CHEST Physician

AstraZeneca was taken to task July 25 by the US Food and Drug Administration’s (FDA’s) Oncology Drug Advisory Committee (ODAC) for failing to heed an agency request about the design of a durvalumab (Imfinzi) trial for non–small cell lung cancer (NSCLC).

The trial in question, AEGEAN, investigated perioperative durvalumab for resectable NSCLC tumors across 802 patients. Patients without EGFR or ALK mutations were randomly assigned to receive durvalumab before surgery alongside platinum-containing chemotherapy and after surgery for a year as monotherapy or to receive chemotherapy and surgery alone. 

Patients receiving durvalumab demonstrated better event-free survival at 1 year (73.4% vs 64.5% without durvalumab) and a better pathologic complete response rate (17.2% vs 4.3% without). Currently, AstraZeneca is seeking to add the indication for durvalumab to those the agent already has. 

However, at the July 25 ODAC meeting, the committee explained that the AEGEAN trial design makes it impossible to tell whether patients benefited from durvalumab before surgery, after it, or at both points. 

Mounting evidence, including from AstraZeneca’s own studies, suggests that the benefit of immune checkpoint inhibitors, such as durvalumab, comes before surgery. That means prescribing durvalumab after surgery could be exposing patients to serious side effects and financial toxicity, with potentially no clinical benefit, “magnifying the risk of potential overtreatment,” the committee cautioned. 

When AEGEAN was being designed in 2018, FDA requested that AstraZeneca address the uncertainty surrounding when to use durvalumab by including separate neoadjuvant and adjuvant arms, or at least an arm where patients were treated with neoadjuvant durvalumab alone to compare with treatment both before and after surgery. 

The company didn’t follow through and, during the July 25 meeting, the committee wanted answers. “Why did you not comply with this?” asked ODAC committee acting chair Daniel Spratt, MD, a radiation oncologist at Case Western Reserve University in Cleveland, Ohio. 

AstraZeneca personnel explained that doing so would have required many more subjects, made the trial more expensive, and added about 2 years to AEGEAN.

One speaker noted that the company, which makes more than $4 billion a year on durvalumab, would have taken about 2 days to recoup that added cost. Others wondered whether the motive was to sell durvalumab for as long as possible across a patient’s course of treatment. 

Perhaps the biggest reason the company ignored the request is that “it wasn’t our understanding at that time that this was a barrier to approval,” an AstraZeneca regulatory affairs specialist said. 

To this end, the agency asked its advisory panel to vote on whether it should require — instead of simply request, as it did with AstraZeneca — companies to prove that patients need immunotherapy both before and after surgery in resectable NSCLC.

The 11-member panel voted unanimously that it should make this a requirement, and several members said it should do so in other cancers as well.

However, when the agency asked whether durvalumab’s resectable NSCLC approval should be delayed until AstraZeneca conducts a trial to answer the neoadjuvant vs adjuvant question, the panel members didn’t think so. 

The consensus was that because AEGEAN showed a decent benefit, patients and physicians should have it as an option, and approval shouldn’t be delayed. The panel said that the bigger question about the benefit of maintenance therapy should be left to future studies. 

FDA usually follows the advice of its advisory panels.
 

A version of this article appeared on Medscape.com.

AstraZeneca was taken to task July 25 by the US Food and Drug Administration’s (FDA’s) Oncology Drug Advisory Committee (ODAC) for failing to heed an agency request about the design of a durvalumab (Imfinzi) trial for non–small cell lung cancer (NSCLC).

The trial in question, AEGEAN, investigated perioperative durvalumab for resectable NSCLC tumors across 802 patients. Patients without EGFR or ALK mutations were randomly assigned to receive durvalumab before surgery alongside platinum-containing chemotherapy and after surgery for a year as monotherapy or to receive chemotherapy and surgery alone. 

Patients receiving durvalumab demonstrated better event-free survival at 1 year (73.4% vs 64.5% without durvalumab) and a better pathologic complete response rate (17.2% vs 4.3% without). Currently, AstraZeneca is seeking to add the indication for durvalumab to those the agent already has. 

However, at the July 25 ODAC meeting, the committee explained that the AEGEAN trial design makes it impossible to tell whether patients benefited from durvalumab before surgery, after it, or at both points. 

Mounting evidence, including from AstraZeneca’s own studies, suggests that the benefit of immune checkpoint inhibitors, such as durvalumab, comes before surgery. That means prescribing durvalumab after surgery could be exposing patients to serious side effects and financial toxicity, with potentially no clinical benefit, “magnifying the risk of potential overtreatment,” the committee cautioned. 

When AEGEAN was being designed in 2018, FDA requested that AstraZeneca address the uncertainty surrounding when to use durvalumab by including separate neoadjuvant and adjuvant arms, or at least an arm where patients were treated with neoadjuvant durvalumab alone to compare with treatment both before and after surgery. 

The company didn’t follow through and, during the July 25 meeting, the committee wanted answers. “Why did you not comply with this?” asked ODAC committee acting chair Daniel Spratt, MD, a radiation oncologist at Case Western Reserve University in Cleveland, Ohio. 

AstraZeneca personnel explained that doing so would have required many more subjects, made the trial more expensive, and added about 2 years to AEGEAN.

One speaker noted that the company, which makes more than $4 billion a year on durvalumab, would have taken about 2 days to recoup that added cost. Others wondered whether the motive was to sell durvalumab for as long as possible across a patient’s course of treatment. 

Perhaps the biggest reason the company ignored the request is that “it wasn’t our understanding at that time that this was a barrier to approval,” an AstraZeneca regulatory affairs specialist said. 

To this end, the agency asked its advisory panel to vote on whether it should require — instead of simply request, as it did with AstraZeneca — companies to prove that patients need immunotherapy both before and after surgery in resectable NSCLC.

The 11-member panel voted unanimously that it should make this a requirement, and several members said it should do so in other cancers as well.

However, when the agency asked whether durvalumab’s resectable NSCLC approval should be delayed until AstraZeneca conducts a trial to answer the neoadjuvant vs adjuvant question, the panel members didn’t think so. 

The consensus was that because AEGEAN showed a decent benefit, patients and physicians should have it as an option, and approval shouldn’t be delayed. The panel said that the bigger question about the benefit of maintenance therapy should be left to future studies. 

FDA usually follows the advice of its advisory panels.
 

A version of this article appeared on Medscape.com.

AstraZeneca was taken to task July 25 by the US Food and Drug Administration’s (FDA’s) Oncology Drug Advisory Committee (ODAC) for failing to heed an agency request about the design of a durvalumab (Imfinzi) trial for non–small cell lung cancer (NSCLC).

The trial in question, AEGEAN, investigated perioperative durvalumab for resectable NSCLC tumors across 802 patients. Patients without EGFR or ALK mutations were randomly assigned to receive durvalumab before surgery alongside platinum-containing chemotherapy and after surgery for a year as monotherapy or to receive chemotherapy and surgery alone. 

Patients receiving durvalumab demonstrated better event-free survival at 1 year (73.4% vs 64.5% without durvalumab) and a better pathologic complete response rate (17.2% vs 4.3% without). Currently, AstraZeneca is seeking to add the indication for durvalumab to those the agent already has. 

However, at the July 25 ODAC meeting, the committee explained that the AEGEAN trial design makes it impossible to tell whether patients benefited from durvalumab before surgery, after it, or at both points. 

Mounting evidence, including from AstraZeneca’s own studies, suggests that the benefit of immune checkpoint inhibitors, such as durvalumab, comes before surgery. That means prescribing durvalumab after surgery could be exposing patients to serious side effects and financial toxicity, with potentially no clinical benefit, “magnifying the risk of potential overtreatment,” the committee cautioned. 

When AEGEAN was being designed in 2018, FDA requested that AstraZeneca address the uncertainty surrounding when to use durvalumab by including separate neoadjuvant and adjuvant arms, or at least an arm where patients were treated with neoadjuvant durvalumab alone to compare with treatment both before and after surgery. 

The company didn’t follow through and, during the July 25 meeting, the committee wanted answers. “Why did you not comply with this?” asked ODAC committee acting chair Daniel Spratt, MD, a radiation oncologist at Case Western Reserve University in Cleveland, Ohio. 

AstraZeneca personnel explained that doing so would have required many more subjects, made the trial more expensive, and added about 2 years to AEGEAN.

One speaker noted that the company, which makes more than $4 billion a year on durvalumab, would have taken about 2 days to recoup that added cost. Others wondered whether the motive was to sell durvalumab for as long as possible across a patient’s course of treatment. 

Perhaps the biggest reason the company ignored the request is that “it wasn’t our understanding at that time that this was a barrier to approval,” an AstraZeneca regulatory affairs specialist said. 

To this end, the agency asked its advisory panel to vote on whether it should require — instead of simply request, as it did with AstraZeneca — companies to prove that patients need immunotherapy both before and after surgery in resectable NSCLC.

The 11-member panel voted unanimously that it should make this a requirement, and several members said it should do so in other cancers as well.

However, when the agency asked whether durvalumab’s resectable NSCLC approval should be delayed until AstraZeneca conducts a trial to answer the neoadjuvant vs adjuvant question, the panel members didn’t think so. 

The consensus was that because AEGEAN showed a decent benefit, patients and physicians should have it as an option, and approval shouldn’t be delayed. The panel said that the bigger question about the benefit of maintenance therapy should be left to future studies. 

FDA usually follows the advice of its advisory panels.
 

A version of this article appeared on Medscape.com.

Eat as fast as you can whenever you can.

That was the med student mindset around food, as Catherine Harmon Toomer, MD, discovered during her school years. “Without a good system in place to counter that,” she explains, “unhealthy eating can get out of control, and that’s what happened to me.”

After med school, things got worse for Dr. Toomer. By her second year in practice as a family medicine physician, she’d gained a lot of weight and had been diagnosed with type 2 diabetes and cardiomyopathy. At 36, she went into congestive heart failure and was told she likely had 5 years to live.

A moment she described as “a huge wake-up call.”

Dr. Toomer is far from alone in her struggles to balance working in medicine and eating healthfully.

“Physicians face unique stresses because of the ubiquity of junk food in the clinical setting, easy use of food as a reward and stress reliever, and lack of time to create better wellness habits while counseling patients to do exactly that,” said John La Puma, MD, FACP, internist and cofounder of ChefMD and founder of Chef Clinic.

There is also the culture of medicine, which Dr. Toomer said looks down on self-care. “Even with break times, patient needs come before our own.” So, you sit down to eat, and there’s an emergency. Your clinic closes for lunch, but the phones still ring, and patients continue to email questions. Charting is also so time-consuming that “everything else gets put on the back burner.”

Sticking to a nutritious diet in this context can feel hopeless. But it isn’t. Really. Here are some doctor-tested, real-life ways you can nourish yourself while getting it all done.
 

Something Is Always Better Than Nothing

Sure, you might not be able to eat a balanced lunch or dinner while at work, conceded Amy Margulies, RD, LDN, owner of The Rebellious RD. But try to focus on the bigger picture and take small steps.

First, make sure you eat something, Ms. Margulies advised. “Skipping meals can lead to overeating later and negatively impact energy levels and concentration.”

Lisa Andrews, MEd, RD, LD, owner of Sound Bites Nutrition, recalled one of her patients, a gastrointestinal surgeon with reactive hypoglycemia and fatigue. “She was experiencing energy crashes mid-afternoon,” she said. It was only after starting to eat every 4-5 hours that her patient felt better.

Of course, this is easier said than done. “When you are running from one patient to the other and trying to keep on time with your schedule, there is very little time for eating and no time at all for cooking or even heating up food,” recalled Hélène Bertrand, MD, author of Low Back Pain: 3 Steps to Relief in 2 Minutes.

But during her 55 years as a family medicine physician, Dr. Bertrand found ways to improve (if not perfect) the situation. She lunched on nuts or seeds during the day or grabbed a 95% cacao chocolate bar — higher in antioxidants and lower in sugar than a candy bar.

If you don’t have time for breakfast, try drinking a complete protein shake while driving to work, Dr. Toomer recommended. “It’s not ideal, but it’s better than nothing.” Similarly, if the only way you’ll eat a high-protein, lower-carb snack like hummus is with potato chips, go for it, she said.

Basically, don’t be type A striving for perfection. Take good enough when you can and balance the rest when you have time.
 

Torpedo Temptation

From free treats in the break room to always-present pizza for residents, high-fat, high-sugar, low-nutrient fare is a constant temptation. “I worked with a physician who would bring a balanced lunch to work every day, then find whatever sweet was around for his afternoon treat,” recalled Ms. Margulies.“The cookies, cakes, and donuts were starting to add up — and stopping at one wasn’t working for him.”

What did work was Ms. Margulies’ suggestion to bring a single serving of dark chocolate and fruit to savor during a longer break. “Bringing your favorite treats in appropriate portions can help you stick with your plan throughout the day,” she explained, and you’ll have an easier time resisting what’s in the break room. “When you desire a treat, tell yourself you have what you need and don’t need to indulge in the ‘free food’ just because it’s there. You have power over your choices.”

How about tricking yourself into perceiving cherry tomatoes as treats? That might be unusual, but one of Dr. La Puma’s physician patients did just that, displaying the produce in a candy dish on his office counter. Not only did this strategy help remind him to snack healthfully, it also prompted his patients to ask about eating better, he said.
 

Preparation Is Still Underrated

Many people find meal prepping intimidating. But it doesn’t need to be complicated. For instance, try purchasing precut veggies, cooked chicken breasts, or other healthy convenience options. You can then combine them in packable containers to prep a few meals at a time. For less busy weeks, consider cooking the protein yourself and whipping up basic sauces (like pesto and vinaigrette) to jazz up your meals.

“I worked with a resident who was gaining weight each month,” recalled Ms. Margulies. “She would skip lunch, grab a random snack, then wait until she got home to eat anything she could find.”

Encouraged by Ms. Margulies, she prepared and portioned one or two balanced dinners each week, which she’d later reheat. She also bought fresh and dried fruit and high-protein snacks, keeping single servings in her car to eat on the way home.

Similarly, Jess DeGore, RD, LDN, CDCES, CHWC, a diabetes educator and owner of Dietitian Jess Nutrition, recalled an ob.gyn. client who constantly skipped meals and relied on vending machine snacks. To combat her resulting energy crashes, she followed Ms. DeGore’s advice to prep workday lunches (like quinoa salads) over the weekend and bring fruit and nut snacks to work.
 

Automate as Much as You Can

If healthy is already on hand, you’ll eat healthy, said Ms. Andrews. Build up a snack stash focusing on fiber and protein. Tote a lunch bag with a cooler pack if needed. Some suggestions:

• Oatmeal packets
• Individual Greek yogurt cups or drinkable yogurts
• Protein bars
• Protein shakes
• Fresh fruit
• Fresh veggie sticks
• Nuts, dried chickpeas, or edamame
• Trail mix
• Single servings of hummus, nut butter, or guacamole
• Dried seaweed snacks
• Whole grain crackers
• Hard-boiled eggs
• String cheese
• Peanut butter sandwich
• 95% cacao chocolate bar

Try a Meal Delivery Service

Meal delivery services can be pricey, but potentially worth the expense. By bringing meals or having them sent to your office, you won’t have to find time to go to the cafeteria and stand in line, noted Janese S. Laster, MD, an internal medicine, gastroenterology, obesity medicine, and nutrition physician and founder of Gut Theory Total Digestive Care. Instead, “you’ll have something to warm up and eat while writing notes or in between patients,” she said. Plus, “you won’t have an excuse to skip meals.”

Hydration Yes, Junk Drinks No

The following can be filed in the Doctors-Know-It-But-Don’t-Always-Do-It section: “Hunger can be mistaken for thirst,” said Ms. Margulies. “Staying hydrated will help you better assess whether you’re hungry or thirsty.” Choose water over soda or energy drinks, she added, to hydrate your body without unnecessary extra sugars, sugar substitutes, calories, caffeine, or sodium — all of which can affect how you feel.

Advocate for Your Health

Convincing your institution to make changes might be difficult or even impossible, but consider asking your workplace to implement initiatives like these to boost provider nutrition, suggested Jabe Brown, BHSc (Nat), founder of Melbourne Functional Medicine:

• Establish protected break times when doctors can step away from their duties to eat
• Add more nutritious cafeteria options, like salads, whole grains, and lean proteins
• Overhaul vending machine offerings
• Offer educational workshops on nutrition

Be Tenacious About Good Eating

For Dr. Toomer, that meant taking several years off from work to improve her health. After losing more than 100 pounds, she founded TOTAL Weight Care Institute to help other healthcare professionals follow in her footsteps.

For you, the path toward a healthier diet might be gradual — grabbing a more nutritious snack, spending an extra hour per week on food shopping or prep, remembering a water bottle. Whatever it looks like, make realistic lifestyle tweaks that work for you.

Maybe even try that apple-a-day thing.
 

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

Eat as fast as you can whenever you can.

That was the med student mindset around food, as Catherine Harmon Toomer, MD, discovered during her school years. “Without a good system in place to counter that,” she explains, “unhealthy eating can get out of control, and that’s what happened to me.”

After med school, things got worse for Dr. Toomer. By her second year in practice as a family medicine physician, she’d gained a lot of weight and had been diagnosed with type 2 diabetes and cardiomyopathy. At 36, she went into congestive heart failure and was told she likely had 5 years to live.

A moment she described as “a huge wake-up call.”

Dr. Toomer is far from alone in her struggles to balance working in medicine and eating healthfully.

“Physicians face unique stresses because of the ubiquity of junk food in the clinical setting, easy use of food as a reward and stress reliever, and lack of time to create better wellness habits while counseling patients to do exactly that,” said John La Puma, MD, FACP, internist and cofounder of ChefMD and founder of Chef Clinic.

There is also the culture of medicine, which Dr. Toomer said looks down on self-care. “Even with break times, patient needs come before our own.” So, you sit down to eat, and there’s an emergency. Your clinic closes for lunch, but the phones still ring, and patients continue to email questions. Charting is also so time-consuming that “everything else gets put on the back burner.”

Sticking to a nutritious diet in this context can feel hopeless. But it isn’t. Really. Here are some doctor-tested, real-life ways you can nourish yourself while getting it all done.
 

Something Is Always Better Than Nothing

Sure, you might not be able to eat a balanced lunch or dinner while at work, conceded Amy Margulies, RD, LDN, owner of The Rebellious RD. But try to focus on the bigger picture and take small steps.

First, make sure you eat something, Ms. Margulies advised. “Skipping meals can lead to overeating later and negatively impact energy levels and concentration.”

Lisa Andrews, MEd, RD, LD, owner of Sound Bites Nutrition, recalled one of her patients, a gastrointestinal surgeon with reactive hypoglycemia and fatigue. “She was experiencing energy crashes mid-afternoon,” she said. It was only after starting to eat every 4-5 hours that her patient felt better.

Of course, this is easier said than done. “When you are running from one patient to the other and trying to keep on time with your schedule, there is very little time for eating and no time at all for cooking or even heating up food,” recalled Hélène Bertrand, MD, author of Low Back Pain: 3 Steps to Relief in 2 Minutes.

But during her 55 years as a family medicine physician, Dr. Bertrand found ways to improve (if not perfect) the situation. She lunched on nuts or seeds during the day or grabbed a 95% cacao chocolate bar — higher in antioxidants and lower in sugar than a candy bar.

If you don’t have time for breakfast, try drinking a complete protein shake while driving to work, Dr. Toomer recommended. “It’s not ideal, but it’s better than nothing.” Similarly, if the only way you’ll eat a high-protein, lower-carb snack like hummus is with potato chips, go for it, she said.

Basically, don’t be type A striving for perfection. Take good enough when you can and balance the rest when you have time.
 

Torpedo Temptation

From free treats in the break room to always-present pizza for residents, high-fat, high-sugar, low-nutrient fare is a constant temptation. “I worked with a physician who would bring a balanced lunch to work every day, then find whatever sweet was around for his afternoon treat,” recalled Ms. Margulies.“The cookies, cakes, and donuts were starting to add up — and stopping at one wasn’t working for him.”

What did work was Ms. Margulies’ suggestion to bring a single serving of dark chocolate and fruit to savor during a longer break. “Bringing your favorite treats in appropriate portions can help you stick with your plan throughout the day,” she explained, and you’ll have an easier time resisting what’s in the break room. “When you desire a treat, tell yourself you have what you need and don’t need to indulge in the ‘free food’ just because it’s there. You have power over your choices.”

How about tricking yourself into perceiving cherry tomatoes as treats? That might be unusual, but one of Dr. La Puma’s physician patients did just that, displaying the produce in a candy dish on his office counter. Not only did this strategy help remind him to snack healthfully, it also prompted his patients to ask about eating better, he said.
 

Preparation Is Still Underrated

Many people find meal prepping intimidating. But it doesn’t need to be complicated. For instance, try purchasing precut veggies, cooked chicken breasts, or other healthy convenience options. You can then combine them in packable containers to prep a few meals at a time. For less busy weeks, consider cooking the protein yourself and whipping up basic sauces (like pesto and vinaigrette) to jazz up your meals.

“I worked with a resident who was gaining weight each month,” recalled Ms. Margulies. “She would skip lunch, grab a random snack, then wait until she got home to eat anything she could find.”

Encouraged by Ms. Margulies, she prepared and portioned one or two balanced dinners each week, which she’d later reheat. She also bought fresh and dried fruit and high-protein snacks, keeping single servings in her car to eat on the way home.

Similarly, Jess DeGore, RD, LDN, CDCES, CHWC, a diabetes educator and owner of Dietitian Jess Nutrition, recalled an ob.gyn. client who constantly skipped meals and relied on vending machine snacks. To combat her resulting energy crashes, she followed Ms. DeGore’s advice to prep workday lunches (like quinoa salads) over the weekend and bring fruit and nut snacks to work.
 

Automate as Much as You Can

If healthy is already on hand, you’ll eat healthy, said Ms. Andrews. Build up a snack stash focusing on fiber and protein. Tote a lunch bag with a cooler pack if needed. Some suggestions:

• Oatmeal packets
• Individual Greek yogurt cups or drinkable yogurts
• Protein bars
• Protein shakes
• Fresh fruit
• Fresh veggie sticks
• Nuts, dried chickpeas, or edamame
• Trail mix
• Single servings of hummus, nut butter, or guacamole
• Dried seaweed snacks
• Whole grain crackers
• Hard-boiled eggs
• String cheese
• Peanut butter sandwich
• 95% cacao chocolate bar

Try a Meal Delivery Service

Meal delivery services can be pricey, but potentially worth the expense. By bringing meals or having them sent to your office, you won’t have to find time to go to the cafeteria and stand in line, noted Janese S. Laster, MD, an internal medicine, gastroenterology, obesity medicine, and nutrition physician and founder of Gut Theory Total Digestive Care. Instead, “you’ll have something to warm up and eat while writing notes or in between patients,” she said. Plus, “you won’t have an excuse to skip meals.”

Hydration Yes, Junk Drinks No

The following can be filed in the Doctors-Know-It-But-Don’t-Always-Do-It section: “Hunger can be mistaken for thirst,” said Ms. Margulies. “Staying hydrated will help you better assess whether you’re hungry or thirsty.” Choose water over soda or energy drinks, she added, to hydrate your body without unnecessary extra sugars, sugar substitutes, calories, caffeine, or sodium — all of which can affect how you feel.

Advocate for Your Health

Convincing your institution to make changes might be difficult or even impossible, but consider asking your workplace to implement initiatives like these to boost provider nutrition, suggested Jabe Brown, BHSc (Nat), founder of Melbourne Functional Medicine:

• Establish protected break times when doctors can step away from their duties to eat
• Add more nutritious cafeteria options, like salads, whole grains, and lean proteins
• Overhaul vending machine offerings
• Offer educational workshops on nutrition

Be Tenacious About Good Eating

For Dr. Toomer, that meant taking several years off from work to improve her health. After losing more than 100 pounds, she founded TOTAL Weight Care Institute to help other healthcare professionals follow in her footsteps.

For you, the path toward a healthier diet might be gradual — grabbing a more nutritious snack, spending an extra hour per week on food shopping or prep, remembering a water bottle. Whatever it looks like, make realistic lifestyle tweaks that work for you.

Maybe even try that apple-a-day thing.
 

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

Eat as fast as you can whenever you can.

That was the med student mindset around food, as Catherine Harmon Toomer, MD, discovered during her school years. “Without a good system in place to counter that,” she explains, “unhealthy eating can get out of control, and that’s what happened to me.”

After med school, things got worse for Dr. Toomer. By her second year in practice as a family medicine physician, she’d gained a lot of weight and had been diagnosed with type 2 diabetes and cardiomyopathy. At 36, she went into congestive heart failure and was told she likely had 5 years to live.

A moment she described as “a huge wake-up call.”

Dr. Toomer is far from alone in her struggles to balance working in medicine and eating healthfully.

“Physicians face unique stresses because of the ubiquity of junk food in the clinical setting, easy use of food as a reward and stress reliever, and lack of time to create better wellness habits while counseling patients to do exactly that,” said John La Puma, MD, FACP, internist and cofounder of ChefMD and founder of Chef Clinic.

There is also the culture of medicine, which Dr. Toomer said looks down on self-care. “Even with break times, patient needs come before our own.” So, you sit down to eat, and there’s an emergency. Your clinic closes for lunch, but the phones still ring, and patients continue to email questions. Charting is also so time-consuming that “everything else gets put on the back burner.”

Sticking to a nutritious diet in this context can feel hopeless. But it isn’t. Really. Here are some doctor-tested, real-life ways you can nourish yourself while getting it all done.
 

Something Is Always Better Than Nothing

Sure, you might not be able to eat a balanced lunch or dinner while at work, conceded Amy Margulies, RD, LDN, owner of The Rebellious RD. But try to focus on the bigger picture and take small steps.

First, make sure you eat something, Ms. Margulies advised. “Skipping meals can lead to overeating later and negatively impact energy levels and concentration.”

Lisa Andrews, MEd, RD, LD, owner of Sound Bites Nutrition, recalled one of her patients, a gastrointestinal surgeon with reactive hypoglycemia and fatigue. “She was experiencing energy crashes mid-afternoon,” she said. It was only after starting to eat every 4-5 hours that her patient felt better.

Of course, this is easier said than done. “When you are running from one patient to the other and trying to keep on time with your schedule, there is very little time for eating and no time at all for cooking or even heating up food,” recalled Hélène Bertrand, MD, author of Low Back Pain: 3 Steps to Relief in 2 Minutes.

But during her 55 years as a family medicine physician, Dr. Bertrand found ways to improve (if not perfect) the situation. She lunched on nuts or seeds during the day or grabbed a 95% cacao chocolate bar — higher in antioxidants and lower in sugar than a candy bar.

If you don’t have time for breakfast, try drinking a complete protein shake while driving to work, Dr. Toomer recommended. “It’s not ideal, but it’s better than nothing.” Similarly, if the only way you’ll eat a high-protein, lower-carb snack like hummus is with potato chips, go for it, she said.

Basically, don’t be type A striving for perfection. Take good enough when you can and balance the rest when you have time.
 

Torpedo Temptation

From free treats in the break room to always-present pizza for residents, high-fat, high-sugar, low-nutrient fare is a constant temptation. “I worked with a physician who would bring a balanced lunch to work every day, then find whatever sweet was around for his afternoon treat,” recalled Ms. Margulies.“The cookies, cakes, and donuts were starting to add up — and stopping at one wasn’t working for him.”

What did work was Ms. Margulies’ suggestion to bring a single serving of dark chocolate and fruit to savor during a longer break. “Bringing your favorite treats in appropriate portions can help you stick with your plan throughout the day,” she explained, and you’ll have an easier time resisting what’s in the break room. “When you desire a treat, tell yourself you have what you need and don’t need to indulge in the ‘free food’ just because it’s there. You have power over your choices.”

How about tricking yourself into perceiving cherry tomatoes as treats? That might be unusual, but one of Dr. La Puma’s physician patients did just that, displaying the produce in a candy dish on his office counter. Not only did this strategy help remind him to snack healthfully, it also prompted his patients to ask about eating better, he said.
 

Preparation Is Still Underrated

Many people find meal prepping intimidating. But it doesn’t need to be complicated. For instance, try purchasing precut veggies, cooked chicken breasts, or other healthy convenience options. You can then combine them in packable containers to prep a few meals at a time. For less busy weeks, consider cooking the protein yourself and whipping up basic sauces (like pesto and vinaigrette) to jazz up your meals.

“I worked with a resident who was gaining weight each month,” recalled Ms. Margulies. “She would skip lunch, grab a random snack, then wait until she got home to eat anything she could find.”

Encouraged by Ms. Margulies, she prepared and portioned one or two balanced dinners each week, which she’d later reheat. She also bought fresh and dried fruit and high-protein snacks, keeping single servings in her car to eat on the way home.

Similarly, Jess DeGore, RD, LDN, CDCES, CHWC, a diabetes educator and owner of Dietitian Jess Nutrition, recalled an ob.gyn. client who constantly skipped meals and relied on vending machine snacks. To combat her resulting energy crashes, she followed Ms. DeGore’s advice to prep workday lunches (like quinoa salads) over the weekend and bring fruit and nut snacks to work.
 

Automate as Much as You Can

If healthy is already on hand, you’ll eat healthy, said Ms. Andrews. Build up a snack stash focusing on fiber and protein. Tote a lunch bag with a cooler pack if needed. Some suggestions:

• Oatmeal packets
• Individual Greek yogurt cups or drinkable yogurts
• Protein bars
• Protein shakes
• Fresh fruit
• Fresh veggie sticks
• Nuts, dried chickpeas, or edamame
• Trail mix
• Single servings of hummus, nut butter, or guacamole
• Dried seaweed snacks
• Whole grain crackers
• Hard-boiled eggs
• String cheese
• Peanut butter sandwich
• 95% cacao chocolate bar

Try a Meal Delivery Service

Meal delivery services can be pricey, but potentially worth the expense. By bringing meals or having them sent to your office, you won’t have to find time to go to the cafeteria and stand in line, noted Janese S. Laster, MD, an internal medicine, gastroenterology, obesity medicine, and nutrition physician and founder of Gut Theory Total Digestive Care. Instead, “you’ll have something to warm up and eat while writing notes or in between patients,” she said. Plus, “you won’t have an excuse to skip meals.”

Hydration Yes, Junk Drinks No

The following can be filed in the Doctors-Know-It-But-Don’t-Always-Do-It section: “Hunger can be mistaken for thirst,” said Ms. Margulies. “Staying hydrated will help you better assess whether you’re hungry or thirsty.” Choose water over soda or energy drinks, she added, to hydrate your body without unnecessary extra sugars, sugar substitutes, calories, caffeine, or sodium — all of which can affect how you feel.

Advocate for Your Health

Convincing your institution to make changes might be difficult or even impossible, but consider asking your workplace to implement initiatives like these to boost provider nutrition, suggested Jabe Brown, BHSc (Nat), founder of Melbourne Functional Medicine:

• Establish protected break times when doctors can step away from their duties to eat
• Add more nutritious cafeteria options, like salads, whole grains, and lean proteins
• Overhaul vending machine offerings
• Offer educational workshops on nutrition

Be Tenacious About Good Eating

For Dr. Toomer, that meant taking several years off from work to improve her health. After losing more than 100 pounds, she founded TOTAL Weight Care Institute to help other healthcare professionals follow in her footsteps.

For you, the path toward a healthier diet might be gradual — grabbing a more nutritious snack, spending an extra hour per week on food shopping or prep, remembering a water bottle. Whatever it looks like, make realistic lifestyle tweaks that work for you.

Maybe even try that apple-a-day thing.
 

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

Paxlovid, an antiviral approved in 2023 to treat acute infections of COVID-19, is showing great potential as a new treatment for long COVID and may be the most promising experimental therapy now being studied for treating the condition.

New research offers strong evidence that Paxlovid provides significant benefits for COVID-19 patients who are at high risk for severe or prolonged disease, particularly older adults and those who are immunocompromised, said Lisa Sanders, MD, medical director of Yale’s Long COVID Multidisciplinary Care Center, New Haven, Connecticut. 

“We all know that long COVID is a disease smorgasbord of illnesses that have been somehow triggered by COVID. So, the question is, are there some types of these disorders that can respond to Paxlovid?” Dr. Sanders said. 

Some patients have also benefited from supplements such as N-acetyl cysteine (NAC), as well as vitamins B, C, D and alpha lipoic acid, in which the risks are low and there are potential benefits, Dr. Sanders said.

As researchers continue to study new treatments for long COVID, for which there are no standard approved therapies, Dr. Sanders suggested doctors might turn to Paxlovid and other promising therapeutics that have shown benefits in preliminary study findings.

A study published in 2023 by JAMA Internal Medicine reviewed the charts of nearly 300,000 veterans with severe acute COVID infections. The study found that Paxlovid treatment reduced the likelihood of developing long COVID. But a more recent study at Stanford University, Palo Alto, California — the STOP-PASC trial— did not find Paxlovid improved symptoms when given to 155 patients who had already recovered from acute infection. Participants with long COVID symptoms — and who had on average recovered from acute infection around 16 months earlier — were given a 15-day course of Paxlovid. Common symptoms like fog, fatigue, and cardiovascular or gastrointestinal symptoms did not improve.

However, long COVID likely has multiple drivers. Viral persistence may still be at play for a subset of patients. This means that, despite the fact that patients recover from acute infection, hidden reservoirs of SARS-CoV-2 are still present in the body, possibly bringing on long COVID symptoms. Which means Paxlovid may help some long COVID patients but not others, Dr. Sanders explained. That’s why research needs to continue to identify the best cases for Paxlovid’s use and to identify other treatments for those who do not benefit from Paxlovid.

The PAX LC trial at Yale suggests there may not be a one-size-fits-all treatment for the condition, but a range of factors that may determine the best therapy for individual patients. Led by Yale School of Medicine’s Harlan Krumholz, MD, and Akiko Iwasaki, PhD, the study tested the effects of Paxlovid overall and was designed to determine who is most likely to benefit from antiviral treatment and gain further understanding of the immune response in long COVID. Results should be reported soon. 

“This acknowledges one line of thinking that long COVID is caused by viral persistence,” Dr. Sanders said. “Do these people have hidden reservoirs of the virus? The question is, are there people who seem to respond [to Paxlovid]? And if so, what characterizes these people?”
 

Low-Risk, High-Reward Supplements

Some of Dr. Sanders’ colleagues at Yale are focusing on long COVID’s neurological symptoms and neuropathogenesis. There’s evidence showing these symptoms — notably brain fog — can be treated with supplements. 

In 2022, a Yale study by Arman Fesharaki-Zadeh, MD, PhD, found promise in treating brain fog through a combination supplement of NAC and guanfacine — the latter developed by Yale neuroscientist, Amy Arnsten, PhD. 

The two published their study in Neuroimmunology Reports in November 2023. NAC is available over the counter and patients can get a prescription for guanfacine off label from their physician. Guanfacine is approved to treat high blood pressure by decreasing heart rate and relaxing blood vessels. But it’s also been shown to treat attention-deficit/hyperactivity disorder (ADHD) and other cognitive issues. 

Though NAC can treat respiratory problems, it’s also commonly used to treat postconcussion symptoms. Dr. Fesharaki-Zadeh found that it helps treat brain fog, increases energy, and improves memory. When paired with guanfacine, substantial benefits were reported, such as better multitasking abilities and markedly improved organizational skills. 

Dr. Sanders is now using NAC and guanfacine for patients in her clinic. 
 

‘Mitochondrial Enhancement’ Through Vitamins

Dr. Sanders has also used a combination of alpha lipoic acid and vitamin C, and a combo of B vitamins that make up what’s called a “mitochondrial enhancement regimen.”

To treat a very common symptom like fatigue, Dr. Sanders prefers supplement combinations over other drugs like Modafinil or Adderall. 

Modafinil is a central nervous system stimulant used to reduce extreme sleepiness caused by narcolepsy or other sleep disorders. Adderall is an amphetamine also used to treat narcolepsy as well as ADHD. Both work on your sleep and alertness, but long COVID affects the whole body, causing a physical fatigue similar to postexertional malaise (PEM) that isn’t remedied by those kinds of drugs, as studies suggest what’s involved in PEM is mitochondria, Dr. Sanders said. 

PEM is a worsening of symptoms that occurs after minimal physical or mental exertion. These are activities that should be well tolerated, but PEM causes extreme fatigue and flu-like symptoms. It’s become a hallmark symptom of long COVID after having already been a key diagnostic factor in myalgic encephalomyelitis/chronic fatigue syndrome.

As Dr. Sanders noted in her long COVID blog, which tracks the latest research and treatment options for doctors who treat long COVID patients, previous studies have shown low vitamin D levels may not only increase the risk for severe COVID-19 but delay recovery from long COVID. Those without long COVID had higher levels of vitamin D, compared with long COVID patients. Vitamin D is known to boost the immune system.

Dr. Sanders found that those with vitamin D deficiencies are most likely to benefit from this approach. For people who don’t have sufficient sun exposure, which prompts the production of vitamin D, she says supplementation with 1000 IUs of vitamin D3 daily is enough for most adults.

Research is also currently being underway on the use of the diabetes drug metformin in people with acute COVID infections to determine if it may reduce the likelihood of developing long COVID. In a recent long COVID clinical trial, early outpatient COVID-19 treatment with metformin decreased the subsequent risk for long COVID by 41.3% during 10-month follow-up. 
 

Other New Treatments Under Study

Dr. Sanders believes the foundation for many of long COVID’s symptoms could be neurological. 

“I think that long COVID is probably a neurologic disorder,” Dr. Sanders said. 

Lindsey McAlpine, MD, director of the Yale Medicine NeuroCovid Clinic, is focusing on neuropsychiatric long COVID and the causes of neurologic post-acute sequelae of SARS-CoV-2 infection (neuro-PASC). Symptoms of neuro-PASC include cognitive impairment, headaches, and dizziness.

“Lindsey is trying to see which parts of the brain are involved and see if there are phenotypes of brain abnormalities that match up with clinical abnormalities,” Dr. Sanders said.

The National Institute of Neurological Disorders and Stroke recently awarded her a 5-year K23 grant to support her ongoing study, “Magnetic Resonance Imaging Biomarkers of Post-COVID-19 Cerebral Microvascular Dysfunction.”

Utilizing advanced MRI techniques to identify microvascular dysfunction biomarkers in the brain, Dr. McAlpine hopes to unearth and better understand the pathophysiology behind neurological issues post COVID.

Many of Dr. McAlpine’s patients with cognitive symptoms have responded well to NAC and guanfacine. 

Still, the hope is that her brain-imaging studies will bear fruit that leads to a better understanding of long COVID and new treatment methods.

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

Paxlovid, an antiviral approved in 2023 to treat acute infections of COVID-19, is showing great potential as a new treatment for long COVID and may be the most promising experimental therapy now being studied for treating the condition.

New research offers strong evidence that Paxlovid provides significant benefits for COVID-19 patients who are at high risk for severe or prolonged disease, particularly older adults and those who are immunocompromised, said Lisa Sanders, MD, medical director of Yale’s Long COVID Multidisciplinary Care Center, New Haven, Connecticut. 

“We all know that long COVID is a disease smorgasbord of illnesses that have been somehow triggered by COVID. So, the question is, are there some types of these disorders that can respond to Paxlovid?” Dr. Sanders said. 

Some patients have also benefited from supplements such as N-acetyl cysteine (NAC), as well as vitamins B, C, D and alpha lipoic acid, in which the risks are low and there are potential benefits, Dr. Sanders said.

As researchers continue to study new treatments for long COVID, for which there are no standard approved therapies, Dr. Sanders suggested doctors might turn to Paxlovid and other promising therapeutics that have shown benefits in preliminary study findings.

A study published in 2023 by JAMA Internal Medicine reviewed the charts of nearly 300,000 veterans with severe acute COVID infections. The study found that Paxlovid treatment reduced the likelihood of developing long COVID. But a more recent study at Stanford University, Palo Alto, California — the STOP-PASC trial— did not find Paxlovid improved symptoms when given to 155 patients who had already recovered from acute infection. Participants with long COVID symptoms — and who had on average recovered from acute infection around 16 months earlier — were given a 15-day course of Paxlovid. Common symptoms like fog, fatigue, and cardiovascular or gastrointestinal symptoms did not improve.

However, long COVID likely has multiple drivers. Viral persistence may still be at play for a subset of patients. This means that, despite the fact that patients recover from acute infection, hidden reservoirs of SARS-CoV-2 are still present in the body, possibly bringing on long COVID symptoms. Which means Paxlovid may help some long COVID patients but not others, Dr. Sanders explained. That’s why research needs to continue to identify the best cases for Paxlovid’s use and to identify other treatments for those who do not benefit from Paxlovid.

The PAX LC trial at Yale suggests there may not be a one-size-fits-all treatment for the condition, but a range of factors that may determine the best therapy for individual patients. Led by Yale School of Medicine’s Harlan Krumholz, MD, and Akiko Iwasaki, PhD, the study tested the effects of Paxlovid overall and was designed to determine who is most likely to benefit from antiviral treatment and gain further understanding of the immune response in long COVID. Results should be reported soon. 

“This acknowledges one line of thinking that long COVID is caused by viral persistence,” Dr. Sanders said. “Do these people have hidden reservoirs of the virus? The question is, are there people who seem to respond [to Paxlovid]? And if so, what characterizes these people?”
 

Low-Risk, High-Reward Supplements

Some of Dr. Sanders’ colleagues at Yale are focusing on long COVID’s neurological symptoms and neuropathogenesis. There’s evidence showing these symptoms — notably brain fog — can be treated with supplements. 

In 2022, a Yale study by Arman Fesharaki-Zadeh, MD, PhD, found promise in treating brain fog through a combination supplement of NAC and guanfacine — the latter developed by Yale neuroscientist, Amy Arnsten, PhD. 

The two published their study in Neuroimmunology Reports in November 2023. NAC is available over the counter and patients can get a prescription for guanfacine off label from their physician. Guanfacine is approved to treat high blood pressure by decreasing heart rate and relaxing blood vessels. But it’s also been shown to treat attention-deficit/hyperactivity disorder (ADHD) and other cognitive issues. 

Though NAC can treat respiratory problems, it’s also commonly used to treat postconcussion symptoms. Dr. Fesharaki-Zadeh found that it helps treat brain fog, increases energy, and improves memory. When paired with guanfacine, substantial benefits were reported, such as better multitasking abilities and markedly improved organizational skills. 

Dr. Sanders is now using NAC and guanfacine for patients in her clinic. 
 

‘Mitochondrial Enhancement’ Through Vitamins

Dr. Sanders has also used a combination of alpha lipoic acid and vitamin C, and a combo of B vitamins that make up what’s called a “mitochondrial enhancement regimen.”

To treat a very common symptom like fatigue, Dr. Sanders prefers supplement combinations over other drugs like Modafinil or Adderall. 

Modafinil is a central nervous system stimulant used to reduce extreme sleepiness caused by narcolepsy or other sleep disorders. Adderall is an amphetamine also used to treat narcolepsy as well as ADHD. Both work on your sleep and alertness, but long COVID affects the whole body, causing a physical fatigue similar to postexertional malaise (PEM) that isn’t remedied by those kinds of drugs, as studies suggest what’s involved in PEM is mitochondria, Dr. Sanders said. 

PEM is a worsening of symptoms that occurs after minimal physical or mental exertion. These are activities that should be well tolerated, but PEM causes extreme fatigue and flu-like symptoms. It’s become a hallmark symptom of long COVID after having already been a key diagnostic factor in myalgic encephalomyelitis/chronic fatigue syndrome.

As Dr. Sanders noted in her long COVID blog, which tracks the latest research and treatment options for doctors who treat long COVID patients, previous studies have shown low vitamin D levels may not only increase the risk for severe COVID-19 but delay recovery from long COVID. Those without long COVID had higher levels of vitamin D, compared with long COVID patients. Vitamin D is known to boost the immune system.

Dr. Sanders found that those with vitamin D deficiencies are most likely to benefit from this approach. For people who don’t have sufficient sun exposure, which prompts the production of vitamin D, she says supplementation with 1000 IUs of vitamin D3 daily is enough for most adults.

Research is also currently being underway on the use of the diabetes drug metformin in people with acute COVID infections to determine if it may reduce the likelihood of developing long COVID. In a recent long COVID clinical trial, early outpatient COVID-19 treatment with metformin decreased the subsequent risk for long COVID by 41.3% during 10-month follow-up. 
 

Other New Treatments Under Study

Dr. Sanders believes the foundation for many of long COVID’s symptoms could be neurological. 

“I think that long COVID is probably a neurologic disorder,” Dr. Sanders said. 

Lindsey McAlpine, MD, director of the Yale Medicine NeuroCovid Clinic, is focusing on neuropsychiatric long COVID and the causes of neurologic post-acute sequelae of SARS-CoV-2 infection (neuro-PASC). Symptoms of neuro-PASC include cognitive impairment, headaches, and dizziness.

“Lindsey is trying to see which parts of the brain are involved and see if there are phenotypes of brain abnormalities that match up with clinical abnormalities,” Dr. Sanders said.

The National Institute of Neurological Disorders and Stroke recently awarded her a 5-year K23 grant to support her ongoing study, “Magnetic Resonance Imaging Biomarkers of Post-COVID-19 Cerebral Microvascular Dysfunction.”

Utilizing advanced MRI techniques to identify microvascular dysfunction biomarkers in the brain, Dr. McAlpine hopes to unearth and better understand the pathophysiology behind neurological issues post COVID.

Many of Dr. McAlpine’s patients with cognitive symptoms have responded well to NAC and guanfacine. 

Still, the hope is that her brain-imaging studies will bear fruit that leads to a better understanding of long COVID and new treatment methods.

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

Paxlovid, an antiviral approved in 2023 to treat acute infections of COVID-19, is showing great potential as a new treatment for long COVID and may be the most promising experimental therapy now being studied for treating the condition.

New research offers strong evidence that Paxlovid provides significant benefits for COVID-19 patients who are at high risk for severe or prolonged disease, particularly older adults and those who are immunocompromised, said Lisa Sanders, MD, medical director of Yale’s Long COVID Multidisciplinary Care Center, New Haven, Connecticut. 

“We all know that long COVID is a disease smorgasbord of illnesses that have been somehow triggered by COVID. So, the question is, are there some types of these disorders that can respond to Paxlovid?” Dr. Sanders said. 

Some patients have also benefited from supplements such as N-acetyl cysteine (NAC), as well as vitamins B, C, D and alpha lipoic acid, in which the risks are low and there are potential benefits, Dr. Sanders said.

As researchers continue to study new treatments for long COVID, for which there are no standard approved therapies, Dr. Sanders suggested doctors might turn to Paxlovid and other promising therapeutics that have shown benefits in preliminary study findings.

A study published in 2023 by JAMA Internal Medicine reviewed the charts of nearly 300,000 veterans with severe acute COVID infections. The study found that Paxlovid treatment reduced the likelihood of developing long COVID. But a more recent study at Stanford University, Palo Alto, California — the STOP-PASC trial— did not find Paxlovid improved symptoms when given to 155 patients who had already recovered from acute infection. Participants with long COVID symptoms — and who had on average recovered from acute infection around 16 months earlier — were given a 15-day course of Paxlovid. Common symptoms like fog, fatigue, and cardiovascular or gastrointestinal symptoms did not improve.

However, long COVID likely has multiple drivers. Viral persistence may still be at play for a subset of patients. This means that, despite the fact that patients recover from acute infection, hidden reservoirs of SARS-CoV-2 are still present in the body, possibly bringing on long COVID symptoms. Which means Paxlovid may help some long COVID patients but not others, Dr. Sanders explained. That’s why research needs to continue to identify the best cases for Paxlovid’s use and to identify other treatments for those who do not benefit from Paxlovid.

The PAX LC trial at Yale suggests there may not be a one-size-fits-all treatment for the condition, but a range of factors that may determine the best therapy for individual patients. Led by Yale School of Medicine’s Harlan Krumholz, MD, and Akiko Iwasaki, PhD, the study tested the effects of Paxlovid overall and was designed to determine who is most likely to benefit from antiviral treatment and gain further understanding of the immune response in long COVID. Results should be reported soon. 

“This acknowledges one line of thinking that long COVID is caused by viral persistence,” Dr. Sanders said. “Do these people have hidden reservoirs of the virus? The question is, are there people who seem to respond [to Paxlovid]? And if so, what characterizes these people?”
 

Low-Risk, High-Reward Supplements

Some of Dr. Sanders’ colleagues at Yale are focusing on long COVID’s neurological symptoms and neuropathogenesis. There’s evidence showing these symptoms — notably brain fog — can be treated with supplements. 

In 2022, a Yale study by Arman Fesharaki-Zadeh, MD, PhD, found promise in treating brain fog through a combination supplement of NAC and guanfacine — the latter developed by Yale neuroscientist, Amy Arnsten, PhD. 

The two published their study in Neuroimmunology Reports in November 2023. NAC is available over the counter and patients can get a prescription for guanfacine off label from their physician. Guanfacine is approved to treat high blood pressure by decreasing heart rate and relaxing blood vessels. But it’s also been shown to treat attention-deficit/hyperactivity disorder (ADHD) and other cognitive issues. 

Though NAC can treat respiratory problems, it’s also commonly used to treat postconcussion symptoms. Dr. Fesharaki-Zadeh found that it helps treat brain fog, increases energy, and improves memory. When paired with guanfacine, substantial benefits were reported, such as better multitasking abilities and markedly improved organizational skills. 

Dr. Sanders is now using NAC and guanfacine for patients in her clinic. 
 

‘Mitochondrial Enhancement’ Through Vitamins

Dr. Sanders has also used a combination of alpha lipoic acid and vitamin C, and a combo of B vitamins that make up what’s called a “mitochondrial enhancement regimen.”

To treat a very common symptom like fatigue, Dr. Sanders prefers supplement combinations over other drugs like Modafinil or Adderall. 

Modafinil is a central nervous system stimulant used to reduce extreme sleepiness caused by narcolepsy or other sleep disorders. Adderall is an amphetamine also used to treat narcolepsy as well as ADHD. Both work on your sleep and alertness, but long COVID affects the whole body, causing a physical fatigue similar to postexertional malaise (PEM) that isn’t remedied by those kinds of drugs, as studies suggest what’s involved in PEM is mitochondria, Dr. Sanders said. 

PEM is a worsening of symptoms that occurs after minimal physical or mental exertion. These are activities that should be well tolerated, but PEM causes extreme fatigue and flu-like symptoms. It’s become a hallmark symptom of long COVID after having already been a key diagnostic factor in myalgic encephalomyelitis/chronic fatigue syndrome.

As Dr. Sanders noted in her long COVID blog, which tracks the latest research and treatment options for doctors who treat long COVID patients, previous studies have shown low vitamin D levels may not only increase the risk for severe COVID-19 but delay recovery from long COVID. Those without long COVID had higher levels of vitamin D, compared with long COVID patients. Vitamin D is known to boost the immune system.

Dr. Sanders found that those with vitamin D deficiencies are most likely to benefit from this approach. For people who don’t have sufficient sun exposure, which prompts the production of vitamin D, she says supplementation with 1000 IUs of vitamin D3 daily is enough for most adults.

Research is also currently being underway on the use of the diabetes drug metformin in people with acute COVID infections to determine if it may reduce the likelihood of developing long COVID. In a recent long COVID clinical trial, early outpatient COVID-19 treatment with metformin decreased the subsequent risk for long COVID by 41.3% during 10-month follow-up. 
 

Other New Treatments Under Study

Dr. Sanders believes the foundation for many of long COVID’s symptoms could be neurological. 

“I think that long COVID is probably a neurologic disorder,” Dr. Sanders said. 

Lindsey McAlpine, MD, director of the Yale Medicine NeuroCovid Clinic, is focusing on neuropsychiatric long COVID and the causes of neurologic post-acute sequelae of SARS-CoV-2 infection (neuro-PASC). Symptoms of neuro-PASC include cognitive impairment, headaches, and dizziness.

“Lindsey is trying to see which parts of the brain are involved and see if there are phenotypes of brain abnormalities that match up with clinical abnormalities,” Dr. Sanders said.

The National Institute of Neurological Disorders and Stroke recently awarded her a 5-year K23 grant to support her ongoing study, “Magnetic Resonance Imaging Biomarkers of Post-COVID-19 Cerebral Microvascular Dysfunction.”

Utilizing advanced MRI techniques to identify microvascular dysfunction biomarkers in the brain, Dr. McAlpine hopes to unearth and better understand the pathophysiology behind neurological issues post COVID.

Many of Dr. McAlpine’s patients with cognitive symptoms have responded well to NAC and guanfacine. 

Still, the hope is that her brain-imaging studies will bear fruit that leads to a better understanding of long COVID and new treatment methods.

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

The market for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to lower cholesterol is taking off with several new drugs being introduced or nearing the market, which will increase competition and enable more patients to reach low-density lipoprotein (LDL) goals, experts said.

One new anti-PCSK9 agent — lerodalcibep from LIB Therapeutics — is a small protein molecule, which is expected to reach the market by early 2026. It is being positioned as a step forward from the two monoclonal antibody products already available — evolocumab (Repatha; Amgen) and alirocumab (Praluent; Sanofi/Regeneron).

The new option can be given less frequently than the antibodies with a once-a-month injection instead of every 2 weeks. It also does not need to be kept refrigerated like the antibodies, Evan Stein, MD, chief scientific and operating officer of LIB Therapeutics, said in an interview.

Two phase 3 trials have recently been reported, showing impressive reductions in LDL in patients already taking statins.
 

The LIBerate Trials

The LIBerate-HR trial, published in JAMA Cardiology, involved 922 patients who still had LDL above target despite taking maximally tolerated statin therapy plus other lipid-lowering agents in some cases.

The trial found a time-averaged mean reduction in LDL cholesterol of 62%.

“This large reduction resulted in more than 90% of patients reaching the new lower LDL targets set in recent guidelines of less than 55 mg/dL for patients with cardiovascular disease or at very high risk, and less than 70 mg/dL in patients at risk,” said Stein.

Another phase 3 trial, LIBerate-CVD, has also shown reductions in LDL cholesterol levels of more than 60% in patients at high risk for cardiovascular disease on maximally tolerated statins.

LIB Therapeutics plans to file approval applications for lerodalcibep in the United States and Europe later this year.
 

A Crowded Field

Dr. Stein said PCSK9 inhibitors have been underused so far, but this is starting to change.

“The monoclonal antibodies were way overpriced costing around $14,000 per year when they were first introduced, which resulted in huge pushback from insurance companies,” Dr. Stein said, which made the drugs difficult to prescribe. “Then a few years ago, the price dropped a bit, and now they’re probably running at about $4000 per year, which made them more accessible.”

He said the market is now rapidly taking off. Lerodalcibep will compete in the anti-PCSK9 market with not only the two monoclonal antibodies but also with the new short-interfering RNA agent, inclisiran (Leqvio; Novartis) , a novel injectable agent that is given just twice a year but has to be administered at a medical facility.

Despite the crowded field, there appears to be plenty of room in the market. “Last year, growth was just under 40%. The first quarter of this year, it has increased by 44%. While the introduction of inclisiran has added to this growth, it hasn’t dented the sales of the existing monoclonal antibodies,” said Dr. Stein.

He estimates that the anti-PCSK9 market will reach $3 billion globally this year, and by the time lerodalcibep is launched, it could be worth $5 billion.

As well as inclisiran and lerodalcibep, there are other innovations in the anti-PCSK9 field in development, with oral drugs now also in the pipeline. The first one of these, in development by Merck, is in early phase 3 trials, and AstraZeneca has an oral agent in earlier development.
 

Enthusiastic Response

Other experts in the lipid field are also enthusiastic about new developments in the PCSK9s.

Jorge Plutzky, MD, director of preventive cardiology at Brigham and Women’s Hospital in Boston, said he welcomes the prospect of new approaches to PCSK9 inhibition.

“The increase in the number of safe, effective tools for LDL lowering, whether through PCSK9 or other targets, is inevitably beneficial for patients and the field,” he said during an interview.

Dr. Plutzky pointed out that although the current agents are effective, cost and coverage remain issues despite some recent progress in these areas, and new agents will increase competition and should hopefully drive prices down. Having a variety of dosing methods and frequencies provides more options for patients to find the one that works best for them.

Lerodalcibep’s once-monthly dosing schedule and the lack of need for refrigeration may be appreciated by some patients, he said, particularly those who need to travel for long periods.

Connie Newman, MD, adjunct professor of medicine at NYU School of Medicine, New York City, said there is plenty of room in the market to accommodate patient’s needs and preferences.

“Despite the US FDA approval of three medications that target PCSK9, there is a need for more anti-PCSK9 agents that reduce LDL and cardiovascular events,” she said. “In the US alone, 25% of adults have LDL levels of 130 mg/dL and above. Of all the non-statin therapies, medications targeting PCSK9 produce the greatest reduction in LDL. However, some patients may not tolerate one or more of the medications available or may prefer a monthly injection of lower volume.”

Dr. Newman said she believes there will still be a market for injectable formulations of PCSK9 inhibitors in the future, even if oral formulations are approved.

“Oral formulations usually require more frequent administration. Some people prefer longer-acting medications that can be taken less often. This might lead to better adherence,” she said.

Dr. Stein said he agrees there will always be room for different options. “And you only have to look at what is happening with the weight loss drugs to see that there is a market for injectables.” The ability to get patients to the new, more aggressive LDL goals is what is important, he added. “These drugs do that, and offering patients a choice of agents and delivery mechanisms is helpful.”

A version of this article appeared on Medscape.com.

The market for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to lower cholesterol is taking off with several new drugs being introduced or nearing the market, which will increase competition and enable more patients to reach low-density lipoprotein (LDL) goals, experts said.

One new anti-PCSK9 agent — lerodalcibep from LIB Therapeutics — is a small protein molecule, which is expected to reach the market by early 2026. It is being positioned as a step forward from the two monoclonal antibody products already available — evolocumab (Repatha; Amgen) and alirocumab (Praluent; Sanofi/Regeneron).

The new option can be given less frequently than the antibodies with a once-a-month injection instead of every 2 weeks. It also does not need to be kept refrigerated like the antibodies, Evan Stein, MD, chief scientific and operating officer of LIB Therapeutics, said in an interview.

Two phase 3 trials have recently been reported, showing impressive reductions in LDL in patients already taking statins.
 

The LIBerate Trials

The LIBerate-HR trial, published in JAMA Cardiology, involved 922 patients who still had LDL above target despite taking maximally tolerated statin therapy plus other lipid-lowering agents in some cases.

The trial found a time-averaged mean reduction in LDL cholesterol of 62%.

“This large reduction resulted in more than 90% of patients reaching the new lower LDL targets set in recent guidelines of less than 55 mg/dL for patients with cardiovascular disease or at very high risk, and less than 70 mg/dL in patients at risk,” said Stein.

Another phase 3 trial, LIBerate-CVD, has also shown reductions in LDL cholesterol levels of more than 60% in patients at high risk for cardiovascular disease on maximally tolerated statins.

LIB Therapeutics plans to file approval applications for lerodalcibep in the United States and Europe later this year.
 

A Crowded Field

Dr. Stein said PCSK9 inhibitors have been underused so far, but this is starting to change.

“The monoclonal antibodies were way overpriced costing around $14,000 per year when they were first introduced, which resulted in huge pushback from insurance companies,” Dr. Stein said, which made the drugs difficult to prescribe. “Then a few years ago, the price dropped a bit, and now they’re probably running at about $4000 per year, which made them more accessible.”

He said the market is now rapidly taking off. Lerodalcibep will compete in the anti-PCSK9 market with not only the two monoclonal antibodies but also with the new short-interfering RNA agent, inclisiran (Leqvio; Novartis) , a novel injectable agent that is given just twice a year but has to be administered at a medical facility.

Despite the crowded field, there appears to be plenty of room in the market. “Last year, growth was just under 40%. The first quarter of this year, it has increased by 44%. While the introduction of inclisiran has added to this growth, it hasn’t dented the sales of the existing monoclonal antibodies,” said Dr. Stein.

He estimates that the anti-PCSK9 market will reach $3 billion globally this year, and by the time lerodalcibep is launched, it could be worth $5 billion.

As well as inclisiran and lerodalcibep, there are other innovations in the anti-PCSK9 field in development, with oral drugs now also in the pipeline. The first one of these, in development by Merck, is in early phase 3 trials, and AstraZeneca has an oral agent in earlier development.
 

Enthusiastic Response

Other experts in the lipid field are also enthusiastic about new developments in the PCSK9s.

Jorge Plutzky, MD, director of preventive cardiology at Brigham and Women’s Hospital in Boston, said he welcomes the prospect of new approaches to PCSK9 inhibition.

“The increase in the number of safe, effective tools for LDL lowering, whether through PCSK9 or other targets, is inevitably beneficial for patients and the field,” he said during an interview.

Dr. Plutzky pointed out that although the current agents are effective, cost and coverage remain issues despite some recent progress in these areas, and new agents will increase competition and should hopefully drive prices down. Having a variety of dosing methods and frequencies provides more options for patients to find the one that works best for them.

Lerodalcibep’s once-monthly dosing schedule and the lack of need for refrigeration may be appreciated by some patients, he said, particularly those who need to travel for long periods.

Connie Newman, MD, adjunct professor of medicine at NYU School of Medicine, New York City, said there is plenty of room in the market to accommodate patient’s needs and preferences.

“Despite the US FDA approval of three medications that target PCSK9, there is a need for more anti-PCSK9 agents that reduce LDL and cardiovascular events,” she said. “In the US alone, 25% of adults have LDL levels of 130 mg/dL and above. Of all the non-statin therapies, medications targeting PCSK9 produce the greatest reduction in LDL. However, some patients may not tolerate one or more of the medications available or may prefer a monthly injection of lower volume.”

Dr. Newman said she believes there will still be a market for injectable formulations of PCSK9 inhibitors in the future, even if oral formulations are approved.

“Oral formulations usually require more frequent administration. Some people prefer longer-acting medications that can be taken less often. This might lead to better adherence,” she said.

Dr. Stein said he agrees there will always be room for different options. “And you only have to look at what is happening with the weight loss drugs to see that there is a market for injectables.” The ability to get patients to the new, more aggressive LDL goals is what is important, he added. “These drugs do that, and offering patients a choice of agents and delivery mechanisms is helpful.”

A version of this article appeared on Medscape.com.

The market for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to lower cholesterol is taking off with several new drugs being introduced or nearing the market, which will increase competition and enable more patients to reach low-density lipoprotein (LDL) goals, experts said.

One new anti-PCSK9 agent — lerodalcibep from LIB Therapeutics — is a small protein molecule, which is expected to reach the market by early 2026. It is being positioned as a step forward from the two monoclonal antibody products already available — evolocumab (Repatha; Amgen) and alirocumab (Praluent; Sanofi/Regeneron).

The new option can be given less frequently than the antibodies with a once-a-month injection instead of every 2 weeks. It also does not need to be kept refrigerated like the antibodies, Evan Stein, MD, chief scientific and operating officer of LIB Therapeutics, said in an interview.

Two phase 3 trials have recently been reported, showing impressive reductions in LDL in patients already taking statins.
 

The LIBerate Trials

The LIBerate-HR trial, published in JAMA Cardiology, involved 922 patients who still had LDL above target despite taking maximally tolerated statin therapy plus other lipid-lowering agents in some cases.

The trial found a time-averaged mean reduction in LDL cholesterol of 62%.

“This large reduction resulted in more than 90% of patients reaching the new lower LDL targets set in recent guidelines of less than 55 mg/dL for patients with cardiovascular disease or at very high risk, and less than 70 mg/dL in patients at risk,” said Stein.

Another phase 3 trial, LIBerate-CVD, has also shown reductions in LDL cholesterol levels of more than 60% in patients at high risk for cardiovascular disease on maximally tolerated statins.

LIB Therapeutics plans to file approval applications for lerodalcibep in the United States and Europe later this year.
 

A Crowded Field

Dr. Stein said PCSK9 inhibitors have been underused so far, but this is starting to change.

“The monoclonal antibodies were way overpriced costing around $14,000 per year when they were first introduced, which resulted in huge pushback from insurance companies,” Dr. Stein said, which made the drugs difficult to prescribe. “Then a few years ago, the price dropped a bit, and now they’re probably running at about $4000 per year, which made them more accessible.”

He said the market is now rapidly taking off. Lerodalcibep will compete in the anti-PCSK9 market with not only the two monoclonal antibodies but also with the new short-interfering RNA agent, inclisiran (Leqvio; Novartis) , a novel injectable agent that is given just twice a year but has to be administered at a medical facility.

Despite the crowded field, there appears to be plenty of room in the market. “Last year, growth was just under 40%. The first quarter of this year, it has increased by 44%. While the introduction of inclisiran has added to this growth, it hasn’t dented the sales of the existing monoclonal antibodies,” said Dr. Stein.

He estimates that the anti-PCSK9 market will reach $3 billion globally this year, and by the time lerodalcibep is launched, it could be worth $5 billion.

As well as inclisiran and lerodalcibep, there are other innovations in the anti-PCSK9 field in development, with oral drugs now also in the pipeline. The first one of these, in development by Merck, is in early phase 3 trials, and AstraZeneca has an oral agent in earlier development.
 

Enthusiastic Response

Other experts in the lipid field are also enthusiastic about new developments in the PCSK9s.

Jorge Plutzky, MD, director of preventive cardiology at Brigham and Women’s Hospital in Boston, said he welcomes the prospect of new approaches to PCSK9 inhibition.

“The increase in the number of safe, effective tools for LDL lowering, whether through PCSK9 or other targets, is inevitably beneficial for patients and the field,” he said during an interview.

Dr. Plutzky pointed out that although the current agents are effective, cost and coverage remain issues despite some recent progress in these areas, and new agents will increase competition and should hopefully drive prices down. Having a variety of dosing methods and frequencies provides more options for patients to find the one that works best for them.

Lerodalcibep’s once-monthly dosing schedule and the lack of need for refrigeration may be appreciated by some patients, he said, particularly those who need to travel for long periods.

Connie Newman, MD, adjunct professor of medicine at NYU School of Medicine, New York City, said there is plenty of room in the market to accommodate patient’s needs and preferences.

“Despite the US FDA approval of three medications that target PCSK9, there is a need for more anti-PCSK9 agents that reduce LDL and cardiovascular events,” she said. “In the US alone, 25% of adults have LDL levels of 130 mg/dL and above. Of all the non-statin therapies, medications targeting PCSK9 produce the greatest reduction in LDL. However, some patients may not tolerate one or more of the medications available or may prefer a monthly injection of lower volume.”

Dr. Newman said she believes there will still be a market for injectable formulations of PCSK9 inhibitors in the future, even if oral formulations are approved.

“Oral formulations usually require more frequent administration. Some people prefer longer-acting medications that can be taken less often. This might lead to better adherence,” she said.

Dr. Stein said he agrees there will always be room for different options. “And you only have to look at what is happening with the weight loss drugs to see that there is a market for injectables.” The ability to get patients to the new, more aggressive LDL goals is what is important, he added. “These drugs do that, and offering patients a choice of agents and delivery mechanisms is helpful.”

A version of this article appeared on Medscape.com.

Compared with traditional replacement valves, sutureless valves placed through minimally invasive cardiac surgery have less data supporting their use but offer unique features that might make them the preferred option for certain patients, reported specialists.

Two valves placed by minimally invasive surgery received regulatory approval 8 years ago, but they are not widely used to this day.

The sutureless device known as Perceval (Corcym) and a rapidly deployed device called Intuity (Edwards Lifesciences) are used as an alternative to surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). But despite being commercially available since 2016, the devices are still not being used much.

The devices are not discussed in substantial detail in either the joint guidelines from the American College of Cardiology and American Heart Association issued in 2020 or guidelines from the European Society of Cardiology issued in 2022.

Cristiano Spadaccio, MD, PhD, a cardiothoracic surgeon associated with Lancashire Cardiac Centre in Blackpool, England, and his colleagues reviewed the small number of studies evaluating the alternate approach to “make the cardiology world aware” of alternatives “that can relieve the surgical burden by minimizing the implantation time and length of the operation,” he said.

The comprehensive review is published in the Journal of the American College of Cardiology.
 

A Neglected Alternative

The sutureless Perceval device is held in place by a stent frame that self-expands. The Intuity device also relies primarily on its framework to anchor the valve in place but does involve three sutures. Both devices are still referred to as sutureless in the new review of them.

Only a small number of centers perform minimally invasive cardiac surgeries, and the main advantage of the devices — rapid deployment — has been eroded with the advent of automated knotting which has significantly reduced the time to implant and sutured valve.

The underuse of these devices is largely caused by the limited amount of comparative and prospective data, said Dr. Spadaccio. “The entire literature on sutureless aortic valve replacement with the exception of one randomized controlled trial is observational.”

That trial, PERSIST-AVR, found that the sutureless valves were just as good as conventional ones when it comes to major adverse cardiovascular events including all-cause death, myocardial infarction, stroke, or valve reintervention at 1 year.

In a subanalysis limited to patients who had isolated aortic valve replacement, the sutureless procedure was associated with lower adverse events (5.2% vs 10.8%) at the cost of a higher rate of pacemaker implantation (11% vs 1.6%).

There are also multiple retrospective studies and registries that have generated observational data comparing sutureless aortic valve replacement with SAVR and TAVR in various patient populations, said Dr. Spadaccio, and the review was based on more than a dozen studies published since 2015. Long-term follow-up data for sutureless aortic valve replacements, which now exceeds 10 years, suggest rates of structural valve deterioration and reintervention have been acceptably low.

The minimally invasive procedures have other advantages too. For example, relative to the greater trauma associated with open heart surgery, minimally invasive surgeries typically involve faster recovery, an advantage likely to appeal to many patients who are candidates for either.
 

Quicker Recovery

Collectively, these data suggest that sutureless aortic valve replacement might be a reasonable or even a more appropriate alternative to either SAVR or TAVR when considering specific patient characteristics and goals, according to the review, which included an algorithm identifying specifically where sutureless aortic valve replacement fits with SAVR and TAVR.

“The algorithm is based on different clinical scenarios and reflects current guidelines for SAVR,” said Dr. Spadaccio. For example, current guidelines identify SAVR as preferred in patients younger than 65 years and in older patients with a low Society of Thoracic Surgeons (STS) score, but there are many instances in which sutureless aortic valve replacement might be more attractive, such as in those also undergoing mitral valve repair, coronary artery bypass grafting, or another surgical procedure.

Dr. Spadaccio said that the STS score should not be considered in isolation when evaluating a patient for SAVR or TAVR. Other features such as mobility, frailty score, and comorbid liver or renal disease should also be considered when discussing the three options with patients. As a result, the algorithm emphasizes a detailed evaluation of patient characteristics in selecting one procedure over another.

“The treatment should be really tailored on the individual patient basis,” said Dr. Spadaccio.

Dr. Spadaccio acknowledged that there is a need for more comparative trials, particularly in regard to sutureless aortic valve replacement as an alternative to TAVR. “I really think that a 1:1 RCT on sutureless aortic valve replacement vs TAVR could give better answers to all of these interrogatives.”

But despite the limitations outlined in this review, Dr. Spadaccio and colleagues challenged the perception that current data are not sufficient to allow clinicians to consider sutureless aortic valve replacement in the mix of options.
 

A Viable Option

This comprehensive summary of what is known about sutureless aortic valve replacement compared with the other options addresses an important knowledge gap, said S. Chris Malaisrie, MD, a cardiac surgeon at Northwestern University Feinberg School of Medicine, Chicago, Illinois.

He said he agrees this option has unique qualities. “Minimally invasive surgery has been largely ignored by guideline writers, but patients certainly demand options that are less invasive than standard open heart surgery. Sutureless and rapid deployment valves facilitate minimally invasive surgery and offer an advantageous option for younger patients.”

Dr. Malaisrie said the review is generating discussion about a potentially valuable option within the cardiology community. And that is exactly what Dr. Spadaccio was hoping for. “This paper was meant to educate as much as possible on these details to assist and inform decision-making,” he said.

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

Compared with traditional replacement valves, sutureless valves placed through minimally invasive cardiac surgery have less data supporting their use but offer unique features that might make them the preferred option for certain patients, reported specialists.

Two valves placed by minimally invasive surgery received regulatory approval 8 years ago, but they are not widely used to this day.

The sutureless device known as Perceval (Corcym) and a rapidly deployed device called Intuity (Edwards Lifesciences) are used as an alternative to surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). But despite being commercially available since 2016, the devices are still not being used much.

The devices are not discussed in substantial detail in either the joint guidelines from the American College of Cardiology and American Heart Association issued in 2020 or guidelines from the European Society of Cardiology issued in 2022.

Cristiano Spadaccio, MD, PhD, a cardiothoracic surgeon associated with Lancashire Cardiac Centre in Blackpool, England, and his colleagues reviewed the small number of studies evaluating the alternate approach to “make the cardiology world aware” of alternatives “that can relieve the surgical burden by minimizing the implantation time and length of the operation,” he said.

The comprehensive review is published in the Journal of the American College of Cardiology.
 

A Neglected Alternative

The sutureless Perceval device is held in place by a stent frame that self-expands. The Intuity device also relies primarily on its framework to anchor the valve in place but does involve three sutures. Both devices are still referred to as sutureless in the new review of them.

Only a small number of centers perform minimally invasive cardiac surgeries, and the main advantage of the devices — rapid deployment — has been eroded with the advent of automated knotting which has significantly reduced the time to implant and sutured valve.

The underuse of these devices is largely caused by the limited amount of comparative and prospective data, said Dr. Spadaccio. “The entire literature on sutureless aortic valve replacement with the exception of one randomized controlled trial is observational.”

That trial, PERSIST-AVR, found that the sutureless valves were just as good as conventional ones when it comes to major adverse cardiovascular events including all-cause death, myocardial infarction, stroke, or valve reintervention at 1 year.

In a subanalysis limited to patients who had isolated aortic valve replacement, the sutureless procedure was associated with lower adverse events (5.2% vs 10.8%) at the cost of a higher rate of pacemaker implantation (11% vs 1.6%).

There are also multiple retrospective studies and registries that have generated observational data comparing sutureless aortic valve replacement with SAVR and TAVR in various patient populations, said Dr. Spadaccio, and the review was based on more than a dozen studies published since 2015. Long-term follow-up data for sutureless aortic valve replacements, which now exceeds 10 years, suggest rates of structural valve deterioration and reintervention have been acceptably low.

The minimally invasive procedures have other advantages too. For example, relative to the greater trauma associated with open heart surgery, minimally invasive surgeries typically involve faster recovery, an advantage likely to appeal to many patients who are candidates for either.
 

Quicker Recovery

Collectively, these data suggest that sutureless aortic valve replacement might be a reasonable or even a more appropriate alternative to either SAVR or TAVR when considering specific patient characteristics and goals, according to the review, which included an algorithm identifying specifically where sutureless aortic valve replacement fits with SAVR and TAVR.

“The algorithm is based on different clinical scenarios and reflects current guidelines for SAVR,” said Dr. Spadaccio. For example, current guidelines identify SAVR as preferred in patients younger than 65 years and in older patients with a low Society of Thoracic Surgeons (STS) score, but there are many instances in which sutureless aortic valve replacement might be more attractive, such as in those also undergoing mitral valve repair, coronary artery bypass grafting, or another surgical procedure.

Dr. Spadaccio said that the STS score should not be considered in isolation when evaluating a patient for SAVR or TAVR. Other features such as mobility, frailty score, and comorbid liver or renal disease should also be considered when discussing the three options with patients. As a result, the algorithm emphasizes a detailed evaluation of patient characteristics in selecting one procedure over another.

“The treatment should be really tailored on the individual patient basis,” said Dr. Spadaccio.

Dr. Spadaccio acknowledged that there is a need for more comparative trials, particularly in regard to sutureless aortic valve replacement as an alternative to TAVR. “I really think that a 1:1 RCT on sutureless aortic valve replacement vs TAVR could give better answers to all of these interrogatives.”

But despite the limitations outlined in this review, Dr. Spadaccio and colleagues challenged the perception that current data are not sufficient to allow clinicians to consider sutureless aortic valve replacement in the mix of options.
 

A Viable Option

This comprehensive summary of what is known about sutureless aortic valve replacement compared with the other options addresses an important knowledge gap, said S. Chris Malaisrie, MD, a cardiac surgeon at Northwestern University Feinberg School of Medicine, Chicago, Illinois.

He said he agrees this option has unique qualities. “Minimally invasive surgery has been largely ignored by guideline writers, but patients certainly demand options that are less invasive than standard open heart surgery. Sutureless and rapid deployment valves facilitate minimally invasive surgery and offer an advantageous option for younger patients.”

Dr. Malaisrie said the review is generating discussion about a potentially valuable option within the cardiology community. And that is exactly what Dr. Spadaccio was hoping for. “This paper was meant to educate as much as possible on these details to assist and inform decision-making,” he said.

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

Compared with traditional replacement valves, sutureless valves placed through minimally invasive cardiac surgery have less data supporting their use but offer unique features that might make them the preferred option for certain patients, reported specialists.

Two valves placed by minimally invasive surgery received regulatory approval 8 years ago, but they are not widely used to this day.

The sutureless device known as Perceval (Corcym) and a rapidly deployed device called Intuity (Edwards Lifesciences) are used as an alternative to surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). But despite being commercially available since 2016, the devices are still not being used much.

The devices are not discussed in substantial detail in either the joint guidelines from the American College of Cardiology and American Heart Association issued in 2020 or guidelines from the European Society of Cardiology issued in 2022.

Cristiano Spadaccio, MD, PhD, a cardiothoracic surgeon associated with Lancashire Cardiac Centre in Blackpool, England, and his colleagues reviewed the small number of studies evaluating the alternate approach to “make the cardiology world aware” of alternatives “that can relieve the surgical burden by minimizing the implantation time and length of the operation,” he said.

The comprehensive review is published in the Journal of the American College of Cardiology.
 

A Neglected Alternative

The sutureless Perceval device is held in place by a stent frame that self-expands. The Intuity device also relies primarily on its framework to anchor the valve in place but does involve three sutures. Both devices are still referred to as sutureless in the new review of them.

Only a small number of centers perform minimally invasive cardiac surgeries, and the main advantage of the devices — rapid deployment — has been eroded with the advent of automated knotting which has significantly reduced the time to implant and sutured valve.

The underuse of these devices is largely caused by the limited amount of comparative and prospective data, said Dr. Spadaccio. “The entire literature on sutureless aortic valve replacement with the exception of one randomized controlled trial is observational.”

That trial, PERSIST-AVR, found that the sutureless valves were just as good as conventional ones when it comes to major adverse cardiovascular events including all-cause death, myocardial infarction, stroke, or valve reintervention at 1 year.

In a subanalysis limited to patients who had isolated aortic valve replacement, the sutureless procedure was associated with lower adverse events (5.2% vs 10.8%) at the cost of a higher rate of pacemaker implantation (11% vs 1.6%).

There are also multiple retrospective studies and registries that have generated observational data comparing sutureless aortic valve replacement with SAVR and TAVR in various patient populations, said Dr. Spadaccio, and the review was based on more than a dozen studies published since 2015. Long-term follow-up data for sutureless aortic valve replacements, which now exceeds 10 years, suggest rates of structural valve deterioration and reintervention have been acceptably low.

The minimally invasive procedures have other advantages too. For example, relative to the greater trauma associated with open heart surgery, minimally invasive surgeries typically involve faster recovery, an advantage likely to appeal to many patients who are candidates for either.
 

Quicker Recovery

Collectively, these data suggest that sutureless aortic valve replacement might be a reasonable or even a more appropriate alternative to either SAVR or TAVR when considering specific patient characteristics and goals, according to the review, which included an algorithm identifying specifically where sutureless aortic valve replacement fits with SAVR and TAVR.

“The algorithm is based on different clinical scenarios and reflects current guidelines for SAVR,” said Dr. Spadaccio. For example, current guidelines identify SAVR as preferred in patients younger than 65 years and in older patients with a low Society of Thoracic Surgeons (STS) score, but there are many instances in which sutureless aortic valve replacement might be more attractive, such as in those also undergoing mitral valve repair, coronary artery bypass grafting, or another surgical procedure.

Dr. Spadaccio said that the STS score should not be considered in isolation when evaluating a patient for SAVR or TAVR. Other features such as mobility, frailty score, and comorbid liver or renal disease should also be considered when discussing the three options with patients. As a result, the algorithm emphasizes a detailed evaluation of patient characteristics in selecting one procedure over another.

“The treatment should be really tailored on the individual patient basis,” said Dr. Spadaccio.

Dr. Spadaccio acknowledged that there is a need for more comparative trials, particularly in regard to sutureless aortic valve replacement as an alternative to TAVR. “I really think that a 1:1 RCT on sutureless aortic valve replacement vs TAVR could give better answers to all of these interrogatives.”

But despite the limitations outlined in this review, Dr. Spadaccio and colleagues challenged the perception that current data are not sufficient to allow clinicians to consider sutureless aortic valve replacement in the mix of options.
 

A Viable Option

This comprehensive summary of what is known about sutureless aortic valve replacement compared with the other options addresses an important knowledge gap, said S. Chris Malaisrie, MD, a cardiac surgeon at Northwestern University Feinberg School of Medicine, Chicago, Illinois.

He said he agrees this option has unique qualities. “Minimally invasive surgery has been largely ignored by guideline writers, but patients certainly demand options that are less invasive than standard open heart surgery. Sutureless and rapid deployment valves facilitate minimally invasive surgery and offer an advantageous option for younger patients.”

Dr. Malaisrie said the review is generating discussion about a potentially valuable option within the cardiology community. And that is exactly what Dr. Spadaccio was hoping for. “This paper was meant to educate as much as possible on these details to assist and inform decision-making,” he said.

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

Everyone takes a pharmacology class in medical school that includes a lecture on beta receptors. They’re in the heart (beta-1) and lungs (beta-2), and drug compounds agonize or antagonize one or both. The professor will caution against using antagonists (beta blockade) for patients with chronic obstructive pulmonary disease (COPD) lest they further impair the patient’s irreversibly narrowed airways. Obsequious students mature into obsequious doctors, intent on “doing no harm.” For better or worse, you withhold beta-blockers from your patient with COPD and comorbid cardiac disease.

Perhaps because the pulmonologist isn’t usually the one who decides whether a beta-blocker is prescribed, I’ve been napping on this topic since training. Early in fellowship, I read an ACP Journal Club article about a Cochrane systematic review (yes, I read a review of a review) that concluded that beta-blockers are fine in patients with COPD. The summary appealed to my bias towards evidence-based medicine (EBM) supplanting physiology, medical school, and everything else. I was more apt to believe my stodgy residency attendings than the stodgy pharmacology professor. Even though COPD and cardiovascular disease share multiple risk factors, I had never reinvestigated the relationship between beta-blockers and COPD.

Turns out that while I was sleeping, the debate continued. Go figure. Just last month a prospective, observational study published in JAMA Network Open found that beta-blockers did not increase the risk for cardiovascular or respiratory events among patients with COPD being discharged after hospitalization for acute myocardial infarction. Although this could be viewed as a triumph for EBM over physiology and a validation of my decade-plus of intellectual laziness, the results are actually pretty thin. These studies, in which patients with an indication for a therapy (a beta-blocker in this case) are analyzed by whether or not they received it, are problematic. The fanciest statistics — in this case, they used propensity scores — can’t control for residual confounding. What drove the physicians to prescribe in some cases but not others? We can only guess.

This might be okay if there hadn’t been a randomized controlled trial (RCT) published in 2019 in The New England Journal of Medicine that found that beta-blockers increase the risk for severe COPD exacerbations. In EBM, the RCT trumps all. Ironically, this trial was designed to test whether beta-blockers reduce severe COPD exacerbations. Yes, we’d come full circle. There was enough biologic plausibility to support a positive effect, or so thought the study authors and the Department of Defense (DOD) — for reasons I can’t possibly guess, the DOD funded this RCT. My pharmacology professor must be rolling over in his tenure.

The RCT did leave beta-blockers some wiggle room. The authors purposely excluded anyone with a cardiovascular indication for a beta-blocker. The intent was to ensure beneficial effects were isolated to respiratory and not cardiovascular outcomes. Of course, the reason I’m writing and you’re reading this is that COPD and cardiovascular disease co-occur at a high rate. The RCT notwithstanding, we prescribe beta-blockers to patients with COPD because they have a cardiac indication, not to reduce acute COPD exacerbations. So, it’s possible there’d be a net beta-blocker benefit in patients with COPD and comorbid heart disease.

That’s where the JAMA Network Open study comes in, but as discussed, methodologic weaknesses preclude its being the final word. That said, I think it’s unlikely we’ll see a COPD with comorbid cardiac disease RCT performed to assess whether beta-blockers provide a net benefit, unless maybe the DOD wants to fund another one of these. In the meantime, I’m calling clinical equipoise and punting. Fortunately for me, I don’t have to prescribe beta-blockers. I suppose I could consider stopping them in my patient with severe COPD, the one I can’t keep out of the hospital, but I’m not convinced that would make much difference.
 

Dr. Holley is professor of medicine at Uniformed Services University in Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington, DC. He reported conflicts of interest with Metapharm, CHEST College, and WebMD.

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

Everyone takes a pharmacology class in medical school that includes a lecture on beta receptors. They’re in the heart (beta-1) and lungs (beta-2), and drug compounds agonize or antagonize one or both. The professor will caution against using antagonists (beta blockade) for patients with chronic obstructive pulmonary disease (COPD) lest they further impair the patient’s irreversibly narrowed airways. Obsequious students mature into obsequious doctors, intent on “doing no harm.” For better or worse, you withhold beta-blockers from your patient with COPD and comorbid cardiac disease.

Perhaps because the pulmonologist isn’t usually the one who decides whether a beta-blocker is prescribed, I’ve been napping on this topic since training. Early in fellowship, I read an ACP Journal Club article about a Cochrane systematic review (yes, I read a review of a review) that concluded that beta-blockers are fine in patients with COPD. The summary appealed to my bias towards evidence-based medicine (EBM) supplanting physiology, medical school, and everything else. I was more apt to believe my stodgy residency attendings than the stodgy pharmacology professor. Even though COPD and cardiovascular disease share multiple risk factors, I had never reinvestigated the relationship between beta-blockers and COPD.

Turns out that while I was sleeping, the debate continued. Go figure. Just last month a prospective, observational study published in JAMA Network Open found that beta-blockers did not increase the risk for cardiovascular or respiratory events among patients with COPD being discharged after hospitalization for acute myocardial infarction. Although this could be viewed as a triumph for EBM over physiology and a validation of my decade-plus of intellectual laziness, the results are actually pretty thin. These studies, in which patients with an indication for a therapy (a beta-blocker in this case) are analyzed by whether or not they received it, are problematic. The fanciest statistics — in this case, they used propensity scores — can’t control for residual confounding. What drove the physicians to prescribe in some cases but not others? We can only guess.

This might be okay if there hadn’t been a randomized controlled trial (RCT) published in 2019 in The New England Journal of Medicine that found that beta-blockers increase the risk for severe COPD exacerbations. In EBM, the RCT trumps all. Ironically, this trial was designed to test whether beta-blockers reduce severe COPD exacerbations. Yes, we’d come full circle. There was enough biologic plausibility to support a positive effect, or so thought the study authors and the Department of Defense (DOD) — for reasons I can’t possibly guess, the DOD funded this RCT. My pharmacology professor must be rolling over in his tenure.

The RCT did leave beta-blockers some wiggle room. The authors purposely excluded anyone with a cardiovascular indication for a beta-blocker. The intent was to ensure beneficial effects were isolated to respiratory and not cardiovascular outcomes. Of course, the reason I’m writing and you’re reading this is that COPD and cardiovascular disease co-occur at a high rate. The RCT notwithstanding, we prescribe beta-blockers to patients with COPD because they have a cardiac indication, not to reduce acute COPD exacerbations. So, it’s possible there’d be a net beta-blocker benefit in patients with COPD and comorbid heart disease.

That’s where the JAMA Network Open study comes in, but as discussed, methodologic weaknesses preclude its being the final word. That said, I think it’s unlikely we’ll see a COPD with comorbid cardiac disease RCT performed to assess whether beta-blockers provide a net benefit, unless maybe the DOD wants to fund another one of these. In the meantime, I’m calling clinical equipoise and punting. Fortunately for me, I don’t have to prescribe beta-blockers. I suppose I could consider stopping them in my patient with severe COPD, the one I can’t keep out of the hospital, but I’m not convinced that would make much difference.
 

Dr. Holley is professor of medicine at Uniformed Services University in Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington, DC. He reported conflicts of interest with Metapharm, CHEST College, and WebMD.

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

Everyone takes a pharmacology class in medical school that includes a lecture on beta receptors. They’re in the heart (beta-1) and lungs (beta-2), and drug compounds agonize or antagonize one or both. The professor will caution against using antagonists (beta blockade) for patients with chronic obstructive pulmonary disease (COPD) lest they further impair the patient’s irreversibly narrowed airways. Obsequious students mature into obsequious doctors, intent on “doing no harm.” For better or worse, you withhold beta-blockers from your patient with COPD and comorbid cardiac disease.

Perhaps because the pulmonologist isn’t usually the one who decides whether a beta-blocker is prescribed, I’ve been napping on this topic since training. Early in fellowship, I read an ACP Journal Club article about a Cochrane systematic review (yes, I read a review of a review) that concluded that beta-blockers are fine in patients with COPD. The summary appealed to my bias towards evidence-based medicine (EBM) supplanting physiology, medical school, and everything else. I was more apt to believe my stodgy residency attendings than the stodgy pharmacology professor. Even though COPD and cardiovascular disease share multiple risk factors, I had never reinvestigated the relationship between beta-blockers and COPD.

Turns out that while I was sleeping, the debate continued. Go figure. Just last month a prospective, observational study published in JAMA Network Open found that beta-blockers did not increase the risk for cardiovascular or respiratory events among patients with COPD being discharged after hospitalization for acute myocardial infarction. Although this could be viewed as a triumph for EBM over physiology and a validation of my decade-plus of intellectual laziness, the results are actually pretty thin. These studies, in which patients with an indication for a therapy (a beta-blocker in this case) are analyzed by whether or not they received it, are problematic. The fanciest statistics — in this case, they used propensity scores — can’t control for residual confounding. What drove the physicians to prescribe in some cases but not others? We can only guess.

This might be okay if there hadn’t been a randomized controlled trial (RCT) published in 2019 in The New England Journal of Medicine that found that beta-blockers increase the risk for severe COPD exacerbations. In EBM, the RCT trumps all. Ironically, this trial was designed to test whether beta-blockers reduce severe COPD exacerbations. Yes, we’d come full circle. There was enough biologic plausibility to support a positive effect, or so thought the study authors and the Department of Defense (DOD) — for reasons I can’t possibly guess, the DOD funded this RCT. My pharmacology professor must be rolling over in his tenure.

The RCT did leave beta-blockers some wiggle room. The authors purposely excluded anyone with a cardiovascular indication for a beta-blocker. The intent was to ensure beneficial effects were isolated to respiratory and not cardiovascular outcomes. Of course, the reason I’m writing and you’re reading this is that COPD and cardiovascular disease co-occur at a high rate. The RCT notwithstanding, we prescribe beta-blockers to patients with COPD because they have a cardiac indication, not to reduce acute COPD exacerbations. So, it’s possible there’d be a net beta-blocker benefit in patients with COPD and comorbid heart disease.

That’s where the JAMA Network Open study comes in, but as discussed, methodologic weaknesses preclude its being the final word. That said, I think it’s unlikely we’ll see a COPD with comorbid cardiac disease RCT performed to assess whether beta-blockers provide a net benefit, unless maybe the DOD wants to fund another one of these. In the meantime, I’m calling clinical equipoise and punting. Fortunately for me, I don’t have to prescribe beta-blockers. I suppose I could consider stopping them in my patient with severe COPD, the one I can’t keep out of the hospital, but I’m not convinced that would make much difference.
 

Dr. Holley is professor of medicine at Uniformed Services University in Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington, DC. He reported conflicts of interest with Metapharm, CHEST College, and WebMD.

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

Irregular sleep duration was associated with a higher risk for diabetes in middle-aged to older adults in a new UK Biobank study.

The analysis of more than 84,000 participants with 7-day accelerometry data suggested that individuals with the most irregular sleep duration patterns had a 34% higher risk for diabetes compared with their peers who had more consistent sleep patterns.

“It’s recommended to have 7-9 hours of nightly sleep, but what is not considered much in policy guidelines or at the clinical level is how regularly that’s needed,” Sina Kianersi, PhD, of Brigham and Women’s Hospital in Boston, Massachusetts, said in an interview. “What our study added is that it’s not just the duration but keeping it consistent. Patients can reduce their risk of diabetes by maintaining their 7-9 hours of sleep, not just for 1 night but throughout life.”

The study was published online in Diabetes Care.
 

Modifiable Lifestyle Factor

Researchers analyzed data from 84,421 UK Biobank participants who were free of diabetes when they provided accelerometer data in 2013-2015 and who were followed for a median of 7.5 years (622,080 person-years).

Participants had an average age of 62 years, 57% were women, 97% were White individuals, and 50% were employed in non–shift work jobs.

Sleep duration variability was quantified by the within-person standard deviation (SD) of 7-night accelerometer-measured sleep duration.

Participants with higher sleep duration SD were younger and more likely to be women, shift workers, or current smokers; those who reported definite “evening” chronotype (natural preference of the body to sleep at a certain time); those having lower socioeconomic status, higher body mass index, and shorter mean sleep duration; and were less likely to be White individuals.

In addition, a family history of diabetes and of depression was more prevalent among these participants.

A total of 2058 incident diabetes cases occurred during follow-up.

After adjustment for age, sex, and race, compared with a sleep duration SD ≤ 30 minutes, the hazard ratio (HR) was 1.15 for 31-45 minutes, 1.28 for 46-60 minutes, 1.54 for 61-90 minutes, and 1.59 for ≥ 91 minutes.

After the initial adjustment, individuals with a sleep duration SD of > 60 vs ≤ 60 minutes had a 34% higher diabetes risk. However, further adjustment for lifestyle, comorbidities, environmental factors, and adiposity attenuated the association — ie, the HR comparing sleep duration SD of > 60 vs ≤ 60 minutes was 1.11.

Furthermore, researchers found that the association between sleep duration and diabetes was stronger among individuals with lower diabetes polygenic risk score. 

“One possible explanation for this finding is that the impact of sleep irregularity on diabetes risk may be less noticeable in individuals with a high genetic predisposition, where genetic factors dominate,” Dr. Kianersi said. “However, it is important to note that these sleep-gene interaction effects were not consistently observed across different measures and gene-related variables. This is something that remains to be further studied.”

Nevertheless, he added, “I want to emphasize that the association between irregular sleep duration and increased diabetes risk was evident across all levels of diabetes polygenic risk scores.”

The association also was stronger with longer sleep duration. The authors suggested that longer sleep duration “might reduce daylight exposure, which could, in turn, give rise to circadian disruption.”

Overall, Dr. Kianersi said, “Our study identified a modifiable lifestyle factor that can help lower the risk of developing type 2 diabetes.”

The study had several limitations. There was a time lag of a median of 5 years between sleep duration measurements and covariate assessments, which might bias lifestyle behaviors that may vary over time. In addition, a single 7-day sleep duration measurement may not capture long-term sleep patterns. A constrained random sampling approach was used to select participants, raising the potential of selection bias.
 

Regular Sleep Routine Best

Ana Krieger, MD, MPH, director of the Center for Sleep Medicine at Weill Cornell Medicine in New York City, commented on the study for this news organization. “This is a very interesting study, as it adds to the literature,” she said. “Previous research studies have shown metabolic abnormalities with variations in sleep time and duration.”

“This particular study evaluated a large sample of patients in the UK which were mostly White middle-aged and may not be representative of the general population,” she noted. “A similar study in a Hispanic/Latino group failed to demonstrate any significant association between sleep timing variability and incidence of diabetes. It would be desirable to see if prospective studies are able to demonstrate a reduction in diabetes risk by implementing a more regular sleep routine.”

The importance of the body’s natural circadian rhythm in regulating and anchoring many physiological processes was highlighted by the 2017 Nobel Prize of Medicine, which was awarded to three researchers in circadian biology, she pointed out.

“Alterations in the circadian rhythm are known to affect mood regulation, gastrointestinal function, and alertness, among other factors,” she said. “Keeping a regular sleep routine will help to improve our circadian rhythm and better regulate many processes, including our metabolism and appetite-controlling hormones.”

Notably, a study published online in Diabetologia in a racially and economically diverse US population also found that adults with persistent suboptimal sleep durations (< 7 or > 9 hours nightly over a mean of 5 years) were more likely to develop incident diabetes. The strongest association was found among participants reporting extreme changes and higher variability in their sleep durations.

This study was supported by the National Institutes of Health (grant number R01HL155395) and the UKB project 85501. Dr. Kianersi was supported by the American Heart Association Postdoctoral Fellowship. Dr. Kianersi and Dr. Krieger reported no conflicts of interest.

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

Irregular sleep duration was associated with a higher risk for diabetes in middle-aged to older adults in a new UK Biobank study.

The analysis of more than 84,000 participants with 7-day accelerometry data suggested that individuals with the most irregular sleep duration patterns had a 34% higher risk for diabetes compared with their peers who had more consistent sleep patterns.

“It’s recommended to have 7-9 hours of nightly sleep, but what is not considered much in policy guidelines or at the clinical level is how regularly that’s needed,” Sina Kianersi, PhD, of Brigham and Women’s Hospital in Boston, Massachusetts, said in an interview. “What our study added is that it’s not just the duration but keeping it consistent. Patients can reduce their risk of diabetes by maintaining their 7-9 hours of sleep, not just for 1 night but throughout life.”

The study was published online in Diabetes Care.
 

Modifiable Lifestyle Factor

Researchers analyzed data from 84,421 UK Biobank participants who were free of diabetes when they provided accelerometer data in 2013-2015 and who were followed for a median of 7.5 years (622,080 person-years).

Participants had an average age of 62 years, 57% were women, 97% were White individuals, and 50% were employed in non–shift work jobs.

Sleep duration variability was quantified by the within-person standard deviation (SD) of 7-night accelerometer-measured sleep duration.

Participants with higher sleep duration SD were younger and more likely to be women, shift workers, or current smokers; those who reported definite “evening” chronotype (natural preference of the body to sleep at a certain time); those having lower socioeconomic status, higher body mass index, and shorter mean sleep duration; and were less likely to be White individuals.

In addition, a family history of diabetes and of depression was more prevalent among these participants.

A total of 2058 incident diabetes cases occurred during follow-up.

After adjustment for age, sex, and race, compared with a sleep duration SD ≤ 30 minutes, the hazard ratio (HR) was 1.15 for 31-45 minutes, 1.28 for 46-60 minutes, 1.54 for 61-90 minutes, and 1.59 for ≥ 91 minutes.

After the initial adjustment, individuals with a sleep duration SD of > 60 vs ≤ 60 minutes had a 34% higher diabetes risk. However, further adjustment for lifestyle, comorbidities, environmental factors, and adiposity attenuated the association — ie, the HR comparing sleep duration SD of > 60 vs ≤ 60 minutes was 1.11.

Furthermore, researchers found that the association between sleep duration and diabetes was stronger among individuals with lower diabetes polygenic risk score. 

“One possible explanation for this finding is that the impact of sleep irregularity on diabetes risk may be less noticeable in individuals with a high genetic predisposition, where genetic factors dominate,” Dr. Kianersi said. “However, it is important to note that these sleep-gene interaction effects were not consistently observed across different measures and gene-related variables. This is something that remains to be further studied.”

Nevertheless, he added, “I want to emphasize that the association between irregular sleep duration and increased diabetes risk was evident across all levels of diabetes polygenic risk scores.”

The association also was stronger with longer sleep duration. The authors suggested that longer sleep duration “might reduce daylight exposure, which could, in turn, give rise to circadian disruption.”

Overall, Dr. Kianersi said, “Our study identified a modifiable lifestyle factor that can help lower the risk of developing type 2 diabetes.”

The study had several limitations. There was a time lag of a median of 5 years between sleep duration measurements and covariate assessments, which might bias lifestyle behaviors that may vary over time. In addition, a single 7-day sleep duration measurement may not capture long-term sleep patterns. A constrained random sampling approach was used to select participants, raising the potential of selection bias.
 

Regular Sleep Routine Best

Ana Krieger, MD, MPH, director of the Center for Sleep Medicine at Weill Cornell Medicine in New York City, commented on the study for this news organization. “This is a very interesting study, as it adds to the literature,” she said. “Previous research studies have shown metabolic abnormalities with variations in sleep time and duration.”

“This particular study evaluated a large sample of patients in the UK which were mostly White middle-aged and may not be representative of the general population,” she noted. “A similar study in a Hispanic/Latino group failed to demonstrate any significant association between sleep timing variability and incidence of diabetes. It would be desirable to see if prospective studies are able to demonstrate a reduction in diabetes risk by implementing a more regular sleep routine.”

The importance of the body’s natural circadian rhythm in regulating and anchoring many physiological processes was highlighted by the 2017 Nobel Prize of Medicine, which was awarded to three researchers in circadian biology, she pointed out.

“Alterations in the circadian rhythm are known to affect mood regulation, gastrointestinal function, and alertness, among other factors,” she said. “Keeping a regular sleep routine will help to improve our circadian rhythm and better regulate many processes, including our metabolism and appetite-controlling hormones.”

Notably, a study published online in Diabetologia in a racially and economically diverse US population also found that adults with persistent suboptimal sleep durations (< 7 or > 9 hours nightly over a mean of 5 years) were more likely to develop incident diabetes. The strongest association was found among participants reporting extreme changes and higher variability in their sleep durations.

This study was supported by the National Institutes of Health (grant number R01HL155395) and the UKB project 85501. Dr. Kianersi was supported by the American Heart Association Postdoctoral Fellowship. Dr. Kianersi and Dr. Krieger reported no conflicts of interest.

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

Irregular sleep duration was associated with a higher risk for diabetes in middle-aged to older adults in a new UK Biobank study.

The analysis of more than 84,000 participants with 7-day accelerometry data suggested that individuals with the most irregular sleep duration patterns had a 34% higher risk for diabetes compared with their peers who had more consistent sleep patterns.

“It’s recommended to have 7-9 hours of nightly sleep, but what is not considered much in policy guidelines or at the clinical level is how regularly that’s needed,” Sina Kianersi, PhD, of Brigham and Women’s Hospital in Boston, Massachusetts, said in an interview. “What our study added is that it’s not just the duration but keeping it consistent. Patients can reduce their risk of diabetes by maintaining their 7-9 hours of sleep, not just for 1 night but throughout life.”

The study was published online in Diabetes Care.
 

Modifiable Lifestyle Factor

Researchers analyzed data from 84,421 UK Biobank participants who were free of diabetes when they provided accelerometer data in 2013-2015 and who were followed for a median of 7.5 years (622,080 person-years).

Participants had an average age of 62 years, 57% were women, 97% were White individuals, and 50% were employed in non–shift work jobs.

Sleep duration variability was quantified by the within-person standard deviation (SD) of 7-night accelerometer-measured sleep duration.

Participants with higher sleep duration SD were younger and more likely to be women, shift workers, or current smokers; those who reported definite “evening” chronotype (natural preference of the body to sleep at a certain time); those having lower socioeconomic status, higher body mass index, and shorter mean sleep duration; and were less likely to be White individuals.

In addition, a family history of diabetes and of depression was more prevalent among these participants.

A total of 2058 incident diabetes cases occurred during follow-up.

After adjustment for age, sex, and race, compared with a sleep duration SD ≤ 30 minutes, the hazard ratio (HR) was 1.15 for 31-45 minutes, 1.28 for 46-60 minutes, 1.54 for 61-90 minutes, and 1.59 for ≥ 91 minutes.

After the initial adjustment, individuals with a sleep duration SD of > 60 vs ≤ 60 minutes had a 34% higher diabetes risk. However, further adjustment for lifestyle, comorbidities, environmental factors, and adiposity attenuated the association — ie, the HR comparing sleep duration SD of > 60 vs ≤ 60 minutes was 1.11.

Furthermore, researchers found that the association between sleep duration and diabetes was stronger among individuals with lower diabetes polygenic risk score. 

“One possible explanation for this finding is that the impact of sleep irregularity on diabetes risk may be less noticeable in individuals with a high genetic predisposition, where genetic factors dominate,” Dr. Kianersi said. “However, it is important to note that these sleep-gene interaction effects were not consistently observed across different measures and gene-related variables. This is something that remains to be further studied.”

Nevertheless, he added, “I want to emphasize that the association between irregular sleep duration and increased diabetes risk was evident across all levels of diabetes polygenic risk scores.”

The association also was stronger with longer sleep duration. The authors suggested that longer sleep duration “might reduce daylight exposure, which could, in turn, give rise to circadian disruption.”

Overall, Dr. Kianersi said, “Our study identified a modifiable lifestyle factor that can help lower the risk of developing type 2 diabetes.”

The study had several limitations. There was a time lag of a median of 5 years between sleep duration measurements and covariate assessments, which might bias lifestyle behaviors that may vary over time. In addition, a single 7-day sleep duration measurement may not capture long-term sleep patterns. A constrained random sampling approach was used to select participants, raising the potential of selection bias.
 

Regular Sleep Routine Best

Ana Krieger, MD, MPH, director of the Center for Sleep Medicine at Weill Cornell Medicine in New York City, commented on the study for this news organization. “This is a very interesting study, as it adds to the literature,” she said. “Previous research studies have shown metabolic abnormalities with variations in sleep time and duration.”

“This particular study evaluated a large sample of patients in the UK which were mostly White middle-aged and may not be representative of the general population,” she noted. “A similar study in a Hispanic/Latino group failed to demonstrate any significant association between sleep timing variability and incidence of diabetes. It would be desirable to see if prospective studies are able to demonstrate a reduction in diabetes risk by implementing a more regular sleep routine.”

The importance of the body’s natural circadian rhythm in regulating and anchoring many physiological processes was highlighted by the 2017 Nobel Prize of Medicine, which was awarded to three researchers in circadian biology, she pointed out.

“Alterations in the circadian rhythm are known to affect mood regulation, gastrointestinal function, and alertness, among other factors,” she said. “Keeping a regular sleep routine will help to improve our circadian rhythm and better regulate many processes, including our metabolism and appetite-controlling hormones.”

Notably, a study published online in Diabetologia in a racially and economically diverse US population also found that adults with persistent suboptimal sleep durations (< 7 or > 9 hours nightly over a mean of 5 years) were more likely to develop incident diabetes. The strongest association was found among participants reporting extreme changes and higher variability in their sleep durations.

This study was supported by the National Institutes of Health (grant number R01HL155395) and the UKB project 85501. Dr. Kianersi was supported by the American Heart Association Postdoctoral Fellowship. Dr. Kianersi and Dr. Krieger reported no conflicts of interest.

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

Ahmad Reza Djalali, an Iranian-Swedish physician specializing in disaster medicine, has begun a hunger strike after being sentenced to death in 2017.

Last year, Iran set a grim record, leading the world in executions. The country carried out at least 853 executions, which accounted for three quarters of the officially recorded executions worldwide. The Iranian government uses the death penalty to intimidate political opponents, especially since the women’s uprising in 2022, and to exert pressure on Western states in diplomatic standoffs.

Among the thousands of political prisoners currently on death row in Tehran’s notorious Evin prison is Dr. Djalali, a 52-year-old physician.

He emigrated to Sweden in 2009 and joined the Karolinska Institutet in Stockholm, Sweden. Over the years, he became one of Europe’s leading experts in disaster medicine. His work has been cited more than 700 times in medical literature, and he played a key role in establishing the emergency and disaster research center at the University of Piedmont.

In Italy, Denmark, and Sweden, Dr. Djalali helped hospitals and healthcare professionals in preparing for earthquakes, nuclear accidents, and terrorist attacks and designed several disaster medicine training programs.
 

‘Spreading Corruption’

Despite settling in Sweden with his family, Dr. Djalali never forgot his Iranian roots. His doctoral thesis was dedicated to the victims of the 2003 Bam earthquake in Iran, which killed 23,000 people. He expressed a desire to share his knowledge with his Iranian colleagues to help people. So when he was invited to participate in a 2016 conference at the University of Tehran, he accepted without hesitation.

Unfortunately, this decision had severe consequences. On April 25, 2016, as he was concluding his trip to Iran, the researcher was arrested by intelligence agents. After being held incommunicado for several days, he was officially accused of passing confidential information to Israeli intelligence services. According to his family, this accusation was baseless. They believed he was targeted for refusing to work for Iranian intelligence services in Europe.

On October 21, 2017, Dr. Djalali was sentenced to death for “spreading corruption on Earth,” a vague charge often used by Islamic courts against those who allegedly have challenged the regime. A few days later, a video of his “confessions” was broadcast on Iranian television. These confessions were coerced; Dr. Djalali later revealed that Iranian police had threatened to harm his mother in Iran and his family in Sweden.

Since then, Dr. Djalali and his loved ones have anxiously awaited the moment when the regime might carry out the sentence. Several times over the years, he has seemed on the verge of execution, only to receive a last-minute reprieve each time.

His imprisonment has taken a severe toll on his physical and mental health. He has reportedly lost 24 kg since his incarceration, and his family, who receive sporadic updates, suspect he has leukemia. Despite his deteriorating condition, the authorities have refused him access to a hematologist.
 

‘Forgotten’ in Exchange

The international medical community has rallied to secure Dr. Djalali’s release, but their efforts have so far been fruitless. The United Nations, the European Union, Amnesty International, several universities, and the World Medical Association have called for his release. In 2018, Sweden granted him citizenship in an attempt to increase pressure on Tehran, but Iranian law does not recognize dual citizenship.

On June 16, after nearly 7 years on death row, Dr. Djalali informed his family that he had begun a hunger strike. “It’s the only way to make my voice heard in the world,” he explained. “As a doctor, Ahmad Reza knows all too well that his fragile physical state makes a hunger strike potentially fatal, but he sees no other option. He suffers from cardiac arrhythmia, bradycardia, hypotension, chronic gastritis, anemia, and extreme weight loss following his two previous hunger strikes,” his wife told the press.

Aside from a potential (and unlikely) act of clemency by the Iranian authorities, Dr. Djalali’s best hope lies in a prisoner exchange. The Iranian government often imprisons foreign nationals to exchange them for Iranians detained in Western countries.

On June 15, Sweden agreed to release an Iranian dignitary serving a life sentence in exchange for the release of Swedish nationals detained in Iran. For a long time, Dr. Djalali’s family had hoped he would be included in this exchange.

However, to avoid jeopardizing the deal, the Swedish prime minister chose to accept the release of only two other Swedish nationals, leaving Dr. Djalali to his grim fate. “Mr Prime Minister, you have decided to abandon me at the enormous risk of being executed,” Dr. Djalali responded bitterly, knowing he could be hanged at any moment.
 

This story was translated from JIM using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Ahmad Reza Djalali, an Iranian-Swedish physician specializing in disaster medicine, has begun a hunger strike after being sentenced to death in 2017.

Last year, Iran set a grim record, leading the world in executions. The country carried out at least 853 executions, which accounted for three quarters of the officially recorded executions worldwide. The Iranian government uses the death penalty to intimidate political opponents, especially since the women’s uprising in 2022, and to exert pressure on Western states in diplomatic standoffs.

Among the thousands of political prisoners currently on death row in Tehran’s notorious Evin prison is Dr. Djalali, a 52-year-old physician.

He emigrated to Sweden in 2009 and joined the Karolinska Institutet in Stockholm, Sweden. Over the years, he became one of Europe’s leading experts in disaster medicine. His work has been cited more than 700 times in medical literature, and he played a key role in establishing the emergency and disaster research center at the University of Piedmont.

In Italy, Denmark, and Sweden, Dr. Djalali helped hospitals and healthcare professionals in preparing for earthquakes, nuclear accidents, and terrorist attacks and designed several disaster medicine training programs.
 

‘Spreading Corruption’

Despite settling in Sweden with his family, Dr. Djalali never forgot his Iranian roots. His doctoral thesis was dedicated to the victims of the 2003 Bam earthquake in Iran, which killed 23,000 people. He expressed a desire to share his knowledge with his Iranian colleagues to help people. So when he was invited to participate in a 2016 conference at the University of Tehran, he accepted without hesitation.

Unfortunately, this decision had severe consequences. On April 25, 2016, as he was concluding his trip to Iran, the researcher was arrested by intelligence agents. After being held incommunicado for several days, he was officially accused of passing confidential information to Israeli intelligence services. According to his family, this accusation was baseless. They believed he was targeted for refusing to work for Iranian intelligence services in Europe.

On October 21, 2017, Dr. Djalali was sentenced to death for “spreading corruption on Earth,” a vague charge often used by Islamic courts against those who allegedly have challenged the regime. A few days later, a video of his “confessions” was broadcast on Iranian television. These confessions were coerced; Dr. Djalali later revealed that Iranian police had threatened to harm his mother in Iran and his family in Sweden.

Since then, Dr. Djalali and his loved ones have anxiously awaited the moment when the regime might carry out the sentence. Several times over the years, he has seemed on the verge of execution, only to receive a last-minute reprieve each time.

His imprisonment has taken a severe toll on his physical and mental health. He has reportedly lost 24 kg since his incarceration, and his family, who receive sporadic updates, suspect he has leukemia. Despite his deteriorating condition, the authorities have refused him access to a hematologist.
 

‘Forgotten’ in Exchange

The international medical community has rallied to secure Dr. Djalali’s release, but their efforts have so far been fruitless. The United Nations, the European Union, Amnesty International, several universities, and the World Medical Association have called for his release. In 2018, Sweden granted him citizenship in an attempt to increase pressure on Tehran, but Iranian law does not recognize dual citizenship.

On June 16, after nearly 7 years on death row, Dr. Djalali informed his family that he had begun a hunger strike. “It’s the only way to make my voice heard in the world,” he explained. “As a doctor, Ahmad Reza knows all too well that his fragile physical state makes a hunger strike potentially fatal, but he sees no other option. He suffers from cardiac arrhythmia, bradycardia, hypotension, chronic gastritis, anemia, and extreme weight loss following his two previous hunger strikes,” his wife told the press.

Aside from a potential (and unlikely) act of clemency by the Iranian authorities, Dr. Djalali’s best hope lies in a prisoner exchange. The Iranian government often imprisons foreign nationals to exchange them for Iranians detained in Western countries.

On June 15, Sweden agreed to release an Iranian dignitary serving a life sentence in exchange for the release of Swedish nationals detained in Iran. For a long time, Dr. Djalali’s family had hoped he would be included in this exchange.

However, to avoid jeopardizing the deal, the Swedish prime minister chose to accept the release of only two other Swedish nationals, leaving Dr. Djalali to his grim fate. “Mr Prime Minister, you have decided to abandon me at the enormous risk of being executed,” Dr. Djalali responded bitterly, knowing he could be hanged at any moment.
 

This story was translated from JIM using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Ahmad Reza Djalali, an Iranian-Swedish physician specializing in disaster medicine, has begun a hunger strike after being sentenced to death in 2017.

Last year, Iran set a grim record, leading the world in executions. The country carried out at least 853 executions, which accounted for three quarters of the officially recorded executions worldwide. The Iranian government uses the death penalty to intimidate political opponents, especially since the women’s uprising in 2022, and to exert pressure on Western states in diplomatic standoffs.

Among the thousands of political prisoners currently on death row in Tehran’s notorious Evin prison is Dr. Djalali, a 52-year-old physician.

He emigrated to Sweden in 2009 and joined the Karolinska Institutet in Stockholm, Sweden. Over the years, he became one of Europe’s leading experts in disaster medicine. His work has been cited more than 700 times in medical literature, and he played a key role in establishing the emergency and disaster research center at the University of Piedmont.

In Italy, Denmark, and Sweden, Dr. Djalali helped hospitals and healthcare professionals in preparing for earthquakes, nuclear accidents, and terrorist attacks and designed several disaster medicine training programs.
 

‘Spreading Corruption’

Despite settling in Sweden with his family, Dr. Djalali never forgot his Iranian roots. His doctoral thesis was dedicated to the victims of the 2003 Bam earthquake in Iran, which killed 23,000 people. He expressed a desire to share his knowledge with his Iranian colleagues to help people. So when he was invited to participate in a 2016 conference at the University of Tehran, he accepted without hesitation.

Unfortunately, this decision had severe consequences. On April 25, 2016, as he was concluding his trip to Iran, the researcher was arrested by intelligence agents. After being held incommunicado for several days, he was officially accused of passing confidential information to Israeli intelligence services. According to his family, this accusation was baseless. They believed he was targeted for refusing to work for Iranian intelligence services in Europe.

On October 21, 2017, Dr. Djalali was sentenced to death for “spreading corruption on Earth,” a vague charge often used by Islamic courts against those who allegedly have challenged the regime. A few days later, a video of his “confessions” was broadcast on Iranian television. These confessions were coerced; Dr. Djalali later revealed that Iranian police had threatened to harm his mother in Iran and his family in Sweden.

Since then, Dr. Djalali and his loved ones have anxiously awaited the moment when the regime might carry out the sentence. Several times over the years, he has seemed on the verge of execution, only to receive a last-minute reprieve each time.

His imprisonment has taken a severe toll on his physical and mental health. He has reportedly lost 24 kg since his incarceration, and his family, who receive sporadic updates, suspect he has leukemia. Despite his deteriorating condition, the authorities have refused him access to a hematologist.
 

‘Forgotten’ in Exchange

The international medical community has rallied to secure Dr. Djalali’s release, but their efforts have so far been fruitless. The United Nations, the European Union, Amnesty International, several universities, and the World Medical Association have called for his release. In 2018, Sweden granted him citizenship in an attempt to increase pressure on Tehran, but Iranian law does not recognize dual citizenship.

On June 16, after nearly 7 years on death row, Dr. Djalali informed his family that he had begun a hunger strike. “It’s the only way to make my voice heard in the world,” he explained. “As a doctor, Ahmad Reza knows all too well that his fragile physical state makes a hunger strike potentially fatal, but he sees no other option. He suffers from cardiac arrhythmia, bradycardia, hypotension, chronic gastritis, anemia, and extreme weight loss following his two previous hunger strikes,” his wife told the press.

Aside from a potential (and unlikely) act of clemency by the Iranian authorities, Dr. Djalali’s best hope lies in a prisoner exchange. The Iranian government often imprisons foreign nationals to exchange them for Iranians detained in Western countries.

On June 15, Sweden agreed to release an Iranian dignitary serving a life sentence in exchange for the release of Swedish nationals detained in Iran. For a long time, Dr. Djalali’s family had hoped he would be included in this exchange.

However, to avoid jeopardizing the deal, the Swedish prime minister chose to accept the release of only two other Swedish nationals, leaving Dr. Djalali to his grim fate. “Mr Prime Minister, you have decided to abandon me at the enormous risk of being executed,” Dr. Djalali responded bitterly, knowing he could be hanged at any moment.
 

This story was translated from JIM using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Individuals with preexisting sleep disturbances including obstructive sleep apnea (OSA), insomnia, and abnormal sleep duration showed significantly increased vulnerability to COVID-19, as well as an increased risk for hospitalization, mortality, and long COVID, according to new data from more than 8 million individuals.

Sleep disturbances, though common in the general population, are generally overlooked as a risk factor for COVID-19, wrote Jiawei Zhou, MD, of The First Hospital of China Medical University, Shenyang, China, and colleagues. Most previous research has focused on the impact of COVID-19 on sleep disturbances, not the impact of sleep disturbances on COVID-19, and most studies on the latter topic have focused only on OSA, the researchers wrote.

In a meta-analysis published in eClinicalMedicine, part of The Lancet Discovery Science, the researchers identified 48 observational studies published between October 27, 2023, and May 8, 2024, that involved COVID-19 and sleep disturbances including OSA, insomnia, abnormal sleep duration, and night shift work, among others. The study population included 8,664,026 adults.

The primary outcomes were COVID-19 susceptibility, hospitalization, mortality, and long COVID. Overall, the presence of preexisting sleep disturbances was associated with a significantly increased risk for each of these outcomes, with odds ratios (ORs) of 1.12, 1.25, 1.45, and 1.36, respectively.

In subgroup analyses, the association between preexisting sleep disturbances and greater susceptibility and hospitalization was higher in younger adults (younger than 60 years) than in older adults (aged 60 years and older), but the risk for death was lower in younger adults with sleep disturbances than in older adults with sleep disturbances (OR, 1.22 vs OR, 2.07, respectively). Men with sleep disturbances had a higher risk for COVID-19 mortality than women with sleep disturbances.

Preexisting sleep disturbances overall were significantly associated with long COVID and more so in a subgroup analysis of patients whose definition of long COVID was symptoms lasting 3 or more months vs those lasting 1 month (P = .029).

When the researchers broke down associations with COVID-19 outcomes and specific sleep disturbances, they found significant associations between OSA and all four primary outcomes. Abnormal sleep duration was associated with an increased risk for COVID-19 susceptibility, hospitalization, and long COVID. Night shift work was associated with an increased risk for COVID-19 susceptibility and hospitalization, and insomnia was associated with an increased risk for long COVID.

Although the exact mechanism behind the associations between preexisting sleep disturbances and COVID-19 outcomes is uncertain, persistent sleep deprivation could set the stage in various ways, including the promotion of elevated C-reactive protein and interleukin-6 levels, the researchers wrote.

“Overall, the compromised innate and adaptive immune functions combined with a persistent inflammatory state may explain the higher risk of susceptibility, severity, and longer recovery time observed in patients with sleep disturbances. Fortunately, early intervention for sleep disturbances could attenuate the adverse effects of COVID-19,” they noted in their discussion.

The findings were limited by several factors including the observational nature of the studies and the heterogeneity of outcomes, the researchers wrote. Looking ahead, randomized, controlled trials are needed to examine the effect of interventions for sleep disturbances in the prevention and course of COVID-19, they said.

However, the study is the first known to examine multiple types of sleep disturbances and their possible influences on the full clinical course of COVID-19 and support the need for early evaluation and intervention for individuals with sleep disturbances to reduce short-term and long-term effects of the disease, the researchers concluded.
 

Findings Reflect the Need to Address Sleep Issues Early

Although the results of the current study were not surprising, “it is always worth doing meta-analyses to see if there is a potential signal in the published data to suggest a need for a new study,” Arun Chatterjee, MD, professor of pulmonary, critical care, allergy, and immunologic diseases at Wake Forest University, Winston-Salem, North Carolina, said in an interview.

“Lack of sleep, whether acute active deprivation (zero sleep for one night) or subacute/chronic sleep debt, such as only 5 hours per night, has been demonstrated to affect lymphocyte proliferation, reduce immune globulin levels, increase inflammatory markers, shorten telomeres, and affect the immune system in various ways,” said Dr. Chatterjee, who was not involved in the meta-analysis.

The clinical takeaway from the current meta-analysis is that adequate sleep is important for various reasons, Dr. Chatterjee said. “Sleep disruption affects health across a spectrum of systems; adding an annual sleep wellness and screening event to healthcare visits is probably worth the investment,” he noted.

Much more is needed in the way of additional research, Dr. Chatterjee told this news organization. Notably, studies are needed to examine what sleep disruption does to immune status, as well as all other physiologic and mental health systems, he said.

The study was supported by the National Natural Science Foundation of China and the Key Laboratory of Respiratory Diseases of Liaoning Province. The researchers had no financial conflicts to disclose. Chatterjee had no financial conflicts to disclose.
 

A version of this article appeared on Medscape.com.

Individuals with preexisting sleep disturbances including obstructive sleep apnea (OSA), insomnia, and abnormal sleep duration showed significantly increased vulnerability to COVID-19, as well as an increased risk for hospitalization, mortality, and long COVID, according to new data from more than 8 million individuals.

Sleep disturbances, though common in the general population, are generally overlooked as a risk factor for COVID-19, wrote Jiawei Zhou, MD, of The First Hospital of China Medical University, Shenyang, China, and colleagues. Most previous research has focused on the impact of COVID-19 on sleep disturbances, not the impact of sleep disturbances on COVID-19, and most studies on the latter topic have focused only on OSA, the researchers wrote.

In a meta-analysis published in eClinicalMedicine, part of The Lancet Discovery Science, the researchers identified 48 observational studies published between October 27, 2023, and May 8, 2024, that involved COVID-19 and sleep disturbances including OSA, insomnia, abnormal sleep duration, and night shift work, among others. The study population included 8,664,026 adults.

The primary outcomes were COVID-19 susceptibility, hospitalization, mortality, and long COVID. Overall, the presence of preexisting sleep disturbances was associated with a significantly increased risk for each of these outcomes, with odds ratios (ORs) of 1.12, 1.25, 1.45, and 1.36, respectively.

In subgroup analyses, the association between preexisting sleep disturbances and greater susceptibility and hospitalization was higher in younger adults (younger than 60 years) than in older adults (aged 60 years and older), but the risk for death was lower in younger adults with sleep disturbances than in older adults with sleep disturbances (OR, 1.22 vs OR, 2.07, respectively). Men with sleep disturbances had a higher risk for COVID-19 mortality than women with sleep disturbances.

Preexisting sleep disturbances overall were significantly associated with long COVID and more so in a subgroup analysis of patients whose definition of long COVID was symptoms lasting 3 or more months vs those lasting 1 month (P = .029).

When the researchers broke down associations with COVID-19 outcomes and specific sleep disturbances, they found significant associations between OSA and all four primary outcomes. Abnormal sleep duration was associated with an increased risk for COVID-19 susceptibility, hospitalization, and long COVID. Night shift work was associated with an increased risk for COVID-19 susceptibility and hospitalization, and insomnia was associated with an increased risk for long COVID.

Although the exact mechanism behind the associations between preexisting sleep disturbances and COVID-19 outcomes is uncertain, persistent sleep deprivation could set the stage in various ways, including the promotion of elevated C-reactive protein and interleukin-6 levels, the researchers wrote.

“Overall, the compromised innate and adaptive immune functions combined with a persistent inflammatory state may explain the higher risk of susceptibility, severity, and longer recovery time observed in patients with sleep disturbances. Fortunately, early intervention for sleep disturbances could attenuate the adverse effects of COVID-19,” they noted in their discussion.

The findings were limited by several factors including the observational nature of the studies and the heterogeneity of outcomes, the researchers wrote. Looking ahead, randomized, controlled trials are needed to examine the effect of interventions for sleep disturbances in the prevention and course of COVID-19, they said.

However, the study is the first known to examine multiple types of sleep disturbances and their possible influences on the full clinical course of COVID-19 and support the need for early evaluation and intervention for individuals with sleep disturbances to reduce short-term and long-term effects of the disease, the researchers concluded.
 

Findings Reflect the Need to Address Sleep Issues Early

Although the results of the current study were not surprising, “it is always worth doing meta-analyses to see if there is a potential signal in the published data to suggest a need for a new study,” Arun Chatterjee, MD, professor of pulmonary, critical care, allergy, and immunologic diseases at Wake Forest University, Winston-Salem, North Carolina, said in an interview.

“Lack of sleep, whether acute active deprivation (zero sleep for one night) or subacute/chronic sleep debt, such as only 5 hours per night, has been demonstrated to affect lymphocyte proliferation, reduce immune globulin levels, increase inflammatory markers, shorten telomeres, and affect the immune system in various ways,” said Dr. Chatterjee, who was not involved in the meta-analysis.

The clinical takeaway from the current meta-analysis is that adequate sleep is important for various reasons, Dr. Chatterjee said. “Sleep disruption affects health across a spectrum of systems; adding an annual sleep wellness and screening event to healthcare visits is probably worth the investment,” he noted.

Much more is needed in the way of additional research, Dr. Chatterjee told this news organization. Notably, studies are needed to examine what sleep disruption does to immune status, as well as all other physiologic and mental health systems, he said.

The study was supported by the National Natural Science Foundation of China and the Key Laboratory of Respiratory Diseases of Liaoning Province. The researchers had no financial conflicts to disclose. Chatterjee had no financial conflicts to disclose.
 

A version of this article appeared on Medscape.com.

Individuals with preexisting sleep disturbances including obstructive sleep apnea (OSA), insomnia, and abnormal sleep duration showed significantly increased vulnerability to COVID-19, as well as an increased risk for hospitalization, mortality, and long COVID, according to new data from more than 8 million individuals.

Sleep disturbances, though common in the general population, are generally overlooked as a risk factor for COVID-19, wrote Jiawei Zhou, MD, of The First Hospital of China Medical University, Shenyang, China, and colleagues. Most previous research has focused on the impact of COVID-19 on sleep disturbances, not the impact of sleep disturbances on COVID-19, and most studies on the latter topic have focused only on OSA, the researchers wrote.

In a meta-analysis published in eClinicalMedicine, part of The Lancet Discovery Science, the researchers identified 48 observational studies published between October 27, 2023, and May 8, 2024, that involved COVID-19 and sleep disturbances including OSA, insomnia, abnormal sleep duration, and night shift work, among others. The study population included 8,664,026 adults.

The primary outcomes were COVID-19 susceptibility, hospitalization, mortality, and long COVID. Overall, the presence of preexisting sleep disturbances was associated with a significantly increased risk for each of these outcomes, with odds ratios (ORs) of 1.12, 1.25, 1.45, and 1.36, respectively.

In subgroup analyses, the association between preexisting sleep disturbances and greater susceptibility and hospitalization was higher in younger adults (younger than 60 years) than in older adults (aged 60 years and older), but the risk for death was lower in younger adults with sleep disturbances than in older adults with sleep disturbances (OR, 1.22 vs OR, 2.07, respectively). Men with sleep disturbances had a higher risk for COVID-19 mortality than women with sleep disturbances.

Preexisting sleep disturbances overall were significantly associated with long COVID and more so in a subgroup analysis of patients whose definition of long COVID was symptoms lasting 3 or more months vs those lasting 1 month (P = .029).

When the researchers broke down associations with COVID-19 outcomes and specific sleep disturbances, they found significant associations between OSA and all four primary outcomes. Abnormal sleep duration was associated with an increased risk for COVID-19 susceptibility, hospitalization, and long COVID. Night shift work was associated with an increased risk for COVID-19 susceptibility and hospitalization, and insomnia was associated with an increased risk for long COVID.

Although the exact mechanism behind the associations between preexisting sleep disturbances and COVID-19 outcomes is uncertain, persistent sleep deprivation could set the stage in various ways, including the promotion of elevated C-reactive protein and interleukin-6 levels, the researchers wrote.

“Overall, the compromised innate and adaptive immune functions combined with a persistent inflammatory state may explain the higher risk of susceptibility, severity, and longer recovery time observed in patients with sleep disturbances. Fortunately, early intervention for sleep disturbances could attenuate the adverse effects of COVID-19,” they noted in their discussion.

The findings were limited by several factors including the observational nature of the studies and the heterogeneity of outcomes, the researchers wrote. Looking ahead, randomized, controlled trials are needed to examine the effect of interventions for sleep disturbances in the prevention and course of COVID-19, they said.

However, the study is the first known to examine multiple types of sleep disturbances and their possible influences on the full clinical course of COVID-19 and support the need for early evaluation and intervention for individuals with sleep disturbances to reduce short-term and long-term effects of the disease, the researchers concluded.
 

Findings Reflect the Need to Address Sleep Issues Early

Although the results of the current study were not surprising, “it is always worth doing meta-analyses to see if there is a potential signal in the published data to suggest a need for a new study,” Arun Chatterjee, MD, professor of pulmonary, critical care, allergy, and immunologic diseases at Wake Forest University, Winston-Salem, North Carolina, said in an interview.

“Lack of sleep, whether acute active deprivation (zero sleep for one night) or subacute/chronic sleep debt, such as only 5 hours per night, has been demonstrated to affect lymphocyte proliferation, reduce immune globulin levels, increase inflammatory markers, shorten telomeres, and affect the immune system in various ways,” said Dr. Chatterjee, who was not involved in the meta-analysis.

The clinical takeaway from the current meta-analysis is that adequate sleep is important for various reasons, Dr. Chatterjee said. “Sleep disruption affects health across a spectrum of systems; adding an annual sleep wellness and screening event to healthcare visits is probably worth the investment,” he noted.

Much more is needed in the way of additional research, Dr. Chatterjee told this news organization. Notably, studies are needed to examine what sleep disruption does to immune status, as well as all other physiologic and mental health systems, he said.

The study was supported by the National Natural Science Foundation of China and the Key Laboratory of Respiratory Diseases of Liaoning Province. The researchers had no financial conflicts to disclose. Chatterjee had no financial conflicts to disclose.
 

A version of this article appeared on Medscape.com.

Three-quarters of oncologists participating in a recent global survey failed to identify one or more situations representing a conflict of interest, according to a new study.

The findings reflect limited awareness in low-income countries about what scenarios constitute a conflict of interest, first author, Khalid El Bairi, MD, said during an interview. “There is a lack of training in ethics and integrity in medical schools [in countries in Africa], so people are not informed about conflicts of interest,” continued Dr. El Bairi, who presented the new research at the annual meeting of the American Society of Clinical Oncology. “There is also a lack of policies in universities and hospitals to guide clinicians about conflict of interest reporting.”

Overall, 58.5% of survey participants categorized honoraria as a conflict of interest that required disclosure, while 50% said the same of gifts from pharmaceutical representatives, and 44.5% identified travel grants for attending conferences as conflicts of interests. The report was published in JCO Global Oncology. Less often considered conflicts of interest were personal and institutional research funding, trips to conferences, consulting or advisory roles, food and beverages, expert testimony, and sample drugs provided by the pharmaceutical industry.

Just 24% of participants indicated that all of the listed items were deemed conflicts of interest. The survey — called Oncology Transparency Under Scrutiny and Tracking, or ONCOTRUST-1 — considered the perceptions of 200 oncologists, about 70% of whom practice in low- and middle-income countries.

What’s more, 37.5% of respondents identified fear of losing financial support as a reason not to report a conflict of interest. Still, 75% indicated that industry-sponsored speaking does not affect treatment decisions, and 60% said conflicts of interest do not impair objective appraisal of clinical trials.

Dr. El Bairi, a research associate in the department of medical oncology at Mohammed VI University Hospital, Oujda, Morocco, and his colleagues undertook the study in part because of an editorial published in The Lancet Oncology last year. First author Fidel Rubagumya, MD, a consultant oncologist and director of research at Rwanda Military Hospital, Kigali, and colleagues called for more research on the ties between oncologists and industry in Africa. The ONCOTRUST-1 findings set the stage for a planned follow-up study, which aims to compare views surrounding conflicts of interests between oncologists in different economic settings.
 

Open Payments Houses US Physicians’ Conflicts of Interest

To be sure, many authors of research published in major US journals are based outside of the United States. According to JAMA Network Open, 69% of submissions to the journal are from international authors. However, Dr. El Bairi also raised other potential signs of industry influence that he said need global discussion, such as the role of pharmaceutical companies in presentations of clinical trial findings at large cancer societies’ conferences, a shift toward progression-free survival as the endpoint in clinical cancer trials, and the rise of third-party writing assistance.

“There are two sides of the story,” Dr. El Bairi said. “The good side is that unfortunately, sometimes [industry money is] the only way for African oncologists to go abroad for training, to conferences for their continuous medical education. The bad is now we may harm patients, we might harm science by having conflicts of interest not reported.”

Unlike other countries, the United States has plentiful data on the scale of physicians’ financial conflicts of interest in the form of the Open Payments platform. Championed by Sen. Chuck Grassley (R-Iowa), the federal repository of payments to doctors and teaching hospitals by drug and medical device companies was established as part of the Affordable Care Act (ACA).

The health care reform law, which passed in 2010, requires pharmaceutical companies and medical device makers to report this information.

From 2013 to 2021, the pharmaceutical and medical device industry paid physicians $12.1 billion, according to a research letter published in JAMA in March of 2024 that reviewed Open Payments data.

Ranked by specialty, hematologists and oncologists received the fourth-largest amount of money in aggregate, the study shows. Their total of $825.8 million trailed only physicians in orthopedics ($1.36 billion), neurology and psychiatry ($1.32 billion) and cardiology ($1.29 billion). What’s more, this specialty had the biggest share of physicians taking industry money, with 74.2% of hematologists and oncologists receiving payments.

The payments from industry include fees for consulting services and speaking, as well as food and beverages, travel and lodging, education, gifts, grants, and honoraria.

Joseph S. Ross, MD, MHS, one of the JAMA study’s coauthors, said in an interview that the continued prevalence of such funding runs counter to the expectation behind the measure, which was that transparency would lead to physicians’ becoming less likely to accept a payment.

“We as a profession need to take a cold hard look in the mirror,” he said, referring to physicians in general.

Dr. Ross, professor of medicine at Yale University School of Medicine, New Haven, Connecticut, said he hopes that the profession will self-police, and that patients will make a bigger deal of the issue. Still, he acknowledged that “the vast majority” of patient advocacy groups, too, are funded by the pharmaceutical industry.
 

Exposing Industry Payments May Have Perverse Effect

A growing body of research explores the effect that physicians’ financial relationships with pharmaceutical companies can have on their prescribing practices. Indeed, oncologists taking industry payments seem to be more likely to prescribe nonrecommended and low-value drugs in some clinical settings, according to a study published in The BMJ last year.

That study’s first author, Aaron P. Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center, New York City, suggested in an interview that exposing industry payments to the sunlight may have had a perverse effect on physicians.

“There’s this idea of having license to do something,” Dr. Mitchell said, speaking broadly about human psychology rather than drawing on empirical data. “You might feel a little less bad about then prescribing more of that company’s drug, because the disclosure has already been done.”

The influence of pharmaceutical industry money on oncologists goes beyond what’s prescribed to which treatments get studied, approved, and recommended by guidelines, Dr. Mitchell said. He was also first author of a 2016 paper published in JAMA Oncology that found 86% of authors of the National Comprehensive Cancer Network guidelines had at least one conflict of interest reported on Open Systems in 2014.

Meanwhile, the fact that physicians’ payments from industry are a matter of public record on Open Systems has not guaranteed that doctors will disclose their conflicts of interest in other forums. A study published in JAMA earlier this year, for which Dr. Mitchell served as first author, found that almost one in three physicians endorsing drugs and devices on the social media platform X failed to disclose that the manufacturer paid them.

The lack of disclosure seems to extend beyond social media. A 2018 study published in JAMA Oncology found that 32% of oncologist authors of clinical drug trials for drugs approved over a 20-month period from 2016 to 2017 did not fully disclose payments from the trial sponsor when checked against the Open Payments database.

A lion’s share of industry payments within oncology appears to be going to a small group of high-profile physicians, suggested a 2022 study published in JCO Oncology Practice. It found that just 1% of all US oncologists accounted for 37% of industry payments, with each receiving more than $100,000 a year.
 

Experts: Professional Societies Should Further Limit Industry Payments

While partnerships between drug companies and physicians are necessary and have often been positive, more than disclosure is needed to minimize the risk of patient harm, according to an editorial published in March in JCO Oncology Practice. In it, Nina Niu Sanford, MD, a radiation oncologist UT Southwestern Medical Center, Dallas, and Bishal Gyawali, MD, PhD, a medical oncologist at Queen’s University, Kingston, Ontario, Canada, argue that following a specific blueprint could help mitigate financial conflicts of interest.

For starters, Dr. Sanford and Dr. Gyawali contend in the editorial that the maximum general payment NCCN members are allowed to receive from industry should be $0, compared with a current bar of $20,000 from a single entity or $50,000 from all external entities combined. They also urge professional societies to follow the current policy of the American Society of Clinical Oncology and ban members serving in their leadership from receiving any general payments from the industry.

The authors further suggest that investigators of clinical trials should be barred from holding stock for the drug or product while it is under study and that editorialists should not have conflicts of interest with the company whose drug or product they are discussing.

Pharmaceutical money can harm patients in ways that are not always obvious, Dr. Gyawali said in an interview.

“It can dominate the conversation by removing critical viewpoints from these top people about certain drugs,” he said. “It’s not always about saying good things about the drug.”

For instance, he suggested, a doctor receiving payments from Pfizer might openly criticize perceived flaws in drugs from other companies but refrain from weighing in negatively on a Pfizer drug.

From 2016 to 2018, industry made general payments to more than 52,000 physicians for 137 unique cancer drugs, according to a separate 2021 study published in the Journal of Cancer Policy, for which Dr. Gyawali served as one of the coauthors.

The results suggest that pharmaceutical money affects the entire cancer system, not relatively few oncology leaders. The amounts and dollar values grew each year covered by the study, to nearly 466,000 payments totaling $98.5 million in 2018.

Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, Washington, DC, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices, has called for a ban on industry gifts to physicians.

When a publication asks physicians to disclose relevant conflicts of interest, physicians may choose not to disclose, because they don’t feel that their conflicts are relevant, Dr. Fugh-Berman said. Drug and device makers have also grown sophisticated about how they work with physicians, she suggested. “It’s illegal to market a drug before it comes on the market, but it’s not illegal to market the disease,” said Dr. Fugh-Berman, noting that drugmakers often work on long timelines.

“The doctor is going around saying we don’t have good therapies. They’re not pushing a drug. And so they feel totally fine about it.”

Anecdotally, Dr. Fugh-Berman noted that, if anything, speaking fees and similar payments only improve doctors’ reputations. She said that’s especially true if the physicians are paid by multiple companies, on the supposed theory that their conflicts of interest cancel each other out.

“I’m not defending this,” added Dr. Fugh-Berman, observing that, at the end of the day, such conflicts may go against the interests of patients.

“Sometimes the best drugs are older, generic, cheap drugs, and if oncologists or other specialists are only choosing among the most promoted drugs, they’re not necessarily choosing the best drugs.”

Beyond any prestige, doctors have other possible nonfinancial incentives for receiving industry payments. “It’s the relationships,” Dr. Fugh-Berman said. “Companies are very good at offering friendship.”

Dr. El Bairi reported NCODA leadership and honoraria along with expert testimony through techspert.io. Dr. Ross reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of or the review of the manuscript he authored and discussed in this article. Dr. Ross also reported receiving grants from the Food and Drug Administration, Johnson & Johnson, the Medical Device Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Mitchell reported no relevant financial relationships. Dr. Gyawali reported a consulting or advisory role with Vivio Health. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

Three-quarters of oncologists participating in a recent global survey failed to identify one or more situations representing a conflict of interest, according to a new study.

The findings reflect limited awareness in low-income countries about what scenarios constitute a conflict of interest, first author, Khalid El Bairi, MD, said during an interview. “There is a lack of training in ethics and integrity in medical schools [in countries in Africa], so people are not informed about conflicts of interest,” continued Dr. El Bairi, who presented the new research at the annual meeting of the American Society of Clinical Oncology. “There is also a lack of policies in universities and hospitals to guide clinicians about conflict of interest reporting.”

Overall, 58.5% of survey participants categorized honoraria as a conflict of interest that required disclosure, while 50% said the same of gifts from pharmaceutical representatives, and 44.5% identified travel grants for attending conferences as conflicts of interests. The report was published in JCO Global Oncology. Less often considered conflicts of interest were personal and institutional research funding, trips to conferences, consulting or advisory roles, food and beverages, expert testimony, and sample drugs provided by the pharmaceutical industry.

Just 24% of participants indicated that all of the listed items were deemed conflicts of interest. The survey — called Oncology Transparency Under Scrutiny and Tracking, or ONCOTRUST-1 — considered the perceptions of 200 oncologists, about 70% of whom practice in low- and middle-income countries.

What’s more, 37.5% of respondents identified fear of losing financial support as a reason not to report a conflict of interest. Still, 75% indicated that industry-sponsored speaking does not affect treatment decisions, and 60% said conflicts of interest do not impair objective appraisal of clinical trials.

Dr. El Bairi, a research associate in the department of medical oncology at Mohammed VI University Hospital, Oujda, Morocco, and his colleagues undertook the study in part because of an editorial published in The Lancet Oncology last year. First author Fidel Rubagumya, MD, a consultant oncologist and director of research at Rwanda Military Hospital, Kigali, and colleagues called for more research on the ties between oncologists and industry in Africa. The ONCOTRUST-1 findings set the stage for a planned follow-up study, which aims to compare views surrounding conflicts of interests between oncologists in different economic settings.
 

Open Payments Houses US Physicians’ Conflicts of Interest

To be sure, many authors of research published in major US journals are based outside of the United States. According to JAMA Network Open, 69% of submissions to the journal are from international authors. However, Dr. El Bairi also raised other potential signs of industry influence that he said need global discussion, such as the role of pharmaceutical companies in presentations of clinical trial findings at large cancer societies’ conferences, a shift toward progression-free survival as the endpoint in clinical cancer trials, and the rise of third-party writing assistance.

“There are two sides of the story,” Dr. El Bairi said. “The good side is that unfortunately, sometimes [industry money is] the only way for African oncologists to go abroad for training, to conferences for their continuous medical education. The bad is now we may harm patients, we might harm science by having conflicts of interest not reported.”

Unlike other countries, the United States has plentiful data on the scale of physicians’ financial conflicts of interest in the form of the Open Payments platform. Championed by Sen. Chuck Grassley (R-Iowa), the federal repository of payments to doctors and teaching hospitals by drug and medical device companies was established as part of the Affordable Care Act (ACA).

The health care reform law, which passed in 2010, requires pharmaceutical companies and medical device makers to report this information.

From 2013 to 2021, the pharmaceutical and medical device industry paid physicians $12.1 billion, according to a research letter published in JAMA in March of 2024 that reviewed Open Payments data.

Ranked by specialty, hematologists and oncologists received the fourth-largest amount of money in aggregate, the study shows. Their total of $825.8 million trailed only physicians in orthopedics ($1.36 billion), neurology and psychiatry ($1.32 billion) and cardiology ($1.29 billion). What’s more, this specialty had the biggest share of physicians taking industry money, with 74.2% of hematologists and oncologists receiving payments.

The payments from industry include fees for consulting services and speaking, as well as food and beverages, travel and lodging, education, gifts, grants, and honoraria.

Joseph S. Ross, MD, MHS, one of the JAMA study’s coauthors, said in an interview that the continued prevalence of such funding runs counter to the expectation behind the measure, which was that transparency would lead to physicians’ becoming less likely to accept a payment.

“We as a profession need to take a cold hard look in the mirror,” he said, referring to physicians in general.

Dr. Ross, professor of medicine at Yale University School of Medicine, New Haven, Connecticut, said he hopes that the profession will self-police, and that patients will make a bigger deal of the issue. Still, he acknowledged that “the vast majority” of patient advocacy groups, too, are funded by the pharmaceutical industry.
 

Exposing Industry Payments May Have Perverse Effect

A growing body of research explores the effect that physicians’ financial relationships with pharmaceutical companies can have on their prescribing practices. Indeed, oncologists taking industry payments seem to be more likely to prescribe nonrecommended and low-value drugs in some clinical settings, according to a study published in The BMJ last year.

That study’s first author, Aaron P. Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center, New York City, suggested in an interview that exposing industry payments to the sunlight may have had a perverse effect on physicians.

“There’s this idea of having license to do something,” Dr. Mitchell said, speaking broadly about human psychology rather than drawing on empirical data. “You might feel a little less bad about then prescribing more of that company’s drug, because the disclosure has already been done.”

The influence of pharmaceutical industry money on oncologists goes beyond what’s prescribed to which treatments get studied, approved, and recommended by guidelines, Dr. Mitchell said. He was also first author of a 2016 paper published in JAMA Oncology that found 86% of authors of the National Comprehensive Cancer Network guidelines had at least one conflict of interest reported on Open Systems in 2014.

Meanwhile, the fact that physicians’ payments from industry are a matter of public record on Open Systems has not guaranteed that doctors will disclose their conflicts of interest in other forums. A study published in JAMA earlier this year, for which Dr. Mitchell served as first author, found that almost one in three physicians endorsing drugs and devices on the social media platform X failed to disclose that the manufacturer paid them.

The lack of disclosure seems to extend beyond social media. A 2018 study published in JAMA Oncology found that 32% of oncologist authors of clinical drug trials for drugs approved over a 20-month period from 2016 to 2017 did not fully disclose payments from the trial sponsor when checked against the Open Payments database.

A lion’s share of industry payments within oncology appears to be going to a small group of high-profile physicians, suggested a 2022 study published in JCO Oncology Practice. It found that just 1% of all US oncologists accounted for 37% of industry payments, with each receiving more than $100,000 a year.
 

Experts: Professional Societies Should Further Limit Industry Payments

While partnerships between drug companies and physicians are necessary and have often been positive, more than disclosure is needed to minimize the risk of patient harm, according to an editorial published in March in JCO Oncology Practice. In it, Nina Niu Sanford, MD, a radiation oncologist UT Southwestern Medical Center, Dallas, and Bishal Gyawali, MD, PhD, a medical oncologist at Queen’s University, Kingston, Ontario, Canada, argue that following a specific blueprint could help mitigate financial conflicts of interest.

For starters, Dr. Sanford and Dr. Gyawali contend in the editorial that the maximum general payment NCCN members are allowed to receive from industry should be $0, compared with a current bar of $20,000 from a single entity or $50,000 from all external entities combined. They also urge professional societies to follow the current policy of the American Society of Clinical Oncology and ban members serving in their leadership from receiving any general payments from the industry.

The authors further suggest that investigators of clinical trials should be barred from holding stock for the drug or product while it is under study and that editorialists should not have conflicts of interest with the company whose drug or product they are discussing.

Pharmaceutical money can harm patients in ways that are not always obvious, Dr. Gyawali said in an interview.

“It can dominate the conversation by removing critical viewpoints from these top people about certain drugs,” he said. “It’s not always about saying good things about the drug.”

For instance, he suggested, a doctor receiving payments from Pfizer might openly criticize perceived flaws in drugs from other companies but refrain from weighing in negatively on a Pfizer drug.

From 2016 to 2018, industry made general payments to more than 52,000 physicians for 137 unique cancer drugs, according to a separate 2021 study published in the Journal of Cancer Policy, for which Dr. Gyawali served as one of the coauthors.

The results suggest that pharmaceutical money affects the entire cancer system, not relatively few oncology leaders. The amounts and dollar values grew each year covered by the study, to nearly 466,000 payments totaling $98.5 million in 2018.

Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, Washington, DC, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices, has called for a ban on industry gifts to physicians.

When a publication asks physicians to disclose relevant conflicts of interest, physicians may choose not to disclose, because they don’t feel that their conflicts are relevant, Dr. Fugh-Berman said. Drug and device makers have also grown sophisticated about how they work with physicians, she suggested. “It’s illegal to market a drug before it comes on the market, but it’s not illegal to market the disease,” said Dr. Fugh-Berman, noting that drugmakers often work on long timelines.

“The doctor is going around saying we don’t have good therapies. They’re not pushing a drug. And so they feel totally fine about it.”

Anecdotally, Dr. Fugh-Berman noted that, if anything, speaking fees and similar payments only improve doctors’ reputations. She said that’s especially true if the physicians are paid by multiple companies, on the supposed theory that their conflicts of interest cancel each other out.

“I’m not defending this,” added Dr. Fugh-Berman, observing that, at the end of the day, such conflicts may go against the interests of patients.

“Sometimes the best drugs are older, generic, cheap drugs, and if oncologists or other specialists are only choosing among the most promoted drugs, they’re not necessarily choosing the best drugs.”

Beyond any prestige, doctors have other possible nonfinancial incentives for receiving industry payments. “It’s the relationships,” Dr. Fugh-Berman said. “Companies are very good at offering friendship.”

Dr. El Bairi reported NCODA leadership and honoraria along with expert testimony through techspert.io. Dr. Ross reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of or the review of the manuscript he authored and discussed in this article. Dr. Ross also reported receiving grants from the Food and Drug Administration, Johnson & Johnson, the Medical Device Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Mitchell reported no relevant financial relationships. Dr. Gyawali reported a consulting or advisory role with Vivio Health. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

Three-quarters of oncologists participating in a recent global survey failed to identify one or more situations representing a conflict of interest, according to a new study.

The findings reflect limited awareness in low-income countries about what scenarios constitute a conflict of interest, first author, Khalid El Bairi, MD, said during an interview. “There is a lack of training in ethics and integrity in medical schools [in countries in Africa], so people are not informed about conflicts of interest,” continued Dr. El Bairi, who presented the new research at the annual meeting of the American Society of Clinical Oncology. “There is also a lack of policies in universities and hospitals to guide clinicians about conflict of interest reporting.”

Overall, 58.5% of survey participants categorized honoraria as a conflict of interest that required disclosure, while 50% said the same of gifts from pharmaceutical representatives, and 44.5% identified travel grants for attending conferences as conflicts of interests. The report was published in JCO Global Oncology. Less often considered conflicts of interest were personal and institutional research funding, trips to conferences, consulting or advisory roles, food and beverages, expert testimony, and sample drugs provided by the pharmaceutical industry.

Just 24% of participants indicated that all of the listed items were deemed conflicts of interest. The survey — called Oncology Transparency Under Scrutiny and Tracking, or ONCOTRUST-1 — considered the perceptions of 200 oncologists, about 70% of whom practice in low- and middle-income countries.

What’s more, 37.5% of respondents identified fear of losing financial support as a reason not to report a conflict of interest. Still, 75% indicated that industry-sponsored speaking does not affect treatment decisions, and 60% said conflicts of interest do not impair objective appraisal of clinical trials.

Dr. El Bairi, a research associate in the department of medical oncology at Mohammed VI University Hospital, Oujda, Morocco, and his colleagues undertook the study in part because of an editorial published in The Lancet Oncology last year. First author Fidel Rubagumya, MD, a consultant oncologist and director of research at Rwanda Military Hospital, Kigali, and colleagues called for more research on the ties between oncologists and industry in Africa. The ONCOTRUST-1 findings set the stage for a planned follow-up study, which aims to compare views surrounding conflicts of interests between oncologists in different economic settings.
 

Open Payments Houses US Physicians’ Conflicts of Interest

To be sure, many authors of research published in major US journals are based outside of the United States. According to JAMA Network Open, 69% of submissions to the journal are from international authors. However, Dr. El Bairi also raised other potential signs of industry influence that he said need global discussion, such as the role of pharmaceutical companies in presentations of clinical trial findings at large cancer societies’ conferences, a shift toward progression-free survival as the endpoint in clinical cancer trials, and the rise of third-party writing assistance.

“There are two sides of the story,” Dr. El Bairi said. “The good side is that unfortunately, sometimes [industry money is] the only way for African oncologists to go abroad for training, to conferences for their continuous medical education. The bad is now we may harm patients, we might harm science by having conflicts of interest not reported.”

Unlike other countries, the United States has plentiful data on the scale of physicians’ financial conflicts of interest in the form of the Open Payments platform. Championed by Sen. Chuck Grassley (R-Iowa), the federal repository of payments to doctors and teaching hospitals by drug and medical device companies was established as part of the Affordable Care Act (ACA).

The health care reform law, which passed in 2010, requires pharmaceutical companies and medical device makers to report this information.

From 2013 to 2021, the pharmaceutical and medical device industry paid physicians $12.1 billion, according to a research letter published in JAMA in March of 2024 that reviewed Open Payments data.

Ranked by specialty, hematologists and oncologists received the fourth-largest amount of money in aggregate, the study shows. Their total of $825.8 million trailed only physicians in orthopedics ($1.36 billion), neurology and psychiatry ($1.32 billion) and cardiology ($1.29 billion). What’s more, this specialty had the biggest share of physicians taking industry money, with 74.2% of hematologists and oncologists receiving payments.

The payments from industry include fees for consulting services and speaking, as well as food and beverages, travel and lodging, education, gifts, grants, and honoraria.

Joseph S. Ross, MD, MHS, one of the JAMA study’s coauthors, said in an interview that the continued prevalence of such funding runs counter to the expectation behind the measure, which was that transparency would lead to physicians’ becoming less likely to accept a payment.

“We as a profession need to take a cold hard look in the mirror,” he said, referring to physicians in general.

Dr. Ross, professor of medicine at Yale University School of Medicine, New Haven, Connecticut, said he hopes that the profession will self-police, and that patients will make a bigger deal of the issue. Still, he acknowledged that “the vast majority” of patient advocacy groups, too, are funded by the pharmaceutical industry.
 

Exposing Industry Payments May Have Perverse Effect

A growing body of research explores the effect that physicians’ financial relationships with pharmaceutical companies can have on their prescribing practices. Indeed, oncologists taking industry payments seem to be more likely to prescribe nonrecommended and low-value drugs in some clinical settings, according to a study published in The BMJ last year.

That study’s first author, Aaron P. Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center, New York City, suggested in an interview that exposing industry payments to the sunlight may have had a perverse effect on physicians.

“There’s this idea of having license to do something,” Dr. Mitchell said, speaking broadly about human psychology rather than drawing on empirical data. “You might feel a little less bad about then prescribing more of that company’s drug, because the disclosure has already been done.”

The influence of pharmaceutical industry money on oncologists goes beyond what’s prescribed to which treatments get studied, approved, and recommended by guidelines, Dr. Mitchell said. He was also first author of a 2016 paper published in JAMA Oncology that found 86% of authors of the National Comprehensive Cancer Network guidelines had at least one conflict of interest reported on Open Systems in 2014.

Meanwhile, the fact that physicians’ payments from industry are a matter of public record on Open Systems has not guaranteed that doctors will disclose their conflicts of interest in other forums. A study published in JAMA earlier this year, for which Dr. Mitchell served as first author, found that almost one in three physicians endorsing drugs and devices on the social media platform X failed to disclose that the manufacturer paid them.

The lack of disclosure seems to extend beyond social media. A 2018 study published in JAMA Oncology found that 32% of oncologist authors of clinical drug trials for drugs approved over a 20-month period from 2016 to 2017 did not fully disclose payments from the trial sponsor when checked against the Open Payments database.

A lion’s share of industry payments within oncology appears to be going to a small group of high-profile physicians, suggested a 2022 study published in JCO Oncology Practice. It found that just 1% of all US oncologists accounted for 37% of industry payments, with each receiving more than $100,000 a year.
 

Experts: Professional Societies Should Further Limit Industry Payments

While partnerships between drug companies and physicians are necessary and have often been positive, more than disclosure is needed to minimize the risk of patient harm, according to an editorial published in March in JCO Oncology Practice. In it, Nina Niu Sanford, MD, a radiation oncologist UT Southwestern Medical Center, Dallas, and Bishal Gyawali, MD, PhD, a medical oncologist at Queen’s University, Kingston, Ontario, Canada, argue that following a specific blueprint could help mitigate financial conflicts of interest.

For starters, Dr. Sanford and Dr. Gyawali contend in the editorial that the maximum general payment NCCN members are allowed to receive from industry should be $0, compared with a current bar of $20,000 from a single entity or $50,000 from all external entities combined. They also urge professional societies to follow the current policy of the American Society of Clinical Oncology and ban members serving in their leadership from receiving any general payments from the industry.

The authors further suggest that investigators of clinical trials should be barred from holding stock for the drug or product while it is under study and that editorialists should not have conflicts of interest with the company whose drug or product they are discussing.

Pharmaceutical money can harm patients in ways that are not always obvious, Dr. Gyawali said in an interview.

“It can dominate the conversation by removing critical viewpoints from these top people about certain drugs,” he said. “It’s not always about saying good things about the drug.”

For instance, he suggested, a doctor receiving payments from Pfizer might openly criticize perceived flaws in drugs from other companies but refrain from weighing in negatively on a Pfizer drug.

From 2016 to 2018, industry made general payments to more than 52,000 physicians for 137 unique cancer drugs, according to a separate 2021 study published in the Journal of Cancer Policy, for which Dr. Gyawali served as one of the coauthors.

The results suggest that pharmaceutical money affects the entire cancer system, not relatively few oncology leaders. The amounts and dollar values grew each year covered by the study, to nearly 466,000 payments totaling $98.5 million in 2018.

Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, Washington, DC, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices, has called for a ban on industry gifts to physicians.

When a publication asks physicians to disclose relevant conflicts of interest, physicians may choose not to disclose, because they don’t feel that their conflicts are relevant, Dr. Fugh-Berman said. Drug and device makers have also grown sophisticated about how they work with physicians, she suggested. “It’s illegal to market a drug before it comes on the market, but it’s not illegal to market the disease,” said Dr. Fugh-Berman, noting that drugmakers often work on long timelines.

“The doctor is going around saying we don’t have good therapies. They’re not pushing a drug. And so they feel totally fine about it.”

Anecdotally, Dr. Fugh-Berman noted that, if anything, speaking fees and similar payments only improve doctors’ reputations. She said that’s especially true if the physicians are paid by multiple companies, on the supposed theory that their conflicts of interest cancel each other out.

“I’m not defending this,” added Dr. Fugh-Berman, observing that, at the end of the day, such conflicts may go against the interests of patients.

“Sometimes the best drugs are older, generic, cheap drugs, and if oncologists or other specialists are only choosing among the most promoted drugs, they’re not necessarily choosing the best drugs.”

Beyond any prestige, doctors have other possible nonfinancial incentives for receiving industry payments. “It’s the relationships,” Dr. Fugh-Berman said. “Companies are very good at offering friendship.”

Dr. El Bairi reported NCODA leadership and honoraria along with expert testimony through techspert.io. Dr. Ross reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of or the review of the manuscript he authored and discussed in this article. Dr. Ross also reported receiving grants from the Food and Drug Administration, Johnson & Johnson, the Medical Device Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Mitchell reported no relevant financial relationships. Dr. Gyawali reported a consulting or advisory role with Vivio Health. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.