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extacy
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A peer-reviewed clinical journal serving healthcare professionals working with the Department of Veterans Affairs, the Department of Defense, and the Public Health Service.
Urinary Metals Linked to Increased Dementia Risk
TOPLINE:
METHODOLOGY:
- This multicenter prospective cohort study included 6303 participants from six US study centers from 2000 to 2002, with follow-up through 2018.
- Participants were aged 45-84 years (median age at baseline, 60 years; 52% women) and were free of diagnosed cardiovascular disease.
- Researchers measured urinary levels of arsenic, cadmium, cobalt, copper, lead, manganese, tungsten, uranium, and zinc.
- Neuropsychological assessments included the Digit Symbol Coding, Cognitive Abilities Screening Instrument, and Digit Span tests.
- The median follow-up duration was 11.7 years for participants with dementia and 16.8 years for those without; 559 cases of dementia were identified during the study.
TAKEAWAY:
- Lower Digit Symbol Coding scores were associated with higher urinary concentrations of arsenic (mean difference [MD] in score per interquartile range [IQR] increase, –0.03), cobalt (MD per IQR increase, –0.05), copper (MD per IQR increase, –0.05), uranium (MD per IQR increase, –0.04), and zinc (MD per IQR increase, –0.03).
- Effects for cobalt, uranium, and zinc were stronger in apolipoprotein epsilon 4 allele (APOE4) carriers vs noncarriers.
- Higher urinary levels of copper were associated with lower Digit Span scores (MD, –0.043) and elevated levels of copper (MD, –0.028) and zinc (MD, –0.024) were associated with lower global cognitive scores.
- Individuals with urinary levels of the nine-metal mixture at the 95th percentile had a 71% higher risk for dementia compared to those with levels at the 25th percentile, with the risk more pronounced in APOE4 carriers than in noncarriers (MD, –0.30 vs –0.10, respectively).
IN PRACTICE:
“We found an inverse association of essential and nonessential metals in urine, both individually and as a mixture, with the speed of mental operations, as well as a positive association of urinary metal levels with dementia risk. As metal exposure and levels in the body are modifiable, these findings could inform early screening and precision interventions for dementia prevention based on individuals’ metal exposure and genetic profiles,” the investigators wrote.
SOURCE:
The study was led by Arce Domingo-Relloso, PhD, Columbia University Mailman School of Public Health, New York City. It was published online in JAMA Network Open.
LIMITATIONS:
Data may have been missed for patients with dementia who were never hospitalized, died, or were lost to follow-up. The dementia diagnosis included nonspecific International Classification of Diseases codes, potentially leading to false-positive reports. In addition, the sample size was not sufficient to evaluate the associations between metal exposure and cognitive test scores for carriers of two APOE4 alleles.
DISCLOSURES:
The study was supported by the National Heart, Lung, and Blood Institute. Several authors reported receiving grants from the National Institutes of Health and consulting fees, editorial stipends, teaching fees, or unrelated grant funding from various sources, which are fully listed in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- This multicenter prospective cohort study included 6303 participants from six US study centers from 2000 to 2002, with follow-up through 2018.
- Participants were aged 45-84 years (median age at baseline, 60 years; 52% women) and were free of diagnosed cardiovascular disease.
- Researchers measured urinary levels of arsenic, cadmium, cobalt, copper, lead, manganese, tungsten, uranium, and zinc.
- Neuropsychological assessments included the Digit Symbol Coding, Cognitive Abilities Screening Instrument, and Digit Span tests.
- The median follow-up duration was 11.7 years for participants with dementia and 16.8 years for those without; 559 cases of dementia were identified during the study.
TAKEAWAY:
- Lower Digit Symbol Coding scores were associated with higher urinary concentrations of arsenic (mean difference [MD] in score per interquartile range [IQR] increase, –0.03), cobalt (MD per IQR increase, –0.05), copper (MD per IQR increase, –0.05), uranium (MD per IQR increase, –0.04), and zinc (MD per IQR increase, –0.03).
- Effects for cobalt, uranium, and zinc were stronger in apolipoprotein epsilon 4 allele (APOE4) carriers vs noncarriers.
- Higher urinary levels of copper were associated with lower Digit Span scores (MD, –0.043) and elevated levels of copper (MD, –0.028) and zinc (MD, –0.024) were associated with lower global cognitive scores.
- Individuals with urinary levels of the nine-metal mixture at the 95th percentile had a 71% higher risk for dementia compared to those with levels at the 25th percentile, with the risk more pronounced in APOE4 carriers than in noncarriers (MD, –0.30 vs –0.10, respectively).
IN PRACTICE:
“We found an inverse association of essential and nonessential metals in urine, both individually and as a mixture, with the speed of mental operations, as well as a positive association of urinary metal levels with dementia risk. As metal exposure and levels in the body are modifiable, these findings could inform early screening and precision interventions for dementia prevention based on individuals’ metal exposure and genetic profiles,” the investigators wrote.
SOURCE:
The study was led by Arce Domingo-Relloso, PhD, Columbia University Mailman School of Public Health, New York City. It was published online in JAMA Network Open.
LIMITATIONS:
Data may have been missed for patients with dementia who were never hospitalized, died, or were lost to follow-up. The dementia diagnosis included nonspecific International Classification of Diseases codes, potentially leading to false-positive reports. In addition, the sample size was not sufficient to evaluate the associations between metal exposure and cognitive test scores for carriers of two APOE4 alleles.
DISCLOSURES:
The study was supported by the National Heart, Lung, and Blood Institute. Several authors reported receiving grants from the National Institutes of Health and consulting fees, editorial stipends, teaching fees, or unrelated grant funding from various sources, which are fully listed in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- This multicenter prospective cohort study included 6303 participants from six US study centers from 2000 to 2002, with follow-up through 2018.
- Participants were aged 45-84 years (median age at baseline, 60 years; 52% women) and were free of diagnosed cardiovascular disease.
- Researchers measured urinary levels of arsenic, cadmium, cobalt, copper, lead, manganese, tungsten, uranium, and zinc.
- Neuropsychological assessments included the Digit Symbol Coding, Cognitive Abilities Screening Instrument, and Digit Span tests.
- The median follow-up duration was 11.7 years for participants with dementia and 16.8 years for those without; 559 cases of dementia were identified during the study.
TAKEAWAY:
- Lower Digit Symbol Coding scores were associated with higher urinary concentrations of arsenic (mean difference [MD] in score per interquartile range [IQR] increase, –0.03), cobalt (MD per IQR increase, –0.05), copper (MD per IQR increase, –0.05), uranium (MD per IQR increase, –0.04), and zinc (MD per IQR increase, –0.03).
- Effects for cobalt, uranium, and zinc were stronger in apolipoprotein epsilon 4 allele (APOE4) carriers vs noncarriers.
- Higher urinary levels of copper were associated with lower Digit Span scores (MD, –0.043) and elevated levels of copper (MD, –0.028) and zinc (MD, –0.024) were associated with lower global cognitive scores.
- Individuals with urinary levels of the nine-metal mixture at the 95th percentile had a 71% higher risk for dementia compared to those with levels at the 25th percentile, with the risk more pronounced in APOE4 carriers than in noncarriers (MD, –0.30 vs –0.10, respectively).
IN PRACTICE:
“We found an inverse association of essential and nonessential metals in urine, both individually and as a mixture, with the speed of mental operations, as well as a positive association of urinary metal levels with dementia risk. As metal exposure and levels in the body are modifiable, these findings could inform early screening and precision interventions for dementia prevention based on individuals’ metal exposure and genetic profiles,” the investigators wrote.
SOURCE:
The study was led by Arce Domingo-Relloso, PhD, Columbia University Mailman School of Public Health, New York City. It was published online in JAMA Network Open.
LIMITATIONS:
Data may have been missed for patients with dementia who were never hospitalized, died, or were lost to follow-up. The dementia diagnosis included nonspecific International Classification of Diseases codes, potentially leading to false-positive reports. In addition, the sample size was not sufficient to evaluate the associations between metal exposure and cognitive test scores for carriers of two APOE4 alleles.
DISCLOSURES:
The study was supported by the National Heart, Lung, and Blood Institute. Several authors reported receiving grants from the National Institutes of Health and consulting fees, editorial stipends, teaching fees, or unrelated grant funding from various sources, which are fully listed in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Reality of Night Shifts: How to Stay Sharp and Healthy
Laura Vater remembers sneaking into her home after 12-hour night shifts during medical training while her husband distracted their toddler. The stealthy tag-teaming effort helped her get enough undisturbed sleep before returning to an Indiana University hospital the following night to repeat the pattern.
“He would pretend to take out the trash when I pulled in,” said Vater, MD, now a gastrointestinal oncologist and assistant professor of medicine at IU Health Simon Cancer Center in Indianapolis. “I would sneak in so she [their daughter] wouldn’t see me, and then he would go back in.”
For Vater, prioritizing sleep during the day to combat sleep deprivation common among doctors-in-training on night shifts required enlisting a supportive spouse. It’s just one of the tips she and a few chief residents shared with this news organization for staying sharp and healthy during overnight rotations.
While the pace of patient rounds may slow from the frenetic daytime rush, training as a doctor after the sun goes down can be quite challenging for residents, they told this news organization. From sleep deprivation working while the rest of us slumbers to the after-effects of late-night caffeine, learning to manage night rotations requires a balance of preparation and attention to personal health while caring for others, the residents and adviser said.
Compromised sleep is one of the biggest hurdles residents have to overcome. Sleep loss comes with risks to cardiovascular disease and type 2 diabetes, among other heath conditions, according to Medscape Medical News reports. And night shift workers who sleep 6 or fewer hours a night have at least one sleep disorder.
Sleep deprivation associated with overnight call schedules also can worsen a resident’s mood and motivation while impairing their judgment, leading to medical errors, according to a new study published in JAMA Open Network. The study proposed shorter consecutive night shifts and naps as ways to offset the results of sleep loss, especially for interns or first-year residents.
Residency programs recently have been experimenting with shorter call schedules.
Catching Zzs
Working the night shift demands a disciplined sleep schedule, said Nat deQuillfeldt, MD, a Denver Health chief resident in the University of Colorado’s internal medicine residency program.
“When I was on night admissions, I was very strict about going to sleep at 8 AM and waking at 3 PM every single day. It can be very tempting to try to stay up and spend time with loved ones, but my husband and I both prioritized my physical well-being for those weeks,” said deQuillfeldt, a PGY-4 resident. “It was especially challenging for me because I had to commute about 50 minutes each way and without such a rigid schedule I would have struggled to be on time.”
deQuillfeldt doesn’t have young children at home, a noisy community, or other distractions to interrupt sleep during the day. But it was still difficult for her to sleep while the sun was out. “I used an eye mask and ear plugs but definitely woke up more often than I would at night.”
Blackout curtains may have helped, she added.
“Without adequate sleep, your clinical thinking is not as sharp. When emergencies happen overnight, you’re often the first person to arrive and need to be able to make rapid, accurate assessments and decisions.”
As a chief resident, she chooses never to sleep during night shifts.
“I personally didn’t want to leave my interns alone or make them feel like they were waking me up or bothering me if they needed help, and I also didn’t want to be groggy in case of a rapid response or code blue.”
But napping on night shift is definitely possible, deQuillfeldt said. Between following up on overnight lab results, answering nurses’ questions, and responding to emergencies, she found downtime on night shift to eat and hydrate. She believes others can catch an hour or 2 of shut eye, even if they work in the intensive care unit, or 3-4 hours on rare quiet nights.
Vater suggests residents transitioning from daytime work to night shift prepare by trying to catch an afternoon nap, staying up later the night before the change, and banking sleep hours in advance.
When he knows he’s starting night shifts, Apurva Popat, MD, said he tries to go to sleep an hour or so later nights before to avoid becoming sleep deprived. The chief resident of internal medicine at Marshfield Clinic Health System in Marshfield, Wisconsin, doesn’t recommend sleeping during the night shift.
“I typically try not to sleep, even if I have time, so I can go home and sleep later in the morning,” said Popat, a PGY-3 resident.
To help him snooze, he uses blackout curtains and a fan to block out noise. His wife, a first-year internal medicine intern, often works a different shift, so she helps set up his sleeping environment and he reciprocates when it’s her turn for night shifts.
Some interns may need to catch a 20- to 30-minute nap on the first night shift, he said.
Popat also seeks out brighter areas of the hospital, such as the emergency department, where there are more people and colleagues to keep him alert.
Bypass Vending Machines
Lack of sleep makes it even more difficult to eat healthy on night shift, said Vater, who advises residents about wellness issues at IU and on social media.
“When you are sleep deprived, when you do not get enough sleep, you eat but you don’t feel full,” she said. “It’s hard to eat well on night shift. It’s harder if you go to the break room and there’s candy and junk food.”
Vater said that, as a resident, she brought a lunch bag to the hospital during night shifts. “I never had time to prep food, so I’d bring a whole apple, a whole orange, a whole avocado or nuts. It allowed me to eat more fruits and vegetables than I normally would.”
She advises caution when considering coffee to stay awake, especially after about 9 PM, which could interfere with sleep residents need later when they finish their shifts. Caffeine may help in the moment, but it prevents deep sleep, Vater said. So when residents finally get sleep after their shifts, they may wake up feeling tired, she said.
To avoid sleepiness, Popat brings protein shakes with him to night shifts. They stave off sugar spikes and keep his energy level high, he said. He might have a protein shake and fruit before he leaves home and carry his vegetarian dinner with him to eat in the early morning hours when the hospital is calm.
Eating small and frequent meals also helps ward off sleepiness, deQuillfeldt said.
Take the Stairs
Trying to stay healthy on night shifts, Vater also checked on patients by taking the stairs. “I’d set the timer on my phone for 30 minutes and if I got paged at 15, I’d pause the timer and reset it if I had a moment later. I’d get at least 30 minutes in, although not always continuous. I think some activity is better than none.”
Vater said her hospital had a gym, but it wasn’t practical for her because it was further away from where she worked. “Sometimes my coresidents would be more creative, and we would do squats.”
Popat tries to lift weights 2 hours before his night shift, but he also takes short walks between patients’ rooms in the early morning hours when it’s quietest. He also promotes deep breathing to stay alert.
Ask for a Ride
Vater urges those coming off night shifts, especially those transitioning for the first time from daytime rotations, not to drive if they’re exhausted. “Get an Uber. ... Make sure you get a ride home.”
The CU residency program covers the cost of a ridesharing service when doctors-in-training are too tired to drive home, deQuillfeldt said. “We really try to encourage people to use this to reduce the risk of car accidents.”
Promoting Mental Health
The residency program also links residents with primary care and mental health services. People who really struggle with shift work sleep disorder may qualify for medications to help them stay awake overnight, in addition to sleep hygiene apps and sleep aides.
“Night shifts can put a strain on mental health, especially when you’re only working, eating, and sleeping and not spending any time with family and friends,” deQuillfeldt said. “My husband works late afternoons, so we often would go weeks seeing each other for 15-20 minutes a day.”
“Sleeping when the sun is out often leads to a lack of light exposure which can compound the problem. Seeking mental health support early is really important to avoiding burnout,” she said.
She also recommended planning a fun weekend activity, trip, or celebration with friends or family after night shifts end “so you have something to look forward to…It’s so important to have a light at the end of the tunnel, which will allow you to enjoy the sense of accomplishment even more.”
For more advice on the subject, consider the American Medical Association guide to managing sleep deprivation in residency or Laura Vater’s tips for night shifts.
A version of this article first appeared on Medscape.com.
Laura Vater remembers sneaking into her home after 12-hour night shifts during medical training while her husband distracted their toddler. The stealthy tag-teaming effort helped her get enough undisturbed sleep before returning to an Indiana University hospital the following night to repeat the pattern.
“He would pretend to take out the trash when I pulled in,” said Vater, MD, now a gastrointestinal oncologist and assistant professor of medicine at IU Health Simon Cancer Center in Indianapolis. “I would sneak in so she [their daughter] wouldn’t see me, and then he would go back in.”
For Vater, prioritizing sleep during the day to combat sleep deprivation common among doctors-in-training on night shifts required enlisting a supportive spouse. It’s just one of the tips she and a few chief residents shared with this news organization for staying sharp and healthy during overnight rotations.
While the pace of patient rounds may slow from the frenetic daytime rush, training as a doctor after the sun goes down can be quite challenging for residents, they told this news organization. From sleep deprivation working while the rest of us slumbers to the after-effects of late-night caffeine, learning to manage night rotations requires a balance of preparation and attention to personal health while caring for others, the residents and adviser said.
Compromised sleep is one of the biggest hurdles residents have to overcome. Sleep loss comes with risks to cardiovascular disease and type 2 diabetes, among other heath conditions, according to Medscape Medical News reports. And night shift workers who sleep 6 or fewer hours a night have at least one sleep disorder.
Sleep deprivation associated with overnight call schedules also can worsen a resident’s mood and motivation while impairing their judgment, leading to medical errors, according to a new study published in JAMA Open Network. The study proposed shorter consecutive night shifts and naps as ways to offset the results of sleep loss, especially for interns or first-year residents.
Residency programs recently have been experimenting with shorter call schedules.
Catching Zzs
Working the night shift demands a disciplined sleep schedule, said Nat deQuillfeldt, MD, a Denver Health chief resident in the University of Colorado’s internal medicine residency program.
“When I was on night admissions, I was very strict about going to sleep at 8 AM and waking at 3 PM every single day. It can be very tempting to try to stay up and spend time with loved ones, but my husband and I both prioritized my physical well-being for those weeks,” said deQuillfeldt, a PGY-4 resident. “It was especially challenging for me because I had to commute about 50 minutes each way and without such a rigid schedule I would have struggled to be on time.”
deQuillfeldt doesn’t have young children at home, a noisy community, or other distractions to interrupt sleep during the day. But it was still difficult for her to sleep while the sun was out. “I used an eye mask and ear plugs but definitely woke up more often than I would at night.”
Blackout curtains may have helped, she added.
“Without adequate sleep, your clinical thinking is not as sharp. When emergencies happen overnight, you’re often the first person to arrive and need to be able to make rapid, accurate assessments and decisions.”
As a chief resident, she chooses never to sleep during night shifts.
“I personally didn’t want to leave my interns alone or make them feel like they were waking me up or bothering me if they needed help, and I also didn’t want to be groggy in case of a rapid response or code blue.”
But napping on night shift is definitely possible, deQuillfeldt said. Between following up on overnight lab results, answering nurses’ questions, and responding to emergencies, she found downtime on night shift to eat and hydrate. She believes others can catch an hour or 2 of shut eye, even if they work in the intensive care unit, or 3-4 hours on rare quiet nights.
Vater suggests residents transitioning from daytime work to night shift prepare by trying to catch an afternoon nap, staying up later the night before the change, and banking sleep hours in advance.
When he knows he’s starting night shifts, Apurva Popat, MD, said he tries to go to sleep an hour or so later nights before to avoid becoming sleep deprived. The chief resident of internal medicine at Marshfield Clinic Health System in Marshfield, Wisconsin, doesn’t recommend sleeping during the night shift.
“I typically try not to sleep, even if I have time, so I can go home and sleep later in the morning,” said Popat, a PGY-3 resident.
To help him snooze, he uses blackout curtains and a fan to block out noise. His wife, a first-year internal medicine intern, often works a different shift, so she helps set up his sleeping environment and he reciprocates when it’s her turn for night shifts.
Some interns may need to catch a 20- to 30-minute nap on the first night shift, he said.
Popat also seeks out brighter areas of the hospital, such as the emergency department, where there are more people and colleagues to keep him alert.
Bypass Vending Machines
Lack of sleep makes it even more difficult to eat healthy on night shift, said Vater, who advises residents about wellness issues at IU and on social media.
“When you are sleep deprived, when you do not get enough sleep, you eat but you don’t feel full,” she said. “It’s hard to eat well on night shift. It’s harder if you go to the break room and there’s candy and junk food.”
Vater said that, as a resident, she brought a lunch bag to the hospital during night shifts. “I never had time to prep food, so I’d bring a whole apple, a whole orange, a whole avocado or nuts. It allowed me to eat more fruits and vegetables than I normally would.”
She advises caution when considering coffee to stay awake, especially after about 9 PM, which could interfere with sleep residents need later when they finish their shifts. Caffeine may help in the moment, but it prevents deep sleep, Vater said. So when residents finally get sleep after their shifts, they may wake up feeling tired, she said.
To avoid sleepiness, Popat brings protein shakes with him to night shifts. They stave off sugar spikes and keep his energy level high, he said. He might have a protein shake and fruit before he leaves home and carry his vegetarian dinner with him to eat in the early morning hours when the hospital is calm.
Eating small and frequent meals also helps ward off sleepiness, deQuillfeldt said.
Take the Stairs
Trying to stay healthy on night shifts, Vater also checked on patients by taking the stairs. “I’d set the timer on my phone for 30 minutes and if I got paged at 15, I’d pause the timer and reset it if I had a moment later. I’d get at least 30 minutes in, although not always continuous. I think some activity is better than none.”
Vater said her hospital had a gym, but it wasn’t practical for her because it was further away from where she worked. “Sometimes my coresidents would be more creative, and we would do squats.”
Popat tries to lift weights 2 hours before his night shift, but he also takes short walks between patients’ rooms in the early morning hours when it’s quietest. He also promotes deep breathing to stay alert.
Ask for a Ride
Vater urges those coming off night shifts, especially those transitioning for the first time from daytime rotations, not to drive if they’re exhausted. “Get an Uber. ... Make sure you get a ride home.”
The CU residency program covers the cost of a ridesharing service when doctors-in-training are too tired to drive home, deQuillfeldt said. “We really try to encourage people to use this to reduce the risk of car accidents.”
Promoting Mental Health
The residency program also links residents with primary care and mental health services. People who really struggle with shift work sleep disorder may qualify for medications to help them stay awake overnight, in addition to sleep hygiene apps and sleep aides.
“Night shifts can put a strain on mental health, especially when you’re only working, eating, and sleeping and not spending any time with family and friends,” deQuillfeldt said. “My husband works late afternoons, so we often would go weeks seeing each other for 15-20 minutes a day.”
“Sleeping when the sun is out often leads to a lack of light exposure which can compound the problem. Seeking mental health support early is really important to avoiding burnout,” she said.
She also recommended planning a fun weekend activity, trip, or celebration with friends or family after night shifts end “so you have something to look forward to…It’s so important to have a light at the end of the tunnel, which will allow you to enjoy the sense of accomplishment even more.”
For more advice on the subject, consider the American Medical Association guide to managing sleep deprivation in residency or Laura Vater’s tips for night shifts.
A version of this article first appeared on Medscape.com.
Laura Vater remembers sneaking into her home after 12-hour night shifts during medical training while her husband distracted their toddler. The stealthy tag-teaming effort helped her get enough undisturbed sleep before returning to an Indiana University hospital the following night to repeat the pattern.
“He would pretend to take out the trash when I pulled in,” said Vater, MD, now a gastrointestinal oncologist and assistant professor of medicine at IU Health Simon Cancer Center in Indianapolis. “I would sneak in so she [their daughter] wouldn’t see me, and then he would go back in.”
For Vater, prioritizing sleep during the day to combat sleep deprivation common among doctors-in-training on night shifts required enlisting a supportive spouse. It’s just one of the tips she and a few chief residents shared with this news organization for staying sharp and healthy during overnight rotations.
While the pace of patient rounds may slow from the frenetic daytime rush, training as a doctor after the sun goes down can be quite challenging for residents, they told this news organization. From sleep deprivation working while the rest of us slumbers to the after-effects of late-night caffeine, learning to manage night rotations requires a balance of preparation and attention to personal health while caring for others, the residents and adviser said.
Compromised sleep is one of the biggest hurdles residents have to overcome. Sleep loss comes with risks to cardiovascular disease and type 2 diabetes, among other heath conditions, according to Medscape Medical News reports. And night shift workers who sleep 6 or fewer hours a night have at least one sleep disorder.
Sleep deprivation associated with overnight call schedules also can worsen a resident’s mood and motivation while impairing their judgment, leading to medical errors, according to a new study published in JAMA Open Network. The study proposed shorter consecutive night shifts and naps as ways to offset the results of sleep loss, especially for interns or first-year residents.
Residency programs recently have been experimenting with shorter call schedules.
Catching Zzs
Working the night shift demands a disciplined sleep schedule, said Nat deQuillfeldt, MD, a Denver Health chief resident in the University of Colorado’s internal medicine residency program.
“When I was on night admissions, I was very strict about going to sleep at 8 AM and waking at 3 PM every single day. It can be very tempting to try to stay up and spend time with loved ones, but my husband and I both prioritized my physical well-being for those weeks,” said deQuillfeldt, a PGY-4 resident. “It was especially challenging for me because I had to commute about 50 minutes each way and without such a rigid schedule I would have struggled to be on time.”
deQuillfeldt doesn’t have young children at home, a noisy community, or other distractions to interrupt sleep during the day. But it was still difficult for her to sleep while the sun was out. “I used an eye mask and ear plugs but definitely woke up more often than I would at night.”
Blackout curtains may have helped, she added.
“Without adequate sleep, your clinical thinking is not as sharp. When emergencies happen overnight, you’re often the first person to arrive and need to be able to make rapid, accurate assessments and decisions.”
As a chief resident, she chooses never to sleep during night shifts.
“I personally didn’t want to leave my interns alone or make them feel like they were waking me up or bothering me if they needed help, and I also didn’t want to be groggy in case of a rapid response or code blue.”
But napping on night shift is definitely possible, deQuillfeldt said. Between following up on overnight lab results, answering nurses’ questions, and responding to emergencies, she found downtime on night shift to eat and hydrate. She believes others can catch an hour or 2 of shut eye, even if they work in the intensive care unit, or 3-4 hours on rare quiet nights.
Vater suggests residents transitioning from daytime work to night shift prepare by trying to catch an afternoon nap, staying up later the night before the change, and banking sleep hours in advance.
When he knows he’s starting night shifts, Apurva Popat, MD, said he tries to go to sleep an hour or so later nights before to avoid becoming sleep deprived. The chief resident of internal medicine at Marshfield Clinic Health System in Marshfield, Wisconsin, doesn’t recommend sleeping during the night shift.
“I typically try not to sleep, even if I have time, so I can go home and sleep later in the morning,” said Popat, a PGY-3 resident.
To help him snooze, he uses blackout curtains and a fan to block out noise. His wife, a first-year internal medicine intern, often works a different shift, so she helps set up his sleeping environment and he reciprocates when it’s her turn for night shifts.
Some interns may need to catch a 20- to 30-minute nap on the first night shift, he said.
Popat also seeks out brighter areas of the hospital, such as the emergency department, where there are more people and colleagues to keep him alert.
Bypass Vending Machines
Lack of sleep makes it even more difficult to eat healthy on night shift, said Vater, who advises residents about wellness issues at IU and on social media.
“When you are sleep deprived, when you do not get enough sleep, you eat but you don’t feel full,” she said. “It’s hard to eat well on night shift. It’s harder if you go to the break room and there’s candy and junk food.”
Vater said that, as a resident, she brought a lunch bag to the hospital during night shifts. “I never had time to prep food, so I’d bring a whole apple, a whole orange, a whole avocado or nuts. It allowed me to eat more fruits and vegetables than I normally would.”
She advises caution when considering coffee to stay awake, especially after about 9 PM, which could interfere with sleep residents need later when they finish their shifts. Caffeine may help in the moment, but it prevents deep sleep, Vater said. So when residents finally get sleep after their shifts, they may wake up feeling tired, she said.
To avoid sleepiness, Popat brings protein shakes with him to night shifts. They stave off sugar spikes and keep his energy level high, he said. He might have a protein shake and fruit before he leaves home and carry his vegetarian dinner with him to eat in the early morning hours when the hospital is calm.
Eating small and frequent meals also helps ward off sleepiness, deQuillfeldt said.
Take the Stairs
Trying to stay healthy on night shifts, Vater also checked on patients by taking the stairs. “I’d set the timer on my phone for 30 minutes and if I got paged at 15, I’d pause the timer and reset it if I had a moment later. I’d get at least 30 minutes in, although not always continuous. I think some activity is better than none.”
Vater said her hospital had a gym, but it wasn’t practical for her because it was further away from where she worked. “Sometimes my coresidents would be more creative, and we would do squats.”
Popat tries to lift weights 2 hours before his night shift, but he also takes short walks between patients’ rooms in the early morning hours when it’s quietest. He also promotes deep breathing to stay alert.
Ask for a Ride
Vater urges those coming off night shifts, especially those transitioning for the first time from daytime rotations, not to drive if they’re exhausted. “Get an Uber. ... Make sure you get a ride home.”
The CU residency program covers the cost of a ridesharing service when doctors-in-training are too tired to drive home, deQuillfeldt said. “We really try to encourage people to use this to reduce the risk of car accidents.”
Promoting Mental Health
The residency program also links residents with primary care and mental health services. People who really struggle with shift work sleep disorder may qualify for medications to help them stay awake overnight, in addition to sleep hygiene apps and sleep aides.
“Night shifts can put a strain on mental health, especially when you’re only working, eating, and sleeping and not spending any time with family and friends,” deQuillfeldt said. “My husband works late afternoons, so we often would go weeks seeing each other for 15-20 minutes a day.”
“Sleeping when the sun is out often leads to a lack of light exposure which can compound the problem. Seeking mental health support early is really important to avoiding burnout,” she said.
She also recommended planning a fun weekend activity, trip, or celebration with friends or family after night shifts end “so you have something to look forward to…It’s so important to have a light at the end of the tunnel, which will allow you to enjoy the sense of accomplishment even more.”
For more advice on the subject, consider the American Medical Association guide to managing sleep deprivation in residency or Laura Vater’s tips for night shifts.
A version of this article first appeared on Medscape.com.
Finally, a New Drug for Posttraumatic Stress Disorder?
A drug that combines the atypical antipsychotic brexpiprazole and the selective serotonin reuptake inhibitor sertraline provides significantly greater relief of posttraumatic stress disorder (PTSD) symptoms than sertraline plus placebo, results of a phase 3 trial showed.
The medication is currently under review by the Food and Drug Administration (FDA) and if approved, will be the first pharmacologic option for PTSD in more than 20 years.
The trial met its primary endpoint of change in the Clinician Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) (CAPS-5) total score at week 10 and secondary patient-reported outcomes of PTSD symptoms, anxiety, and depression.
“And what is really cool, what’s really impactful is the combination worked better than sertraline plus placebo on a brief inventory of psychosocial functioning,” study investigator Lori L. Davis, a senior research psychiatrist, Birmingham Veterans Affairs Health Care System in Alabama, said in an interview.
“We can treat symptoms but that’s where the rubber meets the road, in terms of are they functioning better,” added Davis, who is also an adjunct professor of psychiatry, Heersink School of Medicine, University of Alabama at Birmingham.
The findings were published online on December 18 in JAMA Psychiatry and reported in May 2024 as part of a trio of trials conducted by Otsuka Pharmaceutical and Lundbeck Pharmaceuticals, codevelopers of the drug.
Clinically Meaningful
“This study provides promising results for a medication that may be an important new option for PTSD,” John Krystal, MD, director, Clinical Neuroscience Division, National Center for PTSD, US Department of Veterans Affairs, who was not involved in the research, said in an interview. “New PTSD treatments are a high priority.”
Currently, there are two FDA-approved medication treatments for PTSD — sertraline and paroxetine.
“They are helpful for many people, but patients are often left with residual symptoms or tolerability issues,” noted Krystal, who is also professor and chair of psychiatry, Yale University, New Haven, Connecticut.
“New medications that might address the important ‘effectiveness gap’ in PTSD could help to reduce the remaining distress, disability, and suicide risk associated with PTSD.”
The double-blind, phase 3 trial included 416 adults aged 18-65 years with a DSM-5 diagnosis of PTSD and symptoms for at least 6 months prior to screening. Patients underwent a 1-week placebo-run in period followed by randomization to daily oral brexpiprazole 2-3 mg plus sertraline 150 mg or daily sertraline 150 mg plus placebo for 11 weeks.
Participants’ mean age was 37.4 years, 74.5% were women, and mean CAPS-5 total score was 38.4, suggesting moderate to high severity PTSD, Davis said. The average time from the index traumatic event was 4 years and three fourths had no prior exposure to PTSD prescription medications.
At week 10, the mean change in CAPS-5 score from randomization was –19.2 points in the brexpiprazole plus sertraline group and –13.6 points in the sertraline plus placebo group (95% CI, –8.79 to –2.38; P < .001).
Asked whether the 5.59-point treatment difference is clinically meaningful, Davis said there is no widely agreed definition for change in CAPS-5 total score but that a within-group reduction of more than 10-13 points is most-often cited as being clinically meaningful.
The key secondary endpoint of least square mean change in the patient-reported Brief Inventory of Psychosocial Function total score from baseline to week 12 was –33.8 with the combination vs –21.8 with sertraline plus placebo (95% CI, –19.4 to –4.62; P = .002).
“That’s clinically meaningful for me as a provider and a clinician and a researcher when you’re getting the PTSD symptom change differences in parallel with the improvement in functional outcome,” she said. “I see that as the clinically meaningful gauge.”
In terms of safety, 3.9% of the participants in the brexpiprazole/sertraline group and 10.2% of those in the sertraline/placebo group discontinued treatment because of adverse events.
In both the combination and control groups, the only treatment-emergent adverse event with an incidence of more than 10% was nausea (12.2% vs 11.7%, respectively).
At the last visit, the mean change in body weight from baseline was an increase of 1.3 kg for brexpiprazole plus sertraline vs 0 kg for sertraline alone. Rates of fatigue (6.8% vs 4.1%) and somnolence (5.4% vs 2.6%) were also higher with brexpiprazole plus sertraline.
A Trio of Clinical Trials
The findings are part of a larger program reported by the drug makers that includes a flexible-dose brexpiprazole phase 2 trial that met the same CAPS-5 primary endpoint and a second phase 3 trial (072 study) that did not.
“We’ve looked at that data and the sertraline/placebo response was a lot higher, so it was not due to a lack of response with the combination but due to a more robust response with the active control,” Davis said. “But we want to point out for that 072 study, there was still important separation between the combination and sertraline plus placebo on the functional outcome.”
All three trials ran for 12 weeks, so longer-term efficacy and safety data are needed, she said. Other limitations of the published phase 3 study are the patient eligibility criteria, restrictions on concomitant therapy, and lack of non-US sites, which many limit generalizability, the authors noted.
“Specifically, the exclusion of patients with a current major depressive episode is both a strength (to show a specific effect on PTSD) and a limitation (given the high prevalence of comorbid depression in PTSD),” they added.
Kudos, Caveats
Reached for comment, Vincent F. Capaldi, II, MD, ScM, professor and chair, department of psychiatry, Uniformed Services University of the Health Sciences School of Medicine, Bethesda, Maryland, said the exclusion of these patients is a limitation but that the study was well designed and conducted in a large sample across the United States.
“The findings suggest that brexpiprazole plus sertraline is a more effective treatment for PTSD than sertraline alone,” he said. “This finding is significant for our service members, who suffer from PTSD at higher rates than the general population.”
Additionally, the significant improvement in psychosocial functioning at week 12 “is important because PTSD is known to cause significant social and occupational disability, as well as quality-of-life issues,” he said.
Capaldi pointed out, however, that the study was conducted only at US sites and did not specifically target military/veteran persons, which may limit applicability to these unique populations.
“While subgroup analyses were generally consistent with the primary analysis, the study was not powered to detect differences between subgroups,” he added. “These subgroup analyses are quite important when considering military and veteran populations.”
Further research is needed to explore whether certain traumas are more responsive to combination treatment, the efficacy of augmenting existing sertraline therapy, and the specific mechanisms of brexpiprazole driving the improved outcomes, Capaldi said.
This study was funded by Otsuka Pharmaceutical Development & Commercialization, which was involved in the design, conduct, and data analysis. Davis reported receiving advisory board fees from Otsuka and Boehringer Ingelheim; lecture fees from Clinical Care Options; and grants from Alkermes, the Veterans Affairs, Patient-Centered Outcomes Research Institute, Department of Defense, and Social Finance. Several coauthors are employees of Otsuka. Krystal reported serving as a consultant for Otsuka America Pharmaceutical, Aptinyx, Biogen, IDEC, Bionomics, Boehringer Ingelheim International, Clearmind Medicine, Cybin IRL, Enveric Biosciences, Epiodyne, EpiVario, Janssen, Jazz Pharmaceuticals, Perception Neuroscience, Praxis Precision Medicines, Springcare, and Sunovion Pharmaceuticals. Krystal also reported serving as a scientific advisory board member for several companies and holding several patents.
A version of this article appeared on Medscape.com.
A drug that combines the atypical antipsychotic brexpiprazole and the selective serotonin reuptake inhibitor sertraline provides significantly greater relief of posttraumatic stress disorder (PTSD) symptoms than sertraline plus placebo, results of a phase 3 trial showed.
The medication is currently under review by the Food and Drug Administration (FDA) and if approved, will be the first pharmacologic option for PTSD in more than 20 years.
The trial met its primary endpoint of change in the Clinician Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) (CAPS-5) total score at week 10 and secondary patient-reported outcomes of PTSD symptoms, anxiety, and depression.
“And what is really cool, what’s really impactful is the combination worked better than sertraline plus placebo on a brief inventory of psychosocial functioning,” study investigator Lori L. Davis, a senior research psychiatrist, Birmingham Veterans Affairs Health Care System in Alabama, said in an interview.
“We can treat symptoms but that’s where the rubber meets the road, in terms of are they functioning better,” added Davis, who is also an adjunct professor of psychiatry, Heersink School of Medicine, University of Alabama at Birmingham.
The findings were published online on December 18 in JAMA Psychiatry and reported in May 2024 as part of a trio of trials conducted by Otsuka Pharmaceutical and Lundbeck Pharmaceuticals, codevelopers of the drug.
Clinically Meaningful
“This study provides promising results for a medication that may be an important new option for PTSD,” John Krystal, MD, director, Clinical Neuroscience Division, National Center for PTSD, US Department of Veterans Affairs, who was not involved in the research, said in an interview. “New PTSD treatments are a high priority.”
Currently, there are two FDA-approved medication treatments for PTSD — sertraline and paroxetine.
“They are helpful for many people, but patients are often left with residual symptoms or tolerability issues,” noted Krystal, who is also professor and chair of psychiatry, Yale University, New Haven, Connecticut.
“New medications that might address the important ‘effectiveness gap’ in PTSD could help to reduce the remaining distress, disability, and suicide risk associated with PTSD.”
The double-blind, phase 3 trial included 416 adults aged 18-65 years with a DSM-5 diagnosis of PTSD and symptoms for at least 6 months prior to screening. Patients underwent a 1-week placebo-run in period followed by randomization to daily oral brexpiprazole 2-3 mg plus sertraline 150 mg or daily sertraline 150 mg plus placebo for 11 weeks.
Participants’ mean age was 37.4 years, 74.5% were women, and mean CAPS-5 total score was 38.4, suggesting moderate to high severity PTSD, Davis said. The average time from the index traumatic event was 4 years and three fourths had no prior exposure to PTSD prescription medications.
At week 10, the mean change in CAPS-5 score from randomization was –19.2 points in the brexpiprazole plus sertraline group and –13.6 points in the sertraline plus placebo group (95% CI, –8.79 to –2.38; P < .001).
Asked whether the 5.59-point treatment difference is clinically meaningful, Davis said there is no widely agreed definition for change in CAPS-5 total score but that a within-group reduction of more than 10-13 points is most-often cited as being clinically meaningful.
The key secondary endpoint of least square mean change in the patient-reported Brief Inventory of Psychosocial Function total score from baseline to week 12 was –33.8 with the combination vs –21.8 with sertraline plus placebo (95% CI, –19.4 to –4.62; P = .002).
“That’s clinically meaningful for me as a provider and a clinician and a researcher when you’re getting the PTSD symptom change differences in parallel with the improvement in functional outcome,” she said. “I see that as the clinically meaningful gauge.”
In terms of safety, 3.9% of the participants in the brexpiprazole/sertraline group and 10.2% of those in the sertraline/placebo group discontinued treatment because of adverse events.
In both the combination and control groups, the only treatment-emergent adverse event with an incidence of more than 10% was nausea (12.2% vs 11.7%, respectively).
At the last visit, the mean change in body weight from baseline was an increase of 1.3 kg for brexpiprazole plus sertraline vs 0 kg for sertraline alone. Rates of fatigue (6.8% vs 4.1%) and somnolence (5.4% vs 2.6%) were also higher with brexpiprazole plus sertraline.
A Trio of Clinical Trials
The findings are part of a larger program reported by the drug makers that includes a flexible-dose brexpiprazole phase 2 trial that met the same CAPS-5 primary endpoint and a second phase 3 trial (072 study) that did not.
“We’ve looked at that data and the sertraline/placebo response was a lot higher, so it was not due to a lack of response with the combination but due to a more robust response with the active control,” Davis said. “But we want to point out for that 072 study, there was still important separation between the combination and sertraline plus placebo on the functional outcome.”
All three trials ran for 12 weeks, so longer-term efficacy and safety data are needed, she said. Other limitations of the published phase 3 study are the patient eligibility criteria, restrictions on concomitant therapy, and lack of non-US sites, which many limit generalizability, the authors noted.
“Specifically, the exclusion of patients with a current major depressive episode is both a strength (to show a specific effect on PTSD) and a limitation (given the high prevalence of comorbid depression in PTSD),” they added.
Kudos, Caveats
Reached for comment, Vincent F. Capaldi, II, MD, ScM, professor and chair, department of psychiatry, Uniformed Services University of the Health Sciences School of Medicine, Bethesda, Maryland, said the exclusion of these patients is a limitation but that the study was well designed and conducted in a large sample across the United States.
“The findings suggest that brexpiprazole plus sertraline is a more effective treatment for PTSD than sertraline alone,” he said. “This finding is significant for our service members, who suffer from PTSD at higher rates than the general population.”
Additionally, the significant improvement in psychosocial functioning at week 12 “is important because PTSD is known to cause significant social and occupational disability, as well as quality-of-life issues,” he said.
Capaldi pointed out, however, that the study was conducted only at US sites and did not specifically target military/veteran persons, which may limit applicability to these unique populations.
“While subgroup analyses were generally consistent with the primary analysis, the study was not powered to detect differences between subgroups,” he added. “These subgroup analyses are quite important when considering military and veteran populations.”
Further research is needed to explore whether certain traumas are more responsive to combination treatment, the efficacy of augmenting existing sertraline therapy, and the specific mechanisms of brexpiprazole driving the improved outcomes, Capaldi said.
This study was funded by Otsuka Pharmaceutical Development & Commercialization, which was involved in the design, conduct, and data analysis. Davis reported receiving advisory board fees from Otsuka and Boehringer Ingelheim; lecture fees from Clinical Care Options; and grants from Alkermes, the Veterans Affairs, Patient-Centered Outcomes Research Institute, Department of Defense, and Social Finance. Several coauthors are employees of Otsuka. Krystal reported serving as a consultant for Otsuka America Pharmaceutical, Aptinyx, Biogen, IDEC, Bionomics, Boehringer Ingelheim International, Clearmind Medicine, Cybin IRL, Enveric Biosciences, Epiodyne, EpiVario, Janssen, Jazz Pharmaceuticals, Perception Neuroscience, Praxis Precision Medicines, Springcare, and Sunovion Pharmaceuticals. Krystal also reported serving as a scientific advisory board member for several companies and holding several patents.
A version of this article appeared on Medscape.com.
A drug that combines the atypical antipsychotic brexpiprazole and the selective serotonin reuptake inhibitor sertraline provides significantly greater relief of posttraumatic stress disorder (PTSD) symptoms than sertraline plus placebo, results of a phase 3 trial showed.
The medication is currently under review by the Food and Drug Administration (FDA) and if approved, will be the first pharmacologic option for PTSD in more than 20 years.
The trial met its primary endpoint of change in the Clinician Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) (CAPS-5) total score at week 10 and secondary patient-reported outcomes of PTSD symptoms, anxiety, and depression.
“And what is really cool, what’s really impactful is the combination worked better than sertraline plus placebo on a brief inventory of psychosocial functioning,” study investigator Lori L. Davis, a senior research psychiatrist, Birmingham Veterans Affairs Health Care System in Alabama, said in an interview.
“We can treat symptoms but that’s where the rubber meets the road, in terms of are they functioning better,” added Davis, who is also an adjunct professor of psychiatry, Heersink School of Medicine, University of Alabama at Birmingham.
The findings were published online on December 18 in JAMA Psychiatry and reported in May 2024 as part of a trio of trials conducted by Otsuka Pharmaceutical and Lundbeck Pharmaceuticals, codevelopers of the drug.
Clinically Meaningful
“This study provides promising results for a medication that may be an important new option for PTSD,” John Krystal, MD, director, Clinical Neuroscience Division, National Center for PTSD, US Department of Veterans Affairs, who was not involved in the research, said in an interview. “New PTSD treatments are a high priority.”
Currently, there are two FDA-approved medication treatments for PTSD — sertraline and paroxetine.
“They are helpful for many people, but patients are often left with residual symptoms or tolerability issues,” noted Krystal, who is also professor and chair of psychiatry, Yale University, New Haven, Connecticut.
“New medications that might address the important ‘effectiveness gap’ in PTSD could help to reduce the remaining distress, disability, and suicide risk associated with PTSD.”
The double-blind, phase 3 trial included 416 adults aged 18-65 years with a DSM-5 diagnosis of PTSD and symptoms for at least 6 months prior to screening. Patients underwent a 1-week placebo-run in period followed by randomization to daily oral brexpiprazole 2-3 mg plus sertraline 150 mg or daily sertraline 150 mg plus placebo for 11 weeks.
Participants’ mean age was 37.4 years, 74.5% were women, and mean CAPS-5 total score was 38.4, suggesting moderate to high severity PTSD, Davis said. The average time from the index traumatic event was 4 years and three fourths had no prior exposure to PTSD prescription medications.
At week 10, the mean change in CAPS-5 score from randomization was –19.2 points in the brexpiprazole plus sertraline group and –13.6 points in the sertraline plus placebo group (95% CI, –8.79 to –2.38; P < .001).
Asked whether the 5.59-point treatment difference is clinically meaningful, Davis said there is no widely agreed definition for change in CAPS-5 total score but that a within-group reduction of more than 10-13 points is most-often cited as being clinically meaningful.
The key secondary endpoint of least square mean change in the patient-reported Brief Inventory of Psychosocial Function total score from baseline to week 12 was –33.8 with the combination vs –21.8 with sertraline plus placebo (95% CI, –19.4 to –4.62; P = .002).
“That’s clinically meaningful for me as a provider and a clinician and a researcher when you’re getting the PTSD symptom change differences in parallel with the improvement in functional outcome,” she said. “I see that as the clinically meaningful gauge.”
In terms of safety, 3.9% of the participants in the brexpiprazole/sertraline group and 10.2% of those in the sertraline/placebo group discontinued treatment because of adverse events.
In both the combination and control groups, the only treatment-emergent adverse event with an incidence of more than 10% was nausea (12.2% vs 11.7%, respectively).
At the last visit, the mean change in body weight from baseline was an increase of 1.3 kg for brexpiprazole plus sertraline vs 0 kg for sertraline alone. Rates of fatigue (6.8% vs 4.1%) and somnolence (5.4% vs 2.6%) were also higher with brexpiprazole plus sertraline.
A Trio of Clinical Trials
The findings are part of a larger program reported by the drug makers that includes a flexible-dose brexpiprazole phase 2 trial that met the same CAPS-5 primary endpoint and a second phase 3 trial (072 study) that did not.
“We’ve looked at that data and the sertraline/placebo response was a lot higher, so it was not due to a lack of response with the combination but due to a more robust response with the active control,” Davis said. “But we want to point out for that 072 study, there was still important separation between the combination and sertraline plus placebo on the functional outcome.”
All three trials ran for 12 weeks, so longer-term efficacy and safety data are needed, she said. Other limitations of the published phase 3 study are the patient eligibility criteria, restrictions on concomitant therapy, and lack of non-US sites, which many limit generalizability, the authors noted.
“Specifically, the exclusion of patients with a current major depressive episode is both a strength (to show a specific effect on PTSD) and a limitation (given the high prevalence of comorbid depression in PTSD),” they added.
Kudos, Caveats
Reached for comment, Vincent F. Capaldi, II, MD, ScM, professor and chair, department of psychiatry, Uniformed Services University of the Health Sciences School of Medicine, Bethesda, Maryland, said the exclusion of these patients is a limitation but that the study was well designed and conducted in a large sample across the United States.
“The findings suggest that brexpiprazole plus sertraline is a more effective treatment for PTSD than sertraline alone,” he said. “This finding is significant for our service members, who suffer from PTSD at higher rates than the general population.”
Additionally, the significant improvement in psychosocial functioning at week 12 “is important because PTSD is known to cause significant social and occupational disability, as well as quality-of-life issues,” he said.
Capaldi pointed out, however, that the study was conducted only at US sites and did not specifically target military/veteran persons, which may limit applicability to these unique populations.
“While subgroup analyses were generally consistent with the primary analysis, the study was not powered to detect differences between subgroups,” he added. “These subgroup analyses are quite important when considering military and veteran populations.”
Further research is needed to explore whether certain traumas are more responsive to combination treatment, the efficacy of augmenting existing sertraline therapy, and the specific mechanisms of brexpiprazole driving the improved outcomes, Capaldi said.
This study was funded by Otsuka Pharmaceutical Development & Commercialization, which was involved in the design, conduct, and data analysis. Davis reported receiving advisory board fees from Otsuka and Boehringer Ingelheim; lecture fees from Clinical Care Options; and grants from Alkermes, the Veterans Affairs, Patient-Centered Outcomes Research Institute, Department of Defense, and Social Finance. Several coauthors are employees of Otsuka. Krystal reported serving as a consultant for Otsuka America Pharmaceutical, Aptinyx, Biogen, IDEC, Bionomics, Boehringer Ingelheim International, Clearmind Medicine, Cybin IRL, Enveric Biosciences, Epiodyne, EpiVario, Janssen, Jazz Pharmaceuticals, Perception Neuroscience, Praxis Precision Medicines, Springcare, and Sunovion Pharmaceuticals. Krystal also reported serving as a scientific advisory board member for several companies and holding several patents.
A version of this article appeared on Medscape.com.
VA Launches New Campaign to Attract More Veterans to Health Care
A new US Department of Veterans Affairs (VA) outreach campaign is encouraging all eligible veterans to enroll in VA health care, aiming to connect the roughly 1 million unenrolled veterans to care.
The campaign was prompted following reports of concerns from veterans about health issues—including mental health hurdles and thoughts of suicide—potentially related to repeated low-level artillery blasts, improvised explosive devices, missile launches, heavy fire, and other blast exposures.
Veterans enrolled in VA health care have access to specialty screenings and services to address issues related to blast exposure. Those who served in Vietnam, the Gulf War, Iraq, Afghanistan, and other specific locations are eligible for these benefits based on their deployments. They do not need to have any health conditions specifically associated with their service to be eligible.
“We take veteran concerns about repeated blast exposure very seriously, and we are studying this matter urgently to learn more about potential health impacts,” VA Secretary Denis McDonough said. “While we do that, we don’t want veterans to wait—they should enroll in VA health care today to get full access to primary care, mental health care, regular screenings, specialty care, and more. That’s what this outreach effort is all about: getting veterans in our care, because veterans who come to VA are proven to do better.”
The campaign will consist of text messages and emails sent directly to veterans, in addition to thousands of nationwide events, advertising, and social media campaigns. It is the latest effort to appeal to more veterans and is part of the largest outreach campaign in VA history, which began when President Joseph R. Biden signed the PACT Act into law in 2022. As a result > 835,000 veterans have enrolled in VA health care (a 37% increase), > 900,000 veterans have upgraded their priority groups, making them eligible for health care with fewer copays (a record), and > 4.4 million veterans and survivors have applied for disability compensation benefits (another record).
Increased enrollment benefits not only the individuals enrolled in VA health care, but those who come after.
"[W]e are constantly looking for ways to improve that care as science and research tells us about new concerns," said VA Under Secretary for Health Shereef Elnahal, MD. "The more veterans who enroll, the more we can learn about the impact of blast exposure—and the better care we can ultimately provide those who served."
A new US Department of Veterans Affairs (VA) outreach campaign is encouraging all eligible veterans to enroll in VA health care, aiming to connect the roughly 1 million unenrolled veterans to care.
The campaign was prompted following reports of concerns from veterans about health issues—including mental health hurdles and thoughts of suicide—potentially related to repeated low-level artillery blasts, improvised explosive devices, missile launches, heavy fire, and other blast exposures.
Veterans enrolled in VA health care have access to specialty screenings and services to address issues related to blast exposure. Those who served in Vietnam, the Gulf War, Iraq, Afghanistan, and other specific locations are eligible for these benefits based on their deployments. They do not need to have any health conditions specifically associated with their service to be eligible.
“We take veteran concerns about repeated blast exposure very seriously, and we are studying this matter urgently to learn more about potential health impacts,” VA Secretary Denis McDonough said. “While we do that, we don’t want veterans to wait—they should enroll in VA health care today to get full access to primary care, mental health care, regular screenings, specialty care, and more. That’s what this outreach effort is all about: getting veterans in our care, because veterans who come to VA are proven to do better.”
The campaign will consist of text messages and emails sent directly to veterans, in addition to thousands of nationwide events, advertising, and social media campaigns. It is the latest effort to appeal to more veterans and is part of the largest outreach campaign in VA history, which began when President Joseph R. Biden signed the PACT Act into law in 2022. As a result > 835,000 veterans have enrolled in VA health care (a 37% increase), > 900,000 veterans have upgraded their priority groups, making them eligible for health care with fewer copays (a record), and > 4.4 million veterans and survivors have applied for disability compensation benefits (another record).
Increased enrollment benefits not only the individuals enrolled in VA health care, but those who come after.
"[W]e are constantly looking for ways to improve that care as science and research tells us about new concerns," said VA Under Secretary for Health Shereef Elnahal, MD. "The more veterans who enroll, the more we can learn about the impact of blast exposure—and the better care we can ultimately provide those who served."
A new US Department of Veterans Affairs (VA) outreach campaign is encouraging all eligible veterans to enroll in VA health care, aiming to connect the roughly 1 million unenrolled veterans to care.
The campaign was prompted following reports of concerns from veterans about health issues—including mental health hurdles and thoughts of suicide—potentially related to repeated low-level artillery blasts, improvised explosive devices, missile launches, heavy fire, and other blast exposures.
Veterans enrolled in VA health care have access to specialty screenings and services to address issues related to blast exposure. Those who served in Vietnam, the Gulf War, Iraq, Afghanistan, and other specific locations are eligible for these benefits based on their deployments. They do not need to have any health conditions specifically associated with their service to be eligible.
“We take veteran concerns about repeated blast exposure very seriously, and we are studying this matter urgently to learn more about potential health impacts,” VA Secretary Denis McDonough said. “While we do that, we don’t want veterans to wait—they should enroll in VA health care today to get full access to primary care, mental health care, regular screenings, specialty care, and more. That’s what this outreach effort is all about: getting veterans in our care, because veterans who come to VA are proven to do better.”
The campaign will consist of text messages and emails sent directly to veterans, in addition to thousands of nationwide events, advertising, and social media campaigns. It is the latest effort to appeal to more veterans and is part of the largest outreach campaign in VA history, which began when President Joseph R. Biden signed the PACT Act into law in 2022. As a result > 835,000 veterans have enrolled in VA health care (a 37% increase), > 900,000 veterans have upgraded their priority groups, making them eligible for health care with fewer copays (a record), and > 4.4 million veterans and survivors have applied for disability compensation benefits (another record).
Increased enrollment benefits not only the individuals enrolled in VA health care, but those who come after.
"[W]e are constantly looking for ways to improve that care as science and research tells us about new concerns," said VA Under Secretary for Health Shereef Elnahal, MD. "The more veterans who enroll, the more we can learn about the impact of blast exposure—and the better care we can ultimately provide those who served."
Impact of NSAID Use on Bleeding Rates for Patients Taking Rivaroxaban or Apixaban
Impact of NSAID Use on Bleeding Rates for Patients Taking Rivaroxaban or Apixaban
Clinical practice has shifted from vitamin K antagonists to direct oral anticoagulants (DOACs) for atrial fibrillation treatment due to their more favorable risk-benefit profile and less lifestyle modification required.1,2 However, the advantage of a lower bleeding risk with DOACs could be compromised by potentially problematic pharmacokinetic interactions like those conferred by antiplatelets or nonsteroidal anti-inflammatory drugs (NSAIDs).3,4 Treating a patient needing anticoagulation with a DOAC who has comorbidities may introduce unavoidable drug-drug interactions. This particularly happens with over-the-counter and prescription NSAIDs used for the management of pain and inflammatory conditions.5
NSAIDs primarily affect 2 cyclooxygenase (COX) enzyme isomers, COX-1 and COX-2.6 COX-1 helps maintain gastrointestinal (GI) mucosa integrity and platelet aggregation processes, whereas COX-2 is engaged in pain signaling and inflammation mediation. COX-1 inhibition is associated with more bleeding-related adverse events (AEs), especially in the GI tract. COX-2 inhibition is thought to provide analgesia and anti-inflammatory properties without elevating bleeding risk. This premise is responsible for the preferential use of celecoxib, a COX-2 selective NSAID, which should confer a lower bleeding risk compared to nonselective NSAIDs such as ibuprofen and naproxen.7 NSAIDs have been documented as independent risk factors for bleeding. NSAID users are about 3 times as likely to develop GI AEs compared to nonNSAID users.8
Many clinicians aim to further mitigate NSAID-associated bleeding risk by coprescribing a proton pump inhibitor (PPI). PPIs provide gastroprotection against NSAID-induced mucosal injury and sequential complication of GI bleeding. In a multicenter randomized control trial, patients who received concomitant PPI therapy while undergoing chronic NSAID therapy—including nonselective and COX-2 selective NSAIDs—had a significantly lower risk of GI ulcer development (placebo, 17.0%; 20 mg esomeprazole, 5.2%; 40 mg esomeprazole, 4.6%).9 Current clinical guidelines for preventing NSAIDassociated bleeding complications recommend using a COX-2 selective NSAID in combination with PPI therapy for patients at high risk for GI-related bleeding, including the concomitant use of anticoagulants.10
There is evidence suggesting an increased bleeding risk with NSAIDs when used in combination with vitamin K antagonists such as warfarin.11,12 A systematic review of warfarin and concomitant NSAID use found an increased risk of overall bleeding with NSAID use in combination with warfarin (odds ratio 1.58; 95% CI, 1.18-2.12), compared to warfarin alone.12
Posthoc analyses of randomized clinical trials have also demonstrated an increased bleeding risk with oral anticoagulation and concomitant NSAID use.13,14 In the RE-LY trial, NSAID users on warfarin or dabigatran had a statistically significant increased risk of major bleeding compared to non-NSAID users (hazard ratio [HR] 1.68; 95% CI, 1.40- 2.02; P < .001).13 In the ARISTOTLE trial, patients on warfarin or apixaban who were incident NSAID users were found to have an increased risk of major bleeding (HR 1.61; 95% CI, 1.11-2.33) and clinically relevant nonmajor bleeding (HR 1.70; 95% CI, 1.16- 2.48).14 These trials found a statistically significant increased bleeding risk associated with NSAID use, though the populations evaluated included patients taking warfarin and patients taking DOACs. These trials did not evaluate the bleeding risk of concomitant NSAID use among DOACs alone.
Evidence on NSAID-associated bleeding risk with DOACs is lacking in settings where the patient population, prescribing practices, and monitoring levels are variable. Within the Veterans Health Administration, clinical pharmacist practitioners (CPPs) in anticoagulation clinics oversee DOAC therapy management. CPPs monitor safety and efficacy of DOAC therapies through a population health management tool, the DOAC Dashboard.15 The DOAC Dashboard creates alerts for patients who may require an intervention based on certain clinical parameters, such as drug-drug interactions.16 Whenever a patient on a DOAC is prescribed an NSAID, an alert is generated on the DOAC Dashboard to flag the CPPs for the potential need for an intervention. If NSAID therapy remains clinically indicated, CPPs may recommend risk reduction strategies such as a COX-2 selective NSAID or coprescribing a PPI.10
The DOAC Dashboard provides an ideal setting for investigating the effects of NSAID use, NSAID selectivity, and PPI coprescribing on DOAC bleeding rates. With an increasing population of patients receiving anticoagulation therapy with a DOAC, more guidance regarding the bleeding risk of concomitant NSAID use with DOACs is needed. Studies evaluating the bleeding risk with concomitant NSAID use in patients on a DOAC alone are limited. This is the first study to date to compare bleeding risk with concomitant NSAID use between DOACs. This study provides information on bleeding risk with NSAID use among commonly prescribed DOACs, rivaroxaban and apixaban, and the potential impacts of current risk reduction strategies.
METHODS
This single-center retrospective cohort review was performed using the electronic health records (EHRs) of patients enrolled in the US Department of Veterans Affairs (VA) Mountain Home Healthcare System who received rivaroxaban or apixaban from December 2020 to December 2022. This study received approval from the East Tennessee State University/VA Institutional Review Board committee.
Patients were identified through the DOAC Dashboard, aged 21 to 100 years, and received rivaroxaban or apixaban at a therapeutic dose: rivaroxaban 10 to 20 mg daily or apixaban 2.5 to 5 mg twice daily. Patients were excluded if they were prescribed dual antiplatelet therapy, received rivaroxaban at dosing indicated for peripheral vascular disease, were undergoing dialysis, had evidence of moderate to severe hepatic impairment or any hepatic disease with coagulopathy, were undergoing chemotherapy or radiation, or had hematological conditions with predisposed bleeding risk. These patients were excluded to mitigate the potential confounding impact from nontherapeutic DOAC dosing strategies and conditions associated with an increased bleeding risk.
Eligible patients were stratified based on NSAID use. NSAID users were defined as patients prescribed an oral NSAID, including both acute and chronic courses, at any point during the study time frame while actively on a DOAC. Bleeding events were reviewed to evaluate rates between rivaroxaban and apixaban among NSAID and nonNSAID users. Identified NSAID users were further assessed for NSAID selectivity and PPI coprescribing as a subgroup analysis for the secondary assessment.
Data Collection
Baseline data were collected, including age, body mass index, anticoagulation indication, DOAC agent, DOAC dose, and DOAC total daily dose. Baseline serum creatinine levels, liver function tests, hemoglobin levels, and platelet counts were collected from the most recent data available immediately prior to the bleeding event, if applicable.
The DOAC Dashboard was reviewed for active and dismissed drug interaction alerts to identify patients taking rivaroxaban or apixaban who were prescribed an NSAID. Patients were categorized in the NSAID group if an interacting drug alert with an NSAID was reported during the study time frame. Data available through the interacting drug alerts on NSAID use were limited to the interacting drug name and date of the reported flag. Manual EHR review was required to confirm dates of NSAID therapy initiation and NSAID discontinuation, if applicable.
Data regarding concomitant antiplatelet use were obtained through review of the active and dismissed drug interaction alerts on the DOAC Dashboard. Concomitant antiplatelet use was defined as the prescribing of a single antiplatelet agent at any point while receiving DOAC therapy. Data on concomitant antiplatelets were collected regardless of NSAID status.
Data on coprescribed PPI therapy were obtained through manual EHR review of identified NSAID users. Coprescribed PPI therapy was defined as the prescribing of a PPI at any point during NSAID therapy. Data regarding PPI use among non-NSAID users were not collected because the secondary endpoint was designed to assess PPI use only among patients coprescribed a DOAC and NSAID.
Outcomes
Bleeding events were identified through an outcomes report generated by the DOAC Dashboard based on International Classification of Diseases, Tenth Revision diagnosis codes associated with a bleeding event. The outcomes report captures diagnoses from the outpatient and inpatient care settings. Reported bleeding events were limited to patients who received a DOAC at any point in the 6 months prior to the event and excluded patients with recent DOAC initiation within 7 days of the event, as these patients are not captured on the DOAC Dashboard.
All reported bleeding events were manually reviewed in the EHR and categorized as a major or clinically relevant nonmajor bleed, according to International Society of Thrombosis and Haemostasis criteria. Validated bleeding events were then crossreferenced with the interacting drug alerts report to identify events with potentially overlapping NSAID therapy at the time of the event. Overlapping NSAID therapy was defined as the prescribing of an NSAID at any point in the 6 months prior to the event. All events with potential overlapping NSAID therapies were manually reviewed for confirmation of NSAID status at the time of the event.
The primary endpoint was a composite of any bleeding event per International Society of Thrombosis and Haemostasis criteria. The secondary endpoint evaluated the potential impact of NSAID selectivity or PPI coprescribing on the bleeding rate among the NSAID user groups.
Statistical Analysis
Analyses were performed consistent with the methods used in the ARISTOTLE and RE-LY trials. It was determined that a sample size of 504 patients, with ≥ 168 patients in each group, would provide 80% power using a 2-sided a of 0.05. HRs with 95% CIs and respective P values were calculated using a SPSS-adapted online calculator.
RESULTS
The DOAC Dashboard identified 681 patients on rivaroxaban and 3225 patients on apixaban; 72 patients on rivaroxaban (10.6%) and 300 patients on apixaban (9.3%) were NSAID users. The mean age of NSAID users was 66.9 years in the rivaroxaban group and 72.4 years in the apixaban group. The mean age of non-NSAID users was 71.5 years in the rivaroxaban group and 75.6 years in the apixaban group. No appreciable differences were observed among subgroups in body mass index, renal function, hepatic function, hemoglobin, or platelet counts, and no statistically significant differences were identified (Table 1). Antiplatelet agents identified included aspirin, clopidogrel, prasugrel, and ticagrelor. Fifteen patients (20.3%) in the rivaroxaban group and 87 patients (28.7%) in the apixaban group had concomitant antiplatelet and NSAID use. Forty-five patients on rivaroxaban (60.8%) and 170 (55.9%) on apixaban were prescribed concomitant PPI and NSAID at baseline. Among non-NSAID users, there was concomitant antiplatelet use for 265 patients (43.6%) in the rivaroxaban group and 1401 patients (47.9%) in the apixaban group. Concomitant PPI use was identified among 63 patients (60.0%) taking selective NSAIDs and 182 (57.2%) taking nonselective NSAIDs.

A total of 423 courses of NSAIDs were identified: 85 NSAID courses in the rivaroxaban group and 338 NSAID courses in the apixaban group. Most NSAID courses involved a nonselective NSAID in the rivaroxaban and apixaban NSAID user groups: 75.2% (n = 318) aggregately compared to 71.8% (n = 61) and 76.0% (n = 257) in the rivaroxaban and apixaban groups, respectively. The most frequent NSAID courses identified were meloxicam (26.7%; n = 113), celecoxib (24.8%; n = 105), ibuprofen (19.1%; n = 81), and naproxen (13.5%; n = 57). Data regarding NSAID therapy initiation and discontinuation dates were not readily available. As a result, the duration of NSAID courses was not captured.
There was no statistically significant difference in bleeding rates between rivaroxaban and apixaban among NSAID users (HR 1.04; 95% CI, 0.98-1.12) or non-NSAID users (HR 1.15; 95% CI, 0.80-1.66) (Table 2). Apixaban non-NSAID users had a higher rate of major bleeds (HR 0.32; 95% CI, 0.17-0.61) while rivaroxaban non-NSAID users had a higher rate of clinically relevant nonmajor bleeds (HR 1.63; 95% CI, 1.10-2.54).

The sample size for the secondary endpoint consisted of bleeding events that were confirmed to have had an overlapping NSAID prescribed at the time of the event. For this secondary assessment, there was 1 rivaroxaban NSAID user bleeding event and 4 apixaban NSAID user bleeding events. For the rivaroxaban NSAID user bleeding event, the NSAID was nonselective and a PPI was not coprescribed. For the apixaban NSAID user bleeding events, 2 NSAIDs were nonselective and 2 were selective. All patients with apixaban and NSAID bleeding events had a coprescribed PPI. There was no clinically significant difference in the bleeding rates observed for NSAID selectivity or PPI coprescribing among the NSAID user subgroups.
DISCUSSION
This study found that there was no statistically significant difference for bleeding rates of major and nonmajor bleeding events between rivaroxaban and apixaban among NSAID users and non-NSAID users. This study did not identify a clinically significant impact on bleeding rates from NSAID selectivity or PPI coprescribing among the NSAID users.
There were notable but not statistically significant differences in baseline characteristics observed between the NSAID and non-NSAID user groups. On average, the rivaroxaban and apixaban NSAID users were younger compared with those not taking NSAIDs. NSAIDs, specifically nonselective NSAIDs, are recognized as potentially inappropriate medications for older adults given that this population is at an increased risk for GI ulcer development and/or GI bleeding.17 The non-NSAID user group likely consisted of older patients compared to the NSAID user group as clinicians may avoid prescribing NSAIDs to older adults regardless of concomitant DOAC therapy.
In addition to having an older patient population, non-NSAID users were more frequently prescribed a concomitant antiplatelet when compared with NSAID users. This prescribing pattern may be due to clinicians avoiding the use of NSAIDs in patients receiving DOAC therapy in combination with antiplatelet therapy, as these patients have been found to have an increased bleeding rate compared to DOAC therapy alone.18
Non-NSAID users had an overall higher bleeding rate for both major and nonmajor bleeding events. Based on this observation, it could be hypothesized that antiplatelet agents have a higher risk of bleeding in comparison to NSAIDs. In a subanalysis of the EXPAND study evaluating risk factors of major bleeding in patients receiving rivaroxaban, concomitant use of antiplatelet agents demonstrated a statistically significant increased risk of bleeding (HR 1.6; 95% CI, 1.2-2.3; P = .003) while concomitant use of NSAIDs did not (HR 0.8; 95% CI, 0.3-2.2; P = .67).19
In assessing PPI status at baseline, a majority of both rivaroxaban and apixaban NSAID users were coprescribed a PPI. This trend aligns with current clinical guideline recommendations for the prescribing of PPI therapy for GI protection in high-risk patients, such as those on DOAC therapy and concomitant NSAID therapy.10 Given the high proportion of NSAID users coprescribed a PPI at baseline, it may be possible that the true incidence of NSAID-associated bleeding events was higher than what this study found. This observation may reflect the impact from timely implementation of risk mitigation strategies by CPPs in the anticoagulation clinic. However, this study was not constructed to assess the efficacy of PPI use in this manner.
It is important to note the patients included in this study were followed by a pharmacist in an anticoagulation clinic using the DOAC Dashboard.15 This population management tool allows CPPs to make proactive interventions when a patient taking a DOAC receives an NSAID prescription, such as recommending the coprescribing of a PPI or use of a selective NSAID.10,16 These standards of care may have contributed to an overall reduced bleeding rate among the NSAID user group and may not be reflective of private practice.
The planned analysis of this study was modeled after the posthoc analysis of the RE-LY and ARISTOTLE trials. Both trials demonstrated an increased risk of bleeding with oral anticoagulation, including DOAC and warfarin, in combination with NSAID use. However, both trials found that NSAID use in patients treated with a DOAC was not independently associated with increased bleeding events compared with warfarin.13,14 The results of this study are comparable to the RE-LY and ARISTOTLE findings that NSAID use among patients treated with rivaroxaban or apixaban did not demonstrate a statistically significant increased bleeding risk.
Studies of NSAID use in combination with DOAC therapy have been limited to patient populations consisting of both DOAC and warfarin. Evidence from these trials outlines the increased bleeding risk associated with NSAID use in combination with oral anticoagulation; however, these patient populations include those on a DOAC and warfarin.13,14,19,20 Given the limited evidence on NSAID use among DOACs alone, it is assumed NSAID use in combination with DOACs has a similar risk of bleeding as warfarin use. This may cause clinicians to automatically exclude NSAID therapy as a treatment option for patients on a DOAC who are otherwise clinically appropriate candidates, such as those with underlying inflammatory conditions. Avoiding NSAID therapy in this patient population may lead to suboptimal pain management and increase the risk of patient harm from methods such as inappropriate opioid therapy prescribing.
DOAC therapy should not be a universal limitation to the use of NSAIDs. Although the risk of bleeding with NSAID therapy is always present, deliberate NSAID prescribing in addition to the timely implementation of risk mitigation strategies may provide an avenue for safe NSAID prescribing in patients receiving a DOAC. A population health-based approach to DOAC management, such as the DOAC Dashboard, appears to be effective at preventing patient harm when NSAIDs are prescribed in conjunction with DOACs.
Limitations
The DOAC Dashboard has been shown to be effective and efficient at monitoring DOAC therapy from a population-based approach.16 Reports generated through the DOAC Dashboard provide convenient access to patient data which allows for timely interventions; however, there are limits to its use for data collection. All the data elements necessary to properly assess bleeding risk with validated tools, such as HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/ alcohol concomitantly), are not available on DOAC Dashboard reports. Due to this constraint, bleeding risk assessments were not conducted at baseline and this study was unable to include risk modeling. Additionally, data elements like initiation and discontinuation dates and duration of therapies were not readily available. As a result, this study was unable to incorporate time as a data point.
This was a retrospective study that relied on manual review of chart documentation to verify bleeding events, but data obtained through the DOAC Dashboard were transferred directly from the EHR.15 Bleeding events available for evaluation were restricted to those that occurred at a VA facility. Additionally, the sample size within the rivaroxaban NSAID user group did not reach the predefined sample size required to reach power and may have been too small to detect a difference if one did exist. The secondary assessment had a low sample size of NSAID user bleeding events, making it difficult to fully assess its impact on NSAID selectivity and PPI coprescribing on bleeding rates. All courses of NSAIDs were equally valued regardless of the dose or therapy duration; however, this is consistent with how NSAID use was defined in the RE-LY and ARISTOTLE trials.
CONCLUSIONS
This retrospective cohort review found no statistically significant difference in the composite bleeding rates between rivaroxaban and apixaban among NSAID users and non-NSAID users. Moreover, there was no clinically significant impact observed for bleeding rates in regard to NSAID selectivity and PPI coprescribing among NSAID users. However, coprescribing of PPI therapy to patients on a DOAC who are clinically indicated for an NSAID may reduce the risk of bleeding. Population health management tools, such as the DOAC Dashboard, may also allow clinicians to safely prescribe NSAIDs to patients on a DOAC. Further large-scale observational studies are needed to quantify the real-world risk of bleeding with concomitant NSAID use among DOACs alone and to evaluate the impact from NSAID selectivity or PPI coprescribing.
- Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014;383(9921):955-962. doi:10.1016/S0140-6736(13)62343-0
- Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G. Oral anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e44S-e88S. doi:10.1378/chest.11-2292
- Eikelboom J, Merli G. Bleeding with direct oral anticoagulants vs warfarin: clinical experience. Am J Med. 2016;129(11S):S33-S40. doi:10.1016/j.amjmed.2016.06.003
- Vranckx P, Valgimigli M, Heidbuchel H. The significance of drug-drug and drug-food interactions of oral anticoagulation. Arrhythm Electrophysiol Rev. 2018;7(1):55-61. doi:10.15420/aer.2017.50.1
- Davis JS, Lee HY, Kim J, et al. Use of non-steroidal antiinflammatory drugs in US adults: changes over time and by demographic. Open Heart. 2017;4(1):e000550. doi:10.1136/openhrt-2016-000550
- Schafer AI. Effects of nonsteroidal antiinflammatory drugs on platelet function and systemic hemostasis. J Clin Pharmacol. 1995;35(3):209-219. doi:10.1002/j.1552-4604.1995.tb04050.x
- Al-Saeed A. Gastrointestinal and cardiovascular risk of nonsteroidal anti-inflammatory drugs. Oman Med J. 2011;26(6):385-391. doi:10.5001/omj.2011.101
- Gabriel SE, Jaakkimainen L, Bombardier C. Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs. Ann Intern Med. 1991;115(10):787-796. doi:10.7326/0003-4819-115-10-787
- Scheiman JM, Yeomans ND, Talley NJ, et al. Prevention of ulcers by esomeprazole in at-risk patients using non-selective NSAIDs and COX-2 inhibitors. Am J Gastroenterol. 2006;101(4):701-710. doi:10.1111/j.1572-0241.2006.00499.x
- Freedberg DE, Kim LS, Yang YX. The risks and benefits of long-term use of proton pump inhibitors: expert review and best practice advice from the American Gastroenterological Association. Gastroenterology. 2017;152(4):706-715. doi:10.1053/j.gastro.2017.01.031
- Lamberts M, Lip GYH, Hansen ML, et al. Relation of nonsteroidal anti-inflammatory drugs to serious bleeding and thromboembolism risk in patients with atrial fibrillation receiving antithrombotic therapy: a nationwide cohort study. Ann Intern Med. 2014;161(10):690-698. doi:10.7326/M13-1581
- Villa Zapata L, Hansten PD, Panic J, et al. Risk of bleeding with exposure to warfarin and nonsteroidal anti-inflammatory drugs: a systematic review and metaanalysis. Thromb Haemost. 2020;120(7):1066-1074. doi:10.1055/s-0040-1710592
- Kent AP, Brueckmann M, Fraessdorf M, et al. Concomitant oral anticoagulant and nonsteroidal anti-inflammatory drug therapy in patients with atrial fibrillation. J Am Coll Cardiol. 2018;72(3):255-267. doi:10.1016/j.jacc.2018.04.063
- Dalgaard F, Mulder H, Wojdyla DM, et al. Patients with atrial fibrillation taking nonsteroidal antiinflammatory drugs and oral anticoagulants in the ARISTOTLE Trial. Circulation. 2020;141(1):10-20. doi:10.1161/CIRCULATIONAHA.119.041296
- Allen AL, Lucas J, Parra D, et al. Shifting the paradigm: a population health approach to the management of direct oral anticoagulants. J Am Heart Asssoc. 2021;10(24):e022758. doi:10.1161/JAHA.121.022758
- . Valencia D, Spoutz P, Stoppi J, et al. Impact of a direct oral anticoagulant population management tool on anticoagulation therapy monitoring in clinical practice. Ann Pharmacother. 2019;53(8):806-811. doi:10.1177/1060028019835843
- By the 2023 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2023 Updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023;71(7):2052-2081. doi:10.1111/jgs.18372
- Kumar S, Danik SB, Altman RK, et al. Non-vitamin K antagonist oral anticoagulants and antiplatelet therapy for stroke prevention in patients with atrial fibrillation. Cardiol Rev. 2016;24(5):218-223. doi:10.1097/CRD.0000000000000088
- Sakuma I, Uchiyama S, Atarashi H, et al. Clinical risk factors of stroke and major bleeding in patients with nonvalvular atrial fibrillation under rivaroxaban: the EXPAND study sub-analysis. Heart Vessels. 2019;34(11):1839-1851. doi:10.1007/s00380-019-01425-x
- Davidson BL, Verheijen S, Lensing AWA, et al. Bleeding risk of patients with acute venous thromboembolism taking nonsteroidal anti-inflammatory drugs or aspirin. JAMA Intern Med. 2014;174(6):947-953. doi:10.1001/jamainternmed.2014.946
Clinical practice has shifted from vitamin K antagonists to direct oral anticoagulants (DOACs) for atrial fibrillation treatment due to their more favorable risk-benefit profile and less lifestyle modification required.1,2 However, the advantage of a lower bleeding risk with DOACs could be compromised by potentially problematic pharmacokinetic interactions like those conferred by antiplatelets or nonsteroidal anti-inflammatory drugs (NSAIDs).3,4 Treating a patient needing anticoagulation with a DOAC who has comorbidities may introduce unavoidable drug-drug interactions. This particularly happens with over-the-counter and prescription NSAIDs used for the management of pain and inflammatory conditions.5
NSAIDs primarily affect 2 cyclooxygenase (COX) enzyme isomers, COX-1 and COX-2.6 COX-1 helps maintain gastrointestinal (GI) mucosa integrity and platelet aggregation processes, whereas COX-2 is engaged in pain signaling and inflammation mediation. COX-1 inhibition is associated with more bleeding-related adverse events (AEs), especially in the GI tract. COX-2 inhibition is thought to provide analgesia and anti-inflammatory properties without elevating bleeding risk. This premise is responsible for the preferential use of celecoxib, a COX-2 selective NSAID, which should confer a lower bleeding risk compared to nonselective NSAIDs such as ibuprofen and naproxen.7 NSAIDs have been documented as independent risk factors for bleeding. NSAID users are about 3 times as likely to develop GI AEs compared to nonNSAID users.8
Many clinicians aim to further mitigate NSAID-associated bleeding risk by coprescribing a proton pump inhibitor (PPI). PPIs provide gastroprotection against NSAID-induced mucosal injury and sequential complication of GI bleeding. In a multicenter randomized control trial, patients who received concomitant PPI therapy while undergoing chronic NSAID therapy—including nonselective and COX-2 selective NSAIDs—had a significantly lower risk of GI ulcer development (placebo, 17.0%; 20 mg esomeprazole, 5.2%; 40 mg esomeprazole, 4.6%).9 Current clinical guidelines for preventing NSAIDassociated bleeding complications recommend using a COX-2 selective NSAID in combination with PPI therapy for patients at high risk for GI-related bleeding, including the concomitant use of anticoagulants.10
There is evidence suggesting an increased bleeding risk with NSAIDs when used in combination with vitamin K antagonists such as warfarin.11,12 A systematic review of warfarin and concomitant NSAID use found an increased risk of overall bleeding with NSAID use in combination with warfarin (odds ratio 1.58; 95% CI, 1.18-2.12), compared to warfarin alone.12
Posthoc analyses of randomized clinical trials have also demonstrated an increased bleeding risk with oral anticoagulation and concomitant NSAID use.13,14 In the RE-LY trial, NSAID users on warfarin or dabigatran had a statistically significant increased risk of major bleeding compared to non-NSAID users (hazard ratio [HR] 1.68; 95% CI, 1.40- 2.02; P < .001).13 In the ARISTOTLE trial, patients on warfarin or apixaban who were incident NSAID users were found to have an increased risk of major bleeding (HR 1.61; 95% CI, 1.11-2.33) and clinically relevant nonmajor bleeding (HR 1.70; 95% CI, 1.16- 2.48).14 These trials found a statistically significant increased bleeding risk associated with NSAID use, though the populations evaluated included patients taking warfarin and patients taking DOACs. These trials did not evaluate the bleeding risk of concomitant NSAID use among DOACs alone.
Evidence on NSAID-associated bleeding risk with DOACs is lacking in settings where the patient population, prescribing practices, and monitoring levels are variable. Within the Veterans Health Administration, clinical pharmacist practitioners (CPPs) in anticoagulation clinics oversee DOAC therapy management. CPPs monitor safety and efficacy of DOAC therapies through a population health management tool, the DOAC Dashboard.15 The DOAC Dashboard creates alerts for patients who may require an intervention based on certain clinical parameters, such as drug-drug interactions.16 Whenever a patient on a DOAC is prescribed an NSAID, an alert is generated on the DOAC Dashboard to flag the CPPs for the potential need for an intervention. If NSAID therapy remains clinically indicated, CPPs may recommend risk reduction strategies such as a COX-2 selective NSAID or coprescribing a PPI.10
The DOAC Dashboard provides an ideal setting for investigating the effects of NSAID use, NSAID selectivity, and PPI coprescribing on DOAC bleeding rates. With an increasing population of patients receiving anticoagulation therapy with a DOAC, more guidance regarding the bleeding risk of concomitant NSAID use with DOACs is needed. Studies evaluating the bleeding risk with concomitant NSAID use in patients on a DOAC alone are limited. This is the first study to date to compare bleeding risk with concomitant NSAID use between DOACs. This study provides information on bleeding risk with NSAID use among commonly prescribed DOACs, rivaroxaban and apixaban, and the potential impacts of current risk reduction strategies.
METHODS
This single-center retrospective cohort review was performed using the electronic health records (EHRs) of patients enrolled in the US Department of Veterans Affairs (VA) Mountain Home Healthcare System who received rivaroxaban or apixaban from December 2020 to December 2022. This study received approval from the East Tennessee State University/VA Institutional Review Board committee.
Patients were identified through the DOAC Dashboard, aged 21 to 100 years, and received rivaroxaban or apixaban at a therapeutic dose: rivaroxaban 10 to 20 mg daily or apixaban 2.5 to 5 mg twice daily. Patients were excluded if they were prescribed dual antiplatelet therapy, received rivaroxaban at dosing indicated for peripheral vascular disease, were undergoing dialysis, had evidence of moderate to severe hepatic impairment or any hepatic disease with coagulopathy, were undergoing chemotherapy or radiation, or had hematological conditions with predisposed bleeding risk. These patients were excluded to mitigate the potential confounding impact from nontherapeutic DOAC dosing strategies and conditions associated with an increased bleeding risk.
Eligible patients were stratified based on NSAID use. NSAID users were defined as patients prescribed an oral NSAID, including both acute and chronic courses, at any point during the study time frame while actively on a DOAC. Bleeding events were reviewed to evaluate rates between rivaroxaban and apixaban among NSAID and nonNSAID users. Identified NSAID users were further assessed for NSAID selectivity and PPI coprescribing as a subgroup analysis for the secondary assessment.
Data Collection
Baseline data were collected, including age, body mass index, anticoagulation indication, DOAC agent, DOAC dose, and DOAC total daily dose. Baseline serum creatinine levels, liver function tests, hemoglobin levels, and platelet counts were collected from the most recent data available immediately prior to the bleeding event, if applicable.
The DOAC Dashboard was reviewed for active and dismissed drug interaction alerts to identify patients taking rivaroxaban or apixaban who were prescribed an NSAID. Patients were categorized in the NSAID group if an interacting drug alert with an NSAID was reported during the study time frame. Data available through the interacting drug alerts on NSAID use were limited to the interacting drug name and date of the reported flag. Manual EHR review was required to confirm dates of NSAID therapy initiation and NSAID discontinuation, if applicable.
Data regarding concomitant antiplatelet use were obtained through review of the active and dismissed drug interaction alerts on the DOAC Dashboard. Concomitant antiplatelet use was defined as the prescribing of a single antiplatelet agent at any point while receiving DOAC therapy. Data on concomitant antiplatelets were collected regardless of NSAID status.
Data on coprescribed PPI therapy were obtained through manual EHR review of identified NSAID users. Coprescribed PPI therapy was defined as the prescribing of a PPI at any point during NSAID therapy. Data regarding PPI use among non-NSAID users were not collected because the secondary endpoint was designed to assess PPI use only among patients coprescribed a DOAC and NSAID.
Outcomes
Bleeding events were identified through an outcomes report generated by the DOAC Dashboard based on International Classification of Diseases, Tenth Revision diagnosis codes associated with a bleeding event. The outcomes report captures diagnoses from the outpatient and inpatient care settings. Reported bleeding events were limited to patients who received a DOAC at any point in the 6 months prior to the event and excluded patients with recent DOAC initiation within 7 days of the event, as these patients are not captured on the DOAC Dashboard.
All reported bleeding events were manually reviewed in the EHR and categorized as a major or clinically relevant nonmajor bleed, according to International Society of Thrombosis and Haemostasis criteria. Validated bleeding events were then crossreferenced with the interacting drug alerts report to identify events with potentially overlapping NSAID therapy at the time of the event. Overlapping NSAID therapy was defined as the prescribing of an NSAID at any point in the 6 months prior to the event. All events with potential overlapping NSAID therapies were manually reviewed for confirmation of NSAID status at the time of the event.
The primary endpoint was a composite of any bleeding event per International Society of Thrombosis and Haemostasis criteria. The secondary endpoint evaluated the potential impact of NSAID selectivity or PPI coprescribing on the bleeding rate among the NSAID user groups.
Statistical Analysis
Analyses were performed consistent with the methods used in the ARISTOTLE and RE-LY trials. It was determined that a sample size of 504 patients, with ≥ 168 patients in each group, would provide 80% power using a 2-sided a of 0.05. HRs with 95% CIs and respective P values were calculated using a SPSS-adapted online calculator.
RESULTS
The DOAC Dashboard identified 681 patients on rivaroxaban and 3225 patients on apixaban; 72 patients on rivaroxaban (10.6%) and 300 patients on apixaban (9.3%) were NSAID users. The mean age of NSAID users was 66.9 years in the rivaroxaban group and 72.4 years in the apixaban group. The mean age of non-NSAID users was 71.5 years in the rivaroxaban group and 75.6 years in the apixaban group. No appreciable differences were observed among subgroups in body mass index, renal function, hepatic function, hemoglobin, or platelet counts, and no statistically significant differences were identified (Table 1). Antiplatelet agents identified included aspirin, clopidogrel, prasugrel, and ticagrelor. Fifteen patients (20.3%) in the rivaroxaban group and 87 patients (28.7%) in the apixaban group had concomitant antiplatelet and NSAID use. Forty-five patients on rivaroxaban (60.8%) and 170 (55.9%) on apixaban were prescribed concomitant PPI and NSAID at baseline. Among non-NSAID users, there was concomitant antiplatelet use for 265 patients (43.6%) in the rivaroxaban group and 1401 patients (47.9%) in the apixaban group. Concomitant PPI use was identified among 63 patients (60.0%) taking selective NSAIDs and 182 (57.2%) taking nonselective NSAIDs.

A total of 423 courses of NSAIDs were identified: 85 NSAID courses in the rivaroxaban group and 338 NSAID courses in the apixaban group. Most NSAID courses involved a nonselective NSAID in the rivaroxaban and apixaban NSAID user groups: 75.2% (n = 318) aggregately compared to 71.8% (n = 61) and 76.0% (n = 257) in the rivaroxaban and apixaban groups, respectively. The most frequent NSAID courses identified were meloxicam (26.7%; n = 113), celecoxib (24.8%; n = 105), ibuprofen (19.1%; n = 81), and naproxen (13.5%; n = 57). Data regarding NSAID therapy initiation and discontinuation dates were not readily available. As a result, the duration of NSAID courses was not captured.
There was no statistically significant difference in bleeding rates between rivaroxaban and apixaban among NSAID users (HR 1.04; 95% CI, 0.98-1.12) or non-NSAID users (HR 1.15; 95% CI, 0.80-1.66) (Table 2). Apixaban non-NSAID users had a higher rate of major bleeds (HR 0.32; 95% CI, 0.17-0.61) while rivaroxaban non-NSAID users had a higher rate of clinically relevant nonmajor bleeds (HR 1.63; 95% CI, 1.10-2.54).

The sample size for the secondary endpoint consisted of bleeding events that were confirmed to have had an overlapping NSAID prescribed at the time of the event. For this secondary assessment, there was 1 rivaroxaban NSAID user bleeding event and 4 apixaban NSAID user bleeding events. For the rivaroxaban NSAID user bleeding event, the NSAID was nonselective and a PPI was not coprescribed. For the apixaban NSAID user bleeding events, 2 NSAIDs were nonselective and 2 were selective. All patients with apixaban and NSAID bleeding events had a coprescribed PPI. There was no clinically significant difference in the bleeding rates observed for NSAID selectivity or PPI coprescribing among the NSAID user subgroups.
DISCUSSION
This study found that there was no statistically significant difference for bleeding rates of major and nonmajor bleeding events between rivaroxaban and apixaban among NSAID users and non-NSAID users. This study did not identify a clinically significant impact on bleeding rates from NSAID selectivity or PPI coprescribing among the NSAID users.
There were notable but not statistically significant differences in baseline characteristics observed between the NSAID and non-NSAID user groups. On average, the rivaroxaban and apixaban NSAID users were younger compared with those not taking NSAIDs. NSAIDs, specifically nonselective NSAIDs, are recognized as potentially inappropriate medications for older adults given that this population is at an increased risk for GI ulcer development and/or GI bleeding.17 The non-NSAID user group likely consisted of older patients compared to the NSAID user group as clinicians may avoid prescribing NSAIDs to older adults regardless of concomitant DOAC therapy.
In addition to having an older patient population, non-NSAID users were more frequently prescribed a concomitant antiplatelet when compared with NSAID users. This prescribing pattern may be due to clinicians avoiding the use of NSAIDs in patients receiving DOAC therapy in combination with antiplatelet therapy, as these patients have been found to have an increased bleeding rate compared to DOAC therapy alone.18
Non-NSAID users had an overall higher bleeding rate for both major and nonmajor bleeding events. Based on this observation, it could be hypothesized that antiplatelet agents have a higher risk of bleeding in comparison to NSAIDs. In a subanalysis of the EXPAND study evaluating risk factors of major bleeding in patients receiving rivaroxaban, concomitant use of antiplatelet agents demonstrated a statistically significant increased risk of bleeding (HR 1.6; 95% CI, 1.2-2.3; P = .003) while concomitant use of NSAIDs did not (HR 0.8; 95% CI, 0.3-2.2; P = .67).19
In assessing PPI status at baseline, a majority of both rivaroxaban and apixaban NSAID users were coprescribed a PPI. This trend aligns with current clinical guideline recommendations for the prescribing of PPI therapy for GI protection in high-risk patients, such as those on DOAC therapy and concomitant NSAID therapy.10 Given the high proportion of NSAID users coprescribed a PPI at baseline, it may be possible that the true incidence of NSAID-associated bleeding events was higher than what this study found. This observation may reflect the impact from timely implementation of risk mitigation strategies by CPPs in the anticoagulation clinic. However, this study was not constructed to assess the efficacy of PPI use in this manner.
It is important to note the patients included in this study were followed by a pharmacist in an anticoagulation clinic using the DOAC Dashboard.15 This population management tool allows CPPs to make proactive interventions when a patient taking a DOAC receives an NSAID prescription, such as recommending the coprescribing of a PPI or use of a selective NSAID.10,16 These standards of care may have contributed to an overall reduced bleeding rate among the NSAID user group and may not be reflective of private practice.
The planned analysis of this study was modeled after the posthoc analysis of the RE-LY and ARISTOTLE trials. Both trials demonstrated an increased risk of bleeding with oral anticoagulation, including DOAC and warfarin, in combination with NSAID use. However, both trials found that NSAID use in patients treated with a DOAC was not independently associated with increased bleeding events compared with warfarin.13,14 The results of this study are comparable to the RE-LY and ARISTOTLE findings that NSAID use among patients treated with rivaroxaban or apixaban did not demonstrate a statistically significant increased bleeding risk.
Studies of NSAID use in combination with DOAC therapy have been limited to patient populations consisting of both DOAC and warfarin. Evidence from these trials outlines the increased bleeding risk associated with NSAID use in combination with oral anticoagulation; however, these patient populations include those on a DOAC and warfarin.13,14,19,20 Given the limited evidence on NSAID use among DOACs alone, it is assumed NSAID use in combination with DOACs has a similar risk of bleeding as warfarin use. This may cause clinicians to automatically exclude NSAID therapy as a treatment option for patients on a DOAC who are otherwise clinically appropriate candidates, such as those with underlying inflammatory conditions. Avoiding NSAID therapy in this patient population may lead to suboptimal pain management and increase the risk of patient harm from methods such as inappropriate opioid therapy prescribing.
DOAC therapy should not be a universal limitation to the use of NSAIDs. Although the risk of bleeding with NSAID therapy is always present, deliberate NSAID prescribing in addition to the timely implementation of risk mitigation strategies may provide an avenue for safe NSAID prescribing in patients receiving a DOAC. A population health-based approach to DOAC management, such as the DOAC Dashboard, appears to be effective at preventing patient harm when NSAIDs are prescribed in conjunction with DOACs.
Limitations
The DOAC Dashboard has been shown to be effective and efficient at monitoring DOAC therapy from a population-based approach.16 Reports generated through the DOAC Dashboard provide convenient access to patient data which allows for timely interventions; however, there are limits to its use for data collection. All the data elements necessary to properly assess bleeding risk with validated tools, such as HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/ alcohol concomitantly), are not available on DOAC Dashboard reports. Due to this constraint, bleeding risk assessments were not conducted at baseline and this study was unable to include risk modeling. Additionally, data elements like initiation and discontinuation dates and duration of therapies were not readily available. As a result, this study was unable to incorporate time as a data point.
This was a retrospective study that relied on manual review of chart documentation to verify bleeding events, but data obtained through the DOAC Dashboard were transferred directly from the EHR.15 Bleeding events available for evaluation were restricted to those that occurred at a VA facility. Additionally, the sample size within the rivaroxaban NSAID user group did not reach the predefined sample size required to reach power and may have been too small to detect a difference if one did exist. The secondary assessment had a low sample size of NSAID user bleeding events, making it difficult to fully assess its impact on NSAID selectivity and PPI coprescribing on bleeding rates. All courses of NSAIDs were equally valued regardless of the dose or therapy duration; however, this is consistent with how NSAID use was defined in the RE-LY and ARISTOTLE trials.
CONCLUSIONS
This retrospective cohort review found no statistically significant difference in the composite bleeding rates between rivaroxaban and apixaban among NSAID users and non-NSAID users. Moreover, there was no clinically significant impact observed for bleeding rates in regard to NSAID selectivity and PPI coprescribing among NSAID users. However, coprescribing of PPI therapy to patients on a DOAC who are clinically indicated for an NSAID may reduce the risk of bleeding. Population health management tools, such as the DOAC Dashboard, may also allow clinicians to safely prescribe NSAIDs to patients on a DOAC. Further large-scale observational studies are needed to quantify the real-world risk of bleeding with concomitant NSAID use among DOACs alone and to evaluate the impact from NSAID selectivity or PPI coprescribing.
Clinical practice has shifted from vitamin K antagonists to direct oral anticoagulants (DOACs) for atrial fibrillation treatment due to their more favorable risk-benefit profile and less lifestyle modification required.1,2 However, the advantage of a lower bleeding risk with DOACs could be compromised by potentially problematic pharmacokinetic interactions like those conferred by antiplatelets or nonsteroidal anti-inflammatory drugs (NSAIDs).3,4 Treating a patient needing anticoagulation with a DOAC who has comorbidities may introduce unavoidable drug-drug interactions. This particularly happens with over-the-counter and prescription NSAIDs used for the management of pain and inflammatory conditions.5
NSAIDs primarily affect 2 cyclooxygenase (COX) enzyme isomers, COX-1 and COX-2.6 COX-1 helps maintain gastrointestinal (GI) mucosa integrity and platelet aggregation processes, whereas COX-2 is engaged in pain signaling and inflammation mediation. COX-1 inhibition is associated with more bleeding-related adverse events (AEs), especially in the GI tract. COX-2 inhibition is thought to provide analgesia and anti-inflammatory properties without elevating bleeding risk. This premise is responsible for the preferential use of celecoxib, a COX-2 selective NSAID, which should confer a lower bleeding risk compared to nonselective NSAIDs such as ibuprofen and naproxen.7 NSAIDs have been documented as independent risk factors for bleeding. NSAID users are about 3 times as likely to develop GI AEs compared to nonNSAID users.8
Many clinicians aim to further mitigate NSAID-associated bleeding risk by coprescribing a proton pump inhibitor (PPI). PPIs provide gastroprotection against NSAID-induced mucosal injury and sequential complication of GI bleeding. In a multicenter randomized control trial, patients who received concomitant PPI therapy while undergoing chronic NSAID therapy—including nonselective and COX-2 selective NSAIDs—had a significantly lower risk of GI ulcer development (placebo, 17.0%; 20 mg esomeprazole, 5.2%; 40 mg esomeprazole, 4.6%).9 Current clinical guidelines for preventing NSAIDassociated bleeding complications recommend using a COX-2 selective NSAID in combination with PPI therapy for patients at high risk for GI-related bleeding, including the concomitant use of anticoagulants.10
There is evidence suggesting an increased bleeding risk with NSAIDs when used in combination with vitamin K antagonists such as warfarin.11,12 A systematic review of warfarin and concomitant NSAID use found an increased risk of overall bleeding with NSAID use in combination with warfarin (odds ratio 1.58; 95% CI, 1.18-2.12), compared to warfarin alone.12
Posthoc analyses of randomized clinical trials have also demonstrated an increased bleeding risk with oral anticoagulation and concomitant NSAID use.13,14 In the RE-LY trial, NSAID users on warfarin or dabigatran had a statistically significant increased risk of major bleeding compared to non-NSAID users (hazard ratio [HR] 1.68; 95% CI, 1.40- 2.02; P < .001).13 In the ARISTOTLE trial, patients on warfarin or apixaban who were incident NSAID users were found to have an increased risk of major bleeding (HR 1.61; 95% CI, 1.11-2.33) and clinically relevant nonmajor bleeding (HR 1.70; 95% CI, 1.16- 2.48).14 These trials found a statistically significant increased bleeding risk associated with NSAID use, though the populations evaluated included patients taking warfarin and patients taking DOACs. These trials did not evaluate the bleeding risk of concomitant NSAID use among DOACs alone.
Evidence on NSAID-associated bleeding risk with DOACs is lacking in settings where the patient population, prescribing practices, and monitoring levels are variable. Within the Veterans Health Administration, clinical pharmacist practitioners (CPPs) in anticoagulation clinics oversee DOAC therapy management. CPPs monitor safety and efficacy of DOAC therapies through a population health management tool, the DOAC Dashboard.15 The DOAC Dashboard creates alerts for patients who may require an intervention based on certain clinical parameters, such as drug-drug interactions.16 Whenever a patient on a DOAC is prescribed an NSAID, an alert is generated on the DOAC Dashboard to flag the CPPs for the potential need for an intervention. If NSAID therapy remains clinically indicated, CPPs may recommend risk reduction strategies such as a COX-2 selective NSAID or coprescribing a PPI.10
The DOAC Dashboard provides an ideal setting for investigating the effects of NSAID use, NSAID selectivity, and PPI coprescribing on DOAC bleeding rates. With an increasing population of patients receiving anticoagulation therapy with a DOAC, more guidance regarding the bleeding risk of concomitant NSAID use with DOACs is needed. Studies evaluating the bleeding risk with concomitant NSAID use in patients on a DOAC alone are limited. This is the first study to date to compare bleeding risk with concomitant NSAID use between DOACs. This study provides information on bleeding risk with NSAID use among commonly prescribed DOACs, rivaroxaban and apixaban, and the potential impacts of current risk reduction strategies.
METHODS
This single-center retrospective cohort review was performed using the electronic health records (EHRs) of patients enrolled in the US Department of Veterans Affairs (VA) Mountain Home Healthcare System who received rivaroxaban or apixaban from December 2020 to December 2022. This study received approval from the East Tennessee State University/VA Institutional Review Board committee.
Patients were identified through the DOAC Dashboard, aged 21 to 100 years, and received rivaroxaban or apixaban at a therapeutic dose: rivaroxaban 10 to 20 mg daily or apixaban 2.5 to 5 mg twice daily. Patients were excluded if they were prescribed dual antiplatelet therapy, received rivaroxaban at dosing indicated for peripheral vascular disease, were undergoing dialysis, had evidence of moderate to severe hepatic impairment or any hepatic disease with coagulopathy, were undergoing chemotherapy or radiation, or had hematological conditions with predisposed bleeding risk. These patients were excluded to mitigate the potential confounding impact from nontherapeutic DOAC dosing strategies and conditions associated with an increased bleeding risk.
Eligible patients were stratified based on NSAID use. NSAID users were defined as patients prescribed an oral NSAID, including both acute and chronic courses, at any point during the study time frame while actively on a DOAC. Bleeding events were reviewed to evaluate rates between rivaroxaban and apixaban among NSAID and nonNSAID users. Identified NSAID users were further assessed for NSAID selectivity and PPI coprescribing as a subgroup analysis for the secondary assessment.
Data Collection
Baseline data were collected, including age, body mass index, anticoagulation indication, DOAC agent, DOAC dose, and DOAC total daily dose. Baseline serum creatinine levels, liver function tests, hemoglobin levels, and platelet counts were collected from the most recent data available immediately prior to the bleeding event, if applicable.
The DOAC Dashboard was reviewed for active and dismissed drug interaction alerts to identify patients taking rivaroxaban or apixaban who were prescribed an NSAID. Patients were categorized in the NSAID group if an interacting drug alert with an NSAID was reported during the study time frame. Data available through the interacting drug alerts on NSAID use were limited to the interacting drug name and date of the reported flag. Manual EHR review was required to confirm dates of NSAID therapy initiation and NSAID discontinuation, if applicable.
Data regarding concomitant antiplatelet use were obtained through review of the active and dismissed drug interaction alerts on the DOAC Dashboard. Concomitant antiplatelet use was defined as the prescribing of a single antiplatelet agent at any point while receiving DOAC therapy. Data on concomitant antiplatelets were collected regardless of NSAID status.
Data on coprescribed PPI therapy were obtained through manual EHR review of identified NSAID users. Coprescribed PPI therapy was defined as the prescribing of a PPI at any point during NSAID therapy. Data regarding PPI use among non-NSAID users were not collected because the secondary endpoint was designed to assess PPI use only among patients coprescribed a DOAC and NSAID.
Outcomes
Bleeding events were identified through an outcomes report generated by the DOAC Dashboard based on International Classification of Diseases, Tenth Revision diagnosis codes associated with a bleeding event. The outcomes report captures diagnoses from the outpatient and inpatient care settings. Reported bleeding events were limited to patients who received a DOAC at any point in the 6 months prior to the event and excluded patients with recent DOAC initiation within 7 days of the event, as these patients are not captured on the DOAC Dashboard.
All reported bleeding events were manually reviewed in the EHR and categorized as a major or clinically relevant nonmajor bleed, according to International Society of Thrombosis and Haemostasis criteria. Validated bleeding events were then crossreferenced with the interacting drug alerts report to identify events with potentially overlapping NSAID therapy at the time of the event. Overlapping NSAID therapy was defined as the prescribing of an NSAID at any point in the 6 months prior to the event. All events with potential overlapping NSAID therapies were manually reviewed for confirmation of NSAID status at the time of the event.
The primary endpoint was a composite of any bleeding event per International Society of Thrombosis and Haemostasis criteria. The secondary endpoint evaluated the potential impact of NSAID selectivity or PPI coprescribing on the bleeding rate among the NSAID user groups.
Statistical Analysis
Analyses were performed consistent with the methods used in the ARISTOTLE and RE-LY trials. It was determined that a sample size of 504 patients, with ≥ 168 patients in each group, would provide 80% power using a 2-sided a of 0.05. HRs with 95% CIs and respective P values were calculated using a SPSS-adapted online calculator.
RESULTS
The DOAC Dashboard identified 681 patients on rivaroxaban and 3225 patients on apixaban; 72 patients on rivaroxaban (10.6%) and 300 patients on apixaban (9.3%) were NSAID users. The mean age of NSAID users was 66.9 years in the rivaroxaban group and 72.4 years in the apixaban group. The mean age of non-NSAID users was 71.5 years in the rivaroxaban group and 75.6 years in the apixaban group. No appreciable differences were observed among subgroups in body mass index, renal function, hepatic function, hemoglobin, or platelet counts, and no statistically significant differences were identified (Table 1). Antiplatelet agents identified included aspirin, clopidogrel, prasugrel, and ticagrelor. Fifteen patients (20.3%) in the rivaroxaban group and 87 patients (28.7%) in the apixaban group had concomitant antiplatelet and NSAID use. Forty-five patients on rivaroxaban (60.8%) and 170 (55.9%) on apixaban were prescribed concomitant PPI and NSAID at baseline. Among non-NSAID users, there was concomitant antiplatelet use for 265 patients (43.6%) in the rivaroxaban group and 1401 patients (47.9%) in the apixaban group. Concomitant PPI use was identified among 63 patients (60.0%) taking selective NSAIDs and 182 (57.2%) taking nonselective NSAIDs.

A total of 423 courses of NSAIDs were identified: 85 NSAID courses in the rivaroxaban group and 338 NSAID courses in the apixaban group. Most NSAID courses involved a nonselective NSAID in the rivaroxaban and apixaban NSAID user groups: 75.2% (n = 318) aggregately compared to 71.8% (n = 61) and 76.0% (n = 257) in the rivaroxaban and apixaban groups, respectively. The most frequent NSAID courses identified were meloxicam (26.7%; n = 113), celecoxib (24.8%; n = 105), ibuprofen (19.1%; n = 81), and naproxen (13.5%; n = 57). Data regarding NSAID therapy initiation and discontinuation dates were not readily available. As a result, the duration of NSAID courses was not captured.
There was no statistically significant difference in bleeding rates between rivaroxaban and apixaban among NSAID users (HR 1.04; 95% CI, 0.98-1.12) or non-NSAID users (HR 1.15; 95% CI, 0.80-1.66) (Table 2). Apixaban non-NSAID users had a higher rate of major bleeds (HR 0.32; 95% CI, 0.17-0.61) while rivaroxaban non-NSAID users had a higher rate of clinically relevant nonmajor bleeds (HR 1.63; 95% CI, 1.10-2.54).

The sample size for the secondary endpoint consisted of bleeding events that were confirmed to have had an overlapping NSAID prescribed at the time of the event. For this secondary assessment, there was 1 rivaroxaban NSAID user bleeding event and 4 apixaban NSAID user bleeding events. For the rivaroxaban NSAID user bleeding event, the NSAID was nonselective and a PPI was not coprescribed. For the apixaban NSAID user bleeding events, 2 NSAIDs were nonselective and 2 were selective. All patients with apixaban and NSAID bleeding events had a coprescribed PPI. There was no clinically significant difference in the bleeding rates observed for NSAID selectivity or PPI coprescribing among the NSAID user subgroups.
DISCUSSION
This study found that there was no statistically significant difference for bleeding rates of major and nonmajor bleeding events between rivaroxaban and apixaban among NSAID users and non-NSAID users. This study did not identify a clinically significant impact on bleeding rates from NSAID selectivity or PPI coprescribing among the NSAID users.
There were notable but not statistically significant differences in baseline characteristics observed between the NSAID and non-NSAID user groups. On average, the rivaroxaban and apixaban NSAID users were younger compared with those not taking NSAIDs. NSAIDs, specifically nonselective NSAIDs, are recognized as potentially inappropriate medications for older adults given that this population is at an increased risk for GI ulcer development and/or GI bleeding.17 The non-NSAID user group likely consisted of older patients compared to the NSAID user group as clinicians may avoid prescribing NSAIDs to older adults regardless of concomitant DOAC therapy.
In addition to having an older patient population, non-NSAID users were more frequently prescribed a concomitant antiplatelet when compared with NSAID users. This prescribing pattern may be due to clinicians avoiding the use of NSAIDs in patients receiving DOAC therapy in combination with antiplatelet therapy, as these patients have been found to have an increased bleeding rate compared to DOAC therapy alone.18
Non-NSAID users had an overall higher bleeding rate for both major and nonmajor bleeding events. Based on this observation, it could be hypothesized that antiplatelet agents have a higher risk of bleeding in comparison to NSAIDs. In a subanalysis of the EXPAND study evaluating risk factors of major bleeding in patients receiving rivaroxaban, concomitant use of antiplatelet agents demonstrated a statistically significant increased risk of bleeding (HR 1.6; 95% CI, 1.2-2.3; P = .003) while concomitant use of NSAIDs did not (HR 0.8; 95% CI, 0.3-2.2; P = .67).19
In assessing PPI status at baseline, a majority of both rivaroxaban and apixaban NSAID users were coprescribed a PPI. This trend aligns with current clinical guideline recommendations for the prescribing of PPI therapy for GI protection in high-risk patients, such as those on DOAC therapy and concomitant NSAID therapy.10 Given the high proportion of NSAID users coprescribed a PPI at baseline, it may be possible that the true incidence of NSAID-associated bleeding events was higher than what this study found. This observation may reflect the impact from timely implementation of risk mitigation strategies by CPPs in the anticoagulation clinic. However, this study was not constructed to assess the efficacy of PPI use in this manner.
It is important to note the patients included in this study were followed by a pharmacist in an anticoagulation clinic using the DOAC Dashboard.15 This population management tool allows CPPs to make proactive interventions when a patient taking a DOAC receives an NSAID prescription, such as recommending the coprescribing of a PPI or use of a selective NSAID.10,16 These standards of care may have contributed to an overall reduced bleeding rate among the NSAID user group and may not be reflective of private practice.
The planned analysis of this study was modeled after the posthoc analysis of the RE-LY and ARISTOTLE trials. Both trials demonstrated an increased risk of bleeding with oral anticoagulation, including DOAC and warfarin, in combination with NSAID use. However, both trials found that NSAID use in patients treated with a DOAC was not independently associated with increased bleeding events compared with warfarin.13,14 The results of this study are comparable to the RE-LY and ARISTOTLE findings that NSAID use among patients treated with rivaroxaban or apixaban did not demonstrate a statistically significant increased bleeding risk.
Studies of NSAID use in combination with DOAC therapy have been limited to patient populations consisting of both DOAC and warfarin. Evidence from these trials outlines the increased bleeding risk associated with NSAID use in combination with oral anticoagulation; however, these patient populations include those on a DOAC and warfarin.13,14,19,20 Given the limited evidence on NSAID use among DOACs alone, it is assumed NSAID use in combination with DOACs has a similar risk of bleeding as warfarin use. This may cause clinicians to automatically exclude NSAID therapy as a treatment option for patients on a DOAC who are otherwise clinically appropriate candidates, such as those with underlying inflammatory conditions. Avoiding NSAID therapy in this patient population may lead to suboptimal pain management and increase the risk of patient harm from methods such as inappropriate opioid therapy prescribing.
DOAC therapy should not be a universal limitation to the use of NSAIDs. Although the risk of bleeding with NSAID therapy is always present, deliberate NSAID prescribing in addition to the timely implementation of risk mitigation strategies may provide an avenue for safe NSAID prescribing in patients receiving a DOAC. A population health-based approach to DOAC management, such as the DOAC Dashboard, appears to be effective at preventing patient harm when NSAIDs are prescribed in conjunction with DOACs.
Limitations
The DOAC Dashboard has been shown to be effective and efficient at monitoring DOAC therapy from a population-based approach.16 Reports generated through the DOAC Dashboard provide convenient access to patient data which allows for timely interventions; however, there are limits to its use for data collection. All the data elements necessary to properly assess bleeding risk with validated tools, such as HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/ alcohol concomitantly), are not available on DOAC Dashboard reports. Due to this constraint, bleeding risk assessments were not conducted at baseline and this study was unable to include risk modeling. Additionally, data elements like initiation and discontinuation dates and duration of therapies were not readily available. As a result, this study was unable to incorporate time as a data point.
This was a retrospective study that relied on manual review of chart documentation to verify bleeding events, but data obtained through the DOAC Dashboard were transferred directly from the EHR.15 Bleeding events available for evaluation were restricted to those that occurred at a VA facility. Additionally, the sample size within the rivaroxaban NSAID user group did not reach the predefined sample size required to reach power and may have been too small to detect a difference if one did exist. The secondary assessment had a low sample size of NSAID user bleeding events, making it difficult to fully assess its impact on NSAID selectivity and PPI coprescribing on bleeding rates. All courses of NSAIDs were equally valued regardless of the dose or therapy duration; however, this is consistent with how NSAID use was defined in the RE-LY and ARISTOTLE trials.
CONCLUSIONS
This retrospective cohort review found no statistically significant difference in the composite bleeding rates between rivaroxaban and apixaban among NSAID users and non-NSAID users. Moreover, there was no clinically significant impact observed for bleeding rates in regard to NSAID selectivity and PPI coprescribing among NSAID users. However, coprescribing of PPI therapy to patients on a DOAC who are clinically indicated for an NSAID may reduce the risk of bleeding. Population health management tools, such as the DOAC Dashboard, may also allow clinicians to safely prescribe NSAIDs to patients on a DOAC. Further large-scale observational studies are needed to quantify the real-world risk of bleeding with concomitant NSAID use among DOACs alone and to evaluate the impact from NSAID selectivity or PPI coprescribing.
- Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014;383(9921):955-962. doi:10.1016/S0140-6736(13)62343-0
- Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G. Oral anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e44S-e88S. doi:10.1378/chest.11-2292
- Eikelboom J, Merli G. Bleeding with direct oral anticoagulants vs warfarin: clinical experience. Am J Med. 2016;129(11S):S33-S40. doi:10.1016/j.amjmed.2016.06.003
- Vranckx P, Valgimigli M, Heidbuchel H. The significance of drug-drug and drug-food interactions of oral anticoagulation. Arrhythm Electrophysiol Rev. 2018;7(1):55-61. doi:10.15420/aer.2017.50.1
- Davis JS, Lee HY, Kim J, et al. Use of non-steroidal antiinflammatory drugs in US adults: changes over time and by demographic. Open Heart. 2017;4(1):e000550. doi:10.1136/openhrt-2016-000550
- Schafer AI. Effects of nonsteroidal antiinflammatory drugs on platelet function and systemic hemostasis. J Clin Pharmacol. 1995;35(3):209-219. doi:10.1002/j.1552-4604.1995.tb04050.x
- Al-Saeed A. Gastrointestinal and cardiovascular risk of nonsteroidal anti-inflammatory drugs. Oman Med J. 2011;26(6):385-391. doi:10.5001/omj.2011.101
- Gabriel SE, Jaakkimainen L, Bombardier C. Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs. Ann Intern Med. 1991;115(10):787-796. doi:10.7326/0003-4819-115-10-787
- Scheiman JM, Yeomans ND, Talley NJ, et al. Prevention of ulcers by esomeprazole in at-risk patients using non-selective NSAIDs and COX-2 inhibitors. Am J Gastroenterol. 2006;101(4):701-710. doi:10.1111/j.1572-0241.2006.00499.x
- Freedberg DE, Kim LS, Yang YX. The risks and benefits of long-term use of proton pump inhibitors: expert review and best practice advice from the American Gastroenterological Association. Gastroenterology. 2017;152(4):706-715. doi:10.1053/j.gastro.2017.01.031
- Lamberts M, Lip GYH, Hansen ML, et al. Relation of nonsteroidal anti-inflammatory drugs to serious bleeding and thromboembolism risk in patients with atrial fibrillation receiving antithrombotic therapy: a nationwide cohort study. Ann Intern Med. 2014;161(10):690-698. doi:10.7326/M13-1581
- Villa Zapata L, Hansten PD, Panic J, et al. Risk of bleeding with exposure to warfarin and nonsteroidal anti-inflammatory drugs: a systematic review and metaanalysis. Thromb Haemost. 2020;120(7):1066-1074. doi:10.1055/s-0040-1710592
- Kent AP, Brueckmann M, Fraessdorf M, et al. Concomitant oral anticoagulant and nonsteroidal anti-inflammatory drug therapy in patients with atrial fibrillation. J Am Coll Cardiol. 2018;72(3):255-267. doi:10.1016/j.jacc.2018.04.063
- Dalgaard F, Mulder H, Wojdyla DM, et al. Patients with atrial fibrillation taking nonsteroidal antiinflammatory drugs and oral anticoagulants in the ARISTOTLE Trial. Circulation. 2020;141(1):10-20. doi:10.1161/CIRCULATIONAHA.119.041296
- Allen AL, Lucas J, Parra D, et al. Shifting the paradigm: a population health approach to the management of direct oral anticoagulants. J Am Heart Asssoc. 2021;10(24):e022758. doi:10.1161/JAHA.121.022758
- . Valencia D, Spoutz P, Stoppi J, et al. Impact of a direct oral anticoagulant population management tool on anticoagulation therapy monitoring in clinical practice. Ann Pharmacother. 2019;53(8):806-811. doi:10.1177/1060028019835843
- By the 2023 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2023 Updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023;71(7):2052-2081. doi:10.1111/jgs.18372
- Kumar S, Danik SB, Altman RK, et al. Non-vitamin K antagonist oral anticoagulants and antiplatelet therapy for stroke prevention in patients with atrial fibrillation. Cardiol Rev. 2016;24(5):218-223. doi:10.1097/CRD.0000000000000088
- Sakuma I, Uchiyama S, Atarashi H, et al. Clinical risk factors of stroke and major bleeding in patients with nonvalvular atrial fibrillation under rivaroxaban: the EXPAND study sub-analysis. Heart Vessels. 2019;34(11):1839-1851. doi:10.1007/s00380-019-01425-x
- Davidson BL, Verheijen S, Lensing AWA, et al. Bleeding risk of patients with acute venous thromboembolism taking nonsteroidal anti-inflammatory drugs or aspirin. JAMA Intern Med. 2014;174(6):947-953. doi:10.1001/jamainternmed.2014.946
- Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014;383(9921):955-962. doi:10.1016/S0140-6736(13)62343-0
- Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G. Oral anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e44S-e88S. doi:10.1378/chest.11-2292
- Eikelboom J, Merli G. Bleeding with direct oral anticoagulants vs warfarin: clinical experience. Am J Med. 2016;129(11S):S33-S40. doi:10.1016/j.amjmed.2016.06.003
- Vranckx P, Valgimigli M, Heidbuchel H. The significance of drug-drug and drug-food interactions of oral anticoagulation. Arrhythm Electrophysiol Rev. 2018;7(1):55-61. doi:10.15420/aer.2017.50.1
- Davis JS, Lee HY, Kim J, et al. Use of non-steroidal antiinflammatory drugs in US adults: changes over time and by demographic. Open Heart. 2017;4(1):e000550. doi:10.1136/openhrt-2016-000550
- Schafer AI. Effects of nonsteroidal antiinflammatory drugs on platelet function and systemic hemostasis. J Clin Pharmacol. 1995;35(3):209-219. doi:10.1002/j.1552-4604.1995.tb04050.x
- Al-Saeed A. Gastrointestinal and cardiovascular risk of nonsteroidal anti-inflammatory drugs. Oman Med J. 2011;26(6):385-391. doi:10.5001/omj.2011.101
- Gabriel SE, Jaakkimainen L, Bombardier C. Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs. Ann Intern Med. 1991;115(10):787-796. doi:10.7326/0003-4819-115-10-787
- Scheiman JM, Yeomans ND, Talley NJ, et al. Prevention of ulcers by esomeprazole in at-risk patients using non-selective NSAIDs and COX-2 inhibitors. Am J Gastroenterol. 2006;101(4):701-710. doi:10.1111/j.1572-0241.2006.00499.x
- Freedberg DE, Kim LS, Yang YX. The risks and benefits of long-term use of proton pump inhibitors: expert review and best practice advice from the American Gastroenterological Association. Gastroenterology. 2017;152(4):706-715. doi:10.1053/j.gastro.2017.01.031
- Lamberts M, Lip GYH, Hansen ML, et al. Relation of nonsteroidal anti-inflammatory drugs to serious bleeding and thromboembolism risk in patients with atrial fibrillation receiving antithrombotic therapy: a nationwide cohort study. Ann Intern Med. 2014;161(10):690-698. doi:10.7326/M13-1581
- Villa Zapata L, Hansten PD, Panic J, et al. Risk of bleeding with exposure to warfarin and nonsteroidal anti-inflammatory drugs: a systematic review and metaanalysis. Thromb Haemost. 2020;120(7):1066-1074. doi:10.1055/s-0040-1710592
- Kent AP, Brueckmann M, Fraessdorf M, et al. Concomitant oral anticoagulant and nonsteroidal anti-inflammatory drug therapy in patients with atrial fibrillation. J Am Coll Cardiol. 2018;72(3):255-267. doi:10.1016/j.jacc.2018.04.063
- Dalgaard F, Mulder H, Wojdyla DM, et al. Patients with atrial fibrillation taking nonsteroidal antiinflammatory drugs and oral anticoagulants in the ARISTOTLE Trial. Circulation. 2020;141(1):10-20. doi:10.1161/CIRCULATIONAHA.119.041296
- Allen AL, Lucas J, Parra D, et al. Shifting the paradigm: a population health approach to the management of direct oral anticoagulants. J Am Heart Asssoc. 2021;10(24):e022758. doi:10.1161/JAHA.121.022758
- . Valencia D, Spoutz P, Stoppi J, et al. Impact of a direct oral anticoagulant population management tool on anticoagulation therapy monitoring in clinical practice. Ann Pharmacother. 2019;53(8):806-811. doi:10.1177/1060028019835843
- By the 2023 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2023 Updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023;71(7):2052-2081. doi:10.1111/jgs.18372
- Kumar S, Danik SB, Altman RK, et al. Non-vitamin K antagonist oral anticoagulants and antiplatelet therapy for stroke prevention in patients with atrial fibrillation. Cardiol Rev. 2016;24(5):218-223. doi:10.1097/CRD.0000000000000088
- Sakuma I, Uchiyama S, Atarashi H, et al. Clinical risk factors of stroke and major bleeding in patients with nonvalvular atrial fibrillation under rivaroxaban: the EXPAND study sub-analysis. Heart Vessels. 2019;34(11):1839-1851. doi:10.1007/s00380-019-01425-x
- Davidson BL, Verheijen S, Lensing AWA, et al. Bleeding risk of patients with acute venous thromboembolism taking nonsteroidal anti-inflammatory drugs or aspirin. JAMA Intern Med. 2014;174(6):947-953. doi:10.1001/jamainternmed.2014.946
Impact of NSAID Use on Bleeding Rates for Patients Taking Rivaroxaban or Apixaban
Impact of NSAID Use on Bleeding Rates for Patients Taking Rivaroxaban or Apixaban
Physician Attitudes About Veterans Affairs Video Connect Encounters
Physician Attitudes About Veterans Affairs Video Connect Encounters
Prior to the COVID-19 pandemic, health care systems had been increasingly focused on expanding care delivery through clinical video telehealth (CVT) services.1-3 These modalities offer clinicians and patients opportunities to interact without needing face-to-face visits. CVT services offer significant advantages to patients who encounter challenges accessing traditional face-to-face services, including those living in rural or underserved areas, individuals with mobility limitations, and those with difficulty attending appointments due to work or caregiving commitments.4 The COVID-19 pandemic accelerated the expansion of CVT services to mitigate the spread of the virus.1
Despite its evident advantages, widespread adoption of CVT has encountered resistance.2 Physicians have frequently expressed concerns about the reliability and functionality of CVT platforms for scheduled encounters and frustration with inadequate training.4-6 Additionally, there is a lack trust in the technology, as physicians are unfamiliar with reimbursement or workload capture associated with CVT. Physicians have concerns that telecommunication may diminish the intangible aspects of the “art of medicine.”4 As a result, the implementation of telehealth services has been inconsistent, with successful adoption limited to specific medical and surgical specialties.4 Only recently have entire departments within major health care systems expressed interest in providing comprehensive CVT services in response to the challenges posed by the COVID-19 pandemic.4
The Veterans Health Administration (VHA) of the US Department of Veterans Affairs (VA) provides an appropriate setting for assessing clinician perceptions of telehealth services. Since 2003, the VHA has significantly expanded CVT services to eligible veterans and has used the VA Video Connect (VVC) platform since 2018.7-10 Through VVC, VA staff and clinicians may schedule video visits with patients, meet with patients through virtual face-to-face interaction, and share relevant laboratory results and imaging through screen sharing. Prior research has shown increased accessibility to care through VVC. For example, a single-site study demonstrated that VVC implementation for delivering psychotherapies significantly increased CVT encounters from 15% to 85% among veterans with anxiety and/or depression.11
The VA New Mexico Healthcare System (VANMHCS) serves a high volume of veterans living in remote and rural regions and significantly increased its use of CVT during the COVID-19 pandemic to reduce in-person visits. Expectedly, this was met with a variety of challenges. Herein, we sought to assess physician perspectives, concerns, and attitudes toward VVC via semistructured interviews. Our hypothesis was that VA physicians may feel uncomfortable with video encounters but recognize the growing importance of such practices providing specialty care to veterans in rural areas.
METHODS
A semistructured interview protocol was created following discussions with physicians from the VANMHCS Medicine Service. Questions were constructed to assess the following domains: overarching views of video telehealth, perceptions of various applications for conducting VVC encounters, and barriers to the broad implementation of video telehealth. A qualitative investigation specialist aided with question development. Two pilot interviews were conducted prior to performing the interviews with the recruited participants to evaluate the quality and delivery of questions.
All VANMHCS physicians who provided outpatient care within the Department of Medicine and had completed ≥ 1 VVC encounter were eligible to participate. Invitations were disseminated via email, and follow-up emails to encourage participation were sent periodically for 2 months following the initial request. Union approval was obtained to interview employees for a research study. In total, 64 physicians were invited and 13 (20%) chose to participate. As the study did not involve assessing medical interventions among patients, a waiver of informed consent was granted by the VANMHCS Institutional Review Board. Physicians who participated in this study were informed that their responses would be used for reporting purposes and could be rescinded at any time.
Data Analysis
Semistructured interviews were conducted by a single interviewer and recorded using Microsoft Teams. The interviews took place between February 2021 and December 2021 and lasted 5 to 15 minutes, with a mean duration of 9 minutes. Verbal informed consent was obtained from all participants before the interviews. Interviewees were encouraged to expand on their responses to structured questions by recounting past experiences with VVC. Recorded audio was additionally transcribed via Microsoft Teams, and the research team reviewed the transcriptions to ensure accuracy.
The tracking and coding of responses to interview questions were conducted using Microsoft Excel. Initially, 5 transcripts were reviewed and responses were assessed by 2 study team members through open coding. All team members examined the 5 coded transcripts to identify differences and reach a consensus for any discrepancies. Based on recommendations from all team members regarding nuanced excerpts of transcripts, 1 study team member coded the remaining interviews. Thematic analysis was subsequently conducted according to the method described by Braun and Clarke.12 Themes were developed both deductively and inductively by reviewing the direct responses to interview questions and identifying emerging patterns of data, respectively. Indicative quotes representing each theme were carefully chosen for reporting.
RESULTS
Thirteen interviews were conducted and 9 participants (69%) were female. Participating physicians included 3 internal medicine/primary care physicians (23%), 2 nephrologists (15%), and 1 (8%) from cardiology, endocrinology, hematology, infectious diseases, palliative care, critical care, pulmonology, and sleep medicine. Years of post training experience among physicians ranged from 1 to 9 years (n = 5, 38%), 10 to 19 years (n = 3, 23%), and . 20 years (n = 5, 38%). Seven participants (54%) had conducted ≥ 5 VVC visits, with 1 physician completing > 50 video visits (Table).

Using open coding and a deductive approach to thematic analysis, 5 themes were identified: (1) VVC software and internet connection issues affected implementation; (2) patient technological literacy affected veteran and physician comfort with VVC; (3) integration of supportive measures was desired; (4) CVT services may increasingly be used to enhance access to care; and (5) in-person encounters afforded unique advantages over CVT. Illustrative quotes from physicians that reflect these themes can be found in the Appendix.
Theme 1: VVC software and internet connection issues affected its implementation. Most participants expressed concern about the technical challenges with VVC. Interviewees cited inconsistencies for both patients and physicians receiving emails with links to join VVC visits, which should be generated when appointments are scheduled. Some physicians were unaware of scheduled VVC visits until the day of the appointment and only received the link via email. Such issues appeared to occur regardless whether the physicians or support staff scheduled the encounter. Poor video and audio quality was also cited as significant barriers to successful VVC visits and were often not resolvable through troubleshooting efforts by physicians, patients, or support personnel. Given the limited time allotted to each patient encounter, such issues could significantly impact the physician’s ability to remain on schedule. Moreover, connectivity problems led to significant lapses, delays in audio and video transmission, and complete disconnections from the VVC encounter. This was a significant concern for participants, given the rural nature of New Mexico and the large geographical gaps in internet service throughout the state.
Theme 2: Patient technological literacy affected veteran and physician comfort with VVC. Successful VVC appointments require high-speed Internet and compatible hardware. Physicians indicated that some patients reported difficulties with critical steps in the process, such as logging into the VVC platform or ensuring their microphones and cameras were active. Physicians also expressed concern about older veterans’ ability to utilize electronic devices, noting they may generally be less technology savvy. Additionally, physicians reported that despite offering the option of a virtual visit, many veterans preferred in-person visits, regardless of the drive time required. This appeared related to a fear of using the technology, which led veterans to believe that virtual visits do not provide the same quality of care as in-person visits.
Theme 3: Integration of supportive measures is desired. Interviewees felt that integrated VVC technical assistance and technology literacy education were imperative. First, training the patient or the patient’s caregiver on how to complete a VVC encounter using the preferred device and the VVC platform would be beneficial. Second, education to inform physicians about common troubleshooting issues could help streamline VVC encounters. Third, managing a VVC encounter similarly to standard in-person visits could allow for better patient and physician experience. For example, physicians suggested that a medical assistant or a nurse triage the patient, take vital signs, and set them up in a room, potentially at a regional VA community based outpatient clinic. Such efforts would also allow patients to receive specialty care in remote areas where only primary care is generally offered. Support staff could assist with technological issues, such as setting up the VVC encounter and addressing potential problems before the physician joins the encounter, thereby preventing delays in patient care. Finally, physicians felt that designating a day solely for CVT visits would help prevent disruption in care with in-person visits.
Theme 4: CVT services may increasingly be used to enhance access to care. Physicians felt that VVC would help patients encountering obstacles in accessing conventional in person services, including patients in rural and underserved areas, with disabilities, or with scheduling challenges.4 Patients with chronic conditions might drive the use of virtual visits, as many of these patients are already accustomed to remote medical monitoring. Data from devices such as scales and continuous glucose monitors can be easily reviewed during VVC visits. Second, video encounters facilitate closer monitoring that some patients might otherwise skip due to significant travel barriers, especially in a rural state like New Mexico. Lastly, VVC may be more efficient than in person visits as they eliminate the need for lengthy parking, checking in, and checking out processes. Thus, if technological issues are resolved, a typical physician’s day in the clinic may be more efficient with virtual visits.
Theme 5: In-person encounters afforded unique advantages over CVT. Some physicians felt in-person visits still offer unique advantages. They opined that the selection of appropriate candidates for CVT is critical. Patients requiring a physical examination should be scheduled for in person visits. For example, patients with advanced chronic kidney disease who require accurate volume status assessment or patients who have recently undergone surgery and need detailed wound inspection should be seen in the clinic. In-person visits may also be preferable for patients with recurrent admissions, or those whose condition is difficult to assess; accurate assessments of such patients may help prevent readmissions. Finally, many patients are more comfortable and satisfied with in-person visits, which are perceived as a more standard or traditional process. Respondents noted that some patients felt physicians may not focus as much attention during a VVC visit as they do during in-person visits. There were also concerns that some patients feel more motivation to come to in-person visits, as they see the VA as a place to interact with other veterans and staff with whom they are familiar and comfortable.
DISCUSSION
VANMHCS physicians, which serves veterans across an expansive territory ranging from Southern Colorado to West Texas. About 4.6 million veterans reside in rural regions, constituting roughly 25% of the total veteran population, a pattern mirrored in New Mexico.13 Medicine Service physicians agreed on a number of themes: VVC user-interface issues may affect its use and effectiveness, technological literacy was important for both patients and health care staff, technical support staff roles before and during VVC visits should be standardized, CVT is likely to increase health care delivery, and in-person encounters are preferred for many patients.
This is the first study to qualitatively evaluate a diverse group of physicians at a VA medical center incorporating CVT services across specialties. A few related qualitative studies have been conducted external to VHA, generally evaluating clinicians within a single specialty. Kalicki and colleagues surveyed 16 physicians working at a large home-based primary care program in New York City between April and June 2020 to identify and explore barriers to telehealth among homebound older adults. Similarly to our study, physicians noted that many patients required assistance (family members or caregivers) with the visit, either due to technological literacy issues or medical conditions like dementia.14
Heyer and colleagues surveyed 29 oncologists at an urban academic center prior to the COVID-19 pandemic. Similar to our observations, the oncologists said telemedicine helped eliminate travel as a barrier to health care. Heyer and colleagues noted difficulty for oncologists in performing virtual physical examinations, despite training. This group did note the benefits when being selective as to which clinical issues they would handle virtually vs in person.15
Budhwani and colleagues reported that mental health professionals in an academic setting cited difficulty establishing therapeutic relationships via telehealth and felt that this affected quality of care.16 While this was not a topic during our interviews, it is reasonable to question how potentially missed nonverbal cues may impact patient assessments.
Notably, technological issues were common among all reviewed studies. These ranged from internet connectivity issues to necessary electronic devices. As mentioned, these barriers are more prevalent in rural states like New Mexico.
Limitations
All participants in this study were Medicine Service physicians of a single VA health care system, which may limit generalizability. Many of our respondents were female (69%), compared with 39.2% of active internal medicine physicians and therefore may not be representative.17 Nearly one-half of our participants only completed 1 to 4 VVC encounters, which may have contributed to the emergence of a common theme regarding technological issues. Physicians with more experience with CVT services may be more skilled at troubleshooting technological issues that arise during visits.
CONCLUSIONS
Our study, conducted with VANMHCS physicians, illuminated 5 key themes influencing the use and implementation of video encounters: technological issues, technological literacy, a desire for integrated support measures, perceived future growth of video telehealth, and the unique advantages of in-person visits. Addressing technological barriers and providing more extensive training may streamline CVT use. However, it is vital to recognize the unique benefits of in-person visits and consider the benefits of each modality along with patient preferences when selecting the best care venue. As health care evolves, better understanding and acting upon these themes will optimize telehealth services, particularly in rural areas. Future research should involve patients and other health care team members to further explore strategies for effective CVT service integration.
Appendix

- Monaghesh E, Hajizadeh A. The role of telehealth during covid-19 outbreak: a systematic review based on current evidence. BMC Public Health. 2020;20(1):1193. doi:10.1186/s12889-020-09301-4
- Scott Kruse C, Karem P, Shifflett K, Vegi L, Ravi K, Brooks M. Evaluating barriers to adopting telemedicine worldwide: a systematic review. J Telemed Telecare. 2018;24(1):4-12. doi:10.1177/1357633X16674087
- Bashshur RL, Howell JD, Krupinski EA, Harms KM, Bashshur N, Doarn CR. The empirical foundations of telemedicine interventions in primary care. Telemed J E Health. 2016;22(5):342-375. doi:10.1089/tmj.2016.0045
- Yellowlees P, Nakagawa K, Pakyurek M, Hanson A, Elder J, Kales HC. Rapid conversion of an outpatient psychiatric clinic to a 100% virtual telepsychiatry clinic in response to covid-19. Pyschiatr Serv. 2020;71(7):749-752. doi:10.1176/appi.ps.202000230
- Hailey D, Ohinmaa A, Roine R. Study quality and evidence of benefit in recent assessments of telemedicine. J Telemed Telecare. 2004;10(6):318-324. doi:10.1258/1357633042602053
- Osuji TA, Macias M, McMullen C, et al. Clinician perspectives on implementing video visits in home-based palliative care. Palliat Med Rep. 2020;1(1):221-226. doi:10.1089/pmr.2020.0074
- Darkins A. The growth of telehealth services in the Veterans Health Administration between 1994 and 2014: a study in the diffusion of innovation. Telemed J E Health. 2014;20(9):761-768. doi:10.1089/tmj.2014.0143
- Dorsey ER, Topol EJ. State of telehealth. N Engl J Med. 2016;375(2):154-161. doi:10.1056/nejmra1601705
- Alexander NB, Phillips K, Wagner-Felkey J, et al. Team VA video connect (VVC) to optimize mobility and physical activity in post-hospital discharge older veterans: Baseline assessment. BMC Geriatr. 2021;21(1):502. doi:10.1186/s12877-021-02454-w
- Padala KP, Wilson KB, Gauss CH, Stovall JD, Padala PR. VA video connect for clinical care in older adults in a rural state during the covid-19 pandemic: cross-sectional study. J Med Internet Res. 2020;22(9)e21561. doi:10.2196/21561
- Myers US, Coulon S, Knies K, et al. Lessons learned in implementing VA video connect for evidence-based psychotherapies for anxiety and depression in the veterans healthcare administration. J Technol Behav Sci. 2020;6(2):320-326. doi:10.1007/s41347-020-00161-8
- Braun V, Clarke V. Using thematic analysis in psychology. Qual Res Psychol. 2006;3(2):77-101. doi:10.1191/1478088706qp063oa
- US Department of Veterans Affairs, National Center for Feterans Analysis and Statistics. Accessed September 18, 2024. www.va.gov/vetdata/report.asp
- Kalicki AV, Moody KA, Franzosa E, Gliatto PM, Ornstein KA. Barriers to telehealth access among homebound older adults. J Am Geriatr Soc. 2021;69(9):2404-2411. doi:10.1111/jgs.17163
- Heyer A, Granberg RE, Rising KL, Binder AF, Gentsch AT, Handley NR. Medical oncology professionals’ perceptions of telehealth video visits. JAMA Netw Open. 2021;4(1) e2033967. doi:10.1001/jamanetworkopen.2020.33967
- Budhwani S, Fujioka JK, Chu C, et al. Delivering mental health care virtually during the COVID-19 pandemic: qualitative evaluation of provider experiences in a scaled context. JMIR Form Res. 2021;5(9)e30280. doi:10.2196/30280
- Association of American Medical Colleges. Active physicians by sex and specialty, 2021. AAMC. Accessed September 18, 2024. https://www.aamc.org/data-reports/workforce/data/active-physicians-sex-specialty-2021
Prior to the COVID-19 pandemic, health care systems had been increasingly focused on expanding care delivery through clinical video telehealth (CVT) services.1-3 These modalities offer clinicians and patients opportunities to interact without needing face-to-face visits. CVT services offer significant advantages to patients who encounter challenges accessing traditional face-to-face services, including those living in rural or underserved areas, individuals with mobility limitations, and those with difficulty attending appointments due to work or caregiving commitments.4 The COVID-19 pandemic accelerated the expansion of CVT services to mitigate the spread of the virus.1
Despite its evident advantages, widespread adoption of CVT has encountered resistance.2 Physicians have frequently expressed concerns about the reliability and functionality of CVT platforms for scheduled encounters and frustration with inadequate training.4-6 Additionally, there is a lack trust in the technology, as physicians are unfamiliar with reimbursement or workload capture associated with CVT. Physicians have concerns that telecommunication may diminish the intangible aspects of the “art of medicine.”4 As a result, the implementation of telehealth services has been inconsistent, with successful adoption limited to specific medical and surgical specialties.4 Only recently have entire departments within major health care systems expressed interest in providing comprehensive CVT services in response to the challenges posed by the COVID-19 pandemic.4
The Veterans Health Administration (VHA) of the US Department of Veterans Affairs (VA) provides an appropriate setting for assessing clinician perceptions of telehealth services. Since 2003, the VHA has significantly expanded CVT services to eligible veterans and has used the VA Video Connect (VVC) platform since 2018.7-10 Through VVC, VA staff and clinicians may schedule video visits with patients, meet with patients through virtual face-to-face interaction, and share relevant laboratory results and imaging through screen sharing. Prior research has shown increased accessibility to care through VVC. For example, a single-site study demonstrated that VVC implementation for delivering psychotherapies significantly increased CVT encounters from 15% to 85% among veterans with anxiety and/or depression.11
The VA New Mexico Healthcare System (VANMHCS) serves a high volume of veterans living in remote and rural regions and significantly increased its use of CVT during the COVID-19 pandemic to reduce in-person visits. Expectedly, this was met with a variety of challenges. Herein, we sought to assess physician perspectives, concerns, and attitudes toward VVC via semistructured interviews. Our hypothesis was that VA physicians may feel uncomfortable with video encounters but recognize the growing importance of such practices providing specialty care to veterans in rural areas.
METHODS
A semistructured interview protocol was created following discussions with physicians from the VANMHCS Medicine Service. Questions were constructed to assess the following domains: overarching views of video telehealth, perceptions of various applications for conducting VVC encounters, and barriers to the broad implementation of video telehealth. A qualitative investigation specialist aided with question development. Two pilot interviews were conducted prior to performing the interviews with the recruited participants to evaluate the quality and delivery of questions.
All VANMHCS physicians who provided outpatient care within the Department of Medicine and had completed ≥ 1 VVC encounter were eligible to participate. Invitations were disseminated via email, and follow-up emails to encourage participation were sent periodically for 2 months following the initial request. Union approval was obtained to interview employees for a research study. In total, 64 physicians were invited and 13 (20%) chose to participate. As the study did not involve assessing medical interventions among patients, a waiver of informed consent was granted by the VANMHCS Institutional Review Board. Physicians who participated in this study were informed that their responses would be used for reporting purposes and could be rescinded at any time.
Data Analysis
Semistructured interviews were conducted by a single interviewer and recorded using Microsoft Teams. The interviews took place between February 2021 and December 2021 and lasted 5 to 15 minutes, with a mean duration of 9 minutes. Verbal informed consent was obtained from all participants before the interviews. Interviewees were encouraged to expand on their responses to structured questions by recounting past experiences with VVC. Recorded audio was additionally transcribed via Microsoft Teams, and the research team reviewed the transcriptions to ensure accuracy.
The tracking and coding of responses to interview questions were conducted using Microsoft Excel. Initially, 5 transcripts were reviewed and responses were assessed by 2 study team members through open coding. All team members examined the 5 coded transcripts to identify differences and reach a consensus for any discrepancies. Based on recommendations from all team members regarding nuanced excerpts of transcripts, 1 study team member coded the remaining interviews. Thematic analysis was subsequently conducted according to the method described by Braun and Clarke.12 Themes were developed both deductively and inductively by reviewing the direct responses to interview questions and identifying emerging patterns of data, respectively. Indicative quotes representing each theme were carefully chosen for reporting.
RESULTS
Thirteen interviews were conducted and 9 participants (69%) were female. Participating physicians included 3 internal medicine/primary care physicians (23%), 2 nephrologists (15%), and 1 (8%) from cardiology, endocrinology, hematology, infectious diseases, palliative care, critical care, pulmonology, and sleep medicine. Years of post training experience among physicians ranged from 1 to 9 years (n = 5, 38%), 10 to 19 years (n = 3, 23%), and . 20 years (n = 5, 38%). Seven participants (54%) had conducted ≥ 5 VVC visits, with 1 physician completing > 50 video visits (Table).

Using open coding and a deductive approach to thematic analysis, 5 themes were identified: (1) VVC software and internet connection issues affected implementation; (2) patient technological literacy affected veteran and physician comfort with VVC; (3) integration of supportive measures was desired; (4) CVT services may increasingly be used to enhance access to care; and (5) in-person encounters afforded unique advantages over CVT. Illustrative quotes from physicians that reflect these themes can be found in the Appendix.
Theme 1: VVC software and internet connection issues affected its implementation. Most participants expressed concern about the technical challenges with VVC. Interviewees cited inconsistencies for both patients and physicians receiving emails with links to join VVC visits, which should be generated when appointments are scheduled. Some physicians were unaware of scheduled VVC visits until the day of the appointment and only received the link via email. Such issues appeared to occur regardless whether the physicians or support staff scheduled the encounter. Poor video and audio quality was also cited as significant barriers to successful VVC visits and were often not resolvable through troubleshooting efforts by physicians, patients, or support personnel. Given the limited time allotted to each patient encounter, such issues could significantly impact the physician’s ability to remain on schedule. Moreover, connectivity problems led to significant lapses, delays in audio and video transmission, and complete disconnections from the VVC encounter. This was a significant concern for participants, given the rural nature of New Mexico and the large geographical gaps in internet service throughout the state.
Theme 2: Patient technological literacy affected veteran and physician comfort with VVC. Successful VVC appointments require high-speed Internet and compatible hardware. Physicians indicated that some patients reported difficulties with critical steps in the process, such as logging into the VVC platform or ensuring their microphones and cameras were active. Physicians also expressed concern about older veterans’ ability to utilize electronic devices, noting they may generally be less technology savvy. Additionally, physicians reported that despite offering the option of a virtual visit, many veterans preferred in-person visits, regardless of the drive time required. This appeared related to a fear of using the technology, which led veterans to believe that virtual visits do not provide the same quality of care as in-person visits.
Theme 3: Integration of supportive measures is desired. Interviewees felt that integrated VVC technical assistance and technology literacy education were imperative. First, training the patient or the patient’s caregiver on how to complete a VVC encounter using the preferred device and the VVC platform would be beneficial. Second, education to inform physicians about common troubleshooting issues could help streamline VVC encounters. Third, managing a VVC encounter similarly to standard in-person visits could allow for better patient and physician experience. For example, physicians suggested that a medical assistant or a nurse triage the patient, take vital signs, and set them up in a room, potentially at a regional VA community based outpatient clinic. Such efforts would also allow patients to receive specialty care in remote areas where only primary care is generally offered. Support staff could assist with technological issues, such as setting up the VVC encounter and addressing potential problems before the physician joins the encounter, thereby preventing delays in patient care. Finally, physicians felt that designating a day solely for CVT visits would help prevent disruption in care with in-person visits.
Theme 4: CVT services may increasingly be used to enhance access to care. Physicians felt that VVC would help patients encountering obstacles in accessing conventional in person services, including patients in rural and underserved areas, with disabilities, or with scheduling challenges.4 Patients with chronic conditions might drive the use of virtual visits, as many of these patients are already accustomed to remote medical monitoring. Data from devices such as scales and continuous glucose monitors can be easily reviewed during VVC visits. Second, video encounters facilitate closer monitoring that some patients might otherwise skip due to significant travel barriers, especially in a rural state like New Mexico. Lastly, VVC may be more efficient than in person visits as they eliminate the need for lengthy parking, checking in, and checking out processes. Thus, if technological issues are resolved, a typical physician’s day in the clinic may be more efficient with virtual visits.
Theme 5: In-person encounters afforded unique advantages over CVT. Some physicians felt in-person visits still offer unique advantages. They opined that the selection of appropriate candidates for CVT is critical. Patients requiring a physical examination should be scheduled for in person visits. For example, patients with advanced chronic kidney disease who require accurate volume status assessment or patients who have recently undergone surgery and need detailed wound inspection should be seen in the clinic. In-person visits may also be preferable for patients with recurrent admissions, or those whose condition is difficult to assess; accurate assessments of such patients may help prevent readmissions. Finally, many patients are more comfortable and satisfied with in-person visits, which are perceived as a more standard or traditional process. Respondents noted that some patients felt physicians may not focus as much attention during a VVC visit as they do during in-person visits. There were also concerns that some patients feel more motivation to come to in-person visits, as they see the VA as a place to interact with other veterans and staff with whom they are familiar and comfortable.
DISCUSSION
VANMHCS physicians, which serves veterans across an expansive territory ranging from Southern Colorado to West Texas. About 4.6 million veterans reside in rural regions, constituting roughly 25% of the total veteran population, a pattern mirrored in New Mexico.13 Medicine Service physicians agreed on a number of themes: VVC user-interface issues may affect its use and effectiveness, technological literacy was important for both patients and health care staff, technical support staff roles before and during VVC visits should be standardized, CVT is likely to increase health care delivery, and in-person encounters are preferred for many patients.
This is the first study to qualitatively evaluate a diverse group of physicians at a VA medical center incorporating CVT services across specialties. A few related qualitative studies have been conducted external to VHA, generally evaluating clinicians within a single specialty. Kalicki and colleagues surveyed 16 physicians working at a large home-based primary care program in New York City between April and June 2020 to identify and explore barriers to telehealth among homebound older adults. Similarly to our study, physicians noted that many patients required assistance (family members or caregivers) with the visit, either due to technological literacy issues or medical conditions like dementia.14
Heyer and colleagues surveyed 29 oncologists at an urban academic center prior to the COVID-19 pandemic. Similar to our observations, the oncologists said telemedicine helped eliminate travel as a barrier to health care. Heyer and colleagues noted difficulty for oncologists in performing virtual physical examinations, despite training. This group did note the benefits when being selective as to which clinical issues they would handle virtually vs in person.15
Budhwani and colleagues reported that mental health professionals in an academic setting cited difficulty establishing therapeutic relationships via telehealth and felt that this affected quality of care.16 While this was not a topic during our interviews, it is reasonable to question how potentially missed nonverbal cues may impact patient assessments.
Notably, technological issues were common among all reviewed studies. These ranged from internet connectivity issues to necessary electronic devices. As mentioned, these barriers are more prevalent in rural states like New Mexico.
Limitations
All participants in this study were Medicine Service physicians of a single VA health care system, which may limit generalizability. Many of our respondents were female (69%), compared with 39.2% of active internal medicine physicians and therefore may not be representative.17 Nearly one-half of our participants only completed 1 to 4 VVC encounters, which may have contributed to the emergence of a common theme regarding technological issues. Physicians with more experience with CVT services may be more skilled at troubleshooting technological issues that arise during visits.
CONCLUSIONS
Our study, conducted with VANMHCS physicians, illuminated 5 key themes influencing the use and implementation of video encounters: technological issues, technological literacy, a desire for integrated support measures, perceived future growth of video telehealth, and the unique advantages of in-person visits. Addressing technological barriers and providing more extensive training may streamline CVT use. However, it is vital to recognize the unique benefits of in-person visits and consider the benefits of each modality along with patient preferences when selecting the best care venue. As health care evolves, better understanding and acting upon these themes will optimize telehealth services, particularly in rural areas. Future research should involve patients and other health care team members to further explore strategies for effective CVT service integration.
Appendix

Prior to the COVID-19 pandemic, health care systems had been increasingly focused on expanding care delivery through clinical video telehealth (CVT) services.1-3 These modalities offer clinicians and patients opportunities to interact without needing face-to-face visits. CVT services offer significant advantages to patients who encounter challenges accessing traditional face-to-face services, including those living in rural or underserved areas, individuals with mobility limitations, and those with difficulty attending appointments due to work or caregiving commitments.4 The COVID-19 pandemic accelerated the expansion of CVT services to mitigate the spread of the virus.1
Despite its evident advantages, widespread adoption of CVT has encountered resistance.2 Physicians have frequently expressed concerns about the reliability and functionality of CVT platforms for scheduled encounters and frustration with inadequate training.4-6 Additionally, there is a lack trust in the technology, as physicians are unfamiliar with reimbursement or workload capture associated with CVT. Physicians have concerns that telecommunication may diminish the intangible aspects of the “art of medicine.”4 As a result, the implementation of telehealth services has been inconsistent, with successful adoption limited to specific medical and surgical specialties.4 Only recently have entire departments within major health care systems expressed interest in providing comprehensive CVT services in response to the challenges posed by the COVID-19 pandemic.4
The Veterans Health Administration (VHA) of the US Department of Veterans Affairs (VA) provides an appropriate setting for assessing clinician perceptions of telehealth services. Since 2003, the VHA has significantly expanded CVT services to eligible veterans and has used the VA Video Connect (VVC) platform since 2018.7-10 Through VVC, VA staff and clinicians may schedule video visits with patients, meet with patients through virtual face-to-face interaction, and share relevant laboratory results and imaging through screen sharing. Prior research has shown increased accessibility to care through VVC. For example, a single-site study demonstrated that VVC implementation for delivering psychotherapies significantly increased CVT encounters from 15% to 85% among veterans with anxiety and/or depression.11
The VA New Mexico Healthcare System (VANMHCS) serves a high volume of veterans living in remote and rural regions and significantly increased its use of CVT during the COVID-19 pandemic to reduce in-person visits. Expectedly, this was met with a variety of challenges. Herein, we sought to assess physician perspectives, concerns, and attitudes toward VVC via semistructured interviews. Our hypothesis was that VA physicians may feel uncomfortable with video encounters but recognize the growing importance of such practices providing specialty care to veterans in rural areas.
METHODS
A semistructured interview protocol was created following discussions with physicians from the VANMHCS Medicine Service. Questions were constructed to assess the following domains: overarching views of video telehealth, perceptions of various applications for conducting VVC encounters, and barriers to the broad implementation of video telehealth. A qualitative investigation specialist aided with question development. Two pilot interviews were conducted prior to performing the interviews with the recruited participants to evaluate the quality and delivery of questions.
All VANMHCS physicians who provided outpatient care within the Department of Medicine and had completed ≥ 1 VVC encounter were eligible to participate. Invitations were disseminated via email, and follow-up emails to encourage participation were sent periodically for 2 months following the initial request. Union approval was obtained to interview employees for a research study. In total, 64 physicians were invited and 13 (20%) chose to participate. As the study did not involve assessing medical interventions among patients, a waiver of informed consent was granted by the VANMHCS Institutional Review Board. Physicians who participated in this study were informed that their responses would be used for reporting purposes and could be rescinded at any time.
Data Analysis
Semistructured interviews were conducted by a single interviewer and recorded using Microsoft Teams. The interviews took place between February 2021 and December 2021 and lasted 5 to 15 minutes, with a mean duration of 9 minutes. Verbal informed consent was obtained from all participants before the interviews. Interviewees were encouraged to expand on their responses to structured questions by recounting past experiences with VVC. Recorded audio was additionally transcribed via Microsoft Teams, and the research team reviewed the transcriptions to ensure accuracy.
The tracking and coding of responses to interview questions were conducted using Microsoft Excel. Initially, 5 transcripts were reviewed and responses were assessed by 2 study team members through open coding. All team members examined the 5 coded transcripts to identify differences and reach a consensus for any discrepancies. Based on recommendations from all team members regarding nuanced excerpts of transcripts, 1 study team member coded the remaining interviews. Thematic analysis was subsequently conducted according to the method described by Braun and Clarke.12 Themes were developed both deductively and inductively by reviewing the direct responses to interview questions and identifying emerging patterns of data, respectively. Indicative quotes representing each theme were carefully chosen for reporting.
RESULTS
Thirteen interviews were conducted and 9 participants (69%) were female. Participating physicians included 3 internal medicine/primary care physicians (23%), 2 nephrologists (15%), and 1 (8%) from cardiology, endocrinology, hematology, infectious diseases, palliative care, critical care, pulmonology, and sleep medicine. Years of post training experience among physicians ranged from 1 to 9 years (n = 5, 38%), 10 to 19 years (n = 3, 23%), and . 20 years (n = 5, 38%). Seven participants (54%) had conducted ≥ 5 VVC visits, with 1 physician completing > 50 video visits (Table).

Using open coding and a deductive approach to thematic analysis, 5 themes were identified: (1) VVC software and internet connection issues affected implementation; (2) patient technological literacy affected veteran and physician comfort with VVC; (3) integration of supportive measures was desired; (4) CVT services may increasingly be used to enhance access to care; and (5) in-person encounters afforded unique advantages over CVT. Illustrative quotes from physicians that reflect these themes can be found in the Appendix.
Theme 1: VVC software and internet connection issues affected its implementation. Most participants expressed concern about the technical challenges with VVC. Interviewees cited inconsistencies for both patients and physicians receiving emails with links to join VVC visits, which should be generated when appointments are scheduled. Some physicians were unaware of scheduled VVC visits until the day of the appointment and only received the link via email. Such issues appeared to occur regardless whether the physicians or support staff scheduled the encounter. Poor video and audio quality was also cited as significant barriers to successful VVC visits and were often not resolvable through troubleshooting efforts by physicians, patients, or support personnel. Given the limited time allotted to each patient encounter, such issues could significantly impact the physician’s ability to remain on schedule. Moreover, connectivity problems led to significant lapses, delays in audio and video transmission, and complete disconnections from the VVC encounter. This was a significant concern for participants, given the rural nature of New Mexico and the large geographical gaps in internet service throughout the state.
Theme 2: Patient technological literacy affected veteran and physician comfort with VVC. Successful VVC appointments require high-speed Internet and compatible hardware. Physicians indicated that some patients reported difficulties with critical steps in the process, such as logging into the VVC platform or ensuring their microphones and cameras were active. Physicians also expressed concern about older veterans’ ability to utilize electronic devices, noting they may generally be less technology savvy. Additionally, physicians reported that despite offering the option of a virtual visit, many veterans preferred in-person visits, regardless of the drive time required. This appeared related to a fear of using the technology, which led veterans to believe that virtual visits do not provide the same quality of care as in-person visits.
Theme 3: Integration of supportive measures is desired. Interviewees felt that integrated VVC technical assistance and technology literacy education were imperative. First, training the patient or the patient’s caregiver on how to complete a VVC encounter using the preferred device and the VVC platform would be beneficial. Second, education to inform physicians about common troubleshooting issues could help streamline VVC encounters. Third, managing a VVC encounter similarly to standard in-person visits could allow for better patient and physician experience. For example, physicians suggested that a medical assistant or a nurse triage the patient, take vital signs, and set them up in a room, potentially at a regional VA community based outpatient clinic. Such efforts would also allow patients to receive specialty care in remote areas where only primary care is generally offered. Support staff could assist with technological issues, such as setting up the VVC encounter and addressing potential problems before the physician joins the encounter, thereby preventing delays in patient care. Finally, physicians felt that designating a day solely for CVT visits would help prevent disruption in care with in-person visits.
Theme 4: CVT services may increasingly be used to enhance access to care. Physicians felt that VVC would help patients encountering obstacles in accessing conventional in person services, including patients in rural and underserved areas, with disabilities, or with scheduling challenges.4 Patients with chronic conditions might drive the use of virtual visits, as many of these patients are already accustomed to remote medical monitoring. Data from devices such as scales and continuous glucose monitors can be easily reviewed during VVC visits. Second, video encounters facilitate closer monitoring that some patients might otherwise skip due to significant travel barriers, especially in a rural state like New Mexico. Lastly, VVC may be more efficient than in person visits as they eliminate the need for lengthy parking, checking in, and checking out processes. Thus, if technological issues are resolved, a typical physician’s day in the clinic may be more efficient with virtual visits.
Theme 5: In-person encounters afforded unique advantages over CVT. Some physicians felt in-person visits still offer unique advantages. They opined that the selection of appropriate candidates for CVT is critical. Patients requiring a physical examination should be scheduled for in person visits. For example, patients with advanced chronic kidney disease who require accurate volume status assessment or patients who have recently undergone surgery and need detailed wound inspection should be seen in the clinic. In-person visits may also be preferable for patients with recurrent admissions, or those whose condition is difficult to assess; accurate assessments of such patients may help prevent readmissions. Finally, many patients are more comfortable and satisfied with in-person visits, which are perceived as a more standard or traditional process. Respondents noted that some patients felt physicians may not focus as much attention during a VVC visit as they do during in-person visits. There were also concerns that some patients feel more motivation to come to in-person visits, as they see the VA as a place to interact with other veterans and staff with whom they are familiar and comfortable.
DISCUSSION
VANMHCS physicians, which serves veterans across an expansive territory ranging from Southern Colorado to West Texas. About 4.6 million veterans reside in rural regions, constituting roughly 25% of the total veteran population, a pattern mirrored in New Mexico.13 Medicine Service physicians agreed on a number of themes: VVC user-interface issues may affect its use and effectiveness, technological literacy was important for both patients and health care staff, technical support staff roles before and during VVC visits should be standardized, CVT is likely to increase health care delivery, and in-person encounters are preferred for many patients.
This is the first study to qualitatively evaluate a diverse group of physicians at a VA medical center incorporating CVT services across specialties. A few related qualitative studies have been conducted external to VHA, generally evaluating clinicians within a single specialty. Kalicki and colleagues surveyed 16 physicians working at a large home-based primary care program in New York City between April and June 2020 to identify and explore barriers to telehealth among homebound older adults. Similarly to our study, physicians noted that many patients required assistance (family members or caregivers) with the visit, either due to technological literacy issues or medical conditions like dementia.14
Heyer and colleagues surveyed 29 oncologists at an urban academic center prior to the COVID-19 pandemic. Similar to our observations, the oncologists said telemedicine helped eliminate travel as a barrier to health care. Heyer and colleagues noted difficulty for oncologists in performing virtual physical examinations, despite training. This group did note the benefits when being selective as to which clinical issues they would handle virtually vs in person.15
Budhwani and colleagues reported that mental health professionals in an academic setting cited difficulty establishing therapeutic relationships via telehealth and felt that this affected quality of care.16 While this was not a topic during our interviews, it is reasonable to question how potentially missed nonverbal cues may impact patient assessments.
Notably, technological issues were common among all reviewed studies. These ranged from internet connectivity issues to necessary electronic devices. As mentioned, these barriers are more prevalent in rural states like New Mexico.
Limitations
All participants in this study were Medicine Service physicians of a single VA health care system, which may limit generalizability. Many of our respondents were female (69%), compared with 39.2% of active internal medicine physicians and therefore may not be representative.17 Nearly one-half of our participants only completed 1 to 4 VVC encounters, which may have contributed to the emergence of a common theme regarding technological issues. Physicians with more experience with CVT services may be more skilled at troubleshooting technological issues that arise during visits.
CONCLUSIONS
Our study, conducted with VANMHCS physicians, illuminated 5 key themes influencing the use and implementation of video encounters: technological issues, technological literacy, a desire for integrated support measures, perceived future growth of video telehealth, and the unique advantages of in-person visits. Addressing technological barriers and providing more extensive training may streamline CVT use. However, it is vital to recognize the unique benefits of in-person visits and consider the benefits of each modality along with patient preferences when selecting the best care venue. As health care evolves, better understanding and acting upon these themes will optimize telehealth services, particularly in rural areas. Future research should involve patients and other health care team members to further explore strategies for effective CVT service integration.
Appendix

- Monaghesh E, Hajizadeh A. The role of telehealth during covid-19 outbreak: a systematic review based on current evidence. BMC Public Health. 2020;20(1):1193. doi:10.1186/s12889-020-09301-4
- Scott Kruse C, Karem P, Shifflett K, Vegi L, Ravi K, Brooks M. Evaluating barriers to adopting telemedicine worldwide: a systematic review. J Telemed Telecare. 2018;24(1):4-12. doi:10.1177/1357633X16674087
- Bashshur RL, Howell JD, Krupinski EA, Harms KM, Bashshur N, Doarn CR. The empirical foundations of telemedicine interventions in primary care. Telemed J E Health. 2016;22(5):342-375. doi:10.1089/tmj.2016.0045
- Yellowlees P, Nakagawa K, Pakyurek M, Hanson A, Elder J, Kales HC. Rapid conversion of an outpatient psychiatric clinic to a 100% virtual telepsychiatry clinic in response to covid-19. Pyschiatr Serv. 2020;71(7):749-752. doi:10.1176/appi.ps.202000230
- Hailey D, Ohinmaa A, Roine R. Study quality and evidence of benefit in recent assessments of telemedicine. J Telemed Telecare. 2004;10(6):318-324. doi:10.1258/1357633042602053
- Osuji TA, Macias M, McMullen C, et al. Clinician perspectives on implementing video visits in home-based palliative care. Palliat Med Rep. 2020;1(1):221-226. doi:10.1089/pmr.2020.0074
- Darkins A. The growth of telehealth services in the Veterans Health Administration between 1994 and 2014: a study in the diffusion of innovation. Telemed J E Health. 2014;20(9):761-768. doi:10.1089/tmj.2014.0143
- Dorsey ER, Topol EJ. State of telehealth. N Engl J Med. 2016;375(2):154-161. doi:10.1056/nejmra1601705
- Alexander NB, Phillips K, Wagner-Felkey J, et al. Team VA video connect (VVC) to optimize mobility and physical activity in post-hospital discharge older veterans: Baseline assessment. BMC Geriatr. 2021;21(1):502. doi:10.1186/s12877-021-02454-w
- Padala KP, Wilson KB, Gauss CH, Stovall JD, Padala PR. VA video connect for clinical care in older adults in a rural state during the covid-19 pandemic: cross-sectional study. J Med Internet Res. 2020;22(9)e21561. doi:10.2196/21561
- Myers US, Coulon S, Knies K, et al. Lessons learned in implementing VA video connect for evidence-based psychotherapies for anxiety and depression in the veterans healthcare administration. J Technol Behav Sci. 2020;6(2):320-326. doi:10.1007/s41347-020-00161-8
- Braun V, Clarke V. Using thematic analysis in psychology. Qual Res Psychol. 2006;3(2):77-101. doi:10.1191/1478088706qp063oa
- US Department of Veterans Affairs, National Center for Feterans Analysis and Statistics. Accessed September 18, 2024. www.va.gov/vetdata/report.asp
- Kalicki AV, Moody KA, Franzosa E, Gliatto PM, Ornstein KA. Barriers to telehealth access among homebound older adults. J Am Geriatr Soc. 2021;69(9):2404-2411. doi:10.1111/jgs.17163
- Heyer A, Granberg RE, Rising KL, Binder AF, Gentsch AT, Handley NR. Medical oncology professionals’ perceptions of telehealth video visits. JAMA Netw Open. 2021;4(1) e2033967. doi:10.1001/jamanetworkopen.2020.33967
- Budhwani S, Fujioka JK, Chu C, et al. Delivering mental health care virtually during the COVID-19 pandemic: qualitative evaluation of provider experiences in a scaled context. JMIR Form Res. 2021;5(9)e30280. doi:10.2196/30280
- Association of American Medical Colleges. Active physicians by sex and specialty, 2021. AAMC. Accessed September 18, 2024. https://www.aamc.org/data-reports/workforce/data/active-physicians-sex-specialty-2021
- Monaghesh E, Hajizadeh A. The role of telehealth during covid-19 outbreak: a systematic review based on current evidence. BMC Public Health. 2020;20(1):1193. doi:10.1186/s12889-020-09301-4
- Scott Kruse C, Karem P, Shifflett K, Vegi L, Ravi K, Brooks M. Evaluating barriers to adopting telemedicine worldwide: a systematic review. J Telemed Telecare. 2018;24(1):4-12. doi:10.1177/1357633X16674087
- Bashshur RL, Howell JD, Krupinski EA, Harms KM, Bashshur N, Doarn CR. The empirical foundations of telemedicine interventions in primary care. Telemed J E Health. 2016;22(5):342-375. doi:10.1089/tmj.2016.0045
- Yellowlees P, Nakagawa K, Pakyurek M, Hanson A, Elder J, Kales HC. Rapid conversion of an outpatient psychiatric clinic to a 100% virtual telepsychiatry clinic in response to covid-19. Pyschiatr Serv. 2020;71(7):749-752. doi:10.1176/appi.ps.202000230
- Hailey D, Ohinmaa A, Roine R. Study quality and evidence of benefit in recent assessments of telemedicine. J Telemed Telecare. 2004;10(6):318-324. doi:10.1258/1357633042602053
- Osuji TA, Macias M, McMullen C, et al. Clinician perspectives on implementing video visits in home-based palliative care. Palliat Med Rep. 2020;1(1):221-226. doi:10.1089/pmr.2020.0074
- Darkins A. The growth of telehealth services in the Veterans Health Administration between 1994 and 2014: a study in the diffusion of innovation. Telemed J E Health. 2014;20(9):761-768. doi:10.1089/tmj.2014.0143
- Dorsey ER, Topol EJ. State of telehealth. N Engl J Med. 2016;375(2):154-161. doi:10.1056/nejmra1601705
- Alexander NB, Phillips K, Wagner-Felkey J, et al. Team VA video connect (VVC) to optimize mobility and physical activity in post-hospital discharge older veterans: Baseline assessment. BMC Geriatr. 2021;21(1):502. doi:10.1186/s12877-021-02454-w
- Padala KP, Wilson KB, Gauss CH, Stovall JD, Padala PR. VA video connect for clinical care in older adults in a rural state during the covid-19 pandemic: cross-sectional study. J Med Internet Res. 2020;22(9)e21561. doi:10.2196/21561
- Myers US, Coulon S, Knies K, et al. Lessons learned in implementing VA video connect for evidence-based psychotherapies for anxiety and depression in the veterans healthcare administration. J Technol Behav Sci. 2020;6(2):320-326. doi:10.1007/s41347-020-00161-8
- Braun V, Clarke V. Using thematic analysis in psychology. Qual Res Psychol. 2006;3(2):77-101. doi:10.1191/1478088706qp063oa
- US Department of Veterans Affairs, National Center for Feterans Analysis and Statistics. Accessed September 18, 2024. www.va.gov/vetdata/report.asp
- Kalicki AV, Moody KA, Franzosa E, Gliatto PM, Ornstein KA. Barriers to telehealth access among homebound older adults. J Am Geriatr Soc. 2021;69(9):2404-2411. doi:10.1111/jgs.17163
- Heyer A, Granberg RE, Rising KL, Binder AF, Gentsch AT, Handley NR. Medical oncology professionals’ perceptions of telehealth video visits. JAMA Netw Open. 2021;4(1) e2033967. doi:10.1001/jamanetworkopen.2020.33967
- Budhwani S, Fujioka JK, Chu C, et al. Delivering mental health care virtually during the COVID-19 pandemic: qualitative evaluation of provider experiences in a scaled context. JMIR Form Res. 2021;5(9)e30280. doi:10.2196/30280
- Association of American Medical Colleges. Active physicians by sex and specialty, 2021. AAMC. Accessed September 18, 2024. https://www.aamc.org/data-reports/workforce/data/active-physicians-sex-specialty-2021
Physician Attitudes About Veterans Affairs Video Connect Encounters
Physician Attitudes About Veterans Affairs Video Connect Encounters
Flu Shot Reminders Improve Use in Heart Attack Survivors
, showed the NUDGE FLU series of clinical trials.
Influenza has the potential to be a dangerous infection on its own, but it increases the risk for cardiovascular events among people with a history of heart attack, said the study’s lead author, Ankeet Bhatt, MD, a cardiologist at Kaiser Permanente San Francisco Medical Center, San Francisco.
“Yearly influenza vaccines help prevent influenza infection and, in patients with a heart attack, are potentially cardioprotective,” he said during his presentation at the American Heart Association (AHA) Scientific Sessions 2024 in Chicago. The NUDGE FLU results were simultaneously published online in JAMA Cardiology.
In Denmark, where the trials were conducted, about 80% of older adults get flu shots, but only about 40% of younger adults with chronic diseases do, Bhatt reported. In the United States, about 45% of adults and 55% of children received at least one dose of the flu vaccine in the 2023/24 flu season, according to the US Centers for Disease Control and Prevention (CDC).
The NUDGE FLU Trials
Bhatt and his colleagues conducted three related clinical trials during the 2022/23 and 2023/24 flu seasons: NUDGE-FLU and NUDGE-FLU-2 targeted older adults, whereas NUDGE-FLU-CHRONIC targeted younger adults with chronic diseases. Nearly 2 million people were involved in the three trials.
Participants were randomized to receive one of a series of different behavioral-science-informed letters, delivered through a government-run electronic communication system, or no reminder.
People who received any of the nudges had higher rates of vaccination; among heart attack survivors, there was a 1.8% improvement and among adults without a history of heart attack, there was a 1.3% improvement. But a nudge that explained the potential cardiovascular benefits of flu shots was even more effective, leading to a 3.9% increase among people with a history of heart attack and a 2% increase among those with no heart attack history.
“A simple sentence resulted in a durable improvement in the vaccination rate,” said Bhatt.
The effect was even greater among those who had not been vaccinated in the previous flu season. Among heart attack survivors, nearly 14% more people got the vaccine compared with just 1.5% more survivors who were previously vaccinated. And it was most effective among younger adults who had experienced a recent heart attack, resulting in a 26% increase.
“The impact was larger in patients with a history of acute myocardial infarction, in those who were vaccine-hesitant, and in younger people” — all groups with the most to gain from vaccination in terms of cardiovascular protection — Bhatt reported.
About 25% of people in the United States are unsure about whether to get a flu shot, said Orly Vardeny, PharmD, professor of medicine at the University of Minnesota Medical School in Minneapolis, who was not involved in the study. The fact that previously unvaccinated people were convinced by the nudges is reassuring. “That’s the group where this intervention is most likely to move the needle,” she said.
Around half of all people hospitalized for flu in the United States have cardiovascular disease, CDC data showed, so “even a small increase in the number of patients who get vaccinated has substantial public health benefits,” Vardeny said.
The NUDGE FLU series showed that nudges like this should be employed as a simple tool to improve vaccination rates, but the system would be much more difficult to implement in the United States, Bhatt said.
Denmark has a national health service and a preexisting government electronic communication system, whereas the US system is privately run and more fractured. It would be possible to make it work, he pointed out, but would take some effort.
A version of this article first appeared on Medscape.com.
, showed the NUDGE FLU series of clinical trials.
Influenza has the potential to be a dangerous infection on its own, but it increases the risk for cardiovascular events among people with a history of heart attack, said the study’s lead author, Ankeet Bhatt, MD, a cardiologist at Kaiser Permanente San Francisco Medical Center, San Francisco.
“Yearly influenza vaccines help prevent influenza infection and, in patients with a heart attack, are potentially cardioprotective,” he said during his presentation at the American Heart Association (AHA) Scientific Sessions 2024 in Chicago. The NUDGE FLU results were simultaneously published online in JAMA Cardiology.
In Denmark, where the trials were conducted, about 80% of older adults get flu shots, but only about 40% of younger adults with chronic diseases do, Bhatt reported. In the United States, about 45% of adults and 55% of children received at least one dose of the flu vaccine in the 2023/24 flu season, according to the US Centers for Disease Control and Prevention (CDC).
The NUDGE FLU Trials
Bhatt and his colleagues conducted three related clinical trials during the 2022/23 and 2023/24 flu seasons: NUDGE-FLU and NUDGE-FLU-2 targeted older adults, whereas NUDGE-FLU-CHRONIC targeted younger adults with chronic diseases. Nearly 2 million people were involved in the three trials.
Participants were randomized to receive one of a series of different behavioral-science-informed letters, delivered through a government-run electronic communication system, or no reminder.
People who received any of the nudges had higher rates of vaccination; among heart attack survivors, there was a 1.8% improvement and among adults without a history of heart attack, there was a 1.3% improvement. But a nudge that explained the potential cardiovascular benefits of flu shots was even more effective, leading to a 3.9% increase among people with a history of heart attack and a 2% increase among those with no heart attack history.
“A simple sentence resulted in a durable improvement in the vaccination rate,” said Bhatt.
The effect was even greater among those who had not been vaccinated in the previous flu season. Among heart attack survivors, nearly 14% more people got the vaccine compared with just 1.5% more survivors who were previously vaccinated. And it was most effective among younger adults who had experienced a recent heart attack, resulting in a 26% increase.
“The impact was larger in patients with a history of acute myocardial infarction, in those who were vaccine-hesitant, and in younger people” — all groups with the most to gain from vaccination in terms of cardiovascular protection — Bhatt reported.
About 25% of people in the United States are unsure about whether to get a flu shot, said Orly Vardeny, PharmD, professor of medicine at the University of Minnesota Medical School in Minneapolis, who was not involved in the study. The fact that previously unvaccinated people were convinced by the nudges is reassuring. “That’s the group where this intervention is most likely to move the needle,” she said.
Around half of all people hospitalized for flu in the United States have cardiovascular disease, CDC data showed, so “even a small increase in the number of patients who get vaccinated has substantial public health benefits,” Vardeny said.
The NUDGE FLU series showed that nudges like this should be employed as a simple tool to improve vaccination rates, but the system would be much more difficult to implement in the United States, Bhatt said.
Denmark has a national health service and a preexisting government electronic communication system, whereas the US system is privately run and more fractured. It would be possible to make it work, he pointed out, but would take some effort.
A version of this article first appeared on Medscape.com.
, showed the NUDGE FLU series of clinical trials.
Influenza has the potential to be a dangerous infection on its own, but it increases the risk for cardiovascular events among people with a history of heart attack, said the study’s lead author, Ankeet Bhatt, MD, a cardiologist at Kaiser Permanente San Francisco Medical Center, San Francisco.
“Yearly influenza vaccines help prevent influenza infection and, in patients with a heart attack, are potentially cardioprotective,” he said during his presentation at the American Heart Association (AHA) Scientific Sessions 2024 in Chicago. The NUDGE FLU results were simultaneously published online in JAMA Cardiology.
In Denmark, where the trials were conducted, about 80% of older adults get flu shots, but only about 40% of younger adults with chronic diseases do, Bhatt reported. In the United States, about 45% of adults and 55% of children received at least one dose of the flu vaccine in the 2023/24 flu season, according to the US Centers for Disease Control and Prevention (CDC).
The NUDGE FLU Trials
Bhatt and his colleagues conducted three related clinical trials during the 2022/23 and 2023/24 flu seasons: NUDGE-FLU and NUDGE-FLU-2 targeted older adults, whereas NUDGE-FLU-CHRONIC targeted younger adults with chronic diseases. Nearly 2 million people were involved in the three trials.
Participants were randomized to receive one of a series of different behavioral-science-informed letters, delivered through a government-run electronic communication system, or no reminder.
People who received any of the nudges had higher rates of vaccination; among heart attack survivors, there was a 1.8% improvement and among adults without a history of heart attack, there was a 1.3% improvement. But a nudge that explained the potential cardiovascular benefits of flu shots was even more effective, leading to a 3.9% increase among people with a history of heart attack and a 2% increase among those with no heart attack history.
“A simple sentence resulted in a durable improvement in the vaccination rate,” said Bhatt.
The effect was even greater among those who had not been vaccinated in the previous flu season. Among heart attack survivors, nearly 14% more people got the vaccine compared with just 1.5% more survivors who were previously vaccinated. And it was most effective among younger adults who had experienced a recent heart attack, resulting in a 26% increase.
“The impact was larger in patients with a history of acute myocardial infarction, in those who were vaccine-hesitant, and in younger people” — all groups with the most to gain from vaccination in terms of cardiovascular protection — Bhatt reported.
About 25% of people in the United States are unsure about whether to get a flu shot, said Orly Vardeny, PharmD, professor of medicine at the University of Minnesota Medical School in Minneapolis, who was not involved in the study. The fact that previously unvaccinated people were convinced by the nudges is reassuring. “That’s the group where this intervention is most likely to move the needle,” she said.
Around half of all people hospitalized for flu in the United States have cardiovascular disease, CDC data showed, so “even a small increase in the number of patients who get vaccinated has substantial public health benefits,” Vardeny said.
The NUDGE FLU series showed that nudges like this should be employed as a simple tool to improve vaccination rates, but the system would be much more difficult to implement in the United States, Bhatt said.
Denmark has a national health service and a preexisting government electronic communication system, whereas the US system is privately run and more fractured. It would be possible to make it work, he pointed out, but would take some effort.
A version of this article first appeared on Medscape.com.
FROM AHA 2024
Communicating the Benefits of Prenatal Vaccination to Patients
Vaccines recommended by the Advisory Committee on Immunization Practices (ACIP) offer important protection against severe illness for pregnant people and their babies.1 However, vaccination coverage estimates among pregnant people remain suboptimal.2-5 Additionally, some measures indicate that vaccine hesitancy among pregnant people is increasing; for example, 17.5% of surveyed pregnant women reported being very hesitant about influenza vaccination during pregnancy in 2019-2020, compared with 24.7% in 2022-2023.6 Explore updated provider toolkits and prenatal vaccination patient education resources, including fact sheets, social media assets, posters, and short videos on respiratory syncytial virus (RSV), Tdap, COVID-19, influenza, and hepatitis B.
In an interview, CDC’s Haben Debessai, MD, an adjunct instructor in obstetrics and gynecology at Emory School of Medicine, Atlanta, Georgia, contextualizes the data to help healthcare professionals communicate effectively with their pregnant patients.
What can practitioners communicate to patients about why it is important to get vaccinated during their pregnancy?
When communicating with their patients, practitioners can consider opportunities to discuss how vaccines work during pregnancy, emphasizing that prenatal vaccinations are beneficial for both the pregnant person and the fetus. It can be helpful to educate patients on how a pregnant person’s immune system can develop antibodies that will then pass to the fetus during the pregnancy and confer protection during the infant’s early months of life — when they are highly susceptible to illnesses that can be severe, such as RSV-associated lower respiratory tract infections. It can also be useful to discuss pregnancy’s impact on the immune system, which contributes to pregnant people being at higher risk for severe illness from infections like COVID-19 and flu, if contracted. The outcomes of severe illness can be dire for both the pregnant person and their pregnancy, which is why vaccination is the best mitigation option. It can also be beneficial to share with patients that some vaccines, like RSV and Tdap, are specifically for neonatal benefit, which could help patients understand why some vaccines are recommended at a specific gestational age and in each pregnancy or subsequent pregnancies.
What is known about pregnant populations that experience disparities in vaccination coverage?
While vaccination coverage among pregnant people is suboptimal, coverage estimates are often lowest among Black pregnant people, some of whom report experiencing mistreatment and discrimination during pregnancy and delivery.7 It is important to recognize that there are many intersecting factors that may impact vaccination coverage. Systemic and structural factors may prohibit some patient populations from accessing vaccinations (eg, transportation barriers, difficulty accessing adequate healthcare for those on government assistance, language barriers). To be responsive to the intersectional lived realities of each of these communities, the medical and public health community continually strives to increase trustworthiness, which can lead to increased uptake of vaccinations in these populations.
What vaccines are available and recommended for pregnant people?
Four vaccines are routinely recommended during pregnancy: Tdap, COVID-19, influenza (seasonal), and RSV (seasonal). CDC recommends getting a Tdap vaccine between the 27th and 36th week of each pregnancy, preferably during the earlier part of this time period. CDC recommends that everyone 6 months or older in the United States, including pregnant people, stay up to date on COVID-19 vaccines. A COVID-19 vaccine can be given during any trimester of pregnancy. CDC recommends an annual flu vaccine during each flu season (fall/winter) for everyone 6 months or older in the United States, including pregnant people. A flu vaccine can be given during any trimester of pregnancy. For individuals who will be between 32 and 36 weeks pregnant during September through January, CDC recommends getting an RSV vaccine. RSV season and timing of vaccination may vary depending on geography. If a pregnant patient does not get the RSV vaccine during their pregnancy, CDC recommends that their baby receive an RSV monoclonal antibody (nirsevimab) to provide additional protection during the infant’s first RSV season, if they are younger than 8 months. At this time, pregnant people who received an RSV vaccine during a previous pregnancy (last year) are not recommended to receive another RSV vaccine during pregnancy. The current recommendation is for babies born during subsequent pregnancies to receive nirsevimab. Some pregnant people may also need other vaccines, such as hepatitis B.
How can practitioners approach conversations about vaccination during pregnancy amid increasing vaccine hesitancy?
Many pregnant people who do get vaccinated describe their provider’s recommendation as an important motivator toward vaccination.8-11 Communications research suggests that practitioners can further increase trustworthiness by openly discussing potential side effects of prenatal vaccinations and providing patients with a rationale for why each vaccine is recommended. Practitioners can also utilize opportunities to communicate that the risk for severe illness from whooping cough, COVID-19, flu, and RSV in pregnancy and among neonates in the first few months of life is often higher than the risk for an adverse reaction from receiving ACIP-recommended vaccines. Finally, practitioners can consider sharing tested and refined patient education resources at least one appointment prior to the recommended administration of each vaccine, providing individuals with time to process the information they need to facilitate their vaccine decision-making process.
Some patients may be more comfortable with older, well-known prenatal vaccinations but have skepticism about newer vaccines like COVID-19 and RSV. How can practitioners respond to these concerns?
As pregnant people navigate the challenges of making health decisions that could impact their developing baby, practitioners can build trust through empathetically responding to safety concerns and questions, particularly with respect to newly authorized vaccines. Vaccine confidence may be strengthened by communicating to patients that all recommended vaccinations, including those that have been newly authorized, have been rigorously tested prior to being recommended for pregnant people. Additionally, in my clinical practice, I see that patients are often more comfortable accepting vaccines when the benefit for the baby is clearly communicated. I have been pleasantly surprised that most patients I have counseled on the new maternal RSV vaccine have been receptive, making statements like, “If this will help protect my baby from getting sick, then yes, I will get it.”
As you and your staff care for pregnant patients during fall and winter virus season, remember that a provider recommendation remains one of the strongest known predictors of vaccination uptake.12 As a trusted source of information about prenatal vaccination, consider further incorporating patient education resources to help communicate how prenatal vaccination helps pregnant people share important protection against severe illnesses with their babies.
Haben Debessai, MD, is a Gilstrap Fellow at the CDC Foundation. Debessai also serves as an Emory Obstetrics/Gynecology Adjunct Instructor at Grady Health System in Atlanta, Georgia. She disclosed no relevant conflicts of interest.
References
1. ACOG Committee Opinion No. 741: Maternal Immunization. Obstet Gynecol. 2018;131:e214-e217. doi:10.1097/AOG.0000000000002662
2. Centers for Disease Control and Prevention. Flu, Tdap, and COVID-19 vaccination coverage among pregnant women – United States, April 2024. 2024 Sep 23. 3. Centers for Disease Control and Prevention. Respiratory syncytial virus (rsv) vaccination coverage, pregnant persons. 2024 Nov 19. 4. Centers for Disease Control and Prevention. COVID-19 vaccination coverage, pregnant persons. 2024 Nov 19. 5. Centers for Disease Control and Prevention. Influenza vaccination coverage, pregnant persons. 2024 Nov 19.6. Razzaghi H et al. IMMWR Morb Mortal Wkly Rep. 2023;72:1065-1071. Published 2023 Sep 29. doi: 10.15585/mmwr.mm7239a4
7. Mohamoud YA et al. MMWR Morb Mortal Wkly Rep 2023;72:961-967. doi: https://dx.doi.org/10.15585/mmwr.mm7235e1.
8. Kiefer MK et al. Am J Obstet Gynecol MFM. 2022;4:100603. doi: 10.1016/j.ajogmf.2022.100603
9. Spires B et al. Obstet Gynecol Clin North Am. 2023;50:401-419. doi: 10.1016/j.ogc.2023.02.013
10. Wales DP et al. Public Health. 2020;179:38-44. doi: 10.1016/j.puhe.2019.10.001
11. Zimmerman M et al. J Natl Med Assoc. 2023;115:362-376. doi:10.1016/j.jnma.2023.04.003
12. Castillo E et al. Best Pract Res Clin Obstet Gynaecol. 2021;76:83-95. doi:10.1016/j.bpobgyn.2021.03.008
Vaccines recommended by the Advisory Committee on Immunization Practices (ACIP) offer important protection against severe illness for pregnant people and their babies.1 However, vaccination coverage estimates among pregnant people remain suboptimal.2-5 Additionally, some measures indicate that vaccine hesitancy among pregnant people is increasing; for example, 17.5% of surveyed pregnant women reported being very hesitant about influenza vaccination during pregnancy in 2019-2020, compared with 24.7% in 2022-2023.6 Explore updated provider toolkits and prenatal vaccination patient education resources, including fact sheets, social media assets, posters, and short videos on respiratory syncytial virus (RSV), Tdap, COVID-19, influenza, and hepatitis B.
In an interview, CDC’s Haben Debessai, MD, an adjunct instructor in obstetrics and gynecology at Emory School of Medicine, Atlanta, Georgia, contextualizes the data to help healthcare professionals communicate effectively with their pregnant patients.
What can practitioners communicate to patients about why it is important to get vaccinated during their pregnancy?
When communicating with their patients, practitioners can consider opportunities to discuss how vaccines work during pregnancy, emphasizing that prenatal vaccinations are beneficial for both the pregnant person and the fetus. It can be helpful to educate patients on how a pregnant person’s immune system can develop antibodies that will then pass to the fetus during the pregnancy and confer protection during the infant’s early months of life — when they are highly susceptible to illnesses that can be severe, such as RSV-associated lower respiratory tract infections. It can also be useful to discuss pregnancy’s impact on the immune system, which contributes to pregnant people being at higher risk for severe illness from infections like COVID-19 and flu, if contracted. The outcomes of severe illness can be dire for both the pregnant person and their pregnancy, which is why vaccination is the best mitigation option. It can also be beneficial to share with patients that some vaccines, like RSV and Tdap, are specifically for neonatal benefit, which could help patients understand why some vaccines are recommended at a specific gestational age and in each pregnancy or subsequent pregnancies.
What is known about pregnant populations that experience disparities in vaccination coverage?
While vaccination coverage among pregnant people is suboptimal, coverage estimates are often lowest among Black pregnant people, some of whom report experiencing mistreatment and discrimination during pregnancy and delivery.7 It is important to recognize that there are many intersecting factors that may impact vaccination coverage. Systemic and structural factors may prohibit some patient populations from accessing vaccinations (eg, transportation barriers, difficulty accessing adequate healthcare for those on government assistance, language barriers). To be responsive to the intersectional lived realities of each of these communities, the medical and public health community continually strives to increase trustworthiness, which can lead to increased uptake of vaccinations in these populations.
What vaccines are available and recommended for pregnant people?
Four vaccines are routinely recommended during pregnancy: Tdap, COVID-19, influenza (seasonal), and RSV (seasonal). CDC recommends getting a Tdap vaccine between the 27th and 36th week of each pregnancy, preferably during the earlier part of this time period. CDC recommends that everyone 6 months or older in the United States, including pregnant people, stay up to date on COVID-19 vaccines. A COVID-19 vaccine can be given during any trimester of pregnancy. CDC recommends an annual flu vaccine during each flu season (fall/winter) for everyone 6 months or older in the United States, including pregnant people. A flu vaccine can be given during any trimester of pregnancy. For individuals who will be between 32 and 36 weeks pregnant during September through January, CDC recommends getting an RSV vaccine. RSV season and timing of vaccination may vary depending on geography. If a pregnant patient does not get the RSV vaccine during their pregnancy, CDC recommends that their baby receive an RSV monoclonal antibody (nirsevimab) to provide additional protection during the infant’s first RSV season, if they are younger than 8 months. At this time, pregnant people who received an RSV vaccine during a previous pregnancy (last year) are not recommended to receive another RSV vaccine during pregnancy. The current recommendation is for babies born during subsequent pregnancies to receive nirsevimab. Some pregnant people may also need other vaccines, such as hepatitis B.
How can practitioners approach conversations about vaccination during pregnancy amid increasing vaccine hesitancy?
Many pregnant people who do get vaccinated describe their provider’s recommendation as an important motivator toward vaccination.8-11 Communications research suggests that practitioners can further increase trustworthiness by openly discussing potential side effects of prenatal vaccinations and providing patients with a rationale for why each vaccine is recommended. Practitioners can also utilize opportunities to communicate that the risk for severe illness from whooping cough, COVID-19, flu, and RSV in pregnancy and among neonates in the first few months of life is often higher than the risk for an adverse reaction from receiving ACIP-recommended vaccines. Finally, practitioners can consider sharing tested and refined patient education resources at least one appointment prior to the recommended administration of each vaccine, providing individuals with time to process the information they need to facilitate their vaccine decision-making process.
Some patients may be more comfortable with older, well-known prenatal vaccinations but have skepticism about newer vaccines like COVID-19 and RSV. How can practitioners respond to these concerns?
As pregnant people navigate the challenges of making health decisions that could impact their developing baby, practitioners can build trust through empathetically responding to safety concerns and questions, particularly with respect to newly authorized vaccines. Vaccine confidence may be strengthened by communicating to patients that all recommended vaccinations, including those that have been newly authorized, have been rigorously tested prior to being recommended for pregnant people. Additionally, in my clinical practice, I see that patients are often more comfortable accepting vaccines when the benefit for the baby is clearly communicated. I have been pleasantly surprised that most patients I have counseled on the new maternal RSV vaccine have been receptive, making statements like, “If this will help protect my baby from getting sick, then yes, I will get it.”
As you and your staff care for pregnant patients during fall and winter virus season, remember that a provider recommendation remains one of the strongest known predictors of vaccination uptake.12 As a trusted source of information about prenatal vaccination, consider further incorporating patient education resources to help communicate how prenatal vaccination helps pregnant people share important protection against severe illnesses with their babies.
Haben Debessai, MD, is a Gilstrap Fellow at the CDC Foundation. Debessai also serves as an Emory Obstetrics/Gynecology Adjunct Instructor at Grady Health System in Atlanta, Georgia. She disclosed no relevant conflicts of interest.
References
1. ACOG Committee Opinion No. 741: Maternal Immunization. Obstet Gynecol. 2018;131:e214-e217. doi:10.1097/AOG.0000000000002662
2. Centers for Disease Control and Prevention. Flu, Tdap, and COVID-19 vaccination coverage among pregnant women – United States, April 2024. 2024 Sep 23. 3. Centers for Disease Control and Prevention. Respiratory syncytial virus (rsv) vaccination coverage, pregnant persons. 2024 Nov 19. 4. Centers for Disease Control and Prevention. COVID-19 vaccination coverage, pregnant persons. 2024 Nov 19. 5. Centers for Disease Control and Prevention. Influenza vaccination coverage, pregnant persons. 2024 Nov 19.6. Razzaghi H et al. IMMWR Morb Mortal Wkly Rep. 2023;72:1065-1071. Published 2023 Sep 29. doi: 10.15585/mmwr.mm7239a4
7. Mohamoud YA et al. MMWR Morb Mortal Wkly Rep 2023;72:961-967. doi: https://dx.doi.org/10.15585/mmwr.mm7235e1.
8. Kiefer MK et al. Am J Obstet Gynecol MFM. 2022;4:100603. doi: 10.1016/j.ajogmf.2022.100603
9. Spires B et al. Obstet Gynecol Clin North Am. 2023;50:401-419. doi: 10.1016/j.ogc.2023.02.013
10. Wales DP et al. Public Health. 2020;179:38-44. doi: 10.1016/j.puhe.2019.10.001
11. Zimmerman M et al. J Natl Med Assoc. 2023;115:362-376. doi:10.1016/j.jnma.2023.04.003
12. Castillo E et al. Best Pract Res Clin Obstet Gynaecol. 2021;76:83-95. doi:10.1016/j.bpobgyn.2021.03.008
Vaccines recommended by the Advisory Committee on Immunization Practices (ACIP) offer important protection against severe illness for pregnant people and their babies.1 However, vaccination coverage estimates among pregnant people remain suboptimal.2-5 Additionally, some measures indicate that vaccine hesitancy among pregnant people is increasing; for example, 17.5% of surveyed pregnant women reported being very hesitant about influenza vaccination during pregnancy in 2019-2020, compared with 24.7% in 2022-2023.6 Explore updated provider toolkits and prenatal vaccination patient education resources, including fact sheets, social media assets, posters, and short videos on respiratory syncytial virus (RSV), Tdap, COVID-19, influenza, and hepatitis B.
In an interview, CDC’s Haben Debessai, MD, an adjunct instructor in obstetrics and gynecology at Emory School of Medicine, Atlanta, Georgia, contextualizes the data to help healthcare professionals communicate effectively with their pregnant patients.
What can practitioners communicate to patients about why it is important to get vaccinated during their pregnancy?
When communicating with their patients, practitioners can consider opportunities to discuss how vaccines work during pregnancy, emphasizing that prenatal vaccinations are beneficial for both the pregnant person and the fetus. It can be helpful to educate patients on how a pregnant person’s immune system can develop antibodies that will then pass to the fetus during the pregnancy and confer protection during the infant’s early months of life — when they are highly susceptible to illnesses that can be severe, such as RSV-associated lower respiratory tract infections. It can also be useful to discuss pregnancy’s impact on the immune system, which contributes to pregnant people being at higher risk for severe illness from infections like COVID-19 and flu, if contracted. The outcomes of severe illness can be dire for both the pregnant person and their pregnancy, which is why vaccination is the best mitigation option. It can also be beneficial to share with patients that some vaccines, like RSV and Tdap, are specifically for neonatal benefit, which could help patients understand why some vaccines are recommended at a specific gestational age and in each pregnancy or subsequent pregnancies.
What is known about pregnant populations that experience disparities in vaccination coverage?
While vaccination coverage among pregnant people is suboptimal, coverage estimates are often lowest among Black pregnant people, some of whom report experiencing mistreatment and discrimination during pregnancy and delivery.7 It is important to recognize that there are many intersecting factors that may impact vaccination coverage. Systemic and structural factors may prohibit some patient populations from accessing vaccinations (eg, transportation barriers, difficulty accessing adequate healthcare for those on government assistance, language barriers). To be responsive to the intersectional lived realities of each of these communities, the medical and public health community continually strives to increase trustworthiness, which can lead to increased uptake of vaccinations in these populations.
What vaccines are available and recommended for pregnant people?
Four vaccines are routinely recommended during pregnancy: Tdap, COVID-19, influenza (seasonal), and RSV (seasonal). CDC recommends getting a Tdap vaccine between the 27th and 36th week of each pregnancy, preferably during the earlier part of this time period. CDC recommends that everyone 6 months or older in the United States, including pregnant people, stay up to date on COVID-19 vaccines. A COVID-19 vaccine can be given during any trimester of pregnancy. CDC recommends an annual flu vaccine during each flu season (fall/winter) for everyone 6 months or older in the United States, including pregnant people. A flu vaccine can be given during any trimester of pregnancy. For individuals who will be between 32 and 36 weeks pregnant during September through January, CDC recommends getting an RSV vaccine. RSV season and timing of vaccination may vary depending on geography. If a pregnant patient does not get the RSV vaccine during their pregnancy, CDC recommends that their baby receive an RSV monoclonal antibody (nirsevimab) to provide additional protection during the infant’s first RSV season, if they are younger than 8 months. At this time, pregnant people who received an RSV vaccine during a previous pregnancy (last year) are not recommended to receive another RSV vaccine during pregnancy. The current recommendation is for babies born during subsequent pregnancies to receive nirsevimab. Some pregnant people may also need other vaccines, such as hepatitis B.
How can practitioners approach conversations about vaccination during pregnancy amid increasing vaccine hesitancy?
Many pregnant people who do get vaccinated describe their provider’s recommendation as an important motivator toward vaccination.8-11 Communications research suggests that practitioners can further increase trustworthiness by openly discussing potential side effects of prenatal vaccinations and providing patients with a rationale for why each vaccine is recommended. Practitioners can also utilize opportunities to communicate that the risk for severe illness from whooping cough, COVID-19, flu, and RSV in pregnancy and among neonates in the first few months of life is often higher than the risk for an adverse reaction from receiving ACIP-recommended vaccines. Finally, practitioners can consider sharing tested and refined patient education resources at least one appointment prior to the recommended administration of each vaccine, providing individuals with time to process the information they need to facilitate their vaccine decision-making process.
Some patients may be more comfortable with older, well-known prenatal vaccinations but have skepticism about newer vaccines like COVID-19 and RSV. How can practitioners respond to these concerns?
As pregnant people navigate the challenges of making health decisions that could impact their developing baby, practitioners can build trust through empathetically responding to safety concerns and questions, particularly with respect to newly authorized vaccines. Vaccine confidence may be strengthened by communicating to patients that all recommended vaccinations, including those that have been newly authorized, have been rigorously tested prior to being recommended for pregnant people. Additionally, in my clinical practice, I see that patients are often more comfortable accepting vaccines when the benefit for the baby is clearly communicated. I have been pleasantly surprised that most patients I have counseled on the new maternal RSV vaccine have been receptive, making statements like, “If this will help protect my baby from getting sick, then yes, I will get it.”
As you and your staff care for pregnant patients during fall and winter virus season, remember that a provider recommendation remains one of the strongest known predictors of vaccination uptake.12 As a trusted source of information about prenatal vaccination, consider further incorporating patient education resources to help communicate how prenatal vaccination helps pregnant people share important protection against severe illnesses with their babies.
Haben Debessai, MD, is a Gilstrap Fellow at the CDC Foundation. Debessai also serves as an Emory Obstetrics/Gynecology Adjunct Instructor at Grady Health System in Atlanta, Georgia. She disclosed no relevant conflicts of interest.
References
1. ACOG Committee Opinion No. 741: Maternal Immunization. Obstet Gynecol. 2018;131:e214-e217. doi:10.1097/AOG.0000000000002662
2. Centers for Disease Control and Prevention. Flu, Tdap, and COVID-19 vaccination coverage among pregnant women – United States, April 2024. 2024 Sep 23. 3. Centers for Disease Control and Prevention. Respiratory syncytial virus (rsv) vaccination coverage, pregnant persons. 2024 Nov 19. 4. Centers for Disease Control and Prevention. COVID-19 vaccination coverage, pregnant persons. 2024 Nov 19. 5. Centers for Disease Control and Prevention. Influenza vaccination coverage, pregnant persons. 2024 Nov 19.6. Razzaghi H et al. IMMWR Morb Mortal Wkly Rep. 2023;72:1065-1071. Published 2023 Sep 29. doi: 10.15585/mmwr.mm7239a4
7. Mohamoud YA et al. MMWR Morb Mortal Wkly Rep 2023;72:961-967. doi: https://dx.doi.org/10.15585/mmwr.mm7235e1.
8. Kiefer MK et al. Am J Obstet Gynecol MFM. 2022;4:100603. doi: 10.1016/j.ajogmf.2022.100603
9. Spires B et al. Obstet Gynecol Clin North Am. 2023;50:401-419. doi: 10.1016/j.ogc.2023.02.013
10. Wales DP et al. Public Health. 2020;179:38-44. doi: 10.1016/j.puhe.2019.10.001
11. Zimmerman M et al. J Natl Med Assoc. 2023;115:362-376. doi:10.1016/j.jnma.2023.04.003
12. Castillo E et al. Best Pract Res Clin Obstet Gynaecol. 2021;76:83-95. doi:10.1016/j.bpobgyn.2021.03.008
Does Intensive Follow-Up Testing Improve Survival in CRC?
TOPLINE:
, according to findings from a secondary analysis.
METHODOLOGY:
- After curative surgery for CRC, intensive patient follow-up is common in clinical practice. However, there’s limited evidence to suggest that more frequent testing provides a long-term survival benefit.
- In the COLOFOL trial, patients with stage II or III CRC who had undergone curative resection were randomly assigned to either high-frequency follow-up (CT scans and CEA screening at 6, 12, 18, 24, and 36 months) or low-frequency follow-up (testing at 12 and 36 months) after surgery.
- This secondary analysis of the COLOFOL trial included 2456 patients (median age, 65 years), 1227 of whom received high-frequency follow-up and 1229 of whom received low-frequency follow-up.
- The main outcome of the secondary analysis was 10-year overall mortality and CRC–specific mortality rates.
- The analysis included both intention-to-treat and per-protocol approaches, with outcomes measured through December 2020.
TAKEAWAY:
- In the intention-to-treat analysis, the 10-year overall mortality rates were similar between the high- and low-frequency follow-up groups — 27.1% and 28.4%, respectively (risk difference, 1.3%; P = .46).
- A per-protocol analysis confirmed these findings: The 10-year overall mortality risk was 26.4% in the high-frequency group and 27.8% in the low-frequency group.
- The 10-year CRC–specific mortality rate was also similar between the high-frequency and low-frequency groups — 15.6% and 16.0%, respectively — (risk difference, 0.4%; P = .72). The same pattern was seen in the per-protocol analysis, which found a 10-year CRC–specific mortality risk of 15.6% in the high-frequency group and 15.9% in the low-frequency group.
- Subgroup analyses by cancer stage and location (rectal and colon) also revealed no significant differences in mortality outcomes between the two follow-up groups.
IN PRACTICE:
“This secondary analysis of the COLOFOL randomized clinical trial found that, among patients with stage II or III colorectal cancer, more frequent follow-up testing with CT scan and CEA screening, compared with less frequent follow-up, did not result in a significant rate reduction in 10-year overall mortality or colorectal cancer-specific mortality,” the authors concluded. “The results of this trial should be considered as the evidence base for updating clinical guidelines.”
SOURCE:
The study, led by Henrik Toft Sørensen, MD, PhD, DMSc, DSc, Aarhus University Hospital and Aarhus University, Aarhus, Denmark, was published online in JAMA Network Open.
LIMITATIONS:
The staff turnover at recruitment centers potentially affected protocol adherence. The inability to blind patients and physicians to the follow-up frequency was another limitation. The low-frequency follow-up protocol was less intensive than that recommended in the current guidelines by the National Comprehensive Cancer Network and the American Society of Clinical Oncology, potentially limiting comparisons to current standard practices.
DISCLOSURES:
The initial trial received unrestricted grants from multiple organizations including the Nordic Cancer Union, A.P. Møller Foundation, Beckett Foundation, Danish Cancer Society, and Swedish Cancer Foundation project. The authors reported no relevant conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
, according to findings from a secondary analysis.
METHODOLOGY:
- After curative surgery for CRC, intensive patient follow-up is common in clinical practice. However, there’s limited evidence to suggest that more frequent testing provides a long-term survival benefit.
- In the COLOFOL trial, patients with stage II or III CRC who had undergone curative resection were randomly assigned to either high-frequency follow-up (CT scans and CEA screening at 6, 12, 18, 24, and 36 months) or low-frequency follow-up (testing at 12 and 36 months) after surgery.
- This secondary analysis of the COLOFOL trial included 2456 patients (median age, 65 years), 1227 of whom received high-frequency follow-up and 1229 of whom received low-frequency follow-up.
- The main outcome of the secondary analysis was 10-year overall mortality and CRC–specific mortality rates.
- The analysis included both intention-to-treat and per-protocol approaches, with outcomes measured through December 2020.
TAKEAWAY:
- In the intention-to-treat analysis, the 10-year overall mortality rates were similar between the high- and low-frequency follow-up groups — 27.1% and 28.4%, respectively (risk difference, 1.3%; P = .46).
- A per-protocol analysis confirmed these findings: The 10-year overall mortality risk was 26.4% in the high-frequency group and 27.8% in the low-frequency group.
- The 10-year CRC–specific mortality rate was also similar between the high-frequency and low-frequency groups — 15.6% and 16.0%, respectively — (risk difference, 0.4%; P = .72). The same pattern was seen in the per-protocol analysis, which found a 10-year CRC–specific mortality risk of 15.6% in the high-frequency group and 15.9% in the low-frequency group.
- Subgroup analyses by cancer stage and location (rectal and colon) also revealed no significant differences in mortality outcomes between the two follow-up groups.
IN PRACTICE:
“This secondary analysis of the COLOFOL randomized clinical trial found that, among patients with stage II or III colorectal cancer, more frequent follow-up testing with CT scan and CEA screening, compared with less frequent follow-up, did not result in a significant rate reduction in 10-year overall mortality or colorectal cancer-specific mortality,” the authors concluded. “The results of this trial should be considered as the evidence base for updating clinical guidelines.”
SOURCE:
The study, led by Henrik Toft Sørensen, MD, PhD, DMSc, DSc, Aarhus University Hospital and Aarhus University, Aarhus, Denmark, was published online in JAMA Network Open.
LIMITATIONS:
The staff turnover at recruitment centers potentially affected protocol adherence. The inability to blind patients and physicians to the follow-up frequency was another limitation. The low-frequency follow-up protocol was less intensive than that recommended in the current guidelines by the National Comprehensive Cancer Network and the American Society of Clinical Oncology, potentially limiting comparisons to current standard practices.
DISCLOSURES:
The initial trial received unrestricted grants from multiple organizations including the Nordic Cancer Union, A.P. Møller Foundation, Beckett Foundation, Danish Cancer Society, and Swedish Cancer Foundation project. The authors reported no relevant conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
, according to findings from a secondary analysis.
METHODOLOGY:
- After curative surgery for CRC, intensive patient follow-up is common in clinical practice. However, there’s limited evidence to suggest that more frequent testing provides a long-term survival benefit.
- In the COLOFOL trial, patients with stage II or III CRC who had undergone curative resection were randomly assigned to either high-frequency follow-up (CT scans and CEA screening at 6, 12, 18, 24, and 36 months) or low-frequency follow-up (testing at 12 and 36 months) after surgery.
- This secondary analysis of the COLOFOL trial included 2456 patients (median age, 65 years), 1227 of whom received high-frequency follow-up and 1229 of whom received low-frequency follow-up.
- The main outcome of the secondary analysis was 10-year overall mortality and CRC–specific mortality rates.
- The analysis included both intention-to-treat and per-protocol approaches, with outcomes measured through December 2020.
TAKEAWAY:
- In the intention-to-treat analysis, the 10-year overall mortality rates were similar between the high- and low-frequency follow-up groups — 27.1% and 28.4%, respectively (risk difference, 1.3%; P = .46).
- A per-protocol analysis confirmed these findings: The 10-year overall mortality risk was 26.4% in the high-frequency group and 27.8% in the low-frequency group.
- The 10-year CRC–specific mortality rate was also similar between the high-frequency and low-frequency groups — 15.6% and 16.0%, respectively — (risk difference, 0.4%; P = .72). The same pattern was seen in the per-protocol analysis, which found a 10-year CRC–specific mortality risk of 15.6% in the high-frequency group and 15.9% in the low-frequency group.
- Subgroup analyses by cancer stage and location (rectal and colon) also revealed no significant differences in mortality outcomes between the two follow-up groups.
IN PRACTICE:
“This secondary analysis of the COLOFOL randomized clinical trial found that, among patients with stage II or III colorectal cancer, more frequent follow-up testing with CT scan and CEA screening, compared with less frequent follow-up, did not result in a significant rate reduction in 10-year overall mortality or colorectal cancer-specific mortality,” the authors concluded. “The results of this trial should be considered as the evidence base for updating clinical guidelines.”
SOURCE:
The study, led by Henrik Toft Sørensen, MD, PhD, DMSc, DSc, Aarhus University Hospital and Aarhus University, Aarhus, Denmark, was published online in JAMA Network Open.
LIMITATIONS:
The staff turnover at recruitment centers potentially affected protocol adherence. The inability to blind patients and physicians to the follow-up frequency was another limitation. The low-frequency follow-up protocol was less intensive than that recommended in the current guidelines by the National Comprehensive Cancer Network and the American Society of Clinical Oncology, potentially limiting comparisons to current standard practices.
DISCLOSURES:
The initial trial received unrestricted grants from multiple organizations including the Nordic Cancer Union, A.P. Møller Foundation, Beckett Foundation, Danish Cancer Society, and Swedish Cancer Foundation project. The authors reported no relevant conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Veterans Enroll in VA MDMA and PTSD Phase 2 Trial
The first study funded by the US Department of Veterans Affairs (VA) for psychedelic-assisted therapy since the 1960s is currently enrolling veterans. Researchers are set to evaluate the potential of methylenedioxymethamphetamine (MDMA) for veterans with posttraumatic stress disorder (PTSD) and alcohol use disorder.
The grant—about $1.5 million over 5 years—will fund a randomized, placebo-controlled trial at the Providence VA Medical Center in Rhode Island and the West Haven VA Medical Center in Connecticut by VA researchers affiliated with Brown University and Yale University. Pharmaceutical-grade MDMA will be used, and some participants will be randomly selected to receive an active placebo (lower dose of MDMA). MDMA is a psychedelic compound believed to increase emotional openness, reduce fear, and promote introspection during therapy.
The study is part of the VA’s broader effort to gather definitive scientific evidence on the potential efficacy and safety of psychedelic compounds used in conjunction with psychotherapy to treat PTSD, depression, and related mental health conditions. Veterans service organizations like the American Legion and Disabled American Veterans in addition to mental health clinician groups have also called for expanded research into psychedelic compounds. The National Defense Authorization Act for fiscal year 2024 also authorized the US Department of Defense to perform research on psychedelics within military populations.
In September 2023, VA and other federal clinicians, scientists, and policy makers assessed the state of scientific evidence regarding psychedelic-assisted therapies. The working groups provided advice to VA leadership, including the recommendation for the VA to begin funding its own research into these areas of care.
The guidance was based on previously published studies that have found encouraging results but included few or no veteran participants. For example, a confirmatory phase 3 study by the MAPP2 Study Collaborator Group involved 104 patients, of whom only 16 were veterans.
However, the findings of that study underscored the potential of the treatment: MDMA significantly improved PTSD symptoms and functional impairment, compared with placebo with therapy over 18 weeks. Notably, 45 of 52 (86%) participants treated with MDMA achieved a clinically meaningful benefit, and 37 of 52 (71%) participants no longer met criteria for PTSD by the end of the study. Consistent with an earlier study, no new major safety issues were reported. Common treatment-emergent adverse effects were like those of previous research and consistent with expected effects of MDMA. MDMA did not appear to increase the risk of suicidal ideation, and no suicidal behavior was observed.
The VA researchers has conducted a limited number of small studies on psychedelics in VA facilities using non-VA funding. “VA is on the cutting edge of clinical research for veteran health, including in the investigation of psychedelics for mental health,” said Under Secretary for Health Shereef Elnahal, MD.
The FDA granted breakthrough therapy status for MDMA in the treatment of PTSD and psilocybin for the treatment of depression in 2017 and 2018, respectively, based on promising preliminary research evidence. However, in June 2024 an FDA panel voted against approving a MDMA therapy for PTSD, citing concerns about research practices, a lack of diversity in the trials, and a failure to provide data on adverse effects such as potential for abuse.
In August, the FDA formally rejected the treatment and called for another phase 3 study. “The FDA’s decision is disgraceful,” said Heroic Hearts Project, a veterans organization that had lobbied for FDA approval citing the many veteran suicides in a statement. “This is the epitome of bureaucratic red tape—and the result is people will keep dying.”
Meanwhile, VA Press Secretary Terrence Hayes said in a statement: “VA is committed to high-quality research that safely promotes the health of our nation’s Veterans … VA anticipates that additional insights on the efficacy and safety of these therapies will add to the broader body of knowledge on MDMA-assisted psychotherapy.”
The first study funded by the US Department of Veterans Affairs (VA) for psychedelic-assisted therapy since the 1960s is currently enrolling veterans. Researchers are set to evaluate the potential of methylenedioxymethamphetamine (MDMA) for veterans with posttraumatic stress disorder (PTSD) and alcohol use disorder.
The grant—about $1.5 million over 5 years—will fund a randomized, placebo-controlled trial at the Providence VA Medical Center in Rhode Island and the West Haven VA Medical Center in Connecticut by VA researchers affiliated with Brown University and Yale University. Pharmaceutical-grade MDMA will be used, and some participants will be randomly selected to receive an active placebo (lower dose of MDMA). MDMA is a psychedelic compound believed to increase emotional openness, reduce fear, and promote introspection during therapy.
The study is part of the VA’s broader effort to gather definitive scientific evidence on the potential efficacy and safety of psychedelic compounds used in conjunction with psychotherapy to treat PTSD, depression, and related mental health conditions. Veterans service organizations like the American Legion and Disabled American Veterans in addition to mental health clinician groups have also called for expanded research into psychedelic compounds. The National Defense Authorization Act for fiscal year 2024 also authorized the US Department of Defense to perform research on psychedelics within military populations.
In September 2023, VA and other federal clinicians, scientists, and policy makers assessed the state of scientific evidence regarding psychedelic-assisted therapies. The working groups provided advice to VA leadership, including the recommendation for the VA to begin funding its own research into these areas of care.
The guidance was based on previously published studies that have found encouraging results but included few or no veteran participants. For example, a confirmatory phase 3 study by the MAPP2 Study Collaborator Group involved 104 patients, of whom only 16 were veterans.
However, the findings of that study underscored the potential of the treatment: MDMA significantly improved PTSD symptoms and functional impairment, compared with placebo with therapy over 18 weeks. Notably, 45 of 52 (86%) participants treated with MDMA achieved a clinically meaningful benefit, and 37 of 52 (71%) participants no longer met criteria for PTSD by the end of the study. Consistent with an earlier study, no new major safety issues were reported. Common treatment-emergent adverse effects were like those of previous research and consistent with expected effects of MDMA. MDMA did not appear to increase the risk of suicidal ideation, and no suicidal behavior was observed.
The VA researchers has conducted a limited number of small studies on psychedelics in VA facilities using non-VA funding. “VA is on the cutting edge of clinical research for veteran health, including in the investigation of psychedelics for mental health,” said Under Secretary for Health Shereef Elnahal, MD.
The FDA granted breakthrough therapy status for MDMA in the treatment of PTSD and psilocybin for the treatment of depression in 2017 and 2018, respectively, based on promising preliminary research evidence. However, in June 2024 an FDA panel voted against approving a MDMA therapy for PTSD, citing concerns about research practices, a lack of diversity in the trials, and a failure to provide data on adverse effects such as potential for abuse.
In August, the FDA formally rejected the treatment and called for another phase 3 study. “The FDA’s decision is disgraceful,” said Heroic Hearts Project, a veterans organization that had lobbied for FDA approval citing the many veteran suicides in a statement. “This is the epitome of bureaucratic red tape—and the result is people will keep dying.”
Meanwhile, VA Press Secretary Terrence Hayes said in a statement: “VA is committed to high-quality research that safely promotes the health of our nation’s Veterans … VA anticipates that additional insights on the efficacy and safety of these therapies will add to the broader body of knowledge on MDMA-assisted psychotherapy.”
The first study funded by the US Department of Veterans Affairs (VA) for psychedelic-assisted therapy since the 1960s is currently enrolling veterans. Researchers are set to evaluate the potential of methylenedioxymethamphetamine (MDMA) for veterans with posttraumatic stress disorder (PTSD) and alcohol use disorder.
The grant—about $1.5 million over 5 years—will fund a randomized, placebo-controlled trial at the Providence VA Medical Center in Rhode Island and the West Haven VA Medical Center in Connecticut by VA researchers affiliated with Brown University and Yale University. Pharmaceutical-grade MDMA will be used, and some participants will be randomly selected to receive an active placebo (lower dose of MDMA). MDMA is a psychedelic compound believed to increase emotional openness, reduce fear, and promote introspection during therapy.
The study is part of the VA’s broader effort to gather definitive scientific evidence on the potential efficacy and safety of psychedelic compounds used in conjunction with psychotherapy to treat PTSD, depression, and related mental health conditions. Veterans service organizations like the American Legion and Disabled American Veterans in addition to mental health clinician groups have also called for expanded research into psychedelic compounds. The National Defense Authorization Act for fiscal year 2024 also authorized the US Department of Defense to perform research on psychedelics within military populations.
In September 2023, VA and other federal clinicians, scientists, and policy makers assessed the state of scientific evidence regarding psychedelic-assisted therapies. The working groups provided advice to VA leadership, including the recommendation for the VA to begin funding its own research into these areas of care.
The guidance was based on previously published studies that have found encouraging results but included few or no veteran participants. For example, a confirmatory phase 3 study by the MAPP2 Study Collaborator Group involved 104 patients, of whom only 16 were veterans.
However, the findings of that study underscored the potential of the treatment: MDMA significantly improved PTSD symptoms and functional impairment, compared with placebo with therapy over 18 weeks. Notably, 45 of 52 (86%) participants treated with MDMA achieved a clinically meaningful benefit, and 37 of 52 (71%) participants no longer met criteria for PTSD by the end of the study. Consistent with an earlier study, no new major safety issues were reported. Common treatment-emergent adverse effects were like those of previous research and consistent with expected effects of MDMA. MDMA did not appear to increase the risk of suicidal ideation, and no suicidal behavior was observed.
The VA researchers has conducted a limited number of small studies on psychedelics in VA facilities using non-VA funding. “VA is on the cutting edge of clinical research for veteran health, including in the investigation of psychedelics for mental health,” said Under Secretary for Health Shereef Elnahal, MD.
The FDA granted breakthrough therapy status for MDMA in the treatment of PTSD and psilocybin for the treatment of depression in 2017 and 2018, respectively, based on promising preliminary research evidence. However, in June 2024 an FDA panel voted against approving a MDMA therapy for PTSD, citing concerns about research practices, a lack of diversity in the trials, and a failure to provide data on adverse effects such as potential for abuse.
In August, the FDA formally rejected the treatment and called for another phase 3 study. “The FDA’s decision is disgraceful,” said Heroic Hearts Project, a veterans organization that had lobbied for FDA approval citing the many veteran suicides in a statement. “This is the epitome of bureaucratic red tape—and the result is people will keep dying.”
Meanwhile, VA Press Secretary Terrence Hayes said in a statement: “VA is committed to high-quality research that safely promotes the health of our nation’s Veterans … VA anticipates that additional insights on the efficacy and safety of these therapies will add to the broader body of knowledge on MDMA-assisted psychotherapy.”