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Middle-aged women who did many short bursts of vigorous-intensity exercise — amounting to as little as 3 min/d — had a 45% lower risk for major adverse cardiovascular events, reported investigators.

This doesn’t mean just a walk in the park, explained Emmanuel Stamatakis, PhD, a researcher with the University of Sydney in Australia. He said the activity can be as short as 20-30 seconds, but it must be high intensity — “movement that gets us out of breath, gets our heart rate up” — and repeated several times daily.

Stamatakis and colleagues call this type of exercise vigorous intermittent lifestyle physical activity, and it involves intense movement in very short bouts that are part of daily life, like a quick stair climb or running for a bus.

In their study, published in The British Journal of Sports Medicine, most exercise bursts were less than a minute, and few were over 2 minutes.

This is the third study in which the international network of researchers has shown the health benefits of vigorous physical activity. They are upending the common view that “any physical activity under 10 minutes doesn’t count for health,” said Stamatakis.

 

Bursts of Energy

The three studies looked at data for thousands of middle-aged men and women aged 40-69 years collected in the UK Biobank. Their daily activity was measured using accelerometers worn on the wrist for 7 days. This is preferable to survey data, which Stamatakis said is often unreliable.

The analysis looked at people who reported that they did not do any other exercise, taking no more than a single walk during the week. Then their cardiovascular health was tracked for almost 8 years.

Previous studies of the same data have shown benefits of vigorous physical activity for risk for cancer and for risk for death, both overall and due to cardiovascular disease or cancer.

In this study, women who did even less than 2 minutes of vigorous physical activity a day but no other exercise had a lower risk for all major cardiovascular events and for heart attack and heart failure. Women who did the median daily vigorous exercise time — 3.4 minutes — had an even lower risk. In fact, in women, there was a direct relationship between daily exercise time and risk reduction.

In men, the study showed some benefit of vigorous physical activity, but the relationship was not as clear, said Stamatakis. “The effects were much subtler and, in most cases, did not reach statistical significance.”

 

Good News for Women

Stamatakis said it is unclear why there was such a gap in the benefits between men and women. “Studies like ours are not designed to explain the difference,” he added.

“This study does not show that [vigorous physical activity] is effective in women but not men,” said Yasina Somani, PhD, an exercise physiology researcher at the University of Leeds in England, who was not involved in the work. Because the study just observed people’s behavior, rather than studying people in controlled conditions such as a lab, she said you cannot reach conclusions about the benefits for men. “You still need some further research.”

Somani pointed out that a study like this one cannot determine how vigorous physical activity protects the heart. In her research, she has studied the ways that exercise exerts effects on the heart. Exercise stresses the cardiovascular system, leading to physiological adaptation, and this may differ between men and women.

“Seeing this article motivates me to understand why women are responding even more than men. Do men need a greater volume of this exercise? If you’re carrying a 10-pound grocery bag up a flight of stairs, who is getting the greater stimulus?”

In fact, the study researchers think women’s exercise bursts might simply be harder for them. For some of the sample, the researchers had data on maximal oxygen consumption (VO₂ max), a measure of cardiovascular fitness. During vigorous physical activity bouts, this measure showed that the effort for women averaged 83.2% of VO₂ max, whereas it was 70.5% for men.

Somani said, “For men, there needs to be more clarity and more understanding of what it is that provides that stimulus — the intensity, the mode of exercise.”

“People are very surprised that 20-30 seconds of high-intensity exercise several times a day can make a difference to their health,” said Stamatakis. “They think they need to do structured exercise,” such as at a gym, to benefit.

He said the message that even quick exercise hits are beneficial can help healthcare professionals foster preventive behavior. “Any health professional who deals with patients on a regular basis knows that physical activity is important for people’s overall well-being and prevention of chronic disease.” The difficulty is that many people cannot or simply do not exercise. “Some people cannot afford it, and some do not have the motivation to stick to a structured exercise program.”

But anyone can do vigorous physical activity, he said. “The entry level is very low. There are no special preparations, no special clothes, no money to spend, no time commitment. You are interspersing exercise across your day.”

The researchers are currently studying how to foster vigorous physical activity in everyday behavior. “We are codesigning programs with participants, engaging with middle-aged people who have never exercised, so that the program has the highest chance to be successful.” Stamatakis is looking at encouraging vigorous physical activity through wearable devices and coaching, including online options.

Somani said the study adds weight to the message that any exercise is worthwhile. “These are simple choices that you can make that don’t require engaging in more structured exercise. Whatever you can do — little things outside of a gym — can have a lot of benefit for you.”

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

Middle-aged women who did many short bursts of vigorous-intensity exercise — amounting to as little as 3 min/d — had a 45% lower risk for major adverse cardiovascular events, reported investigators.

This doesn’t mean just a walk in the park, explained Emmanuel Stamatakis, PhD, a researcher with the University of Sydney in Australia. He said the activity can be as short as 20-30 seconds, but it must be high intensity — “movement that gets us out of breath, gets our heart rate up” — and repeated several times daily.

Stamatakis and colleagues call this type of exercise vigorous intermittent lifestyle physical activity, and it involves intense movement in very short bouts that are part of daily life, like a quick stair climb or running for a bus.

In their study, published in The British Journal of Sports Medicine, most exercise bursts were less than a minute, and few were over 2 minutes.

This is the third study in which the international network of researchers has shown the health benefits of vigorous physical activity. They are upending the common view that “any physical activity under 10 minutes doesn’t count for health,” said Stamatakis.

 

Bursts of Energy

The three studies looked at data for thousands of middle-aged men and women aged 40-69 years collected in the UK Biobank. Their daily activity was measured using accelerometers worn on the wrist for 7 days. This is preferable to survey data, which Stamatakis said is often unreliable.

The analysis looked at people who reported that they did not do any other exercise, taking no more than a single walk during the week. Then their cardiovascular health was tracked for almost 8 years.

Previous studies of the same data have shown benefits of vigorous physical activity for risk for cancer and for risk for death, both overall and due to cardiovascular disease or cancer.

In this study, women who did even less than 2 minutes of vigorous physical activity a day but no other exercise had a lower risk for all major cardiovascular events and for heart attack and heart failure. Women who did the median daily vigorous exercise time — 3.4 minutes — had an even lower risk. In fact, in women, there was a direct relationship between daily exercise time and risk reduction.

In men, the study showed some benefit of vigorous physical activity, but the relationship was not as clear, said Stamatakis. “The effects were much subtler and, in most cases, did not reach statistical significance.”

 

Good News for Women

Stamatakis said it is unclear why there was such a gap in the benefits between men and women. “Studies like ours are not designed to explain the difference,” he added.

“This study does not show that [vigorous physical activity] is effective in women but not men,” said Yasina Somani, PhD, an exercise physiology researcher at the University of Leeds in England, who was not involved in the work. Because the study just observed people’s behavior, rather than studying people in controlled conditions such as a lab, she said you cannot reach conclusions about the benefits for men. “You still need some further research.”

Somani pointed out that a study like this one cannot determine how vigorous physical activity protects the heart. In her research, she has studied the ways that exercise exerts effects on the heart. Exercise stresses the cardiovascular system, leading to physiological adaptation, and this may differ between men and women.

“Seeing this article motivates me to understand why women are responding even more than men. Do men need a greater volume of this exercise? If you’re carrying a 10-pound grocery bag up a flight of stairs, who is getting the greater stimulus?”

In fact, the study researchers think women’s exercise bursts might simply be harder for them. For some of the sample, the researchers had data on maximal oxygen consumption (VO₂ max), a measure of cardiovascular fitness. During vigorous physical activity bouts, this measure showed that the effort for women averaged 83.2% of VO₂ max, whereas it was 70.5% for men.

Somani said, “For men, there needs to be more clarity and more understanding of what it is that provides that stimulus — the intensity, the mode of exercise.”

“People are very surprised that 20-30 seconds of high-intensity exercise several times a day can make a difference to their health,” said Stamatakis. “They think they need to do structured exercise,” such as at a gym, to benefit.

He said the message that even quick exercise hits are beneficial can help healthcare professionals foster preventive behavior. “Any health professional who deals with patients on a regular basis knows that physical activity is important for people’s overall well-being and prevention of chronic disease.” The difficulty is that many people cannot or simply do not exercise. “Some people cannot afford it, and some do not have the motivation to stick to a structured exercise program.”

But anyone can do vigorous physical activity, he said. “The entry level is very low. There are no special preparations, no special clothes, no money to spend, no time commitment. You are interspersing exercise across your day.”

The researchers are currently studying how to foster vigorous physical activity in everyday behavior. “We are codesigning programs with participants, engaging with middle-aged people who have never exercised, so that the program has the highest chance to be successful.” Stamatakis is looking at encouraging vigorous physical activity through wearable devices and coaching, including online options.

Somani said the study adds weight to the message that any exercise is worthwhile. “These are simple choices that you can make that don’t require engaging in more structured exercise. Whatever you can do — little things outside of a gym — can have a lot of benefit for you.”

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

Middle-aged women who did many short bursts of vigorous-intensity exercise — amounting to as little as 3 min/d — had a 45% lower risk for major adverse cardiovascular events, reported investigators.

This doesn’t mean just a walk in the park, explained Emmanuel Stamatakis, PhD, a researcher with the University of Sydney in Australia. He said the activity can be as short as 20-30 seconds, but it must be high intensity — “movement that gets us out of breath, gets our heart rate up” — and repeated several times daily.

Stamatakis and colleagues call this type of exercise vigorous intermittent lifestyle physical activity, and it involves intense movement in very short bouts that are part of daily life, like a quick stair climb or running for a bus.

In their study, published in The British Journal of Sports Medicine, most exercise bursts were less than a minute, and few were over 2 minutes.

This is the third study in which the international network of researchers has shown the health benefits of vigorous physical activity. They are upending the common view that “any physical activity under 10 minutes doesn’t count for health,” said Stamatakis.

 

Bursts of Energy

The three studies looked at data for thousands of middle-aged men and women aged 40-69 years collected in the UK Biobank. Their daily activity was measured using accelerometers worn on the wrist for 7 days. This is preferable to survey data, which Stamatakis said is often unreliable.

The analysis looked at people who reported that they did not do any other exercise, taking no more than a single walk during the week. Then their cardiovascular health was tracked for almost 8 years.

Previous studies of the same data have shown benefits of vigorous physical activity for risk for cancer and for risk for death, both overall and due to cardiovascular disease or cancer.

In this study, women who did even less than 2 minutes of vigorous physical activity a day but no other exercise had a lower risk for all major cardiovascular events and for heart attack and heart failure. Women who did the median daily vigorous exercise time — 3.4 minutes — had an even lower risk. In fact, in women, there was a direct relationship between daily exercise time and risk reduction.

In men, the study showed some benefit of vigorous physical activity, but the relationship was not as clear, said Stamatakis. “The effects were much subtler and, in most cases, did not reach statistical significance.”

 

Good News for Women

Stamatakis said it is unclear why there was such a gap in the benefits between men and women. “Studies like ours are not designed to explain the difference,” he added.

“This study does not show that [vigorous physical activity] is effective in women but not men,” said Yasina Somani, PhD, an exercise physiology researcher at the University of Leeds in England, who was not involved in the work. Because the study just observed people’s behavior, rather than studying people in controlled conditions such as a lab, she said you cannot reach conclusions about the benefits for men. “You still need some further research.”

Somani pointed out that a study like this one cannot determine how vigorous physical activity protects the heart. In her research, she has studied the ways that exercise exerts effects on the heart. Exercise stresses the cardiovascular system, leading to physiological adaptation, and this may differ between men and women.

“Seeing this article motivates me to understand why women are responding even more than men. Do men need a greater volume of this exercise? If you’re carrying a 10-pound grocery bag up a flight of stairs, who is getting the greater stimulus?”

In fact, the study researchers think women’s exercise bursts might simply be harder for them. For some of the sample, the researchers had data on maximal oxygen consumption (VO₂ max), a measure of cardiovascular fitness. During vigorous physical activity bouts, this measure showed that the effort for women averaged 83.2% of VO₂ max, whereas it was 70.5% for men.

Somani said, “For men, there needs to be more clarity and more understanding of what it is that provides that stimulus — the intensity, the mode of exercise.”

“People are very surprised that 20-30 seconds of high-intensity exercise several times a day can make a difference to their health,” said Stamatakis. “They think they need to do structured exercise,” such as at a gym, to benefit.

He said the message that even quick exercise hits are beneficial can help healthcare professionals foster preventive behavior. “Any health professional who deals with patients on a regular basis knows that physical activity is important for people’s overall well-being and prevention of chronic disease.” The difficulty is that many people cannot or simply do not exercise. “Some people cannot afford it, and some do not have the motivation to stick to a structured exercise program.”

But anyone can do vigorous physical activity, he said. “The entry level is very low. There are no special preparations, no special clothes, no money to spend, no time commitment. You are interspersing exercise across your day.”

The researchers are currently studying how to foster vigorous physical activity in everyday behavior. “We are codesigning programs with participants, engaging with middle-aged people who have never exercised, so that the program has the highest chance to be successful.” Stamatakis is looking at encouraging vigorous physical activity through wearable devices and coaching, including online options.

Somani said the study adds weight to the message that any exercise is worthwhile. “These are simple choices that you can make that don’t require engaging in more structured exercise. Whatever you can do — little things outside of a gym — can have a lot of benefit for you.”

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

The Food and Drug Administration (FDA) has approved the obesity treatment tirzepatide (Zepbound, Eli Lilly) for treating moderate to severe obstructive sleep apnea (OSA) in adults with obesity.

The new indication is for use in combination with reduced-calorie diet and increased physical activity. The once-weekly injectable is the first-ever drug treatment for OSA. Until now, OSA treatment has focused on mechanical support during sleep in the form of positive airway pressure (PAP) therapy. 

“Today’s approval marks the first drug treatment option for certain patients with obstructive sleep apnea,” said Sally Seymour, MD, director of the Division of Pulmonology, Allergy, and Critical Care in the FDA’s Center for Drug Evaluation and Research. “This is a major step forward for patients with obstructive sleep apnea.”

Excess weight is a major risk factor for OSA, in which the upper airways become blocked multiple times during sleep and obstruct breathing. The condition causes loud snoring, recurrent awakenings, and daytime sleepiness. It is also associated with cardiovascular disease.

Tirzepatide, a dual glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide receptor agonist, was initially approved with brand name Mounjaro in May 2022 for the treatment of type 2 diabetes, and as Zepbound for weight loss in November 2023.

The new OSA approval was based on two phase 3, double-blind randomized controlled trials, SURMOUNT-OSA, in patients with obesity and moderate to severe OSA, conducted at 60 sites in nine countries. Results from both were presented in June 2024 at the annual Scientific Sessions of the American Diabetes Association and were simultaneously published in The New England Journal of Medicine.

The first trial enrolled 469 participants who were unable or unwilling to use PAP therapy, while the second included 234 who had been using PAP for at least 3 months and planned to continue during the trial. In both, the participants randomly received either 10 mg or 15 mg of tirzepatide or placebo once weekly for 52 weeks.

At baseline, 65%-70% of participants had severe OSA, with more than 30 events/h on the apnea-hypopnea index (AHI) and a mean of 51.5 events/h. By 52 weeks, those randomized to tirzepatide had 27-30 fewer events/h, compared with 4-6 fewer events/h for those taking placebo. In addition, significantly more of those on tirzepatide achieved OSA remission or severity reduction to mild.

Those randomized to tirzepatide also averaged up to 20% weight loss, significantly more than with placebo. “The improvement in AHI in participants with OSA is likely related to body weight reduction with Zepbound,” according to an FDA statement.

Side effects of tirzepatide include nausea, diarrhea, vomiting, constipation, abdominal discomfort and pain, injection site reactions, fatigue, hypersensitivity reactions (typically fever and rash), burping, hair loss, and gastroesophageal reflux disease.

In an editorial accompanying The New England Journal of Medicine publication of the SURMOUNT-OSA results, Sanjay R. Patel, MD, wrote: “The potential incorporation of tirzepatide into treatment algorithms for obstructive sleep apnea should include consideration of the challenges of adherence to treatment and the imperative to address racial disparities in medical care.”

Patel, who is professor of medicine and epidemiology at the University of Pittsburgh in Pennsylvania, and medical director of the University of Pittsburgh Medical Center’s Comprehensive Sleep Disorders program, pointed out that suboptimal adherence to continuous PAP therapy has been a major limitation, but that adherence to the GLP-1 drug class has also been suboptimal.

“Although adherence to tirzepatide therapy in the SURMOUNT-OSA trial was high, real-world evidence suggests that nearly 50% of patients who begin treatment with a GLP-1 receptor agonist for obesity discontinue therapy within 12 months. Thus, it is likely that any incorporation of tirzepatide into treatment pathways for obstructive sleep apnea will not diminish the importance of long-term strategies to optimize adherence to treatment.”

Moreover, Patel noted, “racial disparities in the use of GLP-1 receptor agonists among patients with diabetes arouse concern that the addition of tirzepatide as a treatment option for obstructive sleep apnea without directly addressing policies relative to coverage of care will only further exacerbate already pervasive disparities in clinical care for obstructive sleep apnea.”

Patel reported consulting for Apnimed, Bayer Pharmaceuticals, Lilly USA, NovaResp Technologies, Philips Respironics, and Powell Mansfield. He is a fiduciary officer of BreathPA.

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

The Food and Drug Administration (FDA) has approved the obesity treatment tirzepatide (Zepbound, Eli Lilly) for treating moderate to severe obstructive sleep apnea (OSA) in adults with obesity.

The new indication is for use in combination with reduced-calorie diet and increased physical activity. The once-weekly injectable is the first-ever drug treatment for OSA. Until now, OSA treatment has focused on mechanical support during sleep in the form of positive airway pressure (PAP) therapy. 

“Today’s approval marks the first drug treatment option for certain patients with obstructive sleep apnea,” said Sally Seymour, MD, director of the Division of Pulmonology, Allergy, and Critical Care in the FDA’s Center for Drug Evaluation and Research. “This is a major step forward for patients with obstructive sleep apnea.”

Excess weight is a major risk factor for OSA, in which the upper airways become blocked multiple times during sleep and obstruct breathing. The condition causes loud snoring, recurrent awakenings, and daytime sleepiness. It is also associated with cardiovascular disease.

Tirzepatide, a dual glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide receptor agonist, was initially approved with brand name Mounjaro in May 2022 for the treatment of type 2 diabetes, and as Zepbound for weight loss in November 2023.

The new OSA approval was based on two phase 3, double-blind randomized controlled trials, SURMOUNT-OSA, in patients with obesity and moderate to severe OSA, conducted at 60 sites in nine countries. Results from both were presented in June 2024 at the annual Scientific Sessions of the American Diabetes Association and were simultaneously published in The New England Journal of Medicine.

The first trial enrolled 469 participants who were unable or unwilling to use PAP therapy, while the second included 234 who had been using PAP for at least 3 months and planned to continue during the trial. In both, the participants randomly received either 10 mg or 15 mg of tirzepatide or placebo once weekly for 52 weeks.

At baseline, 65%-70% of participants had severe OSA, with more than 30 events/h on the apnea-hypopnea index (AHI) and a mean of 51.5 events/h. By 52 weeks, those randomized to tirzepatide had 27-30 fewer events/h, compared with 4-6 fewer events/h for those taking placebo. In addition, significantly more of those on tirzepatide achieved OSA remission or severity reduction to mild.

Those randomized to tirzepatide also averaged up to 20% weight loss, significantly more than with placebo. “The improvement in AHI in participants with OSA is likely related to body weight reduction with Zepbound,” according to an FDA statement.

Side effects of tirzepatide include nausea, diarrhea, vomiting, constipation, abdominal discomfort and pain, injection site reactions, fatigue, hypersensitivity reactions (typically fever and rash), burping, hair loss, and gastroesophageal reflux disease.

In an editorial accompanying The New England Journal of Medicine publication of the SURMOUNT-OSA results, Sanjay R. Patel, MD, wrote: “The potential incorporation of tirzepatide into treatment algorithms for obstructive sleep apnea should include consideration of the challenges of adherence to treatment and the imperative to address racial disparities in medical care.”

Patel, who is professor of medicine and epidemiology at the University of Pittsburgh in Pennsylvania, and medical director of the University of Pittsburgh Medical Center’s Comprehensive Sleep Disorders program, pointed out that suboptimal adherence to continuous PAP therapy has been a major limitation, but that adherence to the GLP-1 drug class has also been suboptimal.

“Although adherence to tirzepatide therapy in the SURMOUNT-OSA trial was high, real-world evidence suggests that nearly 50% of patients who begin treatment with a GLP-1 receptor agonist for obesity discontinue therapy within 12 months. Thus, it is likely that any incorporation of tirzepatide into treatment pathways for obstructive sleep apnea will not diminish the importance of long-term strategies to optimize adherence to treatment.”

Moreover, Patel noted, “racial disparities in the use of GLP-1 receptor agonists among patients with diabetes arouse concern that the addition of tirzepatide as a treatment option for obstructive sleep apnea without directly addressing policies relative to coverage of care will only further exacerbate already pervasive disparities in clinical care for obstructive sleep apnea.”

Patel reported consulting for Apnimed, Bayer Pharmaceuticals, Lilly USA, NovaResp Technologies, Philips Respironics, and Powell Mansfield. He is a fiduciary officer of BreathPA.

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

The Food and Drug Administration (FDA) has approved the obesity treatment tirzepatide (Zepbound, Eli Lilly) for treating moderate to severe obstructive sleep apnea (OSA) in adults with obesity.

The new indication is for use in combination with reduced-calorie diet and increased physical activity. The once-weekly injectable is the first-ever drug treatment for OSA. Until now, OSA treatment has focused on mechanical support during sleep in the form of positive airway pressure (PAP) therapy. 

“Today’s approval marks the first drug treatment option for certain patients with obstructive sleep apnea,” said Sally Seymour, MD, director of the Division of Pulmonology, Allergy, and Critical Care in the FDA’s Center for Drug Evaluation and Research. “This is a major step forward for patients with obstructive sleep apnea.”

Excess weight is a major risk factor for OSA, in which the upper airways become blocked multiple times during sleep and obstruct breathing. The condition causes loud snoring, recurrent awakenings, and daytime sleepiness. It is also associated with cardiovascular disease.

Tirzepatide, a dual glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide receptor agonist, was initially approved with brand name Mounjaro in May 2022 for the treatment of type 2 diabetes, and as Zepbound for weight loss in November 2023.

The new OSA approval was based on two phase 3, double-blind randomized controlled trials, SURMOUNT-OSA, in patients with obesity and moderate to severe OSA, conducted at 60 sites in nine countries. Results from both were presented in June 2024 at the annual Scientific Sessions of the American Diabetes Association and were simultaneously published in The New England Journal of Medicine.

The first trial enrolled 469 participants who were unable or unwilling to use PAP therapy, while the second included 234 who had been using PAP for at least 3 months and planned to continue during the trial. In both, the participants randomly received either 10 mg or 15 mg of tirzepatide or placebo once weekly for 52 weeks.

At baseline, 65%-70% of participants had severe OSA, with more than 30 events/h on the apnea-hypopnea index (AHI) and a mean of 51.5 events/h. By 52 weeks, those randomized to tirzepatide had 27-30 fewer events/h, compared with 4-6 fewer events/h for those taking placebo. In addition, significantly more of those on tirzepatide achieved OSA remission or severity reduction to mild.

Those randomized to tirzepatide also averaged up to 20% weight loss, significantly more than with placebo. “The improvement in AHI in participants with OSA is likely related to body weight reduction with Zepbound,” according to an FDA statement.

Side effects of tirzepatide include nausea, diarrhea, vomiting, constipation, abdominal discomfort and pain, injection site reactions, fatigue, hypersensitivity reactions (typically fever and rash), burping, hair loss, and gastroesophageal reflux disease.

In an editorial accompanying The New England Journal of Medicine publication of the SURMOUNT-OSA results, Sanjay R. Patel, MD, wrote: “The potential incorporation of tirzepatide into treatment algorithms for obstructive sleep apnea should include consideration of the challenges of adherence to treatment and the imperative to address racial disparities in medical care.”

Patel, who is professor of medicine and epidemiology at the University of Pittsburgh in Pennsylvania, and medical director of the University of Pittsburgh Medical Center’s Comprehensive Sleep Disorders program, pointed out that suboptimal adherence to continuous PAP therapy has been a major limitation, but that adherence to the GLP-1 drug class has also been suboptimal.

“Although adherence to tirzepatide therapy in the SURMOUNT-OSA trial was high, real-world evidence suggests that nearly 50% of patients who begin treatment with a GLP-1 receptor agonist for obesity discontinue therapy within 12 months. Thus, it is likely that any incorporation of tirzepatide into treatment pathways for obstructive sleep apnea will not diminish the importance of long-term strategies to optimize adherence to treatment.”

Moreover, Patel noted, “racial disparities in the use of GLP-1 receptor agonists among patients with diabetes arouse concern that the addition of tirzepatide as a treatment option for obstructive sleep apnea without directly addressing policies relative to coverage of care will only further exacerbate already pervasive disparities in clinical care for obstructive sleep apnea.”

Patel reported consulting for Apnimed, Bayer Pharmaceuticals, Lilly USA, NovaResp Technologies, Philips Respironics, and Powell Mansfield. He is a fiduciary officer of BreathPA.

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.

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.

Keith Poulsen’s jaw dropped when farmers showed him images on their cellphones at the World Dairy Expo in Wisconsin in October. A livestock veterinarian at the University of Wisconsin-Madison, Poulsen had seen sick cows before, with their noses dripping and udders slack.

But the scale of the farmers’ efforts to treat the sick cows stunned him. They showed videos of systems they built to hydrate hundreds of cattle at once. In 14-hour shifts, dairy workers pumped gallons of electrolyte-rich fluids into ailing cows through metal tubes inserted into the esophagus.

“It was like watching a field hospital on an active battlefront treating hundreds of wounded soldiers,” he said.

Nearly a year into the first outbreak of the bird flu among cattle, the virus shows no sign of slowing. The US government failed to eliminate the virus on dairy farms when it was confined to a handful of states, by quickly identifying infected cows and taking measures to keep their infections from spreading. Now at least 875 herds across 16 states have tested positive.

Experts say they have lost faith in the government’s ability to contain the outbreak.

“We are in a terrible situation and going into a worse situation,” said Angela Rasmussen, a virologist at the University of Saskatchewan in Canada. “I don’t know if the bird flu will become a pandemic, but if it does, we are screwed.”

To understand how the bird flu got out of hand, KFF Health News interviewed nearly 70 government officials, farmers and farmworkers, and researchers with expertise in virology, pandemics, veterinary medicine, and more.

Together with emails obtained from local health departments through public records requests, this investigation revealed key problems, including deference to the farm industry, eroded public health budgets, neglect for the safety of agriculture workers, and the sluggish pace of federal interventions.

Case in point: The US Department of Agriculture this month announced a federal order to test milk nationwide. Researchers welcomed the news but said it should have happened months ago — before the virus was so entrenched.

“It’s disheartening to see so many of the same failures that emerged during the COVID-19 crisis reemerge,” said Tom Bollyky, director of the Global Health Program at the Council on Foreign Relations.

Far more bird flu damage is inevitable, but the extent of it will be left to the Trump administration and Mother Nature. Already, the USDA has funneled more than $1.7 billion into tamping down the bird flu on poultry farms since 2022, which includes reimbursing farmers who’ve had to cull their flocks, and more than $430 million into combating the bird flu on dairy farms. In coming years, the bird flu may cost billions of dollars more in expenses and losses. Dairy industry experts say the virus kills roughly 2%-5% of infected dairy cows and reduces a herd’s milk production by about 20%.

Worse, the outbreak poses the threat of a pandemic. More than 60 people in the US have been infected, mainly by cows or poultry, but cases could skyrocket if the virus evolves to spread efficiently from person to person. And the recent news of a person critically ill in Louisiana with the bird flu shows that the virus can be dangerous.

Just a few mutations could allow the bird flu to spread between people. Because viruses mutate within human and animal bodies, each infection is like a pull of a slot machine lever.

“Even if there’s only a 5% chance of a bird flu pandemic happening, we’re talking about a pandemic that probably looks like 2020 or worse,” said Tom Peacock, a bird flu researcher at the Pirbright Institute in the United Kingdom, referring to COVID. “The US knows the risk but hasn’t done anything to slow this down,” he added.

Beyond the bird flu, the federal government’s handling of the outbreak reveals cracks in the US health security system that would allow other risky new pathogens to take root. “This virus may not be the one that takes off,” said Maria Van Kerkhove, director of the emerging diseases group at the World Health Organization. “But this is a real-fire exercise right now, and it demonstrates what needs to be improved.”

 

A Slow Start

It may have been a grackle, a goose, or some other wild bird that infected a cow in northern Texas. In February, the state’s dairy farmers took note when cows stopped making milk. They worked alongside veterinarians to figure out why. In less than two months, veterinary researchers identified the highly pathogenic H5N1 bird flu virus as the culprit.

Long listed among pathogens with pandemic potential, the bird flu’s unprecedented spread among cows marked a worrying shift. It had evolved to thrive in animals that are more like people biologically than birds.

After the USDA announced the dairy outbreak on March 25, control shifted from farmers, veterinarians, and local officials to state and federal agencies. Collaboration disintegrated almost immediately.

Farmers worried the government might block their milk sales or even demand sick cows be killed, as poultry are, said Kay Russo, a livestock veterinarian in Fort Collins, Colorado.

Instead, Russo and other veterinarians said, they were dismayed by inaction. The USDA didn’t respond to their urgent requests to support studies on dairy farms — and for money and confidentiality policies to protect farmers from financial loss if they agreed to test animals.

The USDA announced that it would conduct studies itself. But researchers grew anxious as weeks passed without results. “Probably the biggest mistake from the USDA was not involving the boots-on-the-ground veterinarians,” Russo said.

Will Clement, a USDA senior adviser for communications, said in an email: “Since first learning of H5N1 in dairy cattle in late March 2024, USDA has worked swiftly and diligently to assess the prevalence of the virus in US dairy herds.” The agency provided research funds to state and national animal health labs beginning in April, he added.

The USDA didn’t require lactating cows to be tested before interstate travel until April 29. By then, the outbreak had spread to eight other states. Farmers often move cattle across great distances, for calving in one place, raising in warm, dry climates, and milking in cooler ones. Analyses of the virus’s genes implied that it spread between cows rather than repeatedly jumping from birds into herds.

Milking equipment was a likely source of infection, and there were hints of other possibilities, such as through the air as cows coughed or in droplets on objects, like work boots. But not enough data had been collected to know how exactly it was happening. Many farmers declined to test their herds, despite an announcement of funds to compensate them for lost milk production in May.

“There is a fear within the dairy farmer community that if they become officially listed as an affected farm, they may lose their milk market,” said Jamie Jonker, chief science officer at the National Milk Producers Federation, an organization that represents dairy farmers. To his knowledge, he added, this hasn’t happened.

Speculation filled knowledge gaps. Zach Riley, head of the Colorado Livestock Association, said he suspected that wild birds may be spreading the virus to herds across the country, despite scientific data suggesting otherwise. Riley said farmers were considering whether to install “floppy inflatable men you see outside of car dealerships” to ward off the birds.

Advisories from agriculture departments to farmers were somewhat speculative, too. Officials recommended biosecurity measures such as disinfecting equipment and limiting visitors. As the virus kept spreading throughout the summer, USDA senior official Eric Deeble said at a press briefing, “The response is adequate.”

The USDA, the Centers for Disease Control and Prevention, and the Food and Drug Administration presented a united front at these briefings, calling it a “One Health” approach. In reality, agriculture agencies took the lead.

This was explicit in an email from a local health department in Colorado to the county’s commissioners. “The State is treating this primarily as an agriculture issue (rightly so) and the public health part is secondary,” wrote Jason Chessher, public health director in Weld County, Colorado. The state’s leading agriculture county, Weld’s livestock and poultry industry produces about $1.9 billion in sales each year.

 

Patchy Surveillance

In July, the bird flu spread from dairies in Colorado to poultry farms. To contain it, two poultry operations employed about 650 temporary workers — Spanish-speaking immigrants as young as 15 — to cull flocks. Inside hot barns, they caught infected birds, gassed them with carbon dioxide, and disposed of the carcasses. Many did the hazardous job without goggles, face masks, and gloves.

By the time Colorado’s health department asked if workers felt sick, five women and four men had been infected. They all had red, swollen eyes — conjunctivitis — and several had such symptoms as fevers, body aches, and nausea.

State health departments posted online notices offering farms protective gear, but dairy workers in several states told KFF Health News that they had none. They also hadn’t heard about the bird flu, never mind tests for it.

Studies in Colorado, Michigan, and Texas would later show that bird flu cases had gone under the radar. In one analysis, eight dairy workers who hadn’t been tested — 7% of those studied — had antibodies against the virus, a sign that they had been infected.

Missed cases made it impossible to determine how the virus jumped into people and whether it was growing more infectious or dangerous. “I have been distressed and depressed by the lack of epidemiologic data and the lack of surveillance,” said Nicole Lurie, an executive director at the international organization the Coalition for Epidemic Preparedness Innovations, who served as assistant secretary for preparedness and response in the Obama administration.

Citing “insufficient data,” the British government raised its assessment of the risk posed by the US dairy outbreak in July from three to four on a six-tier scale.

Virologists around the world said they were flabbergasted by how poorly the United States was tracking the situation. “You are surrounded by highly pathogenic viruses in the wild and in farm animals,” said Marion Koopmans, head of virology at Erasmus Medical Center in the Netherlands. “If 3 months from now we are at the start of the pandemic, it is nobody’s surprise.”

Although the bird flu is not yet spreading swiftly between people, a shift in that direction could cause immense suffering. The CDC has repeatedly described the cases among farmworkers this year as mild — they weren’t hospitalized. But that doesn’t mean symptoms are a breeze, or that the virus can’t cause worse.

“It does not look pleasant,” wrote Sean Roberts, an emergency services specialist at the Tulare County, California, health department in an email to colleagues in May. He described photographs of an infected dairy worker in another state: “Apparently, the conjunctivitis that this is causing is not a mild one, but rather ruptured blood vessels and bleeding conjunctiva.”

Over the past 30 years, half of around 900 people diagnosed with bird flu around the world have died. Even if the case fatality rate is much lower for this strain of the bird flu, COVID showed how devastating a 1% death rate can be when a virus spreads easily.

Like other cases around the world, the person now hospitalized with the bird flu in Louisiana appears to have gotten the virus directly from birds. After the case was announced, the CDC released a statement saying, “A sporadic case of severe H5N1 bird flu illness in a person is not unexpected.”

 

‘The Cows Are More Valuable Than Us’

Local health officials were trying hard to track infections, according to hundreds of emails from county health departments in five states. But their efforts were stymied. Even if farmers reported infected herds to the USDA and agriculture agencies told health departments where the infected cows were, health officials had to rely on farm owners for access.

“The agriculture community has dictated the rules of engagement from the start,” said Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota. “That was a big mistake.”

Some farmers told health officials not to visit and declined to monitor their employees for signs of sickness. Sending workers to clinics for testing could leave them shorthanded when cattle needed care. “Producer refuses to send workers to Sunrise [clinic] to get tested since they’re too busy. He has pink eye, too,” said an email from the Weld, Colorado, health department.

“We know of 386 persons exposed — but we know this is far from the total,” said an email from a public health specialist to officials at Tulare’s health department recounting a call with state health officials. “Employers do not want to run this through worker’s compensation. Workers are hesitant to get tested due to cost,” she wrote.

Jennifer Morse, medical director of the Mid-Michigan District Health Department, said local health officials have been hesitant to apply pressure after the backlash many faced at the peak of COVID. Describing the 19 rural counties she serves as “very minimal government–minded,” she said, “if you try to work against them, it will not go well.”

Rural health departments are also stretched thin. Organizations that specialize in outreach to farmworkers offered to assist health officials early in the outbreak, but months passed without contracts or funding. During the first years of COVID, lagging government funds for outreach to farmworkers and other historically marginalized groups led to a disproportionate toll of the disease among people of color.

Kevin Griffis, director of communications at the CDC, said the agency worked with the National Center for Farmworker Health throughout the summer “to reach every farmworker impacted by H5N1.” But Bethany Boggess Alcauter, the center’s director of public health programs, said it didn’t receive a CDC grant for bird flu outreach until October, to the tune of $4 million. Before then, she said, the group had very limited funds for the task. “We are certainly not reaching ‘every farmworker,’” she added.

Farmworker advocates also pressed the CDC for money to offset workers’ financial concerns about testing, including paying for medical care, sick leave, and the risk of being fired. This amounted to an offer of $75 each. “Outreach is clearly not a huge priority,” Boggess said. “I hear over and over from workers, ‘The cows are more valuable than us.’ ”

The USDA has so far put more than $2.1 billion into reimbursing poultry and dairy farmers for losses due to the bird flu and other measures to control the spread on farms. Federal agencies have also put $292 million into developing and stockpiling bird flu vaccines for animals and people. In a controversial decision, the CDC has advised against offering the ones on hand to farmworkers.

“If you want to keep this from becoming a human pandemic, you focus on protecting farmworkers, since that’s the most likely way that this will enter the human population,” said Peg Seminario, an occupational health researcher in Bethesda, Maryland. “The fact that this isn’t happening drives me crazy.”

Nirav Shah, principal deputy director of the CDC, said the agency aims to keep workers safe. “Widespread awareness does take time,” he said. “And that’s the work we’re committed to doing.”

As President-elect Donald Trump comes into office in January, farmworkers may be even less protected. Trump’s pledge of mass deportations will have repercussions whether they happen or not, said Tania Pacheco-Werner, director of the Central Valley Health Policy Institute in California.

Many dairy and poultry workers are living in the United States without authorization or on temporary visas linked to their employers. Such precarity made people less willing to see doctors about COVID symptoms or complain about unsafe working conditions in 2020. Pacheco-Werner said, “Mass deportation is an astronomical challenge for public health.”

 

Not ‘Immaculate Conception’

A switch flipped in September among experts who study pandemics as national security threats. A patient in Missouri had the bird flu, and no one knew why. “Evidence points to this being a one-off case,” Shah said at a briefing with journalists. About a month later, the agency revealed it was not.

Antibody tests found that a person who lived with the patient had been infected, too. The CDC didn’t know how the two had gotten the virus, and the possibility of human transmission couldn’t be ruled out.

Nonetheless, at an October briefing, Shah said the public risk remained low and Deeble said he was optimistic that the dairy outbreak could be eliminated.

Experts were perturbed by such confident statements in the face of uncertainty, especially as California’s outbreak spiked and a child was mysteriously infected by the same strain of virus found on dairy farms.

“This wasn’t just immaculate conception,” said Stephen Morrison, director of the Global Health Policy Center at the Center for Strategic and International Studies. “It came from somewhere and we don’t know where, but that hasn’t triggered any kind of reset in approach — just the same kind of complacency and low energy.”

Sam Scarpino, a disease surveillance specialist in the Boston area, wondered how many other mysterious infections had gone undetected. Surveillance outside of farms was even patchier than on them, and bird flu tests have been hard to get.

Although pandemic experts had identified the CDC’s singular hold on testing for new viruses as a key explanation for why America was hit so hard by COVID in 2020, the system remained the same. Bird flu tests could be run only by the CDC and public health labs until this month, even though commercial and academic diagnostic laboratories had inquired about running tests since April. The CDC and FDA should have tried to help them along months ago, said Ali Khan, a former top CDC official who now leads the University of Nebraska Medical Center College of Public Health.

As winter sets in, the bird flu becomes harder to spot because patient symptoms may be mistaken for the seasonal flu. Flu season also raises a risk that the two flu viruses could swap genes if they infect a person simultaneously. That could form a hybrid bird flu that spreads swiftly through coughs and sneezes.

A sluggish response to emerging outbreaks may simply be a new, unfortunate norm for America, said Bollyky, at the Council on Foreign Relations. If so, the nation has gotten lucky that the bird flu still can’t spread easily between people. Controlling the virus will be much harder and costlier than it would have been when the outbreak was small. But it’s possible.

Agriculture officials could start testing every silo of bulk milk, in every state, monthly, said Poulsen, the livestock veterinarian. “Not one and done,” he added. If they detect the virus, they’d need to determine the affected farm in time to stop sick cows from spreading infections to the rest of the herd — or at least to other farms. Cows can spread the bird flu before they’re sick, he said, so speed is crucial.

Curtailing the virus on farms is the best way to prevent human infections, said Jennifer Nuzzo, director of the Pandemic Center at Brown University, but human surveillance must be stepped up, too. Every clinic serving communities where farmworkers live should have easy access to bird flu tests — and be encouraged to use them. Funds for farmworker outreach must be boosted. And, she added, the CDC should change its position and offer farmworkers bird flu vaccines to protect them and ward off the chance of a hybrid bird flu that spreads quickly.

The rising number of cases not linked to farms signals a need for more testing in general. When patients are positive on a general flu test — a common diagnostic that indicates human, swine, or bird flu — clinics should probe more deeply, Nuzzo said.

The alternative is a wait-and-see approach in which the nation responds only after enormous damage to lives or businesses. This tack tends to rely on mass vaccination. But an effort analogous to Trump’s Operation Warp Speed is not assured, and neither is rollout like that for the first COVID shots, given a rise in vaccine skepticism among Republican lawmakers.

Change may instead need to start from the bottom up — on dairy farms, still the most common source of human infections, said Poulsen. He noticed a shift in attitudes among farmers at the Dairy Expo: “They’re starting to say, ‘How do I save my dairy for the next generation?’ They recognize how severe this is, and that it’s not just going away.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF — the independent source for health policy research, polling, and journalism.

 

Keith Poulsen’s jaw dropped when farmers showed him images on their cellphones at the World Dairy Expo in Wisconsin in October. A livestock veterinarian at the University of Wisconsin-Madison, Poulsen had seen sick cows before, with their noses dripping and udders slack.

But the scale of the farmers’ efforts to treat the sick cows stunned him. They showed videos of systems they built to hydrate hundreds of cattle at once. In 14-hour shifts, dairy workers pumped gallons of electrolyte-rich fluids into ailing cows through metal tubes inserted into the esophagus.

“It was like watching a field hospital on an active battlefront treating hundreds of wounded soldiers,” he said.

Nearly a year into the first outbreak of the bird flu among cattle, the virus shows no sign of slowing. The US government failed to eliminate the virus on dairy farms when it was confined to a handful of states, by quickly identifying infected cows and taking measures to keep their infections from spreading. Now at least 875 herds across 16 states have tested positive.

Experts say they have lost faith in the government’s ability to contain the outbreak.

“We are in a terrible situation and going into a worse situation,” said Angela Rasmussen, a virologist at the University of Saskatchewan in Canada. “I don’t know if the bird flu will become a pandemic, but if it does, we are screwed.”

To understand how the bird flu got out of hand, KFF Health News interviewed nearly 70 government officials, farmers and farmworkers, and researchers with expertise in virology, pandemics, veterinary medicine, and more.

Together with emails obtained from local health departments through public records requests, this investigation revealed key problems, including deference to the farm industry, eroded public health budgets, neglect for the safety of agriculture workers, and the sluggish pace of federal interventions.

Case in point: The US Department of Agriculture this month announced a federal order to test milk nationwide. Researchers welcomed the news but said it should have happened months ago — before the virus was so entrenched.

“It’s disheartening to see so many of the same failures that emerged during the COVID-19 crisis reemerge,” said Tom Bollyky, director of the Global Health Program at the Council on Foreign Relations.

Far more bird flu damage is inevitable, but the extent of it will be left to the Trump administration and Mother Nature. Already, the USDA has funneled more than $1.7 billion into tamping down the bird flu on poultry farms since 2022, which includes reimbursing farmers who’ve had to cull their flocks, and more than $430 million into combating the bird flu on dairy farms. In coming years, the bird flu may cost billions of dollars more in expenses and losses. Dairy industry experts say the virus kills roughly 2%-5% of infected dairy cows and reduces a herd’s milk production by about 20%.

Worse, the outbreak poses the threat of a pandemic. More than 60 people in the US have been infected, mainly by cows or poultry, but cases could skyrocket if the virus evolves to spread efficiently from person to person. And the recent news of a person critically ill in Louisiana with the bird flu shows that the virus can be dangerous.

Just a few mutations could allow the bird flu to spread between people. Because viruses mutate within human and animal bodies, each infection is like a pull of a slot machine lever.

“Even if there’s only a 5% chance of a bird flu pandemic happening, we’re talking about a pandemic that probably looks like 2020 or worse,” said Tom Peacock, a bird flu researcher at the Pirbright Institute in the United Kingdom, referring to COVID. “The US knows the risk but hasn’t done anything to slow this down,” he added.

Beyond the bird flu, the federal government’s handling of the outbreak reveals cracks in the US health security system that would allow other risky new pathogens to take root. “This virus may not be the one that takes off,” said Maria Van Kerkhove, director of the emerging diseases group at the World Health Organization. “But this is a real-fire exercise right now, and it demonstrates what needs to be improved.”

 

A Slow Start

It may have been a grackle, a goose, or some other wild bird that infected a cow in northern Texas. In February, the state’s dairy farmers took note when cows stopped making milk. They worked alongside veterinarians to figure out why. In less than two months, veterinary researchers identified the highly pathogenic H5N1 bird flu virus as the culprit.

Long listed among pathogens with pandemic potential, the bird flu’s unprecedented spread among cows marked a worrying shift. It had evolved to thrive in animals that are more like people biologically than birds.

After the USDA announced the dairy outbreak on March 25, control shifted from farmers, veterinarians, and local officials to state and federal agencies. Collaboration disintegrated almost immediately.

Farmers worried the government might block their milk sales or even demand sick cows be killed, as poultry are, said Kay Russo, a livestock veterinarian in Fort Collins, Colorado.

Instead, Russo and other veterinarians said, they were dismayed by inaction. The USDA didn’t respond to their urgent requests to support studies on dairy farms — and for money and confidentiality policies to protect farmers from financial loss if they agreed to test animals.

The USDA announced that it would conduct studies itself. But researchers grew anxious as weeks passed without results. “Probably the biggest mistake from the USDA was not involving the boots-on-the-ground veterinarians,” Russo said.

Will Clement, a USDA senior adviser for communications, said in an email: “Since first learning of H5N1 in dairy cattle in late March 2024, USDA has worked swiftly and diligently to assess the prevalence of the virus in US dairy herds.” The agency provided research funds to state and national animal health labs beginning in April, he added.

The USDA didn’t require lactating cows to be tested before interstate travel until April 29. By then, the outbreak had spread to eight other states. Farmers often move cattle across great distances, for calving in one place, raising in warm, dry climates, and milking in cooler ones. Analyses of the virus’s genes implied that it spread between cows rather than repeatedly jumping from birds into herds.

Milking equipment was a likely source of infection, and there were hints of other possibilities, such as through the air as cows coughed or in droplets on objects, like work boots. But not enough data had been collected to know how exactly it was happening. Many farmers declined to test their herds, despite an announcement of funds to compensate them for lost milk production in May.

“There is a fear within the dairy farmer community that if they become officially listed as an affected farm, they may lose their milk market,” said Jamie Jonker, chief science officer at the National Milk Producers Federation, an organization that represents dairy farmers. To his knowledge, he added, this hasn’t happened.

Speculation filled knowledge gaps. Zach Riley, head of the Colorado Livestock Association, said he suspected that wild birds may be spreading the virus to herds across the country, despite scientific data suggesting otherwise. Riley said farmers were considering whether to install “floppy inflatable men you see outside of car dealerships” to ward off the birds.

Advisories from agriculture departments to farmers were somewhat speculative, too. Officials recommended biosecurity measures such as disinfecting equipment and limiting visitors. As the virus kept spreading throughout the summer, USDA senior official Eric Deeble said at a press briefing, “The response is adequate.”

The USDA, the Centers for Disease Control and Prevention, and the Food and Drug Administration presented a united front at these briefings, calling it a “One Health” approach. In reality, agriculture agencies took the lead.

This was explicit in an email from a local health department in Colorado to the county’s commissioners. “The State is treating this primarily as an agriculture issue (rightly so) and the public health part is secondary,” wrote Jason Chessher, public health director in Weld County, Colorado. The state’s leading agriculture county, Weld’s livestock and poultry industry produces about $1.9 billion in sales each year.

 

Patchy Surveillance

In July, the bird flu spread from dairies in Colorado to poultry farms. To contain it, two poultry operations employed about 650 temporary workers — Spanish-speaking immigrants as young as 15 — to cull flocks. Inside hot barns, they caught infected birds, gassed them with carbon dioxide, and disposed of the carcasses. Many did the hazardous job without goggles, face masks, and gloves.

By the time Colorado’s health department asked if workers felt sick, five women and four men had been infected. They all had red, swollen eyes — conjunctivitis — and several had such symptoms as fevers, body aches, and nausea.

State health departments posted online notices offering farms protective gear, but dairy workers in several states told KFF Health News that they had none. They also hadn’t heard about the bird flu, never mind tests for it.

Studies in Colorado, Michigan, and Texas would later show that bird flu cases had gone under the radar. In one analysis, eight dairy workers who hadn’t been tested — 7% of those studied — had antibodies against the virus, a sign that they had been infected.

Missed cases made it impossible to determine how the virus jumped into people and whether it was growing more infectious or dangerous. “I have been distressed and depressed by the lack of epidemiologic data and the lack of surveillance,” said Nicole Lurie, an executive director at the international organization the Coalition for Epidemic Preparedness Innovations, who served as assistant secretary for preparedness and response in the Obama administration.

Citing “insufficient data,” the British government raised its assessment of the risk posed by the US dairy outbreak in July from three to four on a six-tier scale.

Virologists around the world said they were flabbergasted by how poorly the United States was tracking the situation. “You are surrounded by highly pathogenic viruses in the wild and in farm animals,” said Marion Koopmans, head of virology at Erasmus Medical Center in the Netherlands. “If 3 months from now we are at the start of the pandemic, it is nobody’s surprise.”

Although the bird flu is not yet spreading swiftly between people, a shift in that direction could cause immense suffering. The CDC has repeatedly described the cases among farmworkers this year as mild — they weren’t hospitalized. But that doesn’t mean symptoms are a breeze, or that the virus can’t cause worse.

“It does not look pleasant,” wrote Sean Roberts, an emergency services specialist at the Tulare County, California, health department in an email to colleagues in May. He described photographs of an infected dairy worker in another state: “Apparently, the conjunctivitis that this is causing is not a mild one, but rather ruptured blood vessels and bleeding conjunctiva.”

Over the past 30 years, half of around 900 people diagnosed with bird flu around the world have died. Even if the case fatality rate is much lower for this strain of the bird flu, COVID showed how devastating a 1% death rate can be when a virus spreads easily.

Like other cases around the world, the person now hospitalized with the bird flu in Louisiana appears to have gotten the virus directly from birds. After the case was announced, the CDC released a statement saying, “A sporadic case of severe H5N1 bird flu illness in a person is not unexpected.”

 

‘The Cows Are More Valuable Than Us’

Local health officials were trying hard to track infections, according to hundreds of emails from county health departments in five states. But their efforts were stymied. Even if farmers reported infected herds to the USDA and agriculture agencies told health departments where the infected cows were, health officials had to rely on farm owners for access.

“The agriculture community has dictated the rules of engagement from the start,” said Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota. “That was a big mistake.”

Some farmers told health officials not to visit and declined to monitor their employees for signs of sickness. Sending workers to clinics for testing could leave them shorthanded when cattle needed care. “Producer refuses to send workers to Sunrise [clinic] to get tested since they’re too busy. He has pink eye, too,” said an email from the Weld, Colorado, health department.

“We know of 386 persons exposed — but we know this is far from the total,” said an email from a public health specialist to officials at Tulare’s health department recounting a call with state health officials. “Employers do not want to run this through worker’s compensation. Workers are hesitant to get tested due to cost,” she wrote.

Jennifer Morse, medical director of the Mid-Michigan District Health Department, said local health officials have been hesitant to apply pressure after the backlash many faced at the peak of COVID. Describing the 19 rural counties she serves as “very minimal government–minded,” she said, “if you try to work against them, it will not go well.”

Rural health departments are also stretched thin. Organizations that specialize in outreach to farmworkers offered to assist health officials early in the outbreak, but months passed without contracts or funding. During the first years of COVID, lagging government funds for outreach to farmworkers and other historically marginalized groups led to a disproportionate toll of the disease among people of color.

Kevin Griffis, director of communications at the CDC, said the agency worked with the National Center for Farmworker Health throughout the summer “to reach every farmworker impacted by H5N1.” But Bethany Boggess Alcauter, the center’s director of public health programs, said it didn’t receive a CDC grant for bird flu outreach until October, to the tune of $4 million. Before then, she said, the group had very limited funds for the task. “We are certainly not reaching ‘every farmworker,’” she added.

Farmworker advocates also pressed the CDC for money to offset workers’ financial concerns about testing, including paying for medical care, sick leave, and the risk of being fired. This amounted to an offer of $75 each. “Outreach is clearly not a huge priority,” Boggess said. “I hear over and over from workers, ‘The cows are more valuable than us.’ ”

The USDA has so far put more than $2.1 billion into reimbursing poultry and dairy farmers for losses due to the bird flu and other measures to control the spread on farms. Federal agencies have also put $292 million into developing and stockpiling bird flu vaccines for animals and people. In a controversial decision, the CDC has advised against offering the ones on hand to farmworkers.

“If you want to keep this from becoming a human pandemic, you focus on protecting farmworkers, since that’s the most likely way that this will enter the human population,” said Peg Seminario, an occupational health researcher in Bethesda, Maryland. “The fact that this isn’t happening drives me crazy.”

Nirav Shah, principal deputy director of the CDC, said the agency aims to keep workers safe. “Widespread awareness does take time,” he said. “And that’s the work we’re committed to doing.”

As President-elect Donald Trump comes into office in January, farmworkers may be even less protected. Trump’s pledge of mass deportations will have repercussions whether they happen or not, said Tania Pacheco-Werner, director of the Central Valley Health Policy Institute in California.

Many dairy and poultry workers are living in the United States without authorization or on temporary visas linked to their employers. Such precarity made people less willing to see doctors about COVID symptoms or complain about unsafe working conditions in 2020. Pacheco-Werner said, “Mass deportation is an astronomical challenge for public health.”

 

Not ‘Immaculate Conception’

A switch flipped in September among experts who study pandemics as national security threats. A patient in Missouri had the bird flu, and no one knew why. “Evidence points to this being a one-off case,” Shah said at a briefing with journalists. About a month later, the agency revealed it was not.

Antibody tests found that a person who lived with the patient had been infected, too. The CDC didn’t know how the two had gotten the virus, and the possibility of human transmission couldn’t be ruled out.

Nonetheless, at an October briefing, Shah said the public risk remained low and Deeble said he was optimistic that the dairy outbreak could be eliminated.

Experts were perturbed by such confident statements in the face of uncertainty, especially as California’s outbreak spiked and a child was mysteriously infected by the same strain of virus found on dairy farms.

“This wasn’t just immaculate conception,” said Stephen Morrison, director of the Global Health Policy Center at the Center for Strategic and International Studies. “It came from somewhere and we don’t know where, but that hasn’t triggered any kind of reset in approach — just the same kind of complacency and low energy.”

Sam Scarpino, a disease surveillance specialist in the Boston area, wondered how many other mysterious infections had gone undetected. Surveillance outside of farms was even patchier than on them, and bird flu tests have been hard to get.

Although pandemic experts had identified the CDC’s singular hold on testing for new viruses as a key explanation for why America was hit so hard by COVID in 2020, the system remained the same. Bird flu tests could be run only by the CDC and public health labs until this month, even though commercial and academic diagnostic laboratories had inquired about running tests since April. The CDC and FDA should have tried to help them along months ago, said Ali Khan, a former top CDC official who now leads the University of Nebraska Medical Center College of Public Health.

As winter sets in, the bird flu becomes harder to spot because patient symptoms may be mistaken for the seasonal flu. Flu season also raises a risk that the two flu viruses could swap genes if they infect a person simultaneously. That could form a hybrid bird flu that spreads swiftly through coughs and sneezes.

A sluggish response to emerging outbreaks may simply be a new, unfortunate norm for America, said Bollyky, at the Council on Foreign Relations. If so, the nation has gotten lucky that the bird flu still can’t spread easily between people. Controlling the virus will be much harder and costlier than it would have been when the outbreak was small. But it’s possible.

Agriculture officials could start testing every silo of bulk milk, in every state, monthly, said Poulsen, the livestock veterinarian. “Not one and done,” he added. If they detect the virus, they’d need to determine the affected farm in time to stop sick cows from spreading infections to the rest of the herd — or at least to other farms. Cows can spread the bird flu before they’re sick, he said, so speed is crucial.

Curtailing the virus on farms is the best way to prevent human infections, said Jennifer Nuzzo, director of the Pandemic Center at Brown University, but human surveillance must be stepped up, too. Every clinic serving communities where farmworkers live should have easy access to bird flu tests — and be encouraged to use them. Funds for farmworker outreach must be boosted. And, she added, the CDC should change its position and offer farmworkers bird flu vaccines to protect them and ward off the chance of a hybrid bird flu that spreads quickly.

The rising number of cases not linked to farms signals a need for more testing in general. When patients are positive on a general flu test — a common diagnostic that indicates human, swine, or bird flu — clinics should probe more deeply, Nuzzo said.

The alternative is a wait-and-see approach in which the nation responds only after enormous damage to lives or businesses. This tack tends to rely on mass vaccination. But an effort analogous to Trump’s Operation Warp Speed is not assured, and neither is rollout like that for the first COVID shots, given a rise in vaccine skepticism among Republican lawmakers.

Change may instead need to start from the bottom up — on dairy farms, still the most common source of human infections, said Poulsen. He noticed a shift in attitudes among farmers at the Dairy Expo: “They’re starting to say, ‘How do I save my dairy for the next generation?’ They recognize how severe this is, and that it’s not just going away.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF — the independent source for health policy research, polling, and journalism.

 

Keith Poulsen’s jaw dropped when farmers showed him images on their cellphones at the World Dairy Expo in Wisconsin in October. A livestock veterinarian at the University of Wisconsin-Madison, Poulsen had seen sick cows before, with their noses dripping and udders slack.

But the scale of the farmers’ efforts to treat the sick cows stunned him. They showed videos of systems they built to hydrate hundreds of cattle at once. In 14-hour shifts, dairy workers pumped gallons of electrolyte-rich fluids into ailing cows through metal tubes inserted into the esophagus.

“It was like watching a field hospital on an active battlefront treating hundreds of wounded soldiers,” he said.

Nearly a year into the first outbreak of the bird flu among cattle, the virus shows no sign of slowing. The US government failed to eliminate the virus on dairy farms when it was confined to a handful of states, by quickly identifying infected cows and taking measures to keep their infections from spreading. Now at least 875 herds across 16 states have tested positive.

Experts say they have lost faith in the government’s ability to contain the outbreak.

“We are in a terrible situation and going into a worse situation,” said Angela Rasmussen, a virologist at the University of Saskatchewan in Canada. “I don’t know if the bird flu will become a pandemic, but if it does, we are screwed.”

To understand how the bird flu got out of hand, KFF Health News interviewed nearly 70 government officials, farmers and farmworkers, and researchers with expertise in virology, pandemics, veterinary medicine, and more.

Together with emails obtained from local health departments through public records requests, this investigation revealed key problems, including deference to the farm industry, eroded public health budgets, neglect for the safety of agriculture workers, and the sluggish pace of federal interventions.

Case in point: The US Department of Agriculture this month announced a federal order to test milk nationwide. Researchers welcomed the news but said it should have happened months ago — before the virus was so entrenched.

“It’s disheartening to see so many of the same failures that emerged during the COVID-19 crisis reemerge,” said Tom Bollyky, director of the Global Health Program at the Council on Foreign Relations.

Far more bird flu damage is inevitable, but the extent of it will be left to the Trump administration and Mother Nature. Already, the USDA has funneled more than $1.7 billion into tamping down the bird flu on poultry farms since 2022, which includes reimbursing farmers who’ve had to cull their flocks, and more than $430 million into combating the bird flu on dairy farms. In coming years, the bird flu may cost billions of dollars more in expenses and losses. Dairy industry experts say the virus kills roughly 2%-5% of infected dairy cows and reduces a herd’s milk production by about 20%.

Worse, the outbreak poses the threat of a pandemic. More than 60 people in the US have been infected, mainly by cows or poultry, but cases could skyrocket if the virus evolves to spread efficiently from person to person. And the recent news of a person critically ill in Louisiana with the bird flu shows that the virus can be dangerous.

Just a few mutations could allow the bird flu to spread between people. Because viruses mutate within human and animal bodies, each infection is like a pull of a slot machine lever.

“Even if there’s only a 5% chance of a bird flu pandemic happening, we’re talking about a pandemic that probably looks like 2020 or worse,” said Tom Peacock, a bird flu researcher at the Pirbright Institute in the United Kingdom, referring to COVID. “The US knows the risk but hasn’t done anything to slow this down,” he added.

Beyond the bird flu, the federal government’s handling of the outbreak reveals cracks in the US health security system that would allow other risky new pathogens to take root. “This virus may not be the one that takes off,” said Maria Van Kerkhove, director of the emerging diseases group at the World Health Organization. “But this is a real-fire exercise right now, and it demonstrates what needs to be improved.”

 

A Slow Start

It may have been a grackle, a goose, or some other wild bird that infected a cow in northern Texas. In February, the state’s dairy farmers took note when cows stopped making milk. They worked alongside veterinarians to figure out why. In less than two months, veterinary researchers identified the highly pathogenic H5N1 bird flu virus as the culprit.

Long listed among pathogens with pandemic potential, the bird flu’s unprecedented spread among cows marked a worrying shift. It had evolved to thrive in animals that are more like people biologically than birds.

After the USDA announced the dairy outbreak on March 25, control shifted from farmers, veterinarians, and local officials to state and federal agencies. Collaboration disintegrated almost immediately.

Farmers worried the government might block their milk sales or even demand sick cows be killed, as poultry are, said Kay Russo, a livestock veterinarian in Fort Collins, Colorado.

Instead, Russo and other veterinarians said, they were dismayed by inaction. The USDA didn’t respond to their urgent requests to support studies on dairy farms — and for money and confidentiality policies to protect farmers from financial loss if they agreed to test animals.

The USDA announced that it would conduct studies itself. But researchers grew anxious as weeks passed without results. “Probably the biggest mistake from the USDA was not involving the boots-on-the-ground veterinarians,” Russo said.

Will Clement, a USDA senior adviser for communications, said in an email: “Since first learning of H5N1 in dairy cattle in late March 2024, USDA has worked swiftly and diligently to assess the prevalence of the virus in US dairy herds.” The agency provided research funds to state and national animal health labs beginning in April, he added.

The USDA didn’t require lactating cows to be tested before interstate travel until April 29. By then, the outbreak had spread to eight other states. Farmers often move cattle across great distances, for calving in one place, raising in warm, dry climates, and milking in cooler ones. Analyses of the virus’s genes implied that it spread between cows rather than repeatedly jumping from birds into herds.

Milking equipment was a likely source of infection, and there were hints of other possibilities, such as through the air as cows coughed or in droplets on objects, like work boots. But not enough data had been collected to know how exactly it was happening. Many farmers declined to test their herds, despite an announcement of funds to compensate them for lost milk production in May.

“There is a fear within the dairy farmer community that if they become officially listed as an affected farm, they may lose their milk market,” said Jamie Jonker, chief science officer at the National Milk Producers Federation, an organization that represents dairy farmers. To his knowledge, he added, this hasn’t happened.

Speculation filled knowledge gaps. Zach Riley, head of the Colorado Livestock Association, said he suspected that wild birds may be spreading the virus to herds across the country, despite scientific data suggesting otherwise. Riley said farmers were considering whether to install “floppy inflatable men you see outside of car dealerships” to ward off the birds.

Advisories from agriculture departments to farmers were somewhat speculative, too. Officials recommended biosecurity measures such as disinfecting equipment and limiting visitors. As the virus kept spreading throughout the summer, USDA senior official Eric Deeble said at a press briefing, “The response is adequate.”

The USDA, the Centers for Disease Control and Prevention, and the Food and Drug Administration presented a united front at these briefings, calling it a “One Health” approach. In reality, agriculture agencies took the lead.

This was explicit in an email from a local health department in Colorado to the county’s commissioners. “The State is treating this primarily as an agriculture issue (rightly so) and the public health part is secondary,” wrote Jason Chessher, public health director in Weld County, Colorado. The state’s leading agriculture county, Weld’s livestock and poultry industry produces about $1.9 billion in sales each year.

 

Patchy Surveillance

In July, the bird flu spread from dairies in Colorado to poultry farms. To contain it, two poultry operations employed about 650 temporary workers — Spanish-speaking immigrants as young as 15 — to cull flocks. Inside hot barns, they caught infected birds, gassed them with carbon dioxide, and disposed of the carcasses. Many did the hazardous job without goggles, face masks, and gloves.

By the time Colorado’s health department asked if workers felt sick, five women and four men had been infected. They all had red, swollen eyes — conjunctivitis — and several had such symptoms as fevers, body aches, and nausea.

State health departments posted online notices offering farms protective gear, but dairy workers in several states told KFF Health News that they had none. They also hadn’t heard about the bird flu, never mind tests for it.

Studies in Colorado, Michigan, and Texas would later show that bird flu cases had gone under the radar. In one analysis, eight dairy workers who hadn’t been tested — 7% of those studied — had antibodies against the virus, a sign that they had been infected.

Missed cases made it impossible to determine how the virus jumped into people and whether it was growing more infectious or dangerous. “I have been distressed and depressed by the lack of epidemiologic data and the lack of surveillance,” said Nicole Lurie, an executive director at the international organization the Coalition for Epidemic Preparedness Innovations, who served as assistant secretary for preparedness and response in the Obama administration.

Citing “insufficient data,” the British government raised its assessment of the risk posed by the US dairy outbreak in July from three to four on a six-tier scale.

Virologists around the world said they were flabbergasted by how poorly the United States was tracking the situation. “You are surrounded by highly pathogenic viruses in the wild and in farm animals,” said Marion Koopmans, head of virology at Erasmus Medical Center in the Netherlands. “If 3 months from now we are at the start of the pandemic, it is nobody’s surprise.”

Although the bird flu is not yet spreading swiftly between people, a shift in that direction could cause immense suffering. The CDC has repeatedly described the cases among farmworkers this year as mild — they weren’t hospitalized. But that doesn’t mean symptoms are a breeze, or that the virus can’t cause worse.

“It does not look pleasant,” wrote Sean Roberts, an emergency services specialist at the Tulare County, California, health department in an email to colleagues in May. He described photographs of an infected dairy worker in another state: “Apparently, the conjunctivitis that this is causing is not a mild one, but rather ruptured blood vessels and bleeding conjunctiva.”

Over the past 30 years, half of around 900 people diagnosed with bird flu around the world have died. Even if the case fatality rate is much lower for this strain of the bird flu, COVID showed how devastating a 1% death rate can be when a virus spreads easily.

Like other cases around the world, the person now hospitalized with the bird flu in Louisiana appears to have gotten the virus directly from birds. After the case was announced, the CDC released a statement saying, “A sporadic case of severe H5N1 bird flu illness in a person is not unexpected.”

 

‘The Cows Are More Valuable Than Us’

Local health officials were trying hard to track infections, according to hundreds of emails from county health departments in five states. But their efforts were stymied. Even if farmers reported infected herds to the USDA and agriculture agencies told health departments where the infected cows were, health officials had to rely on farm owners for access.

“The agriculture community has dictated the rules of engagement from the start,” said Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota. “That was a big mistake.”

Some farmers told health officials not to visit and declined to monitor their employees for signs of sickness. Sending workers to clinics for testing could leave them shorthanded when cattle needed care. “Producer refuses to send workers to Sunrise [clinic] to get tested since they’re too busy. He has pink eye, too,” said an email from the Weld, Colorado, health department.

“We know of 386 persons exposed — but we know this is far from the total,” said an email from a public health specialist to officials at Tulare’s health department recounting a call with state health officials. “Employers do not want to run this through worker’s compensation. Workers are hesitant to get tested due to cost,” she wrote.

Jennifer Morse, medical director of the Mid-Michigan District Health Department, said local health officials have been hesitant to apply pressure after the backlash many faced at the peak of COVID. Describing the 19 rural counties she serves as “very minimal government–minded,” she said, “if you try to work against them, it will not go well.”

Rural health departments are also stretched thin. Organizations that specialize in outreach to farmworkers offered to assist health officials early in the outbreak, but months passed without contracts or funding. During the first years of COVID, lagging government funds for outreach to farmworkers and other historically marginalized groups led to a disproportionate toll of the disease among people of color.

Kevin Griffis, director of communications at the CDC, said the agency worked with the National Center for Farmworker Health throughout the summer “to reach every farmworker impacted by H5N1.” But Bethany Boggess Alcauter, the center’s director of public health programs, said it didn’t receive a CDC grant for bird flu outreach until October, to the tune of $4 million. Before then, she said, the group had very limited funds for the task. “We are certainly not reaching ‘every farmworker,’” she added.

Farmworker advocates also pressed the CDC for money to offset workers’ financial concerns about testing, including paying for medical care, sick leave, and the risk of being fired. This amounted to an offer of $75 each. “Outreach is clearly not a huge priority,” Boggess said. “I hear over and over from workers, ‘The cows are more valuable than us.’ ”

The USDA has so far put more than $2.1 billion into reimbursing poultry and dairy farmers for losses due to the bird flu and other measures to control the spread on farms. Federal agencies have also put $292 million into developing and stockpiling bird flu vaccines for animals and people. In a controversial decision, the CDC has advised against offering the ones on hand to farmworkers.

“If you want to keep this from becoming a human pandemic, you focus on protecting farmworkers, since that’s the most likely way that this will enter the human population,” said Peg Seminario, an occupational health researcher in Bethesda, Maryland. “The fact that this isn’t happening drives me crazy.”

Nirav Shah, principal deputy director of the CDC, said the agency aims to keep workers safe. “Widespread awareness does take time,” he said. “And that’s the work we’re committed to doing.”

As President-elect Donald Trump comes into office in January, farmworkers may be even less protected. Trump’s pledge of mass deportations will have repercussions whether they happen or not, said Tania Pacheco-Werner, director of the Central Valley Health Policy Institute in California.

Many dairy and poultry workers are living in the United States without authorization or on temporary visas linked to their employers. Such precarity made people less willing to see doctors about COVID symptoms or complain about unsafe working conditions in 2020. Pacheco-Werner said, “Mass deportation is an astronomical challenge for public health.”

 

Not ‘Immaculate Conception’

A switch flipped in September among experts who study pandemics as national security threats. A patient in Missouri had the bird flu, and no one knew why. “Evidence points to this being a one-off case,” Shah said at a briefing with journalists. About a month later, the agency revealed it was not.

Antibody tests found that a person who lived with the patient had been infected, too. The CDC didn’t know how the two had gotten the virus, and the possibility of human transmission couldn’t be ruled out.

Nonetheless, at an October briefing, Shah said the public risk remained low and Deeble said he was optimistic that the dairy outbreak could be eliminated.

Experts were perturbed by such confident statements in the face of uncertainty, especially as California’s outbreak spiked and a child was mysteriously infected by the same strain of virus found on dairy farms.

“This wasn’t just immaculate conception,” said Stephen Morrison, director of the Global Health Policy Center at the Center for Strategic and International Studies. “It came from somewhere and we don’t know where, but that hasn’t triggered any kind of reset in approach — just the same kind of complacency and low energy.”

Sam Scarpino, a disease surveillance specialist in the Boston area, wondered how many other mysterious infections had gone undetected. Surveillance outside of farms was even patchier than on them, and bird flu tests have been hard to get.

Although pandemic experts had identified the CDC’s singular hold on testing for new viruses as a key explanation for why America was hit so hard by COVID in 2020, the system remained the same. Bird flu tests could be run only by the CDC and public health labs until this month, even though commercial and academic diagnostic laboratories had inquired about running tests since April. The CDC and FDA should have tried to help them along months ago, said Ali Khan, a former top CDC official who now leads the University of Nebraska Medical Center College of Public Health.

As winter sets in, the bird flu becomes harder to spot because patient symptoms may be mistaken for the seasonal flu. Flu season also raises a risk that the two flu viruses could swap genes if they infect a person simultaneously. That could form a hybrid bird flu that spreads swiftly through coughs and sneezes.

A sluggish response to emerging outbreaks may simply be a new, unfortunate norm for America, said Bollyky, at the Council on Foreign Relations. If so, the nation has gotten lucky that the bird flu still can’t spread easily between people. Controlling the virus will be much harder and costlier than it would have been when the outbreak was small. But it’s possible.

Agriculture officials could start testing every silo of bulk milk, in every state, monthly, said Poulsen, the livestock veterinarian. “Not one and done,” he added. If they detect the virus, they’d need to determine the affected farm in time to stop sick cows from spreading infections to the rest of the herd — or at least to other farms. Cows can spread the bird flu before they’re sick, he said, so speed is crucial.

Curtailing the virus on farms is the best way to prevent human infections, said Jennifer Nuzzo, director of the Pandemic Center at Brown University, but human surveillance must be stepped up, too. Every clinic serving communities where farmworkers live should have easy access to bird flu tests — and be encouraged to use them. Funds for farmworker outreach must be boosted. And, she added, the CDC should change its position and offer farmworkers bird flu vaccines to protect them and ward off the chance of a hybrid bird flu that spreads quickly.

The rising number of cases not linked to farms signals a need for more testing in general. When patients are positive on a general flu test — a common diagnostic that indicates human, swine, or bird flu — clinics should probe more deeply, Nuzzo said.

The alternative is a wait-and-see approach in which the nation responds only after enormous damage to lives or businesses. This tack tends to rely on mass vaccination. But an effort analogous to Trump’s Operation Warp Speed is not assured, and neither is rollout like that for the first COVID shots, given a rise in vaccine skepticism among Republican lawmakers.

Change may instead need to start from the bottom up — on dairy farms, still the most common source of human infections, said Poulsen. He noticed a shift in attitudes among farmers at the Dairy Expo: “They’re starting to say, ‘How do I save my dairy for the next generation?’ They recognize how severe this is, and that it’s not just going away.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF — the independent source for health policy research, polling, and journalism.

 

Current management of children and adolescents with long COVID was the focus of various presentations at the 3rd Long COVID Congress in Berlin in November. The congress aimed to facilitate in-depth discussions on recent research projects, diagnostic procedures, and therapeutic approaches to enhance care for long COVID patients. In 2024, the focus was on research into long COVID in children and adolescents and how to improve their care.

Uta Behrends, MD, head of the Munich Chronic Fatigue Center, Center for Pediatric and Adolescent Medicine at the Technical University of Munich in Germany, and Nicole Toepfner, MD, a pediatrician at the University Hospital in Dresden, Germany, provided an initial overview.

 

Prevalence Data Are Limited

Data on the incidence and prevalence of the condition in children and adolescents are limited because most studies have primarily examined adults. A 2022 Swiss study estimated that it affects between 2% and 3.5% of children and adolescents who contract COVID-19. A recent study published in JAMA involving 5367 children and adolescents found that 20% of children aged 6-11 years and 14% of adolescents met the researchers’ criteria for long COVID.

Impaired Mental Health

Initial data from the latest wave of the population-based longitudinal COPSY (Corona and Psyche) study showed that, compared with their peer group, children and adolescents diagnosed with long COVID exhibit significantly higher rates of psychological issues and depressive symptoms. Although no significant differences were found in anxiety levels, study leader Ulrike Ravens-Sieberer, PhD, from the University Medical Center Hamburg-Eppendorf, Germany, told the congress that those with long COVID also report more frequent somatic or psychological health complaints and lower health-related quality of life than peers.

Addressing Data Gaps

Another study due to launch in January 2025 and run through to 2028 is the COVYOUTH data study, which aims to better understand the nature, frequency, and risk factors of COVID-related sequelae in children and adolescents.

Study centers include Ruhr University Bochum, University Hospital Cologne, the Paul-Ehrlich-Institut, and University Medical Center Hamburg-Eppendorf. Using routine data from statutory health insurance and newly developed case definitions, researchers aim to investigate psychological stress caused by COVID-19 measures, post-COVID syndrome and myocarditis, and adverse effects of COVID-19 vaccinations. 

Specialized Diagnostics and Care

The Post-COVID Kids Bavaria project offers specialized diagnostics and care for children and adolescents, including a day clinic, telemedical follow-ups, and an inpatient pain therapy module providing age-appropriate care as close to patients’ homes as possible.

MOVE-COVID is a model project for patient-focused research on long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) involving university pediatric hospitals in Freiburg, Heidelberg, Tübingen, and Ulm. It also aims to establish a care network across the state of Baden-Württemberg, including the establishment of long COVID outpatient clinics at social pediatric centers in the network hospitals, as well as enhanced telemedical support and standardized diagnostic and treatment protocols. “MOVE-COVID has successfully consolidated competencies and capacities in patient care, health services research, and patient-focused studies across multiple centers,” Behrends said.

 

Chronic Pain and Fatigue

Post-COVID syndromes in children and adolescents may feature profound fatigue, unrefreshing sleep, post-exertional malaise, cognitive dysfunction, and orthostatic intolerance and overlap with conditions such as ME/CFS. According to the German patient association Fatigatio, Berlin, research and studies for these conditions in children remain limited compared with those in adults. However, the US Centers for Disease Control estimates that around 2% of ME/CFS patients are children or adolescents, with the majority being teenagers.

Two inpatient treatment concepts, SHARK and TIGER, developed by Lea Höfel, PhD, head of the Centre for Pain Therapy for Young People and the Psychological Service at the Children’s Hospital in Garmisch-Partenkirchen, address chronic pain, fatigue, and ME/CFS in young people. These programs integrate structured breaks and flexible access to multiple therapists as needed. The TIGER program focuses on those with post-exertional malaise, while the SHARK program is designed for adolescents without this symptom. Both programs last 4.5 to 5 weeks and emphasize symptom reduction, education, and energy management.

 

Preliminary Results

SHARK included 30 participants (7 men; average age, 16 years), of whom 12 had a history of SARS-CoV-2 infection. TIGER involved 100 participants (24 men; average age, 16.7 years), of whom 32 had a SARS-CoV-2 infection as a triggering event. Other triggers included Epstein-Barr virus and other infections.

Preliminary findings from the projects indicate that optimized management with outpatient and follow-up care can yield positive, sometimes lasting effects. No significant differences between SARS-CoV-2 and other triggers emerged, but pain proved more manageable in the SHARK group than in the TIGER group, suggesting they may involve different pathological mechanisms.

 

Hope for Improved Outcomes

“It’s important to move away from the idea that nothing can be done,” Behrends said. This is a common attitude with children and adolescents displaying these types of symptoms, but it’s simply not true. “Even in pediatrics, we have numerous therapeutic options that may offer relief, from medication to psychosocial interventions.”

This story was translated from Medscape’s German edition 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.

Current management of children and adolescents with long COVID was the focus of various presentations at the 3rd Long COVID Congress in Berlin in November. The congress aimed to facilitate in-depth discussions on recent research projects, diagnostic procedures, and therapeutic approaches to enhance care for long COVID patients. In 2024, the focus was on research into long COVID in children and adolescents and how to improve their care.

Uta Behrends, MD, head of the Munich Chronic Fatigue Center, Center for Pediatric and Adolescent Medicine at the Technical University of Munich in Germany, and Nicole Toepfner, MD, a pediatrician at the University Hospital in Dresden, Germany, provided an initial overview.

 

Prevalence Data Are Limited

Data on the incidence and prevalence of the condition in children and adolescents are limited because most studies have primarily examined adults. A 2022 Swiss study estimated that it affects between 2% and 3.5% of children and adolescents who contract COVID-19. A recent study published in JAMA involving 5367 children and adolescents found that 20% of children aged 6-11 years and 14% of adolescents met the researchers’ criteria for long COVID.

Impaired Mental Health

Initial data from the latest wave of the population-based longitudinal COPSY (Corona and Psyche) study showed that, compared with their peer group, children and adolescents diagnosed with long COVID exhibit significantly higher rates of psychological issues and depressive symptoms. Although no significant differences were found in anxiety levels, study leader Ulrike Ravens-Sieberer, PhD, from the University Medical Center Hamburg-Eppendorf, Germany, told the congress that those with long COVID also report more frequent somatic or psychological health complaints and lower health-related quality of life than peers.

Addressing Data Gaps

Another study due to launch in January 2025 and run through to 2028 is the COVYOUTH data study, which aims to better understand the nature, frequency, and risk factors of COVID-related sequelae in children and adolescents.

Study centers include Ruhr University Bochum, University Hospital Cologne, the Paul-Ehrlich-Institut, and University Medical Center Hamburg-Eppendorf. Using routine data from statutory health insurance and newly developed case definitions, researchers aim to investigate psychological stress caused by COVID-19 measures, post-COVID syndrome and myocarditis, and adverse effects of COVID-19 vaccinations. 

Specialized Diagnostics and Care

The Post-COVID Kids Bavaria project offers specialized diagnostics and care for children and adolescents, including a day clinic, telemedical follow-ups, and an inpatient pain therapy module providing age-appropriate care as close to patients’ homes as possible.

MOVE-COVID is a model project for patient-focused research on long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) involving university pediatric hospitals in Freiburg, Heidelberg, Tübingen, and Ulm. It also aims to establish a care network across the state of Baden-Württemberg, including the establishment of long COVID outpatient clinics at social pediatric centers in the network hospitals, as well as enhanced telemedical support and standardized diagnostic and treatment protocols. “MOVE-COVID has successfully consolidated competencies and capacities in patient care, health services research, and patient-focused studies across multiple centers,” Behrends said.

 

Chronic Pain and Fatigue

Post-COVID syndromes in children and adolescents may feature profound fatigue, unrefreshing sleep, post-exertional malaise, cognitive dysfunction, and orthostatic intolerance and overlap with conditions such as ME/CFS. According to the German patient association Fatigatio, Berlin, research and studies for these conditions in children remain limited compared with those in adults. However, the US Centers for Disease Control estimates that around 2% of ME/CFS patients are children or adolescents, with the majority being teenagers.

Two inpatient treatment concepts, SHARK and TIGER, developed by Lea Höfel, PhD, head of the Centre for Pain Therapy for Young People and the Psychological Service at the Children’s Hospital in Garmisch-Partenkirchen, address chronic pain, fatigue, and ME/CFS in young people. These programs integrate structured breaks and flexible access to multiple therapists as needed. The TIGER program focuses on those with post-exertional malaise, while the SHARK program is designed for adolescents without this symptom. Both programs last 4.5 to 5 weeks and emphasize symptom reduction, education, and energy management.

 

Preliminary Results

SHARK included 30 participants (7 men; average age, 16 years), of whom 12 had a history of SARS-CoV-2 infection. TIGER involved 100 participants (24 men; average age, 16.7 years), of whom 32 had a SARS-CoV-2 infection as a triggering event. Other triggers included Epstein-Barr virus and other infections.

Preliminary findings from the projects indicate that optimized management with outpatient and follow-up care can yield positive, sometimes lasting effects. No significant differences between SARS-CoV-2 and other triggers emerged, but pain proved more manageable in the SHARK group than in the TIGER group, suggesting they may involve different pathological mechanisms.

 

Hope for Improved Outcomes

“It’s important to move away from the idea that nothing can be done,” Behrends said. This is a common attitude with children and adolescents displaying these types of symptoms, but it’s simply not true. “Even in pediatrics, we have numerous therapeutic options that may offer relief, from medication to psychosocial interventions.”

This story was translated from Medscape’s German edition 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.

Current management of children and adolescents with long COVID was the focus of various presentations at the 3rd Long COVID Congress in Berlin in November. The congress aimed to facilitate in-depth discussions on recent research projects, diagnostic procedures, and therapeutic approaches to enhance care for long COVID patients. In 2024, the focus was on research into long COVID in children and adolescents and how to improve their care.

Uta Behrends, MD, head of the Munich Chronic Fatigue Center, Center for Pediatric and Adolescent Medicine at the Technical University of Munich in Germany, and Nicole Toepfner, MD, a pediatrician at the University Hospital in Dresden, Germany, provided an initial overview.

 

Prevalence Data Are Limited

Data on the incidence and prevalence of the condition in children and adolescents are limited because most studies have primarily examined adults. A 2022 Swiss study estimated that it affects between 2% and 3.5% of children and adolescents who contract COVID-19. A recent study published in JAMA involving 5367 children and adolescents found that 20% of children aged 6-11 years and 14% of adolescents met the researchers’ criteria for long COVID.

Impaired Mental Health

Initial data from the latest wave of the population-based longitudinal COPSY (Corona and Psyche) study showed that, compared with their peer group, children and adolescents diagnosed with long COVID exhibit significantly higher rates of psychological issues and depressive symptoms. Although no significant differences were found in anxiety levels, study leader Ulrike Ravens-Sieberer, PhD, from the University Medical Center Hamburg-Eppendorf, Germany, told the congress that those with long COVID also report more frequent somatic or psychological health complaints and lower health-related quality of life than peers.

Addressing Data Gaps

Another study due to launch in January 2025 and run through to 2028 is the COVYOUTH data study, which aims to better understand the nature, frequency, and risk factors of COVID-related sequelae in children and adolescents.

Study centers include Ruhr University Bochum, University Hospital Cologne, the Paul-Ehrlich-Institut, and University Medical Center Hamburg-Eppendorf. Using routine data from statutory health insurance and newly developed case definitions, researchers aim to investigate psychological stress caused by COVID-19 measures, post-COVID syndrome and myocarditis, and adverse effects of COVID-19 vaccinations. 

Specialized Diagnostics and Care

The Post-COVID Kids Bavaria project offers specialized diagnostics and care for children and adolescents, including a day clinic, telemedical follow-ups, and an inpatient pain therapy module providing age-appropriate care as close to patients’ homes as possible.

MOVE-COVID is a model project for patient-focused research on long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) involving university pediatric hospitals in Freiburg, Heidelberg, Tübingen, and Ulm. It also aims to establish a care network across the state of Baden-Württemberg, including the establishment of long COVID outpatient clinics at social pediatric centers in the network hospitals, as well as enhanced telemedical support and standardized diagnostic and treatment protocols. “MOVE-COVID has successfully consolidated competencies and capacities in patient care, health services research, and patient-focused studies across multiple centers,” Behrends said.

 

Chronic Pain and Fatigue

Post-COVID syndromes in children and adolescents may feature profound fatigue, unrefreshing sleep, post-exertional malaise, cognitive dysfunction, and orthostatic intolerance and overlap with conditions such as ME/CFS. According to the German patient association Fatigatio, Berlin, research and studies for these conditions in children remain limited compared with those in adults. However, the US Centers for Disease Control estimates that around 2% of ME/CFS patients are children or adolescents, with the majority being teenagers.

Two inpatient treatment concepts, SHARK and TIGER, developed by Lea Höfel, PhD, head of the Centre for Pain Therapy for Young People and the Psychological Service at the Children’s Hospital in Garmisch-Partenkirchen, address chronic pain, fatigue, and ME/CFS in young people. These programs integrate structured breaks and flexible access to multiple therapists as needed. The TIGER program focuses on those with post-exertional malaise, while the SHARK program is designed for adolescents without this symptom. Both programs last 4.5 to 5 weeks and emphasize symptom reduction, education, and energy management.

 

Preliminary Results

SHARK included 30 participants (7 men; average age, 16 years), of whom 12 had a history of SARS-CoV-2 infection. TIGER involved 100 participants (24 men; average age, 16.7 years), of whom 32 had a SARS-CoV-2 infection as a triggering event. Other triggers included Epstein-Barr virus and other infections.

Preliminary findings from the projects indicate that optimized management with outpatient and follow-up care can yield positive, sometimes lasting effects. No significant differences between SARS-CoV-2 and other triggers emerged, but pain proved more manageable in the SHARK group than in the TIGER group, suggesting they may involve different pathological mechanisms.

 

Hope for Improved Outcomes

“It’s important to move away from the idea that nothing can be done,” Behrends said. This is a common attitude with children and adolescents displaying these types of symptoms, but it’s simply not true. “Even in pediatrics, we have numerous therapeutic options that may offer relief, from medication to psychosocial interventions.”

This story was translated from Medscape’s German edition 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:

Long-term daily supplementation with moderate (1600 international units [IU]) or high (3200 IU) doses of vitamin D3 doesn’t reduce the risk for type 2 diabetes (T2D) among generally healthy older adults who have serum vitamin D levels sufficient for bone health.

 

METHODOLOGY:

• Observational studies have consistently linked low vitamin D levels with an increased risk for T2D, and short-term randomized trials have shown a protective effect of vitamin D supplementation for those with impaired glucose metabolism but not in populations of average risk-taking low doses.
• The Finnish Vitamin D Trial, conducted from 2012 to 2018 in generally healthy men (≥ 60 years) and women (≥ 65 years) without a history of cardiovascular disease or cancer, assessed the effects of 5 years of moderate and high vitamin D3 supplementation on the incidence of major chronic diseases.
• This analysis of T2D incidence included 2271 older participants (mean age, 68.2 years; 43.9% women) without self-reported use of diabetes medications at baseline.
• Participants were randomly assigned to receive placebo (n = 760), 1600 IU/d of vitamin D3 (n = 744), or 3200 IU/d of vitamin D3 (n = 767) and followed for a mean duration of 4.2 years, with T2D incidence assessed by diagnostic code from health registries.
• A representative subcohort of 505 participants underwent detailed investigations including blood sampling at months 0, 6, 12, and 24 for serum 25-hydroxyvitamin D3 [25(OH)D3], plasma glucose, and insulin concentrations.

TAKEAWAY:

• No significant difference in T2D incidence was observed between groups: Placebo (5.0%; 38 people), 1600 IU/d (4.2%; 31 people), and 3200 IU/d (4.7%; 36 people; P = .731 for trend), with no appreciable sex differences.
• When stratified by body mass index (BMI), a lower incidence of T2D with vitamin D supplementation was observed among those with a BMI < 25 (with wide CIs), but not among those with a higher BMI.
• In the subcohort, no significant differences in changes in plasma glucose, insulin concentrations, BMI, or waist circumference with vitamin D3 were observed between the three treatment groups during the 24-month follow-up (P ≥ .19).
• In an analysis excluding T2D from the first 2 years, researchers observed a potentially increased risk for T2D with increasing vitamin D dose (with wide CIs).

IN PRACTICE:

“Our findings do not suggest benefits of long-term moderate- or high-dose vitamin D3 supplementation for incidence of type 2 diabetes or glucose metabolism or body size among generally healthy older vitamin D–sufficient men and women who were not at high risk for type 2 diabetes,” the authors wrote.

SOURCE:

The study was led by Jyrki K. Virtanen, University of Eastern Finland, Institute of Public Health and Clinical Nutrition, Kuopio, and was published online in Diabetologia.

LIMITATIONS:

The study relied on national health registries to collect data on incident T2D events, which may have led to some T2D cases being missed. Data on serum 25(OH)D3 concentrations were available for the subcohort only, which prevented the investigation of whether vitamin D–deficient participants would have benefited from supplementation. The study was not specifically designed or powered for diabetes prevention, and information on participants’ diabetes history at baseline was not available. Wide CIs suggest uncertainty around some of the findings. Study participants were White and older, so caution is needed in generalizing results to groups of other ages, races and ethnicities, and different vitamin D levels.

DISCLOSURES:

The study received funding from the Academy of Finland, University of Eastern Finland, Juho Vainio Foundation, and other sources. Some authors reported receiving grants or travel support from pharmaceutical companies and certain institutions.

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:

Long-term daily supplementation with moderate (1600 international units [IU]) or high (3200 IU) doses of vitamin D3 doesn’t reduce the risk for type 2 diabetes (T2D) among generally healthy older adults who have serum vitamin D levels sufficient for bone health.

 

METHODOLOGY:

• Observational studies have consistently linked low vitamin D levels with an increased risk for T2D, and short-term randomized trials have shown a protective effect of vitamin D supplementation for those with impaired glucose metabolism but not in populations of average risk-taking low doses.
• The Finnish Vitamin D Trial, conducted from 2012 to 2018 in generally healthy men (≥ 60 years) and women (≥ 65 years) without a history of cardiovascular disease or cancer, assessed the effects of 5 years of moderate and high vitamin D3 supplementation on the incidence of major chronic diseases.
• This analysis of T2D incidence included 2271 older participants (mean age, 68.2 years; 43.9% women) without self-reported use of diabetes medications at baseline.
• Participants were randomly assigned to receive placebo (n = 760), 1600 IU/d of vitamin D3 (n = 744), or 3200 IU/d of vitamin D3 (n = 767) and followed for a mean duration of 4.2 years, with T2D incidence assessed by diagnostic code from health registries.
• A representative subcohort of 505 participants underwent detailed investigations including blood sampling at months 0, 6, 12, and 24 for serum 25-hydroxyvitamin D3 [25(OH)D3], plasma glucose, and insulin concentrations.

TAKEAWAY:

• No significant difference in T2D incidence was observed between groups: Placebo (5.0%; 38 people), 1600 IU/d (4.2%; 31 people), and 3200 IU/d (4.7%; 36 people; P = .731 for trend), with no appreciable sex differences.
• When stratified by body mass index (BMI), a lower incidence of T2D with vitamin D supplementation was observed among those with a BMI < 25 (with wide CIs), but not among those with a higher BMI.
• In the subcohort, no significant differences in changes in plasma glucose, insulin concentrations, BMI, or waist circumference with vitamin D3 were observed between the three treatment groups during the 24-month follow-up (P ≥ .19).
• In an analysis excluding T2D from the first 2 years, researchers observed a potentially increased risk for T2D with increasing vitamin D dose (with wide CIs).

IN PRACTICE:

“Our findings do not suggest benefits of long-term moderate- or high-dose vitamin D3 supplementation for incidence of type 2 diabetes or glucose metabolism or body size among generally healthy older vitamin D–sufficient men and women who were not at high risk for type 2 diabetes,” the authors wrote.

SOURCE:

The study was led by Jyrki K. Virtanen, University of Eastern Finland, Institute of Public Health and Clinical Nutrition, Kuopio, and was published online in Diabetologia.

LIMITATIONS:

The study relied on national health registries to collect data on incident T2D events, which may have led to some T2D cases being missed. Data on serum 25(OH)D3 concentrations were available for the subcohort only, which prevented the investigation of whether vitamin D–deficient participants would have benefited from supplementation. The study was not specifically designed or powered for diabetes prevention, and information on participants’ diabetes history at baseline was not available. Wide CIs suggest uncertainty around some of the findings. Study participants were White and older, so caution is needed in generalizing results to groups of other ages, races and ethnicities, and different vitamin D levels.

DISCLOSURES:

The study received funding from the Academy of Finland, University of Eastern Finland, Juho Vainio Foundation, and other sources. Some authors reported receiving grants or travel support from pharmaceutical companies and certain institutions.

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:

Long-term daily supplementation with moderate (1600 international units [IU]) or high (3200 IU) doses of vitamin D3 doesn’t reduce the risk for type 2 diabetes (T2D) among generally healthy older adults who have serum vitamin D levels sufficient for bone health.

 

METHODOLOGY:

• Observational studies have consistently linked low vitamin D levels with an increased risk for T2D, and short-term randomized trials have shown a protective effect of vitamin D supplementation for those with impaired glucose metabolism but not in populations of average risk-taking low doses.
• The Finnish Vitamin D Trial, conducted from 2012 to 2018 in generally healthy men (≥ 60 years) and women (≥ 65 years) without a history of cardiovascular disease or cancer, assessed the effects of 5 years of moderate and high vitamin D3 supplementation on the incidence of major chronic diseases.
• This analysis of T2D incidence included 2271 older participants (mean age, 68.2 years; 43.9% women) without self-reported use of diabetes medications at baseline.
• Participants were randomly assigned to receive placebo (n = 760), 1600 IU/d of vitamin D3 (n = 744), or 3200 IU/d of vitamin D3 (n = 767) and followed for a mean duration of 4.2 years, with T2D incidence assessed by diagnostic code from health registries.
• A representative subcohort of 505 participants underwent detailed investigations including blood sampling at months 0, 6, 12, and 24 for serum 25-hydroxyvitamin D3 [25(OH)D3], plasma glucose, and insulin concentrations.

TAKEAWAY:

• No significant difference in T2D incidence was observed between groups: Placebo (5.0%; 38 people), 1600 IU/d (4.2%; 31 people), and 3200 IU/d (4.7%; 36 people; P = .731 for trend), with no appreciable sex differences.
• When stratified by body mass index (BMI), a lower incidence of T2D with vitamin D supplementation was observed among those with a BMI < 25 (with wide CIs), but not among those with a higher BMI.
• In the subcohort, no significant differences in changes in plasma glucose, insulin concentrations, BMI, or waist circumference with vitamin D3 were observed between the three treatment groups during the 24-month follow-up (P ≥ .19).
• In an analysis excluding T2D from the first 2 years, researchers observed a potentially increased risk for T2D with increasing vitamin D dose (with wide CIs).

IN PRACTICE:

“Our findings do not suggest benefits of long-term moderate- or high-dose vitamin D3 supplementation for incidence of type 2 diabetes or glucose metabolism or body size among generally healthy older vitamin D–sufficient men and women who were not at high risk for type 2 diabetes,” the authors wrote.

SOURCE:

The study was led by Jyrki K. Virtanen, University of Eastern Finland, Institute of Public Health and Clinical Nutrition, Kuopio, and was published online in Diabetologia.

LIMITATIONS:

The study relied on national health registries to collect data on incident T2D events, which may have led to some T2D cases being missed. Data on serum 25(OH)D3 concentrations were available for the subcohort only, which prevented the investigation of whether vitamin D–deficient participants would have benefited from supplementation. The study was not specifically designed or powered for diabetes prevention, and information on participants’ diabetes history at baseline was not available. Wide CIs suggest uncertainty around some of the findings. Study participants were White and older, so caution is needed in generalizing results to groups of other ages, races and ethnicities, and different vitamin D levels.

DISCLOSURES:

The study received funding from the Academy of Finland, University of Eastern Finland, Juho Vainio Foundation, and other sources. Some authors reported receiving grants or travel support from pharmaceutical companies and certain institutions.

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.

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

The FDA accepted the companies’ supplemental new drug application in June with a decision on approval expected in early February 2025.

“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

The FDA accepted the companies’ supplemental new drug application in June with a decision on approval expected in early February 2025.

“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

The FDA accepted the companies’ supplemental new drug application in June with a decision on approval expected in early February 2025.

“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.

TOPLINE:

Ivarmacitinib, a novel Janus kinase 1 inhibitor, alleviates symptoms, reduces disease activity, and improves physical function and quality of life in patients with moderate to severe rheumatoid arthritis (RA) who have an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).

METHODOLOGY:

• This phase 3 trial, conducted across 59 sites in China, evaluated the efficacy and safety of ivarmacitinib in patients with moderate to severe active RA despite treatment with one or more csDMARDs.
• The patients were randomly assigned to receive either placebo (n = 188; mean age, 50.9 years; 85.6% women) or 4 mg ivarmacitinib (n = 189; mean age, 49.7 years; 91% women) or 8 mg ivarmacitinib (n = 189; mean age, 49.8 years; 83.6% women) once daily for 24 weeks, alongside background csDMARDs.
• After 24 weeks, the patients receiving placebo were switched to receive 4 mg ivarmacitinib for the additional 28-week extension period, whereas those receiving ivarmacitinib continued their initial dosage.
• Secondary endpoints included the proportion of patients achieving American College of Rheumatology (ACR) 50/70 responses and, Disease Activity Score 28-joint count C-reactive protein (DAS28(CRP)) score < 2.6 or ≤ 3.2, as well as measures of other patient-reported outcomes such as pain, physical function, and quality of life at 24 and 52 weeks.

TAKEAWAY:

• At 24 weeks, the proportion of patients achieving a 20% improvement in the ACR20 response — the primary endpoint — was higher among those receiving 4 mg ivarmacitinib (70.4%) or 8 mg ivarmacitinib (75.1%) than among those receiving placebo (40.4%; P < .0001 for both comparisons), with the efficacy either maintained or improved through 52 weeks.
• The proportion of patients achieving ACR50/70 responses or a DAS28(CRP) score < 2.6 or ≤ 3.2 was higher in the ivarmacitinib groups than in the placebo group (P < .0001 for all comparisons).
• Compared with the placebo group, both the ivarmacitinib groups showed improvements in patient-reported outcomes such as pain, physical function, quality of life, and duration and severity of morning stiffness.
• The overall rates of treatment discontinuation caused by adverse events were low across all the groups, with no deaths, tuberculosis or gastrointestinal perforations reported throughout the 52 weeks.
•  

IN PRACTICE:

“Based on these findings, ivarmacitinib with background csDMARDs allowed, could be considered a treatment option in patients with moderate to severe active RA who have an inadequate response to csDMARDs,” the authors wrote.

SOURCE:

This study was led by Jinjing Liu and Xiaofeng Zeng, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Beijing, China. It was published online on November 27, 2024, in Annals of the Rheumatic Diseases.

LIMITATIONS:

As the study was conducted in a Chinese population, the findings may have limited applicability across diverse global populations. Additionally, as the placebo-controlled period was limited to 24 weeks because of ethical concerns, comparisons between placebo and ivarmacitinib beyond that period were restricted. Lastly, this study was not powered to compare efficacy and safety between the two active dose regimens.

DISCLOSURES:

This study was funded by Jiangsu Hengrui Pharmaceuticals. Two authors declared being employees of the company. The other authors reported no competing interests.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Ivarmacitinib, a novel Janus kinase 1 inhibitor, alleviates symptoms, reduces disease activity, and improves physical function and quality of life in patients with moderate to severe rheumatoid arthritis (RA) who have an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).

METHODOLOGY:

• This phase 3 trial, conducted across 59 sites in China, evaluated the efficacy and safety of ivarmacitinib in patients with moderate to severe active RA despite treatment with one or more csDMARDs.
• The patients were randomly assigned to receive either placebo (n = 188; mean age, 50.9 years; 85.6% women) or 4 mg ivarmacitinib (n = 189; mean age, 49.7 years; 91% women) or 8 mg ivarmacitinib (n = 189; mean age, 49.8 years; 83.6% women) once daily for 24 weeks, alongside background csDMARDs.
• After 24 weeks, the patients receiving placebo were switched to receive 4 mg ivarmacitinib for the additional 28-week extension period, whereas those receiving ivarmacitinib continued their initial dosage.
• Secondary endpoints included the proportion of patients achieving American College of Rheumatology (ACR) 50/70 responses and, Disease Activity Score 28-joint count C-reactive protein (DAS28(CRP)) score < 2.6 or ≤ 3.2, as well as measures of other patient-reported outcomes such as pain, physical function, and quality of life at 24 and 52 weeks.

TAKEAWAY:

• At 24 weeks, the proportion of patients achieving a 20% improvement in the ACR20 response — the primary endpoint — was higher among those receiving 4 mg ivarmacitinib (70.4%) or 8 mg ivarmacitinib (75.1%) than among those receiving placebo (40.4%; P < .0001 for both comparisons), with the efficacy either maintained or improved through 52 weeks.
• The proportion of patients achieving ACR50/70 responses or a DAS28(CRP) score < 2.6 or ≤ 3.2 was higher in the ivarmacitinib groups than in the placebo group (P < .0001 for all comparisons).
• Compared with the placebo group, both the ivarmacitinib groups showed improvements in patient-reported outcomes such as pain, physical function, quality of life, and duration and severity of morning stiffness.
• The overall rates of treatment discontinuation caused by adverse events were low across all the groups, with no deaths, tuberculosis or gastrointestinal perforations reported throughout the 52 weeks.
•  

IN PRACTICE:

“Based on these findings, ivarmacitinib with background csDMARDs allowed, could be considered a treatment option in patients with moderate to severe active RA who have an inadequate response to csDMARDs,” the authors wrote.

SOURCE:

This study was led by Jinjing Liu and Xiaofeng Zeng, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Beijing, China. It was published online on November 27, 2024, in Annals of the Rheumatic Diseases.

LIMITATIONS:

As the study was conducted in a Chinese population, the findings may have limited applicability across diverse global populations. Additionally, as the placebo-controlled period was limited to 24 weeks because of ethical concerns, comparisons between placebo and ivarmacitinib beyond that period were restricted. Lastly, this study was not powered to compare efficacy and safety between the two active dose regimens.

DISCLOSURES:

This study was funded by Jiangsu Hengrui Pharmaceuticals. Two authors declared being employees of the company. The other authors reported no competing interests.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Ivarmacitinib, a novel Janus kinase 1 inhibitor, alleviates symptoms, reduces disease activity, and improves physical function and quality of life in patients with moderate to severe rheumatoid arthritis (RA) who have an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).

METHODOLOGY:

• This phase 3 trial, conducted across 59 sites in China, evaluated the efficacy and safety of ivarmacitinib in patients with moderate to severe active RA despite treatment with one or more csDMARDs.
• The patients were randomly assigned to receive either placebo (n = 188; mean age, 50.9 years; 85.6% women) or 4 mg ivarmacitinib (n = 189; mean age, 49.7 years; 91% women) or 8 mg ivarmacitinib (n = 189; mean age, 49.8 years; 83.6% women) once daily for 24 weeks, alongside background csDMARDs.
• After 24 weeks, the patients receiving placebo were switched to receive 4 mg ivarmacitinib for the additional 28-week extension period, whereas those receiving ivarmacitinib continued their initial dosage.
• Secondary endpoints included the proportion of patients achieving American College of Rheumatology (ACR) 50/70 responses and, Disease Activity Score 28-joint count C-reactive protein (DAS28(CRP)) score < 2.6 or ≤ 3.2, as well as measures of other patient-reported outcomes such as pain, physical function, and quality of life at 24 and 52 weeks.

TAKEAWAY:

• At 24 weeks, the proportion of patients achieving a 20% improvement in the ACR20 response — the primary endpoint — was higher among those receiving 4 mg ivarmacitinib (70.4%) or 8 mg ivarmacitinib (75.1%) than among those receiving placebo (40.4%; P < .0001 for both comparisons), with the efficacy either maintained or improved through 52 weeks.
• The proportion of patients achieving ACR50/70 responses or a DAS28(CRP) score < 2.6 or ≤ 3.2 was higher in the ivarmacitinib groups than in the placebo group (P < .0001 for all comparisons).
• Compared with the placebo group, both the ivarmacitinib groups showed improvements in patient-reported outcomes such as pain, physical function, quality of life, and duration and severity of morning stiffness.
• The overall rates of treatment discontinuation caused by adverse events were low across all the groups, with no deaths, tuberculosis or gastrointestinal perforations reported throughout the 52 weeks.
•  

IN PRACTICE:

“Based on these findings, ivarmacitinib with background csDMARDs allowed, could be considered a treatment option in patients with moderate to severe active RA who have an inadequate response to csDMARDs,” the authors wrote.

SOURCE:

This study was led by Jinjing Liu and Xiaofeng Zeng, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Beijing, China. It was published online on November 27, 2024, in Annals of the Rheumatic Diseases.

LIMITATIONS:

As the study was conducted in a Chinese population, the findings may have limited applicability across diverse global populations. Additionally, as the placebo-controlled period was limited to 24 weeks because of ethical concerns, comparisons between placebo and ivarmacitinib beyond that period were restricted. Lastly, this study was not powered to compare efficacy and safety between the two active dose regimens.

DISCLOSURES:

This study was funded by Jiangsu Hengrui Pharmaceuticals. Two authors declared being employees of the company. The other authors reported no competing interests.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Estimation of cardiovascular risk (CVR) in individuals living with type 1 diabetes (T1D) was a key topic presented by Sophie Borot, MD, from Besançon University Hospital, Besançon, France, at the 40th congress of the French Society of Endocrinology. Borot highlighted the complexities of this subject, outlining several factors that contribute to its challenges.

A Heterogeneous Disease

T1D is a highly heterogeneous condition, and the patients included in studies reflect this diversity:

• The impact of blood glucose levels on CVR changes depending on diabetes duration, its history, the frequency of hypoglycemic episodes, average A1c levels over several years, and the patient’s age at diagnosis.
• A T1D diagnosis from the 1980s involved different management strategies compared with a diagnosis today.
• Patient profiles also vary based on complications such as nephropathy or cardiac autonomic neuropathy.
• Diffuse and distal arterial damage in T1D leads to more subtle and delayed pathologic events than in type 2 diabetes (T2D).
• Most clinical studies assess CVR over 10 years, but a 20- or 30-year evaluation would be more relevant.
• Patients may share CVR factors with the general population (eg, family history, smoking, sedentary lifestyle, obesity, hypertension, or elevated low-density lipoprotein [LDL] levels), raising questions about possible overlap with metabolic syndrome.
• Study criteria differ, with a focus on outcomes such as cardiovascular death, major adverse cardiovascular events like myocardial infarction and stroke, or other endpoints.
• CVR is measured using either absolute or relative values, with varying units of measurement.

A Recent Awareness

The concept of CVR in T1D is relatively new. Until the publication of the prospective Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study in 2005, it was believed that T1D control had no impact on CVR. However, follow-up results from the same cohort of 50,000 patients, published in 2022 after 30 years of observation, revealed that CVR was 20% higher in patients who received conventional hyperglycemia-targeted treatment than those undergoing intensive treatment. The CVR increases in conjunction with diabetes duration. The study also showed that even well-controlled glycemia in T1D carries CVR (primarily due to microangiopathy), and that the most critical factor for CVR is not A1c control but rather LDL cholesterol levels.

These findings were corroborated by a Danish prospective study, which demonstrated that while CVR increased in conjunction with the number of risk factors, it was 82% higher in patients with T1D than in a control group — even in the absence of risk factors.
 

Key Takeaways

At diagnosis, a fundamental difference exists between T1D and T2D in terms of the urgency to address CVR. In T2D, diabetes may have progressed for years before diagnosis, necessitating immediate CVR reduction efforts. In contrast, T1D is often diagnosed in younger patients with initially low CVR, raising questions about the optimal timing for interventions such as statin prescriptions.

Recommendations

The American Diabetes Association/European Association for the Study of Diabetes guidelines (2024) include the following recommendations:

For adults with T1D, treatment should mirror that for T2D:

• Between ages 20 and 40, statins are recommended if at least one CVR factor is present.
• For children 10 years of age or older with T1D, the LDL target is < 1.0 g/L. Statins are prescribed if LDL exceeds 1.6 g/L without CVR factors or 1.3 g/L with at least one CVR factor.

The European Society of Cardiology guidelines (2023) include the following:

• For the first time, a dedicated chapter addresses T1D. Like the American guidelines, routine statin use after age 40 is recommended.
• Before age 40, statins are prescribed if there is at least one CVR factor (microangiopathy) or a 10-year CVR ≥ 10% (based on a CVR calculator).

The International Society for Pediatric and Adolescent Diabetes guidelines (2022) recommend:

• For children 10 years of age or older, the LDL target is < 1.0 g/L. Statins are recommended if LDL exceeds 1.3 g/L.

CAC Score in High CVR

The French Society of Cardiology and the French-speaking Society of Diabetology recommend incorporating the coronary artery calcium (CAC) score to refine CVR classification in high-risk patients. For those without prior cardiovascular events, LDL targets vary based on CAC and age. For example:

• High-risk patients with a CAC of 0-10 are reclassified as moderate risk, with an LDL target of < 1 g/L.
• A CAC ≥ 400 indicates very high risk, warranting coronary exploration.
• Patients under 50 years of age with a CAC of 11-100 remain high risk, with an LDL target of 0.7 g/L.

Conclusion

CVR in patients with T1D remains challenging to define. However, it is essential to consider long-term outcomes, planning for 30 or 40 years into the future. This involves educating patients about the importance of prevention, even when reassuring numbers are seen in their youth.

This story was translated from Univadis France 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.

Estimation of cardiovascular risk (CVR) in individuals living with type 1 diabetes (T1D) was a key topic presented by Sophie Borot, MD, from Besançon University Hospital, Besançon, France, at the 40th congress of the French Society of Endocrinology. Borot highlighted the complexities of this subject, outlining several factors that contribute to its challenges.

A Heterogeneous Disease

T1D is a highly heterogeneous condition, and the patients included in studies reflect this diversity:

• The impact of blood glucose levels on CVR changes depending on diabetes duration, its history, the frequency of hypoglycemic episodes, average A1c levels over several years, and the patient’s age at diagnosis.
• A T1D diagnosis from the 1980s involved different management strategies compared with a diagnosis today.
• Patient profiles also vary based on complications such as nephropathy or cardiac autonomic neuropathy.
• Diffuse and distal arterial damage in T1D leads to more subtle and delayed pathologic events than in type 2 diabetes (T2D).
• Most clinical studies assess CVR over 10 years, but a 20- or 30-year evaluation would be more relevant.
• Patients may share CVR factors with the general population (eg, family history, smoking, sedentary lifestyle, obesity, hypertension, or elevated low-density lipoprotein [LDL] levels), raising questions about possible overlap with metabolic syndrome.
• Study criteria differ, with a focus on outcomes such as cardiovascular death, major adverse cardiovascular events like myocardial infarction and stroke, or other endpoints.
• CVR is measured using either absolute or relative values, with varying units of measurement.

A Recent Awareness

The concept of CVR in T1D is relatively new. Until the publication of the prospective Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study in 2005, it was believed that T1D control had no impact on CVR. However, follow-up results from the same cohort of 50,000 patients, published in 2022 after 30 years of observation, revealed that CVR was 20% higher in patients who received conventional hyperglycemia-targeted treatment than those undergoing intensive treatment. The CVR increases in conjunction with diabetes duration. The study also showed that even well-controlled glycemia in T1D carries CVR (primarily due to microangiopathy), and that the most critical factor for CVR is not A1c control but rather LDL cholesterol levels.

These findings were corroborated by a Danish prospective study, which demonstrated that while CVR increased in conjunction with the number of risk factors, it was 82% higher in patients with T1D than in a control group — even in the absence of risk factors.
 

Key Takeaways

At diagnosis, a fundamental difference exists between T1D and T2D in terms of the urgency to address CVR. In T2D, diabetes may have progressed for years before diagnosis, necessitating immediate CVR reduction efforts. In contrast, T1D is often diagnosed in younger patients with initially low CVR, raising questions about the optimal timing for interventions such as statin prescriptions.

Recommendations

The American Diabetes Association/European Association for the Study of Diabetes guidelines (2024) include the following recommendations:

For adults with T1D, treatment should mirror that for T2D:

• Between ages 20 and 40, statins are recommended if at least one CVR factor is present.
• For children 10 years of age or older with T1D, the LDL target is < 1.0 g/L. Statins are prescribed if LDL exceeds 1.6 g/L without CVR factors or 1.3 g/L with at least one CVR factor.

The European Society of Cardiology guidelines (2023) include the following:

• For the first time, a dedicated chapter addresses T1D. Like the American guidelines, routine statin use after age 40 is recommended.
• Before age 40, statins are prescribed if there is at least one CVR factor (microangiopathy) or a 10-year CVR ≥ 10% (based on a CVR calculator).

The International Society for Pediatric and Adolescent Diabetes guidelines (2022) recommend:

• For children 10 years of age or older, the LDL target is < 1.0 g/L. Statins are recommended if LDL exceeds 1.3 g/L.

CAC Score in High CVR

The French Society of Cardiology and the French-speaking Society of Diabetology recommend incorporating the coronary artery calcium (CAC) score to refine CVR classification in high-risk patients. For those without prior cardiovascular events, LDL targets vary based on CAC and age. For example:

• High-risk patients with a CAC of 0-10 are reclassified as moderate risk, with an LDL target of < 1 g/L.
• A CAC ≥ 400 indicates very high risk, warranting coronary exploration.
• Patients under 50 years of age with a CAC of 11-100 remain high risk, with an LDL target of 0.7 g/L.

Conclusion

CVR in patients with T1D remains challenging to define. However, it is essential to consider long-term outcomes, planning for 30 or 40 years into the future. This involves educating patients about the importance of prevention, even when reassuring numbers are seen in their youth.

This story was translated from Univadis France 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.

Estimation of cardiovascular risk (CVR) in individuals living with type 1 diabetes (T1D) was a key topic presented by Sophie Borot, MD, from Besançon University Hospital, Besançon, France, at the 40th congress of the French Society of Endocrinology. Borot highlighted the complexities of this subject, outlining several factors that contribute to its challenges.

A Heterogeneous Disease

T1D is a highly heterogeneous condition, and the patients included in studies reflect this diversity:

• The impact of blood glucose levels on CVR changes depending on diabetes duration, its history, the frequency of hypoglycemic episodes, average A1c levels over several years, and the patient’s age at diagnosis.
• A T1D diagnosis from the 1980s involved different management strategies compared with a diagnosis today.
• Patient profiles also vary based on complications such as nephropathy or cardiac autonomic neuropathy.
• Diffuse and distal arterial damage in T1D leads to more subtle and delayed pathologic events than in type 2 diabetes (T2D).
• Most clinical studies assess CVR over 10 years, but a 20- or 30-year evaluation would be more relevant.
• Patients may share CVR factors with the general population (eg, family history, smoking, sedentary lifestyle, obesity, hypertension, or elevated low-density lipoprotein [LDL] levels), raising questions about possible overlap with metabolic syndrome.
• Study criteria differ, with a focus on outcomes such as cardiovascular death, major adverse cardiovascular events like myocardial infarction and stroke, or other endpoints.
• CVR is measured using either absolute or relative values, with varying units of measurement.

A Recent Awareness

The concept of CVR in T1D is relatively new. Until the publication of the prospective Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study in 2005, it was believed that T1D control had no impact on CVR. However, follow-up results from the same cohort of 50,000 patients, published in 2022 after 30 years of observation, revealed that CVR was 20% higher in patients who received conventional hyperglycemia-targeted treatment than those undergoing intensive treatment. The CVR increases in conjunction with diabetes duration. The study also showed that even well-controlled glycemia in T1D carries CVR (primarily due to microangiopathy), and that the most critical factor for CVR is not A1c control but rather LDL cholesterol levels.

These findings were corroborated by a Danish prospective study, which demonstrated that while CVR increased in conjunction with the number of risk factors, it was 82% higher in patients with T1D than in a control group — even in the absence of risk factors.
 

Key Takeaways

At diagnosis, a fundamental difference exists between T1D and T2D in terms of the urgency to address CVR. In T2D, diabetes may have progressed for years before diagnosis, necessitating immediate CVR reduction efforts. In contrast, T1D is often diagnosed in younger patients with initially low CVR, raising questions about the optimal timing for interventions such as statin prescriptions.

Recommendations

The American Diabetes Association/European Association for the Study of Diabetes guidelines (2024) include the following recommendations:

For adults with T1D, treatment should mirror that for T2D:

• Between ages 20 and 40, statins are recommended if at least one CVR factor is present.
• For children 10 years of age or older with T1D, the LDL target is < 1.0 g/L. Statins are prescribed if LDL exceeds 1.6 g/L without CVR factors or 1.3 g/L with at least one CVR factor.

The European Society of Cardiology guidelines (2023) include the following:

• For the first time, a dedicated chapter addresses T1D. Like the American guidelines, routine statin use after age 40 is recommended.
• Before age 40, statins are prescribed if there is at least one CVR factor (microangiopathy) or a 10-year CVR ≥ 10% (based on a CVR calculator).

The International Society for Pediatric and Adolescent Diabetes guidelines (2022) recommend:

• For children 10 years of age or older, the LDL target is < 1.0 g/L. Statins are recommended if LDL exceeds 1.3 g/L.

CAC Score in High CVR

The French Society of Cardiology and the French-speaking Society of Diabetology recommend incorporating the coronary artery calcium (CAC) score to refine CVR classification in high-risk patients. For those without prior cardiovascular events, LDL targets vary based on CAC and age. For example:

• High-risk patients with a CAC of 0-10 are reclassified as moderate risk, with an LDL target of < 1 g/L.
• A CAC ≥ 400 indicates very high risk, warranting coronary exploration.
• Patients under 50 years of age with a CAC of 11-100 remain high risk, with an LDL target of 0.7 g/L.

Conclusion

CVR in patients with T1D remains challenging to define. However, it is essential to consider long-term outcomes, planning for 30 or 40 years into the future. This involves educating patients about the importance of prevention, even when reassuring numbers are seen in their youth.

This story was translated from Univadis France 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.

A new evidence-based guideline recommends prescribing metformin when initiating antipsychotic treatment to help mitigate weight gain in certain instances.

There is “good evidence” that metformin can prevent weight gain caused by antipsychotics, first author Aoife Carolan, MPharm, with Saint John of God Hospital and the Royal College of Surgeons, Dublin, Ireland, said in an interview.

“While there have been some general recommendations to use metformin for this purpose, until now, clear guidance on how to prevent this side effect of treatment has been lacking,” Carolan said. “At present, it is likely that metformin is underused and when used, it is likely to be started after the weight gain occurs. Therefore, this guideline will reflect a new practice for most clinicians.” 

The guideline was published online on December 9 in Schizophrenia Bulletin.

It offers three key recommendations:

• Initiate metformin when prescribing a high-risk weight-inducing antipsychotic, such as olanzapine or clozapine.
• Initiate metformin with a medium-risk antipsychotic (quetiapine, paliperidone, or risperidone) in patients with one or more cardiometabolic risk factors; in patients aged 10-25 years; or in patients with a body mass index (BMI) between 25 and 30.
• Initiate metformin with any antipsychotic if > 3% increase in baseline body weight is observed during the first 12 months of treatment.

The guideline authors noted that a recent Cochrane review of pharmacological interventions for the prevention of antipsychotic-induced weight gain showed that metformin is the only pharmacological agent that may be effective for preventing weight gain.

The review showed that starting metformin with antipsychotic medicines can reduce the extent of weight gain by 4.03 kg, compared with controls.

In terms of dose, the guideline recommends escalating from 500 mg daily to 500 mg twice daily over 2 weeks, followed by biweekly increases of 500 mg as tolerated up to 1 g twice daily at week 6.

Metformin should be discontinued if risks for lactic acidosis are present, or the condition is suspected; if BMI falls below 20; or if the antipsychotic medicine is discontinued. Metformin should be avoided where there is harmful use of alcohol.

While the guideline focused on metformin, it also recommends that, if available, glucagon-like peptide 1 (GLP-1) agonists, should be considered for patients with a BMI > 30, certain cardiometabolic diseases, or obstructive sleep apnea.

“At present, there is insufficient evidence for the risk benefit calculation for GLP-1 agonists as a preventative agent, but we will continue to monitor the evidence and update the guideline if it is needed,” Carolan said.

 

Experts Weigh In

This news organization asked several psychiatrists not involved in the guideline development for their thoughts on it.

Ipsit Vahia, MD, McLean Hospital, Belmont, and Harvard Medical School, Boston, both in Massachusetts, said: “There is an urgent need for evidence to guide treatments that can mitigate the metabolic side effects of antipsychotics.”

While metformin has shown some potential based on preliminary studies, this paper offers more substantial evidence to guide clinicians in using these medications and marks a significant step forward in clinical psychiatry, Vahia said.

Lynn DeLisi, MD, also with Harvard Medical School, emphasized that decisions about the use of metformin in patients taking antipsychotics should be made on an individual basis.

“It should not be used routinely with all antipsychotics, as metformin has its own set of side effects,” said DeLisi.

Xiaoduo Fan, MD, MPH, with UMass Chan Medical School, Worcester, Massachusetts, director of UMass MIND, noted that the evidence regarding metformin’s benefits to prevent or mitigate antipsychotic-induced weight gain and other metabolic disturbances is clear.

“It was somewhat controversial when psychiatrists started to prescribe metformin 15-20 years ago, but now many psychiatrists feel comfortable doing so. In many clinical settings, especially in academically affiliated hospitals, using metformin to address antipsychotic-associated metabolic concerns has become part of the routine practice,” said Fan.

“The guideline recommendations are generally consistent with what we have been doing clinically. The publication of the guideline may help promote wider use of metformin in the patient population we serve,” Fan added.

Fan also noted that a growing body of the literature has demonstrated the weight loss effect and other metabolic benefits of GLP-1 agonists. “Compared with metformin, GLP-1 agonists are more effective in inducing weight loss and mitigating cardiometabolic risks,” he said.

Fan said his group has completed a double-blind, placebo-controlled trial of 6-month weekly injection of the GLP-1 receptor agonist exenatide, as an adjunctive treatment in 70 patients with schizophrenia. “Preliminary data analysis suggests positive metabolic benefits,” he reported.

This research had no commercial funding. Carolan had no relevant disclosures. A complete list of disclosures for the guideline authors is available with the original article. DeLisi had no relevant disclosures. Fan had received research support from Alkermes, Eli Lilly, Janssen, Otsuka Pharmaceutical, Roche, Lundbeck, Boehringer Ingelheim, Neurocrine Biosciences, Intra-Cellular Therapies, Teva, and Bristol-Myers Squibb. He served on the BMJ Best Practice’s US Advisory Panel and as the contributor for the BMJ Best Practice — Schizophrenia Topic. Vahia had served as a consultant for Otsuka.

A version of this article appeared on Medscape.com.

A new evidence-based guideline recommends prescribing metformin when initiating antipsychotic treatment to help mitigate weight gain in certain instances.

There is “good evidence” that metformin can prevent weight gain caused by antipsychotics, first author Aoife Carolan, MPharm, with Saint John of God Hospital and the Royal College of Surgeons, Dublin, Ireland, said in an interview.

“While there have been some general recommendations to use metformin for this purpose, until now, clear guidance on how to prevent this side effect of treatment has been lacking,” Carolan said. “At present, it is likely that metformin is underused and when used, it is likely to be started after the weight gain occurs. Therefore, this guideline will reflect a new practice for most clinicians.” 

The guideline was published online on December 9 in Schizophrenia Bulletin.

It offers three key recommendations:

• Initiate metformin when prescribing a high-risk weight-inducing antipsychotic, such as olanzapine or clozapine.
• Initiate metformin with a medium-risk antipsychotic (quetiapine, paliperidone, or risperidone) in patients with one or more cardiometabolic risk factors; in patients aged 10-25 years; or in patients with a body mass index (BMI) between 25 and 30.
• Initiate metformin with any antipsychotic if > 3% increase in baseline body weight is observed during the first 12 months of treatment.

The guideline authors noted that a recent Cochrane review of pharmacological interventions for the prevention of antipsychotic-induced weight gain showed that metformin is the only pharmacological agent that may be effective for preventing weight gain.

The review showed that starting metformin with antipsychotic medicines can reduce the extent of weight gain by 4.03 kg, compared with controls.

In terms of dose, the guideline recommends escalating from 500 mg daily to 500 mg twice daily over 2 weeks, followed by biweekly increases of 500 mg as tolerated up to 1 g twice daily at week 6.

Metformin should be discontinued if risks for lactic acidosis are present, or the condition is suspected; if BMI falls below 20; or if the antipsychotic medicine is discontinued. Metformin should be avoided where there is harmful use of alcohol.

While the guideline focused on metformin, it also recommends that, if available, glucagon-like peptide 1 (GLP-1) agonists, should be considered for patients with a BMI > 30, certain cardiometabolic diseases, or obstructive sleep apnea.

“At present, there is insufficient evidence for the risk benefit calculation for GLP-1 agonists as a preventative agent, but we will continue to monitor the evidence and update the guideline if it is needed,” Carolan said.

 

Experts Weigh In

This news organization asked several psychiatrists not involved in the guideline development for their thoughts on it.

Ipsit Vahia, MD, McLean Hospital, Belmont, and Harvard Medical School, Boston, both in Massachusetts, said: “There is an urgent need for evidence to guide treatments that can mitigate the metabolic side effects of antipsychotics.”

While metformin has shown some potential based on preliminary studies, this paper offers more substantial evidence to guide clinicians in using these medications and marks a significant step forward in clinical psychiatry, Vahia said.

Lynn DeLisi, MD, also with Harvard Medical School, emphasized that decisions about the use of metformin in patients taking antipsychotics should be made on an individual basis.

“It should not be used routinely with all antipsychotics, as metformin has its own set of side effects,” said DeLisi.

Xiaoduo Fan, MD, MPH, with UMass Chan Medical School, Worcester, Massachusetts, director of UMass MIND, noted that the evidence regarding metformin’s benefits to prevent or mitigate antipsychotic-induced weight gain and other metabolic disturbances is clear.

“It was somewhat controversial when psychiatrists started to prescribe metformin 15-20 years ago, but now many psychiatrists feel comfortable doing so. In many clinical settings, especially in academically affiliated hospitals, using metformin to address antipsychotic-associated metabolic concerns has become part of the routine practice,” said Fan.

“The guideline recommendations are generally consistent with what we have been doing clinically. The publication of the guideline may help promote wider use of metformin in the patient population we serve,” Fan added.

Fan also noted that a growing body of the literature has demonstrated the weight loss effect and other metabolic benefits of GLP-1 agonists. “Compared with metformin, GLP-1 agonists are more effective in inducing weight loss and mitigating cardiometabolic risks,” he said.

Fan said his group has completed a double-blind, placebo-controlled trial of 6-month weekly injection of the GLP-1 receptor agonist exenatide, as an adjunctive treatment in 70 patients with schizophrenia. “Preliminary data analysis suggests positive metabolic benefits,” he reported.

This research had no commercial funding. Carolan had no relevant disclosures. A complete list of disclosures for the guideline authors is available with the original article. DeLisi had no relevant disclosures. Fan had received research support from Alkermes, Eli Lilly, Janssen, Otsuka Pharmaceutical, Roche, Lundbeck, Boehringer Ingelheim, Neurocrine Biosciences, Intra-Cellular Therapies, Teva, and Bristol-Myers Squibb. He served on the BMJ Best Practice’s US Advisory Panel and as the contributor for the BMJ Best Practice — Schizophrenia Topic. Vahia had served as a consultant for Otsuka.

A version of this article appeared on Medscape.com.

A new evidence-based guideline recommends prescribing metformin when initiating antipsychotic treatment to help mitigate weight gain in certain instances.

There is “good evidence” that metformin can prevent weight gain caused by antipsychotics, first author Aoife Carolan, MPharm, with Saint John of God Hospital and the Royal College of Surgeons, Dublin, Ireland, said in an interview.

“While there have been some general recommendations to use metformin for this purpose, until now, clear guidance on how to prevent this side effect of treatment has been lacking,” Carolan said. “At present, it is likely that metformin is underused and when used, it is likely to be started after the weight gain occurs. Therefore, this guideline will reflect a new practice for most clinicians.” 

The guideline was published online on December 9 in Schizophrenia Bulletin.

It offers three key recommendations:

• Initiate metformin when prescribing a high-risk weight-inducing antipsychotic, such as olanzapine or clozapine.
• Initiate metformin with a medium-risk antipsychotic (quetiapine, paliperidone, or risperidone) in patients with one or more cardiometabolic risk factors; in patients aged 10-25 years; or in patients with a body mass index (BMI) between 25 and 30.
• Initiate metformin with any antipsychotic if > 3% increase in baseline body weight is observed during the first 12 months of treatment.

The guideline authors noted that a recent Cochrane review of pharmacological interventions for the prevention of antipsychotic-induced weight gain showed that metformin is the only pharmacological agent that may be effective for preventing weight gain.

The review showed that starting metformin with antipsychotic medicines can reduce the extent of weight gain by 4.03 kg, compared with controls.

In terms of dose, the guideline recommends escalating from 500 mg daily to 500 mg twice daily over 2 weeks, followed by biweekly increases of 500 mg as tolerated up to 1 g twice daily at week 6.

Metformin should be discontinued if risks for lactic acidosis are present, or the condition is suspected; if BMI falls below 20; or if the antipsychotic medicine is discontinued. Metformin should be avoided where there is harmful use of alcohol.

While the guideline focused on metformin, it also recommends that, if available, glucagon-like peptide 1 (GLP-1) agonists, should be considered for patients with a BMI > 30, certain cardiometabolic diseases, or obstructive sleep apnea.

“At present, there is insufficient evidence for the risk benefit calculation for GLP-1 agonists as a preventative agent, but we will continue to monitor the evidence and update the guideline if it is needed,” Carolan said.

 

Experts Weigh In

This news organization asked several psychiatrists not involved in the guideline development for their thoughts on it.

Ipsit Vahia, MD, McLean Hospital, Belmont, and Harvard Medical School, Boston, both in Massachusetts, said: “There is an urgent need for evidence to guide treatments that can mitigate the metabolic side effects of antipsychotics.”

While metformin has shown some potential based on preliminary studies, this paper offers more substantial evidence to guide clinicians in using these medications and marks a significant step forward in clinical psychiatry, Vahia said.

Lynn DeLisi, MD, also with Harvard Medical School, emphasized that decisions about the use of metformin in patients taking antipsychotics should be made on an individual basis.

“It should not be used routinely with all antipsychotics, as metformin has its own set of side effects,” said DeLisi.

Xiaoduo Fan, MD, MPH, with UMass Chan Medical School, Worcester, Massachusetts, director of UMass MIND, noted that the evidence regarding metformin’s benefits to prevent or mitigate antipsychotic-induced weight gain and other metabolic disturbances is clear.

“It was somewhat controversial when psychiatrists started to prescribe metformin 15-20 years ago, but now many psychiatrists feel comfortable doing so. In many clinical settings, especially in academically affiliated hospitals, using metformin to address antipsychotic-associated metabolic concerns has become part of the routine practice,” said Fan.

“The guideline recommendations are generally consistent with what we have been doing clinically. The publication of the guideline may help promote wider use of metformin in the patient population we serve,” Fan added.

Fan also noted that a growing body of the literature has demonstrated the weight loss effect and other metabolic benefits of GLP-1 agonists. “Compared with metformin, GLP-1 agonists are more effective in inducing weight loss and mitigating cardiometabolic risks,” he said.

Fan said his group has completed a double-blind, placebo-controlled trial of 6-month weekly injection of the GLP-1 receptor agonist exenatide, as an adjunctive treatment in 70 patients with schizophrenia. “Preliminary data analysis suggests positive metabolic benefits,” he reported.

This research had no commercial funding. Carolan had no relevant disclosures. A complete list of disclosures for the guideline authors is available with the original article. DeLisi had no relevant disclosures. Fan had received research support from Alkermes, Eli Lilly, Janssen, Otsuka Pharmaceutical, Roche, Lundbeck, Boehringer Ingelheim, Neurocrine Biosciences, Intra-Cellular Therapies, Teva, and Bristol-Myers Squibb. He served on the BMJ Best Practice’s US Advisory Panel and as the contributor for the BMJ Best Practice — Schizophrenia Topic. Vahia had served as a consultant for Otsuka.

A version of this article appeared on Medscape.com.