SAN DIEGO –After fashion model Linda Evangelista filed and ultimately settled a lawsuit against Zeltiq Aesthetics in 2022 subsequent to developing paradoxical adipose hyperplasia she claimed was caused by several sessions of CoolSculpting, some aesthetic experts wondered how consumers would embrace the fat reduction procedure going forward.

The negative publicity surrounding this case “is thought to have detracted from some of the volume of it [in terms of demand], but it looks like it’s coming back again,” Omar A. Ibrahimi, MD, PhD, medical director of the Connecticut Skin Institute, Stamford, said during a presentation on noninvasive fat removal treatment options at the annual Masters of Aesthetics Symposium.

In fact, he said, CoolSculpting accounts for an estimated 72% of noninvasive fat removal treatments performed in the United States. “By and large, there is high satisfaction with this procedure,” said Dr. Ibrahimi. “There have been about 17 million procedures done worldwide. Paradoxical adipose hyperplasia is a very rare side effect. As newer iterations of this technology have come out, I think there is an even lower incidence.”

CoolSculpting, or cryolipolysis, freezes excess fat to remove it from stubborn areas via panniculitis. The technology was developed by Dieter Manstein MD, PhD, and R. Rox Anderson, MD, at Massachusetts General Hospital and Harvard Medical School, both in Boston, and cleared by the U.S. Food and Drug Administration for noninvasive fat removal in 2010.

“If you kill a fat cell in an adult, it can’t come back,” Dr. Ibrahimi said. “When this technology first came out it was very simple. We treated an area once and were done. Now we know to treat the area multiple times, and you can treat a much larger volume in a patient during one session safely. You can bring about dramatic results, but it often takes a series of 35-minute treatment cycles and about 3 months to see clinical results. There are published studies showing that results are persisting even 10 years after treatment. This is nice, because I tell my patients, ‘if you keep up with your diet and exercise, we don’t expect the fat to come back.’ ”

Other noninvasive options for fat removal include the following:

• Ultrasound. Options include high-intensity focused ultrasound (Liposonix) and pulsed focused ultrasound (UltraShape). Dr. Ibrahimi described these devices as “very painful, and the results were very difficult to reproduce from the initial clinical studies.”
• Low-level light therapy. Early devices on the market include Zerona and UltraSlim. “Oftentimes these lacked any sort of histological analysis,” he said. “There was no obvious mechanism of action, and questionable efficacy.”
• Laser. Powered by a 1060-nm laser, SculpSure can reduce fat cells safely in 25-minute treatment sessions, Dr. Ibrahimi said. Each session is delivered with one of four available applicators and involves 4 minutes of heating and the next 21 minutes alternating between heating and cooling. “You’re trying to reach a target temperature that kills fat cells,” he explained. “The beauty of having these applicators is that you can kind of customize to the individual patient; it uses contact cooling, and it’s safe for all Fitzpatrick skin types. This device results in a 10%-12% reduction in fat, so it’s clinically significant but very modest.”

A robotic version of the technology, known as the Robotic Fat Killer, is also available. So is the EON, a touchless 1064-nm laser FDA cleared for abdominal, flank, thigh, and back fat reduction. “It adapts to the body shape of the area and individual to deliver a customized treatment,” Dr. Ibrahimi said.

• Radiofrequency. Most devices on the market, such as truSculpt and Vanquish, are powered by monopolar radiofrequency (RF) energy. “Similar to the 1060-nm laser, you can customize these treatments,” he said. “You’re treating to a target temperature. It involves 15-minute cycles, and there are clinical, histology, and ultrasound data supporting this technology.”

Dr. Ibrahimi uses truSculpt and CoolSculpting in his practice, “but sometimes you have patients who are ‘too fit’ for CoolSculpting; they don’t fit the handpiece perfectly,” he said. “That’s where having a monopolar RF or a 1060-nm laser is useful, to help you hone in on those stubborn pockets of fat.”

• Deoxycholic acid. While not a device, deoxycholic acid (Kybella), administered subcutaneously, is approved by the FDA for improving “the appearance of moderate to severe convexity or fullness associated with submental fat” in adults. “A lot of people use it off-label on the abdomen and other stubborn areas,” Dr. Ibrahimi said. “It often requires a series of treatments. That’s the biggest limiting issue with using this technology. It works well, but compared to CoolSculpting, there is a lot of swelling and bruising, which you would expect with an injectable. Managing that down time and hand holding is difficult. But if you can get patients to buy into the downtime, [it yields] pretty impressive results.”

Dr. Ibrahimi also discussed the promise of electrical muscle stimulation for strengthening, firming, and toning muscles. The technology applies an electrical current through electrodes placed on the skin, which stimulates muscles, or through an electromagnetic field.

In a published study of 45 men and women, Dr. Ibrahimi, Anne Chapas, MD, medical director of UnionDerm in New York, and colleagues evaluated the safety and efficacy of an electrical muscle stimulation system for improving muscle strength and toning of the upper extremities.

For the treatments, they used disposable contact pads to place pairs of electrodes on the biceps and on the triceps. All patients (median age 42) received 30-minute treatments twice weekly for 2 or 3 weeks, corresponding to four or six total sessions respectively, depending on the study site. Follow-ups were conducted 30 and 90 days after treatment. They used a validated dynamometer device to measure strength at baseline, at the final treatment session, and at the post-treatment 30- and 90-day visits.

“We saw about a 40% increase in strength in the biceps and about a 30% increase in strength in the triceps,” Dr. Ibrahimi said. “Interestingly, the effect got greater at 30 and 90 days, so this is something that lingers on for quite a while.” In addition to the increase in strength, the researchers and patients noted an improvement in the appearance of the arms. He predicted that this technology “is going to play a role in functional medicine and getting injured athletes back to their sports faster.”

Dr. Ibrahimi disclosed that he is a member of the Advisory Board for Accure Acne, AbbVie, Cutera (manufacturer of truSculpt), Lutronic, Blueberry Therapeutics, Cytrellis, and Quthero. He also holds stock in many device and pharmaceutical companies (none are relevant to the treatments mentioned in this story).

SAN DIEGO –After fashion model Linda Evangelista filed and ultimately settled a lawsuit against Zeltiq Aesthetics in 2022 subsequent to developing paradoxical adipose hyperplasia she claimed was caused by several sessions of CoolSculpting, some aesthetic experts wondered how consumers would embrace the fat reduction procedure going forward.

The negative publicity surrounding this case “is thought to have detracted from some of the volume of it [in terms of demand], but it looks like it’s coming back again,” Omar A. Ibrahimi, MD, PhD, medical director of the Connecticut Skin Institute, Stamford, said during a presentation on noninvasive fat removal treatment options at the annual Masters of Aesthetics Symposium.

In fact, he said, CoolSculpting accounts for an estimated 72% of noninvasive fat removal treatments performed in the United States. “By and large, there is high satisfaction with this procedure,” said Dr. Ibrahimi. “There have been about 17 million procedures done worldwide. Paradoxical adipose hyperplasia is a very rare side effect. As newer iterations of this technology have come out, I think there is an even lower incidence.”

CoolSculpting, or cryolipolysis, freezes excess fat to remove it from stubborn areas via panniculitis. The technology was developed by Dieter Manstein MD, PhD, and R. Rox Anderson, MD, at Massachusetts General Hospital and Harvard Medical School, both in Boston, and cleared by the U.S. Food and Drug Administration for noninvasive fat removal in 2010.

“If you kill a fat cell in an adult, it can’t come back,” Dr. Ibrahimi said. “When this technology first came out it was very simple. We treated an area once and were done. Now we know to treat the area multiple times, and you can treat a much larger volume in a patient during one session safely. You can bring about dramatic results, but it often takes a series of 35-minute treatment cycles and about 3 months to see clinical results. There are published studies showing that results are persisting even 10 years after treatment. This is nice, because I tell my patients, ‘if you keep up with your diet and exercise, we don’t expect the fat to come back.’ ”

Other noninvasive options for fat removal include the following:

• Ultrasound. Options include high-intensity focused ultrasound (Liposonix) and pulsed focused ultrasound (UltraShape). Dr. Ibrahimi described these devices as “very painful, and the results were very difficult to reproduce from the initial clinical studies.”
• Low-level light therapy. Early devices on the market include Zerona and UltraSlim. “Oftentimes these lacked any sort of histological analysis,” he said. “There was no obvious mechanism of action, and questionable efficacy.”
• Laser. Powered by a 1060-nm laser, SculpSure can reduce fat cells safely in 25-minute treatment sessions, Dr. Ibrahimi said. Each session is delivered with one of four available applicators and involves 4 minutes of heating and the next 21 minutes alternating between heating and cooling. “You’re trying to reach a target temperature that kills fat cells,” he explained. “The beauty of having these applicators is that you can kind of customize to the individual patient; it uses contact cooling, and it’s safe for all Fitzpatrick skin types. This device results in a 10%-12% reduction in fat, so it’s clinically significant but very modest.”

A robotic version of the technology, known as the Robotic Fat Killer, is also available. So is the EON, a touchless 1064-nm laser FDA cleared for abdominal, flank, thigh, and back fat reduction. “It adapts to the body shape of the area and individual to deliver a customized treatment,” Dr. Ibrahimi said.

• Radiofrequency. Most devices on the market, such as truSculpt and Vanquish, are powered by monopolar radiofrequency (RF) energy. “Similar to the 1060-nm laser, you can customize these treatments,” he said. “You’re treating to a target temperature. It involves 15-minute cycles, and there are clinical, histology, and ultrasound data supporting this technology.”

Dr. Ibrahimi uses truSculpt and CoolSculpting in his practice, “but sometimes you have patients who are ‘too fit’ for CoolSculpting; they don’t fit the handpiece perfectly,” he said. “That’s where having a monopolar RF or a 1060-nm laser is useful, to help you hone in on those stubborn pockets of fat.”

• Deoxycholic acid. While not a device, deoxycholic acid (Kybella), administered subcutaneously, is approved by the FDA for improving “the appearance of moderate to severe convexity or fullness associated with submental fat” in adults. “A lot of people use it off-label on the abdomen and other stubborn areas,” Dr. Ibrahimi said. “It often requires a series of treatments. That’s the biggest limiting issue with using this technology. It works well, but compared to CoolSculpting, there is a lot of swelling and bruising, which you would expect with an injectable. Managing that down time and hand holding is difficult. But if you can get patients to buy into the downtime, [it yields] pretty impressive results.”

Dr. Ibrahimi also discussed the promise of electrical muscle stimulation for strengthening, firming, and toning muscles. The technology applies an electrical current through electrodes placed on the skin, which stimulates muscles, or through an electromagnetic field.

In a published study of 45 men and women, Dr. Ibrahimi, Anne Chapas, MD, medical director of UnionDerm in New York, and colleagues evaluated the safety and efficacy of an electrical muscle stimulation system for improving muscle strength and toning of the upper extremities.

For the treatments, they used disposable contact pads to place pairs of electrodes on the biceps and on the triceps. All patients (median age 42) received 30-minute treatments twice weekly for 2 or 3 weeks, corresponding to four or six total sessions respectively, depending on the study site. Follow-ups were conducted 30 and 90 days after treatment. They used a validated dynamometer device to measure strength at baseline, at the final treatment session, and at the post-treatment 30- and 90-day visits.

“We saw about a 40% increase in strength in the biceps and about a 30% increase in strength in the triceps,” Dr. Ibrahimi said. “Interestingly, the effect got greater at 30 and 90 days, so this is something that lingers on for quite a while.” In addition to the increase in strength, the researchers and patients noted an improvement in the appearance of the arms. He predicted that this technology “is going to play a role in functional medicine and getting injured athletes back to their sports faster.”

Dr. Ibrahimi disclosed that he is a member of the Advisory Board for Accure Acne, AbbVie, Cutera (manufacturer of truSculpt), Lutronic, Blueberry Therapeutics, Cytrellis, and Quthero. He also holds stock in many device and pharmaceutical companies (none are relevant to the treatments mentioned in this story).

SAN DIEGO –After fashion model Linda Evangelista filed and ultimately settled a lawsuit against Zeltiq Aesthetics in 2022 subsequent to developing paradoxical adipose hyperplasia she claimed was caused by several sessions of CoolSculpting, some aesthetic experts wondered how consumers would embrace the fat reduction procedure going forward.

The negative publicity surrounding this case “is thought to have detracted from some of the volume of it [in terms of demand], but it looks like it’s coming back again,” Omar A. Ibrahimi, MD, PhD, medical director of the Connecticut Skin Institute, Stamford, said during a presentation on noninvasive fat removal treatment options at the annual Masters of Aesthetics Symposium.

In fact, he said, CoolSculpting accounts for an estimated 72% of noninvasive fat removal treatments performed in the United States. “By and large, there is high satisfaction with this procedure,” said Dr. Ibrahimi. “There have been about 17 million procedures done worldwide. Paradoxical adipose hyperplasia is a very rare side effect. As newer iterations of this technology have come out, I think there is an even lower incidence.”

CoolSculpting, or cryolipolysis, freezes excess fat to remove it from stubborn areas via panniculitis. The technology was developed by Dieter Manstein MD, PhD, and R. Rox Anderson, MD, at Massachusetts General Hospital and Harvard Medical School, both in Boston, and cleared by the U.S. Food and Drug Administration for noninvasive fat removal in 2010.

“If you kill a fat cell in an adult, it can’t come back,” Dr. Ibrahimi said. “When this technology first came out it was very simple. We treated an area once and were done. Now we know to treat the area multiple times, and you can treat a much larger volume in a patient during one session safely. You can bring about dramatic results, but it often takes a series of 35-minute treatment cycles and about 3 months to see clinical results. There are published studies showing that results are persisting even 10 years after treatment. This is nice, because I tell my patients, ‘if you keep up with your diet and exercise, we don’t expect the fat to come back.’ ”

Other noninvasive options for fat removal include the following:

• Ultrasound. Options include high-intensity focused ultrasound (Liposonix) and pulsed focused ultrasound (UltraShape). Dr. Ibrahimi described these devices as “very painful, and the results were very difficult to reproduce from the initial clinical studies.”
• Low-level light therapy. Early devices on the market include Zerona and UltraSlim. “Oftentimes these lacked any sort of histological analysis,” he said. “There was no obvious mechanism of action, and questionable efficacy.”
• Laser. Powered by a 1060-nm laser, SculpSure can reduce fat cells safely in 25-minute treatment sessions, Dr. Ibrahimi said. Each session is delivered with one of four available applicators and involves 4 minutes of heating and the next 21 minutes alternating between heating and cooling. “You’re trying to reach a target temperature that kills fat cells,” he explained. “The beauty of having these applicators is that you can kind of customize to the individual patient; it uses contact cooling, and it’s safe for all Fitzpatrick skin types. This device results in a 10%-12% reduction in fat, so it’s clinically significant but very modest.”

A robotic version of the technology, known as the Robotic Fat Killer, is also available. So is the EON, a touchless 1064-nm laser FDA cleared for abdominal, flank, thigh, and back fat reduction. “It adapts to the body shape of the area and individual to deliver a customized treatment,” Dr. Ibrahimi said.

• Radiofrequency. Most devices on the market, such as truSculpt and Vanquish, are powered by monopolar radiofrequency (RF) energy. “Similar to the 1060-nm laser, you can customize these treatments,” he said. “You’re treating to a target temperature. It involves 15-minute cycles, and there are clinical, histology, and ultrasound data supporting this technology.”

Dr. Ibrahimi uses truSculpt and CoolSculpting in his practice, “but sometimes you have patients who are ‘too fit’ for CoolSculpting; they don’t fit the handpiece perfectly,” he said. “That’s where having a monopolar RF or a 1060-nm laser is useful, to help you hone in on those stubborn pockets of fat.”

• Deoxycholic acid. While not a device, deoxycholic acid (Kybella), administered subcutaneously, is approved by the FDA for improving “the appearance of moderate to severe convexity or fullness associated with submental fat” in adults. “A lot of people use it off-label on the abdomen and other stubborn areas,” Dr. Ibrahimi said. “It often requires a series of treatments. That’s the biggest limiting issue with using this technology. It works well, but compared to CoolSculpting, there is a lot of swelling and bruising, which you would expect with an injectable. Managing that down time and hand holding is difficult. But if you can get patients to buy into the downtime, [it yields] pretty impressive results.”

Dr. Ibrahimi also discussed the promise of electrical muscle stimulation for strengthening, firming, and toning muscles. The technology applies an electrical current through electrodes placed on the skin, which stimulates muscles, or through an electromagnetic field.

In a published study of 45 men and women, Dr. Ibrahimi, Anne Chapas, MD, medical director of UnionDerm in New York, and colleagues evaluated the safety and efficacy of an electrical muscle stimulation system for improving muscle strength and toning of the upper extremities.

For the treatments, they used disposable contact pads to place pairs of electrodes on the biceps and on the triceps. All patients (median age 42) received 30-minute treatments twice weekly for 2 or 3 weeks, corresponding to four or six total sessions respectively, depending on the study site. Follow-ups were conducted 30 and 90 days after treatment. They used a validated dynamometer device to measure strength at baseline, at the final treatment session, and at the post-treatment 30- and 90-day visits.

“We saw about a 40% increase in strength in the biceps and about a 30% increase in strength in the triceps,” Dr. Ibrahimi said. “Interestingly, the effect got greater at 30 and 90 days, so this is something that lingers on for quite a while.” In addition to the increase in strength, the researchers and patients noted an improvement in the appearance of the arms. He predicted that this technology “is going to play a role in functional medicine and getting injured athletes back to their sports faster.”

Dr. Ibrahimi disclosed that he is a member of the Advisory Board for Accure Acne, AbbVie, Cutera (manufacturer of truSculpt), Lutronic, Blueberry Therapeutics, Cytrellis, and Quthero. He also holds stock in many device and pharmaceutical companies (none are relevant to the treatments mentioned in this story).

TOPLINE:

In contrast to an overall decline in cardiovascular mortality, obesity-related cardiovascular deaths have risen substantially in the past 2 decades, most prominently among Black women. “We observed a threefold increase in obesity-related cardiovascular age-adjusted mortality rates between 1999 and 2020,” wrote the authors.

METHODOLOGY:

Data from the U.S. population-level Multiple Cause of Death database were analyzed, including 281,135 deaths in 1999-2020 for which obesity was listed as a contributing factor.

TAKEAWAY:

• Overall, the crude rate of all cardiovascular deaths dropped by 17.6% across all races.
• However, age-adjusted obesity-related cardiovascular mortality tripled from 2.2/100,000 to 6.6/100,000 from 1999 to 2020, consistent across all racial groups.
• Blacks had the highest age-adjusted obesity-related cardiovascular mortality (rising from 4.2/100,000 in 1999 to 11.6/100,000 in 2000).
• Ischemic heart disease was the most common cardiovascular cause of death across all races, and hypertensive disease was second.
• Age-adjusted obesity-related cardiovascular mortality was higher among Blacks (6.7/100,000) than any other racial group, followed by American Indians or Alaskan Natives (3.8/100,000), and lowest among Asian or Pacific Islanders (0.9/100,000).
• The risk of obesity-related cardiovascular disease death rose most rapidly among American Indians and Alaskan Natives.
• Among Blacks, age-adjusted mortality was slightly higher among women than men (6.7/100,000 vs. 6.6/100,000), whereas the reverse was true for all other races (0.6-3.0/100,000 vs. 1.2-6.0/100,000).
• Blacks living in urban settings experienced higher rates of age-adjusted cardiovascular mortality than those living in rural areas (6.8/100,000 vs. 5.9/100,000), whereas the opposite was true for all other racial groups (0.9-3.5/100,000 vs. 2.2-5.4/100,000).

IN PRACTICE:

“There is need for dedicated health strategies aimed at individual communities to better understand and tackle the social determinants of obesity and to design interventions that may alleviate the population burden of both obesity and cardiovascular disease,” the authors wrote.

SOURCE:

The study, by Zahra Raisi-Estabragh, MD, PhD, Queen Mary University, London, and colleagues, was published online Sept. 6 in the Journal of the American Heart Association.

LIMITATIONS:

• Database limited to U.S. residents.
• Possible miscoding or diagnostic errors.
• Potential for residual confounding.
• No data on underlying drivers of observed trends.

DISCLOSURES:

Dr. Raisi-Estabragh has reported receiving funding from the Integrated Academic Training program of the National Institute for Health Research and a Clinical Research Training Fellowship from the British Heart Foundation. Another author has reported receiving research support from the National Heart, Lung, and Blood Institute.

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

TOPLINE:

In contrast to an overall decline in cardiovascular mortality, obesity-related cardiovascular deaths have risen substantially in the past 2 decades, most prominently among Black women. “We observed a threefold increase in obesity-related cardiovascular age-adjusted mortality rates between 1999 and 2020,” wrote the authors.

METHODOLOGY:

Data from the U.S. population-level Multiple Cause of Death database were analyzed, including 281,135 deaths in 1999-2020 for which obesity was listed as a contributing factor.

TAKEAWAY:

• Overall, the crude rate of all cardiovascular deaths dropped by 17.6% across all races.
• However, age-adjusted obesity-related cardiovascular mortality tripled from 2.2/100,000 to 6.6/100,000 from 1999 to 2020, consistent across all racial groups.
• Blacks had the highest age-adjusted obesity-related cardiovascular mortality (rising from 4.2/100,000 in 1999 to 11.6/100,000 in 2000).
• Ischemic heart disease was the most common cardiovascular cause of death across all races, and hypertensive disease was second.
• Age-adjusted obesity-related cardiovascular mortality was higher among Blacks (6.7/100,000) than any other racial group, followed by American Indians or Alaskan Natives (3.8/100,000), and lowest among Asian or Pacific Islanders (0.9/100,000).
• The risk of obesity-related cardiovascular disease death rose most rapidly among American Indians and Alaskan Natives.
• Among Blacks, age-adjusted mortality was slightly higher among women than men (6.7/100,000 vs. 6.6/100,000), whereas the reverse was true for all other races (0.6-3.0/100,000 vs. 1.2-6.0/100,000).
• Blacks living in urban settings experienced higher rates of age-adjusted cardiovascular mortality than those living in rural areas (6.8/100,000 vs. 5.9/100,000), whereas the opposite was true for all other racial groups (0.9-3.5/100,000 vs. 2.2-5.4/100,000).

IN PRACTICE:

“There is need for dedicated health strategies aimed at individual communities to better understand and tackle the social determinants of obesity and to design interventions that may alleviate the population burden of both obesity and cardiovascular disease,” the authors wrote.

SOURCE:

The study, by Zahra Raisi-Estabragh, MD, PhD, Queen Mary University, London, and colleagues, was published online Sept. 6 in the Journal of the American Heart Association.

LIMITATIONS:

• Database limited to U.S. residents.
• Possible miscoding or diagnostic errors.
• Potential for residual confounding.
• No data on underlying drivers of observed trends.

DISCLOSURES:

Dr. Raisi-Estabragh has reported receiving funding from the Integrated Academic Training program of the National Institute for Health Research and a Clinical Research Training Fellowship from the British Heart Foundation. Another author has reported receiving research support from the National Heart, Lung, and Blood Institute.

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

TOPLINE:

In contrast to an overall decline in cardiovascular mortality, obesity-related cardiovascular deaths have risen substantially in the past 2 decades, most prominently among Black women. “We observed a threefold increase in obesity-related cardiovascular age-adjusted mortality rates between 1999 and 2020,” wrote the authors.

METHODOLOGY:

Data from the U.S. population-level Multiple Cause of Death database were analyzed, including 281,135 deaths in 1999-2020 for which obesity was listed as a contributing factor.

TAKEAWAY:

• Overall, the crude rate of all cardiovascular deaths dropped by 17.6% across all races.
• However, age-adjusted obesity-related cardiovascular mortality tripled from 2.2/100,000 to 6.6/100,000 from 1999 to 2020, consistent across all racial groups.
• Blacks had the highest age-adjusted obesity-related cardiovascular mortality (rising from 4.2/100,000 in 1999 to 11.6/100,000 in 2000).
• Ischemic heart disease was the most common cardiovascular cause of death across all races, and hypertensive disease was second.
• Age-adjusted obesity-related cardiovascular mortality was higher among Blacks (6.7/100,000) than any other racial group, followed by American Indians or Alaskan Natives (3.8/100,000), and lowest among Asian or Pacific Islanders (0.9/100,000).
• The risk of obesity-related cardiovascular disease death rose most rapidly among American Indians and Alaskan Natives.
• Among Blacks, age-adjusted mortality was slightly higher among women than men (6.7/100,000 vs. 6.6/100,000), whereas the reverse was true for all other races (0.6-3.0/100,000 vs. 1.2-6.0/100,000).
• Blacks living in urban settings experienced higher rates of age-adjusted cardiovascular mortality than those living in rural areas (6.8/100,000 vs. 5.9/100,000), whereas the opposite was true for all other racial groups (0.9-3.5/100,000 vs. 2.2-5.4/100,000).

IN PRACTICE:

“There is need for dedicated health strategies aimed at individual communities to better understand and tackle the social determinants of obesity and to design interventions that may alleviate the population burden of both obesity and cardiovascular disease,” the authors wrote.

SOURCE:

The study, by Zahra Raisi-Estabragh, MD, PhD, Queen Mary University, London, and colleagues, was published online Sept. 6 in the Journal of the American Heart Association.

LIMITATIONS:

• Database limited to U.S. residents.
• Possible miscoding or diagnostic errors.
• Potential for residual confounding.
• No data on underlying drivers of observed trends.

DISCLOSURES:

Dr. Raisi-Estabragh has reported receiving funding from the Integrated Academic Training program of the National Institute for Health Research and a Clinical Research Training Fellowship from the British Heart Foundation. Another author has reported receiving research support from the National Heart, Lung, and Blood Institute.

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

In medical school, we were repeatedly advised that there is both a science and an art to the practice of medicine. In these days of doc-in-a-box online consultations for obesity, it’s tempting to think that there’s a one-size-fits-all purely scientific approach for these new weight loss medications. Yet, for every nine patients who lose weight seemingly effortlessly on this class of medication, there is always one whose body stubbornly refuses to submit.

Adam is a 58-year-old man who came to me recently because he was having difficulty losing weight. Over the past 20 years, he’d been steadily gaining weight and now, technically has morbid obesity (a term which should arguably be obsolete). His weight gain is complicated by high blood pressure, high cholesterol, and obstructive sleep apnea. His sleep apnea has caused such profound exhaustion that he no longer has the energy to work out. He also has significant ADHD, which has been left untreated because of his ability to white-knuckle it through his many daily meetings and calls. A married father of three, he is a successful portfolio manager at a high-yield bond fund.

Adam tends to eat minimally during the day, thereby baffling his colleagues with the stark contrast between his minimal caloric intake and his large belly. However, when he returns from work late at night (kids safely tucked into bed), the floodgates open. He reports polishing off pints of ice cream, scarfing down bags of cookies, inhaling trays of brownies. No carbohydrate is off limits to him once he steps off the Metro North train and crosses the threshold from work to home. 

Does Adam simply lack the desire or common-sense willpower to make the necessary changes in his lifestyle or is there something more complicated at play?

I would argue that Adam’s ADHD triggered a binge-eating disorder (BED) that festered unchecked over the past 20 years. Patients with BED typically eat massive quantities of food over short periods of time – often when they’re not even hungry. Adam admitted that he would generally continue to eat well after feeling stuffed to the brim. It is well known that ADHD is a leading cause of binge-eating tendencies. So, what is the link between these two seemingly unrelated disorders?

The answer probably lies with dopamine, a neurotransmitter produced in the reward centers of the brain that regulates how people experience pleasure and control impulses. We believe that people with ADHD have low levels of dopamine (it’s actually a bit more complicated, but this is the general idea). These low levels of dopamine lead people to self-medicate with sugars, salt, and fats to increase dopamine levels.

Lisdexamfetamine (Vyvanse) is a Food and Drug Administration–approved treatment option for both ADHD and binge eating. It raises the levels of dopamine (as well as norepinephrine) in the brain’s reward center. Often, the strong urge to binge subsides rapidly once ADHD is properly treated.

Rather than starting Adam on a semaglutide or similar agent, I opted to start him on lisdexamfetamine. When I spoke to him 1 week later, he confided that the world suddenly shifted into focus, and he was able to plan his meals throughout the day and resist the urge to binge late at night.

I may eventually add a semaglutide-like medication if his weight loss plateaus, but for now, I will focus on raising his dopamine levels to tackle the underlying cause of his weight gain.

Dr. Messer is a clinical assistant professor at the Icahn School of Medicine at Mount Sinai, New York. She disclosed no relevant conflicts of interest.

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

In medical school, we were repeatedly advised that there is both a science and an art to the practice of medicine. In these days of doc-in-a-box online consultations for obesity, it’s tempting to think that there’s a one-size-fits-all purely scientific approach for these new weight loss medications. Yet, for every nine patients who lose weight seemingly effortlessly on this class of medication, there is always one whose body stubbornly refuses to submit.

Adam is a 58-year-old man who came to me recently because he was having difficulty losing weight. Over the past 20 years, he’d been steadily gaining weight and now, technically has morbid obesity (a term which should arguably be obsolete). His weight gain is complicated by high blood pressure, high cholesterol, and obstructive sleep apnea. His sleep apnea has caused such profound exhaustion that he no longer has the energy to work out. He also has significant ADHD, which has been left untreated because of his ability to white-knuckle it through his many daily meetings and calls. A married father of three, he is a successful portfolio manager at a high-yield bond fund.

Adam tends to eat minimally during the day, thereby baffling his colleagues with the stark contrast between his minimal caloric intake and his large belly. However, when he returns from work late at night (kids safely tucked into bed), the floodgates open. He reports polishing off pints of ice cream, scarfing down bags of cookies, inhaling trays of brownies. No carbohydrate is off limits to him once he steps off the Metro North train and crosses the threshold from work to home. 

Does Adam simply lack the desire or common-sense willpower to make the necessary changes in his lifestyle or is there something more complicated at play?

I would argue that Adam’s ADHD triggered a binge-eating disorder (BED) that festered unchecked over the past 20 years. Patients with BED typically eat massive quantities of food over short periods of time – often when they’re not even hungry. Adam admitted that he would generally continue to eat well after feeling stuffed to the brim. It is well known that ADHD is a leading cause of binge-eating tendencies. So, what is the link between these two seemingly unrelated disorders?

The answer probably lies with dopamine, a neurotransmitter produced in the reward centers of the brain that regulates how people experience pleasure and control impulses. We believe that people with ADHD have low levels of dopamine (it’s actually a bit more complicated, but this is the general idea). These low levels of dopamine lead people to self-medicate with sugars, salt, and fats to increase dopamine levels.

Lisdexamfetamine (Vyvanse) is a Food and Drug Administration–approved treatment option for both ADHD and binge eating. It raises the levels of dopamine (as well as norepinephrine) in the brain’s reward center. Often, the strong urge to binge subsides rapidly once ADHD is properly treated.

Rather than starting Adam on a semaglutide or similar agent, I opted to start him on lisdexamfetamine. When I spoke to him 1 week later, he confided that the world suddenly shifted into focus, and he was able to plan his meals throughout the day and resist the urge to binge late at night.

I may eventually add a semaglutide-like medication if his weight loss plateaus, but for now, I will focus on raising his dopamine levels to tackle the underlying cause of his weight gain.

Dr. Messer is a clinical assistant professor at the Icahn School of Medicine at Mount Sinai, New York. She disclosed no relevant conflicts of interest.

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

In medical school, we were repeatedly advised that there is both a science and an art to the practice of medicine. In these days of doc-in-a-box online consultations for obesity, it’s tempting to think that there’s a one-size-fits-all purely scientific approach for these new weight loss medications. Yet, for every nine patients who lose weight seemingly effortlessly on this class of medication, there is always one whose body stubbornly refuses to submit.

Adam is a 58-year-old man who came to me recently because he was having difficulty losing weight. Over the past 20 years, he’d been steadily gaining weight and now, technically has morbid obesity (a term which should arguably be obsolete). His weight gain is complicated by high blood pressure, high cholesterol, and obstructive sleep apnea. His sleep apnea has caused such profound exhaustion that he no longer has the energy to work out. He also has significant ADHD, which has been left untreated because of his ability to white-knuckle it through his many daily meetings and calls. A married father of three, he is a successful portfolio manager at a high-yield bond fund.

Adam tends to eat minimally during the day, thereby baffling his colleagues with the stark contrast between his minimal caloric intake and his large belly. However, when he returns from work late at night (kids safely tucked into bed), the floodgates open. He reports polishing off pints of ice cream, scarfing down bags of cookies, inhaling trays of brownies. No carbohydrate is off limits to him once he steps off the Metro North train and crosses the threshold from work to home. 

Does Adam simply lack the desire or common-sense willpower to make the necessary changes in his lifestyle or is there something more complicated at play?

I would argue that Adam’s ADHD triggered a binge-eating disorder (BED) that festered unchecked over the past 20 years. Patients with BED typically eat massive quantities of food over short periods of time – often when they’re not even hungry. Adam admitted that he would generally continue to eat well after feeling stuffed to the brim. It is well known that ADHD is a leading cause of binge-eating tendencies. So, what is the link between these two seemingly unrelated disorders?

The answer probably lies with dopamine, a neurotransmitter produced in the reward centers of the brain that regulates how people experience pleasure and control impulses. We believe that people with ADHD have low levels of dopamine (it’s actually a bit more complicated, but this is the general idea). These low levels of dopamine lead people to self-medicate with sugars, salt, and fats to increase dopamine levels.

Lisdexamfetamine (Vyvanse) is a Food and Drug Administration–approved treatment option for both ADHD and binge eating. It raises the levels of dopamine (as well as norepinephrine) in the brain’s reward center. Often, the strong urge to binge subsides rapidly once ADHD is properly treated.

Rather than starting Adam on a semaglutide or similar agent, I opted to start him on lisdexamfetamine. When I spoke to him 1 week later, he confided that the world suddenly shifted into focus, and he was able to plan his meals throughout the day and resist the urge to binge late at night.

I may eventually add a semaglutide-like medication if his weight loss plateaus, but for now, I will focus on raising his dopamine levels to tackle the underlying cause of his weight gain.

Dr. Messer is a clinical assistant professor at the Icahn School of Medicine at Mount Sinai, New York. She disclosed no relevant conflicts of interest.

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

While half the fracture-prevention battle is getting people diagnosed with low bone density, nearly 80% of older Americans who suffer bone breaks are not tested or treated for osteoporosis. Fractures associated with aging and diminished bone mineral density exact an enormous toll on patients’ lives and cost the health care system billions of dollars annually according to Bone Health and Osteoporosis: A Report of the Surgeon General. But current gaps in patient education and bone density screening are huge.

“It’s concerning that older patients at risk for fracture are often not screened to determine their risk factors contributing to osteoporosis and patients are not educated about fracture prevention,” said Meryl S. LeBoff, MD, an endocrinologist at Brigham and Women’s Hospital, and chief of calcium and bone section, and professor of medicine, at Harvard Medical School, Boston. “Furthermore, the majority of highest-risk women and men who do have fractures are not screened and they do not receive effective, [Food and Drug Administration]–approved therapies.”

Brigham and Women's Hospital

Recent guidelines

Screening with dual-energy x-ray absorptiometry (DEXA) is recommended for all women at age 65 and all men at age 70. But the occasion of a fracture in an older person who has not yet met these age thresholds should prompt a bone density assessment.

“Doctors need to stress that one in two women and one in four men over age 50 will have a fracture in their remaining lifetimes,” Dr. LeBoff said. ”Primary care doctors play a critical role in ordering timely bone densitometry for both sexes.

If an older patient has been treated for a fracture, the main goal going forward is to prevent another one, for which the risk is highest in the 2 years after the incident fracture.”

Johns Hopkins Medicine

According to Kendall F. Moseley, MD, clinical director of the division of endocrinology, diabetes & metabolism at Johns Hopkins Medicine in Baltimore, “Elderly patients need to understand that a fracture at their age is like a heart attack of the bone,” she said, adding that just as cardiovascular risk factors such as high blood pressure and blood lipids are silent before a stroke or infarction, the bone thinning of old age is also silent.

Endocrinologist Jennifer J. Kelly, DO, director of the metabolic bone program and an associate professor at the University of Vermont Medical Center in Burlington, said a fracture in anyone over age 50 that appears not to have resulted from a traumatic blow, is a compelling reason to order a DEXA exam.

University of Vermont Medicine

UTHealth McGovern Medical School

Fracture management

Whether a senior suffers a traumatic fracture or an osteoporosis-related fragility fracture, older age can impede the healing process in some. Senescence may also increase systemic proinflammatory status, according to Clark and colleagues, writing in Current Osteoporosis Reports.

They called for research to develop more directed treatment options for the elderly population.

Dr. Rianon noted that healing may also be affected by a decrease in muscle mass, which plays a role in holding the bone in place. “But it is still controversial how changing metabolic factors affect bone healing in the elderly.”

However, countered Dr. Kelly, fractures in elderly patients are not necessarily less likely to mend – if osteoporosis is not present. “Many heal very well – it really depends more upon their overall health and medical history. Whether or not a person requires surgery depends more upon the extent of the fracture and if the bone is able to align and heal appropriately without surgery.”

Fracture sites

Spine. According to the American Academy of Orthopedic Surgeons the earliest and most frequent site of fragility fractures in the elderly is the spine. Most vertebral fracture pain improves within 3 months without specific treatment. A short period of rest, limited analgesic use, and possible back bracing may help as the fractures heal on their own. But if pain is severe and persistent, vertebral augmentation with percutaneous kyphoplasty or vertebroplasty may be an option. These procedures, however, can destabilize surrounding discs because of the greater thickness of the injected cement.

Hip. The most dangerous fractures occur in the hip. These carry at least a 20% risk of death in the first postoperative year and must be treated surgically. Those in the proximal femur, the head, or the femoral neck will usually need hip replacement, but if the break is farther down, it may be repaired with cement, screws, plates, and rods.

Distal radius. Outcomes of wrist fractures may be positive without surgical intervention, according to a recent retrospective analysis from Turkey by Yalin and colleagues. In a comparison of clinical outcomes in seniors aged 70-89 and assigned to cast immobilization or various surgical treatments for distal radius fractures, no statistically significant difference was found in patient-reported disability scores and range of motion values between casting and surgery in the first postoperative year.

Other sites. Fractures in the elderly are not uncommon in the shoulder, distal radius, cubitus, proximal humerus, and humerus. These fractures are often treated without surgery, but nevertheless signal a high risk for additional fractures.

Bone-enhancing medications

Even in the absence of diagnosed low bone density or osteoporosis, anabolic agents such as the synthetic human parathyroid hormones abaloparatide (Tymlos) and teriparatide (Forteo) may be used to help in some cases with a bad healing prognosis and may also be used for people undergoing surgeries such as a spinal fusion, but there are not clinical guidelines. “We receive referrals regularly for this treatment from our orthopedics colleagues, but it is considered an off-label use,” Dr. Kelly said.

The anabolics teriparatide and romosozumab (Evenity) have proved effective in lowering fractures in high-risk older women.

Post fracture

After recovering from a fracture, elderly people are strongly advised to make lifestyle changes to boost bone health and reduce risk of further fractures, said Willy M. Valencia, MD, a geriatrician-endocrinologist at the Cleveland Clinic. Apart from active daily living, he recommends several types of formal exercise to promote bone formation; increase muscle mass, strength, and flexibility; and improve endurance, balance, and gait. The National Institute on Aging outlines suitable exercise programs for seniors.

Cleveland Clinic

“These exercises will help reduce the risk of falling and to avoid more fractures,” he said. “Whether a patient has been exercising before the fracture or not, they may feel some reticence or reluctance to take up exercise afterwards because they’re afraid of having another fracture, but they should understand that their fracture risk increases if they remain sedentary. They should start slowly but they can’t be sitting all day.”

Even before it’s possible to exercise at the healing fracture site, added Dr. Rianon, its advisable to work other areas of the body. “Overall mobility is important, and exercising other parts of the body can stimulate strength and help prevent falling.”

In other postsurgical measures, a bone-friendly diet rich in calcium and vitamin D, as well as supplementation with these vital nutrients, is essential to lower the risk of falling.

Fall prevention is paramount, said Dr. Valencia. While exercise can improve, gait, balance, and endurance, logistical measures may also be necessary. Seniors may have to move to a one-floor domicile with no stairs to negotiate. At the very least, they need to fall-proof their daily lives by upgrading their eyeglasses and home lighting, eliminating obstacles and loose carpets, fixing bannisters, and installing bathroom handrails. Some may need assistive devices for walking, especially outdoors in slippery conditions.

At the end of the day, the role of the primary physician in screening for bone problems before fracture and postsurgical care is key. “Risk factors for osteoporosis and fracture risk must be added to the patient’s chart,” said Dr. Rianon. Added Dr. Moseley. “No matter how busy they are, my hope is that primary care physicians will not put patients’ bone health at the bottom of the clinical agenda.”

While half the fracture-prevention battle is getting people diagnosed with low bone density, nearly 80% of older Americans who suffer bone breaks are not tested or treated for osteoporosis. Fractures associated with aging and diminished bone mineral density exact an enormous toll on patients’ lives and cost the health care system billions of dollars annually according to Bone Health and Osteoporosis: A Report of the Surgeon General. But current gaps in patient education and bone density screening are huge.

“It’s concerning that older patients at risk for fracture are often not screened to determine their risk factors contributing to osteoporosis and patients are not educated about fracture prevention,” said Meryl S. LeBoff, MD, an endocrinologist at Brigham and Women’s Hospital, and chief of calcium and bone section, and professor of medicine, at Harvard Medical School, Boston. “Furthermore, the majority of highest-risk women and men who do have fractures are not screened and they do not receive effective, [Food and Drug Administration]–approved therapies.”

Brigham and Women's Hospital

Recent guidelines

Screening with dual-energy x-ray absorptiometry (DEXA) is recommended for all women at age 65 and all men at age 70. But the occasion of a fracture in an older person who has not yet met these age thresholds should prompt a bone density assessment.

“Doctors need to stress that one in two women and one in four men over age 50 will have a fracture in their remaining lifetimes,” Dr. LeBoff said. ”Primary care doctors play a critical role in ordering timely bone densitometry for both sexes.

If an older patient has been treated for a fracture, the main goal going forward is to prevent another one, for which the risk is highest in the 2 years after the incident fracture.”

Johns Hopkins Medicine

According to Kendall F. Moseley, MD, clinical director of the division of endocrinology, diabetes & metabolism at Johns Hopkins Medicine in Baltimore, “Elderly patients need to understand that a fracture at their age is like a heart attack of the bone,” she said, adding that just as cardiovascular risk factors such as high blood pressure and blood lipids are silent before a stroke or infarction, the bone thinning of old age is also silent.

Endocrinologist Jennifer J. Kelly, DO, director of the metabolic bone program and an associate professor at the University of Vermont Medical Center in Burlington, said a fracture in anyone over age 50 that appears not to have resulted from a traumatic blow, is a compelling reason to order a DEXA exam.

University of Vermont Medicine

UTHealth McGovern Medical School

Fracture management

Whether a senior suffers a traumatic fracture or an osteoporosis-related fragility fracture, older age can impede the healing process in some. Senescence may also increase systemic proinflammatory status, according to Clark and colleagues, writing in Current Osteoporosis Reports.

They called for research to develop more directed treatment options for the elderly population.

Dr. Rianon noted that healing may also be affected by a decrease in muscle mass, which plays a role in holding the bone in place. “But it is still controversial how changing metabolic factors affect bone healing in the elderly.”

However, countered Dr. Kelly, fractures in elderly patients are not necessarily less likely to mend – if osteoporosis is not present. “Many heal very well – it really depends more upon their overall health and medical history. Whether or not a person requires surgery depends more upon the extent of the fracture and if the bone is able to align and heal appropriately without surgery.”

Fracture sites

Spine. According to the American Academy of Orthopedic Surgeons the earliest and most frequent site of fragility fractures in the elderly is the spine. Most vertebral fracture pain improves within 3 months without specific treatment. A short period of rest, limited analgesic use, and possible back bracing may help as the fractures heal on their own. But if pain is severe and persistent, vertebral augmentation with percutaneous kyphoplasty or vertebroplasty may be an option. These procedures, however, can destabilize surrounding discs because of the greater thickness of the injected cement.

Hip. The most dangerous fractures occur in the hip. These carry at least a 20% risk of death in the first postoperative year and must be treated surgically. Those in the proximal femur, the head, or the femoral neck will usually need hip replacement, but if the break is farther down, it may be repaired with cement, screws, plates, and rods.

Distal radius. Outcomes of wrist fractures may be positive without surgical intervention, according to a recent retrospective analysis from Turkey by Yalin and colleagues. In a comparison of clinical outcomes in seniors aged 70-89 and assigned to cast immobilization or various surgical treatments for distal radius fractures, no statistically significant difference was found in patient-reported disability scores and range of motion values between casting and surgery in the first postoperative year.

Other sites. Fractures in the elderly are not uncommon in the shoulder, distal radius, cubitus, proximal humerus, and humerus. These fractures are often treated without surgery, but nevertheless signal a high risk for additional fractures.

Bone-enhancing medications

Even in the absence of diagnosed low bone density or osteoporosis, anabolic agents such as the synthetic human parathyroid hormones abaloparatide (Tymlos) and teriparatide (Forteo) may be used to help in some cases with a bad healing prognosis and may also be used for people undergoing surgeries such as a spinal fusion, but there are not clinical guidelines. “We receive referrals regularly for this treatment from our orthopedics colleagues, but it is considered an off-label use,” Dr. Kelly said.

The anabolics teriparatide and romosozumab (Evenity) have proved effective in lowering fractures in high-risk older women.

Post fracture

After recovering from a fracture, elderly people are strongly advised to make lifestyle changes to boost bone health and reduce risk of further fractures, said Willy M. Valencia, MD, a geriatrician-endocrinologist at the Cleveland Clinic. Apart from active daily living, he recommends several types of formal exercise to promote bone formation; increase muscle mass, strength, and flexibility; and improve endurance, balance, and gait. The National Institute on Aging outlines suitable exercise programs for seniors.

Cleveland Clinic

“These exercises will help reduce the risk of falling and to avoid more fractures,” he said. “Whether a patient has been exercising before the fracture or not, they may feel some reticence or reluctance to take up exercise afterwards because they’re afraid of having another fracture, but they should understand that their fracture risk increases if they remain sedentary. They should start slowly but they can’t be sitting all day.”

Even before it’s possible to exercise at the healing fracture site, added Dr. Rianon, its advisable to work other areas of the body. “Overall mobility is important, and exercising other parts of the body can stimulate strength and help prevent falling.”

In other postsurgical measures, a bone-friendly diet rich in calcium and vitamin D, as well as supplementation with these vital nutrients, is essential to lower the risk of falling.

Fall prevention is paramount, said Dr. Valencia. While exercise can improve, gait, balance, and endurance, logistical measures may also be necessary. Seniors may have to move to a one-floor domicile with no stairs to negotiate. At the very least, they need to fall-proof their daily lives by upgrading their eyeglasses and home lighting, eliminating obstacles and loose carpets, fixing bannisters, and installing bathroom handrails. Some may need assistive devices for walking, especially outdoors in slippery conditions.

At the end of the day, the role of the primary physician in screening for bone problems before fracture and postsurgical care is key. “Risk factors for osteoporosis and fracture risk must be added to the patient’s chart,” said Dr. Rianon. Added Dr. Moseley. “No matter how busy they are, my hope is that primary care physicians will not put patients’ bone health at the bottom of the clinical agenda.”

While half the fracture-prevention battle is getting people diagnosed with low bone density, nearly 80% of older Americans who suffer bone breaks are not tested or treated for osteoporosis. Fractures associated with aging and diminished bone mineral density exact an enormous toll on patients’ lives and cost the health care system billions of dollars annually according to Bone Health and Osteoporosis: A Report of the Surgeon General. But current gaps in patient education and bone density screening are huge.

“It’s concerning that older patients at risk for fracture are often not screened to determine their risk factors contributing to osteoporosis and patients are not educated about fracture prevention,” said Meryl S. LeBoff, MD, an endocrinologist at Brigham and Women’s Hospital, and chief of calcium and bone section, and professor of medicine, at Harvard Medical School, Boston. “Furthermore, the majority of highest-risk women and men who do have fractures are not screened and they do not receive effective, [Food and Drug Administration]–approved therapies.”

Brigham and Women's Hospital

Recent guidelines

Screening with dual-energy x-ray absorptiometry (DEXA) is recommended for all women at age 65 and all men at age 70. But the occasion of a fracture in an older person who has not yet met these age thresholds should prompt a bone density assessment.

“Doctors need to stress that one in two women and one in four men over age 50 will have a fracture in their remaining lifetimes,” Dr. LeBoff said. ”Primary care doctors play a critical role in ordering timely bone densitometry for both sexes.

If an older patient has been treated for a fracture, the main goal going forward is to prevent another one, for which the risk is highest in the 2 years after the incident fracture.”

Johns Hopkins Medicine

According to Kendall F. Moseley, MD, clinical director of the division of endocrinology, diabetes & metabolism at Johns Hopkins Medicine in Baltimore, “Elderly patients need to understand that a fracture at their age is like a heart attack of the bone,” she said, adding that just as cardiovascular risk factors such as high blood pressure and blood lipids are silent before a stroke or infarction, the bone thinning of old age is also silent.

Endocrinologist Jennifer J. Kelly, DO, director of the metabolic bone program and an associate professor at the University of Vermont Medical Center in Burlington, said a fracture in anyone over age 50 that appears not to have resulted from a traumatic blow, is a compelling reason to order a DEXA exam.

University of Vermont Medicine

UTHealth McGovern Medical School

Fracture management

Whether a senior suffers a traumatic fracture or an osteoporosis-related fragility fracture, older age can impede the healing process in some. Senescence may also increase systemic proinflammatory status, according to Clark and colleagues, writing in Current Osteoporosis Reports.

They called for research to develop more directed treatment options for the elderly population.

Dr. Rianon noted that healing may also be affected by a decrease in muscle mass, which plays a role in holding the bone in place. “But it is still controversial how changing metabolic factors affect bone healing in the elderly.”

However, countered Dr. Kelly, fractures in elderly patients are not necessarily less likely to mend – if osteoporosis is not present. “Many heal very well – it really depends more upon their overall health and medical history. Whether or not a person requires surgery depends more upon the extent of the fracture and if the bone is able to align and heal appropriately without surgery.”

Fracture sites

Spine. According to the American Academy of Orthopedic Surgeons the earliest and most frequent site of fragility fractures in the elderly is the spine. Most vertebral fracture pain improves within 3 months without specific treatment. A short period of rest, limited analgesic use, and possible back bracing may help as the fractures heal on their own. But if pain is severe and persistent, vertebral augmentation with percutaneous kyphoplasty or vertebroplasty may be an option. These procedures, however, can destabilize surrounding discs because of the greater thickness of the injected cement.

Hip. The most dangerous fractures occur in the hip. These carry at least a 20% risk of death in the first postoperative year and must be treated surgically. Those in the proximal femur, the head, or the femoral neck will usually need hip replacement, but if the break is farther down, it may be repaired with cement, screws, plates, and rods.

Distal radius. Outcomes of wrist fractures may be positive without surgical intervention, according to a recent retrospective analysis from Turkey by Yalin and colleagues. In a comparison of clinical outcomes in seniors aged 70-89 and assigned to cast immobilization or various surgical treatments for distal radius fractures, no statistically significant difference was found in patient-reported disability scores and range of motion values between casting and surgery in the first postoperative year.

Other sites. Fractures in the elderly are not uncommon in the shoulder, distal radius, cubitus, proximal humerus, and humerus. These fractures are often treated without surgery, but nevertheless signal a high risk for additional fractures.

Bone-enhancing medications

Even in the absence of diagnosed low bone density or osteoporosis, anabolic agents such as the synthetic human parathyroid hormones abaloparatide (Tymlos) and teriparatide (Forteo) may be used to help in some cases with a bad healing prognosis and may also be used for people undergoing surgeries such as a spinal fusion, but there are not clinical guidelines. “We receive referrals regularly for this treatment from our orthopedics colleagues, but it is considered an off-label use,” Dr. Kelly said.

The anabolics teriparatide and romosozumab (Evenity) have proved effective in lowering fractures in high-risk older women.

Post fracture

After recovering from a fracture, elderly people are strongly advised to make lifestyle changes to boost bone health and reduce risk of further fractures, said Willy M. Valencia, MD, a geriatrician-endocrinologist at the Cleveland Clinic. Apart from active daily living, he recommends several types of formal exercise to promote bone formation; increase muscle mass, strength, and flexibility; and improve endurance, balance, and gait. The National Institute on Aging outlines suitable exercise programs for seniors.

Cleveland Clinic

“These exercises will help reduce the risk of falling and to avoid more fractures,” he said. “Whether a patient has been exercising before the fracture or not, they may feel some reticence or reluctance to take up exercise afterwards because they’re afraid of having another fracture, but they should understand that their fracture risk increases if they remain sedentary. They should start slowly but they can’t be sitting all day.”

Even before it’s possible to exercise at the healing fracture site, added Dr. Rianon, its advisable to work other areas of the body. “Overall mobility is important, and exercising other parts of the body can stimulate strength and help prevent falling.”

In other postsurgical measures, a bone-friendly diet rich in calcium and vitamin D, as well as supplementation with these vital nutrients, is essential to lower the risk of falling.

Fall prevention is paramount, said Dr. Valencia. While exercise can improve, gait, balance, and endurance, logistical measures may also be necessary. Seniors may have to move to a one-floor domicile with no stairs to negotiate. At the very least, they need to fall-proof their daily lives by upgrading their eyeglasses and home lighting, eliminating obstacles and loose carpets, fixing bannisters, and installing bathroom handrails. Some may need assistive devices for walking, especially outdoors in slippery conditions.

At the end of the day, the role of the primary physician in screening for bone problems before fracture and postsurgical care is key. “Risk factors for osteoporosis and fracture risk must be added to the patient’s chart,” said Dr. Rianon. Added Dr. Moseley. “No matter how busy they are, my hope is that primary care physicians will not put patients’ bone health at the bottom of the clinical agenda.”

A 70-year-old woman is admitted to the intensive care unit with a pH of 7.1, an acute kidney injury (AKI), and ketonuria. She is volume depleted and her history is consistent with starvation ketosis. This LOL truly is in NAD (that’s little old lady in no acute distress, for those who haven’t read The House of God). She is clinically stable and seemingly unperturbed by the flurry of activity surrounding her admission.

Your resident is concerned by the severity of the acidosis and suggests starting an intravenous bicarbonate drip. The fellow is adamantly against it. He’s been taught that intravenous bicarbonate increases the serum pH but paradoxically causes intracellular acidosis. As the attending you elect to observe fellow autonomy – no bicarb is given. Because any debate on rounds is a “teachable moment,” you decide to review the evidence and physiology behind infusing bicarbonate.
 

What do the data reveal?

An excellent review published in CHEST in 2000 covers the physiologic effects of bicarbonate, specifically related to lactic acidosis, which our patient didn’t have. Aside from that difference, the review validates the fellow’s opinion. In short, the authors stated that a low pH may be a marker of a dangerous systemic condition, but it need not be corrected for its own sake. It is unlikely to provoke hemodynamic or respiratory compromise outside the setting of shock or hypercapnia. Intravenous bicarbonate can lead to intracellular acidosis, hypercapnia, hypocalcemia, and a reduction in oxygen delivery via the Bohr effect. The authors concluded that because the benefits are unproven and the negative effects are real, intravenous bicarbonate should not be used to correct a metabolic acidosis.

The CHEST review hardly settles the issue, though. A survey published a few years later found a majority of intensivists and nephrologists used intravenous bicarbonate to treat metabolic acidosis while the Surviving Sepsis Campaign Guidelines for the Management of Sepsis and Septic Shock published in 2017 recommended against bicarbonate for acidosis. It wasn’t until 2018 that we reached the holy grail: a randomized controlled trial.

The BICAR-ICU study randomly assigned patients with a pH of 7.20 or less, PCO₂ of 45 mm Hg or less, and sodium bicarbonate concentration of 20 mmol/L or less to receive no bicarbonate versus a sodium bicarbonate drip to maintain a pH greater than 7.30. There’s additional nuance to the trial design and even more detail in the results. To summarize, there was signal for an improvement in renal outcomes across all patients, and those with AKI saw a mortality benefit. Post–BICAR-ICU iterations of the Surviving Sepsis Campaign Guidelines have incorporated these findings by recommending intravenous bicarbonate for patients with sepsis who have AKI and a pH of 7.20 or less.

That’s not to say BICAR-ICU has settled the issue. Although it’s far and away the best we have, there were fewer than 400 total patients in their intention-to-treat analysis. It was open label, with lots of crossover. The primary outcome was negative for the entire population, with only a subgroup (albeit a prespecified one) showing benefit. Finally, the results weren’t stratified by etiology for the metabolic acidosis. There was also evidence of alkalosis and hypocalcemia in the treatment group.

Last but not least in terms of importance, in most cases when bicarbonate is being considered, wouldn’t some form of renal replacement therapy (RRT) be preferred? This point was raised by nephrologists and intensivists when we covered BICAR-ICU in a journal club at my former program. It’s also mentioned in an accompanying editorial. RRT timing is controversial, and a detailed discussion is outside the scope of this piece and beyond the limits of my current knowledge base. But I do know that the A in the A-E-I-O-U acute indications for dialysis pneumonic stands for acidosis.

Our patient had AKI, a pH of 7.20 or less, and a pCO₂ well under 45 mm Hg. Does BICAR-ICU support the resident’s inclination to start a drip? Sort of. The majority of patients enrolled in BICAR-ICU were in shock or were recovering from cardiac arrest, so it’s not clear the results can be generalized to our LOL with starvation ketosis. Extrapolating from studies of diabetic ketoacidosis (DKA) seems more appropriate, and here the data are poor but equivocal. Reviews are generally negative but don’t rule out the use of intravenous bicarbonate in certain patients with DKA.
 

Key takeaways

Our patient survived a 24-hour ICU stay with neither cardiopulmonary decompensation nor a need for RRT. Not sure how she did out of the ICU; presumably she was discharged soon after transfer. As is always the case with anecdotal medicine, the absence of a control prevents assessment of the counterfactual. Is it possible she may have done “better” with intravenous bicarbonate? Seems unlikely to me, though I doubt there would have been demonstrable adverse effects. Perhaps next time the fellow can observe resident autonomy?

Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University of the Health Sciences, Bethesda, Md., and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center. He reported conflicts of interest with Metapharm, CHEST College, and WebMD.
 

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

A 70-year-old woman is admitted to the intensive care unit with a pH of 7.1, an acute kidney injury (AKI), and ketonuria. She is volume depleted and her history is consistent with starvation ketosis. This LOL truly is in NAD (that’s little old lady in no acute distress, for those who haven’t read The House of God). She is clinically stable and seemingly unperturbed by the flurry of activity surrounding her admission.

Your resident is concerned by the severity of the acidosis and suggests starting an intravenous bicarbonate drip. The fellow is adamantly against it. He’s been taught that intravenous bicarbonate increases the serum pH but paradoxically causes intracellular acidosis. As the attending you elect to observe fellow autonomy – no bicarb is given. Because any debate on rounds is a “teachable moment,” you decide to review the evidence and physiology behind infusing bicarbonate.
 

What do the data reveal?

An excellent review published in CHEST in 2000 covers the physiologic effects of bicarbonate, specifically related to lactic acidosis, which our patient didn’t have. Aside from that difference, the review validates the fellow’s opinion. In short, the authors stated that a low pH may be a marker of a dangerous systemic condition, but it need not be corrected for its own sake. It is unlikely to provoke hemodynamic or respiratory compromise outside the setting of shock or hypercapnia. Intravenous bicarbonate can lead to intracellular acidosis, hypercapnia, hypocalcemia, and a reduction in oxygen delivery via the Bohr effect. The authors concluded that because the benefits are unproven and the negative effects are real, intravenous bicarbonate should not be used to correct a metabolic acidosis.

The CHEST review hardly settles the issue, though. A survey published a few years later found a majority of intensivists and nephrologists used intravenous bicarbonate to treat metabolic acidosis while the Surviving Sepsis Campaign Guidelines for the Management of Sepsis and Septic Shock published in 2017 recommended against bicarbonate for acidosis. It wasn’t until 2018 that we reached the holy grail: a randomized controlled trial.

The BICAR-ICU study randomly assigned patients with a pH of 7.20 or less, PCO₂ of 45 mm Hg or less, and sodium bicarbonate concentration of 20 mmol/L or less to receive no bicarbonate versus a sodium bicarbonate drip to maintain a pH greater than 7.30. There’s additional nuance to the trial design and even more detail in the results. To summarize, there was signal for an improvement in renal outcomes across all patients, and those with AKI saw a mortality benefit. Post–BICAR-ICU iterations of the Surviving Sepsis Campaign Guidelines have incorporated these findings by recommending intravenous bicarbonate for patients with sepsis who have AKI and a pH of 7.20 or less.

That’s not to say BICAR-ICU has settled the issue. Although it’s far and away the best we have, there were fewer than 400 total patients in their intention-to-treat analysis. It was open label, with lots of crossover. The primary outcome was negative for the entire population, with only a subgroup (albeit a prespecified one) showing benefit. Finally, the results weren’t stratified by etiology for the metabolic acidosis. There was also evidence of alkalosis and hypocalcemia in the treatment group.

Last but not least in terms of importance, in most cases when bicarbonate is being considered, wouldn’t some form of renal replacement therapy (RRT) be preferred? This point was raised by nephrologists and intensivists when we covered BICAR-ICU in a journal club at my former program. It’s also mentioned in an accompanying editorial. RRT timing is controversial, and a detailed discussion is outside the scope of this piece and beyond the limits of my current knowledge base. But I do know that the A in the A-E-I-O-U acute indications for dialysis pneumonic stands for acidosis.

Our patient had AKI, a pH of 7.20 or less, and a pCO₂ well under 45 mm Hg. Does BICAR-ICU support the resident’s inclination to start a drip? Sort of. The majority of patients enrolled in BICAR-ICU were in shock or were recovering from cardiac arrest, so it’s not clear the results can be generalized to our LOL with starvation ketosis. Extrapolating from studies of diabetic ketoacidosis (DKA) seems more appropriate, and here the data are poor but equivocal. Reviews are generally negative but don’t rule out the use of intravenous bicarbonate in certain patients with DKA.
 

Key takeaways

Our patient survived a 24-hour ICU stay with neither cardiopulmonary decompensation nor a need for RRT. Not sure how she did out of the ICU; presumably she was discharged soon after transfer. As is always the case with anecdotal medicine, the absence of a control prevents assessment of the counterfactual. Is it possible she may have done “better” with intravenous bicarbonate? Seems unlikely to me, though I doubt there would have been demonstrable adverse effects. Perhaps next time the fellow can observe resident autonomy?

Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University of the Health Sciences, Bethesda, Md., and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center. He reported conflicts of interest with Metapharm, CHEST College, and WebMD.
 

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

A 70-year-old woman is admitted to the intensive care unit with a pH of 7.1, an acute kidney injury (AKI), and ketonuria. She is volume depleted and her history is consistent with starvation ketosis. This LOL truly is in NAD (that’s little old lady in no acute distress, for those who haven’t read The House of God). She is clinically stable and seemingly unperturbed by the flurry of activity surrounding her admission.

Your resident is concerned by the severity of the acidosis and suggests starting an intravenous bicarbonate drip. The fellow is adamantly against it. He’s been taught that intravenous bicarbonate increases the serum pH but paradoxically causes intracellular acidosis. As the attending you elect to observe fellow autonomy – no bicarb is given. Because any debate on rounds is a “teachable moment,” you decide to review the evidence and physiology behind infusing bicarbonate.
 

What do the data reveal?

An excellent review published in CHEST in 2000 covers the physiologic effects of bicarbonate, specifically related to lactic acidosis, which our patient didn’t have. Aside from that difference, the review validates the fellow’s opinion. In short, the authors stated that a low pH may be a marker of a dangerous systemic condition, but it need not be corrected for its own sake. It is unlikely to provoke hemodynamic or respiratory compromise outside the setting of shock or hypercapnia. Intravenous bicarbonate can lead to intracellular acidosis, hypercapnia, hypocalcemia, and a reduction in oxygen delivery via the Bohr effect. The authors concluded that because the benefits are unproven and the negative effects are real, intravenous bicarbonate should not be used to correct a metabolic acidosis.

The CHEST review hardly settles the issue, though. A survey published a few years later found a majority of intensivists and nephrologists used intravenous bicarbonate to treat metabolic acidosis while the Surviving Sepsis Campaign Guidelines for the Management of Sepsis and Septic Shock published in 2017 recommended against bicarbonate for acidosis. It wasn’t until 2018 that we reached the holy grail: a randomized controlled trial.

The BICAR-ICU study randomly assigned patients with a pH of 7.20 or less, PCO₂ of 45 mm Hg or less, and sodium bicarbonate concentration of 20 mmol/L or less to receive no bicarbonate versus a sodium bicarbonate drip to maintain a pH greater than 7.30. There’s additional nuance to the trial design and even more detail in the results. To summarize, there was signal for an improvement in renal outcomes across all patients, and those with AKI saw a mortality benefit. Post–BICAR-ICU iterations of the Surviving Sepsis Campaign Guidelines have incorporated these findings by recommending intravenous bicarbonate for patients with sepsis who have AKI and a pH of 7.20 or less.

That’s not to say BICAR-ICU has settled the issue. Although it’s far and away the best we have, there were fewer than 400 total patients in their intention-to-treat analysis. It was open label, with lots of crossover. The primary outcome was negative for the entire population, with only a subgroup (albeit a prespecified one) showing benefit. Finally, the results weren’t stratified by etiology for the metabolic acidosis. There was also evidence of alkalosis and hypocalcemia in the treatment group.

Last but not least in terms of importance, in most cases when bicarbonate is being considered, wouldn’t some form of renal replacement therapy (RRT) be preferred? This point was raised by nephrologists and intensivists when we covered BICAR-ICU in a journal club at my former program. It’s also mentioned in an accompanying editorial. RRT timing is controversial, and a detailed discussion is outside the scope of this piece and beyond the limits of my current knowledge base. But I do know that the A in the A-E-I-O-U acute indications for dialysis pneumonic stands for acidosis.

Our patient had AKI, a pH of 7.20 or less, and a pCO₂ well under 45 mm Hg. Does BICAR-ICU support the resident’s inclination to start a drip? Sort of. The majority of patients enrolled in BICAR-ICU were in shock or were recovering from cardiac arrest, so it’s not clear the results can be generalized to our LOL with starvation ketosis. Extrapolating from studies of diabetic ketoacidosis (DKA) seems more appropriate, and here the data are poor but equivocal. Reviews are generally negative but don’t rule out the use of intravenous bicarbonate in certain patients with DKA.
 

Key takeaways

Our patient survived a 24-hour ICU stay with neither cardiopulmonary decompensation nor a need for RRT. Not sure how she did out of the ICU; presumably she was discharged soon after transfer. As is always the case with anecdotal medicine, the absence of a control prevents assessment of the counterfactual. Is it possible she may have done “better” with intravenous bicarbonate? Seems unlikely to me, though I doubt there would have been demonstrable adverse effects. Perhaps next time the fellow can observe resident autonomy?

Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University of the Health Sciences, Bethesda, Md., and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center. He reported conflicts of interest with Metapharm, CHEST College, and WebMD.
 

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

Asthma is a sneaky foe.

“Asthma may appear controlled until someone exercises,” said Maureen George, PhD,  a professor of nursing at Columbia University and a spokesperson for the Asthma and Allergy Foundation of America. 

But that doesn’t mean exercise should be avoided, she said. 

Exercise, in fact, is one of the best ways to reduce asthma symptoms. Research over the past 2 decades has shown that physical activity can help improve lung function and boost quality of life for someone with asthma. 

As their fitness improves, asthma patients report better sleep, reduced stress, improved weight control, and more days without symptoms. In some cases, they’re able to cut down their medication doses.  

Exercise reduces inflammatory cytokines and increases anti-inflammatory cytokines, according to a 2023 review by researchers in the United Kingdom. That could help calm chronic airway inflammation, easing symptoms of asthma. 

A few simple guidelines can help patients reap those benefits while staying safe.


 

Make sure the first steps aren’t the last steps

For someone who’s new to exercise, there’s only one way to begin: Carefully.

The Global Initiative for Asthma recommends twice-weekly cardio and strength training.

“You always start low and slow,” said Spencer Nadolsky, DO, a board-certified obesity and lipid specialist and medical director of Sequence, a comprehensive weight management program.

“Low” means light loads in the weight room. “Slow” means short, easy walks. 

Many have been put “through the wringer” when starting out, discouraging them from continuing, Dr. Nadolsky said. “They were too sore, and it felt more like punishment.”

An even bigger concern is triggering an asthma attack. Patients should take steps to lower the risk by carrying their rescue inhalers and keeping up on medications, he added.

“A health care professional should be consulted” before the start of a new activity or ramping up a program, or anytime asthma interferes with a workout, Dr. George said. 

Those who exercise outside need to be aware of the air quality, especially at a time when smoke and particulates from a wildfires in Canada can trigger asthma symptoms in people thousands of miles away. 

The harder one works, the higher one’s “ventilation” – taking more air into the lungs, and potentially more allergens and pollutants.

Temperature and humidity also become risky at the extremes. Cold, dry air can dehydrate and constrict the airways, making it hard to breathe. 
 

How to choose the best type of exercise 

Step 1: Be realistic. People with asthma often have less exercise capacity than those who don’t – understandable when shortness of breath is the default setting.

Second, allow for plenty of time to warm up. A solid warm-up routine – particularly one with a mix of lower- and higher-intensity exercises – may help prevent exercise-induced bronchoconstriction causing shortness of breath and wheezing.

For example, warming up on a treadmill or exercise bike could be mixed with a few short bursts of faster running or cycling, with a couple of minutes of recovery at a slower pace in between.

That concept can be expanded into a full-blown workout. 

High-intensity interval training (HIIT) is a promising option for people with asthma. A 2021 study showed that three 20-minute interval workouts per week significantly improved asthma control.

“The benefit of HIIT is that ventilation is able to recover intermittently,” said Carley O’Neill, PhD, an exercise scientist at Acadia University in Nova Scotia and the study’s lead author. 

That’s a key difference from conventional cardio, where the constant exertion can evaporate water from the lungs faster than your body can replenish it. “Dehydrating of the airways can, in some, trigger exercise-induced asthma,” Dr. O’Neill said. 

HIIT, conversely, allows the airways to recover and rehydrate between exercise bouts. 

Another recent study found that people with asthma who did HIIT workouts had fewer breathing problems and felt less fatigued, compared with a matched group who did cardio training at a constant pace. (Both types of cardio led to similar improvements in aerobic fitness.)

Individuals can choose other types of intermittent exercise as well. Strength training, for example, requires relatively short periods of exertion, with plenty of rest in between. 
 

The one choice you don’t want to make

While there are lots of good exercise options for someone with asthma, there’s one clearly bad choice, according to Dr. George: “Avoiding exercise.”  

Being inactive puts one at higher risk for obesity and all the health problems that go with it. And allowing one’s fitness level to decline makes it much harder to move when one needs or wants to.

Any choice is better than that one.

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

Asthma is a sneaky foe.

“Asthma may appear controlled until someone exercises,” said Maureen George, PhD,  a professor of nursing at Columbia University and a spokesperson for the Asthma and Allergy Foundation of America. 

But that doesn’t mean exercise should be avoided, she said. 

Exercise, in fact, is one of the best ways to reduce asthma symptoms. Research over the past 2 decades has shown that physical activity can help improve lung function and boost quality of life for someone with asthma. 

As their fitness improves, asthma patients report better sleep, reduced stress, improved weight control, and more days without symptoms. In some cases, they’re able to cut down their medication doses.  

Exercise reduces inflammatory cytokines and increases anti-inflammatory cytokines, according to a 2023 review by researchers in the United Kingdom. That could help calm chronic airway inflammation, easing symptoms of asthma. 

A few simple guidelines can help patients reap those benefits while staying safe.


 

Make sure the first steps aren’t the last steps

For someone who’s new to exercise, there’s only one way to begin: Carefully.

The Global Initiative for Asthma recommends twice-weekly cardio and strength training.

“You always start low and slow,” said Spencer Nadolsky, DO, a board-certified obesity and lipid specialist and medical director of Sequence, a comprehensive weight management program.

“Low” means light loads in the weight room. “Slow” means short, easy walks. 

Many have been put “through the wringer” when starting out, discouraging them from continuing, Dr. Nadolsky said. “They were too sore, and it felt more like punishment.”

An even bigger concern is triggering an asthma attack. Patients should take steps to lower the risk by carrying their rescue inhalers and keeping up on medications, he added.

“A health care professional should be consulted” before the start of a new activity or ramping up a program, or anytime asthma interferes with a workout, Dr. George said. 

Those who exercise outside need to be aware of the air quality, especially at a time when smoke and particulates from a wildfires in Canada can trigger asthma symptoms in people thousands of miles away. 

The harder one works, the higher one’s “ventilation” – taking more air into the lungs, and potentially more allergens and pollutants.

Temperature and humidity also become risky at the extremes. Cold, dry air can dehydrate and constrict the airways, making it hard to breathe. 
 

How to choose the best type of exercise 

Step 1: Be realistic. People with asthma often have less exercise capacity than those who don’t – understandable when shortness of breath is the default setting.

Second, allow for plenty of time to warm up. A solid warm-up routine – particularly one with a mix of lower- and higher-intensity exercises – may help prevent exercise-induced bronchoconstriction causing shortness of breath and wheezing.

For example, warming up on a treadmill or exercise bike could be mixed with a few short bursts of faster running or cycling, with a couple of minutes of recovery at a slower pace in between.

That concept can be expanded into a full-blown workout. 

High-intensity interval training (HIIT) is a promising option for people with asthma. A 2021 study showed that three 20-minute interval workouts per week significantly improved asthma control.

“The benefit of HIIT is that ventilation is able to recover intermittently,” said Carley O’Neill, PhD, an exercise scientist at Acadia University in Nova Scotia and the study’s lead author. 

That’s a key difference from conventional cardio, where the constant exertion can evaporate water from the lungs faster than your body can replenish it. “Dehydrating of the airways can, in some, trigger exercise-induced asthma,” Dr. O’Neill said. 

HIIT, conversely, allows the airways to recover and rehydrate between exercise bouts. 

Another recent study found that people with asthma who did HIIT workouts had fewer breathing problems and felt less fatigued, compared with a matched group who did cardio training at a constant pace. (Both types of cardio led to similar improvements in aerobic fitness.)

Individuals can choose other types of intermittent exercise as well. Strength training, for example, requires relatively short periods of exertion, with plenty of rest in between. 
 

The one choice you don’t want to make

While there are lots of good exercise options for someone with asthma, there’s one clearly bad choice, according to Dr. George: “Avoiding exercise.”  

Being inactive puts one at higher risk for obesity and all the health problems that go with it. And allowing one’s fitness level to decline makes it much harder to move when one needs or wants to.

Any choice is better than that one.

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

Asthma is a sneaky foe.

“Asthma may appear controlled until someone exercises,” said Maureen George, PhD,  a professor of nursing at Columbia University and a spokesperson for the Asthma and Allergy Foundation of America. 

But that doesn’t mean exercise should be avoided, she said. 

Exercise, in fact, is one of the best ways to reduce asthma symptoms. Research over the past 2 decades has shown that physical activity can help improve lung function and boost quality of life for someone with asthma. 

As their fitness improves, asthma patients report better sleep, reduced stress, improved weight control, and more days without symptoms. In some cases, they’re able to cut down their medication doses.  

Exercise reduces inflammatory cytokines and increases anti-inflammatory cytokines, according to a 2023 review by researchers in the United Kingdom. That could help calm chronic airway inflammation, easing symptoms of asthma. 

A few simple guidelines can help patients reap those benefits while staying safe.


 

Make sure the first steps aren’t the last steps

For someone who’s new to exercise, there’s only one way to begin: Carefully.

The Global Initiative for Asthma recommends twice-weekly cardio and strength training.

“You always start low and slow,” said Spencer Nadolsky, DO, a board-certified obesity and lipid specialist and medical director of Sequence, a comprehensive weight management program.

“Low” means light loads in the weight room. “Slow” means short, easy walks. 

Many have been put “through the wringer” when starting out, discouraging them from continuing, Dr. Nadolsky said. “They were too sore, and it felt more like punishment.”

An even bigger concern is triggering an asthma attack. Patients should take steps to lower the risk by carrying their rescue inhalers and keeping up on medications, he added.

“A health care professional should be consulted” before the start of a new activity or ramping up a program, or anytime asthma interferes with a workout, Dr. George said. 

Those who exercise outside need to be aware of the air quality, especially at a time when smoke and particulates from a wildfires in Canada can trigger asthma symptoms in people thousands of miles away. 

The harder one works, the higher one’s “ventilation” – taking more air into the lungs, and potentially more allergens and pollutants.

Temperature and humidity also become risky at the extremes. Cold, dry air can dehydrate and constrict the airways, making it hard to breathe. 
 

How to choose the best type of exercise 

Step 1: Be realistic. People with asthma often have less exercise capacity than those who don’t – understandable when shortness of breath is the default setting.

Second, allow for plenty of time to warm up. A solid warm-up routine – particularly one with a mix of lower- and higher-intensity exercises – may help prevent exercise-induced bronchoconstriction causing shortness of breath and wheezing.

For example, warming up on a treadmill or exercise bike could be mixed with a few short bursts of faster running or cycling, with a couple of minutes of recovery at a slower pace in between.

That concept can be expanded into a full-blown workout. 

High-intensity interval training (HIIT) is a promising option for people with asthma. A 2021 study showed that three 20-minute interval workouts per week significantly improved asthma control.

“The benefit of HIIT is that ventilation is able to recover intermittently,” said Carley O’Neill, PhD, an exercise scientist at Acadia University in Nova Scotia and the study’s lead author. 

That’s a key difference from conventional cardio, where the constant exertion can evaporate water from the lungs faster than your body can replenish it. “Dehydrating of the airways can, in some, trigger exercise-induced asthma,” Dr. O’Neill said. 

HIIT, conversely, allows the airways to recover and rehydrate between exercise bouts. 

Another recent study found that people with asthma who did HIIT workouts had fewer breathing problems and felt less fatigued, compared with a matched group who did cardio training at a constant pace. (Both types of cardio led to similar improvements in aerobic fitness.)

Individuals can choose other types of intermittent exercise as well. Strength training, for example, requires relatively short periods of exertion, with plenty of rest in between. 
 

The one choice you don’t want to make

While there are lots of good exercise options for someone with asthma, there’s one clearly bad choice, according to Dr. George: “Avoiding exercise.”  

Being inactive puts one at higher risk for obesity and all the health problems that go with it. And allowing one’s fitness level to decline makes it much harder to move when one needs or wants to.

Any choice is better than that one.

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

A single dose of an experimental psilocybin drug offered significant sustained improvement in symptoms and disability in patients with major depressive disorder (MDD) over a 6-week period, results of a study suggest.

The randomized, phase 2 trial was conducted at 11 sites across the United States and is the latest to demonstrate the psychedelic drug’s potential as a treatment for depression.

The project was funded by Usona Institute, a nonprofit medical research organization based in Madison, Wisc. The institute issued a press statement, but researchers did not comment further on the findings.

“As the largest and most rigorous study conducted across a wide spectrum of individuals with major depressive disorder, the results show promise for all people struggling with this condition,” lead author Charles Raison, MD, director of clinical and translational research at Usona, said in the statement. 

The 34 coauthors on the study are affiliated with public universities, research centers, and private companies. Eight of the investigators are identified as employees of Usona Institute.

Declining further comment, an institute spokesperson told this news organization that, “Usona has chosen the approach of no interviews, and this applies for all coauthors.”

The findings were published online in JAMA.
 

Largest study to date

Usona’s investigational psilocybin drug has been granted a breakthrough designation by the Food and Drug Administration, a process designed to speed drug development and review.

Previous smaller studies have suggested a rapid antidepressant response with psilocybin, but they have been small, unblinded, and have had short duration of follow-up, they write. This randomized, double-blind, phase 2 clinical trial is the largest study of psilocybin for depression to date, the researchers note.

It included 104 adults aged 21-65 years with MDD who had a current depressive episode of at least 60 days and a Montgomery-Åsberg Depression Rating Scale (MADRS) total score of 28 or more at baseline.

Participants had to be free of psychedelic drugs for at least 5 years, have had no active suicidal ideation or suicidal behavior in the prior 12 months, no personal or first-degree family history of psychosis or mania, and no history of moderate/severe alcohol or drug use disorder.

Before the study, participants had a 7- to 35-day screening period for psychiatric medication tapering, underwent baseline assessments, and received 6-8 hours of preparation with two facilitators who would be with them during dosing.

Dosing occurred within 7 days of baseline assessments. During the 6- to 8-hour session, participants received either a single 25-mg oral dose of psilocybin or 100-mg dose of niacin. One participant randomly assigned to receive psilocybin received the incorrect treatment, resulting in 50 participants receiving psilocybin and 54 receiving niacin.

Participants returned the next day, the next week, and then every 2 weeks for assessments, for a follow-up of 6 weeks.
 

Psychosocial support

Participants who received psilocybin reported significantly greater improvements in MDD symptoms, compared with those who received niacin. MADRS scores – a scale from 0 to 60 where higher scores indicate more severe depression – showed greater reductions with treatment vs. placebo at 8 days (mean difference, −12.0; 95% confidence interval, −16.6 to −7.4; P < .001), and at day 43 (mean difference, −12.3; 95% CI, −17.5 to −7.2; P < .001).

More participants receiving psilocybin had sustained depressive symptom response (42% vs. 11%; P = .002) and more improvement in the Sheehan Disability Scale score, which measures functional disability, 43 days after treatment (P < .001).

The effects persisted through the end of the study, although the differences between groups were no longer significant by week 6.

“This is another exciting piece of evidence that adds to the current literature regarding the potential efficacy of psilocybin for the treatment of mental health conditions, particularly depression,” said Greg Fonzo, MD, codirector of the Center for Psychedelic Research and Therapy at the University of Texas at Austin, who commented on the findings.

Significantly more people in the psilocybin group reported at least one treatment-related adverse event (AE, 82% vs. 44%), although most were mild to moderate. Headache and nausea were the most common side effects and most resolved within 1 day of dosing.

While those numbers are high, Dr. Fonzo said they’re not out of line with AEs reported in other studies.

“Particularly with the types of adverse events reported here, like headache and nausea, those are things you would typically expect to see in this treatment,” said Dr. Fonzo, who was not part of the research.

“But it is high, and it underscores that this is not a treatment without certain risks, even though it was good that they were primarily mild in severity,” he added.
 

A ‘stepping stone’ to FDA approval?

The use of tools to measure disability in addition to symptoms of depression severity is a strength of the study, Dr. Fonzo added. The use of an active comparator and the 6-week follow-up also offer something new over previous studies.

Despite the longer follow up, questions remain about the durability of response, something only a longer study could answer, Dr. Fonzo said. The small and homogeneous sample-size are also a concern. Nearly 90% of participants were White, and more than half had an income of $75,000 a year or higher.

“It’s another stepping stone in the process to FDA approval, but the next step in that process would be much larger phase 3 trials that would have much larger samples, a longer follow-up, and hopefully have a more inclusive swath of the population,” Dr. Fonzo said.

But perhaps one of the most significant limitations is the use of niacin as an active comparator, said Caleb Alexander, MD, codirector of the Center for Drug Safety and Effectiveness at Johns Hopkins University in Baltimore.

The use of an agent that doesn’t produce effects similar to those expected from a psychedelic introduced the potential for functional unblinding, Dr. Alexander said. Investigators did not ask participants to guess whether they received psilocybin or niacin, so the quality of the blinding was not assessed in the study.

“We’d like to see the use of [an] active comparator that might have a chance of obscuring to people as to whether they’ve been randomized to the treatment arm or control arm,” said Dr. Alexander, who wasn’t involved in the study. “Why not use a benzodiazepine or another drug that produces a transient euphoria that would better obscure whether or not people were receiving the psilocybin?”

The authors of an accompanying editorial shared these concerns, also noting that the study included “a significant number of patients who did not respond to therapy.”

“It is important to analyze and understand adverse outcomes in psychedelic trials and conduct longitudinal studies to determine how sustained the effects will be and what may initiate a recrudescence of symptoms,” write Rachel Yehuda, PhD, and Amy Lehrner, PhD, both of the Peters VA Medical Center and Icahn School of Medicine at Mount Sinai, New York.

“Future studies will help identify who is most likely to benefit from psychedelics, whether booster or repeated treatment is safe and beneficial, and what the optimal dose and therapeutic frameworks are.”

A long-term follow-up of the current trial was terminated last year because of low enrollment. The spokesperson with Usona Institute did not respond to questions about that study, and the institute’s statement only added that preparations are underway to launch another study that “will provide additional safety and efficacy data to support submission of a new drug application to the FDA.”

Usona published its manufacturing process that it used to synthesize psilocybin in an open-access journal and signed a statement on “open science and open praxis” with psilocybin and similar substances, which appears on their website. That statement was signed by 31 research and service organizations around the world and nearly 150 scientists, scholars, and practitioners.

The study was funded by Usona Institute. Dr. Raison reported receiving personal fees from Usona Institute and grants to Usona Institute from Dr. Bronner’s All-One, Fournier Family Foundation, Good Ventures, Steven and Alexandra Cohen Foundation, Tiny Blue Dot Foundation, Turnbull Family Foundation, and William A. Linton during the conduct of the study; and personal fees from Novartis, Sage/Biogen, Emory Healthcare, and Vail Health outside the submitted work. Dr. Fonzo and Dr. Alexander report no relevant financial relationships. Dr. Yehuda reports receiving nonfinancial support from the Multidisciplinary Association for Psychedelic Studies Public Benefit (MAPS PBC) and grants from COMPASS Pathways. Dr. Lehrner is an investigator on trials sponsored by MAPS PBC and COMPASS Pathways.

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

A single dose of an experimental psilocybin drug offered significant sustained improvement in symptoms and disability in patients with major depressive disorder (MDD) over a 6-week period, results of a study suggest.

The randomized, phase 2 trial was conducted at 11 sites across the United States and is the latest to demonstrate the psychedelic drug’s potential as a treatment for depression.

The project was funded by Usona Institute, a nonprofit medical research organization based in Madison, Wisc. The institute issued a press statement, but researchers did not comment further on the findings.

“As the largest and most rigorous study conducted across a wide spectrum of individuals with major depressive disorder, the results show promise for all people struggling with this condition,” lead author Charles Raison, MD, director of clinical and translational research at Usona, said in the statement. 

The 34 coauthors on the study are affiliated with public universities, research centers, and private companies. Eight of the investigators are identified as employees of Usona Institute.

Declining further comment, an institute spokesperson told this news organization that, “Usona has chosen the approach of no interviews, and this applies for all coauthors.”

The findings were published online in JAMA.
 

Largest study to date

Usona’s investigational psilocybin drug has been granted a breakthrough designation by the Food and Drug Administration, a process designed to speed drug development and review.

Previous smaller studies have suggested a rapid antidepressant response with psilocybin, but they have been small, unblinded, and have had short duration of follow-up, they write. This randomized, double-blind, phase 2 clinical trial is the largest study of psilocybin for depression to date, the researchers note.

It included 104 adults aged 21-65 years with MDD who had a current depressive episode of at least 60 days and a Montgomery-Åsberg Depression Rating Scale (MADRS) total score of 28 or more at baseline.

Participants had to be free of psychedelic drugs for at least 5 years, have had no active suicidal ideation or suicidal behavior in the prior 12 months, no personal or first-degree family history of psychosis or mania, and no history of moderate/severe alcohol or drug use disorder.

Before the study, participants had a 7- to 35-day screening period for psychiatric medication tapering, underwent baseline assessments, and received 6-8 hours of preparation with two facilitators who would be with them during dosing.

Dosing occurred within 7 days of baseline assessments. During the 6- to 8-hour session, participants received either a single 25-mg oral dose of psilocybin or 100-mg dose of niacin. One participant randomly assigned to receive psilocybin received the incorrect treatment, resulting in 50 participants receiving psilocybin and 54 receiving niacin.

Participants returned the next day, the next week, and then every 2 weeks for assessments, for a follow-up of 6 weeks.
 

Psychosocial support

Participants who received psilocybin reported significantly greater improvements in MDD symptoms, compared with those who received niacin. MADRS scores – a scale from 0 to 60 where higher scores indicate more severe depression – showed greater reductions with treatment vs. placebo at 8 days (mean difference, −12.0; 95% confidence interval, −16.6 to −7.4; P < .001), and at day 43 (mean difference, −12.3; 95% CI, −17.5 to −7.2; P < .001).

More participants receiving psilocybin had sustained depressive symptom response (42% vs. 11%; P = .002) and more improvement in the Sheehan Disability Scale score, which measures functional disability, 43 days after treatment (P < .001).

The effects persisted through the end of the study, although the differences between groups were no longer significant by week 6.

“This is another exciting piece of evidence that adds to the current literature regarding the potential efficacy of psilocybin for the treatment of mental health conditions, particularly depression,” said Greg Fonzo, MD, codirector of the Center for Psychedelic Research and Therapy at the University of Texas at Austin, who commented on the findings.

Significantly more people in the psilocybin group reported at least one treatment-related adverse event (AE, 82% vs. 44%), although most were mild to moderate. Headache and nausea were the most common side effects and most resolved within 1 day of dosing.

While those numbers are high, Dr. Fonzo said they’re not out of line with AEs reported in other studies.

“Particularly with the types of adverse events reported here, like headache and nausea, those are things you would typically expect to see in this treatment,” said Dr. Fonzo, who was not part of the research.

“But it is high, and it underscores that this is not a treatment without certain risks, even though it was good that they were primarily mild in severity,” he added.
 

A ‘stepping stone’ to FDA approval?

The use of tools to measure disability in addition to symptoms of depression severity is a strength of the study, Dr. Fonzo added. The use of an active comparator and the 6-week follow-up also offer something new over previous studies.

Despite the longer follow up, questions remain about the durability of response, something only a longer study could answer, Dr. Fonzo said. The small and homogeneous sample-size are also a concern. Nearly 90% of participants were White, and more than half had an income of $75,000 a year or higher.

“It’s another stepping stone in the process to FDA approval, but the next step in that process would be much larger phase 3 trials that would have much larger samples, a longer follow-up, and hopefully have a more inclusive swath of the population,” Dr. Fonzo said.

But perhaps one of the most significant limitations is the use of niacin as an active comparator, said Caleb Alexander, MD, codirector of the Center for Drug Safety and Effectiveness at Johns Hopkins University in Baltimore.

The use of an agent that doesn’t produce effects similar to those expected from a psychedelic introduced the potential for functional unblinding, Dr. Alexander said. Investigators did not ask participants to guess whether they received psilocybin or niacin, so the quality of the blinding was not assessed in the study.

“We’d like to see the use of [an] active comparator that might have a chance of obscuring to people as to whether they’ve been randomized to the treatment arm or control arm,” said Dr. Alexander, who wasn’t involved in the study. “Why not use a benzodiazepine or another drug that produces a transient euphoria that would better obscure whether or not people were receiving the psilocybin?”

The authors of an accompanying editorial shared these concerns, also noting that the study included “a significant number of patients who did not respond to therapy.”

“It is important to analyze and understand adverse outcomes in psychedelic trials and conduct longitudinal studies to determine how sustained the effects will be and what may initiate a recrudescence of symptoms,” write Rachel Yehuda, PhD, and Amy Lehrner, PhD, both of the Peters VA Medical Center and Icahn School of Medicine at Mount Sinai, New York.

“Future studies will help identify who is most likely to benefit from psychedelics, whether booster or repeated treatment is safe and beneficial, and what the optimal dose and therapeutic frameworks are.”

A long-term follow-up of the current trial was terminated last year because of low enrollment. The spokesperson with Usona Institute did not respond to questions about that study, and the institute’s statement only added that preparations are underway to launch another study that “will provide additional safety and efficacy data to support submission of a new drug application to the FDA.”

Usona published its manufacturing process that it used to synthesize psilocybin in an open-access journal and signed a statement on “open science and open praxis” with psilocybin and similar substances, which appears on their website. That statement was signed by 31 research and service organizations around the world and nearly 150 scientists, scholars, and practitioners.

The study was funded by Usona Institute. Dr. Raison reported receiving personal fees from Usona Institute and grants to Usona Institute from Dr. Bronner’s All-One, Fournier Family Foundation, Good Ventures, Steven and Alexandra Cohen Foundation, Tiny Blue Dot Foundation, Turnbull Family Foundation, and William A. Linton during the conduct of the study; and personal fees from Novartis, Sage/Biogen, Emory Healthcare, and Vail Health outside the submitted work. Dr. Fonzo and Dr. Alexander report no relevant financial relationships. Dr. Yehuda reports receiving nonfinancial support from the Multidisciplinary Association for Psychedelic Studies Public Benefit (MAPS PBC) and grants from COMPASS Pathways. Dr. Lehrner is an investigator on trials sponsored by MAPS PBC and COMPASS Pathways.

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

A single dose of an experimental psilocybin drug offered significant sustained improvement in symptoms and disability in patients with major depressive disorder (MDD) over a 6-week period, results of a study suggest.

The randomized, phase 2 trial was conducted at 11 sites across the United States and is the latest to demonstrate the psychedelic drug’s potential as a treatment for depression.

The project was funded by Usona Institute, a nonprofit medical research organization based in Madison, Wisc. The institute issued a press statement, but researchers did not comment further on the findings.

“As the largest and most rigorous study conducted across a wide spectrum of individuals with major depressive disorder, the results show promise for all people struggling with this condition,” lead author Charles Raison, MD, director of clinical and translational research at Usona, said in the statement. 

The 34 coauthors on the study are affiliated with public universities, research centers, and private companies. Eight of the investigators are identified as employees of Usona Institute.

Declining further comment, an institute spokesperson told this news organization that, “Usona has chosen the approach of no interviews, and this applies for all coauthors.”

The findings were published online in JAMA.
 

Largest study to date

Usona’s investigational psilocybin drug has been granted a breakthrough designation by the Food and Drug Administration, a process designed to speed drug development and review.

Previous smaller studies have suggested a rapid antidepressant response with psilocybin, but they have been small, unblinded, and have had short duration of follow-up, they write. This randomized, double-blind, phase 2 clinical trial is the largest study of psilocybin for depression to date, the researchers note.

It included 104 adults aged 21-65 years with MDD who had a current depressive episode of at least 60 days and a Montgomery-Åsberg Depression Rating Scale (MADRS) total score of 28 or more at baseline.

Participants had to be free of psychedelic drugs for at least 5 years, have had no active suicidal ideation or suicidal behavior in the prior 12 months, no personal or first-degree family history of psychosis or mania, and no history of moderate/severe alcohol or drug use disorder.

Before the study, participants had a 7- to 35-day screening period for psychiatric medication tapering, underwent baseline assessments, and received 6-8 hours of preparation with two facilitators who would be with them during dosing.

Dosing occurred within 7 days of baseline assessments. During the 6- to 8-hour session, participants received either a single 25-mg oral dose of psilocybin or 100-mg dose of niacin. One participant randomly assigned to receive psilocybin received the incorrect treatment, resulting in 50 participants receiving psilocybin and 54 receiving niacin.

Participants returned the next day, the next week, and then every 2 weeks for assessments, for a follow-up of 6 weeks.
 

Psychosocial support

Participants who received psilocybin reported significantly greater improvements in MDD symptoms, compared with those who received niacin. MADRS scores – a scale from 0 to 60 where higher scores indicate more severe depression – showed greater reductions with treatment vs. placebo at 8 days (mean difference, −12.0; 95% confidence interval, −16.6 to −7.4; P < .001), and at day 43 (mean difference, −12.3; 95% CI, −17.5 to −7.2; P < .001).

More participants receiving psilocybin had sustained depressive symptom response (42% vs. 11%; P = .002) and more improvement in the Sheehan Disability Scale score, which measures functional disability, 43 days after treatment (P < .001).

The effects persisted through the end of the study, although the differences between groups were no longer significant by week 6.

“This is another exciting piece of evidence that adds to the current literature regarding the potential efficacy of psilocybin for the treatment of mental health conditions, particularly depression,” said Greg Fonzo, MD, codirector of the Center for Psychedelic Research and Therapy at the University of Texas at Austin, who commented on the findings.

Significantly more people in the psilocybin group reported at least one treatment-related adverse event (AE, 82% vs. 44%), although most were mild to moderate. Headache and nausea were the most common side effects and most resolved within 1 day of dosing.

While those numbers are high, Dr. Fonzo said they’re not out of line with AEs reported in other studies.

“Particularly with the types of adverse events reported here, like headache and nausea, those are things you would typically expect to see in this treatment,” said Dr. Fonzo, who was not part of the research.

“But it is high, and it underscores that this is not a treatment without certain risks, even though it was good that they were primarily mild in severity,” he added.
 

A ‘stepping stone’ to FDA approval?

The use of tools to measure disability in addition to symptoms of depression severity is a strength of the study, Dr. Fonzo added. The use of an active comparator and the 6-week follow-up also offer something new over previous studies.

Despite the longer follow up, questions remain about the durability of response, something only a longer study could answer, Dr. Fonzo said. The small and homogeneous sample-size are also a concern. Nearly 90% of participants were White, and more than half had an income of $75,000 a year or higher.

“It’s another stepping stone in the process to FDA approval, but the next step in that process would be much larger phase 3 trials that would have much larger samples, a longer follow-up, and hopefully have a more inclusive swath of the population,” Dr. Fonzo said.

But perhaps one of the most significant limitations is the use of niacin as an active comparator, said Caleb Alexander, MD, codirector of the Center for Drug Safety and Effectiveness at Johns Hopkins University in Baltimore.

The use of an agent that doesn’t produce effects similar to those expected from a psychedelic introduced the potential for functional unblinding, Dr. Alexander said. Investigators did not ask participants to guess whether they received psilocybin or niacin, so the quality of the blinding was not assessed in the study.

“We’d like to see the use of [an] active comparator that might have a chance of obscuring to people as to whether they’ve been randomized to the treatment arm or control arm,” said Dr. Alexander, who wasn’t involved in the study. “Why not use a benzodiazepine or another drug that produces a transient euphoria that would better obscure whether or not people were receiving the psilocybin?”

The authors of an accompanying editorial shared these concerns, also noting that the study included “a significant number of patients who did not respond to therapy.”

“It is important to analyze and understand adverse outcomes in psychedelic trials and conduct longitudinal studies to determine how sustained the effects will be and what may initiate a recrudescence of symptoms,” write Rachel Yehuda, PhD, and Amy Lehrner, PhD, both of the Peters VA Medical Center and Icahn School of Medicine at Mount Sinai, New York.

“Future studies will help identify who is most likely to benefit from psychedelics, whether booster or repeated treatment is safe and beneficial, and what the optimal dose and therapeutic frameworks are.”

A long-term follow-up of the current trial was terminated last year because of low enrollment. The spokesperson with Usona Institute did not respond to questions about that study, and the institute’s statement only added that preparations are underway to launch another study that “will provide additional safety and efficacy data to support submission of a new drug application to the FDA.”

Usona published its manufacturing process that it used to synthesize psilocybin in an open-access journal and signed a statement on “open science and open praxis” with psilocybin and similar substances, which appears on their website. That statement was signed by 31 research and service organizations around the world and nearly 150 scientists, scholars, and practitioners.

The study was funded by Usona Institute. Dr. Raison reported receiving personal fees from Usona Institute and grants to Usona Institute from Dr. Bronner’s All-One, Fournier Family Foundation, Good Ventures, Steven and Alexandra Cohen Foundation, Tiny Blue Dot Foundation, Turnbull Family Foundation, and William A. Linton during the conduct of the study; and personal fees from Novartis, Sage/Biogen, Emory Healthcare, and Vail Health outside the submitted work. Dr. Fonzo and Dr. Alexander report no relevant financial relationships. Dr. Yehuda reports receiving nonfinancial support from the Multidisciplinary Association for Psychedelic Studies Public Benefit (MAPS PBC) and grants from COMPASS Pathways. Dr. Lehrner is an investigator on trials sponsored by MAPS PBC and COMPASS Pathways.

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

One in eight primary care clinicians revised prescriptions after receiving electronic alerts that estimated how much patients would pay out of pocket and that offered cheaper alternatives if available, according to findings from a study published in JAMA Internal Medicine.

The findings suggest that incorporating the alerts into electronic health record software could be useful for reducing patient expenses, said lead author Anna D. Sinaiko, PhD, assistant professor of health economics and policy at Harvard T. H. Chan School of Public Health, Boston. Showing clinicians the actual prices of medications their patient would pay led to changes in one in six orders when the potential cost savings to the patient was $20 or more, she said.

“This suggests that clinicians are taking medication out-of-pocket prices into account when they are most meaningful for patients.”

Such “real-time benefit tools” provide more meaningful information about patient drug prices in clinical settings than has previously been available, Dr. Sinaiko said. They provide out-of-pocket price estimates specific to individual patients and account for their health plans as opposed to symbols or colors indicating drugs that are more or less expensive, which has been the status quo.

Also, she said, Medicare has promoted the use of these tools by health systems and health plans.

Dr. Sinaiko and colleagues examined EHR data for 103,953 primary care clinic encounters with 72,420 patients in the University of Colorado Health system (81.5% White; 59.5% female; 51.4% aged 65 years or older; 51.9% on Medicare). The patients were treated from July 2019 to July 2022 by 889 clinicians (physicians, nurse practitioners, and physician assistants), who wrote nearly 1.9 million medication orders. Of those orders, 181,887 (9.7%) included a price estimate.

For each prescription, the EHR displayed out-of-pocket costs for patients and offered alternative drugs if those drugs were at least 15 cents cheaper or if they were available at an on-site pharmacy.

Clinicians changed prescriptions 12.3% of the time after they saw price information. The percentage went up to 14% when possible cost savings were $5 or more.

Researchers also found that, while there was the option for clinicians to click a button in the EHR and learn a patient’s specific medication price before ordering a drug, very few clinicians requested price estimates directly, Dr. Sinaiko said. Fewer than 1% (0.9%) did so. The other 99.1% did not, meaning they received information about prices via alerts only after ordering prescriptions.

Researchers also found that clinicians weren’t more likely to change psychiatric medications when the cost savings for the patient was higher. The demographics of patients – such as whether they were poorer or richer – didn’t affect the willingness of clinicians to change prescriptions after receiving price information.

In the big picture, Dr. Sinaiko said, “The fact that medication orders were changed more often when the potential cost savings for patients were larger suggests to me that clinicians were taking out-of-pocket cost into account when it was most salient for the patient.”

It’s not clear, however, why clinicians did not revise more prescriptions to help patients save money.

One theory is that they may ignore the alerts because of “alert fatigue,” she said. “I’d like to know if clinicians discount or ignore the price estimate because they don’t know where it comes from or whether it is accurate. It’s also possible that clinicians discuss the option to change a medication order with their patient, and for reasons other than cost, they decide to keep the original selection. This suggests that clinicians might be using price information to guide – not dictate – their clinical decisions.”

The study had limitations. The researchers did not assess whether the cheaper alternative medications were appropriate in individual cases. Also, they did not take into account other factors, such as patient preferences, that affect how clinicians make prescription decisions.

Clinicians may also not know whether their patients worry about drug costs.

“There isn’t really good data on who wants to talk to their physician about costs, but it is definitely nowhere near 100%,” said health services researcher Alyna Chien, MD, a pediatrician at Boston Children’s Hospital. “For physicians, there is also good reason to keep cost out of the picture until asked so that patients don’t feel like they’re getting suboptimal choices.”

University of Washington, Seattle, graduate student Shiven Bhardwaj, PharmD, who studies health policy, said in an interview that the new study “suggests that physicians are not frequently selecting less costly agents suggested by the real-time benefit tool, and they may not even be considering these alternatives.”

According to Dr. Bhardwaj, previous research has found that physicians “are unable to estimate what their patients’ out-of-pocket costs may be, which is not surprising, given wide variation in health insurance benefit designs.”

Why aren’t more clinicians choosing cheaper alternatives, even when they’re directly told about them? Dr. Bhardwaj suggests that many health systems may be implementing electronic drug cost alerts in the absence of official notification or training.

“Health systems should be making providers aware of the system and its potential to reduce patients’ out-of-pocket costs.”
 

What’s next for research in this area?

Lead author Dr. Sinaiko said she and her team will interview clinicians and patients in practices at University of Colorado Health to understand how these price estimates are used in clinical encounters and how they affect clinician practice and patient experiences

“We are interested in learning about the cost-savings thresholds that are important to patients,” she said.

The researchers will also examine whether cost information helps to boost access to medications for chronic conditions among Black and Hispanic patients and patients who live in rural areas, she said.

The study was funded by the Harvard School of Public Health Dean’s Fund and the National Institute on Minority Health and Health Disparities. Dr. Sinaiko, Dr. Bhardwaj, and Dr. Chien have no relevant disclosures. Two study authors report having received a grant from the National Institute on Aging and consulting fees from Dispatch Health and Credo Health.

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

One in eight primary care clinicians revised prescriptions after receiving electronic alerts that estimated how much patients would pay out of pocket and that offered cheaper alternatives if available, according to findings from a study published in JAMA Internal Medicine.

The findings suggest that incorporating the alerts into electronic health record software could be useful for reducing patient expenses, said lead author Anna D. Sinaiko, PhD, assistant professor of health economics and policy at Harvard T. H. Chan School of Public Health, Boston. Showing clinicians the actual prices of medications their patient would pay led to changes in one in six orders when the potential cost savings to the patient was $20 or more, she said.

“This suggests that clinicians are taking medication out-of-pocket prices into account when they are most meaningful for patients.”

Such “real-time benefit tools” provide more meaningful information about patient drug prices in clinical settings than has previously been available, Dr. Sinaiko said. They provide out-of-pocket price estimates specific to individual patients and account for their health plans as opposed to symbols or colors indicating drugs that are more or less expensive, which has been the status quo.

Also, she said, Medicare has promoted the use of these tools by health systems and health plans.

Dr. Sinaiko and colleagues examined EHR data for 103,953 primary care clinic encounters with 72,420 patients in the University of Colorado Health system (81.5% White; 59.5% female; 51.4% aged 65 years or older; 51.9% on Medicare). The patients were treated from July 2019 to July 2022 by 889 clinicians (physicians, nurse practitioners, and physician assistants), who wrote nearly 1.9 million medication orders. Of those orders, 181,887 (9.7%) included a price estimate.

For each prescription, the EHR displayed out-of-pocket costs for patients and offered alternative drugs if those drugs were at least 15 cents cheaper or if they were available at an on-site pharmacy.

Clinicians changed prescriptions 12.3% of the time after they saw price information. The percentage went up to 14% when possible cost savings were $5 or more.

Researchers also found that, while there was the option for clinicians to click a button in the EHR and learn a patient’s specific medication price before ordering a drug, very few clinicians requested price estimates directly, Dr. Sinaiko said. Fewer than 1% (0.9%) did so. The other 99.1% did not, meaning they received information about prices via alerts only after ordering prescriptions.

Researchers also found that clinicians weren’t more likely to change psychiatric medications when the cost savings for the patient was higher. The demographics of patients – such as whether they were poorer or richer – didn’t affect the willingness of clinicians to change prescriptions after receiving price information.

In the big picture, Dr. Sinaiko said, “The fact that medication orders were changed more often when the potential cost savings for patients were larger suggests to me that clinicians were taking out-of-pocket cost into account when it was most salient for the patient.”

It’s not clear, however, why clinicians did not revise more prescriptions to help patients save money.

One theory is that they may ignore the alerts because of “alert fatigue,” she said. “I’d like to know if clinicians discount or ignore the price estimate because they don’t know where it comes from or whether it is accurate. It’s also possible that clinicians discuss the option to change a medication order with their patient, and for reasons other than cost, they decide to keep the original selection. This suggests that clinicians might be using price information to guide – not dictate – their clinical decisions.”

The study had limitations. The researchers did not assess whether the cheaper alternative medications were appropriate in individual cases. Also, they did not take into account other factors, such as patient preferences, that affect how clinicians make prescription decisions.

Clinicians may also not know whether their patients worry about drug costs.

“There isn’t really good data on who wants to talk to their physician about costs, but it is definitely nowhere near 100%,” said health services researcher Alyna Chien, MD, a pediatrician at Boston Children’s Hospital. “For physicians, there is also good reason to keep cost out of the picture until asked so that patients don’t feel like they’re getting suboptimal choices.”

University of Washington, Seattle, graduate student Shiven Bhardwaj, PharmD, who studies health policy, said in an interview that the new study “suggests that physicians are not frequently selecting less costly agents suggested by the real-time benefit tool, and they may not even be considering these alternatives.”

According to Dr. Bhardwaj, previous research has found that physicians “are unable to estimate what their patients’ out-of-pocket costs may be, which is not surprising, given wide variation in health insurance benefit designs.”

Why aren’t more clinicians choosing cheaper alternatives, even when they’re directly told about them? Dr. Bhardwaj suggests that many health systems may be implementing electronic drug cost alerts in the absence of official notification or training.

“Health systems should be making providers aware of the system and its potential to reduce patients’ out-of-pocket costs.”
 

What’s next for research in this area?

Lead author Dr. Sinaiko said she and her team will interview clinicians and patients in practices at University of Colorado Health to understand how these price estimates are used in clinical encounters and how they affect clinician practice and patient experiences

“We are interested in learning about the cost-savings thresholds that are important to patients,” she said.

The researchers will also examine whether cost information helps to boost access to medications for chronic conditions among Black and Hispanic patients and patients who live in rural areas, she said.

The study was funded by the Harvard School of Public Health Dean’s Fund and the National Institute on Minority Health and Health Disparities. Dr. Sinaiko, Dr. Bhardwaj, and Dr. Chien have no relevant disclosures. Two study authors report having received a grant from the National Institute on Aging and consulting fees from Dispatch Health and Credo Health.

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

One in eight primary care clinicians revised prescriptions after receiving electronic alerts that estimated how much patients would pay out of pocket and that offered cheaper alternatives if available, according to findings from a study published in JAMA Internal Medicine.

The findings suggest that incorporating the alerts into electronic health record software could be useful for reducing patient expenses, said lead author Anna D. Sinaiko, PhD, assistant professor of health economics and policy at Harvard T. H. Chan School of Public Health, Boston. Showing clinicians the actual prices of medications their patient would pay led to changes in one in six orders when the potential cost savings to the patient was $20 or more, she said.

“This suggests that clinicians are taking medication out-of-pocket prices into account when they are most meaningful for patients.”

Such “real-time benefit tools” provide more meaningful information about patient drug prices in clinical settings than has previously been available, Dr. Sinaiko said. They provide out-of-pocket price estimates specific to individual patients and account for their health plans as opposed to symbols or colors indicating drugs that are more or less expensive, which has been the status quo.

Also, she said, Medicare has promoted the use of these tools by health systems and health plans.

Dr. Sinaiko and colleagues examined EHR data for 103,953 primary care clinic encounters with 72,420 patients in the University of Colorado Health system (81.5% White; 59.5% female; 51.4% aged 65 years or older; 51.9% on Medicare). The patients were treated from July 2019 to July 2022 by 889 clinicians (physicians, nurse practitioners, and physician assistants), who wrote nearly 1.9 million medication orders. Of those orders, 181,887 (9.7%) included a price estimate.

For each prescription, the EHR displayed out-of-pocket costs for patients and offered alternative drugs if those drugs were at least 15 cents cheaper or if they were available at an on-site pharmacy.

Clinicians changed prescriptions 12.3% of the time after they saw price information. The percentage went up to 14% when possible cost savings were $5 or more.

Researchers also found that, while there was the option for clinicians to click a button in the EHR and learn a patient’s specific medication price before ordering a drug, very few clinicians requested price estimates directly, Dr. Sinaiko said. Fewer than 1% (0.9%) did so. The other 99.1% did not, meaning they received information about prices via alerts only after ordering prescriptions.

Researchers also found that clinicians weren’t more likely to change psychiatric medications when the cost savings for the patient was higher. The demographics of patients – such as whether they were poorer or richer – didn’t affect the willingness of clinicians to change prescriptions after receiving price information.

In the big picture, Dr. Sinaiko said, “The fact that medication orders were changed more often when the potential cost savings for patients were larger suggests to me that clinicians were taking out-of-pocket cost into account when it was most salient for the patient.”

It’s not clear, however, why clinicians did not revise more prescriptions to help patients save money.

One theory is that they may ignore the alerts because of “alert fatigue,” she said. “I’d like to know if clinicians discount or ignore the price estimate because they don’t know where it comes from or whether it is accurate. It’s also possible that clinicians discuss the option to change a medication order with their patient, and for reasons other than cost, they decide to keep the original selection. This suggests that clinicians might be using price information to guide – not dictate – their clinical decisions.”

The study had limitations. The researchers did not assess whether the cheaper alternative medications were appropriate in individual cases. Also, they did not take into account other factors, such as patient preferences, that affect how clinicians make prescription decisions.

Clinicians may also not know whether their patients worry about drug costs.

“There isn’t really good data on who wants to talk to their physician about costs, but it is definitely nowhere near 100%,” said health services researcher Alyna Chien, MD, a pediatrician at Boston Children’s Hospital. “For physicians, there is also good reason to keep cost out of the picture until asked so that patients don’t feel like they’re getting suboptimal choices.”

University of Washington, Seattle, graduate student Shiven Bhardwaj, PharmD, who studies health policy, said in an interview that the new study “suggests that physicians are not frequently selecting less costly agents suggested by the real-time benefit tool, and they may not even be considering these alternatives.”

According to Dr. Bhardwaj, previous research has found that physicians “are unable to estimate what their patients’ out-of-pocket costs may be, which is not surprising, given wide variation in health insurance benefit designs.”

Why aren’t more clinicians choosing cheaper alternatives, even when they’re directly told about them? Dr. Bhardwaj suggests that many health systems may be implementing electronic drug cost alerts in the absence of official notification or training.

“Health systems should be making providers aware of the system and its potential to reduce patients’ out-of-pocket costs.”
 

What’s next for research in this area?

Lead author Dr. Sinaiko said she and her team will interview clinicians and patients in practices at University of Colorado Health to understand how these price estimates are used in clinical encounters and how they affect clinician practice and patient experiences

“We are interested in learning about the cost-savings thresholds that are important to patients,” she said.

The researchers will also examine whether cost information helps to boost access to medications for chronic conditions among Black and Hispanic patients and patients who live in rural areas, she said.

The study was funded by the Harvard School of Public Health Dean’s Fund and the National Institute on Minority Health and Health Disparities. Dr. Sinaiko, Dr. Bhardwaj, and Dr. Chien have no relevant disclosures. Two study authors report having received a grant from the National Institute on Aging and consulting fees from Dispatch Health and Credo Health.

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

Patients with major depressive disorder (MDD) and suicidal behavior during the depressive period have more than double the mortality rate of those without a suicide attempt, new research suggests.

Investigators studied close to 143,000 patients, encompassing more than 150,000 MDD episodes. Episodes of depression with suicidal behavior (MDD-SB) were compared to MDD episodes without suicidal behavior (MDD-non-SB).

Suicidal behavior was associated with a 2.6-fold higher rate of all-cause mortality, as well as considerably higher health care resource utilization (HCRU) and work loss, compared with matched controls.

Patients with depression who had attempted suicide were younger and more commonly suffering from other psychiatric comorbidities, such as anxiety and addiction. Important risk factors for suicidal acts within a year after the onset of a depressive episode were previous suicide attempts, substance use disorder, anxiety, and sleeping disorders.

“The findings tell us that the care provided for this particular group needs to be developed,” lead author Johan Lundberg, MD, PhD, adjunct professor in psychiatry and senior physician in psychiatry, Karolinska Institute, Stockholm, told this news organization.

“The take-home message is that, when treating patients with increased risk of suicidal behavior, one should offer treatments with this in mind,” said Dr. Lundberg, also the head of the section of mood disorders, Northern Stockholm Psychiatry Clinic. “One possible option is lithium augmentation.”

The study was published online in JAMA Psychiatry.
 

Identifying subgroups

Depression is associated with increased all-cause mortality, the authors write. Suicidal behavior and previous suicide attempts are known to increase the risk of suicide-associated mortality, with up to 13% of patients with nonfatal suicide attempts dying of suicide at a later time.

Previous studies investigating the association between suicidal behavior and mortality have been limited by nonrandom sampling due to “nonuniversal access to health care and/or exclusion of primary care data,” they state.

For this reason, it’s not established to what extent these estimates actually represent patients with MDD as a whole, or to what extent suicidal behavior is a risk factor for all-cause mortality.

“We think there is a need to identify subgroups within the very large group of individuals with MDD in order to improve treatment outcomes,” Dr. Lundberg said.

To do so, the researchers turned to data from the Stockholm MDD Cohort (SMC), which comprises all patients diagnosed with MDD in any health care setting in the regions of Stockholm from 2010 to 2018. They identified 5 years of recorded MDD episodes (n = 158,169) in patients aged 18 years and older (n = 145,577). A single patient could contribute more than one episode.

At index, MDD-SB patients (n = 2,219; mean age, 41 years) were matched with MDD-non-SB patients (9,574; mean age, 41 years) based on age, sex, year of MDD diagnosis, and socioeconomic status. In total, 2,219 episodes (63.2% in women, 36.8% in men) were compared to 11,109 episodes (63.4% in women, 36.6% in men), respectively.
 

Enhanced monitoring, optimized treatment

The median time from the start of the episode until the first suicidal behavior was 165 days.

The all-cause mortality rate in the MDD-SB and MDD-non-SB groups was 2.5 per 100 person-years vs. 1 per 100 person-years, respectively (based on 466 deaths), corresponding to a hazard ratio of 2.62 (95% confidence interval, 2.15-3.20).

Patients in the MDD-SB group were younger, were more frequently diagnosed while in specialized care, and had sustained more work loss than their counterparts in the MDD-non-SB group. They also showed a gradual increase in the prevalence of comorbid conditions from about 12 months before index, with this increase being “most pronounced” for anxiety, stress, substance use, and personality disorders.

MDD-SB episodes were associated with higher HCRU and more work loss, compared with MDD-non-SB episodes.

Complicated family of destructive behaviors

In a comment, Russell Copelan, MD, a former emergency department psychiatrist at the University of Colorado Affiliated Hospital and currently an expert consultant to the American Association of Suicidology, said a take-home message of the study is that suicide is “a complex and complicated family of destructive behaviors.”

The findings “should not suggest a wait-and-see clinical approach,” warned Dr. Copelan, who wasn’t involved with the study.

Underrecognized or misdiagnosed anxiety, agitation, and insomnia may be “barriers to remission and treatment response,” he noted.

Dr. Copelan, who is also the founder and CEO of eMed Logic, which offers assessment tools for suicide and violence, encouraged clinicians “not to minimize the proportion of patients who experience anxiety, agitation, and insomnia in response to what some may consider a personal misfortune, such as interpersonal, employment, or financial crisis.”

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

Patients with major depressive disorder (MDD) and suicidal behavior during the depressive period have more than double the mortality rate of those without a suicide attempt, new research suggests.

Investigators studied close to 143,000 patients, encompassing more than 150,000 MDD episodes. Episodes of depression with suicidal behavior (MDD-SB) were compared to MDD episodes without suicidal behavior (MDD-non-SB).

Suicidal behavior was associated with a 2.6-fold higher rate of all-cause mortality, as well as considerably higher health care resource utilization (HCRU) and work loss, compared with matched controls.

Patients with depression who had attempted suicide were younger and more commonly suffering from other psychiatric comorbidities, such as anxiety and addiction. Important risk factors for suicidal acts within a year after the onset of a depressive episode were previous suicide attempts, substance use disorder, anxiety, and sleeping disorders.

“The findings tell us that the care provided for this particular group needs to be developed,” lead author Johan Lundberg, MD, PhD, adjunct professor in psychiatry and senior physician in psychiatry, Karolinska Institute, Stockholm, told this news organization.

“The take-home message is that, when treating patients with increased risk of suicidal behavior, one should offer treatments with this in mind,” said Dr. Lundberg, also the head of the section of mood disorders, Northern Stockholm Psychiatry Clinic. “One possible option is lithium augmentation.”

The study was published online in JAMA Psychiatry.
 

Identifying subgroups

Depression is associated with increased all-cause mortality, the authors write. Suicidal behavior and previous suicide attempts are known to increase the risk of suicide-associated mortality, with up to 13% of patients with nonfatal suicide attempts dying of suicide at a later time.

Previous studies investigating the association between suicidal behavior and mortality have been limited by nonrandom sampling due to “nonuniversal access to health care and/or exclusion of primary care data,” they state.

For this reason, it’s not established to what extent these estimates actually represent patients with MDD as a whole, or to what extent suicidal behavior is a risk factor for all-cause mortality.

“We think there is a need to identify subgroups within the very large group of individuals with MDD in order to improve treatment outcomes,” Dr. Lundberg said.

To do so, the researchers turned to data from the Stockholm MDD Cohort (SMC), which comprises all patients diagnosed with MDD in any health care setting in the regions of Stockholm from 2010 to 2018. They identified 5 years of recorded MDD episodes (n = 158,169) in patients aged 18 years and older (n = 145,577). A single patient could contribute more than one episode.

At index, MDD-SB patients (n = 2,219; mean age, 41 years) were matched with MDD-non-SB patients (9,574; mean age, 41 years) based on age, sex, year of MDD diagnosis, and socioeconomic status. In total, 2,219 episodes (63.2% in women, 36.8% in men) were compared to 11,109 episodes (63.4% in women, 36.6% in men), respectively.
 

Enhanced monitoring, optimized treatment

The median time from the start of the episode until the first suicidal behavior was 165 days.

The all-cause mortality rate in the MDD-SB and MDD-non-SB groups was 2.5 per 100 person-years vs. 1 per 100 person-years, respectively (based on 466 deaths), corresponding to a hazard ratio of 2.62 (95% confidence interval, 2.15-3.20).

Patients in the MDD-SB group were younger, were more frequently diagnosed while in specialized care, and had sustained more work loss than their counterparts in the MDD-non-SB group. They also showed a gradual increase in the prevalence of comorbid conditions from about 12 months before index, with this increase being “most pronounced” for anxiety, stress, substance use, and personality disorders.

MDD-SB episodes were associated with higher HCRU and more work loss, compared with MDD-non-SB episodes.

Complicated family of destructive behaviors

In a comment, Russell Copelan, MD, a former emergency department psychiatrist at the University of Colorado Affiliated Hospital and currently an expert consultant to the American Association of Suicidology, said a take-home message of the study is that suicide is “a complex and complicated family of destructive behaviors.”

The findings “should not suggest a wait-and-see clinical approach,” warned Dr. Copelan, who wasn’t involved with the study.

Underrecognized or misdiagnosed anxiety, agitation, and insomnia may be “barriers to remission and treatment response,” he noted.

Dr. Copelan, who is also the founder and CEO of eMed Logic, which offers assessment tools for suicide and violence, encouraged clinicians “not to minimize the proportion of patients who experience anxiety, agitation, and insomnia in response to what some may consider a personal misfortune, such as interpersonal, employment, or financial crisis.”

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

Patients with major depressive disorder (MDD) and suicidal behavior during the depressive period have more than double the mortality rate of those without a suicide attempt, new research suggests.

Investigators studied close to 143,000 patients, encompassing more than 150,000 MDD episodes. Episodes of depression with suicidal behavior (MDD-SB) were compared to MDD episodes without suicidal behavior (MDD-non-SB).

Suicidal behavior was associated with a 2.6-fold higher rate of all-cause mortality, as well as considerably higher health care resource utilization (HCRU) and work loss, compared with matched controls.

Patients with depression who had attempted suicide were younger and more commonly suffering from other psychiatric comorbidities, such as anxiety and addiction. Important risk factors for suicidal acts within a year after the onset of a depressive episode were previous suicide attempts, substance use disorder, anxiety, and sleeping disorders.

“The findings tell us that the care provided for this particular group needs to be developed,” lead author Johan Lundberg, MD, PhD, adjunct professor in psychiatry and senior physician in psychiatry, Karolinska Institute, Stockholm, told this news organization.

“The take-home message is that, when treating patients with increased risk of suicidal behavior, one should offer treatments with this in mind,” said Dr. Lundberg, also the head of the section of mood disorders, Northern Stockholm Psychiatry Clinic. “One possible option is lithium augmentation.”

The study was published online in JAMA Psychiatry.
 

Identifying subgroups

Depression is associated with increased all-cause mortality, the authors write. Suicidal behavior and previous suicide attempts are known to increase the risk of suicide-associated mortality, with up to 13% of patients with nonfatal suicide attempts dying of suicide at a later time.

Previous studies investigating the association between suicidal behavior and mortality have been limited by nonrandom sampling due to “nonuniversal access to health care and/or exclusion of primary care data,” they state.

For this reason, it’s not established to what extent these estimates actually represent patients with MDD as a whole, or to what extent suicidal behavior is a risk factor for all-cause mortality.

“We think there is a need to identify subgroups within the very large group of individuals with MDD in order to improve treatment outcomes,” Dr. Lundberg said.

To do so, the researchers turned to data from the Stockholm MDD Cohort (SMC), which comprises all patients diagnosed with MDD in any health care setting in the regions of Stockholm from 2010 to 2018. They identified 5 years of recorded MDD episodes (n = 158,169) in patients aged 18 years and older (n = 145,577). A single patient could contribute more than one episode.

At index, MDD-SB patients (n = 2,219; mean age, 41 years) were matched with MDD-non-SB patients (9,574; mean age, 41 years) based on age, sex, year of MDD diagnosis, and socioeconomic status. In total, 2,219 episodes (63.2% in women, 36.8% in men) were compared to 11,109 episodes (63.4% in women, 36.6% in men), respectively.
 

Enhanced monitoring, optimized treatment

The median time from the start of the episode until the first suicidal behavior was 165 days.

The all-cause mortality rate in the MDD-SB and MDD-non-SB groups was 2.5 per 100 person-years vs. 1 per 100 person-years, respectively (based on 466 deaths), corresponding to a hazard ratio of 2.62 (95% confidence interval, 2.15-3.20).

Patients in the MDD-SB group were younger, were more frequently diagnosed while in specialized care, and had sustained more work loss than their counterparts in the MDD-non-SB group. They also showed a gradual increase in the prevalence of comorbid conditions from about 12 months before index, with this increase being “most pronounced” for anxiety, stress, substance use, and personality disorders.

MDD-SB episodes were associated with higher HCRU and more work loss, compared with MDD-non-SB episodes.

Complicated family of destructive behaviors

In a comment, Russell Copelan, MD, a former emergency department psychiatrist at the University of Colorado Affiliated Hospital and currently an expert consultant to the American Association of Suicidology, said a take-home message of the study is that suicide is “a complex and complicated family of destructive behaviors.”

The findings “should not suggest a wait-and-see clinical approach,” warned Dr. Copelan, who wasn’t involved with the study.

Underrecognized or misdiagnosed anxiety, agitation, and insomnia may be “barriers to remission and treatment response,” he noted.

Dr. Copelan, who is also the founder and CEO of eMed Logic, which offers assessment tools for suicide and violence, encouraged clinicians “not to minimize the proportion of patients who experience anxiety, agitation, and insomnia in response to what some may consider a personal misfortune, such as interpersonal, employment, or financial crisis.”

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

DNA testing for prostate cancer – of the patients’ inherited DNA and their tumors’ somatic DNA – is increasingly used in the U.S. to determine whether and how to treat low-grade, localized prostate cancers.

Another genetic approach, known as the polygenic risk score (PRS), is emerging as a third genetic approach for sorting out prostate cancer risks.

PRS aims to stratify a person’s disease risk by going beyond rare variants in genes, such as BRCA2, and compiling a weighted score that integrates thousands of common variants whose role in cancer may be unknown but are found more frequently in men with prostate cancer. Traditional germline testing, by contrast, looks for about 30 specific genes directly linked to prostate cancer.

Essentially, “a polygenic risk score estimates your risk by adding together the number of bad cards you were dealt by the impact of each card, such as an ace versus a deuce,” said William Catalona, MD, a urologist at Northwestern University Feinberg School of Medicine, Chicago, known as the father of prostate-specific antigen (PSA) screening.

In combination, these variants can have powerful predictive value.

Having a tool that can mine the depths of a person’s genetic makeup and help doctors devise a nuanced risk assessment for prostate cancer seems like a winning proposition.

Despite its promise, PRS testing is not yet used routinely in practice. The central uncertainty regarding its use lies in whether the risk score can accurately predict who will develop aggressive prostate cancer that needs to be treated and who won’t. The research to date has been mixed, and experts remain polarized.

“PRS absolutely, irrefutably can distinguish between the probability of somebody developing prostate cancer or not. Nobody could look at the data and argue with that,” said Todd Morgan, MD, a genomics researcher from the University of Michigan, Ann Arbor. “What [the data] so far haven’t really been able to do is distinguish whether somebody is likely to have clinically significant prostate cancer versus lower-risk prostate cancer.”
 

The promise of PRS in prostate cancer?

Prostate cancer – the most common type of solid tumor in men and the second most common cancer killer – is a major target for PRS because it is considered one of the most heritable cancers, according to Burcu Darst, PhD, a genetic epidemiologist at Fred Hutchinson Cancer Center, Seattle.

Research in the area has intensified in recent years as genome-wide association studies (GWAS) have become more affordable and the genetic information from these studies has been increasingly aggregated in biobanks.

“Because the sample sizes now are so much bigger than they used to be for GWAS studies, we’re able to develop much better polygenic risk scores than we were before,” said Dr. Darst.

Dr. Darst is lead author on the largest, most diverse prostate GWAS analysis, which led to the development of a PRS that is highly predictive of prostate cancer risk across diverse populations.

In the 2021 meta-analysis, which included 107,247 case patients and 127,006 control patients, Dr. Darst and colleagues identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants.

Compared with men at average genetic risk for prostate cancer – those in the 40%-60% genetic risk score category – men in the top 10% of the risk score (90%-100%) had between a 3.74-fold to fivefold higher risk for prostate cancer. However, the team did not find evidence that the genetic risk score could differentiate a person’s risk for aggressive versus nonaggressive disease.

As Dr. Darst’s team continues to improve the PRS, Dr. Darst says it will get better at predicting aggressive disease. One recent analysis from Dr. Darst and colleagues found that “although the PRS generally did not differentiate aggressive versus nonaggressive prostate cancer,” about 40% of men who will develop aggressive disease have a PRS in the top 20%, whereas only about 7% of men who will develop aggressive tumors have a PRS in the bottom 20%. Another recent study from Dr. Darst and colleagues found that PRS can distinguish between aggressive and nonaggressive disease in men of African ancestry.

These findings highlight “the potential clinical utility of the polygenic risk score,” Dr. Darst said.

Although the growing body of research makes Dr. Catalona, Dr. Darst, and others optimistic about PRS, the landscape is also littered with critics and studies showcasing its limitations.

An analysis, published in JAMA Internal Medicine, found that, compared with a contemporary clinical risk predictor, PRS did not improve prediction of aggressive prostate cancers. Another recent study, which used a 6.6 million–variant PRS to predict the risk of incident prostate cancer among 5,701 healthy men of European descent older than age 69, found that men in the top 20% of the PRS distribution “had an almost three times higher risk of prostate cancer,” compared with men in the lowest quintile; however, a higher PRS was not associated with a higher Gleason grade group, indicative of more aggressive disease.

“While a PRS for prostate cancer is strongly associated with incident risk” in the cohort, “the clinical utility of the PRS as a biomarker is currently limited by its inability to select for clinically significant disease,” the authors concluded.
 

Utility in practice?

Although PRS has been billed as a predictive test, Dr. Catalona believes PRS could have a range of uses both before and after diagnosis.

PRS may, for instance, guide treatment choices for men diagnosed with prostate cancer, Dr. Catalona noted. For men with a PRS that signals a higher risk for aggressive disease, a positive prostate biopsy result could help them decide whether to seek active treatment with surgery or radiation or go on active surveillance.

PRS could also help inform cancer screening. If a PRS test found a patient’s risk for prostate cancer was high, that person could decide to seek PSA screening before age 50 – the recommended age for average-risk men.

However, Aroon Hingorani, MD, a professor of genetic epidemiology at the University College London, expressed concern over using PRS to inform cancer screenings.

Part of the issue, Dr. Hingorani and colleagues explained in a recent article in the BMJ, is that “risk is notoriously difficult to communicate.”

PRS estimates a person’s relative risk for a disease but does not factor in the underlying population risk. Risk prediction should include both, Dr. Hingorani said.

People with high-risk scores may, for instance, discuss earlier screening with their clinician, even if their absolute risk for the disease – which accounts for both relative risk and underlying population disease risk – is still small, Dr. Hingorani and colleagues said. “Conversely, people who do not have ‘high risk’ polygenic scores might be less likely to seek medical attention for concerning symptoms, or their clinicians might be less inclined to investigate.”

Given this, Dr. Hingorani and colleagues believe polygenic scores “will always be limited in their ability to predict disease” and “will always remain one of many risk factors,” such as environmental influences.

Another caveat is that PRS generally is based on data collected from European populations, said Eric Klein, MD, chairman emeritus of urology at the Cleveland Clinic and now a scientist at the biotechnology company Grail, which developed the Galleri blood test that screens for 50 types of cancer. While a valid concern, “that’s easy to fix ultimately,” he said, as the diversity of inputs from various ethnicities increases over time.

Although several companies offer PRS products, moving PRS into the clinic would require an infrastructure for testing which does not yet exist in the U.S., said Dr. Catalona.

Giordano Botta, PhD, CEO of New York–based PRS software start-up Alleica, which bills itself as the Polygenic Risk Score Company, said “test demand is growing rapidly.” His company offers PRS scores that integrate up to 700,000 markers for prostate cancer depending on ancestry and charges patients $250 out of pocket for testing.

Dr. Botta noted that thousands of American patients have undergone PRS testing through his company. Several health systems, including Penn Medicine, Brigham and Women’s Hospital, and the University of Alabama at Birmingham, have been using the test to help “see beyond what traditional risk factors allow,” he said.

However, this and other PRS tests are not yet widely used in the primary care setting.

A major barrier to wider adoption is that experts remain divided on its clinical utility. “People either say it’s ready, and it should be implemented, or they say it’s never going to work,” said Sowmiya Moorthie, PhD, a senior policy analyst with the PHG Foundation, a Cambridge University–associated think tank.

Dr. Klein sits in the optimistic camp. He envisions a day soon when patients will undergo whole-genome testing to collect data on risk scores and incorporate the full genome into the electronic record. At a certain age, primary care physicians would then query the data to determine the patient’s germline risk for a variety of diseases.

“At age 45, if I were a primary care physician seeing a male, I would query the PRS for prostate cancer, and if the risks were low, I would say, ‘You don’t need your first PSA probably until you’re 50,’ ” Dr. Klein said. “If your risk is high, I’d say, ‘Let’s do a baseline PSA now.’ ”

We would then have the data to watch these patients a little more closely, he said.

Dr. Moorthie, however, remains more reserved about the future of PRS. “I take the middle ground and say, I think there is some value because it’s an additional data point,” Dr. Moorthie said. “And I can see it having value in certain scenarios, but we still don’t have a clear picture of what these are and how best to use and communicate this information.”

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

DNA testing for prostate cancer – of the patients’ inherited DNA and their tumors’ somatic DNA – is increasingly used in the U.S. to determine whether and how to treat low-grade, localized prostate cancers.

Another genetic approach, known as the polygenic risk score (PRS), is emerging as a third genetic approach for sorting out prostate cancer risks.

PRS aims to stratify a person’s disease risk by going beyond rare variants in genes, such as BRCA2, and compiling a weighted score that integrates thousands of common variants whose role in cancer may be unknown but are found more frequently in men with prostate cancer. Traditional germline testing, by contrast, looks for about 30 specific genes directly linked to prostate cancer.

Essentially, “a polygenic risk score estimates your risk by adding together the number of bad cards you were dealt by the impact of each card, such as an ace versus a deuce,” said William Catalona, MD, a urologist at Northwestern University Feinberg School of Medicine, Chicago, known as the father of prostate-specific antigen (PSA) screening.

In combination, these variants can have powerful predictive value.

Having a tool that can mine the depths of a person’s genetic makeup and help doctors devise a nuanced risk assessment for prostate cancer seems like a winning proposition.

Despite its promise, PRS testing is not yet used routinely in practice. The central uncertainty regarding its use lies in whether the risk score can accurately predict who will develop aggressive prostate cancer that needs to be treated and who won’t. The research to date has been mixed, and experts remain polarized.

“PRS absolutely, irrefutably can distinguish between the probability of somebody developing prostate cancer or not. Nobody could look at the data and argue with that,” said Todd Morgan, MD, a genomics researcher from the University of Michigan, Ann Arbor. “What [the data] so far haven’t really been able to do is distinguish whether somebody is likely to have clinically significant prostate cancer versus lower-risk prostate cancer.”
 

The promise of PRS in prostate cancer?

Prostate cancer – the most common type of solid tumor in men and the second most common cancer killer – is a major target for PRS because it is considered one of the most heritable cancers, according to Burcu Darst, PhD, a genetic epidemiologist at Fred Hutchinson Cancer Center, Seattle.

Research in the area has intensified in recent years as genome-wide association studies (GWAS) have become more affordable and the genetic information from these studies has been increasingly aggregated in biobanks.

“Because the sample sizes now are so much bigger than they used to be for GWAS studies, we’re able to develop much better polygenic risk scores than we were before,” said Dr. Darst.

Dr. Darst is lead author on the largest, most diverse prostate GWAS analysis, which led to the development of a PRS that is highly predictive of prostate cancer risk across diverse populations.

In the 2021 meta-analysis, which included 107,247 case patients and 127,006 control patients, Dr. Darst and colleagues identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants.

Compared with men at average genetic risk for prostate cancer – those in the 40%-60% genetic risk score category – men in the top 10% of the risk score (90%-100%) had between a 3.74-fold to fivefold higher risk for prostate cancer. However, the team did not find evidence that the genetic risk score could differentiate a person’s risk for aggressive versus nonaggressive disease.

As Dr. Darst’s team continues to improve the PRS, Dr. Darst says it will get better at predicting aggressive disease. One recent analysis from Dr. Darst and colleagues found that “although the PRS generally did not differentiate aggressive versus nonaggressive prostate cancer,” about 40% of men who will develop aggressive disease have a PRS in the top 20%, whereas only about 7% of men who will develop aggressive tumors have a PRS in the bottom 20%. Another recent study from Dr. Darst and colleagues found that PRS can distinguish between aggressive and nonaggressive disease in men of African ancestry.

These findings highlight “the potential clinical utility of the polygenic risk score,” Dr. Darst said.

Although the growing body of research makes Dr. Catalona, Dr. Darst, and others optimistic about PRS, the landscape is also littered with critics and studies showcasing its limitations.

An analysis, published in JAMA Internal Medicine, found that, compared with a contemporary clinical risk predictor, PRS did not improve prediction of aggressive prostate cancers. Another recent study, which used a 6.6 million–variant PRS to predict the risk of incident prostate cancer among 5,701 healthy men of European descent older than age 69, found that men in the top 20% of the PRS distribution “had an almost three times higher risk of prostate cancer,” compared with men in the lowest quintile; however, a higher PRS was not associated with a higher Gleason grade group, indicative of more aggressive disease.

“While a PRS for prostate cancer is strongly associated with incident risk” in the cohort, “the clinical utility of the PRS as a biomarker is currently limited by its inability to select for clinically significant disease,” the authors concluded.
 

Utility in practice?

Although PRS has been billed as a predictive test, Dr. Catalona believes PRS could have a range of uses both before and after diagnosis.

PRS may, for instance, guide treatment choices for men diagnosed with prostate cancer, Dr. Catalona noted. For men with a PRS that signals a higher risk for aggressive disease, a positive prostate biopsy result could help them decide whether to seek active treatment with surgery or radiation or go on active surveillance.

PRS could also help inform cancer screening. If a PRS test found a patient’s risk for prostate cancer was high, that person could decide to seek PSA screening before age 50 – the recommended age for average-risk men.

However, Aroon Hingorani, MD, a professor of genetic epidemiology at the University College London, expressed concern over using PRS to inform cancer screenings.

Part of the issue, Dr. Hingorani and colleagues explained in a recent article in the BMJ, is that “risk is notoriously difficult to communicate.”

PRS estimates a person’s relative risk for a disease but does not factor in the underlying population risk. Risk prediction should include both, Dr. Hingorani said.

People with high-risk scores may, for instance, discuss earlier screening with their clinician, even if their absolute risk for the disease – which accounts for both relative risk and underlying population disease risk – is still small, Dr. Hingorani and colleagues said. “Conversely, people who do not have ‘high risk’ polygenic scores might be less likely to seek medical attention for concerning symptoms, or their clinicians might be less inclined to investigate.”

Given this, Dr. Hingorani and colleagues believe polygenic scores “will always be limited in their ability to predict disease” and “will always remain one of many risk factors,” such as environmental influences.

Another caveat is that PRS generally is based on data collected from European populations, said Eric Klein, MD, chairman emeritus of urology at the Cleveland Clinic and now a scientist at the biotechnology company Grail, which developed the Galleri blood test that screens for 50 types of cancer. While a valid concern, “that’s easy to fix ultimately,” he said, as the diversity of inputs from various ethnicities increases over time.

Although several companies offer PRS products, moving PRS into the clinic would require an infrastructure for testing which does not yet exist in the U.S., said Dr. Catalona.

Giordano Botta, PhD, CEO of New York–based PRS software start-up Alleica, which bills itself as the Polygenic Risk Score Company, said “test demand is growing rapidly.” His company offers PRS scores that integrate up to 700,000 markers for prostate cancer depending on ancestry and charges patients $250 out of pocket for testing.

Dr. Botta noted that thousands of American patients have undergone PRS testing through his company. Several health systems, including Penn Medicine, Brigham and Women’s Hospital, and the University of Alabama at Birmingham, have been using the test to help “see beyond what traditional risk factors allow,” he said.

However, this and other PRS tests are not yet widely used in the primary care setting.

A major barrier to wider adoption is that experts remain divided on its clinical utility. “People either say it’s ready, and it should be implemented, or they say it’s never going to work,” said Sowmiya Moorthie, PhD, a senior policy analyst with the PHG Foundation, a Cambridge University–associated think tank.

Dr. Klein sits in the optimistic camp. He envisions a day soon when patients will undergo whole-genome testing to collect data on risk scores and incorporate the full genome into the electronic record. At a certain age, primary care physicians would then query the data to determine the patient’s germline risk for a variety of diseases.

“At age 45, if I were a primary care physician seeing a male, I would query the PRS for prostate cancer, and if the risks were low, I would say, ‘You don’t need your first PSA probably until you’re 50,’ ” Dr. Klein said. “If your risk is high, I’d say, ‘Let’s do a baseline PSA now.’ ”

We would then have the data to watch these patients a little more closely, he said.

Dr. Moorthie, however, remains more reserved about the future of PRS. “I take the middle ground and say, I think there is some value because it’s an additional data point,” Dr. Moorthie said. “And I can see it having value in certain scenarios, but we still don’t have a clear picture of what these are and how best to use and communicate this information.”

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

DNA testing for prostate cancer – of the patients’ inherited DNA and their tumors’ somatic DNA – is increasingly used in the U.S. to determine whether and how to treat low-grade, localized prostate cancers.

Another genetic approach, known as the polygenic risk score (PRS), is emerging as a third genetic approach for sorting out prostate cancer risks.

PRS aims to stratify a person’s disease risk by going beyond rare variants in genes, such as BRCA2, and compiling a weighted score that integrates thousands of common variants whose role in cancer may be unknown but are found more frequently in men with prostate cancer. Traditional germline testing, by contrast, looks for about 30 specific genes directly linked to prostate cancer.

Essentially, “a polygenic risk score estimates your risk by adding together the number of bad cards you were dealt by the impact of each card, such as an ace versus a deuce,” said William Catalona, MD, a urologist at Northwestern University Feinberg School of Medicine, Chicago, known as the father of prostate-specific antigen (PSA) screening.

In combination, these variants can have powerful predictive value.

Having a tool that can mine the depths of a person’s genetic makeup and help doctors devise a nuanced risk assessment for prostate cancer seems like a winning proposition.

Despite its promise, PRS testing is not yet used routinely in practice. The central uncertainty regarding its use lies in whether the risk score can accurately predict who will develop aggressive prostate cancer that needs to be treated and who won’t. The research to date has been mixed, and experts remain polarized.

“PRS absolutely, irrefutably can distinguish between the probability of somebody developing prostate cancer or not. Nobody could look at the data and argue with that,” said Todd Morgan, MD, a genomics researcher from the University of Michigan, Ann Arbor. “What [the data] so far haven’t really been able to do is distinguish whether somebody is likely to have clinically significant prostate cancer versus lower-risk prostate cancer.”
 

The promise of PRS in prostate cancer?

Prostate cancer – the most common type of solid tumor in men and the second most common cancer killer – is a major target for PRS because it is considered one of the most heritable cancers, according to Burcu Darst, PhD, a genetic epidemiologist at Fred Hutchinson Cancer Center, Seattle.

Research in the area has intensified in recent years as genome-wide association studies (GWAS) have become more affordable and the genetic information from these studies has been increasingly aggregated in biobanks.

“Because the sample sizes now are so much bigger than they used to be for GWAS studies, we’re able to develop much better polygenic risk scores than we were before,” said Dr. Darst.

Dr. Darst is lead author on the largest, most diverse prostate GWAS analysis, which led to the development of a PRS that is highly predictive of prostate cancer risk across diverse populations.

In the 2021 meta-analysis, which included 107,247 case patients and 127,006 control patients, Dr. Darst and colleagues identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants.

Compared with men at average genetic risk for prostate cancer – those in the 40%-60% genetic risk score category – men in the top 10% of the risk score (90%-100%) had between a 3.74-fold to fivefold higher risk for prostate cancer. However, the team did not find evidence that the genetic risk score could differentiate a person’s risk for aggressive versus nonaggressive disease.

As Dr. Darst’s team continues to improve the PRS, Dr. Darst says it will get better at predicting aggressive disease. One recent analysis from Dr. Darst and colleagues found that “although the PRS generally did not differentiate aggressive versus nonaggressive prostate cancer,” about 40% of men who will develop aggressive disease have a PRS in the top 20%, whereas only about 7% of men who will develop aggressive tumors have a PRS in the bottom 20%. Another recent study from Dr. Darst and colleagues found that PRS can distinguish between aggressive and nonaggressive disease in men of African ancestry.

These findings highlight “the potential clinical utility of the polygenic risk score,” Dr. Darst said.

Although the growing body of research makes Dr. Catalona, Dr. Darst, and others optimistic about PRS, the landscape is also littered with critics and studies showcasing its limitations.

An analysis, published in JAMA Internal Medicine, found that, compared with a contemporary clinical risk predictor, PRS did not improve prediction of aggressive prostate cancers. Another recent study, which used a 6.6 million–variant PRS to predict the risk of incident prostate cancer among 5,701 healthy men of European descent older than age 69, found that men in the top 20% of the PRS distribution “had an almost three times higher risk of prostate cancer,” compared with men in the lowest quintile; however, a higher PRS was not associated with a higher Gleason grade group, indicative of more aggressive disease.

“While a PRS for prostate cancer is strongly associated with incident risk” in the cohort, “the clinical utility of the PRS as a biomarker is currently limited by its inability to select for clinically significant disease,” the authors concluded.
 

Utility in practice?

Although PRS has been billed as a predictive test, Dr. Catalona believes PRS could have a range of uses both before and after diagnosis.

PRS may, for instance, guide treatment choices for men diagnosed with prostate cancer, Dr. Catalona noted. For men with a PRS that signals a higher risk for aggressive disease, a positive prostate biopsy result could help them decide whether to seek active treatment with surgery or radiation or go on active surveillance.

PRS could also help inform cancer screening. If a PRS test found a patient’s risk for prostate cancer was high, that person could decide to seek PSA screening before age 50 – the recommended age for average-risk men.

However, Aroon Hingorani, MD, a professor of genetic epidemiology at the University College London, expressed concern over using PRS to inform cancer screenings.

Part of the issue, Dr. Hingorani and colleagues explained in a recent article in the BMJ, is that “risk is notoriously difficult to communicate.”

PRS estimates a person’s relative risk for a disease but does not factor in the underlying population risk. Risk prediction should include both, Dr. Hingorani said.

People with high-risk scores may, for instance, discuss earlier screening with their clinician, even if their absolute risk for the disease – which accounts for both relative risk and underlying population disease risk – is still small, Dr. Hingorani and colleagues said. “Conversely, people who do not have ‘high risk’ polygenic scores might be less likely to seek medical attention for concerning symptoms, or their clinicians might be less inclined to investigate.”

Given this, Dr. Hingorani and colleagues believe polygenic scores “will always be limited in their ability to predict disease” and “will always remain one of many risk factors,” such as environmental influences.

Another caveat is that PRS generally is based on data collected from European populations, said Eric Klein, MD, chairman emeritus of urology at the Cleveland Clinic and now a scientist at the biotechnology company Grail, which developed the Galleri blood test that screens for 50 types of cancer. While a valid concern, “that’s easy to fix ultimately,” he said, as the diversity of inputs from various ethnicities increases over time.

Although several companies offer PRS products, moving PRS into the clinic would require an infrastructure for testing which does not yet exist in the U.S., said Dr. Catalona.

Giordano Botta, PhD, CEO of New York–based PRS software start-up Alleica, which bills itself as the Polygenic Risk Score Company, said “test demand is growing rapidly.” His company offers PRS scores that integrate up to 700,000 markers for prostate cancer depending on ancestry and charges patients $250 out of pocket for testing.

Dr. Botta noted that thousands of American patients have undergone PRS testing through his company. Several health systems, including Penn Medicine, Brigham and Women’s Hospital, and the University of Alabama at Birmingham, have been using the test to help “see beyond what traditional risk factors allow,” he said.

However, this and other PRS tests are not yet widely used in the primary care setting.

A major barrier to wider adoption is that experts remain divided on its clinical utility. “People either say it’s ready, and it should be implemented, or they say it’s never going to work,” said Sowmiya Moorthie, PhD, a senior policy analyst with the PHG Foundation, a Cambridge University–associated think tank.

Dr. Klein sits in the optimistic camp. He envisions a day soon when patients will undergo whole-genome testing to collect data on risk scores and incorporate the full genome into the electronic record. At a certain age, primary care physicians would then query the data to determine the patient’s germline risk for a variety of diseases.

“At age 45, if I were a primary care physician seeing a male, I would query the PRS for prostate cancer, and if the risks were low, I would say, ‘You don’t need your first PSA probably until you’re 50,’ ” Dr. Klein said. “If your risk is high, I’d say, ‘Let’s do a baseline PSA now.’ ”

We would then have the data to watch these patients a little more closely, he said.

Dr. Moorthie, however, remains more reserved about the future of PRS. “I take the middle ground and say, I think there is some value because it’s an additional data point,” Dr. Moorthie said. “And I can see it having value in certain scenarios, but we still don’t have a clear picture of what these are and how best to use and communicate this information.”

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