MDedge Endocrinology

If a patient refuses care from a health care practitioner because of their race or sex, should their request be accommodated?

In a recent blog on Medscape titled “No, You Can’t See a Different Doctor: We Need Zero Tolerance of Patient Bias,” Cleveland Francis Jr., MD, argued no.

Dr. Francis, who is Black, is a recently retired cardiologist who practiced for 50 years. He is currently Diversity, Equity, and Inclusion Advisor at Inova Heart and Vascular Institute in Falls Church, Va.

When Francis was a medical student and was preparing to take a patient’s history and perform a medical exam, the patient refused and requested a “White doctor,” he recounted.

“I can remember the hurt and embarrassment as if it were yesterday,” he wrote.

The blog, especially the title, drew strong reactions. Close to 500 readers weighed in.

“The title of my blog sounds harsh,” Dr. Francis said, “but in reality, a simple conversation with the patient usually resolves these issues. The difference is that in the old days, there was utter silence, and the wishes of the patient would be granted”

Health care practitioners “should expect to be treated with respect,” he concluded his blog.

Readers agreed on that point, but they debated whether being uncomfortable with a health care practitioner of a different sex or race always constituted “patient bias.”

Some noted that difficulty understanding a practitioner’s accent, for example, is a legitimate reason for asking for another clinician.
 

Accents and understanding

“If I am struggling to understand you because your accent is too thick or ... because hearing aids can only do so much, I need to ask for someone else,” a reader commented.

Another chimed in: “My elderly parents changed PCPs frequently during the final years of their lives, mainly due to language barriers encountered with foreign-born providers. Due to progressive hearing loss, they simply couldn’t understand them.”

“It is important to remember that there is a Patient Bill of Rights,” she noted, “the first part of which states, ‘You have the right to safe, considerate, and respectful care, provided in a manner consistent with your beliefs.’ ”

A former charge nurse added: “If a request for change was substantive (poor communication, perceived incompetence, trauma history, etc.), I would move mountains to accommodate it, but IMHO [in my humble opinion], the belief in honoring patient preference doesn’t necessarily need to include rearranging the world in order to accommodate racism, sexism, etc.”

Bias against female doctors, male nurses

Many commenters described how they gladly traded when a patient requested a practitioner of the opposite sex.

A female hospitalist related how she contacted the senior male doctor working with her to arrange a patient trade, adding, “I do agree that racial discrimination ought to be discouraged.”

Similarly, a male ICU RN commented: “Over 13 years, I have had a handful of female (usually older) patients request a female nurse. I have always strived to make this happen.”

However, an older woman related how at first she “had some bias against a male nurse touching me and also felt self-conscious,” she said. “So, I tried to relax ... and let him do his job. He was one of the most compassionate, kind, and sensitive nurses I’ve ever had.”

“I think in some cases,” she noted, “some women have had a history of some sort of abuse by a male, whether it’s sexual or psychological,” but in other cases, “it’s often just a personal preference, not a bias.”

A physician assistant (PA) who worked in a rural ED recounted how “there was only one physician and one PA on at any given evening/night shift, both usually White males.”

“Sometimes, you just have to cope as best you can with whomever is available, and in doing so,” he said, “they might just end up being pleasantly surprised.”
 

Don’t take it personally, move on

“If a patient doesn’t want to see me for whatever reason, then I would rather not treat them,” was a common sentiment.

Patients “should feel comfortable with their provider even if it’s with someone other than myself,” a reader wrote.

A female physician chimed in: “I frequently have older male patients refuse to see me. ... While this is irritating on several levels, I recognize that it is the patient’s choice, sigh, and move on to the next patient.”

“There are many more patients who specifically ask to see me, so I don’t waste my time and energy on being bothered by those who refuse.”

Similarly, a female mental health provider and sometimes patient wrote: “If any patient tells me that they prefer a male ... or someone of a particular race or religion or whatever, I don’t take it personally.”

A female Hispanic doctor chimed in: “Honestly, if a patient does not want to see me due to my race, I’m OK with that. Patients need to feel comfortable with me for the relationship to be therapeutic and effective,” she said.

“Forcing the patient to see me is adding injury to insult to ME! Not to mention increase[d] workload since that patient will take [so] much more time.”

Similarly, an Asian American doctor commented: “There are people who choose not to see me because of my ethnicity. However, I strongly believe that it should always be the patient’s preference. Whatever the reason, do not force the patient to see you in the name of Diversity, Equity, Inclusion, or whatever hurts your feeling. Let the patient go.”
 

Patient bias vs. patient preference

A physician referring to Dr. Francis’s experience suggested that “perhaps there was an opportunity to explore this misconception directly with the patient. If not, your supervising senior resident or attending should have been informed and brought into the process and conversation.”

“If/when I were rejected by a patient for whatever reason,” another physician commented, “I would gracefully accede, and hope that my colleague would tactfully point out to the patient their error.”

“Having a nurse ask the patient ... what they need style-wise (keeping race, gender, etc., out of it) might help identify whether or not the underlying issue(s) are based on style/needs mismatch match rather than bias,” a reader suggested.

A health care worker commented: “We generally assure patients that we are professionals and think nothing of situations that they might find uncomfortable, but don’t realize that our comfort does not translate to theirs.”
 

Maybe a different strategy is needed

“Having been the target of bias many times,” a reader said, “I understand the pain that is inflicted. Unfortunately, a patient bias policy, while a good idea, will not prevent patient bias. This is a much larger societal problem. But we can at least tell patients that it is not okay. On the other hand, I would not want to be the provider for a patient who was biased against me and held me in disdain.”

“I do not like Zero Tolerance policies ever. They are too absolute,” another reader commented. “Sometimes, there are reasons and we do have to listen to our patients for why. ... I do not think a policy of zero tolerance will fix the problem of racism.”

“Instead of trying to educate the general public about how not to be jerks,” another reader suggested, “perhaps it would be easier to provide elective classes for doctors and employees who believe themselves to be at-risk for discrimination, providing them with a ‘toolkit’ of strategies for responding to discrimination in the moment, processing it emotionally later on, and reporting the most egregious events through designated channels.”

Another commenter agreed and wrote that, “While we as doctors need and deserve protection, we are also called to act with compassion. So, rather than ask the system for ‘zero-tolerance’ in either direction, we could encourage our health systems to provide education, support, and mediation to any party who feels or fears that they are not being well served. Such a model would include support for physicians who have been the victims of bias and hurt.”

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

If a patient refuses care from a health care practitioner because of their race or sex, should their request be accommodated?

In a recent blog on Medscape titled “No, You Can’t See a Different Doctor: We Need Zero Tolerance of Patient Bias,” Cleveland Francis Jr., MD, argued no.

Dr. Francis, who is Black, is a recently retired cardiologist who practiced for 50 years. He is currently Diversity, Equity, and Inclusion Advisor at Inova Heart and Vascular Institute in Falls Church, Va.

When Francis was a medical student and was preparing to take a patient’s history and perform a medical exam, the patient refused and requested a “White doctor,” he recounted.

“I can remember the hurt and embarrassment as if it were yesterday,” he wrote.

The blog, especially the title, drew strong reactions. Close to 500 readers weighed in.

“The title of my blog sounds harsh,” Dr. Francis said, “but in reality, a simple conversation with the patient usually resolves these issues. The difference is that in the old days, there was utter silence, and the wishes of the patient would be granted”

Health care practitioners “should expect to be treated with respect,” he concluded his blog.

Readers agreed on that point, but they debated whether being uncomfortable with a health care practitioner of a different sex or race always constituted “patient bias.”

Some noted that difficulty understanding a practitioner’s accent, for example, is a legitimate reason for asking for another clinician.
 

Accents and understanding

“If I am struggling to understand you because your accent is too thick or ... because hearing aids can only do so much, I need to ask for someone else,” a reader commented.

Another chimed in: “My elderly parents changed PCPs frequently during the final years of their lives, mainly due to language barriers encountered with foreign-born providers. Due to progressive hearing loss, they simply couldn’t understand them.”

“It is important to remember that there is a Patient Bill of Rights,” she noted, “the first part of which states, ‘You have the right to safe, considerate, and respectful care, provided in a manner consistent with your beliefs.’ ”

A former charge nurse added: “If a request for change was substantive (poor communication, perceived incompetence, trauma history, etc.), I would move mountains to accommodate it, but IMHO [in my humble opinion], the belief in honoring patient preference doesn’t necessarily need to include rearranging the world in order to accommodate racism, sexism, etc.”

Bias against female doctors, male nurses

Many commenters described how they gladly traded when a patient requested a practitioner of the opposite sex.

A female hospitalist related how she contacted the senior male doctor working with her to arrange a patient trade, adding, “I do agree that racial discrimination ought to be discouraged.”

Similarly, a male ICU RN commented: “Over 13 years, I have had a handful of female (usually older) patients request a female nurse. I have always strived to make this happen.”

However, an older woman related how at first she “had some bias against a male nurse touching me and also felt self-conscious,” she said. “So, I tried to relax ... and let him do his job. He was one of the most compassionate, kind, and sensitive nurses I’ve ever had.”

“I think in some cases,” she noted, “some women have had a history of some sort of abuse by a male, whether it’s sexual or psychological,” but in other cases, “it’s often just a personal preference, not a bias.”

A physician assistant (PA) who worked in a rural ED recounted how “there was only one physician and one PA on at any given evening/night shift, both usually White males.”

“Sometimes, you just have to cope as best you can with whomever is available, and in doing so,” he said, “they might just end up being pleasantly surprised.”
 

Don’t take it personally, move on

“If a patient doesn’t want to see me for whatever reason, then I would rather not treat them,” was a common sentiment.

Patients “should feel comfortable with their provider even if it’s with someone other than myself,” a reader wrote.

A female physician chimed in: “I frequently have older male patients refuse to see me. ... While this is irritating on several levels, I recognize that it is the patient’s choice, sigh, and move on to the next patient.”

“There are many more patients who specifically ask to see me, so I don’t waste my time and energy on being bothered by those who refuse.”

Similarly, a female mental health provider and sometimes patient wrote: “If any patient tells me that they prefer a male ... or someone of a particular race or religion or whatever, I don’t take it personally.”

A female Hispanic doctor chimed in: “Honestly, if a patient does not want to see me due to my race, I’m OK with that. Patients need to feel comfortable with me for the relationship to be therapeutic and effective,” she said.

“Forcing the patient to see me is adding injury to insult to ME! Not to mention increase[d] workload since that patient will take [so] much more time.”

Similarly, an Asian American doctor commented: “There are people who choose not to see me because of my ethnicity. However, I strongly believe that it should always be the patient’s preference. Whatever the reason, do not force the patient to see you in the name of Diversity, Equity, Inclusion, or whatever hurts your feeling. Let the patient go.”
 

Patient bias vs. patient preference

A physician referring to Dr. Francis’s experience suggested that “perhaps there was an opportunity to explore this misconception directly with the patient. If not, your supervising senior resident or attending should have been informed and brought into the process and conversation.”

“If/when I were rejected by a patient for whatever reason,” another physician commented, “I would gracefully accede, and hope that my colleague would tactfully point out to the patient their error.”

“Having a nurse ask the patient ... what they need style-wise (keeping race, gender, etc., out of it) might help identify whether or not the underlying issue(s) are based on style/needs mismatch match rather than bias,” a reader suggested.

A health care worker commented: “We generally assure patients that we are professionals and think nothing of situations that they might find uncomfortable, but don’t realize that our comfort does not translate to theirs.”
 

Maybe a different strategy is needed

“Having been the target of bias many times,” a reader said, “I understand the pain that is inflicted. Unfortunately, a patient bias policy, while a good idea, will not prevent patient bias. This is a much larger societal problem. But we can at least tell patients that it is not okay. On the other hand, I would not want to be the provider for a patient who was biased against me and held me in disdain.”

“I do not like Zero Tolerance policies ever. They are too absolute,” another reader commented. “Sometimes, there are reasons and we do have to listen to our patients for why. ... I do not think a policy of zero tolerance will fix the problem of racism.”

“Instead of trying to educate the general public about how not to be jerks,” another reader suggested, “perhaps it would be easier to provide elective classes for doctors and employees who believe themselves to be at-risk for discrimination, providing them with a ‘toolkit’ of strategies for responding to discrimination in the moment, processing it emotionally later on, and reporting the most egregious events through designated channels.”

Another commenter agreed and wrote that, “While we as doctors need and deserve protection, we are also called to act with compassion. So, rather than ask the system for ‘zero-tolerance’ in either direction, we could encourage our health systems to provide education, support, and mediation to any party who feels or fears that they are not being well served. Such a model would include support for physicians who have been the victims of bias and hurt.”

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

If a patient refuses care from a health care practitioner because of their race or sex, should their request be accommodated?

In a recent blog on Medscape titled “No, You Can’t See a Different Doctor: We Need Zero Tolerance of Patient Bias,” Cleveland Francis Jr., MD, argued no.

Dr. Francis, who is Black, is a recently retired cardiologist who practiced for 50 years. He is currently Diversity, Equity, and Inclusion Advisor at Inova Heart and Vascular Institute in Falls Church, Va.

When Francis was a medical student and was preparing to take a patient’s history and perform a medical exam, the patient refused and requested a “White doctor,” he recounted.

“I can remember the hurt and embarrassment as if it were yesterday,” he wrote.

The blog, especially the title, drew strong reactions. Close to 500 readers weighed in.

“The title of my blog sounds harsh,” Dr. Francis said, “but in reality, a simple conversation with the patient usually resolves these issues. The difference is that in the old days, there was utter silence, and the wishes of the patient would be granted”

Health care practitioners “should expect to be treated with respect,” he concluded his blog.

Readers agreed on that point, but they debated whether being uncomfortable with a health care practitioner of a different sex or race always constituted “patient bias.”

Some noted that difficulty understanding a practitioner’s accent, for example, is a legitimate reason for asking for another clinician.
 

Accents and understanding

“If I am struggling to understand you because your accent is too thick or ... because hearing aids can only do so much, I need to ask for someone else,” a reader commented.

Another chimed in: “My elderly parents changed PCPs frequently during the final years of their lives, mainly due to language barriers encountered with foreign-born providers. Due to progressive hearing loss, they simply couldn’t understand them.”

“It is important to remember that there is a Patient Bill of Rights,” she noted, “the first part of which states, ‘You have the right to safe, considerate, and respectful care, provided in a manner consistent with your beliefs.’ ”

A former charge nurse added: “If a request for change was substantive (poor communication, perceived incompetence, trauma history, etc.), I would move mountains to accommodate it, but IMHO [in my humble opinion], the belief in honoring patient preference doesn’t necessarily need to include rearranging the world in order to accommodate racism, sexism, etc.”

Bias against female doctors, male nurses

Many commenters described how they gladly traded when a patient requested a practitioner of the opposite sex.

A female hospitalist related how she contacted the senior male doctor working with her to arrange a patient trade, adding, “I do agree that racial discrimination ought to be discouraged.”

Similarly, a male ICU RN commented: “Over 13 years, I have had a handful of female (usually older) patients request a female nurse. I have always strived to make this happen.”

However, an older woman related how at first she “had some bias against a male nurse touching me and also felt self-conscious,” she said. “So, I tried to relax ... and let him do his job. He was one of the most compassionate, kind, and sensitive nurses I’ve ever had.”

“I think in some cases,” she noted, “some women have had a history of some sort of abuse by a male, whether it’s sexual or psychological,” but in other cases, “it’s often just a personal preference, not a bias.”

A physician assistant (PA) who worked in a rural ED recounted how “there was only one physician and one PA on at any given evening/night shift, both usually White males.”

“Sometimes, you just have to cope as best you can with whomever is available, and in doing so,” he said, “they might just end up being pleasantly surprised.”
 

Don’t take it personally, move on

“If a patient doesn’t want to see me for whatever reason, then I would rather not treat them,” was a common sentiment.

Patients “should feel comfortable with their provider even if it’s with someone other than myself,” a reader wrote.

A female physician chimed in: “I frequently have older male patients refuse to see me. ... While this is irritating on several levels, I recognize that it is the patient’s choice, sigh, and move on to the next patient.”

“There are many more patients who specifically ask to see me, so I don’t waste my time and energy on being bothered by those who refuse.”

Similarly, a female mental health provider and sometimes patient wrote: “If any patient tells me that they prefer a male ... or someone of a particular race or religion or whatever, I don’t take it personally.”

A female Hispanic doctor chimed in: “Honestly, if a patient does not want to see me due to my race, I’m OK with that. Patients need to feel comfortable with me for the relationship to be therapeutic and effective,” she said.

“Forcing the patient to see me is adding injury to insult to ME! Not to mention increase[d] workload since that patient will take [so] much more time.”

Similarly, an Asian American doctor commented: “There are people who choose not to see me because of my ethnicity. However, I strongly believe that it should always be the patient’s preference. Whatever the reason, do not force the patient to see you in the name of Diversity, Equity, Inclusion, or whatever hurts your feeling. Let the patient go.”
 

Patient bias vs. patient preference

A physician referring to Dr. Francis’s experience suggested that “perhaps there was an opportunity to explore this misconception directly with the patient. If not, your supervising senior resident or attending should have been informed and brought into the process and conversation.”

“If/when I were rejected by a patient for whatever reason,” another physician commented, “I would gracefully accede, and hope that my colleague would tactfully point out to the patient their error.”

“Having a nurse ask the patient ... what they need style-wise (keeping race, gender, etc., out of it) might help identify whether or not the underlying issue(s) are based on style/needs mismatch match rather than bias,” a reader suggested.

A health care worker commented: “We generally assure patients that we are professionals and think nothing of situations that they might find uncomfortable, but don’t realize that our comfort does not translate to theirs.”
 

Maybe a different strategy is needed

“Having been the target of bias many times,” a reader said, “I understand the pain that is inflicted. Unfortunately, a patient bias policy, while a good idea, will not prevent patient bias. This is a much larger societal problem. But we can at least tell patients that it is not okay. On the other hand, I would not want to be the provider for a patient who was biased against me and held me in disdain.”

“I do not like Zero Tolerance policies ever. They are too absolute,” another reader commented. “Sometimes, there are reasons and we do have to listen to our patients for why. ... I do not think a policy of zero tolerance will fix the problem of racism.”

“Instead of trying to educate the general public about how not to be jerks,” another reader suggested, “perhaps it would be easier to provide elective classes for doctors and employees who believe themselves to be at-risk for discrimination, providing them with a ‘toolkit’ of strategies for responding to discrimination in the moment, processing it emotionally later on, and reporting the most egregious events through designated channels.”

Another commenter agreed and wrote that, “While we as doctors need and deserve protection, we are also called to act with compassion. So, rather than ask the system for ‘zero-tolerance’ in either direction, we could encourage our health systems to provide education, support, and mediation to any party who feels or fears that they are not being well served. Such a model would include support for physicians who have been the victims of bias and hurt.”

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

One-eyed, one-horned, flying purple veggie eater

Big Fruits and Vegetables is at it again. You notice how they’re always like “Oh, vegetables are good for your health,” and “Eating fruits every day makes you live longer,” but come on. It’s a marketing ploy, leading us astray from our personal savior, McDonald’s.

PxHere

Just look at this latest bit of research: According to researchers from Finland, eating purple vegetables can protect against diabetes. Considering nearly 40 million Americans have diabetes (and nearly 100 million have prediabetes), anything to reduce the incidence of diabetes (people with diabetes account for one-fourth of every dollar spent in U.S. health care) would be beneficial. So, let’s humor the fruits and veggies people this time and hear them out.

It all comes down to a chemical called anthocyanin, which is a pigment that gives fruits and vegetables such as blueberries, radishes, and red cabbages their purplish color. Anthocyanin also has probiotic and anti-inflammatory effects, meaning it can help improve intestinal lining health and regulate glucose and lipid metabolic pathways. Obviously, good things if you want to avoid diabetes.

The investigators also found that, while standard anthocyanin was beneficial, acylated anthocyanin (which has an acyl group added to the sugar molecules of anthocyanin) is really what you want to go for. The acylated version, found in abundance in purple potatoes, purple carrots, radishes, and red cabbages, is tougher to digest, but the positive effects it has in the body are enhanced over the standard version.

Now, this all a compelling bit of research, but at the end of the day, you’re still eating fruits and vegetables, and we are red-blooded Americans here. We don’t do healthy foods. Although, if you were to dye our burgers with anthocyanin and make them purple, you’d have our attention. Purple is our favorite color.
 

Manuka honey better as building material than antibiotic

Milk, according to the old saying, builds strong bones, but when it comes to patients with bone loss caused by various medical reasons, researchers found that manuka honey, produced only in New Zealand and some parts of Australia, may also do the job. They soaked collagen scaffolds used for bone implants in various concentrations of the honey and found that 5% led to higher mineral formation and osteoprotegerin production, which suggests increased bone production.

Marley Dewey

But, and this is a pretty big one, the other half of the study – testing manuka honey’s ability to ward off bacteria – wasn’t so successful. Bone implants, apparently, count for almost half of all hospital-acquired infections, which obviously can put a damper on the healing process. The hope was that a biomaterial would be more effective than something like metal in lessening bacteria formation. Nope.

When the researchers soaked paper disks in honey and added them to cultures of Pseudomonas aeruginosa and Staphylococcus aureus, none of the various concentrations stopped bacterial growth in the scaffolding, even when they added antibiotics.

The sticky conclusion, you could say, is more bitter than sweet.
 

It may sound like Korn, but can it play ‘Freak on a Leash’?

Like all right-thinking Americans, we love corn, corn-based products, and almost corn. Corn on the cob grilled in the husk? Mmm. Plus, we’re big fans of the band Korn. Also, we once had a reporter here named Tim Kirn. And don’t even get us started with Karn. Best Family Feud host ever.

Quorn

But what about Quorn? Oh sure, the fungi-based meat alternative is full of yummy mycoprotein, but can it prevent colorectal cancer? Can we add Quorn to our favorites list? Let’s see what Science has to say.

Researchers at Northumbria University in Newcastle upon Tyne, England, fed a group of 20 men some meat (240 g/day) for 2 weeks – hopefully, they were allowed to eat some other food as well – and then gave them the same amount of Quorn, excuse us, fungi-derived mycoprotein equivalents, for 2 more weeks, with a 4-week washout period in between.

Levels of cancer-causing chemicals known as genotoxins fell significantly in the mycoprotein phase but rose during the meat phase. The mycoprotein diet also improved gut health “by increasing the abundance of protective bacteria such as Lactobacilli, Roseburia, and Akkermansia, which are associated with offering protection against chemically induced tumours, inflammation and bowel cancer,” they said in a statement from the university.

The meat phase, on the other hand, resulted in an increase in “gut bacteria linked with issues such as cancer, cardiovascular diseases, weight gain and other negative health outcomes,” they noted.

Science, then, seems to approve of Quorn, and that’s good enough for us. We’re adding Quorn to our diet, starting with a fungi-derived mycoproteinburger tonight while we’re watching the Cornell Big Red take the court against their archrivals, the Big Green of Dartmouth College. GO RED!

One-eyed, one-horned, flying purple veggie eater

Big Fruits and Vegetables is at it again. You notice how they’re always like “Oh, vegetables are good for your health,” and “Eating fruits every day makes you live longer,” but come on. It’s a marketing ploy, leading us astray from our personal savior, McDonald’s.

PxHere

Just look at this latest bit of research: According to researchers from Finland, eating purple vegetables can protect against diabetes. Considering nearly 40 million Americans have diabetes (and nearly 100 million have prediabetes), anything to reduce the incidence of diabetes (people with diabetes account for one-fourth of every dollar spent in U.S. health care) would be beneficial. So, let’s humor the fruits and veggies people this time and hear them out.

It all comes down to a chemical called anthocyanin, which is a pigment that gives fruits and vegetables such as blueberries, radishes, and red cabbages their purplish color. Anthocyanin also has probiotic and anti-inflammatory effects, meaning it can help improve intestinal lining health and regulate glucose and lipid metabolic pathways. Obviously, good things if you want to avoid diabetes.

The investigators also found that, while standard anthocyanin was beneficial, acylated anthocyanin (which has an acyl group added to the sugar molecules of anthocyanin) is really what you want to go for. The acylated version, found in abundance in purple potatoes, purple carrots, radishes, and red cabbages, is tougher to digest, but the positive effects it has in the body are enhanced over the standard version.

Now, this all a compelling bit of research, but at the end of the day, you’re still eating fruits and vegetables, and we are red-blooded Americans here. We don’t do healthy foods. Although, if you were to dye our burgers with anthocyanin and make them purple, you’d have our attention. Purple is our favorite color.
 

Manuka honey better as building material than antibiotic

Milk, according to the old saying, builds strong bones, but when it comes to patients with bone loss caused by various medical reasons, researchers found that manuka honey, produced only in New Zealand and some parts of Australia, may also do the job. They soaked collagen scaffolds used for bone implants in various concentrations of the honey and found that 5% led to higher mineral formation and osteoprotegerin production, which suggests increased bone production.

Marley Dewey

But, and this is a pretty big one, the other half of the study – testing manuka honey’s ability to ward off bacteria – wasn’t so successful. Bone implants, apparently, count for almost half of all hospital-acquired infections, which obviously can put a damper on the healing process. The hope was that a biomaterial would be more effective than something like metal in lessening bacteria formation. Nope.

When the researchers soaked paper disks in honey and added them to cultures of Pseudomonas aeruginosa and Staphylococcus aureus, none of the various concentrations stopped bacterial growth in the scaffolding, even when they added antibiotics.

The sticky conclusion, you could say, is more bitter than sweet.
 

It may sound like Korn, but can it play ‘Freak on a Leash’?

Like all right-thinking Americans, we love corn, corn-based products, and almost corn. Corn on the cob grilled in the husk? Mmm. Plus, we’re big fans of the band Korn. Also, we once had a reporter here named Tim Kirn. And don’t even get us started with Karn. Best Family Feud host ever.

Quorn

But what about Quorn? Oh sure, the fungi-based meat alternative is full of yummy mycoprotein, but can it prevent colorectal cancer? Can we add Quorn to our favorites list? Let’s see what Science has to say.

Researchers at Northumbria University in Newcastle upon Tyne, England, fed a group of 20 men some meat (240 g/day) for 2 weeks – hopefully, they were allowed to eat some other food as well – and then gave them the same amount of Quorn, excuse us, fungi-derived mycoprotein equivalents, for 2 more weeks, with a 4-week washout period in between.

Levels of cancer-causing chemicals known as genotoxins fell significantly in the mycoprotein phase but rose during the meat phase. The mycoprotein diet also improved gut health “by increasing the abundance of protective bacteria such as Lactobacilli, Roseburia, and Akkermansia, which are associated with offering protection against chemically induced tumours, inflammation and bowel cancer,” they said in a statement from the university.

The meat phase, on the other hand, resulted in an increase in “gut bacteria linked with issues such as cancer, cardiovascular diseases, weight gain and other negative health outcomes,” they noted.

Science, then, seems to approve of Quorn, and that’s good enough for us. We’re adding Quorn to our diet, starting with a fungi-derived mycoproteinburger tonight while we’re watching the Cornell Big Red take the court against their archrivals, the Big Green of Dartmouth College. GO RED!

One-eyed, one-horned, flying purple veggie eater

Big Fruits and Vegetables is at it again. You notice how they’re always like “Oh, vegetables are good for your health,” and “Eating fruits every day makes you live longer,” but come on. It’s a marketing ploy, leading us astray from our personal savior, McDonald’s.

PxHere

Just look at this latest bit of research: According to researchers from Finland, eating purple vegetables can protect against diabetes. Considering nearly 40 million Americans have diabetes (and nearly 100 million have prediabetes), anything to reduce the incidence of diabetes (people with diabetes account for one-fourth of every dollar spent in U.S. health care) would be beneficial. So, let’s humor the fruits and veggies people this time and hear them out.

It all comes down to a chemical called anthocyanin, which is a pigment that gives fruits and vegetables such as blueberries, radishes, and red cabbages their purplish color. Anthocyanin also has probiotic and anti-inflammatory effects, meaning it can help improve intestinal lining health and regulate glucose and lipid metabolic pathways. Obviously, good things if you want to avoid diabetes.

The investigators also found that, while standard anthocyanin was beneficial, acylated anthocyanin (which has an acyl group added to the sugar molecules of anthocyanin) is really what you want to go for. The acylated version, found in abundance in purple potatoes, purple carrots, radishes, and red cabbages, is tougher to digest, but the positive effects it has in the body are enhanced over the standard version.

Now, this all a compelling bit of research, but at the end of the day, you’re still eating fruits and vegetables, and we are red-blooded Americans here. We don’t do healthy foods. Although, if you were to dye our burgers with anthocyanin and make them purple, you’d have our attention. Purple is our favorite color.
 

Manuka honey better as building material than antibiotic

Milk, according to the old saying, builds strong bones, but when it comes to patients with bone loss caused by various medical reasons, researchers found that manuka honey, produced only in New Zealand and some parts of Australia, may also do the job. They soaked collagen scaffolds used for bone implants in various concentrations of the honey and found that 5% led to higher mineral formation and osteoprotegerin production, which suggests increased bone production.

Marley Dewey

But, and this is a pretty big one, the other half of the study – testing manuka honey’s ability to ward off bacteria – wasn’t so successful. Bone implants, apparently, count for almost half of all hospital-acquired infections, which obviously can put a damper on the healing process. The hope was that a biomaterial would be more effective than something like metal in lessening bacteria formation. Nope.

When the researchers soaked paper disks in honey and added them to cultures of Pseudomonas aeruginosa and Staphylococcus aureus, none of the various concentrations stopped bacterial growth in the scaffolding, even when they added antibiotics.

The sticky conclusion, you could say, is more bitter than sweet.
 

It may sound like Korn, but can it play ‘Freak on a Leash’?

Like all right-thinking Americans, we love corn, corn-based products, and almost corn. Corn on the cob grilled in the husk? Mmm. Plus, we’re big fans of the band Korn. Also, we once had a reporter here named Tim Kirn. And don’t even get us started with Karn. Best Family Feud host ever.

Quorn

But what about Quorn? Oh sure, the fungi-based meat alternative is full of yummy mycoprotein, but can it prevent colorectal cancer? Can we add Quorn to our favorites list? Let’s see what Science has to say.

Researchers at Northumbria University in Newcastle upon Tyne, England, fed a group of 20 men some meat (240 g/day) for 2 weeks – hopefully, they were allowed to eat some other food as well – and then gave them the same amount of Quorn, excuse us, fungi-derived mycoprotein equivalents, for 2 more weeks, with a 4-week washout period in between.

Levels of cancer-causing chemicals known as genotoxins fell significantly in the mycoprotein phase but rose during the meat phase. The mycoprotein diet also improved gut health “by increasing the abundance of protective bacteria such as Lactobacilli, Roseburia, and Akkermansia, which are associated with offering protection against chemically induced tumours, inflammation and bowel cancer,” they said in a statement from the university.

The meat phase, on the other hand, resulted in an increase in “gut bacteria linked with issues such as cancer, cardiovascular diseases, weight gain and other negative health outcomes,” they noted.

Science, then, seems to approve of Quorn, and that’s good enough for us. We’re adding Quorn to our diet, starting with a fungi-derived mycoproteinburger tonight while we’re watching the Cornell Big Red take the court against their archrivals, the Big Green of Dartmouth College. GO RED!

Physician groups saw staff-to-physician ratios decline even as their workforce expenses rose between 2019 and 2021, according to recent reports from the American Medical Group Association (AMGA) and the Medical Group Management Association (MGMA).

As patients started to return to doctors’ offices as the pandemic eased in 2021, physician groups found it increasingly difficult to recruit and retain lower-level clinicians, including medical assistants and LPNs, officials from both associations told this news organization. Many clinics had to raise their pay scales to be competitive with employers in other fields, and some had to hire higher-priced RNs to keep their practices running.

The AMGA report was based largely on data from groups of over 500 physicians, mostly affiliated with health systems. According to a news release accompanying the report, the ratio between full-time equivalent (FTE) clinic staff and health care professionals in direct patient care dropped by 11.3% between 2019 and 2021. The ratio of medical assistants (MAs) to clinicians declined by a greater percentage.

In the MGMA report, which represented about 4,000 practices ranging from very small (two doctors) to very large groups, total support staff per FTE primary-care physician dropped by 18% from 2019 to 2021 in independent groups and by 13% in hospital-affiliated groups. The ratios decreased by smaller amounts in surgical practices.

In contrast, nonsurgical specialty groups under both types of ownership saw their staffing ratios rise slightly.

Although it’s unclear why medical specialties increased their staff while other types of specialties lost employees, Ron Holder, MHA, chief operating officer of MGMA, said that some specialists may have opened more ancillary facilities and hired new employees to recoup revenue lost during the pandemic.
 

Expenses rise sharply

The AMGA report found that staffing expenses for the surveyed groups increased by 15% between 2019 and 2021.

“We saw a decrease in staff and an increase in expenses during that time period, and there are a few reasons for that,” Rose Wagner, RN, chief operating officer of AMGA, said. “Groups increased salaries to maintain staff. We also saw lower-paid staff find other jobs outside of health care. For example, medical assistants and receptionists could find jobs outside of health care that paid more. [Open positions] got back-filled with other higher paid staff, such as RNs, doing lower skilled jobs.”

Mr. Holder added that rising wages in other sectors made leaving physician groups more attractive for employees.

“Three years ago, there weren’t many positions in a medical practice where you were competing with Chick-fil-A or Taco Bell,” he said. In Denver, where Mr. Holder is based, “every restaurant in town is now advertising $17-$19 [hourly] starting pay just to do fast food. That causes practices to either lose employees or pay more for the employees they have. So that raises per-employee expense significantly,” he said.

Mr. Holder noted that inflation also has driven up wages as employees demand higher pay to keep up with the cost of living.
 

Unusual exodus of employees

Fred Horton, MHA, president of AMGA Consulting, said he has never seen so many people leaving health care for other occupations.

Some exits resulted from practices laying people off early in the pandemic, but most staff members who left practices were seeking higher pay, he said. In addition, Ms. Wagner noted, some staff members didn’t want to be exposed to COVID at work.

“There was an exodus from health care that was different from what we’d experienced in the past,” Mr. Horton added. “It’s still extremely challenging to get up to the staffing levels that are appropriate.”

Mr. Holder, however, said that the situation is slowly improving. “Health care is fairly recession-proof, because people need it. So when you see companies in other industries closing shop or reducing their head count, that actually helps health care recruiting in some jobs. And people are coming back to the workplace who previously were worried about COVID or didn’t want to get the vaccine.”
 

Paying more for nurses

In 2021, groups adopted a variety of tactics to adapt to the pandemic and respond to patient demand, the AMGA survey shows. Forty percent of system-affiliated groups and 18% of independent practices changed registered nurses’ responsibilities, in many cases having them do the work of medical assistants who were in short supply.

Some practices hired RNs, who have historically been utilized less by primary care than by surgical specialties, Mr. Holder noted. Other clinics paid temp agencies to supply nurses at a steep cost.

“When you’re short staffed, you end up paying more overtime, you end up paying temporary agencies at higher dollars, and you hire higher skilled people to do lower-skilled work,” Ms. Wagner said.

Meanwhile, many physician groups tried to cope with the physician shortage by bringing on more advanced practice clinicians (APCs), including nurse practitioners (NPs) and physician assistants (PAs). Seventy percent of the AMGA groups used this strategy, the report revealed.

“The use of APCs has been steadily increasing as groups try to adopt a lower-cost care model in the midst of a nationwide physician shortage,” Ms. Wagner said in the press release.
 

Changes in patient care

About half of the groups in the AMGA survey said they changed their staff structure to allow APCs to carry their own patient panels. Although most of these clinicians were probably under physician supervision, nearly half of the states now allow NPs to practice autonomously.

Mr. Horton cautioned that APCs can’t fully substitute for physicians and require the same support staff that doctors do if they have their own panels. In primary care groups, Mr. Holder noted, the average salary of an APC “is continuing to rise, and there isn’t a huge difference between what they and doctors make.”

Nevertheless, he added, “there are more NPs and PAs being added to the marketplace all the time, whereas [physician] residency programs aren’t really growing. There are caps on the number of residency positions, and some physicians are retiring. So the clock is ticking to the point where someday doctors will be grossly outnumbered by NPs.”

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

Physician groups saw staff-to-physician ratios decline even as their workforce expenses rose between 2019 and 2021, according to recent reports from the American Medical Group Association (AMGA) and the Medical Group Management Association (MGMA).

As patients started to return to doctors’ offices as the pandemic eased in 2021, physician groups found it increasingly difficult to recruit and retain lower-level clinicians, including medical assistants and LPNs, officials from both associations told this news organization. Many clinics had to raise their pay scales to be competitive with employers in other fields, and some had to hire higher-priced RNs to keep their practices running.

The AMGA report was based largely on data from groups of over 500 physicians, mostly affiliated with health systems. According to a news release accompanying the report, the ratio between full-time equivalent (FTE) clinic staff and health care professionals in direct patient care dropped by 11.3% between 2019 and 2021. The ratio of medical assistants (MAs) to clinicians declined by a greater percentage.

In the MGMA report, which represented about 4,000 practices ranging from very small (two doctors) to very large groups, total support staff per FTE primary-care physician dropped by 18% from 2019 to 2021 in independent groups and by 13% in hospital-affiliated groups. The ratios decreased by smaller amounts in surgical practices.

In contrast, nonsurgical specialty groups under both types of ownership saw their staffing ratios rise slightly.

Although it’s unclear why medical specialties increased their staff while other types of specialties lost employees, Ron Holder, MHA, chief operating officer of MGMA, said that some specialists may have opened more ancillary facilities and hired new employees to recoup revenue lost during the pandemic.
 

Expenses rise sharply

The AMGA report found that staffing expenses for the surveyed groups increased by 15% between 2019 and 2021.

“We saw a decrease in staff and an increase in expenses during that time period, and there are a few reasons for that,” Rose Wagner, RN, chief operating officer of AMGA, said. “Groups increased salaries to maintain staff. We also saw lower-paid staff find other jobs outside of health care. For example, medical assistants and receptionists could find jobs outside of health care that paid more. [Open positions] got back-filled with other higher paid staff, such as RNs, doing lower skilled jobs.”

Mr. Holder added that rising wages in other sectors made leaving physician groups more attractive for employees.

“Three years ago, there weren’t many positions in a medical practice where you were competing with Chick-fil-A or Taco Bell,” he said. In Denver, where Mr. Holder is based, “every restaurant in town is now advertising $17-$19 [hourly] starting pay just to do fast food. That causes practices to either lose employees or pay more for the employees they have. So that raises per-employee expense significantly,” he said.

Mr. Holder noted that inflation also has driven up wages as employees demand higher pay to keep up with the cost of living.
 

Unusual exodus of employees

Fred Horton, MHA, president of AMGA Consulting, said he has never seen so many people leaving health care for other occupations.

Some exits resulted from practices laying people off early in the pandemic, but most staff members who left practices were seeking higher pay, he said. In addition, Ms. Wagner noted, some staff members didn’t want to be exposed to COVID at work.

“There was an exodus from health care that was different from what we’d experienced in the past,” Mr. Horton added. “It’s still extremely challenging to get up to the staffing levels that are appropriate.”

Mr. Holder, however, said that the situation is slowly improving. “Health care is fairly recession-proof, because people need it. So when you see companies in other industries closing shop or reducing their head count, that actually helps health care recruiting in some jobs. And people are coming back to the workplace who previously were worried about COVID or didn’t want to get the vaccine.”
 

Paying more for nurses

In 2021, groups adopted a variety of tactics to adapt to the pandemic and respond to patient demand, the AMGA survey shows. Forty percent of system-affiliated groups and 18% of independent practices changed registered nurses’ responsibilities, in many cases having them do the work of medical assistants who were in short supply.

Some practices hired RNs, who have historically been utilized less by primary care than by surgical specialties, Mr. Holder noted. Other clinics paid temp agencies to supply nurses at a steep cost.

“When you’re short staffed, you end up paying more overtime, you end up paying temporary agencies at higher dollars, and you hire higher skilled people to do lower-skilled work,” Ms. Wagner said.

Meanwhile, many physician groups tried to cope with the physician shortage by bringing on more advanced practice clinicians (APCs), including nurse practitioners (NPs) and physician assistants (PAs). Seventy percent of the AMGA groups used this strategy, the report revealed.

“The use of APCs has been steadily increasing as groups try to adopt a lower-cost care model in the midst of a nationwide physician shortage,” Ms. Wagner said in the press release.
 

Changes in patient care

About half of the groups in the AMGA survey said they changed their staff structure to allow APCs to carry their own patient panels. Although most of these clinicians were probably under physician supervision, nearly half of the states now allow NPs to practice autonomously.

Mr. Horton cautioned that APCs can’t fully substitute for physicians and require the same support staff that doctors do if they have their own panels. In primary care groups, Mr. Holder noted, the average salary of an APC “is continuing to rise, and there isn’t a huge difference between what they and doctors make.”

Nevertheless, he added, “there are more NPs and PAs being added to the marketplace all the time, whereas [physician] residency programs aren’t really growing. There are caps on the number of residency positions, and some physicians are retiring. So the clock is ticking to the point where someday doctors will be grossly outnumbered by NPs.”

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

Physician groups saw staff-to-physician ratios decline even as their workforce expenses rose between 2019 and 2021, according to recent reports from the American Medical Group Association (AMGA) and the Medical Group Management Association (MGMA).

As patients started to return to doctors’ offices as the pandemic eased in 2021, physician groups found it increasingly difficult to recruit and retain lower-level clinicians, including medical assistants and LPNs, officials from both associations told this news organization. Many clinics had to raise their pay scales to be competitive with employers in other fields, and some had to hire higher-priced RNs to keep their practices running.

The AMGA report was based largely on data from groups of over 500 physicians, mostly affiliated with health systems. According to a news release accompanying the report, the ratio between full-time equivalent (FTE) clinic staff and health care professionals in direct patient care dropped by 11.3% between 2019 and 2021. The ratio of medical assistants (MAs) to clinicians declined by a greater percentage.

In the MGMA report, which represented about 4,000 practices ranging from very small (two doctors) to very large groups, total support staff per FTE primary-care physician dropped by 18% from 2019 to 2021 in independent groups and by 13% in hospital-affiliated groups. The ratios decreased by smaller amounts in surgical practices.

In contrast, nonsurgical specialty groups under both types of ownership saw their staffing ratios rise slightly.

Although it’s unclear why medical specialties increased their staff while other types of specialties lost employees, Ron Holder, MHA, chief operating officer of MGMA, said that some specialists may have opened more ancillary facilities and hired new employees to recoup revenue lost during the pandemic.
 

Expenses rise sharply

The AMGA report found that staffing expenses for the surveyed groups increased by 15% between 2019 and 2021.

“We saw a decrease in staff and an increase in expenses during that time period, and there are a few reasons for that,” Rose Wagner, RN, chief operating officer of AMGA, said. “Groups increased salaries to maintain staff. We also saw lower-paid staff find other jobs outside of health care. For example, medical assistants and receptionists could find jobs outside of health care that paid more. [Open positions] got back-filled with other higher paid staff, such as RNs, doing lower skilled jobs.”

Mr. Holder added that rising wages in other sectors made leaving physician groups more attractive for employees.

“Three years ago, there weren’t many positions in a medical practice where you were competing with Chick-fil-A or Taco Bell,” he said. In Denver, where Mr. Holder is based, “every restaurant in town is now advertising $17-$19 [hourly] starting pay just to do fast food. That causes practices to either lose employees or pay more for the employees they have. So that raises per-employee expense significantly,” he said.

Mr. Holder noted that inflation also has driven up wages as employees demand higher pay to keep up with the cost of living.
 

Unusual exodus of employees

Fred Horton, MHA, president of AMGA Consulting, said he has never seen so many people leaving health care for other occupations.

Some exits resulted from practices laying people off early in the pandemic, but most staff members who left practices were seeking higher pay, he said. In addition, Ms. Wagner noted, some staff members didn’t want to be exposed to COVID at work.

“There was an exodus from health care that was different from what we’d experienced in the past,” Mr. Horton added. “It’s still extremely challenging to get up to the staffing levels that are appropriate.”

Mr. Holder, however, said that the situation is slowly improving. “Health care is fairly recession-proof, because people need it. So when you see companies in other industries closing shop or reducing their head count, that actually helps health care recruiting in some jobs. And people are coming back to the workplace who previously were worried about COVID or didn’t want to get the vaccine.”
 

Paying more for nurses

In 2021, groups adopted a variety of tactics to adapt to the pandemic and respond to patient demand, the AMGA survey shows. Forty percent of system-affiliated groups and 18% of independent practices changed registered nurses’ responsibilities, in many cases having them do the work of medical assistants who were in short supply.

Some practices hired RNs, who have historically been utilized less by primary care than by surgical specialties, Mr. Holder noted. Other clinics paid temp agencies to supply nurses at a steep cost.

“When you’re short staffed, you end up paying more overtime, you end up paying temporary agencies at higher dollars, and you hire higher skilled people to do lower-skilled work,” Ms. Wagner said.

Meanwhile, many physician groups tried to cope with the physician shortage by bringing on more advanced practice clinicians (APCs), including nurse practitioners (NPs) and physician assistants (PAs). Seventy percent of the AMGA groups used this strategy, the report revealed.

“The use of APCs has been steadily increasing as groups try to adopt a lower-cost care model in the midst of a nationwide physician shortage,” Ms. Wagner said in the press release.
 

Changes in patient care

About half of the groups in the AMGA survey said they changed their staff structure to allow APCs to carry their own patient panels. Although most of these clinicians were probably under physician supervision, nearly half of the states now allow NPs to practice autonomously.

Mr. Horton cautioned that APCs can’t fully substitute for physicians and require the same support staff that doctors do if they have their own panels. In primary care groups, Mr. Holder noted, the average salary of an APC “is continuing to rise, and there isn’t a huge difference between what they and doctors make.”

Nevertheless, he added, “there are more NPs and PAs being added to the marketplace all the time, whereas [physician] residency programs aren’t really growing. There are caps on the number of residency positions, and some physicians are retiring. So the clock is ticking to the point where someday doctors will be grossly outnumbered by NPs.”

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

Doctors and their family members are less likely than other people to follow guidelines for taking medication, according to a study by economic professors from the Massachusetts Institute of Technology, Cambridge; Stanford (Calif.) University; and the George Gund Professor of Economics and Business Administration at Harvard University, Boston.

What to know

• Doctors’ medical knowledge may influence them and their families to often ignore medical advice while the rest of the population adheres to general medication guidelines.
• Of the 63 guidelines used in the study, doctors and their families followed the standards less than a third of the time.
• The difference in adherence to guidelines between experts and nonexperts is largest with respect to antibiotics, in which doctors and their families are 5.2 percentage points less in compliance than everyone else.
• Doctors could be more likely to prescribe broader-spectrum antibiotics for themselves and their families, whereas most patients receive more narrow-spectrum antibiotics.
• Many members of the general public don’t understand medical guidelines, finding them too complex to follow, and many people don’t trust their doctors.

This is a summary of the article, “A Taste of Their Own Medicine: Guideline Adherence and Access to Expertise,” published in the American Economic Review: Insights on December 13, 2022. The full article can be found on aeaweb.org.

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

Doctors and their family members are less likely than other people to follow guidelines for taking medication, according to a study by economic professors from the Massachusetts Institute of Technology, Cambridge; Stanford (Calif.) University; and the George Gund Professor of Economics and Business Administration at Harvard University, Boston.

What to know

• Doctors’ medical knowledge may influence them and their families to often ignore medical advice while the rest of the population adheres to general medication guidelines.
• Of the 63 guidelines used in the study, doctors and their families followed the standards less than a third of the time.
• The difference in adherence to guidelines between experts and nonexperts is largest with respect to antibiotics, in which doctors and their families are 5.2 percentage points less in compliance than everyone else.
• Doctors could be more likely to prescribe broader-spectrum antibiotics for themselves and their families, whereas most patients receive more narrow-spectrum antibiotics.
• Many members of the general public don’t understand medical guidelines, finding them too complex to follow, and many people don’t trust their doctors.

This is a summary of the article, “A Taste of Their Own Medicine: Guideline Adherence and Access to Expertise,” published in the American Economic Review: Insights on December 13, 2022. The full article can be found on aeaweb.org.

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

Doctors and their family members are less likely than other people to follow guidelines for taking medication, according to a study by economic professors from the Massachusetts Institute of Technology, Cambridge; Stanford (Calif.) University; and the George Gund Professor of Economics and Business Administration at Harvard University, Boston.

What to know

• Doctors’ medical knowledge may influence them and their families to often ignore medical advice while the rest of the population adheres to general medication guidelines.
• Of the 63 guidelines used in the study, doctors and their families followed the standards less than a third of the time.
• The difference in adherence to guidelines between experts and nonexperts is largest with respect to antibiotics, in which doctors and their families are 5.2 percentage points less in compliance than everyone else.
• Doctors could be more likely to prescribe broader-spectrum antibiotics for themselves and their families, whereas most patients receive more narrow-spectrum antibiotics.
• Many members of the general public don’t understand medical guidelines, finding them too complex to follow, and many people don’t trust their doctors.

This is a summary of the article, “A Taste of Their Own Medicine: Guideline Adherence and Access to Expertise,” published in the American Economic Review: Insights on December 13, 2022. The full article can be found on aeaweb.org.

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

A new study published in JAMA suggests that doctors with one paid malpractice claim are almost four times more likely than their peers to have additional paid claims in the future, regardless of specialty or whether a state publicly discloses paid claims.

In this retrospective case-control study, law and public health researchers from Georgetown University, the National Opinion Research Center, the University of Colorado, and Northwestern University analyzed paid malpractice claims for all licensed U.S. physicians.

The findings suggest that a single malpractice claim may not be a random stroke of bad luck but instead holds some predictive power into the risk for future paid claims.

“A four times increase in risk is huge, particularly since we observe a similar increase in both high-risk and lower-risk specialties,” David Hyman, JD, MD, professor of health law and policy at Georgetown University, Washington, and lead researcher on the study, told this news organization. “There are surely some false positives, but there must be lots of actual negligence too, or we would not see these results.”

For the 881,876 physicians analyzed, researchers looked at malpractice claims paid during two 5-year periods: 2009-2013 and 2014-2018. Nearly 96% of physicians had no paid malpractice claims between 2009 and 2013; 3% had one, and less than 1% had multiple claims. The proportion of physicians with paid claims between 2014 and 2018 was similar.

Compared with physicians with no 2009-2013 claims, a physician with just one paid claim in that time period had a 3.7 times higher risk for a future paid claim. Physicians with two paid claims were nearly 7 times more likely to have a future paid claim, and those with three or more paid claims were more than 11 times more likely to have one.

Approximately 3% of physicians with no paid claims between 2009 and 2013 had a future paid claim, growing to 12.4% of those with one paid claim during that time.

The study’s findings may have implications for medical licensing boards and hospitals granting staff privileges.

“After some number of paid claims, there should be an official response” from these entities, such as a hands-on assessment of technical skills or assignment of a peer mentor, said Dr. Hyman, who is also coauthor of a book titled “Medical Malpractice Litigation: How It Works, Why Tort Reform Hasn’t Helped.” A graduated set of interventions, whether voluntary or mandatory, can reduce future claim risk and patient harm, Dr. Hyman added.

Interventions may include error avoidance and post-error communication training, counseling to improve bedside skills, and encouragement to move into nonclinical practice. Either way, Dr. Hyman says a nuanced intervention strategy would be a welcome shift away from the current “all or nothing approach” that too often ends in the revocation of a physician’s medical license.

Although there are strategies to proactively identify physicians with excess risk for malpractice claims and implement preventive measures – like Vanderbilt University’s Patient Advocacy Reporting System, for example – most hospitals and physician groups fail to initiate even informal interventions after a malpractice settlement or verdict, which is a missed opportunity, Dr. Hyman said.

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

A new study published in JAMA suggests that doctors with one paid malpractice claim are almost four times more likely than their peers to have additional paid claims in the future, regardless of specialty or whether a state publicly discloses paid claims.

In this retrospective case-control study, law and public health researchers from Georgetown University, the National Opinion Research Center, the University of Colorado, and Northwestern University analyzed paid malpractice claims for all licensed U.S. physicians.

The findings suggest that a single malpractice claim may not be a random stroke of bad luck but instead holds some predictive power into the risk for future paid claims.

“A four times increase in risk is huge, particularly since we observe a similar increase in both high-risk and lower-risk specialties,” David Hyman, JD, MD, professor of health law and policy at Georgetown University, Washington, and lead researcher on the study, told this news organization. “There are surely some false positives, but there must be lots of actual negligence too, or we would not see these results.”

For the 881,876 physicians analyzed, researchers looked at malpractice claims paid during two 5-year periods: 2009-2013 and 2014-2018. Nearly 96% of physicians had no paid malpractice claims between 2009 and 2013; 3% had one, and less than 1% had multiple claims. The proportion of physicians with paid claims between 2014 and 2018 was similar.

Compared with physicians with no 2009-2013 claims, a physician with just one paid claim in that time period had a 3.7 times higher risk for a future paid claim. Physicians with two paid claims were nearly 7 times more likely to have a future paid claim, and those with three or more paid claims were more than 11 times more likely to have one.

Approximately 3% of physicians with no paid claims between 2009 and 2013 had a future paid claim, growing to 12.4% of those with one paid claim during that time.

The study’s findings may have implications for medical licensing boards and hospitals granting staff privileges.

“After some number of paid claims, there should be an official response” from these entities, such as a hands-on assessment of technical skills or assignment of a peer mentor, said Dr. Hyman, who is also coauthor of a book titled “Medical Malpractice Litigation: How It Works, Why Tort Reform Hasn’t Helped.” A graduated set of interventions, whether voluntary or mandatory, can reduce future claim risk and patient harm, Dr. Hyman added.

Interventions may include error avoidance and post-error communication training, counseling to improve bedside skills, and encouragement to move into nonclinical practice. Either way, Dr. Hyman says a nuanced intervention strategy would be a welcome shift away from the current “all or nothing approach” that too often ends in the revocation of a physician’s medical license.

Although there are strategies to proactively identify physicians with excess risk for malpractice claims and implement preventive measures – like Vanderbilt University’s Patient Advocacy Reporting System, for example – most hospitals and physician groups fail to initiate even informal interventions after a malpractice settlement or verdict, which is a missed opportunity, Dr. Hyman said.

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

A new study published in JAMA suggests that doctors with one paid malpractice claim are almost four times more likely than their peers to have additional paid claims in the future, regardless of specialty or whether a state publicly discloses paid claims.

In this retrospective case-control study, law and public health researchers from Georgetown University, the National Opinion Research Center, the University of Colorado, and Northwestern University analyzed paid malpractice claims for all licensed U.S. physicians.

The findings suggest that a single malpractice claim may not be a random stroke of bad luck but instead holds some predictive power into the risk for future paid claims.

“A four times increase in risk is huge, particularly since we observe a similar increase in both high-risk and lower-risk specialties,” David Hyman, JD, MD, professor of health law and policy at Georgetown University, Washington, and lead researcher on the study, told this news organization. “There are surely some false positives, but there must be lots of actual negligence too, or we would not see these results.”

For the 881,876 physicians analyzed, researchers looked at malpractice claims paid during two 5-year periods: 2009-2013 and 2014-2018. Nearly 96% of physicians had no paid malpractice claims between 2009 and 2013; 3% had one, and less than 1% had multiple claims. The proportion of physicians with paid claims between 2014 and 2018 was similar.

Compared with physicians with no 2009-2013 claims, a physician with just one paid claim in that time period had a 3.7 times higher risk for a future paid claim. Physicians with two paid claims were nearly 7 times more likely to have a future paid claim, and those with three or more paid claims were more than 11 times more likely to have one.

Approximately 3% of physicians with no paid claims between 2009 and 2013 had a future paid claim, growing to 12.4% of those with one paid claim during that time.

The study’s findings may have implications for medical licensing boards and hospitals granting staff privileges.

“After some number of paid claims, there should be an official response” from these entities, such as a hands-on assessment of technical skills or assignment of a peer mentor, said Dr. Hyman, who is also coauthor of a book titled “Medical Malpractice Litigation: How It Works, Why Tort Reform Hasn’t Helped.” A graduated set of interventions, whether voluntary or mandatory, can reduce future claim risk and patient harm, Dr. Hyman added.

Interventions may include error avoidance and post-error communication training, counseling to improve bedside skills, and encouragement to move into nonclinical practice. Either way, Dr. Hyman says a nuanced intervention strategy would be a welcome shift away from the current “all or nothing approach” that too often ends in the revocation of a physician’s medical license.

Although there are strategies to proactively identify physicians with excess risk for malpractice claims and implement preventive measures – like Vanderbilt University’s Patient Advocacy Reporting System, for example – most hospitals and physician groups fail to initiate even informal interventions after a malpractice settlement or verdict, which is a missed opportunity, Dr. Hyman said.

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

In the first study to examine how intermittent fasting combined with exercise impacts nonalcoholic fatty liver disease (NAFLD), the combined strategy was more effective than aerobic exercise alone or no intervention (control).

However, the combined approach did not give significantly added benefit, compared with fasting alone, the researchers report.

Eighty patients with NAFLD were randomized to one of four lifestyle strategies (alternate-day fasting, aerobic exercise, both, or neither) for 3 months.

The primary outcome was change in intrahepatic triglyceride (IHTG) content from baseline to study end, measured by magnetic resonance imaging proton density fat fraction.

The results suggest that “combining intermittent fasting with exercise is effective for reducing hepatic steatosis [fatty liver] in patients with NAFLD but may offer no additional benefit versus fasting alone,” Mark Ezpeleta, PhD, formerly at the University of Illinois, Chicago, and now at the University of Colorado Anschutz Medical Campus, and colleagues conclude.

“Our findings also indicate that the combination intervention was effective for reducing body weight, fat mass, waist circumference, [the liver enzyme alanine transaminase (ALT)], fasting insulin, [and] insulin resistance and increasing insulin sensitivity, among patients with obesity and NAFLD versus controls,” the group reports.  

“When we compared the results of our study groups, we saw clearly that the most improved patients were in the group that followed the alternate-day fasting diet and exercised 5 days a week,” senior author Krista A. Varady, PhD, professor of nutrition, University of Illinois, said in a press release from the university.

“The people who only dieted or only exercised did not see the same improvements,” she added, “which reinforces the importance of these two relatively inexpensive lifestyle modifications on overall health and on combating chronic diseases like fatty liver disease.”

Moreover, “alternate-day fasting and exercise interventions can be difficult for people to stick to, and in prior studies we have seen significant dropout,” she noted. “It was very interesting to see that in this trial we had very high adherence to the interventions.”

The study was recently published in Cell Metabolism.  

An estimated 65% of people with obesity have NAFLD, or fat in the liver that is not the result of excessive alcohol consumption, which is strongly related to the development of insulin resistance and type 2 diabetes, the group writes.

Thiazolidinediones such as pioglitazone reduce hepatic steatosis, but there is mounting concern about the weight-gaining effect of these compounds.

Recent attention has focused on lifestyle interventions to resolve hepatic steatosis, and previous trials showed that alternate-day fasting was effective for certain outcomes in NAFLD, but those studies did not measure changes in IHTG content or include an exercise intervention.

The researchers enrolled 80 adults with obesity and NAFLD and randomized them to one of four groups for 3 months:

• Alternate day fasting group: Participants were instructed to consume 600 kcal at dinner between 5 PM and 8 PM on a fasting day alternating with food as desired on a feasting day.
• Exercise group: A 60-minute moderate-intensity aerobic exercise session 5 times a week.
• Fasting plus exercise group.
• Control group (no intervention).

Participants were age 23-65 (mean age, 44) and 81% were women.

Half were Hispanic, and the rest were Black (30%), White (11%), or Asian (9%).

They had a mean weight of 99 kg (218 lb) and a mean body mass index of 36 kg/m².

Dropout rates were minimal in the combination group (0%) and fasting groups (5%) and moderately high in the exercise group (25%).

IHTG content was reduced by a significantly greater amount in the combination group (–5.48%) than in the exercise alone group (–1.30%; P = .02) or in the control group (–0.17%; P < .01) and by a greater amount than in the fasting alone group, although this was not significant (–2.25%; P = .05).

Lean mass, aspartate transaminase (AST), A1c, blood pressure, plasma lipids, liver fibrosis score, and hepatokines (fetuin-A, FGF-21, and selenoprotein P) did not differ between groups.

Researchers acknowledge that although the combination intervention resulted in improved NAFLD parameters, IHTG and ALT did not reach the normal range.  

Participants likely had early stage NAFLD (their baseline IHTG was in the 16% to 18% range, where 5% to 33% is mild steatosis) and they were likely highly motivated (indicated by the low dropout rate), so the findings may not be generalizable.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. Dr. Varady has reported receiving author fees from the Hachette Book Group for the book entitled “The Every Other Day Diet.” The other authors have reported no relevant financial relationships.

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

In the first study to examine how intermittent fasting combined with exercise impacts nonalcoholic fatty liver disease (NAFLD), the combined strategy was more effective than aerobic exercise alone or no intervention (control).

However, the combined approach did not give significantly added benefit, compared with fasting alone, the researchers report.

Eighty patients with NAFLD were randomized to one of four lifestyle strategies (alternate-day fasting, aerobic exercise, both, or neither) for 3 months.

The primary outcome was change in intrahepatic triglyceride (IHTG) content from baseline to study end, measured by magnetic resonance imaging proton density fat fraction.

The results suggest that “combining intermittent fasting with exercise is effective for reducing hepatic steatosis [fatty liver] in patients with NAFLD but may offer no additional benefit versus fasting alone,” Mark Ezpeleta, PhD, formerly at the University of Illinois, Chicago, and now at the University of Colorado Anschutz Medical Campus, and colleagues conclude.

“Our findings also indicate that the combination intervention was effective for reducing body weight, fat mass, waist circumference, [the liver enzyme alanine transaminase (ALT)], fasting insulin, [and] insulin resistance and increasing insulin sensitivity, among patients with obesity and NAFLD versus controls,” the group reports.  

“When we compared the results of our study groups, we saw clearly that the most improved patients were in the group that followed the alternate-day fasting diet and exercised 5 days a week,” senior author Krista A. Varady, PhD, professor of nutrition, University of Illinois, said in a press release from the university.

“The people who only dieted or only exercised did not see the same improvements,” she added, “which reinforces the importance of these two relatively inexpensive lifestyle modifications on overall health and on combating chronic diseases like fatty liver disease.”

Moreover, “alternate-day fasting and exercise interventions can be difficult for people to stick to, and in prior studies we have seen significant dropout,” she noted. “It was very interesting to see that in this trial we had very high adherence to the interventions.”

The study was recently published in Cell Metabolism.  

An estimated 65% of people with obesity have NAFLD, or fat in the liver that is not the result of excessive alcohol consumption, which is strongly related to the development of insulin resistance and type 2 diabetes, the group writes.

Thiazolidinediones such as pioglitazone reduce hepatic steatosis, but there is mounting concern about the weight-gaining effect of these compounds.

Recent attention has focused on lifestyle interventions to resolve hepatic steatosis, and previous trials showed that alternate-day fasting was effective for certain outcomes in NAFLD, but those studies did not measure changes in IHTG content or include an exercise intervention.

The researchers enrolled 80 adults with obesity and NAFLD and randomized them to one of four groups for 3 months:

• Alternate day fasting group: Participants were instructed to consume 600 kcal at dinner between 5 PM and 8 PM on a fasting day alternating with food as desired on a feasting day.
• Exercise group: A 60-minute moderate-intensity aerobic exercise session 5 times a week.
• Fasting plus exercise group.
• Control group (no intervention).

Participants were age 23-65 (mean age, 44) and 81% were women.

Half were Hispanic, and the rest were Black (30%), White (11%), or Asian (9%).

They had a mean weight of 99 kg (218 lb) and a mean body mass index of 36 kg/m².

Dropout rates were minimal in the combination group (0%) and fasting groups (5%) and moderately high in the exercise group (25%).

IHTG content was reduced by a significantly greater amount in the combination group (–5.48%) than in the exercise alone group (–1.30%; P = .02) or in the control group (–0.17%; P < .01) and by a greater amount than in the fasting alone group, although this was not significant (–2.25%; P = .05).

Lean mass, aspartate transaminase (AST), A1c, blood pressure, plasma lipids, liver fibrosis score, and hepatokines (fetuin-A, FGF-21, and selenoprotein P) did not differ between groups.

Researchers acknowledge that although the combination intervention resulted in improved NAFLD parameters, IHTG and ALT did not reach the normal range.  

Participants likely had early stage NAFLD (their baseline IHTG was in the 16% to 18% range, where 5% to 33% is mild steatosis) and they were likely highly motivated (indicated by the low dropout rate), so the findings may not be generalizable.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. Dr. Varady has reported receiving author fees from the Hachette Book Group for the book entitled “The Every Other Day Diet.” The other authors have reported no relevant financial relationships.

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

In the first study to examine how intermittent fasting combined with exercise impacts nonalcoholic fatty liver disease (NAFLD), the combined strategy was more effective than aerobic exercise alone or no intervention (control).

However, the combined approach did not give significantly added benefit, compared with fasting alone, the researchers report.

Eighty patients with NAFLD were randomized to one of four lifestyle strategies (alternate-day fasting, aerobic exercise, both, or neither) for 3 months.

The primary outcome was change in intrahepatic triglyceride (IHTG) content from baseline to study end, measured by magnetic resonance imaging proton density fat fraction.

The results suggest that “combining intermittent fasting with exercise is effective for reducing hepatic steatosis [fatty liver] in patients with NAFLD but may offer no additional benefit versus fasting alone,” Mark Ezpeleta, PhD, formerly at the University of Illinois, Chicago, and now at the University of Colorado Anschutz Medical Campus, and colleagues conclude.

“Our findings also indicate that the combination intervention was effective for reducing body weight, fat mass, waist circumference, [the liver enzyme alanine transaminase (ALT)], fasting insulin, [and] insulin resistance and increasing insulin sensitivity, among patients with obesity and NAFLD versus controls,” the group reports.  

“When we compared the results of our study groups, we saw clearly that the most improved patients were in the group that followed the alternate-day fasting diet and exercised 5 days a week,” senior author Krista A. Varady, PhD, professor of nutrition, University of Illinois, said in a press release from the university.

“The people who only dieted or only exercised did not see the same improvements,” she added, “which reinforces the importance of these two relatively inexpensive lifestyle modifications on overall health and on combating chronic diseases like fatty liver disease.”

Moreover, “alternate-day fasting and exercise interventions can be difficult for people to stick to, and in prior studies we have seen significant dropout,” she noted. “It was very interesting to see that in this trial we had very high adherence to the interventions.”

The study was recently published in Cell Metabolism.  

An estimated 65% of people with obesity have NAFLD, or fat in the liver that is not the result of excessive alcohol consumption, which is strongly related to the development of insulin resistance and type 2 diabetes, the group writes.

Thiazolidinediones such as pioglitazone reduce hepatic steatosis, but there is mounting concern about the weight-gaining effect of these compounds.

Recent attention has focused on lifestyle interventions to resolve hepatic steatosis, and previous trials showed that alternate-day fasting was effective for certain outcomes in NAFLD, but those studies did not measure changes in IHTG content or include an exercise intervention.

The researchers enrolled 80 adults with obesity and NAFLD and randomized them to one of four groups for 3 months:

• Alternate day fasting group: Participants were instructed to consume 600 kcal at dinner between 5 PM and 8 PM on a fasting day alternating with food as desired on a feasting day.
• Exercise group: A 60-minute moderate-intensity aerobic exercise session 5 times a week.
• Fasting plus exercise group.
• Control group (no intervention).

Participants were age 23-65 (mean age, 44) and 81% were women.

Half were Hispanic, and the rest were Black (30%), White (11%), or Asian (9%).

They had a mean weight of 99 kg (218 lb) and a mean body mass index of 36 kg/m².

Dropout rates were minimal in the combination group (0%) and fasting groups (5%) and moderately high in the exercise group (25%).

IHTG content was reduced by a significantly greater amount in the combination group (–5.48%) than in the exercise alone group (–1.30%; P = .02) or in the control group (–0.17%; P < .01) and by a greater amount than in the fasting alone group, although this was not significant (–2.25%; P = .05).

Lean mass, aspartate transaminase (AST), A1c, blood pressure, plasma lipids, liver fibrosis score, and hepatokines (fetuin-A, FGF-21, and selenoprotein P) did not differ between groups.

Researchers acknowledge that although the combination intervention resulted in improved NAFLD parameters, IHTG and ALT did not reach the normal range.  

Participants likely had early stage NAFLD (their baseline IHTG was in the 16% to 18% range, where 5% to 33% is mild steatosis) and they were likely highly motivated (indicated by the low dropout rate), so the findings may not be generalizable.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. Dr. Varady has reported receiving author fees from the Hachette Book Group for the book entitled “The Every Other Day Diet.” The other authors have reported no relevant financial relationships.

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

Treatment with the diabetes drug metformin shows a significant, dose-dependent effect in lowering SARS-CoV-2 viral load within days of administration, according to the latest analysis of the phase 3 COVID-OUT trial. These findings add to a multitude of benefits the drug has been shown to have in COVID infection.

COVID-OUT did not meet its primary endpoint, but it did show important secondary outcomes including a 42% reduction in ED visits and in hospitalizations and/or deaths by day 14, and a 58% reduction in hospitalizations/death by day 28. A further subanalysis has shown a 42% reduction in long COVID, compared with placebo.

“In this phase 3 randomized controlled trial, metformin showed prevention of severe COVID, prevention of long COVID, and an antiviral effect, and this is consistent with other data,” said coauthor Carolyn Bramante, MD, University of Minnesota, Minneapolis, in presenting the findings at the Conference on Retroviruses & Opportunistic Infections.
 

Study details

For the new subanalysis, the authors further evaluated the effects of metformin treatment on SARS-CoV-2 viral load.

A total of 1,323 patients in the study, enrolled at six centers, were randomized to treatment either with metformin 1,000 mg per day on days 2-5 and 1,500 mg per day on days 6 to 14 (n = 187), or to ivermectin 390-470 mcg/kg per day for 3 days (n = 187), fluvoxamine 50 mg twice daily for 14 days, and/or an exact-matching placebo in a 2 x 3 factorial trial design.

The subanalysis on viral load included 483 patients from the trial who were treated with metformin versus 462 who received placebo, who were all enrolled within 3 days of a documented SARS-CoV-2 infection and less than 7 days after symptom onset.

The patients had a median age of 46 years, and all had either overweight or obesity. Only about 2% had diabetes, and only patients considered low-risk were excluded from the trial, including those under age 30 and those with a body mass index under 25.

About half of patients had received a primary vaccine and about 5% had received a vaccine booster. SARS-CoV-2 variants that were prominent during the study included Alpha, Delta, and Omicron.

The viral samples available on days 1, 5, and 10 showed a mean change in viral load from baseline to follow-up; the viral load was significantly lower with metformin versus placebo (–0.64 log10 copies/mL), representing a 4.4-fold greater decrease in viral load with metformin.

The mean rate of undetectable SARS-CoV-2 viral load at day 5 was 49.9% in the metformin group versus 54.6% in the placebo group (odds ratio, 1.235), and the undetectable rate at day 10 was 14.3% in the metformin group and 22.6% in the placebo group (OR, 1.663; P = .003).

An increased antiviral effect corresponded with increases in metformin dosing on days 6 through 14. Furthermore, the antiviral effect became stronger when metformin was started earlier in the course of infection.

Of note, the antiviral effect was more pronounced among those who were not vaccinated (mean, –0.95 log copies/mL), compared with the vaccinated (mean, –0.39 log copies/mL).

The antiviral effect with metformin was similar to that seen with nirmatrelvir at day 5 and was greater than nirmatrelvir at day 10.

No similar relationships in SARS-CoV-2 viral load were observed between ivermectin or fluvoxamine and placebo.

The findings are consistent with results of other recent observational studies, including research showing metformin to be associated with reductions in COVID-19 severity in patients with prediabetes, Dr. Bramante noted.

The authors’ previous analysis looking at long COVID in the COVID-OUT study showed that metformin treatment during acute COVID significantly reduced the risk for a diagnosis of long COVID versus placebo at 300 days following randomization, with a hazard ratio of 0.59 after adjustment for the study drug and vaccination at baseline.

Dr. Bramante noted that metformin’s potential antiviral properties have long been speculated, with some of the earliest research on the drug suggesting less severe outcomes in influenza, and more recently, RNA assays suggesting effects against other RNA viruses, including the Zika virus.

In terms of COVID, Dr. Bramante noted that the drug has plenty of potentially favorable benefits.

“Metformin is very safe and is known to have very few contraindications, so the next steps could be to consider looking at this in terms of a combination therapy,” she said.
 

‘Data from other studies are conflicting’

Commenting on the study, Diane V. Havlir, MD, cautioned that “metformin is currently not recommended in treatment guidelines, [and] data from other studies are conflicting; side effects can be an issue, and the study presented here was in a select population,” she said in an interview.

However, “what is both new and interesting in this presentation is the reduction of viral load, which [was observed] in the samples collected not only on days 1-5, but also days 6-14,” said Dr. Havlir, who is professor and associate chair of clinical research, department of medicine, and chief of the division of HIV, infectious diseases and global medicine and director of the AIDS Research Institute at the University of California, San Francisco.

Key questions the findings raise include whether the results correlate with clinical outcomes or transmission, and whether the findings are generalizable to other populations and settings, Dr. Havlir said.

Ultimately, “we need to continue to pursue all aspects of outpatient treatments for COVID to address questions like these for new and existing agents,” she added.

The trial received funding from the Parsemus Foundation, the Rainwater Charitable Foundation, Fast Grants, and the United Health Group. The authors and Dr. Havlir disclosed no relevant financial relationships.

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

Treatment with the diabetes drug metformin shows a significant, dose-dependent effect in lowering SARS-CoV-2 viral load within days of administration, according to the latest analysis of the phase 3 COVID-OUT trial. These findings add to a multitude of benefits the drug has been shown to have in COVID infection.

COVID-OUT did not meet its primary endpoint, but it did show important secondary outcomes including a 42% reduction in ED visits and in hospitalizations and/or deaths by day 14, and a 58% reduction in hospitalizations/death by day 28. A further subanalysis has shown a 42% reduction in long COVID, compared with placebo.

“In this phase 3 randomized controlled trial, metformin showed prevention of severe COVID, prevention of long COVID, and an antiviral effect, and this is consistent with other data,” said coauthor Carolyn Bramante, MD, University of Minnesota, Minneapolis, in presenting the findings at the Conference on Retroviruses & Opportunistic Infections.
 

Study details

For the new subanalysis, the authors further evaluated the effects of metformin treatment on SARS-CoV-2 viral load.

A total of 1,323 patients in the study, enrolled at six centers, were randomized to treatment either with metformin 1,000 mg per day on days 2-5 and 1,500 mg per day on days 6 to 14 (n = 187), or to ivermectin 390-470 mcg/kg per day for 3 days (n = 187), fluvoxamine 50 mg twice daily for 14 days, and/or an exact-matching placebo in a 2 x 3 factorial trial design.

The subanalysis on viral load included 483 patients from the trial who were treated with metformin versus 462 who received placebo, who were all enrolled within 3 days of a documented SARS-CoV-2 infection and less than 7 days after symptom onset.

The patients had a median age of 46 years, and all had either overweight or obesity. Only about 2% had diabetes, and only patients considered low-risk were excluded from the trial, including those under age 30 and those with a body mass index under 25.

About half of patients had received a primary vaccine and about 5% had received a vaccine booster. SARS-CoV-2 variants that were prominent during the study included Alpha, Delta, and Omicron.

The viral samples available on days 1, 5, and 10 showed a mean change in viral load from baseline to follow-up; the viral load was significantly lower with metformin versus placebo (–0.64 log10 copies/mL), representing a 4.4-fold greater decrease in viral load with metformin.

The mean rate of undetectable SARS-CoV-2 viral load at day 5 was 49.9% in the metformin group versus 54.6% in the placebo group (odds ratio, 1.235), and the undetectable rate at day 10 was 14.3% in the metformin group and 22.6% in the placebo group (OR, 1.663; P = .003).

An increased antiviral effect corresponded with increases in metformin dosing on days 6 through 14. Furthermore, the antiviral effect became stronger when metformin was started earlier in the course of infection.

Of note, the antiviral effect was more pronounced among those who were not vaccinated (mean, –0.95 log copies/mL), compared with the vaccinated (mean, –0.39 log copies/mL).

The antiviral effect with metformin was similar to that seen with nirmatrelvir at day 5 and was greater than nirmatrelvir at day 10.

No similar relationships in SARS-CoV-2 viral load were observed between ivermectin or fluvoxamine and placebo.

The findings are consistent with results of other recent observational studies, including research showing metformin to be associated with reductions in COVID-19 severity in patients with prediabetes, Dr. Bramante noted.

The authors’ previous analysis looking at long COVID in the COVID-OUT study showed that metformin treatment during acute COVID significantly reduced the risk for a diagnosis of long COVID versus placebo at 300 days following randomization, with a hazard ratio of 0.59 after adjustment for the study drug and vaccination at baseline.

Dr. Bramante noted that metformin’s potential antiviral properties have long been speculated, with some of the earliest research on the drug suggesting less severe outcomes in influenza, and more recently, RNA assays suggesting effects against other RNA viruses, including the Zika virus.

In terms of COVID, Dr. Bramante noted that the drug has plenty of potentially favorable benefits.

“Metformin is very safe and is known to have very few contraindications, so the next steps could be to consider looking at this in terms of a combination therapy,” she said.
 

‘Data from other studies are conflicting’

Commenting on the study, Diane V. Havlir, MD, cautioned that “metformin is currently not recommended in treatment guidelines, [and] data from other studies are conflicting; side effects can be an issue, and the study presented here was in a select population,” she said in an interview.

However, “what is both new and interesting in this presentation is the reduction of viral load, which [was observed] in the samples collected not only on days 1-5, but also days 6-14,” said Dr. Havlir, who is professor and associate chair of clinical research, department of medicine, and chief of the division of HIV, infectious diseases and global medicine and director of the AIDS Research Institute at the University of California, San Francisco.

Key questions the findings raise include whether the results correlate with clinical outcomes or transmission, and whether the findings are generalizable to other populations and settings, Dr. Havlir said.

Ultimately, “we need to continue to pursue all aspects of outpatient treatments for COVID to address questions like these for new and existing agents,” she added.

The trial received funding from the Parsemus Foundation, the Rainwater Charitable Foundation, Fast Grants, and the United Health Group. The authors and Dr. Havlir disclosed no relevant financial relationships.

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

Treatment with the diabetes drug metformin shows a significant, dose-dependent effect in lowering SARS-CoV-2 viral load within days of administration, according to the latest analysis of the phase 3 COVID-OUT trial. These findings add to a multitude of benefits the drug has been shown to have in COVID infection.

COVID-OUT did not meet its primary endpoint, but it did show important secondary outcomes including a 42% reduction in ED visits and in hospitalizations and/or deaths by day 14, and a 58% reduction in hospitalizations/death by day 28. A further subanalysis has shown a 42% reduction in long COVID, compared with placebo.

“In this phase 3 randomized controlled trial, metformin showed prevention of severe COVID, prevention of long COVID, and an antiviral effect, and this is consistent with other data,” said coauthor Carolyn Bramante, MD, University of Minnesota, Minneapolis, in presenting the findings at the Conference on Retroviruses & Opportunistic Infections.
 

Study details

For the new subanalysis, the authors further evaluated the effects of metformin treatment on SARS-CoV-2 viral load.

A total of 1,323 patients in the study, enrolled at six centers, were randomized to treatment either with metformin 1,000 mg per day on days 2-5 and 1,500 mg per day on days 6 to 14 (n = 187), or to ivermectin 390-470 mcg/kg per day for 3 days (n = 187), fluvoxamine 50 mg twice daily for 14 days, and/or an exact-matching placebo in a 2 x 3 factorial trial design.

The subanalysis on viral load included 483 patients from the trial who were treated with metformin versus 462 who received placebo, who were all enrolled within 3 days of a documented SARS-CoV-2 infection and less than 7 days after symptom onset.

The patients had a median age of 46 years, and all had either overweight or obesity. Only about 2% had diabetes, and only patients considered low-risk were excluded from the trial, including those under age 30 and those with a body mass index under 25.

About half of patients had received a primary vaccine and about 5% had received a vaccine booster. SARS-CoV-2 variants that were prominent during the study included Alpha, Delta, and Omicron.

The viral samples available on days 1, 5, and 10 showed a mean change in viral load from baseline to follow-up; the viral load was significantly lower with metformin versus placebo (–0.64 log10 copies/mL), representing a 4.4-fold greater decrease in viral load with metformin.

The mean rate of undetectable SARS-CoV-2 viral load at day 5 was 49.9% in the metformin group versus 54.6% in the placebo group (odds ratio, 1.235), and the undetectable rate at day 10 was 14.3% in the metformin group and 22.6% in the placebo group (OR, 1.663; P = .003).

An increased antiviral effect corresponded with increases in metformin dosing on days 6 through 14. Furthermore, the antiviral effect became stronger when metformin was started earlier in the course of infection.

Of note, the antiviral effect was more pronounced among those who were not vaccinated (mean, –0.95 log copies/mL), compared with the vaccinated (mean, –0.39 log copies/mL).

The antiviral effect with metformin was similar to that seen with nirmatrelvir at day 5 and was greater than nirmatrelvir at day 10.

No similar relationships in SARS-CoV-2 viral load were observed between ivermectin or fluvoxamine and placebo.

The findings are consistent with results of other recent observational studies, including research showing metformin to be associated with reductions in COVID-19 severity in patients with prediabetes, Dr. Bramante noted.

The authors’ previous analysis looking at long COVID in the COVID-OUT study showed that metformin treatment during acute COVID significantly reduced the risk for a diagnosis of long COVID versus placebo at 300 days following randomization, with a hazard ratio of 0.59 after adjustment for the study drug and vaccination at baseline.

Dr. Bramante noted that metformin’s potential antiviral properties have long been speculated, with some of the earliest research on the drug suggesting less severe outcomes in influenza, and more recently, RNA assays suggesting effects against other RNA viruses, including the Zika virus.

In terms of COVID, Dr. Bramante noted that the drug has plenty of potentially favorable benefits.

“Metformin is very safe and is known to have very few contraindications, so the next steps could be to consider looking at this in terms of a combination therapy,” she said.
 

‘Data from other studies are conflicting’

Commenting on the study, Diane V. Havlir, MD, cautioned that “metformin is currently not recommended in treatment guidelines, [and] data from other studies are conflicting; side effects can be an issue, and the study presented here was in a select population,” she said in an interview.

However, “what is both new and interesting in this presentation is the reduction of viral load, which [was observed] in the samples collected not only on days 1-5, but also days 6-14,” said Dr. Havlir, who is professor and associate chair of clinical research, department of medicine, and chief of the division of HIV, infectious diseases and global medicine and director of the AIDS Research Institute at the University of California, San Francisco.

Key questions the findings raise include whether the results correlate with clinical outcomes or transmission, and whether the findings are generalizable to other populations and settings, Dr. Havlir said.

Ultimately, “we need to continue to pursue all aspects of outpatient treatments for COVID to address questions like these for new and existing agents,” she added.

The trial received funding from the Parsemus Foundation, the Rainwater Charitable Foundation, Fast Grants, and the United Health Group. The authors and Dr. Havlir disclosed no relevant financial relationships.

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

Continuous glucose monitoring (CGM) is gaining ground with both patients and providers because of an array of driving forces, including broadening eligibility, insulin price caps, public awareness, and an increasing number of educational initiatives for doctors.

While professional organizations aim to familiarize doctors with this relatively new technology, more patients are learning independently that finger sticks may be optional, leading them to request CGM from their provider, according to Neil Skolnik, MD.

Overview of online resources and navigating coverage

The latest learning resource on CGM for physicians comes from the American Academy of Family Physicians in the form of a new online educational hub with a 2-credit, ACCME-accredited course. It offers comprehensive guidance for employing CGM in daily practice. Topics include both medical and practical considerations, from interpretation of curves and glucose goal-setting to choosing a device and navigating coverage.

The AAFP’s new offering joins a growing number of similar educational efforts launched over the past few years by the Association of Diabetes Care & Education Specialists, the American Pharmacists Association, the American Diabetes Association, and the American Association of Clinical Endocrinologists.

Checking for coverage is a key first step when considering CGM for a particular patient, Dr. Jones said, noting that CGM, like any new form of care, presents unique challenges with coding and claims that must be overcome to get reimbursed.

“No margin, no mission,” Dr. Jones said. “If you are not able to pay your bills, you can’t be available for your patients. Our goal at the AAFP is to make sure that physicians get this knowledge [about reimbursement].”

To this end, the AAFP’s new online educational hub and the guide provided by APhA present CGM eligibility criteria for various patient groups, including those with Medicare, Medicaid, private insurance, and without coverage.

Medicare criteria include a diagnosis of diabetes, treatment with three or more daily administrations of insulin or continuous infusion via a pump, frequent adjustment to insulin treatment based on glucose readings, and presentation for diabetes in the past 6 months.

Once these requirements are clearly documented in the patient’s record, providers need to write the script, complete a certificate of medical necessity, and choose a supplier. Medicare covers CGM as a durable medical equipment benefit instead of a pharmacy benefit, according to the AAFP and APhA.

Exact coverage criteria and reimbursement processes for non-Medicare patients follow similar paths, although details vary by state and insurer, so personalized investigation is required.

When exploring coverage, the AAFP recommends paying attention to information needed for prior authorization, the patient’s diabetes type and age, and other medical requirements, such as minimum number of daily finger sticks or insulin doses per day.

Looking ahead, Dr. Jones predicted that authorization obstacles stemming from short-term cost concerns are going to fade as long-term savings are uncovered.

“I think pharmacy benefit managers and payers are going to recognize that we have better patient compliance, and that continuous glucose monitoring is going to bring the cost of care down and decrease the rate of hospitalizations,” Dr. Jones said. “So I think they’re going to be willing to pay clinicians to engage in this more readily over time.”

Patients who fail to qualify for personal CGM can still benefit from professional CGM, in which they borrow necessary equipment on a short-term basis. This avenue typically requires minimal or no insurance authorization. In addition, providers have the “opportunity to cover/exceed expenses by enhancing revenue with separately billable procedures, which can be billed in addition to [evaluation and management] if done on same day,” according to the AAFP guide, which goes on to provide appropriate codes.
 

Learning CGM through first-hand experience

Getting started with CGM can be intimidating for providers, Dr. Skolnik said, although he offered some reassurance, suggesting that the learning process may be more forgiving than prescribing a new drug for the first time.

“I think the best way to figure out CGM is to prescribe it to a couple of patients and learn with them,” Dr. Skolnik said. “You can’t do that with medicines. With medicines, you need to know what you’re doing before you choose who to give a medicine to.”

Courtesy Dr. Neil Skolnik

Encouraging patients to start CGM

Like providers, patients may also be intimidated by CGM, Dr. Jones said, typically because they don’t know how it works, or it seems complicated. Fortunately, he said, these fears are easily overcome when patients learn that they don’t need to stick themselves, record any of their readings, or really do anything at all for the first few weeks.

“You don’t even worry about it,” Dr. Jones tells his patients, who typically feel “more in control and engaged in their own care” after experiencing CGM for themselves.

Dr. Jones speaks from both professional and personal experience. A member of his family recently started CGM after being discharged from the hospital, and the benefits have been significant for everyone involved.

“I see how effectively we can control [my family member’s] blood pressure and insulin requirements, as opposed to several months ago when we didn’t have it,” Dr. Jones said. “So I’m giving it to you from two perspectives: one, of the clinician who knows, intellectually, what should go on, and two, experientially, from a family trying to take care of someone they love.”

Dr. Skolnik disclosed relationships with AstraZeneca, Teva, Lilly, Boehringer Ingelheim, Sanofi, GSK, Bayer, Genentech, Abbott, Idorsia, Merck, Novartis, Heartland, and Novo Nordisk. Dr Jones disclosed no relevant conflicts of interest.

Continuous glucose monitoring (CGM) is gaining ground with both patients and providers because of an array of driving forces, including broadening eligibility, insulin price caps, public awareness, and an increasing number of educational initiatives for doctors.

While professional organizations aim to familiarize doctors with this relatively new technology, more patients are learning independently that finger sticks may be optional, leading them to request CGM from their provider, according to Neil Skolnik, MD.

Overview of online resources and navigating coverage

The latest learning resource on CGM for physicians comes from the American Academy of Family Physicians in the form of a new online educational hub with a 2-credit, ACCME-accredited course. It offers comprehensive guidance for employing CGM in daily practice. Topics include both medical and practical considerations, from interpretation of curves and glucose goal-setting to choosing a device and navigating coverage.

The AAFP’s new offering joins a growing number of similar educational efforts launched over the past few years by the Association of Diabetes Care & Education Specialists, the American Pharmacists Association, the American Diabetes Association, and the American Association of Clinical Endocrinologists.

Checking for coverage is a key first step when considering CGM for a particular patient, Dr. Jones said, noting that CGM, like any new form of care, presents unique challenges with coding and claims that must be overcome to get reimbursed.

“No margin, no mission,” Dr. Jones said. “If you are not able to pay your bills, you can’t be available for your patients. Our goal at the AAFP is to make sure that physicians get this knowledge [about reimbursement].”

To this end, the AAFP’s new online educational hub and the guide provided by APhA present CGM eligibility criteria for various patient groups, including those with Medicare, Medicaid, private insurance, and without coverage.

Medicare criteria include a diagnosis of diabetes, treatment with three or more daily administrations of insulin or continuous infusion via a pump, frequent adjustment to insulin treatment based on glucose readings, and presentation for diabetes in the past 6 months.

Once these requirements are clearly documented in the patient’s record, providers need to write the script, complete a certificate of medical necessity, and choose a supplier. Medicare covers CGM as a durable medical equipment benefit instead of a pharmacy benefit, according to the AAFP and APhA.

Exact coverage criteria and reimbursement processes for non-Medicare patients follow similar paths, although details vary by state and insurer, so personalized investigation is required.

When exploring coverage, the AAFP recommends paying attention to information needed for prior authorization, the patient’s diabetes type and age, and other medical requirements, such as minimum number of daily finger sticks or insulin doses per day.

Looking ahead, Dr. Jones predicted that authorization obstacles stemming from short-term cost concerns are going to fade as long-term savings are uncovered.

“I think pharmacy benefit managers and payers are going to recognize that we have better patient compliance, and that continuous glucose monitoring is going to bring the cost of care down and decrease the rate of hospitalizations,” Dr. Jones said. “So I think they’re going to be willing to pay clinicians to engage in this more readily over time.”

Patients who fail to qualify for personal CGM can still benefit from professional CGM, in which they borrow necessary equipment on a short-term basis. This avenue typically requires minimal or no insurance authorization. In addition, providers have the “opportunity to cover/exceed expenses by enhancing revenue with separately billable procedures, which can be billed in addition to [evaluation and management] if done on same day,” according to the AAFP guide, which goes on to provide appropriate codes.
 

Learning CGM through first-hand experience

Getting started with CGM can be intimidating for providers, Dr. Skolnik said, although he offered some reassurance, suggesting that the learning process may be more forgiving than prescribing a new drug for the first time.

“I think the best way to figure out CGM is to prescribe it to a couple of patients and learn with them,” Dr. Skolnik said. “You can’t do that with medicines. With medicines, you need to know what you’re doing before you choose who to give a medicine to.”

Courtesy Dr. Neil Skolnik

Encouraging patients to start CGM

Like providers, patients may also be intimidated by CGM, Dr. Jones said, typically because they don’t know how it works, or it seems complicated. Fortunately, he said, these fears are easily overcome when patients learn that they don’t need to stick themselves, record any of their readings, or really do anything at all for the first few weeks.

“You don’t even worry about it,” Dr. Jones tells his patients, who typically feel “more in control and engaged in their own care” after experiencing CGM for themselves.

Dr. Jones speaks from both professional and personal experience. A member of his family recently started CGM after being discharged from the hospital, and the benefits have been significant for everyone involved.

“I see how effectively we can control [my family member’s] blood pressure and insulin requirements, as opposed to several months ago when we didn’t have it,” Dr. Jones said. “So I’m giving it to you from two perspectives: one, of the clinician who knows, intellectually, what should go on, and two, experientially, from a family trying to take care of someone they love.”

Dr. Skolnik disclosed relationships with AstraZeneca, Teva, Lilly, Boehringer Ingelheim, Sanofi, GSK, Bayer, Genentech, Abbott, Idorsia, Merck, Novartis, Heartland, and Novo Nordisk. Dr Jones disclosed no relevant conflicts of interest.

Continuous glucose monitoring (CGM) is gaining ground with both patients and providers because of an array of driving forces, including broadening eligibility, insulin price caps, public awareness, and an increasing number of educational initiatives for doctors.

While professional organizations aim to familiarize doctors with this relatively new technology, more patients are learning independently that finger sticks may be optional, leading them to request CGM from their provider, according to Neil Skolnik, MD.

Overview of online resources and navigating coverage

The latest learning resource on CGM for physicians comes from the American Academy of Family Physicians in the form of a new online educational hub with a 2-credit, ACCME-accredited course. It offers comprehensive guidance for employing CGM in daily practice. Topics include both medical and practical considerations, from interpretation of curves and glucose goal-setting to choosing a device and navigating coverage.

The AAFP’s new offering joins a growing number of similar educational efforts launched over the past few years by the Association of Diabetes Care & Education Specialists, the American Pharmacists Association, the American Diabetes Association, and the American Association of Clinical Endocrinologists.

Checking for coverage is a key first step when considering CGM for a particular patient, Dr. Jones said, noting that CGM, like any new form of care, presents unique challenges with coding and claims that must be overcome to get reimbursed.

“No margin, no mission,” Dr. Jones said. “If you are not able to pay your bills, you can’t be available for your patients. Our goal at the AAFP is to make sure that physicians get this knowledge [about reimbursement].”

To this end, the AAFP’s new online educational hub and the guide provided by APhA present CGM eligibility criteria for various patient groups, including those with Medicare, Medicaid, private insurance, and without coverage.

Medicare criteria include a diagnosis of diabetes, treatment with three or more daily administrations of insulin or continuous infusion via a pump, frequent adjustment to insulin treatment based on glucose readings, and presentation for diabetes in the past 6 months.

Once these requirements are clearly documented in the patient’s record, providers need to write the script, complete a certificate of medical necessity, and choose a supplier. Medicare covers CGM as a durable medical equipment benefit instead of a pharmacy benefit, according to the AAFP and APhA.

Exact coverage criteria and reimbursement processes for non-Medicare patients follow similar paths, although details vary by state and insurer, so personalized investigation is required.

When exploring coverage, the AAFP recommends paying attention to information needed for prior authorization, the patient’s diabetes type and age, and other medical requirements, such as minimum number of daily finger sticks or insulin doses per day.

Looking ahead, Dr. Jones predicted that authorization obstacles stemming from short-term cost concerns are going to fade as long-term savings are uncovered.

“I think pharmacy benefit managers and payers are going to recognize that we have better patient compliance, and that continuous glucose monitoring is going to bring the cost of care down and decrease the rate of hospitalizations,” Dr. Jones said. “So I think they’re going to be willing to pay clinicians to engage in this more readily over time.”

Patients who fail to qualify for personal CGM can still benefit from professional CGM, in which they borrow necessary equipment on a short-term basis. This avenue typically requires minimal or no insurance authorization. In addition, providers have the “opportunity to cover/exceed expenses by enhancing revenue with separately billable procedures, which can be billed in addition to [evaluation and management] if done on same day,” according to the AAFP guide, which goes on to provide appropriate codes.
 

Learning CGM through first-hand experience

Getting started with CGM can be intimidating for providers, Dr. Skolnik said, although he offered some reassurance, suggesting that the learning process may be more forgiving than prescribing a new drug for the first time.

“I think the best way to figure out CGM is to prescribe it to a couple of patients and learn with them,” Dr. Skolnik said. “You can’t do that with medicines. With medicines, you need to know what you’re doing before you choose who to give a medicine to.”

Courtesy Dr. Neil Skolnik

Encouraging patients to start CGM

Like providers, patients may also be intimidated by CGM, Dr. Jones said, typically because they don’t know how it works, or it seems complicated. Fortunately, he said, these fears are easily overcome when patients learn that they don’t need to stick themselves, record any of their readings, or really do anything at all for the first few weeks.

“You don’t even worry about it,” Dr. Jones tells his patients, who typically feel “more in control and engaged in their own care” after experiencing CGM for themselves.

Dr. Jones speaks from both professional and personal experience. A member of his family recently started CGM after being discharged from the hospital, and the benefits have been significant for everyone involved.

“I see how effectively we can control [my family member’s] blood pressure and insulin requirements, as opposed to several months ago when we didn’t have it,” Dr. Jones said. “So I’m giving it to you from two perspectives: one, of the clinician who knows, intellectually, what should go on, and two, experientially, from a family trying to take care of someone they love.”

Dr. Skolnik disclosed relationships with AstraZeneca, Teva, Lilly, Boehringer Ingelheim, Sanofi, GSK, Bayer, Genentech, Abbott, Idorsia, Merck, Novartis, Heartland, and Novo Nordisk. Dr Jones disclosed no relevant conflicts of interest.

SAN FRANCISCO – For patients with metastatic castration-resistant prostate cancer (mCRPC) with a BRCA alteration whose disease had already progressed with an androgen receptor pathway inhibitor (ARPI), imaging-based progression-free survival (PFS) was significantly longer through treatment with rucaparib (Rubraca, Clovis) than with any other drug chosen by their physician.

The finding, which comes from the TRITON3 clinical trial, provides evidence of clinical benefit for an indication for rucaparib that was granted an accelerated approval in May 2020.

“Rucaparib reduced the risk of progression or death by half in patients with BRCA alterations,” said lead author Alan H. Bryce, MD, medical director of the Genomic Oncology Clinic at Mayo Clinic Arizona, in Phoenix.

For the subgroup of patients with BRCA alterations, the median PFS was 11.2 months with rucaparib vs. 6.4 months (hazard ratio, 0.50; P < .001) among those who received physician’s choice of therapy, which included docetaxel or a second-generation ARPI, such as abiraterone or enzalutamide.

In another subgroup of patients whose disease had ATM alterations, the median PFS was 8.1 months with rucaparib vs. 6.8 months with physician’s choice of drug. The difference was not statistically significant.

However, the difference was significant in the intention-to-treat (ITT) population (comprising both subgroups), for whom the median PFS was 10.2 months with rucaparib vs. 6.4 months with physician’s choice of drug (HR, 0.61; P < .001 by log-rank test).

Dr. Bryce pointed out that three-quarters of the patients in the physician’s-choice arm who had progressive disease crossed over to rucaparib upon progression and that overall survival (OS) results are immature. At 62 months, median OS did not significantly differ in the BRCA subgroup (24.3 vs. 20.8 months favoring rucaparib; P = .21) or in the ITT group (23.6 vs. 20.9 months; P = .67).

Importantly, rucaparib was well tolerated. In all treatment groups, the most frequent adverse events were asthenia and fatigue, Bryce said. “There were no cases of myelodysplastic syndrome or acute myeloid leukemia reported.”

These results from the TRITON3 trial were presented at the 2023 ASCO Genitourinary Cancers Symposium and were published simultaneously in the New England Journal of Medicine.
 

Suggested benefit

Rucaparib is the first PARP inhibitor approved for use in patients with mCRPC that harbors deleterious BRCA mutations (germline and/or somatic) who have already been treated with androgen receptor–directed therapy and a taxane-based chemotherapy. This prostate cancer indication was granted an accelerated approval in May 2020 by the U.S. Food and Drug Administration on the basis of response rates and effect on levels of prostate-specific antigen (PSA) from the TRITON2 clinical trial, the forerunner of the current study.

The TRITON2 study was a single-arm clinical trial that involved three cohorts: 62 patients with a BRCA mutation (germline and/or somatic) and measurable disease; 115 patients with a BRCA mutation (germline and/or somatic) and measurable or nonmeasurable disease; and 209 patients with homologous recombination deficiency–positive mCRPC.

In an analysis of 115 patients with a deleterious BRCA mutation (germline and/or somatic) and measurable or nonmeasurable disease, the confirmed PSA response rate was 55%. For the patients with measurable disease and a BRCA mutation, the objective response rate was 44%. The objective response rate was similar for those with a germline BRCA mutation.
 

Study details

The current phase 3 randomized TRITON3 clinical trial was conducted to confirm the earlier findings and to expand upon the data in mCRPC. The participants in this trial were patients with mCRPC who had specific gene alterations, including BRCA and ATM alterations, who had experienced disease progression after androgen receptor–directed therapy but who had not yet received chemotherapy.

A total of 270 men were assigned to receive rucaparib (600 mg twice daily); 135 patients received their physician’s choice of medication. Within the two study arms, 302 patients had a BRCA alteration, and 103 patients had an ATM alteration. The ITT population consisted of all the patients who had been randomly assigned to either of the two groups. A prespecified subgroup included patients with a BRCA alteration.

The primary outcome was the median duration of imaging-based PSF, as determined through independent review. Key secondary outcomes were overall survival and objective response rate.

The most common adverse events in the rucaparib group were fatigue, nausea, and anemia or decreased hemoglobin. In the control group, the most common adverse events were fatigue, diarrhea, and neuropathy. The most common events of grade 3 or higher were anemia or decreased hemoglobin, neutropenia or a decreased neutrophil count, and fatigue in the rucaparib group, and fatigue and neutropenia or a decreased neutrophil count among control patients.
 

No changes in standard of care

In a discussion of the study, Elena Castro, MD, PhD, of the Instituto de Investigación Biomédica de Málaga, Campanillas, Spain, emphasized that there is a clear benefit from the use of PARP inhibitors (such as rucaparib) for patients with BRCA alterations.

However, she highlighted the absence of convincing overall survival data and the absence of a clear benefit on PFS in the subgroup of patients with ATM alterations.

“These data raise several questions,” she noted, “such as, do patients with ATM alterations benefit at all? And should PARP inhibitors [such as rucaparib] precede or follow docetaxel therapy?”

Because of the high crossover rate, it may be possible to evaluate the directionality of docetaxel followed by PARP inhibitors and the other way around, she suggested.

Dr. Castro said that patients with BRCA alterations benefit from PARP inhibitors and are likely to derive more benefit from them than from taxanes.

“But those with ATM alterations are unlikely to benefit from rucaparib more than from taxanes,” she said.

In a comment, Hank Ng, MD, medical oncologist, NYU Langone Perlmutter Cancer Center, New York, said he is not convinced that the findings from TRITON 3 represent a new standard of care in BRCA 1/2 mutations or ATM.

“Currently, we know that, for patients with prostate cancer with BRCA1/2 or ATM, the standard of care is an androgen receptor pathway inhibitor (ARPI), such as abiraterone or enzalutamide, then docetaxel, and then a PARP inhibitor like rucaparib,” he said.

(Currently, rucaparib is indicated for use in patients with mCRPC with BRCA alterations after they have already received an ARPI and taxane-based chemotherapy.)

Dr. Ng also questioned the control arm of the TRITON 3 trial. All the participants in the trial had already experienced disease progression after treatment with a second-generation ARPI. But the physician’s choice of therapy allowed them to move on to another ARPI or to docetaxel.

Dr. NG commented that, “in almost all cases, after progression of one ARPI, switching to another ARPI does not provide much benefit – from what is visible from this abstract – and only 56% patients received docetaxel, and thus 44% received a not-beneficial treatment,” he said.

“I am not sure what the docetaxel subgroup showed, but potentially, if those numbers are convincing, we could move this [rucaparib] ahead of docetaxel,” he speculated.

However, he also pointed out that an overall survival benefit has not yet been shown; so far, the benefit that has been shown is with respect to imaging-based PFS.

Dr. Ng does agree that rucaparib is indicated in the second line after progression with one ARPI for patients who are not candidates for chemotherapy. “But this has not yet shown me that we should absolutely be offering rucaparib before docetaxel,” he said.

TRITON3 was supported by Clovis Oncology, manufacturer of rucaparib. Dr. Bryce has relationships with Bayer, Foundation Medicine, Janssen, Merck, Myovant Sciences, and Novartis and holds a patent for therapeutic targeting of cancer patients with NRG1 rearrangements. Dr. Castro has relationships with Astellas Pharma, AstraZeneca, Bayer, Clovis Oncology, Janssen-Cilag, Merck, MSD Oncology, Novartis, Pfizer, and Roche.

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

SAN FRANCISCO – For patients with metastatic castration-resistant prostate cancer (mCRPC) with a BRCA alteration whose disease had already progressed with an androgen receptor pathway inhibitor (ARPI), imaging-based progression-free survival (PFS) was significantly longer through treatment with rucaparib (Rubraca, Clovis) than with any other drug chosen by their physician.

The finding, which comes from the TRITON3 clinical trial, provides evidence of clinical benefit for an indication for rucaparib that was granted an accelerated approval in May 2020.

“Rucaparib reduced the risk of progression or death by half in patients with BRCA alterations,” said lead author Alan H. Bryce, MD, medical director of the Genomic Oncology Clinic at Mayo Clinic Arizona, in Phoenix.

For the subgroup of patients with BRCA alterations, the median PFS was 11.2 months with rucaparib vs. 6.4 months (hazard ratio, 0.50; P < .001) among those who received physician’s choice of therapy, which included docetaxel or a second-generation ARPI, such as abiraterone or enzalutamide.

In another subgroup of patients whose disease had ATM alterations, the median PFS was 8.1 months with rucaparib vs. 6.8 months with physician’s choice of drug. The difference was not statistically significant.

However, the difference was significant in the intention-to-treat (ITT) population (comprising both subgroups), for whom the median PFS was 10.2 months with rucaparib vs. 6.4 months with physician’s choice of drug (HR, 0.61; P < .001 by log-rank test).

Dr. Bryce pointed out that three-quarters of the patients in the physician’s-choice arm who had progressive disease crossed over to rucaparib upon progression and that overall survival (OS) results are immature. At 62 months, median OS did not significantly differ in the BRCA subgroup (24.3 vs. 20.8 months favoring rucaparib; P = .21) or in the ITT group (23.6 vs. 20.9 months; P = .67).

Importantly, rucaparib was well tolerated. In all treatment groups, the most frequent adverse events were asthenia and fatigue, Bryce said. “There were no cases of myelodysplastic syndrome or acute myeloid leukemia reported.”

These results from the TRITON3 trial were presented at the 2023 ASCO Genitourinary Cancers Symposium and were published simultaneously in the New England Journal of Medicine.
 

Suggested benefit

Rucaparib is the first PARP inhibitor approved for use in patients with mCRPC that harbors deleterious BRCA mutations (germline and/or somatic) who have already been treated with androgen receptor–directed therapy and a taxane-based chemotherapy. This prostate cancer indication was granted an accelerated approval in May 2020 by the U.S. Food and Drug Administration on the basis of response rates and effect on levels of prostate-specific antigen (PSA) from the TRITON2 clinical trial, the forerunner of the current study.

The TRITON2 study was a single-arm clinical trial that involved three cohorts: 62 patients with a BRCA mutation (germline and/or somatic) and measurable disease; 115 patients with a BRCA mutation (germline and/or somatic) and measurable or nonmeasurable disease; and 209 patients with homologous recombination deficiency–positive mCRPC.

In an analysis of 115 patients with a deleterious BRCA mutation (germline and/or somatic) and measurable or nonmeasurable disease, the confirmed PSA response rate was 55%. For the patients with measurable disease and a BRCA mutation, the objective response rate was 44%. The objective response rate was similar for those with a germline BRCA mutation.
 

Study details

The current phase 3 randomized TRITON3 clinical trial was conducted to confirm the earlier findings and to expand upon the data in mCRPC. The participants in this trial were patients with mCRPC who had specific gene alterations, including BRCA and ATM alterations, who had experienced disease progression after androgen receptor–directed therapy but who had not yet received chemotherapy.

A total of 270 men were assigned to receive rucaparib (600 mg twice daily); 135 patients received their physician’s choice of medication. Within the two study arms, 302 patients had a BRCA alteration, and 103 patients had an ATM alteration. The ITT population consisted of all the patients who had been randomly assigned to either of the two groups. A prespecified subgroup included patients with a BRCA alteration.

The primary outcome was the median duration of imaging-based PSF, as determined through independent review. Key secondary outcomes were overall survival and objective response rate.

The most common adverse events in the rucaparib group were fatigue, nausea, and anemia or decreased hemoglobin. In the control group, the most common adverse events were fatigue, diarrhea, and neuropathy. The most common events of grade 3 or higher were anemia or decreased hemoglobin, neutropenia or a decreased neutrophil count, and fatigue in the rucaparib group, and fatigue and neutropenia or a decreased neutrophil count among control patients.
 

No changes in standard of care

In a discussion of the study, Elena Castro, MD, PhD, of the Instituto de Investigación Biomédica de Málaga, Campanillas, Spain, emphasized that there is a clear benefit from the use of PARP inhibitors (such as rucaparib) for patients with BRCA alterations.

However, she highlighted the absence of convincing overall survival data and the absence of a clear benefit on PFS in the subgroup of patients with ATM alterations.

“These data raise several questions,” she noted, “such as, do patients with ATM alterations benefit at all? And should PARP inhibitors [such as rucaparib] precede or follow docetaxel therapy?”

Because of the high crossover rate, it may be possible to evaluate the directionality of docetaxel followed by PARP inhibitors and the other way around, she suggested.

Dr. Castro said that patients with BRCA alterations benefit from PARP inhibitors and are likely to derive more benefit from them than from taxanes.

“But those with ATM alterations are unlikely to benefit from rucaparib more than from taxanes,” she said.

In a comment, Hank Ng, MD, medical oncologist, NYU Langone Perlmutter Cancer Center, New York, said he is not convinced that the findings from TRITON 3 represent a new standard of care in BRCA 1/2 mutations or ATM.

“Currently, we know that, for patients with prostate cancer with BRCA1/2 or ATM, the standard of care is an androgen receptor pathway inhibitor (ARPI), such as abiraterone or enzalutamide, then docetaxel, and then a PARP inhibitor like rucaparib,” he said.

(Currently, rucaparib is indicated for use in patients with mCRPC with BRCA alterations after they have already received an ARPI and taxane-based chemotherapy.)

Dr. Ng also questioned the control arm of the TRITON 3 trial. All the participants in the trial had already experienced disease progression after treatment with a second-generation ARPI. But the physician’s choice of therapy allowed them to move on to another ARPI or to docetaxel.

Dr. NG commented that, “in almost all cases, after progression of one ARPI, switching to another ARPI does not provide much benefit – from what is visible from this abstract – and only 56% patients received docetaxel, and thus 44% received a not-beneficial treatment,” he said.

“I am not sure what the docetaxel subgroup showed, but potentially, if those numbers are convincing, we could move this [rucaparib] ahead of docetaxel,” he speculated.

However, he also pointed out that an overall survival benefit has not yet been shown; so far, the benefit that has been shown is with respect to imaging-based PFS.

Dr. Ng does agree that rucaparib is indicated in the second line after progression with one ARPI for patients who are not candidates for chemotherapy. “But this has not yet shown me that we should absolutely be offering rucaparib before docetaxel,” he said.

TRITON3 was supported by Clovis Oncology, manufacturer of rucaparib. Dr. Bryce has relationships with Bayer, Foundation Medicine, Janssen, Merck, Myovant Sciences, and Novartis and holds a patent for therapeutic targeting of cancer patients with NRG1 rearrangements. Dr. Castro has relationships with Astellas Pharma, AstraZeneca, Bayer, Clovis Oncology, Janssen-Cilag, Merck, MSD Oncology, Novartis, Pfizer, and Roche.

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

SAN FRANCISCO – For patients with metastatic castration-resistant prostate cancer (mCRPC) with a BRCA alteration whose disease had already progressed with an androgen receptor pathway inhibitor (ARPI), imaging-based progression-free survival (PFS) was significantly longer through treatment with rucaparib (Rubraca, Clovis) than with any other drug chosen by their physician.

The finding, which comes from the TRITON3 clinical trial, provides evidence of clinical benefit for an indication for rucaparib that was granted an accelerated approval in May 2020.

“Rucaparib reduced the risk of progression or death by half in patients with BRCA alterations,” said lead author Alan H. Bryce, MD, medical director of the Genomic Oncology Clinic at Mayo Clinic Arizona, in Phoenix.

For the subgroup of patients with BRCA alterations, the median PFS was 11.2 months with rucaparib vs. 6.4 months (hazard ratio, 0.50; P < .001) among those who received physician’s choice of therapy, which included docetaxel or a second-generation ARPI, such as abiraterone or enzalutamide.

In another subgroup of patients whose disease had ATM alterations, the median PFS was 8.1 months with rucaparib vs. 6.8 months with physician’s choice of drug. The difference was not statistically significant.

However, the difference was significant in the intention-to-treat (ITT) population (comprising both subgroups), for whom the median PFS was 10.2 months with rucaparib vs. 6.4 months with physician’s choice of drug (HR, 0.61; P < .001 by log-rank test).

Dr. Bryce pointed out that three-quarters of the patients in the physician’s-choice arm who had progressive disease crossed over to rucaparib upon progression and that overall survival (OS) results are immature. At 62 months, median OS did not significantly differ in the BRCA subgroup (24.3 vs. 20.8 months favoring rucaparib; P = .21) or in the ITT group (23.6 vs. 20.9 months; P = .67).

Importantly, rucaparib was well tolerated. In all treatment groups, the most frequent adverse events were asthenia and fatigue, Bryce said. “There were no cases of myelodysplastic syndrome or acute myeloid leukemia reported.”

These results from the TRITON3 trial were presented at the 2023 ASCO Genitourinary Cancers Symposium and were published simultaneously in the New England Journal of Medicine.
 

Suggested benefit

Rucaparib is the first PARP inhibitor approved for use in patients with mCRPC that harbors deleterious BRCA mutations (germline and/or somatic) who have already been treated with androgen receptor–directed therapy and a taxane-based chemotherapy. This prostate cancer indication was granted an accelerated approval in May 2020 by the U.S. Food and Drug Administration on the basis of response rates and effect on levels of prostate-specific antigen (PSA) from the TRITON2 clinical trial, the forerunner of the current study.

The TRITON2 study was a single-arm clinical trial that involved three cohorts: 62 patients with a BRCA mutation (germline and/or somatic) and measurable disease; 115 patients with a BRCA mutation (germline and/or somatic) and measurable or nonmeasurable disease; and 209 patients with homologous recombination deficiency–positive mCRPC.

In an analysis of 115 patients with a deleterious BRCA mutation (germline and/or somatic) and measurable or nonmeasurable disease, the confirmed PSA response rate was 55%. For the patients with measurable disease and a BRCA mutation, the objective response rate was 44%. The objective response rate was similar for those with a germline BRCA mutation.
 

Study details

The current phase 3 randomized TRITON3 clinical trial was conducted to confirm the earlier findings and to expand upon the data in mCRPC. The participants in this trial were patients with mCRPC who had specific gene alterations, including BRCA and ATM alterations, who had experienced disease progression after androgen receptor–directed therapy but who had not yet received chemotherapy.

A total of 270 men were assigned to receive rucaparib (600 mg twice daily); 135 patients received their physician’s choice of medication. Within the two study arms, 302 patients had a BRCA alteration, and 103 patients had an ATM alteration. The ITT population consisted of all the patients who had been randomly assigned to either of the two groups. A prespecified subgroup included patients with a BRCA alteration.

The primary outcome was the median duration of imaging-based PSF, as determined through independent review. Key secondary outcomes were overall survival and objective response rate.

The most common adverse events in the rucaparib group were fatigue, nausea, and anemia or decreased hemoglobin. In the control group, the most common adverse events were fatigue, diarrhea, and neuropathy. The most common events of grade 3 or higher were anemia or decreased hemoglobin, neutropenia or a decreased neutrophil count, and fatigue in the rucaparib group, and fatigue and neutropenia or a decreased neutrophil count among control patients.
 

No changes in standard of care

In a discussion of the study, Elena Castro, MD, PhD, of the Instituto de Investigación Biomédica de Málaga, Campanillas, Spain, emphasized that there is a clear benefit from the use of PARP inhibitors (such as rucaparib) for patients with BRCA alterations.

However, she highlighted the absence of convincing overall survival data and the absence of a clear benefit on PFS in the subgroup of patients with ATM alterations.

“These data raise several questions,” she noted, “such as, do patients with ATM alterations benefit at all? And should PARP inhibitors [such as rucaparib] precede or follow docetaxel therapy?”

Because of the high crossover rate, it may be possible to evaluate the directionality of docetaxel followed by PARP inhibitors and the other way around, she suggested.

Dr. Castro said that patients with BRCA alterations benefit from PARP inhibitors and are likely to derive more benefit from them than from taxanes.

“But those with ATM alterations are unlikely to benefit from rucaparib more than from taxanes,” she said.

In a comment, Hank Ng, MD, medical oncologist, NYU Langone Perlmutter Cancer Center, New York, said he is not convinced that the findings from TRITON 3 represent a new standard of care in BRCA 1/2 mutations or ATM.

“Currently, we know that, for patients with prostate cancer with BRCA1/2 or ATM, the standard of care is an androgen receptor pathway inhibitor (ARPI), such as abiraterone or enzalutamide, then docetaxel, and then a PARP inhibitor like rucaparib,” he said.

(Currently, rucaparib is indicated for use in patients with mCRPC with BRCA alterations after they have already received an ARPI and taxane-based chemotherapy.)

Dr. Ng also questioned the control arm of the TRITON 3 trial. All the participants in the trial had already experienced disease progression after treatment with a second-generation ARPI. But the physician’s choice of therapy allowed them to move on to another ARPI or to docetaxel.

Dr. NG commented that, “in almost all cases, after progression of one ARPI, switching to another ARPI does not provide much benefit – from what is visible from this abstract – and only 56% patients received docetaxel, and thus 44% received a not-beneficial treatment,” he said.

“I am not sure what the docetaxel subgroup showed, but potentially, if those numbers are convincing, we could move this [rucaparib] ahead of docetaxel,” he speculated.

However, he also pointed out that an overall survival benefit has not yet been shown; so far, the benefit that has been shown is with respect to imaging-based PFS.

Dr. Ng does agree that rucaparib is indicated in the second line after progression with one ARPI for patients who are not candidates for chemotherapy. “But this has not yet shown me that we should absolutely be offering rucaparib before docetaxel,” he said.

TRITON3 was supported by Clovis Oncology, manufacturer of rucaparib. Dr. Bryce has relationships with Bayer, Foundation Medicine, Janssen, Merck, Myovant Sciences, and Novartis and holds a patent for therapeutic targeting of cancer patients with NRG1 rearrangements. Dr. Castro has relationships with Astellas Pharma, AstraZeneca, Bayer, Clovis Oncology, Janssen-Cilag, Merck, MSD Oncology, Novartis, Pfizer, and Roche.

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

Treatment with the thiazolidinedione pioglitazone may offer the greatest protection against dementia for older adults with newly diagnosed type 2 diabetes mellitus (T2DM) who have a history of stroke or ischemic heart disease, new research suggests.

Overall, in a large cohort study from South Korea, patients who took pioglitazone were 16% less likely to develop dementia over an average of 10 years than peers who did not take the drug.

However, the dementia risk reduction was 54% among those with ischemic heart disease and 43% among those with a history of stroke.

“Our study was to see the association between pioglitazone use and incidence of dementia, not how (with what mechanisms) this drug can suppress dementia pathology,” coinvestigator Eosu Kim, MD, PhD, Yonsei University, Seoul, South Korea, said in an interview.

However, “as we found this drug is more effective in diabetic patients who have blood circulation problems in the heart or brain than in those without such problems, we speculate that pioglitazone’s antidementia action may be related to improving blood vessel’s health,” Dr. Kim said.

This finding suggests that pioglitazone could be used as a personalized treatment approach for dementia prevention in this subgroup of patients with diabetes, the researchers noted.

The results were published online in Neurology.
 

Dose-response relationship

Risk for dementia is doubled in adults with T2DM, the investigators wrote. Prior studies have suggested that pioglitazone may protect against dementia, as well as a first or recurrent stroke, in patients with T2DM.

This led Dr. Kim and colleagues to examine the effects of pioglitazone on dementia risk overall and in relation to stroke and ischemic heart disease.

Using the national Korean health database, the researchers identified 91,218 adults aged 50 and older with new-onset T2DM who did not have dementia. A total of 3,467 were treated with pioglitazone.

Pioglitazone exposure was defined as a total cumulative daily dose of 90 or more calculated from all dispensations during 4 years after T2DM diagnosis, with outcomes assessed after this period.

Over an average of 10 years, 8.3% of pioglitazone users developed dementia, compared with 10.0% of nonusers.

There was a statistically significant 16% lower risk for developing all-cause dementia among pioglitazone users than among nonusers (adjusted hazard ratio, 0.84; 95% confidence interval, 0.75-0.95).

A dose-response relationship was evident; pioglitazone users who received the highest cumulative daily dose were at lower risk for dementia (aHR, 0.72; 95% CI, 0.55-0.94).
 

Several limitations

The reduced risk for dementia was more pronounced among patients who used pioglitazone for 4 years in comparison with patients who did not use the drug (aHR, 0.63; 95% CI, 0.44-0.90).

The apparent protective effect of pioglitazone with regard to dementia was greater among those with a history of ischemic heart disease (aHR, 0.46; 95% CI, 0.24-0.90) or stroke (aHR, 0.57; 95% CI, 0.38-0.86) before diabetes diagnosis.

The incidence of stroke was also reduced with pioglitazone use (aHR, 0.81; 95% CI, 0.66-1.0).

“These results provide valuable information on who could potentially benefit from pioglitazone use for prevention of dementia,” Dr. Kim said in a news release.

However, “the risk and benefit balance of long-term use of this drug to prevent dementia should be prospectively assessed,” he said in an interview.

The researchers cautioned that the study was observational; hence, the reported associations cannot address causal relationships. Also, because of the use of claims data, drug compliance could not be guaranteed, and exposure may have been overestimated.

There is also the potential for selection bias, and no information on apolipoprotein E was available, they noted.
 

More data needed

In an accompanying editorial, Colleen J. Maxwell, PhD, University of Waterloo (Ont.), and colleagues wrote that the results “not only support previous studies showing the potential cognitive benefit of pioglitazone but also extend our understanding of this benefit through the mediating effect of reducing ischemic stroke.”

However, because of their associated risks, which include fractures, weight gain, heart failure, and bladder cancer, thiazolidinediones are not currently favored in diabetes management guidelines – and their use has significantly declined since the mid to late 2000s, the editorialists noted.

They agreed that it will be important to reassess the risk-benefit profile of pioglitazone in T2DM as additional findings emerge.

They also noted that sodium-glucose cotransporter-2 inhibitors, which have significant cardiovascular and renal benefits and minimal side effects, may also lower the risk for dementia.

“As both pioglitazone and SGLT-2 inhibitors are second-line options for physicians, the current decision would easily be in favor of SGLT-2 inhibitors given their safety profile,” Dr. Maxwell and colleagues wrote.

For now, pioglitazone “should not be used to prevent dementia in patients with T2DM,” they concluded.

The study was supported by grants from the National Research Foundation of Korea funded by the Korean government and the Ministry of Health and Welfare. The investigators and editorialists report no relevant financial relationships.

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

Treatment with the thiazolidinedione pioglitazone may offer the greatest protection against dementia for older adults with newly diagnosed type 2 diabetes mellitus (T2DM) who have a history of stroke or ischemic heart disease, new research suggests.

Overall, in a large cohort study from South Korea, patients who took pioglitazone were 16% less likely to develop dementia over an average of 10 years than peers who did not take the drug.

However, the dementia risk reduction was 54% among those with ischemic heart disease and 43% among those with a history of stroke.

“Our study was to see the association between pioglitazone use and incidence of dementia, not how (with what mechanisms) this drug can suppress dementia pathology,” coinvestigator Eosu Kim, MD, PhD, Yonsei University, Seoul, South Korea, said in an interview.

However, “as we found this drug is more effective in diabetic patients who have blood circulation problems in the heart or brain than in those without such problems, we speculate that pioglitazone’s antidementia action may be related to improving blood vessel’s health,” Dr. Kim said.

This finding suggests that pioglitazone could be used as a personalized treatment approach for dementia prevention in this subgroup of patients with diabetes, the researchers noted.

The results were published online in Neurology.
 

Dose-response relationship

Risk for dementia is doubled in adults with T2DM, the investigators wrote. Prior studies have suggested that pioglitazone may protect against dementia, as well as a first or recurrent stroke, in patients with T2DM.

This led Dr. Kim and colleagues to examine the effects of pioglitazone on dementia risk overall and in relation to stroke and ischemic heart disease.

Using the national Korean health database, the researchers identified 91,218 adults aged 50 and older with new-onset T2DM who did not have dementia. A total of 3,467 were treated with pioglitazone.

Pioglitazone exposure was defined as a total cumulative daily dose of 90 or more calculated from all dispensations during 4 years after T2DM diagnosis, with outcomes assessed after this period.

Over an average of 10 years, 8.3% of pioglitazone users developed dementia, compared with 10.0% of nonusers.

There was a statistically significant 16% lower risk for developing all-cause dementia among pioglitazone users than among nonusers (adjusted hazard ratio, 0.84; 95% confidence interval, 0.75-0.95).

A dose-response relationship was evident; pioglitazone users who received the highest cumulative daily dose were at lower risk for dementia (aHR, 0.72; 95% CI, 0.55-0.94).
 

Several limitations

The reduced risk for dementia was more pronounced among patients who used pioglitazone for 4 years in comparison with patients who did not use the drug (aHR, 0.63; 95% CI, 0.44-0.90).

The apparent protective effect of pioglitazone with regard to dementia was greater among those with a history of ischemic heart disease (aHR, 0.46; 95% CI, 0.24-0.90) or stroke (aHR, 0.57; 95% CI, 0.38-0.86) before diabetes diagnosis.

The incidence of stroke was also reduced with pioglitazone use (aHR, 0.81; 95% CI, 0.66-1.0).

“These results provide valuable information on who could potentially benefit from pioglitazone use for prevention of dementia,” Dr. Kim said in a news release.

However, “the risk and benefit balance of long-term use of this drug to prevent dementia should be prospectively assessed,” he said in an interview.

The researchers cautioned that the study was observational; hence, the reported associations cannot address causal relationships. Also, because of the use of claims data, drug compliance could not be guaranteed, and exposure may have been overestimated.

There is also the potential for selection bias, and no information on apolipoprotein E was available, they noted.
 

More data needed

In an accompanying editorial, Colleen J. Maxwell, PhD, University of Waterloo (Ont.), and colleagues wrote that the results “not only support previous studies showing the potential cognitive benefit of pioglitazone but also extend our understanding of this benefit through the mediating effect of reducing ischemic stroke.”

However, because of their associated risks, which include fractures, weight gain, heart failure, and bladder cancer, thiazolidinediones are not currently favored in diabetes management guidelines – and their use has significantly declined since the mid to late 2000s, the editorialists noted.

They agreed that it will be important to reassess the risk-benefit profile of pioglitazone in T2DM as additional findings emerge.

They also noted that sodium-glucose cotransporter-2 inhibitors, which have significant cardiovascular and renal benefits and minimal side effects, may also lower the risk for dementia.

“As both pioglitazone and SGLT-2 inhibitors are second-line options for physicians, the current decision would easily be in favor of SGLT-2 inhibitors given their safety profile,” Dr. Maxwell and colleagues wrote.

For now, pioglitazone “should not be used to prevent dementia in patients with T2DM,” they concluded.

The study was supported by grants from the National Research Foundation of Korea funded by the Korean government and the Ministry of Health and Welfare. The investigators and editorialists report no relevant financial relationships.

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

Treatment with the thiazolidinedione pioglitazone may offer the greatest protection against dementia for older adults with newly diagnosed type 2 diabetes mellitus (T2DM) who have a history of stroke or ischemic heart disease, new research suggests.

Overall, in a large cohort study from South Korea, patients who took pioglitazone were 16% less likely to develop dementia over an average of 10 years than peers who did not take the drug.

However, the dementia risk reduction was 54% among those with ischemic heart disease and 43% among those with a history of stroke.

“Our study was to see the association between pioglitazone use and incidence of dementia, not how (with what mechanisms) this drug can suppress dementia pathology,” coinvestigator Eosu Kim, MD, PhD, Yonsei University, Seoul, South Korea, said in an interview.

However, “as we found this drug is more effective in diabetic patients who have blood circulation problems in the heart or brain than in those without such problems, we speculate that pioglitazone’s antidementia action may be related to improving blood vessel’s health,” Dr. Kim said.

This finding suggests that pioglitazone could be used as a personalized treatment approach for dementia prevention in this subgroup of patients with diabetes, the researchers noted.

The results were published online in Neurology.
 

Dose-response relationship

Risk for dementia is doubled in adults with T2DM, the investigators wrote. Prior studies have suggested that pioglitazone may protect against dementia, as well as a first or recurrent stroke, in patients with T2DM.

This led Dr. Kim and colleagues to examine the effects of pioglitazone on dementia risk overall and in relation to stroke and ischemic heart disease.

Using the national Korean health database, the researchers identified 91,218 adults aged 50 and older with new-onset T2DM who did not have dementia. A total of 3,467 were treated with pioglitazone.

Pioglitazone exposure was defined as a total cumulative daily dose of 90 or more calculated from all dispensations during 4 years after T2DM diagnosis, with outcomes assessed after this period.

Over an average of 10 years, 8.3% of pioglitazone users developed dementia, compared with 10.0% of nonusers.

There was a statistically significant 16% lower risk for developing all-cause dementia among pioglitazone users than among nonusers (adjusted hazard ratio, 0.84; 95% confidence interval, 0.75-0.95).

A dose-response relationship was evident; pioglitazone users who received the highest cumulative daily dose were at lower risk for dementia (aHR, 0.72; 95% CI, 0.55-0.94).
 

Several limitations

The reduced risk for dementia was more pronounced among patients who used pioglitazone for 4 years in comparison with patients who did not use the drug (aHR, 0.63; 95% CI, 0.44-0.90).

The apparent protective effect of pioglitazone with regard to dementia was greater among those with a history of ischemic heart disease (aHR, 0.46; 95% CI, 0.24-0.90) or stroke (aHR, 0.57; 95% CI, 0.38-0.86) before diabetes diagnosis.

The incidence of stroke was also reduced with pioglitazone use (aHR, 0.81; 95% CI, 0.66-1.0).

“These results provide valuable information on who could potentially benefit from pioglitazone use for prevention of dementia,” Dr. Kim said in a news release.

However, “the risk and benefit balance of long-term use of this drug to prevent dementia should be prospectively assessed,” he said in an interview.

The researchers cautioned that the study was observational; hence, the reported associations cannot address causal relationships. Also, because of the use of claims data, drug compliance could not be guaranteed, and exposure may have been overestimated.

There is also the potential for selection bias, and no information on apolipoprotein E was available, they noted.
 

More data needed

In an accompanying editorial, Colleen J. Maxwell, PhD, University of Waterloo (Ont.), and colleagues wrote that the results “not only support previous studies showing the potential cognitive benefit of pioglitazone but also extend our understanding of this benefit through the mediating effect of reducing ischemic stroke.”

However, because of their associated risks, which include fractures, weight gain, heart failure, and bladder cancer, thiazolidinediones are not currently favored in diabetes management guidelines – and their use has significantly declined since the mid to late 2000s, the editorialists noted.

They agreed that it will be important to reassess the risk-benefit profile of pioglitazone in T2DM as additional findings emerge.

They also noted that sodium-glucose cotransporter-2 inhibitors, which have significant cardiovascular and renal benefits and minimal side effects, may also lower the risk for dementia.

“As both pioglitazone and SGLT-2 inhibitors are second-line options for physicians, the current decision would easily be in favor of SGLT-2 inhibitors given their safety profile,” Dr. Maxwell and colleagues wrote.

For now, pioglitazone “should not be used to prevent dementia in patients with T2DM,” they concluded.

The study was supported by grants from the National Research Foundation of Korea funded by the Korean government and the Ministry of Health and Welfare. The investigators and editorialists report no relevant financial relationships.

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