about initiating SSRIs in patients with a history of ICH,” said Hackam, who was not involved with the study.
“There are other nonserotonergic antidepressants that could be used instead, which do not inhibit platelet function. There was still a risk even in the lower-risk ICH survivors. ICH is a highly recurrent disease. We already avoid antiplatelets, anticoagulants, and high dose statins in these patients. I would add SSRI’s to that list, based on this study,” said Hackam.
Also weighing in, Amytis Towfighi, MD, associate professor of neurology, University of Southern California, Los Angeles, said this study addresses a “common clinical dilemma: how to manage depression among individuals with ICH, given the high risk of recurrent ICH among ICH survivors and potential for SSRIs to increase that risk. This scenario is common, and a source of debate for practicing clinicians.”
“The authors conducted an elegant study,” said Towfighi, by considering sociodemographic, historical, imaging, and genetic factors.
“One must interpret this study with caution as it is a single-center cohort study. However, it provides the most rigorous information to date regarding the associations between SSRI use and recurrent ICH,” she told Medscape Medical News.
The study was supported by the National Institutes of Health. Biffi, Hackam, and Towfighi have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
SSRIs effectively treat depression following intracerebral hemorrhage (ICH) but also increase risk for recurrent hemorrhagic stroke, particularly in patients at high risk for repeat ICH, new research indicates.
“Clinicians must exercise judgment when weighing the use of SSRIs for ICH survivors in the high risk category – especially those with multiple ICH events,” study investigator Alessandro Biffi, MD, director, Aging and Brain Health Research (ABHR) Group, Departments of Neurology and Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, told Medscape Medical News.
The study was published online August 31 in JAMA Neurology.
Risks and benefits
Depression is common following stroke. SSRIs are generally considered first-line treatment for post-stroke depression but are associated with increased risk for first ICH, most likely owing to their antithrombotic effects. Less is known about SSRI use and recurrent ICH risk.
To investigate, Biffi and colleagues followed 1,279 adults (mean age, 71.3 years) for a median of 53.2 months (4.5 years) following primary ICH; 602 were women, 1049 were White, 89 Black, 77 Hispanic, and 64 were other race/ethnicity.
During follow-up, 128 adults suffered recurrent ICH (annual rate, 4.2%) and 766 (60%) were diagnosed with depression.
(subhazard ratio, 1.53; 95% CI, 1.12-2.09; P = .009).
However, SSRI use was also an independent risk factor for recurrent ICH (SHR, 1.31; 95% CI, 1.08-1.59; P = .006).
High SSRI dose was associated with higher ICH recurrence risk (SHR, 1.61; 95% CI, 1.15-2.25), with a larger effect size (comparison P = .02) than low SSRI dose (SHR, 1.25; 95% CI, 1.01-1.55), but there was no difference in depression remission comparing low vs. high SSRI dose.
Among individuals at high risk for recurrent ICH, SSRI use was associated with further increased risk for ICH recurrence (SHR, 1.79; 95% CI, 1.22 - 2.64) compared with all other survivors of ICH (SHR, 1.20; 95% CI, 1.01-1.42; P = .008 for comparison of effect sizes).
These higher-risk subgroups included carriers of the APOE e2/e4 alleles, patients with lobar ICH, patients with prior ICH, and minority participants.
“Our analyses identified patients for whom the risks are higher, and therefore additional thought is warranted. This approach may in the future lead to personalized/precision medicine approaches to determining whether these patients should receive SSRIs or not,” said Biffi.
Experts weigh in
Commenting on the research for Medscape Medical News, Daniel G. Hackam, MD, division of clinical pharmacology, Western University, London, Ont., said the study is “an important contribution to the literature, as there are to date no data on the risk of ICH in prior ICH survivors in relation to SSRI exposure.”
“The bottom line is that I would be very cautious about initiating SSRIs in patients with a history of ICH,” said Hackam, who was not involved with the study.
“There are other nonserotonergic antidepressants that could be used instead, which do not inhibit platelet function. There was still a risk even in the lower-risk ICH survivors. ICH is a highly recurrent disease. We already avoid antiplatelets, anticoagulants, and high dose statins in these patients. I would add SSRI’s to that list, based on this study,” said Hackam.
Also weighing in, Amytis Towfighi, MD, associate professor of neurology, University of Southern California, Los Angeles, said this study addresses a “common clinical dilemma: how to manage depression among individuals with ICH, given the high risk of recurrent ICH among ICH survivors and potential for SSRIs to increase that risk. This scenario is common, and a source of debate for practicing clinicians.”
“The authors conducted an elegant study,” said Towfighi, by considering sociodemographic, historical, imaging, and genetic factors.
“One must interpret this study with caution as it is a single-center cohort study. However, it provides the most rigorous information to date regarding the associations between SSRI use and recurrent ICH,” she told Medscape Medical News.
The study was supported by the National Institutes of Health. Biffi, Hackam, and Towfighi have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Small-fiber polyneuropathy may underlie dysautonomia in ME/CFS
A significant proportion of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and dysautonomia may have potentially treatable underlying autoimmune-associated small-fiber polyneuropathy (aaSFPN), pilot data suggest.
The findings, from a single-site study of 61 patients with ME/CFS, were presented August 21 at the virtual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis by Ryan Whelan, BS, a research assistant at Simmaron Research Institute, Incline Village, Nevada.
Recent evidence suggests an autoimmune etiology for some patients with ME/CFS, which is defined as experiencing for a period of at least 6 months profound, unexplained fatigue, postexertional malaise, and unrefreshing sleep, as well as cognitive dysfunction and/or orthostatic intolerance (OI).
OI is part of a spectrum of autonomic dysfunction commonly seen in ME/CFS patients, which may also include postural orthostatic tachycardia (POTS), peripheral temperature dysregulation and light sensitivity, neuropathic pain, and gastrointestinal complaints. Many of these symptoms overlap those reported by patients with aaSFPN, a common but underdiagnosed neurodegenerative disorder characterized by the loss of peripheral autonomic nerve fibers, Whelan explained.
Findings from the current study show that in more than half of ME/CFS patients, levels of at least one autoantibody were elevated. A majority had comorbid POTS or OI, and over a third had biopsy-confirmed aaSFPN.
“Given the overlap of symptoms and common etiological basis, it may be important to identify ME/CFS patients who present with comorbid aaSFPN, as it has been shown that immune modulatory agents, including intravenous gamma globulin [IVIG], reduce the autonomic symptom burden in aaSFPN patients,” Whelan said.
He noted that Anne Louise Oaklander, MD, a neurologist at Massachusetts General Hospital, Harvard Medical School, Boston, and colleagues previously linked aaSFPN with fibromyalgia. In addition, they’ve found a connection between small-fiber dysfunction and postexertional malaise, which is a hallmark ME/CFS symptom.
Asked to comment on Whelan’s presentation, IACFSME co-president Lily Chu, MD, told Medscape Medical News that the new findings are “valuable, because ME/CFS has always been looked upon as just subjective symptoms. When people have laboratory abnormalities, it can be due to a bunch of other causes, but...here’s pathology, here’s a biopsy of actual damage. It’s not just a transient finding. You can actually see it. ... It’s a solid concrete piece of evidence vs something that can fluctuate.”
Autoantibodies, Autonomic Dysfunction, and Small-Fiber Polyneuropathy
Whelan and colleagues conducted an extensive analysis of medical records of 364 patients with ME/CFS (72% female) to identify potential aaSFPN comorbidity. Such identifications were made on the basis of progress notes documenting autonomic dysfunction, laboratory results for serum autoantibodies, and questionnaire symptom self-reports.
They identified 61 patients as possibly having comorbid aaSFPN. Of those, 52% tested positive for at least 1 of 4 autoantibodies, including antimuscarinic cholinergic receptor 4 (47%), anti-beta-2 adrenergic (27%), antimuscarinic cholinergic 3 (25%), and anti-beta-1 adrenergic (13%). These autoantibodies were linked to ME/CFS in a recent Swedish cohort study.
“Evidence supports that these autoantibodies may bind to receptor sites, blocking ligands from reaching these receptors. Disturbances of adrenergic and cholinergic receptors by these autoantibodies may contribute to symptoms of autonomic dysfunction in ME/CFS,” Whelan said.
Although 22% of patients in the study group had POTS and 59% had OI, the authors found no correlation between autoantibody levels and either OI or POTS. However, 38% were confirmed to have small-fiber polyneuropathy on skin biopsy, and the vast majority of those patients (93%) had either POTS or OI.
IVIG May Be a Potential Treatment
Whelan notes that some data suggest that IVIG might help patients with small-fiber neuropathy, including those with autoimmunity.
In addition, he described anecdotal data from a single patient with ME/CFS who had neuropathic symptoms. The patient was treated at Simmaron. The 56-year-old received two IVIG infusions given 6 months apart. The patient experienced a dramatic reduction in levels of all four of the relevant autoantibodies and favorable symptom reduction, as shown in clinician follow-up records. “With the success of this case study, we intend to further evaluate IVIG as a potential treatment in ME/CFS patients. With this research, we hope to identify a subset of ME/CFS patients who will respond favorably to IVIG,” Whelan concluded.
Regarding use of IVIG, Chu commented, “We don’t know exactly how it works, but it seems to help certain conditions.” She pointed to another recent small study that reported clinical improvement in patients with ME/CFS through a different approach, immunoadsorption, for reducing the autoantibody levels.
Overall, Chu said, this line of research “is important because it shows there’s some type of abnormal biomarker for ME/CFS. And, it may lay a path toward understanding the pathophysiology of the disease and why people have certain symptoms, and could be used to target therapies. ... It’s intriguing.”
Whelan and Chu have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
A significant proportion of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and dysautonomia may have potentially treatable underlying autoimmune-associated small-fiber polyneuropathy (aaSFPN), pilot data suggest.
The findings, from a single-site study of 61 patients with ME/CFS, were presented August 21 at the virtual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis by Ryan Whelan, BS, a research assistant at Simmaron Research Institute, Incline Village, Nevada.
Recent evidence suggests an autoimmune etiology for some patients with ME/CFS, which is defined as experiencing for a period of at least 6 months profound, unexplained fatigue, postexertional malaise, and unrefreshing sleep, as well as cognitive dysfunction and/or orthostatic intolerance (OI).
OI is part of a spectrum of autonomic dysfunction commonly seen in ME/CFS patients, which may also include postural orthostatic tachycardia (POTS), peripheral temperature dysregulation and light sensitivity, neuropathic pain, and gastrointestinal complaints. Many of these symptoms overlap those reported by patients with aaSFPN, a common but underdiagnosed neurodegenerative disorder characterized by the loss of peripheral autonomic nerve fibers, Whelan explained.
Findings from the current study show that in more than half of ME/CFS patients, levels of at least one autoantibody were elevated. A majority had comorbid POTS or OI, and over a third had biopsy-confirmed aaSFPN.
“Given the overlap of symptoms and common etiological basis, it may be important to identify ME/CFS patients who present with comorbid aaSFPN, as it has been shown that immune modulatory agents, including intravenous gamma globulin [IVIG], reduce the autonomic symptom burden in aaSFPN patients,” Whelan said.
He noted that Anne Louise Oaklander, MD, a neurologist at Massachusetts General Hospital, Harvard Medical School, Boston, and colleagues previously linked aaSFPN with fibromyalgia. In addition, they’ve found a connection between small-fiber dysfunction and postexertional malaise, which is a hallmark ME/CFS symptom.
Asked to comment on Whelan’s presentation, IACFSME co-president Lily Chu, MD, told Medscape Medical News that the new findings are “valuable, because ME/CFS has always been looked upon as just subjective symptoms. When people have laboratory abnormalities, it can be due to a bunch of other causes, but...here’s pathology, here’s a biopsy of actual damage. It’s not just a transient finding. You can actually see it. ... It’s a solid concrete piece of evidence vs something that can fluctuate.”
Autoantibodies, Autonomic Dysfunction, and Small-Fiber Polyneuropathy
Whelan and colleagues conducted an extensive analysis of medical records of 364 patients with ME/CFS (72% female) to identify potential aaSFPN comorbidity. Such identifications were made on the basis of progress notes documenting autonomic dysfunction, laboratory results for serum autoantibodies, and questionnaire symptom self-reports.
They identified 61 patients as possibly having comorbid aaSFPN. Of those, 52% tested positive for at least 1 of 4 autoantibodies, including antimuscarinic cholinergic receptor 4 (47%), anti-beta-2 adrenergic (27%), antimuscarinic cholinergic 3 (25%), and anti-beta-1 adrenergic (13%). These autoantibodies were linked to ME/CFS in a recent Swedish cohort study.
“Evidence supports that these autoantibodies may bind to receptor sites, blocking ligands from reaching these receptors. Disturbances of adrenergic and cholinergic receptors by these autoantibodies may contribute to symptoms of autonomic dysfunction in ME/CFS,” Whelan said.
Although 22% of patients in the study group had POTS and 59% had OI, the authors found no correlation between autoantibody levels and either OI or POTS. However, 38% were confirmed to have small-fiber polyneuropathy on skin biopsy, and the vast majority of those patients (93%) had either POTS or OI.
IVIG May Be a Potential Treatment
Whelan notes that some data suggest that IVIG might help patients with small-fiber neuropathy, including those with autoimmunity.
In addition, he described anecdotal data from a single patient with ME/CFS who had neuropathic symptoms. The patient was treated at Simmaron. The 56-year-old received two IVIG infusions given 6 months apart. The patient experienced a dramatic reduction in levels of all four of the relevant autoantibodies and favorable symptom reduction, as shown in clinician follow-up records. “With the success of this case study, we intend to further evaluate IVIG as a potential treatment in ME/CFS patients. With this research, we hope to identify a subset of ME/CFS patients who will respond favorably to IVIG,” Whelan concluded.
Regarding use of IVIG, Chu commented, “We don’t know exactly how it works, but it seems to help certain conditions.” She pointed to another recent small study that reported clinical improvement in patients with ME/CFS through a different approach, immunoadsorption, for reducing the autoantibody levels.
Overall, Chu said, this line of research “is important because it shows there’s some type of abnormal biomarker for ME/CFS. And, it may lay a path toward understanding the pathophysiology of the disease and why people have certain symptoms, and could be used to target therapies. ... It’s intriguing.”
Whelan and Chu have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
A significant proportion of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and dysautonomia may have potentially treatable underlying autoimmune-associated small-fiber polyneuropathy (aaSFPN), pilot data suggest.
The findings, from a single-site study of 61 patients with ME/CFS, were presented August 21 at the virtual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis by Ryan Whelan, BS, a research assistant at Simmaron Research Institute, Incline Village, Nevada.
Recent evidence suggests an autoimmune etiology for some patients with ME/CFS, which is defined as experiencing for a period of at least 6 months profound, unexplained fatigue, postexertional malaise, and unrefreshing sleep, as well as cognitive dysfunction and/or orthostatic intolerance (OI).
OI is part of a spectrum of autonomic dysfunction commonly seen in ME/CFS patients, which may also include postural orthostatic tachycardia (POTS), peripheral temperature dysregulation and light sensitivity, neuropathic pain, and gastrointestinal complaints. Many of these symptoms overlap those reported by patients with aaSFPN, a common but underdiagnosed neurodegenerative disorder characterized by the loss of peripheral autonomic nerve fibers, Whelan explained.
Findings from the current study show that in more than half of ME/CFS patients, levels of at least one autoantibody were elevated. A majority had comorbid POTS or OI, and over a third had biopsy-confirmed aaSFPN.
“Given the overlap of symptoms and common etiological basis, it may be important to identify ME/CFS patients who present with comorbid aaSFPN, as it has been shown that immune modulatory agents, including intravenous gamma globulin [IVIG], reduce the autonomic symptom burden in aaSFPN patients,” Whelan said.
He noted that Anne Louise Oaklander, MD, a neurologist at Massachusetts General Hospital, Harvard Medical School, Boston, and colleagues previously linked aaSFPN with fibromyalgia. In addition, they’ve found a connection between small-fiber dysfunction and postexertional malaise, which is a hallmark ME/CFS symptom.
Asked to comment on Whelan’s presentation, IACFSME co-president Lily Chu, MD, told Medscape Medical News that the new findings are “valuable, because ME/CFS has always been looked upon as just subjective symptoms. When people have laboratory abnormalities, it can be due to a bunch of other causes, but...here’s pathology, here’s a biopsy of actual damage. It’s not just a transient finding. You can actually see it. ... It’s a solid concrete piece of evidence vs something that can fluctuate.”
Autoantibodies, Autonomic Dysfunction, and Small-Fiber Polyneuropathy
Whelan and colleagues conducted an extensive analysis of medical records of 364 patients with ME/CFS (72% female) to identify potential aaSFPN comorbidity. Such identifications were made on the basis of progress notes documenting autonomic dysfunction, laboratory results for serum autoantibodies, and questionnaire symptom self-reports.
They identified 61 patients as possibly having comorbid aaSFPN. Of those, 52% tested positive for at least 1 of 4 autoantibodies, including antimuscarinic cholinergic receptor 4 (47%), anti-beta-2 adrenergic (27%), antimuscarinic cholinergic 3 (25%), and anti-beta-1 adrenergic (13%). These autoantibodies were linked to ME/CFS in a recent Swedish cohort study.
“Evidence supports that these autoantibodies may bind to receptor sites, blocking ligands from reaching these receptors. Disturbances of adrenergic and cholinergic receptors by these autoantibodies may contribute to symptoms of autonomic dysfunction in ME/CFS,” Whelan said.
Although 22% of patients in the study group had POTS and 59% had OI, the authors found no correlation between autoantibody levels and either OI or POTS. However, 38% were confirmed to have small-fiber polyneuropathy on skin biopsy, and the vast majority of those patients (93%) had either POTS or OI.
IVIG May Be a Potential Treatment
Whelan notes that some data suggest that IVIG might help patients with small-fiber neuropathy, including those with autoimmunity.
In addition, he described anecdotal data from a single patient with ME/CFS who had neuropathic symptoms. The patient was treated at Simmaron. The 56-year-old received two IVIG infusions given 6 months apart. The patient experienced a dramatic reduction in levels of all four of the relevant autoantibodies and favorable symptom reduction, as shown in clinician follow-up records. “With the success of this case study, we intend to further evaluate IVIG as a potential treatment in ME/CFS patients. With this research, we hope to identify a subset of ME/CFS patients who will respond favorably to IVIG,” Whelan concluded.
Regarding use of IVIG, Chu commented, “We don’t know exactly how it works, but it seems to help certain conditions.” She pointed to another recent small study that reported clinical improvement in patients with ME/CFS through a different approach, immunoadsorption, for reducing the autoantibody levels.
Overall, Chu said, this line of research “is important because it shows there’s some type of abnormal biomarker for ME/CFS. And, it may lay a path toward understanding the pathophysiology of the disease and why people have certain symptoms, and could be used to target therapies. ... It’s intriguing.”
Whelan and Chu have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Minidose edoxaban may safely cut AFib stroke risk in the frail, very elderly
suggests a randomized trial conducted in Japan.
Many of the study’s 984 mostly octogenarian patients were objectively frail with poor renal function, low body weight, a history of serious bleeding, or other conditions that made them poor candidates for regular-dose oral anticoagulation. Yet those who took the factor Xa inhibitor edoxaban (Savaysa) at the off-label dosage of 15 mg once daily showed a two-thirds drop in risk for stroke or systemic embolism (P < .001), compared with patients who received placebo. There were no fatal bleeds and virtually no intracranial hemorrhages.
For such high-risk patients with nonvalvular AFib who otherwise would not be given an OAC, edoxaban 15 mg “can be an acceptable treatment option in decreasing the risk of devastating stroke”; however, “it may increase the risk of gastrointestinal bleeding, so care should be given in every patient,” said Ken Okumura, MD, PhD. Indeed, the rate of gastrointestinal bleeding tripled among the patients who received edoxaban, compared with those given placebo, at about 2.3% per year versus 0.8% per year.
Although their 87% increased risk for major bleeding did not reach significance, it hit close, with a P value of .09 in the trial, called Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients (ELDERCARE-AF).
Dr. Okumura, of Saiseikai Kumamoto (Japan) Hospital, presented the study August 30 during the virtual annual congress of the European Society of Cardiology. He is lead author of an article describing the study, which was simultaneously published in the New England Journal of Medicine.
Many patients with AFib suffer strokes if they are not given oral anticoagulation because of “fear of major bleeding caused by standard OAC therapy,” Dr. Okumura noted. Others are inappropriately administered antiplatelets or anticoagulants at conventional dosages. “There is no standard of practice in Japan for patients like those in the present trial,” Dr. Okumura said. “However, I believe the present study opens a new possible path of thromboprophylaxis in such high-risk patients.”
Even with its relatively few bleeding events, ELDERCARE-AF “does suggest that the risk of the worst types of bleeds is not that high,” said Daniel E. Singer, MD, of Massachusetts General Hospital, Boston. “Gastrointestinal bleeding is annoying, and it will probably stop people from taking their edoxaban, but for the most part it doesn’t kill people.”
Moreover, he added, the trial suggests that low-dose edoxaban, in exchange for a steep reduction in thromboembolic risk, “doesn’t add to your risk of intracranial hemorrhage!”
ELDERCARE-AF may give practitioners “yet another reason to rethink” whether a low-dose DOAC such as edoxaban 15 mg/day may well be a good approach for such patients with AFib who are not receiving standard-dose OAC because of a perceived high risk for serious bleeding, said Dr. Singer, who was not involved in the study.
The trial randomly and evenly assigned 984 patients with AF in Japan to take either edoxaban 15 mg/day or placebo. The patients, who were at least 80 years old and had a CHADS2 score of 2 or higher, were judged inappropriate candidates for OAC at dosages approved for stroke prevention.
The mean age of the patients was 86.6, more than a decade older than patients “in the previous landmark clinical trials of direct oral anticoagulants,” and were 5-10 years older than the general AFib population, reported Dr. Okumura and colleagues.
Their mean weight was 52 kg, and mean creatinine clearance was 36.3 mL/min; 41% were classified as frail according to validated assessment tools.
Of the 303 patients who did not complete the trial, 158 voluntarily withdrew for various reasons. The withdrawal rate was similar in the two treatment arms. Outcomes were analyzed by intention to treat, the report noted.
The annualized rate of stroke or systemic embolism, the primary efficacy endpoint, was 2.3% for those who received edoxaban and 6.7% for the control group. Corresponding rates for the primary safety endpoint, major bleeding as determined by International Society on Thrombosis and Hemostasis criteria, were 3.3% and 1.8%, respectively.
“The question is, can the Food and Drug Administration act on this information? I doubt it can. What will be needed is to reproduce the study in a U.S. population to see if it holds,” Dr. Singer proposed.
“Edoxaban isn’t used much in the U.S. This could heighten interest. And who knows, there may be a gold rush,” he said, if the strategy were to pan out for the other DOACs, rivaroxaban (Xarelto), apixaban (Eliquis), and dabigatran (Pradaxa).
ELDERCARE-AF was funded by Daiichi Sankyo, from which Dr. Okumura reported receiving grants and personal fees; he also disclosed personal fees from Daiichi Sankyo, Boehringer Ingelheim, Bristol-Myers Squibb, Medtronic, Johnson & Johnson, and Bayer.
A version of this article originally appeared on Medscape.com.
suggests a randomized trial conducted in Japan.
Many of the study’s 984 mostly octogenarian patients were objectively frail with poor renal function, low body weight, a history of serious bleeding, or other conditions that made them poor candidates for regular-dose oral anticoagulation. Yet those who took the factor Xa inhibitor edoxaban (Savaysa) at the off-label dosage of 15 mg once daily showed a two-thirds drop in risk for stroke or systemic embolism (P < .001), compared with patients who received placebo. There were no fatal bleeds and virtually no intracranial hemorrhages.
For such high-risk patients with nonvalvular AFib who otherwise would not be given an OAC, edoxaban 15 mg “can be an acceptable treatment option in decreasing the risk of devastating stroke”; however, “it may increase the risk of gastrointestinal bleeding, so care should be given in every patient,” said Ken Okumura, MD, PhD. Indeed, the rate of gastrointestinal bleeding tripled among the patients who received edoxaban, compared with those given placebo, at about 2.3% per year versus 0.8% per year.
Although their 87% increased risk for major bleeding did not reach significance, it hit close, with a P value of .09 in the trial, called Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients (ELDERCARE-AF).
Dr. Okumura, of Saiseikai Kumamoto (Japan) Hospital, presented the study August 30 during the virtual annual congress of the European Society of Cardiology. He is lead author of an article describing the study, which was simultaneously published in the New England Journal of Medicine.
Many patients with AFib suffer strokes if they are not given oral anticoagulation because of “fear of major bleeding caused by standard OAC therapy,” Dr. Okumura noted. Others are inappropriately administered antiplatelets or anticoagulants at conventional dosages. “There is no standard of practice in Japan for patients like those in the present trial,” Dr. Okumura said. “However, I believe the present study opens a new possible path of thromboprophylaxis in such high-risk patients.”
Even with its relatively few bleeding events, ELDERCARE-AF “does suggest that the risk of the worst types of bleeds is not that high,” said Daniel E. Singer, MD, of Massachusetts General Hospital, Boston. “Gastrointestinal bleeding is annoying, and it will probably stop people from taking their edoxaban, but for the most part it doesn’t kill people.”
Moreover, he added, the trial suggests that low-dose edoxaban, in exchange for a steep reduction in thromboembolic risk, “doesn’t add to your risk of intracranial hemorrhage!”
ELDERCARE-AF may give practitioners “yet another reason to rethink” whether a low-dose DOAC such as edoxaban 15 mg/day may well be a good approach for such patients with AFib who are not receiving standard-dose OAC because of a perceived high risk for serious bleeding, said Dr. Singer, who was not involved in the study.
The trial randomly and evenly assigned 984 patients with AF in Japan to take either edoxaban 15 mg/day or placebo. The patients, who were at least 80 years old and had a CHADS2 score of 2 or higher, were judged inappropriate candidates for OAC at dosages approved for stroke prevention.
The mean age of the patients was 86.6, more than a decade older than patients “in the previous landmark clinical trials of direct oral anticoagulants,” and were 5-10 years older than the general AFib population, reported Dr. Okumura and colleagues.
Their mean weight was 52 kg, and mean creatinine clearance was 36.3 mL/min; 41% were classified as frail according to validated assessment tools.
Of the 303 patients who did not complete the trial, 158 voluntarily withdrew for various reasons. The withdrawal rate was similar in the two treatment arms. Outcomes were analyzed by intention to treat, the report noted.
The annualized rate of stroke or systemic embolism, the primary efficacy endpoint, was 2.3% for those who received edoxaban and 6.7% for the control group. Corresponding rates for the primary safety endpoint, major bleeding as determined by International Society on Thrombosis and Hemostasis criteria, were 3.3% and 1.8%, respectively.
“The question is, can the Food and Drug Administration act on this information? I doubt it can. What will be needed is to reproduce the study in a U.S. population to see if it holds,” Dr. Singer proposed.
“Edoxaban isn’t used much in the U.S. This could heighten interest. And who knows, there may be a gold rush,” he said, if the strategy were to pan out for the other DOACs, rivaroxaban (Xarelto), apixaban (Eliquis), and dabigatran (Pradaxa).
ELDERCARE-AF was funded by Daiichi Sankyo, from which Dr. Okumura reported receiving grants and personal fees; he also disclosed personal fees from Daiichi Sankyo, Boehringer Ingelheim, Bristol-Myers Squibb, Medtronic, Johnson & Johnson, and Bayer.
A version of this article originally appeared on Medscape.com.
suggests a randomized trial conducted in Japan.
Many of the study’s 984 mostly octogenarian patients were objectively frail with poor renal function, low body weight, a history of serious bleeding, or other conditions that made them poor candidates for regular-dose oral anticoagulation. Yet those who took the factor Xa inhibitor edoxaban (Savaysa) at the off-label dosage of 15 mg once daily showed a two-thirds drop in risk for stroke or systemic embolism (P < .001), compared with patients who received placebo. There were no fatal bleeds and virtually no intracranial hemorrhages.
For such high-risk patients with nonvalvular AFib who otherwise would not be given an OAC, edoxaban 15 mg “can be an acceptable treatment option in decreasing the risk of devastating stroke”; however, “it may increase the risk of gastrointestinal bleeding, so care should be given in every patient,” said Ken Okumura, MD, PhD. Indeed, the rate of gastrointestinal bleeding tripled among the patients who received edoxaban, compared with those given placebo, at about 2.3% per year versus 0.8% per year.
Although their 87% increased risk for major bleeding did not reach significance, it hit close, with a P value of .09 in the trial, called Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients (ELDERCARE-AF).
Dr. Okumura, of Saiseikai Kumamoto (Japan) Hospital, presented the study August 30 during the virtual annual congress of the European Society of Cardiology. He is lead author of an article describing the study, which was simultaneously published in the New England Journal of Medicine.
Many patients with AFib suffer strokes if they are not given oral anticoagulation because of “fear of major bleeding caused by standard OAC therapy,” Dr. Okumura noted. Others are inappropriately administered antiplatelets or anticoagulants at conventional dosages. “There is no standard of practice in Japan for patients like those in the present trial,” Dr. Okumura said. “However, I believe the present study opens a new possible path of thromboprophylaxis in such high-risk patients.”
Even with its relatively few bleeding events, ELDERCARE-AF “does suggest that the risk of the worst types of bleeds is not that high,” said Daniel E. Singer, MD, of Massachusetts General Hospital, Boston. “Gastrointestinal bleeding is annoying, and it will probably stop people from taking their edoxaban, but for the most part it doesn’t kill people.”
Moreover, he added, the trial suggests that low-dose edoxaban, in exchange for a steep reduction in thromboembolic risk, “doesn’t add to your risk of intracranial hemorrhage!”
ELDERCARE-AF may give practitioners “yet another reason to rethink” whether a low-dose DOAC such as edoxaban 15 mg/day may well be a good approach for such patients with AFib who are not receiving standard-dose OAC because of a perceived high risk for serious bleeding, said Dr. Singer, who was not involved in the study.
The trial randomly and evenly assigned 984 patients with AF in Japan to take either edoxaban 15 mg/day or placebo. The patients, who were at least 80 years old and had a CHADS2 score of 2 or higher, were judged inappropriate candidates for OAC at dosages approved for stroke prevention.
The mean age of the patients was 86.6, more than a decade older than patients “in the previous landmark clinical trials of direct oral anticoagulants,” and were 5-10 years older than the general AFib population, reported Dr. Okumura and colleagues.
Their mean weight was 52 kg, and mean creatinine clearance was 36.3 mL/min; 41% were classified as frail according to validated assessment tools.
Of the 303 patients who did not complete the trial, 158 voluntarily withdrew for various reasons. The withdrawal rate was similar in the two treatment arms. Outcomes were analyzed by intention to treat, the report noted.
The annualized rate of stroke or systemic embolism, the primary efficacy endpoint, was 2.3% for those who received edoxaban and 6.7% for the control group. Corresponding rates for the primary safety endpoint, major bleeding as determined by International Society on Thrombosis and Hemostasis criteria, were 3.3% and 1.8%, respectively.
“The question is, can the Food and Drug Administration act on this information? I doubt it can. What will be needed is to reproduce the study in a U.S. population to see if it holds,” Dr. Singer proposed.
“Edoxaban isn’t used much in the U.S. This could heighten interest. And who knows, there may be a gold rush,” he said, if the strategy were to pan out for the other DOACs, rivaroxaban (Xarelto), apixaban (Eliquis), and dabigatran (Pradaxa).
ELDERCARE-AF was funded by Daiichi Sankyo, from which Dr. Okumura reported receiving grants and personal fees; he also disclosed personal fees from Daiichi Sankyo, Boehringer Ingelheim, Bristol-Myers Squibb, Medtronic, Johnson & Johnson, and Bayer.
A version of this article originally appeared on Medscape.com.
FROM ESC CONGRESS 2020
Nightmares: An independent risk factor for heart disease?
, new research shows. In what researchers describe as “surprising” findings, results from a large study of relatively young military veterans showed those who had nightmares two or more times per week had significantly increased risks for hypertension, myocardial infarction, or other heart problems.
“A diagnosis of PTSD incorporates sleep disturbance as a symptom. Thus, we were surprised to find that nightmares continued to be associated with CVD after controlling not only for PTSD and demographic factors, but also smoking and depression diagnosis,” said Christi Ulmer, PhD, of the department of psychiatry and behavioral sciences, Duke University Medical Center, Durham, N.C.
The findings were presented at the virtual annual meeting of the Associated Professional Sleep Societies.
Unclear mechanism
The study included 3,468 veterans (77% male) with a mean age of 38 years who had served one or two tours of duty since Sept. 11, 2001. Nearly one-third (31%) met criteria for PTSD, and 33% self-reported having at least one cardiovascular condition, such as heart problems, hypertension, stroke, and MI.
Nightmare frequency and severity was assessed using the Davidson Trauma Scale. Nightmares were considered frequent if they occurred two or more times per week and moderate to severe if they were at least moderately distressing. About 31% of veterans reported having frequent nightmares, and 35% reported moderately distressing nightmares over the past week.
After adjusting for age, race, and sex, frequent nightmares were associated with hypertension (odds ratio, 1.51; 95% confidence interval, 1.28-1.78), heart problems (OR, 1.50; 95% CI, 1.11-2.02), and MI (OR, 2.32; 95% CI, 1.18-4.54).
Associations between frequent nightmares and hypertension (OR, 1.43; 95% CI, 1.17-1.73) and heart problems (OR, 1.43; 95% CI, 1.00-2.05) remained significant after further adjusting for smoking, depression, and PTSD.
“Our cross-sectional findings set the stage for future research examining the possibility that nightmares may confer cardiovascular disease risks beyond those conferred by PTSD diagnosis alone,” Dr. Ulmer said in a news release.
Dr. Ulmer also said that, because the study was based on self-reported data, the findings are “very preliminary.” Before doctors adjust clinical practices, it’s important that our findings be replicated using longitudinal studies, clinically diagnosed medical conditions, and objectively assessed sleep,” she said.
She added that more research is needed to uncover mechanisms explaining these associations and determine if reducing the frequency and severity of nightmares can lead to improved cardiovascular health.
Timely research
Reached for comment, Rajkumar (Raj) Dasgupta, MD, of the University of Southern California, Los Angeles, noted “the correlation between nightmares and heart disease is a timely topic right now with COVID-19 as more people may be having nightmares.”
“If a patient mentions nightmares, I do think it’s important not to just glaze over it, but to talk more about it and document it in the patient record, especially in patients with cardiovascular disease, atrial fibrillation, diabetes, and hypertension,” said Dr. Dasgupta, who wasn’t involved in the study.
The research was supported by the Veterans Integrated Service Network 6 Mental Illness Research, Education and Clinical Center and the Department of Veterans Affairs HSR&D ADAPT Center at the Durham VA Health Care System. Dr. Ulmer and Dr. Dasgupta have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
, new research shows. In what researchers describe as “surprising” findings, results from a large study of relatively young military veterans showed those who had nightmares two or more times per week had significantly increased risks for hypertension, myocardial infarction, or other heart problems.
“A diagnosis of PTSD incorporates sleep disturbance as a symptom. Thus, we were surprised to find that nightmares continued to be associated with CVD after controlling not only for PTSD and demographic factors, but also smoking and depression diagnosis,” said Christi Ulmer, PhD, of the department of psychiatry and behavioral sciences, Duke University Medical Center, Durham, N.C.
The findings were presented at the virtual annual meeting of the Associated Professional Sleep Societies.
Unclear mechanism
The study included 3,468 veterans (77% male) with a mean age of 38 years who had served one or two tours of duty since Sept. 11, 2001. Nearly one-third (31%) met criteria for PTSD, and 33% self-reported having at least one cardiovascular condition, such as heart problems, hypertension, stroke, and MI.
Nightmare frequency and severity was assessed using the Davidson Trauma Scale. Nightmares were considered frequent if they occurred two or more times per week and moderate to severe if they were at least moderately distressing. About 31% of veterans reported having frequent nightmares, and 35% reported moderately distressing nightmares over the past week.
After adjusting for age, race, and sex, frequent nightmares were associated with hypertension (odds ratio, 1.51; 95% confidence interval, 1.28-1.78), heart problems (OR, 1.50; 95% CI, 1.11-2.02), and MI (OR, 2.32; 95% CI, 1.18-4.54).
Associations between frequent nightmares and hypertension (OR, 1.43; 95% CI, 1.17-1.73) and heart problems (OR, 1.43; 95% CI, 1.00-2.05) remained significant after further adjusting for smoking, depression, and PTSD.
“Our cross-sectional findings set the stage for future research examining the possibility that nightmares may confer cardiovascular disease risks beyond those conferred by PTSD diagnosis alone,” Dr. Ulmer said in a news release.
Dr. Ulmer also said that, because the study was based on self-reported data, the findings are “very preliminary.” Before doctors adjust clinical practices, it’s important that our findings be replicated using longitudinal studies, clinically diagnosed medical conditions, and objectively assessed sleep,” she said.
She added that more research is needed to uncover mechanisms explaining these associations and determine if reducing the frequency and severity of nightmares can lead to improved cardiovascular health.
Timely research
Reached for comment, Rajkumar (Raj) Dasgupta, MD, of the University of Southern California, Los Angeles, noted “the correlation between nightmares and heart disease is a timely topic right now with COVID-19 as more people may be having nightmares.”
“If a patient mentions nightmares, I do think it’s important not to just glaze over it, but to talk more about it and document it in the patient record, especially in patients with cardiovascular disease, atrial fibrillation, diabetes, and hypertension,” said Dr. Dasgupta, who wasn’t involved in the study.
The research was supported by the Veterans Integrated Service Network 6 Mental Illness Research, Education and Clinical Center and the Department of Veterans Affairs HSR&D ADAPT Center at the Durham VA Health Care System. Dr. Ulmer and Dr. Dasgupta have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
, new research shows. In what researchers describe as “surprising” findings, results from a large study of relatively young military veterans showed those who had nightmares two or more times per week had significantly increased risks for hypertension, myocardial infarction, or other heart problems.
“A diagnosis of PTSD incorporates sleep disturbance as a symptom. Thus, we were surprised to find that nightmares continued to be associated with CVD after controlling not only for PTSD and demographic factors, but also smoking and depression diagnosis,” said Christi Ulmer, PhD, of the department of psychiatry and behavioral sciences, Duke University Medical Center, Durham, N.C.
The findings were presented at the virtual annual meeting of the Associated Professional Sleep Societies.
Unclear mechanism
The study included 3,468 veterans (77% male) with a mean age of 38 years who had served one or two tours of duty since Sept. 11, 2001. Nearly one-third (31%) met criteria for PTSD, and 33% self-reported having at least one cardiovascular condition, such as heart problems, hypertension, stroke, and MI.
Nightmare frequency and severity was assessed using the Davidson Trauma Scale. Nightmares were considered frequent if they occurred two or more times per week and moderate to severe if they were at least moderately distressing. About 31% of veterans reported having frequent nightmares, and 35% reported moderately distressing nightmares over the past week.
After adjusting for age, race, and sex, frequent nightmares were associated with hypertension (odds ratio, 1.51; 95% confidence interval, 1.28-1.78), heart problems (OR, 1.50; 95% CI, 1.11-2.02), and MI (OR, 2.32; 95% CI, 1.18-4.54).
Associations between frequent nightmares and hypertension (OR, 1.43; 95% CI, 1.17-1.73) and heart problems (OR, 1.43; 95% CI, 1.00-2.05) remained significant after further adjusting for smoking, depression, and PTSD.
“Our cross-sectional findings set the stage for future research examining the possibility that nightmares may confer cardiovascular disease risks beyond those conferred by PTSD diagnosis alone,” Dr. Ulmer said in a news release.
Dr. Ulmer also said that, because the study was based on self-reported data, the findings are “very preliminary.” Before doctors adjust clinical practices, it’s important that our findings be replicated using longitudinal studies, clinically diagnosed medical conditions, and objectively assessed sleep,” she said.
She added that more research is needed to uncover mechanisms explaining these associations and determine if reducing the frequency and severity of nightmares can lead to improved cardiovascular health.
Timely research
Reached for comment, Rajkumar (Raj) Dasgupta, MD, of the University of Southern California, Los Angeles, noted “the correlation between nightmares and heart disease is a timely topic right now with COVID-19 as more people may be having nightmares.”
“If a patient mentions nightmares, I do think it’s important not to just glaze over it, but to talk more about it and document it in the patient record, especially in patients with cardiovascular disease, atrial fibrillation, diabetes, and hypertension,” said Dr. Dasgupta, who wasn’t involved in the study.
The research was supported by the Veterans Integrated Service Network 6 Mental Illness Research, Education and Clinical Center and the Department of Veterans Affairs HSR&D ADAPT Center at the Durham VA Health Care System. Dr. Ulmer and Dr. Dasgupta have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM SLEEP 2020
COVID-19 at home: What does optimal care look like?
Marilyn Stebbins, PharmD, fell ill at the end of February 2020. Initially diagnosed with multifocal pneumonia and treated with antibiotics, she later developed severe gastrointestinal symptoms, fatigue, and shortness of breath. She was hospitalized in early March and was diagnosed with COVID-19.
It was still early in the pandemic, and testing was not available for her husband. After she was discharged, her husband isolated himself as much as possible. But that limited the amount of care he could offer.
“When I came home after 8 days in the ICU, I felt completely alone and terrified of not being able to care for myself and not knowing how much care my husband could provide,” said Dr. Stebbins, professor of clinical pharmacy at the University of California, San Francisco.
“I can’t even imagine what it would have been like if I had been home alone without my husband in the house,” she said. “I think about the people who died at home and understand how that might happen.”
Dr. Stebbins is one of tens of thousands of people who, whether hospitalized and discharged or never admitted for inpatient care, needed to find ways to convalesce at home. Data from the Centers for Medicare & Medicaid Services show that, of 326,674 beneficiaries who tested positive for COVID-19 between May 16 and June 11, 2020, 109,607 were hospitalized, suggesting that two-thirds were outpatients.
Most attention has focused on the sickest patients, leaving less severe cases to fall through the cracks. Despite fever, cough, difficulty breathing, and a surfeit of other symptoms, there are few available resources and all too little support to help patients navigate the physical and emotional struggles of contending with COVID-19 at home.
No ‘cookie-cutter’ approach
The speed with which the pandemic progressed caught public health systems off guard, but now, “it is essential to put into place the infrastructure to care for the physical and mental health needs of patients at home because most are in the community and many, if not most, still aren’t receiving sufficient support at home,” said Dr. Stebbins.
said Gary LeRoy, MD, a family physician in Dayton, Ohio. He emphasized that there is “no cookie-cutter formula” for home care, because every patient’s situation is different.
“I begin by having a detailed conversation with each patient to ascertain whether their home environment is safe and to paint a picture of their circumstances,” Dr. LeRoy, who is the president of the American Academy of Family Physicians, said in an interview.
Dr. LeRoy suggested questions that constitute “not just a ‘medical’ checklist but a ‘whole life’ checklist.”
- Do you have access to food, water, medications, sanitation/cleaning supplies, a thermometer, and other necessities? If not, who might assist in providing those?
- Do you need help with activities of daily living and self-care?
- Who else lives in your household? Do they have signs and symptoms of the virus? Have they been tested?
- Do you have enough physical space between you and other household members?
- Do you have children? How are they being cared for?
- What type of work do you do? What are the implications for your employment if you are unable to work for an extended period?
- Do you have an emotional, social, and spiritual support system (e.g., family, friends, community, church)?
- Do you have concerns I haven’t mentioned?
Patients’ responses will inform the management plan and determine what medical and social resources are needed, he said.
Daily check-in
Dr. Stebbins said the nurse case manager from her insurance company called her daily after she came home from the hospital. She was told that a public health nurse would also call, but no one from the health department called for days – a situation she hopes has improved.
One way or another, she said, “health care providers [or their staff] should check in with patients daily, either telephonically or via video.” She noted that video is superior, because “someone who isn’t a family member needs to put eyes on a patient and might be able to detect warning signs that a family member without healthcare training might not notice.”
Dr. LeRoy, who is also an associate professor of medicine at Wright State University, Dayton, Ohio, said that, given his time constraints, a nurse or medical assistant in his practice conducts the daily check-ins and notifies him if the patient has fever or other symptoms.
“Under ordinary circumstances, when a patient comes to see me for some type of medical condition, I get to meet the patient, consider what might be going on, then order a test, wait for the results, and suggest a treatment plan. But these are anything but ordinary circumstances,” said Matthew Exline, MD, a pulmonary and critical care specialist at the Ohio State University Wexner Medical Center, Columbus.
“That traditional structure broke down with COVID-19, when we may have test results without even seeing the patient. And without this interaction, it is harder to know as a physician what course of action to take,” he said in an interview.
Once a diagnosis has been made, the physician has at least some data to help guide next steps, even if there has been no prior meeting with the patient.
For example, a positive test raises a host of issues, not the least of which is the risk of spreading the infection to other household members and questions about whether to go the hospital. Moreover, for patients, positive tests can have serious ramifications.
“Severe shortness of breath at rest is not typical of the flu, nor is loss of taste or smell,” said Dr. Exline. Practitioners must educate patients and families about specific symptoms of COVID-19, including shortness of breath, loss of taste or smell, and gastrointestinal or neurologic symptoms, and when to seek emergency care.
Dr. LeRoy suggests buying a pulse oximeter to gauge blood oxygen levels and pulse rate. Together with a thermometer, a portable blood pressure monitor, and, if indicated, a blood glucose monitor, these devices provide a comprehensive and accurate assessment of vital signs.
Dr. LeRoy also educates patients and their families about when to seek medical attention.
Dr. Stebbins takes a similar approach. “Family members are part of, not apart from, the care of patients with COVID-19, and it’s our responsibility as healthcare providers to consider them in the patient’s care plan.”
Keeping family safe
Beyond care, family members need a plan to keep themselves healthy, too.
“A patient with COVID-19 at home should self-quarantine as much as possible to keep other family members safe, if they continue to live in the same house,” Dr. Exline said.
Ideally, uninfected family members should stay with relatives or friends. When that’s not possible, everyone in the household should wear a mask, be vigilant about hand washing, and wipe down all surfaces – including doorknobs, light switches, faucet handles, cellphones, and utensils – regularly with bleach or an alcohol solution.
Caregivers should also minimize the amount of time they are exposed to the patient.
“Set food, water, and medication on the night table and leave the room rather than spending hours at the bedside, since limiting exposure to viral load reduces the chances of contagion,” said Dr. Exline.
The Centers for Disease Control and Prevention offers guidance for household members caring for COVID-19 patients at home. It provides tips on how to help patients follow the doctor’s instructions and ways to ensure adequate hydration and rest, among others.
Patients with COVID-19 who live alone face more formidable challenges.
Dr. LeRoy says physicians can help patients by educating themselves about available social services in their community so they can provide appropriate referrals and connections. Such initiatives can include meal programs, friendly visit and financial assistance programs, as well as childcare and home health agencies.
He noted that Aunt Bertha, a social care network, provides a guide to social services throughout the United States. Additional resources are available on USA.gov.
Comfort and support
Patients with COVID-19 need to be as comfortable and as supported as possible, both physically and emotionally.
“While I was sick, my dogs curled up next to me and didn’t leave my side, and they were my saving grace. There’s not enough to be said about emotional support,” Dr. Stebbins said.
Although important, emotional support is not enough. For patients with respiratory disorders, such as chronic obstructive pulmonary disease, asthma, heart failure, or pneumonia, their subjective symptoms of shortness of breath, air hunger, or cough may improve with supplemental oxygen at home. Other measures include repositioning of the patient to lessen the body weight over the lungs or the use of lung percussion, Leroy said.
He added that improvement may also come from drainage of sputum from the airway passages, the use of agents to liquefy thick sputum (mucolytics), or aerosolized bronchodilator medications.
However, Dr. LeRoy cautioned, “one remedy does not work for everyone – an individual can improve gradually by using these home support interventions, or their respiratory status can deteriorate rapidly despite all these interventions.”
For this reason, he says patients should consult their personal physician to determine which, if any, of these home treatments would be best for their particular situation.
Patients who need emotional support, psychotherapy, or psychotropic medications may find teletherapy helpful. Guidance for psychiatrists, psychologists, and social workers regarding the treatment of COVID-19 patients via teletherapy can be found on the American Psychiatric Association, the American Psychological Association, and the National Association of Social Workers websites.
Pharmacists can also help ensure patient safety, Dr. Stebbins said.
If a patient has not picked up their usual medications, Dr. Stebbins said, “they may need a check-in call. Some may be ill and alone and may need encouragement to seek medical attention, and some may have no means of getting to the pharmacy and may need medications delivered.”
A home healthcare agency may also be helpful for homebound patients. David Bersson, director of operations at Synergy Home Care of Bergen County, N.J., has arranged in-home caregivers for patients with COVID-19.
The amount of care that professional caregivers provide can range from several hours per week to full-time, depending on the patient’s needs and budget, and can include companionship, Mr. Bersson said in an interview.
Because patient and caregiver safety are paramount, caregivers are thoroughly trained in protection and decontamination procedures and are regularly tested for COVID-19 prior to being sent into a client’s home.
Health insurance companies do not cover this service, Mr. Bersson noted, but the VetAssist program covers home care for veterans and their spouses who meet income requirements.
Caregiving and companionship are both vital pieces of the at-home care puzzle. “It was the virtual emotional support I got from friends, family, coworkers, and healthcare professionals that meant so much to me, and I know they played an important part in my recovery,” Dr. Stebbins said.
Dr. LeRoy agreed, noting that he calls patients, even if they only have mild symptoms and his nurse has already spoken to them. “The call doesn’t take much time – maybe just a 5-minute conversation – but it makes patients aware that I care.”
Dr. Stebbins, Dr. Exline, and Dr. LeRoy report no relevant financial relationships. Mr. Bersson is the director of operations at Synergy Home Care of Bergen County, New Jersey.
This story first appeared on Medscape.com.
Marilyn Stebbins, PharmD, fell ill at the end of February 2020. Initially diagnosed with multifocal pneumonia and treated with antibiotics, she later developed severe gastrointestinal symptoms, fatigue, and shortness of breath. She was hospitalized in early March and was diagnosed with COVID-19.
It was still early in the pandemic, and testing was not available for her husband. After she was discharged, her husband isolated himself as much as possible. But that limited the amount of care he could offer.
“When I came home after 8 days in the ICU, I felt completely alone and terrified of not being able to care for myself and not knowing how much care my husband could provide,” said Dr. Stebbins, professor of clinical pharmacy at the University of California, San Francisco.
“I can’t even imagine what it would have been like if I had been home alone without my husband in the house,” she said. “I think about the people who died at home and understand how that might happen.”
Dr. Stebbins is one of tens of thousands of people who, whether hospitalized and discharged or never admitted for inpatient care, needed to find ways to convalesce at home. Data from the Centers for Medicare & Medicaid Services show that, of 326,674 beneficiaries who tested positive for COVID-19 between May 16 and June 11, 2020, 109,607 were hospitalized, suggesting that two-thirds were outpatients.
Most attention has focused on the sickest patients, leaving less severe cases to fall through the cracks. Despite fever, cough, difficulty breathing, and a surfeit of other symptoms, there are few available resources and all too little support to help patients navigate the physical and emotional struggles of contending with COVID-19 at home.
No ‘cookie-cutter’ approach
The speed with which the pandemic progressed caught public health systems off guard, but now, “it is essential to put into place the infrastructure to care for the physical and mental health needs of patients at home because most are in the community and many, if not most, still aren’t receiving sufficient support at home,” said Dr. Stebbins.
said Gary LeRoy, MD, a family physician in Dayton, Ohio. He emphasized that there is “no cookie-cutter formula” for home care, because every patient’s situation is different.
“I begin by having a detailed conversation with each patient to ascertain whether their home environment is safe and to paint a picture of their circumstances,” Dr. LeRoy, who is the president of the American Academy of Family Physicians, said in an interview.
Dr. LeRoy suggested questions that constitute “not just a ‘medical’ checklist but a ‘whole life’ checklist.”
- Do you have access to food, water, medications, sanitation/cleaning supplies, a thermometer, and other necessities? If not, who might assist in providing those?
- Do you need help with activities of daily living and self-care?
- Who else lives in your household? Do they have signs and symptoms of the virus? Have they been tested?
- Do you have enough physical space between you and other household members?
- Do you have children? How are they being cared for?
- What type of work do you do? What are the implications for your employment if you are unable to work for an extended period?
- Do you have an emotional, social, and spiritual support system (e.g., family, friends, community, church)?
- Do you have concerns I haven’t mentioned?
Patients’ responses will inform the management plan and determine what medical and social resources are needed, he said.
Daily check-in
Dr. Stebbins said the nurse case manager from her insurance company called her daily after she came home from the hospital. She was told that a public health nurse would also call, but no one from the health department called for days – a situation she hopes has improved.
One way or another, she said, “health care providers [or their staff] should check in with patients daily, either telephonically or via video.” She noted that video is superior, because “someone who isn’t a family member needs to put eyes on a patient and might be able to detect warning signs that a family member without healthcare training might not notice.”
Dr. LeRoy, who is also an associate professor of medicine at Wright State University, Dayton, Ohio, said that, given his time constraints, a nurse or medical assistant in his practice conducts the daily check-ins and notifies him if the patient has fever or other symptoms.
“Under ordinary circumstances, when a patient comes to see me for some type of medical condition, I get to meet the patient, consider what might be going on, then order a test, wait for the results, and suggest a treatment plan. But these are anything but ordinary circumstances,” said Matthew Exline, MD, a pulmonary and critical care specialist at the Ohio State University Wexner Medical Center, Columbus.
“That traditional structure broke down with COVID-19, when we may have test results without even seeing the patient. And without this interaction, it is harder to know as a physician what course of action to take,” he said in an interview.
Once a diagnosis has been made, the physician has at least some data to help guide next steps, even if there has been no prior meeting with the patient.
For example, a positive test raises a host of issues, not the least of which is the risk of spreading the infection to other household members and questions about whether to go the hospital. Moreover, for patients, positive tests can have serious ramifications.
“Severe shortness of breath at rest is not typical of the flu, nor is loss of taste or smell,” said Dr. Exline. Practitioners must educate patients and families about specific symptoms of COVID-19, including shortness of breath, loss of taste or smell, and gastrointestinal or neurologic symptoms, and when to seek emergency care.
Dr. LeRoy suggests buying a pulse oximeter to gauge blood oxygen levels and pulse rate. Together with a thermometer, a portable blood pressure monitor, and, if indicated, a blood glucose monitor, these devices provide a comprehensive and accurate assessment of vital signs.
Dr. LeRoy also educates patients and their families about when to seek medical attention.
Dr. Stebbins takes a similar approach. “Family members are part of, not apart from, the care of patients with COVID-19, and it’s our responsibility as healthcare providers to consider them in the patient’s care plan.”
Keeping family safe
Beyond care, family members need a plan to keep themselves healthy, too.
“A patient with COVID-19 at home should self-quarantine as much as possible to keep other family members safe, if they continue to live in the same house,” Dr. Exline said.
Ideally, uninfected family members should stay with relatives or friends. When that’s not possible, everyone in the household should wear a mask, be vigilant about hand washing, and wipe down all surfaces – including doorknobs, light switches, faucet handles, cellphones, and utensils – regularly with bleach or an alcohol solution.
Caregivers should also minimize the amount of time they are exposed to the patient.
“Set food, water, and medication on the night table and leave the room rather than spending hours at the bedside, since limiting exposure to viral load reduces the chances of contagion,” said Dr. Exline.
The Centers for Disease Control and Prevention offers guidance for household members caring for COVID-19 patients at home. It provides tips on how to help patients follow the doctor’s instructions and ways to ensure adequate hydration and rest, among others.
Patients with COVID-19 who live alone face more formidable challenges.
Dr. LeRoy says physicians can help patients by educating themselves about available social services in their community so they can provide appropriate referrals and connections. Such initiatives can include meal programs, friendly visit and financial assistance programs, as well as childcare and home health agencies.
He noted that Aunt Bertha, a social care network, provides a guide to social services throughout the United States. Additional resources are available on USA.gov.
Comfort and support
Patients with COVID-19 need to be as comfortable and as supported as possible, both physically and emotionally.
“While I was sick, my dogs curled up next to me and didn’t leave my side, and they were my saving grace. There’s not enough to be said about emotional support,” Dr. Stebbins said.
Although important, emotional support is not enough. For patients with respiratory disorders, such as chronic obstructive pulmonary disease, asthma, heart failure, or pneumonia, their subjective symptoms of shortness of breath, air hunger, or cough may improve with supplemental oxygen at home. Other measures include repositioning of the patient to lessen the body weight over the lungs or the use of lung percussion, Leroy said.
He added that improvement may also come from drainage of sputum from the airway passages, the use of agents to liquefy thick sputum (mucolytics), or aerosolized bronchodilator medications.
However, Dr. LeRoy cautioned, “one remedy does not work for everyone – an individual can improve gradually by using these home support interventions, or their respiratory status can deteriorate rapidly despite all these interventions.”
For this reason, he says patients should consult their personal physician to determine which, if any, of these home treatments would be best for their particular situation.
Patients who need emotional support, psychotherapy, or psychotropic medications may find teletherapy helpful. Guidance for psychiatrists, psychologists, and social workers regarding the treatment of COVID-19 patients via teletherapy can be found on the American Psychiatric Association, the American Psychological Association, and the National Association of Social Workers websites.
Pharmacists can also help ensure patient safety, Dr. Stebbins said.
If a patient has not picked up their usual medications, Dr. Stebbins said, “they may need a check-in call. Some may be ill and alone and may need encouragement to seek medical attention, and some may have no means of getting to the pharmacy and may need medications delivered.”
A home healthcare agency may also be helpful for homebound patients. David Bersson, director of operations at Synergy Home Care of Bergen County, N.J., has arranged in-home caregivers for patients with COVID-19.
The amount of care that professional caregivers provide can range from several hours per week to full-time, depending on the patient’s needs and budget, and can include companionship, Mr. Bersson said in an interview.
Because patient and caregiver safety are paramount, caregivers are thoroughly trained in protection and decontamination procedures and are regularly tested for COVID-19 prior to being sent into a client’s home.
Health insurance companies do not cover this service, Mr. Bersson noted, but the VetAssist program covers home care for veterans and their spouses who meet income requirements.
Caregiving and companionship are both vital pieces of the at-home care puzzle. “It was the virtual emotional support I got from friends, family, coworkers, and healthcare professionals that meant so much to me, and I know they played an important part in my recovery,” Dr. Stebbins said.
Dr. LeRoy agreed, noting that he calls patients, even if they only have mild symptoms and his nurse has already spoken to them. “The call doesn’t take much time – maybe just a 5-minute conversation – but it makes patients aware that I care.”
Dr. Stebbins, Dr. Exline, and Dr. LeRoy report no relevant financial relationships. Mr. Bersson is the director of operations at Synergy Home Care of Bergen County, New Jersey.
This story first appeared on Medscape.com.
Marilyn Stebbins, PharmD, fell ill at the end of February 2020. Initially diagnosed with multifocal pneumonia and treated with antibiotics, she later developed severe gastrointestinal symptoms, fatigue, and shortness of breath. She was hospitalized in early March and was diagnosed with COVID-19.
It was still early in the pandemic, and testing was not available for her husband. After she was discharged, her husband isolated himself as much as possible. But that limited the amount of care he could offer.
“When I came home after 8 days in the ICU, I felt completely alone and terrified of not being able to care for myself and not knowing how much care my husband could provide,” said Dr. Stebbins, professor of clinical pharmacy at the University of California, San Francisco.
“I can’t even imagine what it would have been like if I had been home alone without my husband in the house,” she said. “I think about the people who died at home and understand how that might happen.”
Dr. Stebbins is one of tens of thousands of people who, whether hospitalized and discharged or never admitted for inpatient care, needed to find ways to convalesce at home. Data from the Centers for Medicare & Medicaid Services show that, of 326,674 beneficiaries who tested positive for COVID-19 between May 16 and June 11, 2020, 109,607 were hospitalized, suggesting that two-thirds were outpatients.
Most attention has focused on the sickest patients, leaving less severe cases to fall through the cracks. Despite fever, cough, difficulty breathing, and a surfeit of other symptoms, there are few available resources and all too little support to help patients navigate the physical and emotional struggles of contending with COVID-19 at home.
No ‘cookie-cutter’ approach
The speed with which the pandemic progressed caught public health systems off guard, but now, “it is essential to put into place the infrastructure to care for the physical and mental health needs of patients at home because most are in the community and many, if not most, still aren’t receiving sufficient support at home,” said Dr. Stebbins.
said Gary LeRoy, MD, a family physician in Dayton, Ohio. He emphasized that there is “no cookie-cutter formula” for home care, because every patient’s situation is different.
“I begin by having a detailed conversation with each patient to ascertain whether their home environment is safe and to paint a picture of their circumstances,” Dr. LeRoy, who is the president of the American Academy of Family Physicians, said in an interview.
Dr. LeRoy suggested questions that constitute “not just a ‘medical’ checklist but a ‘whole life’ checklist.”
- Do you have access to food, water, medications, sanitation/cleaning supplies, a thermometer, and other necessities? If not, who might assist in providing those?
- Do you need help with activities of daily living and self-care?
- Who else lives in your household? Do they have signs and symptoms of the virus? Have they been tested?
- Do you have enough physical space between you and other household members?
- Do you have children? How are they being cared for?
- What type of work do you do? What are the implications for your employment if you are unable to work for an extended period?
- Do you have an emotional, social, and spiritual support system (e.g., family, friends, community, church)?
- Do you have concerns I haven’t mentioned?
Patients’ responses will inform the management plan and determine what medical and social resources are needed, he said.
Daily check-in
Dr. Stebbins said the nurse case manager from her insurance company called her daily after she came home from the hospital. She was told that a public health nurse would also call, but no one from the health department called for days – a situation she hopes has improved.
One way or another, she said, “health care providers [or their staff] should check in with patients daily, either telephonically or via video.” She noted that video is superior, because “someone who isn’t a family member needs to put eyes on a patient and might be able to detect warning signs that a family member without healthcare training might not notice.”
Dr. LeRoy, who is also an associate professor of medicine at Wright State University, Dayton, Ohio, said that, given his time constraints, a nurse or medical assistant in his practice conducts the daily check-ins and notifies him if the patient has fever or other symptoms.
“Under ordinary circumstances, when a patient comes to see me for some type of medical condition, I get to meet the patient, consider what might be going on, then order a test, wait for the results, and suggest a treatment plan. But these are anything but ordinary circumstances,” said Matthew Exline, MD, a pulmonary and critical care specialist at the Ohio State University Wexner Medical Center, Columbus.
“That traditional structure broke down with COVID-19, when we may have test results without even seeing the patient. And without this interaction, it is harder to know as a physician what course of action to take,” he said in an interview.
Once a diagnosis has been made, the physician has at least some data to help guide next steps, even if there has been no prior meeting with the patient.
For example, a positive test raises a host of issues, not the least of which is the risk of spreading the infection to other household members and questions about whether to go the hospital. Moreover, for patients, positive tests can have serious ramifications.
“Severe shortness of breath at rest is not typical of the flu, nor is loss of taste or smell,” said Dr. Exline. Practitioners must educate patients and families about specific symptoms of COVID-19, including shortness of breath, loss of taste or smell, and gastrointestinal or neurologic symptoms, and when to seek emergency care.
Dr. LeRoy suggests buying a pulse oximeter to gauge blood oxygen levels and pulse rate. Together with a thermometer, a portable blood pressure monitor, and, if indicated, a blood glucose monitor, these devices provide a comprehensive and accurate assessment of vital signs.
Dr. LeRoy also educates patients and their families about when to seek medical attention.
Dr. Stebbins takes a similar approach. “Family members are part of, not apart from, the care of patients with COVID-19, and it’s our responsibility as healthcare providers to consider them in the patient’s care plan.”
Keeping family safe
Beyond care, family members need a plan to keep themselves healthy, too.
“A patient with COVID-19 at home should self-quarantine as much as possible to keep other family members safe, if they continue to live in the same house,” Dr. Exline said.
Ideally, uninfected family members should stay with relatives or friends. When that’s not possible, everyone in the household should wear a mask, be vigilant about hand washing, and wipe down all surfaces – including doorknobs, light switches, faucet handles, cellphones, and utensils – regularly with bleach or an alcohol solution.
Caregivers should also minimize the amount of time they are exposed to the patient.
“Set food, water, and medication on the night table and leave the room rather than spending hours at the bedside, since limiting exposure to viral load reduces the chances of contagion,” said Dr. Exline.
The Centers for Disease Control and Prevention offers guidance for household members caring for COVID-19 patients at home. It provides tips on how to help patients follow the doctor’s instructions and ways to ensure adequate hydration and rest, among others.
Patients with COVID-19 who live alone face more formidable challenges.
Dr. LeRoy says physicians can help patients by educating themselves about available social services in their community so they can provide appropriate referrals and connections. Such initiatives can include meal programs, friendly visit and financial assistance programs, as well as childcare and home health agencies.
He noted that Aunt Bertha, a social care network, provides a guide to social services throughout the United States. Additional resources are available on USA.gov.
Comfort and support
Patients with COVID-19 need to be as comfortable and as supported as possible, both physically and emotionally.
“While I was sick, my dogs curled up next to me and didn’t leave my side, and they were my saving grace. There’s not enough to be said about emotional support,” Dr. Stebbins said.
Although important, emotional support is not enough. For patients with respiratory disorders, such as chronic obstructive pulmonary disease, asthma, heart failure, or pneumonia, their subjective symptoms of shortness of breath, air hunger, or cough may improve with supplemental oxygen at home. Other measures include repositioning of the patient to lessen the body weight over the lungs or the use of lung percussion, Leroy said.
He added that improvement may also come from drainage of sputum from the airway passages, the use of agents to liquefy thick sputum (mucolytics), or aerosolized bronchodilator medications.
However, Dr. LeRoy cautioned, “one remedy does not work for everyone – an individual can improve gradually by using these home support interventions, or their respiratory status can deteriorate rapidly despite all these interventions.”
For this reason, he says patients should consult their personal physician to determine which, if any, of these home treatments would be best for their particular situation.
Patients who need emotional support, psychotherapy, or psychotropic medications may find teletherapy helpful. Guidance for psychiatrists, psychologists, and social workers regarding the treatment of COVID-19 patients via teletherapy can be found on the American Psychiatric Association, the American Psychological Association, and the National Association of Social Workers websites.
Pharmacists can also help ensure patient safety, Dr. Stebbins said.
If a patient has not picked up their usual medications, Dr. Stebbins said, “they may need a check-in call. Some may be ill and alone and may need encouragement to seek medical attention, and some may have no means of getting to the pharmacy and may need medications delivered.”
A home healthcare agency may also be helpful for homebound patients. David Bersson, director of operations at Synergy Home Care of Bergen County, N.J., has arranged in-home caregivers for patients with COVID-19.
The amount of care that professional caregivers provide can range from several hours per week to full-time, depending on the patient’s needs and budget, and can include companionship, Mr. Bersson said in an interview.
Because patient and caregiver safety are paramount, caregivers are thoroughly trained in protection and decontamination procedures and are regularly tested for COVID-19 prior to being sent into a client’s home.
Health insurance companies do not cover this service, Mr. Bersson noted, but the VetAssist program covers home care for veterans and their spouses who meet income requirements.
Caregiving and companionship are both vital pieces of the at-home care puzzle. “It was the virtual emotional support I got from friends, family, coworkers, and healthcare professionals that meant so much to me, and I know they played an important part in my recovery,” Dr. Stebbins said.
Dr. LeRoy agreed, noting that he calls patients, even if they only have mild symptoms and his nurse has already spoken to them. “The call doesn’t take much time – maybe just a 5-minute conversation – but it makes patients aware that I care.”
Dr. Stebbins, Dr. Exline, and Dr. LeRoy report no relevant financial relationships. Mr. Bersson is the director of operations at Synergy Home Care of Bergen County, New Jersey.
This story first appeared on Medscape.com.
Mortality burden of dementia may be greater than estimated
This burden may be greatest among non-Hispanic black older adults, compared with Hispanic and non-Hispanic whites. This burden also is significantly greater among people with less than a high school education, compared with those with a college education.
The study results underscore the importance of broadening access to population-based interventions that focus on dementia prevention and care, the investigators wrote. “Future research could examine the extent to which deaths attributable to dementia and underestimation of dementia as an underlying cause of death on death certificates might have changed over time,” wrote Andrew C. Stokes, PhD, assistant professor of global health at the Boston University School of Public Health, and colleagues.
The study was published online Aug. 24 in JAMA Neurology.
In 2019, approximately 5.6 million adults in the United States who were aged 65 years or older had Alzheimer’s disease, vascular dementia, or mixed-cause dementia. A further 18.8% of Americans in this age group had cognitive impairment without dementia (CIND). About one third of patients with CIND may develop Alzheimer’s disease or related dementias (ADRD) within 5 years.
Research suggests that medical examiners significantly underreport ADRD on death certificates. One community-based study, for example, found that only 25% of deaths in patients with dementia had Alzheimer’s disease listed on the death certificates. Other research found that deaths in patients with dementia were often coded using more proximate causes, such as cardiovascular disease, sepsis, and pneumonia.
Health and retirement study
Dr. Stokes and colleagues examined data from the Health and Retirement Study (HRS) to evaluate the association of dementia and CIND with all-cause mortality. The HRS is a longitudinal cohort study of adults older than 50 years who live in the community. Its sample is nationally representative. The HRS investigators also initiated the Aging, Demographics, and Memory study to develop a procedure for assessing cognitive status in the HRS sample.
In their study, Dr. Stokes and colleagues included adults who had been sampled in the 2000 wave of HRS. They focused on participants between ages 70 and 99 years at baseline, and their final sample included 7,342 older adults. To identify dementia status, the researchers used the Langa–Weir score cutoff, which is based on tests of immediate and delayed recall of 10 words, a serial 7-second task, and a backward counting task. They also classified dementia status using the Herzog–Wallace, Wu, Hurd, and modified Hurd algorithms.
At baseline, the researchers measured age, sex, race or ethnicity, educational attainment, smoking status, self-reported disease diagnoses, and U.S. Census division as covariates. The National Center for Health Statistics linked HRS data with National Death Index records. These linked records include underlying cause of death and any mention of a condition or cause of death on the death certificate. The researchers compared the percentage of deaths attributable to ADRD according to a population attributable fraction estimate with the proportion of dementia-related deaths according to underlying causes and with any mention of dementia on death certificates.
The sample of 7,342 older adults included 4,348 (60.3%) women. Data for 1,030 (13.4%) people were reported by proxy. At baseline, most participants (64.0%) were between ages 70 and 79 years, 31% were between ages 80 and 89, and 5% were between ages 90 and 99 years. The prevalence of dementia in the complete sample was 14.3%, and the prevalence of CIND was 24.7%. The prevalence of dementia (22.4%) and CIND (29.3%) was higher among decedents than among the full population.
The hazard ratio (HR) for mortality was 2.53 among participants with dementia and 1.53 among patients with CIND. Although 13.6% of deaths were attributable to dementia, the proportion of deaths assigned to dementia as an underlying cause on death certificates was 5.0%. This discrepancy suggests that dementia is underreported by more than a factor of 2.7.
The mortality burden of dementia was 24.7% in non-Hispanic black older adults, 20.7% in Hispanic white participants, and 12.2% in non-Hispanic white participants. In addition, the mortality burden of dementia was significantly greater among participants with less than a high school education (16.2%) than among participants with a college education (9.8%).
The degree to which the underlying cause of death underestimated the mortality burden of dementia varied by sociodemographic characteristics, health status, and geography. The burden was underestimated by a factor of 7.1 among non-Hispanic black participants, a factor of 4.1 among Hispanic participants, and a factor of 2.3 among non-Hispanic white participants. The burden was underestimated by a factor of 3.5 in men and a factor of 2.4 in women. In addition, the burden was underestimated by a factor of 3.0 among participants with less than a high school education, by a factor of 2.3 among participants with a high school education, by a factor of 1.9 in participants with some college, and by a factor of 2.5 among participants with a college or higher education.
One of the study’s strengths was its population attributable fraction analysis, which reduced the risk of overestimating the mortality burden of dementia, Dr. Stokes and colleagues wrote. Examining CIND is valuable because of its high prevalence and consequent influence on outcomes in the population, even though CIND is associated with a lower mortality risk, they added. Nevertheless, the investigators were unable to assess mortality for dementia subtypes, and the classifications of dementia status and CIND may be subject to measurement error.
Underestimation is systematic
“This study is eye-opening in that it highlights the systematic underestimation of deaths attributable to dementia,” said Costantino Iadecola, MD, Anne Parrish Titzell professor of neurology and director and chair of the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine in New York. The study’s main strength is that it is nationally representative, but the data must be confirmed in a larger population, he added.
The results will clarify the effect of dementia on mortality for neurologists, and geriatricians should be made aware of them, said Dr. Iadecola. “These data should be valuable to rationalize public health efforts and related funding decisions concerning research and community support.”
Further research could determine the mortality of dementia subgroups, “especially dementias linked to vascular factors in which prevention may be effective,” said Dr. Iadecola. “In the older population, vascular factors may play a more preeminent role, and it may help focus preventive approaches.”
The study was supported by a grant from the National Institute on Aging. Dr. Stokes received grants from Ethicon that were unrelated to this study. Dr. Iadecola serves on the scientific advisory board of Broadview Venture.
SOURCE: Stokes AC et al. JAMA Neurol. 2020 Aug 24. doi: 10.1001/jamaneurol.2020.2831.
This burden may be greatest among non-Hispanic black older adults, compared with Hispanic and non-Hispanic whites. This burden also is significantly greater among people with less than a high school education, compared with those with a college education.
The study results underscore the importance of broadening access to population-based interventions that focus on dementia prevention and care, the investigators wrote. “Future research could examine the extent to which deaths attributable to dementia and underestimation of dementia as an underlying cause of death on death certificates might have changed over time,” wrote Andrew C. Stokes, PhD, assistant professor of global health at the Boston University School of Public Health, and colleagues.
The study was published online Aug. 24 in JAMA Neurology.
In 2019, approximately 5.6 million adults in the United States who were aged 65 years or older had Alzheimer’s disease, vascular dementia, or mixed-cause dementia. A further 18.8% of Americans in this age group had cognitive impairment without dementia (CIND). About one third of patients with CIND may develop Alzheimer’s disease or related dementias (ADRD) within 5 years.
Research suggests that medical examiners significantly underreport ADRD on death certificates. One community-based study, for example, found that only 25% of deaths in patients with dementia had Alzheimer’s disease listed on the death certificates. Other research found that deaths in patients with dementia were often coded using more proximate causes, such as cardiovascular disease, sepsis, and pneumonia.
Health and retirement study
Dr. Stokes and colleagues examined data from the Health and Retirement Study (HRS) to evaluate the association of dementia and CIND with all-cause mortality. The HRS is a longitudinal cohort study of adults older than 50 years who live in the community. Its sample is nationally representative. The HRS investigators also initiated the Aging, Demographics, and Memory study to develop a procedure for assessing cognitive status in the HRS sample.
In their study, Dr. Stokes and colleagues included adults who had been sampled in the 2000 wave of HRS. They focused on participants between ages 70 and 99 years at baseline, and their final sample included 7,342 older adults. To identify dementia status, the researchers used the Langa–Weir score cutoff, which is based on tests of immediate and delayed recall of 10 words, a serial 7-second task, and a backward counting task. They also classified dementia status using the Herzog–Wallace, Wu, Hurd, and modified Hurd algorithms.
At baseline, the researchers measured age, sex, race or ethnicity, educational attainment, smoking status, self-reported disease diagnoses, and U.S. Census division as covariates. The National Center for Health Statistics linked HRS data with National Death Index records. These linked records include underlying cause of death and any mention of a condition or cause of death on the death certificate. The researchers compared the percentage of deaths attributable to ADRD according to a population attributable fraction estimate with the proportion of dementia-related deaths according to underlying causes and with any mention of dementia on death certificates.
The sample of 7,342 older adults included 4,348 (60.3%) women. Data for 1,030 (13.4%) people were reported by proxy. At baseline, most participants (64.0%) were between ages 70 and 79 years, 31% were between ages 80 and 89, and 5% were between ages 90 and 99 years. The prevalence of dementia in the complete sample was 14.3%, and the prevalence of CIND was 24.7%. The prevalence of dementia (22.4%) and CIND (29.3%) was higher among decedents than among the full population.
The hazard ratio (HR) for mortality was 2.53 among participants with dementia and 1.53 among patients with CIND. Although 13.6% of deaths were attributable to dementia, the proportion of deaths assigned to dementia as an underlying cause on death certificates was 5.0%. This discrepancy suggests that dementia is underreported by more than a factor of 2.7.
The mortality burden of dementia was 24.7% in non-Hispanic black older adults, 20.7% in Hispanic white participants, and 12.2% in non-Hispanic white participants. In addition, the mortality burden of dementia was significantly greater among participants with less than a high school education (16.2%) than among participants with a college education (9.8%).
The degree to which the underlying cause of death underestimated the mortality burden of dementia varied by sociodemographic characteristics, health status, and geography. The burden was underestimated by a factor of 7.1 among non-Hispanic black participants, a factor of 4.1 among Hispanic participants, and a factor of 2.3 among non-Hispanic white participants. The burden was underestimated by a factor of 3.5 in men and a factor of 2.4 in women. In addition, the burden was underestimated by a factor of 3.0 among participants with less than a high school education, by a factor of 2.3 among participants with a high school education, by a factor of 1.9 in participants with some college, and by a factor of 2.5 among participants with a college or higher education.
One of the study’s strengths was its population attributable fraction analysis, which reduced the risk of overestimating the mortality burden of dementia, Dr. Stokes and colleagues wrote. Examining CIND is valuable because of its high prevalence and consequent influence on outcomes in the population, even though CIND is associated with a lower mortality risk, they added. Nevertheless, the investigators were unable to assess mortality for dementia subtypes, and the classifications of dementia status and CIND may be subject to measurement error.
Underestimation is systematic
“This study is eye-opening in that it highlights the systematic underestimation of deaths attributable to dementia,” said Costantino Iadecola, MD, Anne Parrish Titzell professor of neurology and director and chair of the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine in New York. The study’s main strength is that it is nationally representative, but the data must be confirmed in a larger population, he added.
The results will clarify the effect of dementia on mortality for neurologists, and geriatricians should be made aware of them, said Dr. Iadecola. “These data should be valuable to rationalize public health efforts and related funding decisions concerning research and community support.”
Further research could determine the mortality of dementia subgroups, “especially dementias linked to vascular factors in which prevention may be effective,” said Dr. Iadecola. “In the older population, vascular factors may play a more preeminent role, and it may help focus preventive approaches.”
The study was supported by a grant from the National Institute on Aging. Dr. Stokes received grants from Ethicon that were unrelated to this study. Dr. Iadecola serves on the scientific advisory board of Broadview Venture.
SOURCE: Stokes AC et al. JAMA Neurol. 2020 Aug 24. doi: 10.1001/jamaneurol.2020.2831.
This burden may be greatest among non-Hispanic black older adults, compared with Hispanic and non-Hispanic whites. This burden also is significantly greater among people with less than a high school education, compared with those with a college education.
The study results underscore the importance of broadening access to population-based interventions that focus on dementia prevention and care, the investigators wrote. “Future research could examine the extent to which deaths attributable to dementia and underestimation of dementia as an underlying cause of death on death certificates might have changed over time,” wrote Andrew C. Stokes, PhD, assistant professor of global health at the Boston University School of Public Health, and colleagues.
The study was published online Aug. 24 in JAMA Neurology.
In 2019, approximately 5.6 million adults in the United States who were aged 65 years or older had Alzheimer’s disease, vascular dementia, or mixed-cause dementia. A further 18.8% of Americans in this age group had cognitive impairment without dementia (CIND). About one third of patients with CIND may develop Alzheimer’s disease or related dementias (ADRD) within 5 years.
Research suggests that medical examiners significantly underreport ADRD on death certificates. One community-based study, for example, found that only 25% of deaths in patients with dementia had Alzheimer’s disease listed on the death certificates. Other research found that deaths in patients with dementia were often coded using more proximate causes, such as cardiovascular disease, sepsis, and pneumonia.
Health and retirement study
Dr. Stokes and colleagues examined data from the Health and Retirement Study (HRS) to evaluate the association of dementia and CIND with all-cause mortality. The HRS is a longitudinal cohort study of adults older than 50 years who live in the community. Its sample is nationally representative. The HRS investigators also initiated the Aging, Demographics, and Memory study to develop a procedure for assessing cognitive status in the HRS sample.
In their study, Dr. Stokes and colleagues included adults who had been sampled in the 2000 wave of HRS. They focused on participants between ages 70 and 99 years at baseline, and their final sample included 7,342 older adults. To identify dementia status, the researchers used the Langa–Weir score cutoff, which is based on tests of immediate and delayed recall of 10 words, a serial 7-second task, and a backward counting task. They also classified dementia status using the Herzog–Wallace, Wu, Hurd, and modified Hurd algorithms.
At baseline, the researchers measured age, sex, race or ethnicity, educational attainment, smoking status, self-reported disease diagnoses, and U.S. Census division as covariates. The National Center for Health Statistics linked HRS data with National Death Index records. These linked records include underlying cause of death and any mention of a condition or cause of death on the death certificate. The researchers compared the percentage of deaths attributable to ADRD according to a population attributable fraction estimate with the proportion of dementia-related deaths according to underlying causes and with any mention of dementia on death certificates.
The sample of 7,342 older adults included 4,348 (60.3%) women. Data for 1,030 (13.4%) people were reported by proxy. At baseline, most participants (64.0%) were between ages 70 and 79 years, 31% were between ages 80 and 89, and 5% were between ages 90 and 99 years. The prevalence of dementia in the complete sample was 14.3%, and the prevalence of CIND was 24.7%. The prevalence of dementia (22.4%) and CIND (29.3%) was higher among decedents than among the full population.
The hazard ratio (HR) for mortality was 2.53 among participants with dementia and 1.53 among patients with CIND. Although 13.6% of deaths were attributable to dementia, the proportion of deaths assigned to dementia as an underlying cause on death certificates was 5.0%. This discrepancy suggests that dementia is underreported by more than a factor of 2.7.
The mortality burden of dementia was 24.7% in non-Hispanic black older adults, 20.7% in Hispanic white participants, and 12.2% in non-Hispanic white participants. In addition, the mortality burden of dementia was significantly greater among participants with less than a high school education (16.2%) than among participants with a college education (9.8%).
The degree to which the underlying cause of death underestimated the mortality burden of dementia varied by sociodemographic characteristics, health status, and geography. The burden was underestimated by a factor of 7.1 among non-Hispanic black participants, a factor of 4.1 among Hispanic participants, and a factor of 2.3 among non-Hispanic white participants. The burden was underestimated by a factor of 3.5 in men and a factor of 2.4 in women. In addition, the burden was underestimated by a factor of 3.0 among participants with less than a high school education, by a factor of 2.3 among participants with a high school education, by a factor of 1.9 in participants with some college, and by a factor of 2.5 among participants with a college or higher education.
One of the study’s strengths was its population attributable fraction analysis, which reduced the risk of overestimating the mortality burden of dementia, Dr. Stokes and colleagues wrote. Examining CIND is valuable because of its high prevalence and consequent influence on outcomes in the population, even though CIND is associated with a lower mortality risk, they added. Nevertheless, the investigators were unable to assess mortality for dementia subtypes, and the classifications of dementia status and CIND may be subject to measurement error.
Underestimation is systematic
“This study is eye-opening in that it highlights the systematic underestimation of deaths attributable to dementia,” said Costantino Iadecola, MD, Anne Parrish Titzell professor of neurology and director and chair of the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine in New York. The study’s main strength is that it is nationally representative, but the data must be confirmed in a larger population, he added.
The results will clarify the effect of dementia on mortality for neurologists, and geriatricians should be made aware of them, said Dr. Iadecola. “These data should be valuable to rationalize public health efforts and related funding decisions concerning research and community support.”
Further research could determine the mortality of dementia subgroups, “especially dementias linked to vascular factors in which prevention may be effective,” said Dr. Iadecola. “In the older population, vascular factors may play a more preeminent role, and it may help focus preventive approaches.”
The study was supported by a grant from the National Institute on Aging. Dr. Stokes received grants from Ethicon that were unrelated to this study. Dr. Iadecola serves on the scientific advisory board of Broadview Venture.
SOURCE: Stokes AC et al. JAMA Neurol. 2020 Aug 24. doi: 10.1001/jamaneurol.2020.2831.
FROM JAMA NEUROLOGY