Clinician Reviews

Two commonly used screening tools to detect risk of fracture often fail at that purpose for younger postmenopausal women of every race and ethnicity, according to a study published in JAMA Internal Medicine.

One of the screenings, the U.S. Fracture Risk Assessment Tool (FRAX), proved relatively ineffective at identifying women who developed osteoporosis. The other screening, the Osteoporosis Self-Assessment Tool (OST), excelled at identifying osteoporosis for women in every racial and ethnic group, but also failed at identifying who was most likely to experience a fracture. Osteoporosis experts say that primary care physicians should test for the condition in anyone with any risk factor for it, even if a screening tool suggests doing so is unnecessary.

The United States Preventive Services Task Force (USPSTF) recommends routine testing of bone mineral density in women age 65 years and older to detect risk of developing osteoporosis, which in turn leads to an increased risk for fractures of the hip, spine, shoulder, or forearm. For women aged 50-64, whether bone mineral density accurately reflects who will develop osteoporosis is less clear. In this age range, the USPSTF recommends using either FRAX or OST rather than routine bone mineral density tests.

“I have the utmost respect for the United States Preventive Services Task Force, which lists both of these as valid screening tools for younger postmenopausal women. What I hope this study does is to inform the next iteration of the screening guidelines,” by maintaining the recommendation to use the OST while not keeping FRAX, said Carolyn J. Crandall, MD, MS, an internal medicine physician and health services researcher at University of California, Los Angeles, who helped conduct the research.

The U.S. version of FRAX requires identifying someone’s race, height, and weight, then answering whether they have different risk factors for a fracture such as a previous fracture, rheumatoid arthritis, or smoking. The result was thought to indicate a cumulative risk for major fracture over the next 10 years. Patients at significant risk should then undergo a bone density test.

The tool can also incorporate information about bone mineral density, if available, but the FRAX analyses in Dr. Crandall’s study did not include those data because the study aimed to test the measure’s predictive ability in the absence of a bone scan.

The OST includes only two variables – weight and age – to calculate risk for osteoporosis, and generally takes seconds to complete. It does not include race. As with FRAX, anyone deemed at significant risk for developing osteoporosis should undergo a bone density test.

“OST is really simple; that makes it very appealing,” Dr. Crandall said. “OST could probably be automatically calculated in the electronic medical record.” 

Using data from the Women’s Health Initiative, Dr. Crandall and colleagues tracked more than 67,000 women aged 50-64 years for 10 years following enrollment in the study to see who experienced a fracture or developed osteoporosis over that decade. The investigators found that neither FRAX nor OST was particularly good at predicting who went on to experience a fracture. 

The accuracy of FRAX at fracture prediction peaked at 65% for Asian women (area under the receiver operating curve, 0.65; 95% confidence interval, 0.58-0.71), and was lowest for Black women (AUC 0.55; 95% CI, 0.52-0.59). OST also was most accurate for Asian women, but only up to 62% (AUC 0.62; 95% CI, 0.56-0.69), and was again lowest for Black women (AUC 0.53; 95% CI, 0.50 - 0.57)

“It is just very hard to predict fractures in this age group,” Dr. Crandall said, noting that more evidence exists about risk for fracture in people older than 65.

The story diverges with predicting risk of osteoporosis in the neck. The OST did this roughly 80% of the time, for all racial groups. That figure proved better than FRAX, without including race.
 

Treatment gap

“This evidence supports using OST instead of FRAX” for selecting younger postmenopausal women who should undergo a bone mineral density exam, said E. Michael Lewiecki, MD, director of the New Mexico Clinical Research & Osteoporosis Center in Albuquerque. 

UNM Health Sciences Center

Dr. Lewiecki, who was not involved in the new study, noted that the U.S. version of FRAX specifies race because of some clinical evidence that different races have different rates of fracture. But he and Dr. Crandall said the validity of race-based algorithms to guide clinical care is a controversial and evolving topic in medicine. Dr. Lewiecki said the Canadian version of FRAX, which is similarly applied to a diverse population as in the United States, omits race and works as well as the U.S. version. Future iterations of the instrument in the United States may not include race, Dr. Lewiecki said.

“The study is perfectly valid as far as it goes. But the big gorilla in the room is that most patients who need a bone density test are not getting it,” Dr. Lewiecki added. Sometimes a patient might break a bone in their wrist, for example, and tell their primary care provider that anyone would have broken that bone because the fall was so hard. Even if that’s true, Dr. Lewiecki said, any woman older than 45 who has broken a bone should undergo a bone density test to determine if they have osteoporosis, even if it seems like there are other possible reasons for why the break occurred.

“Most of the clinical practice guidelines that are used by physicians recommend getting a bone density test in postmenopausal women under the age of 65 who have a risk factor for fracture,” Dr. Lewiecki said, with a primary risk factor being a prior fracture. Dr. Lewiecki said he would rather that anyone who could benefit from a bone density test receive it, rather than someone foregoing a scan based on a screening tool that may be flawed.

“Most patients – men and women – who have osteoporosis are currently not being identified. Even when they are being identified, they are commonly not being treated. And when they are started on treatment, many patients discontinue treatment before they’ve taken it long enough to benefit,” Dr. Lewiecki said.

Dr. Crandall and Dr. Lewiecki report no relevant financial relationships.

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

Two commonly used screening tools to detect risk of fracture often fail at that purpose for younger postmenopausal women of every race and ethnicity, according to a study published in JAMA Internal Medicine.

One of the screenings, the U.S. Fracture Risk Assessment Tool (FRAX), proved relatively ineffective at identifying women who developed osteoporosis. The other screening, the Osteoporosis Self-Assessment Tool (OST), excelled at identifying osteoporosis for women in every racial and ethnic group, but also failed at identifying who was most likely to experience a fracture. Osteoporosis experts say that primary care physicians should test for the condition in anyone with any risk factor for it, even if a screening tool suggests doing so is unnecessary.

The United States Preventive Services Task Force (USPSTF) recommends routine testing of bone mineral density in women age 65 years and older to detect risk of developing osteoporosis, which in turn leads to an increased risk for fractures of the hip, spine, shoulder, or forearm. For women aged 50-64, whether bone mineral density accurately reflects who will develop osteoporosis is less clear. In this age range, the USPSTF recommends using either FRAX or OST rather than routine bone mineral density tests.

“I have the utmost respect for the United States Preventive Services Task Force, which lists both of these as valid screening tools for younger postmenopausal women. What I hope this study does is to inform the next iteration of the screening guidelines,” by maintaining the recommendation to use the OST while not keeping FRAX, said Carolyn J. Crandall, MD, MS, an internal medicine physician and health services researcher at University of California, Los Angeles, who helped conduct the research.

The U.S. version of FRAX requires identifying someone’s race, height, and weight, then answering whether they have different risk factors for a fracture such as a previous fracture, rheumatoid arthritis, or smoking. The result was thought to indicate a cumulative risk for major fracture over the next 10 years. Patients at significant risk should then undergo a bone density test.

The tool can also incorporate information about bone mineral density, if available, but the FRAX analyses in Dr. Crandall’s study did not include those data because the study aimed to test the measure’s predictive ability in the absence of a bone scan.

The OST includes only two variables – weight and age – to calculate risk for osteoporosis, and generally takes seconds to complete. It does not include race. As with FRAX, anyone deemed at significant risk for developing osteoporosis should undergo a bone density test.

“OST is really simple; that makes it very appealing,” Dr. Crandall said. “OST could probably be automatically calculated in the electronic medical record.” 

Using data from the Women’s Health Initiative, Dr. Crandall and colleagues tracked more than 67,000 women aged 50-64 years for 10 years following enrollment in the study to see who experienced a fracture or developed osteoporosis over that decade. The investigators found that neither FRAX nor OST was particularly good at predicting who went on to experience a fracture. 

The accuracy of FRAX at fracture prediction peaked at 65% for Asian women (area under the receiver operating curve, 0.65; 95% confidence interval, 0.58-0.71), and was lowest for Black women (AUC 0.55; 95% CI, 0.52-0.59). OST also was most accurate for Asian women, but only up to 62% (AUC 0.62; 95% CI, 0.56-0.69), and was again lowest for Black women (AUC 0.53; 95% CI, 0.50 - 0.57)

“It is just very hard to predict fractures in this age group,” Dr. Crandall said, noting that more evidence exists about risk for fracture in people older than 65.

The story diverges with predicting risk of osteoporosis in the neck. The OST did this roughly 80% of the time, for all racial groups. That figure proved better than FRAX, without including race.
 

Treatment gap

“This evidence supports using OST instead of FRAX” for selecting younger postmenopausal women who should undergo a bone mineral density exam, said E. Michael Lewiecki, MD, director of the New Mexico Clinical Research & Osteoporosis Center in Albuquerque. 

UNM Health Sciences Center

Dr. Lewiecki, who was not involved in the new study, noted that the U.S. version of FRAX specifies race because of some clinical evidence that different races have different rates of fracture. But he and Dr. Crandall said the validity of race-based algorithms to guide clinical care is a controversial and evolving topic in medicine. Dr. Lewiecki said the Canadian version of FRAX, which is similarly applied to a diverse population as in the United States, omits race and works as well as the U.S. version. Future iterations of the instrument in the United States may not include race, Dr. Lewiecki said.

“The study is perfectly valid as far as it goes. But the big gorilla in the room is that most patients who need a bone density test are not getting it,” Dr. Lewiecki added. Sometimes a patient might break a bone in their wrist, for example, and tell their primary care provider that anyone would have broken that bone because the fall was so hard. Even if that’s true, Dr. Lewiecki said, any woman older than 45 who has broken a bone should undergo a bone density test to determine if they have osteoporosis, even if it seems like there are other possible reasons for why the break occurred.

“Most of the clinical practice guidelines that are used by physicians recommend getting a bone density test in postmenopausal women under the age of 65 who have a risk factor for fracture,” Dr. Lewiecki said, with a primary risk factor being a prior fracture. Dr. Lewiecki said he would rather that anyone who could benefit from a bone density test receive it, rather than someone foregoing a scan based on a screening tool that may be flawed.

“Most patients – men and women – who have osteoporosis are currently not being identified. Even when they are being identified, they are commonly not being treated. And when they are started on treatment, many patients discontinue treatment before they’ve taken it long enough to benefit,” Dr. Lewiecki said.

Dr. Crandall and Dr. Lewiecki report no relevant financial relationships.

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

Two commonly used screening tools to detect risk of fracture often fail at that purpose for younger postmenopausal women of every race and ethnicity, according to a study published in JAMA Internal Medicine.

One of the screenings, the U.S. Fracture Risk Assessment Tool (FRAX), proved relatively ineffective at identifying women who developed osteoporosis. The other screening, the Osteoporosis Self-Assessment Tool (OST), excelled at identifying osteoporosis for women in every racial and ethnic group, but also failed at identifying who was most likely to experience a fracture. Osteoporosis experts say that primary care physicians should test for the condition in anyone with any risk factor for it, even if a screening tool suggests doing so is unnecessary.

The United States Preventive Services Task Force (USPSTF) recommends routine testing of bone mineral density in women age 65 years and older to detect risk of developing osteoporosis, which in turn leads to an increased risk for fractures of the hip, spine, shoulder, or forearm. For women aged 50-64, whether bone mineral density accurately reflects who will develop osteoporosis is less clear. In this age range, the USPSTF recommends using either FRAX or OST rather than routine bone mineral density tests.

“I have the utmost respect for the United States Preventive Services Task Force, which lists both of these as valid screening tools for younger postmenopausal women. What I hope this study does is to inform the next iteration of the screening guidelines,” by maintaining the recommendation to use the OST while not keeping FRAX, said Carolyn J. Crandall, MD, MS, an internal medicine physician and health services researcher at University of California, Los Angeles, who helped conduct the research.

The U.S. version of FRAX requires identifying someone’s race, height, and weight, then answering whether they have different risk factors for a fracture such as a previous fracture, rheumatoid arthritis, or smoking. The result was thought to indicate a cumulative risk for major fracture over the next 10 years. Patients at significant risk should then undergo a bone density test.

The tool can also incorporate information about bone mineral density, if available, but the FRAX analyses in Dr. Crandall’s study did not include those data because the study aimed to test the measure’s predictive ability in the absence of a bone scan.

The OST includes only two variables – weight and age – to calculate risk for osteoporosis, and generally takes seconds to complete. It does not include race. As with FRAX, anyone deemed at significant risk for developing osteoporosis should undergo a bone density test.

“OST is really simple; that makes it very appealing,” Dr. Crandall said. “OST could probably be automatically calculated in the electronic medical record.” 

Using data from the Women’s Health Initiative, Dr. Crandall and colleagues tracked more than 67,000 women aged 50-64 years for 10 years following enrollment in the study to see who experienced a fracture or developed osteoporosis over that decade. The investigators found that neither FRAX nor OST was particularly good at predicting who went on to experience a fracture. 

The accuracy of FRAX at fracture prediction peaked at 65% for Asian women (area under the receiver operating curve, 0.65; 95% confidence interval, 0.58-0.71), and was lowest for Black women (AUC 0.55; 95% CI, 0.52-0.59). OST also was most accurate for Asian women, but only up to 62% (AUC 0.62; 95% CI, 0.56-0.69), and was again lowest for Black women (AUC 0.53; 95% CI, 0.50 - 0.57)

“It is just very hard to predict fractures in this age group,” Dr. Crandall said, noting that more evidence exists about risk for fracture in people older than 65.

The story diverges with predicting risk of osteoporosis in the neck. The OST did this roughly 80% of the time, for all racial groups. That figure proved better than FRAX, without including race.
 

Treatment gap

“This evidence supports using OST instead of FRAX” for selecting younger postmenopausal women who should undergo a bone mineral density exam, said E. Michael Lewiecki, MD, director of the New Mexico Clinical Research & Osteoporosis Center in Albuquerque. 

UNM Health Sciences Center

Dr. Lewiecki, who was not involved in the new study, noted that the U.S. version of FRAX specifies race because of some clinical evidence that different races have different rates of fracture. But he and Dr. Crandall said the validity of race-based algorithms to guide clinical care is a controversial and evolving topic in medicine. Dr. Lewiecki said the Canadian version of FRAX, which is similarly applied to a diverse population as in the United States, omits race and works as well as the U.S. version. Future iterations of the instrument in the United States may not include race, Dr. Lewiecki said.

“The study is perfectly valid as far as it goes. But the big gorilla in the room is that most patients who need a bone density test are not getting it,” Dr. Lewiecki added. Sometimes a patient might break a bone in their wrist, for example, and tell their primary care provider that anyone would have broken that bone because the fall was so hard. Even if that’s true, Dr. Lewiecki said, any woman older than 45 who has broken a bone should undergo a bone density test to determine if they have osteoporosis, even if it seems like there are other possible reasons for why the break occurred.

“Most of the clinical practice guidelines that are used by physicians recommend getting a bone density test in postmenopausal women under the age of 65 who have a risk factor for fracture,” Dr. Lewiecki said, with a primary risk factor being a prior fracture. Dr. Lewiecki said he would rather that anyone who could benefit from a bone density test receive it, rather than someone foregoing a scan based on a screening tool that may be flawed.

“Most patients – men and women – who have osteoporosis are currently not being identified. Even when they are being identified, they are commonly not being treated. And when they are started on treatment, many patients discontinue treatment before they’ve taken it long enough to benefit,” Dr. Lewiecki said.

Dr. Crandall and Dr. Lewiecki report no relevant financial relationships.

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

Imagine a day when a simple injection prompts a broken bone to heal. When tiny, ingestible devices linger in the body, unnoticed, tracking our health or delivering life-saving medications. When brain and heart implants mesh with flesh so seamlessly that the body thinks they’ve been there all along.

These are the dreams of materials scientists who have toiled for decades to mimic the complex architecture of the human body in hopes of replacing broken parts or treating disease.

The problem, say bioengineers, is that most replacement and corrective parts – from prosthetics to pacemakers – are made of hard, dry, lifeless materials, like metal or plastic, while biological tissue is soft, wet, and living. 

The body knows the difference and tends to reject imitations.

Enter hydrogels, three-dimensional networks of molecules swollen with – by definition – water. 

First described in 1960 by creators of soft contact lenses, these weird, shape-shifting substances are able to morph from liquid to solid to a squishy in-between. (Early, simple uses include hair gel or Jell-O.). Slow to gain attention, growing to just 1,000 studies published by 1982, they’ve become the subject of intense study recently, with 100,000 papers published by 2020, and 3,800 already this year alone.

As chemists, biologists, and engineers begin to work more with one another and with medical doctors, the burgeoning hydrogel field is poised to transform the way we take medication and treat worn-out joints and pave the way for a seemingly sci-fi future in which organs, including brains, can interact directly with machines.

“We are, essentially, hydrogels,” said Benjamin Wiley, PhD, a chemistry professor at Duke University in Durham, N.C. “As people develop new hydrogels that more closely match the tissues in our body, we’ll be able to treat a whole host of ailments we couldn’t treat before.”
 

From contact lenses to brain implants

Put simply, a hydrogel is like a mesh bag of water. 

The mesh is made of polymers, or spaghetti-like strands of molecules, stitched together in a repeating pattern and swollen with H₂O, much like the way 3D matrixes in our body surround, support, and give structure to our cells and tissues.

“Imagine a soccer net, with all of these long fibers woven together to create the net,” said Eric Appel, PhD, associate professor of materials science and engineering at Stanford (Calif.) University.

While the broader category of “gels” could be filled with anything, including chemical solvents, water is the key ingredient that sets hydrogels apart, making them ideal for, as some scientists put it, “merging humans and machines.”

Human bones are about 25% water, while muscles hover around 70% and the brain is 85%. The precious liquid plays a host of critical roles, from shuttling nutrients in and waste out to helping cells talk to each other. 

Lab-made hydrogels can be loaded with cargo (like a ball in the net), including cells or drugs that help mimic some of those functions.

Hydrogels are soft and pliable like flesh. So, if used in implants, they may be less likely to damage surrounding tissue.

“Think about a metal spoon in your bowl of pudding. As you’re shaking the bowl, the spoon doesn’t stay in place, and you get scarring around the spoon,” said Christina Tringides, PhD, a materials scientist who studies neural engineering. That, she says, is exactly what happens to brain implants when patients breathe or move. “It’s a mechanical mismatch. But with hydrogels, you could get perfect mechanical matching.”

Hydrogels also tend to be nontoxic, so the immune system may be less likely to attack them as foreign bodies.

All this has made hydrogels the new darling of the bioengineering world. 

“There has been an absolute explosion of interest in these materials,” Dr. Appel said.
 

Smarter drug delivery and ingestible electronics

Early versions of hydrogels were thick and gooey, making it hard to get them inside the body.

“Think of a block of Jell-O. You couldn’t inject something like that,” Dr. Appel said.

But Dr. Appel, whose lab develops new drug delivery systems, has been tinkering with gel formulas for years in hopes that these high-tech globs could someday ferry timed-release drugs to just the right spot in the body.

His new hydrogels start as fully formed gels (which help preserve the drug contents) inside a syringe. But once the plunger is pushed, they magically shape-shift to a liquid thin enough to flow easily through a standard needle. Upon exit, they immediately reform into gels, protecting the inherent cargo from degrading.

This could be a game changer at a time when many cutting-edge drugs – think Humira for arthritis or Ozempic for type 2 diabetes – are made of quickly degrading proteins too large and complex to simply jam into a pill. Instead, they must be injected, often frequently.

“Because the gel takes months to dissolve, it slowly delivers the drug over time,” Dr. Appel said. “You could conceivably go from a shot once a week to once every 4 months.”

Such slow-release hydrogels could make vaccines last longer, in turn teaching the body to better resist emerging virus variants, and deliver tumor-busting therapies more precisely, said Dr. Appel, who has formed a startup and hopes to fast-track the first hydrogel drug delivery system to clinical trials within a few years.

Meanwhile, another team at the Massachusetts Institute of Technology has taken a different approach, developing a standard-sized ingestible hydrogel pill that swells up like a puffer fish in the stomach, lasting a month and slowly releasing drugs all the while. To remove the pill, a patient simply drinks a salt-based solution that shrivels the ping-pong ball–sized device so it can be passed out of the body.

In a paper in Nature Communications, the scientists showed the puffer fish pill could also be loaded with tiny cameras or monitors to track conditions like ulcers or cancer.

“The dream is to have a Jell-O-like smart pill that, once swallowed, stays in the stomach and monitors the patient’s health,” said Xuanhe Zhao, PhD, a researcher on the project and associate professor of mechanical engineering at MIT.
 

Building joints and regrowing bones

Since the 1970s, researchers have mulled using hydrogels to replace human cartilage, a remarkably strong and flexible tissue made of about 90% water but able to withstand the weight of a car on an area about the size of a coin.

Until recently, those efforts have largely failed. Meaning when knee cartilage wears down, things like cartilage transplants, drilling holes to stimulate new growth, or total joint replacements – all of which require lengthy rehab – are the only options. 

But that may be about to change.

Dr. Wiley and his colleagues at Duke recently reported that they’d developed the first gel-based cartilage substitute even stronger and more durable than the real thing.

By attaching their hydrogel to a titanium backing to help stick it in place, they hope to repair damaged cartilage “much like a dentist fills a cavity” long before surgery is necessary.

They too have partnered with industry to bring their hydrogel to market – starting with knees.

“Ultimately, the goal is to do any joint – hips, ankles, fingers, and toes,” Dr. Wiley said. 

At the University of Toronto, chemist Karina Carneiro, PhD, and dentist Christopher McCulloch, DDS, are also thinking big.

In a recent paper in Proceedings of the National Academy of Sciences, they describe a hydrogel, designed by Dr. Carneiro and made of DNA, that can be injected, migrate to a defect in bone – an irreparable break, hole from surgery, or jawbone withered by age – and fill in the gap like putty. But not only does it patch the hole, it prompts the bone to regenerate. 

In rats with holes in their skulls due to surgery, they found that the treatment did not work as well as the existing gold standard for repairing holes in bone – grafting bone from elsewhere in the body. But it did work.

“These are very early days for DNA hydrogels,” cautioned Dr. McCulloch, a study coauthor and professor in the Faculty of Dentistry, noting that it will likely be a decade or more before such technology could be available to patients. “But there is the potential that DNA hydrogel could someday grow bone without having to have highly invasive surgical procedures. That’s a significant advancement.”
 

A sci-fi future

Perhaps the wildest, and weirdest, potential applications of hydrogels come in the realm of human-machine interaction.

Numerous companies are already dabbling in neural prosthetic or brain computer interfaces that might someday, for instance, let someone who is paralyzed and can’t speak write on a laptop using their thoughts.

The spoon-in-the-Jell-O problem has been a major stumbling block.

But Dr. Tringides, who recently earned her PhD in biophysics from Harvard, is working on it.

She and her team have developed a seaweed-based hydrogel loaded with tiny flecks of nanomaterials that can not only meld nicely into squishy brain tissue but also conduct electricity.

Within a decade, she says, this could replace the clunky platinum metal discs used for electrocorticography – recording electrical activity in the brain to identify where seizures start or doing precise brain surgery.

In 30 to 50 years? Let your imagination run wild.

“I’m a skeptic. I like to take research step by step,” she said. “But things are definitely progressing in an interesting direction.”
 

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

Imagine a day when a simple injection prompts a broken bone to heal. When tiny, ingestible devices linger in the body, unnoticed, tracking our health or delivering life-saving medications. When brain and heart implants mesh with flesh so seamlessly that the body thinks they’ve been there all along.

These are the dreams of materials scientists who have toiled for decades to mimic the complex architecture of the human body in hopes of replacing broken parts or treating disease.

The problem, say bioengineers, is that most replacement and corrective parts – from prosthetics to pacemakers – are made of hard, dry, lifeless materials, like metal or plastic, while biological tissue is soft, wet, and living. 

The body knows the difference and tends to reject imitations.

Enter hydrogels, three-dimensional networks of molecules swollen with – by definition – water. 

First described in 1960 by creators of soft contact lenses, these weird, shape-shifting substances are able to morph from liquid to solid to a squishy in-between. (Early, simple uses include hair gel or Jell-O.). Slow to gain attention, growing to just 1,000 studies published by 1982, they’ve become the subject of intense study recently, with 100,000 papers published by 2020, and 3,800 already this year alone.

As chemists, biologists, and engineers begin to work more with one another and with medical doctors, the burgeoning hydrogel field is poised to transform the way we take medication and treat worn-out joints and pave the way for a seemingly sci-fi future in which organs, including brains, can interact directly with machines.

“We are, essentially, hydrogels,” said Benjamin Wiley, PhD, a chemistry professor at Duke University in Durham, N.C. “As people develop new hydrogels that more closely match the tissues in our body, we’ll be able to treat a whole host of ailments we couldn’t treat before.”
 

From contact lenses to brain implants

Put simply, a hydrogel is like a mesh bag of water. 

The mesh is made of polymers, or spaghetti-like strands of molecules, stitched together in a repeating pattern and swollen with H₂O, much like the way 3D matrixes in our body surround, support, and give structure to our cells and tissues.

“Imagine a soccer net, with all of these long fibers woven together to create the net,” said Eric Appel, PhD, associate professor of materials science and engineering at Stanford (Calif.) University.

While the broader category of “gels” could be filled with anything, including chemical solvents, water is the key ingredient that sets hydrogels apart, making them ideal for, as some scientists put it, “merging humans and machines.”

Human bones are about 25% water, while muscles hover around 70% and the brain is 85%. The precious liquid plays a host of critical roles, from shuttling nutrients in and waste out to helping cells talk to each other. 

Lab-made hydrogels can be loaded with cargo (like a ball in the net), including cells or drugs that help mimic some of those functions.

Hydrogels are soft and pliable like flesh. So, if used in implants, they may be less likely to damage surrounding tissue.

“Think about a metal spoon in your bowl of pudding. As you’re shaking the bowl, the spoon doesn’t stay in place, and you get scarring around the spoon,” said Christina Tringides, PhD, a materials scientist who studies neural engineering. That, she says, is exactly what happens to brain implants when patients breathe or move. “It’s a mechanical mismatch. But with hydrogels, you could get perfect mechanical matching.”

Hydrogels also tend to be nontoxic, so the immune system may be less likely to attack them as foreign bodies.

All this has made hydrogels the new darling of the bioengineering world. 

“There has been an absolute explosion of interest in these materials,” Dr. Appel said.
 

Smarter drug delivery and ingestible electronics

Early versions of hydrogels were thick and gooey, making it hard to get them inside the body.

“Think of a block of Jell-O. You couldn’t inject something like that,” Dr. Appel said.

But Dr. Appel, whose lab develops new drug delivery systems, has been tinkering with gel formulas for years in hopes that these high-tech globs could someday ferry timed-release drugs to just the right spot in the body.

His new hydrogels start as fully formed gels (which help preserve the drug contents) inside a syringe. But once the plunger is pushed, they magically shape-shift to a liquid thin enough to flow easily through a standard needle. Upon exit, they immediately reform into gels, protecting the inherent cargo from degrading.

This could be a game changer at a time when many cutting-edge drugs – think Humira for arthritis or Ozempic for type 2 diabetes – are made of quickly degrading proteins too large and complex to simply jam into a pill. Instead, they must be injected, often frequently.

“Because the gel takes months to dissolve, it slowly delivers the drug over time,” Dr. Appel said. “You could conceivably go from a shot once a week to once every 4 months.”

Such slow-release hydrogels could make vaccines last longer, in turn teaching the body to better resist emerging virus variants, and deliver tumor-busting therapies more precisely, said Dr. Appel, who has formed a startup and hopes to fast-track the first hydrogel drug delivery system to clinical trials within a few years.

Meanwhile, another team at the Massachusetts Institute of Technology has taken a different approach, developing a standard-sized ingestible hydrogel pill that swells up like a puffer fish in the stomach, lasting a month and slowly releasing drugs all the while. To remove the pill, a patient simply drinks a salt-based solution that shrivels the ping-pong ball–sized device so it can be passed out of the body.

In a paper in Nature Communications, the scientists showed the puffer fish pill could also be loaded with tiny cameras or monitors to track conditions like ulcers or cancer.

“The dream is to have a Jell-O-like smart pill that, once swallowed, stays in the stomach and monitors the patient’s health,” said Xuanhe Zhao, PhD, a researcher on the project and associate professor of mechanical engineering at MIT.
 

Building joints and regrowing bones

Since the 1970s, researchers have mulled using hydrogels to replace human cartilage, a remarkably strong and flexible tissue made of about 90% water but able to withstand the weight of a car on an area about the size of a coin.

Until recently, those efforts have largely failed. Meaning when knee cartilage wears down, things like cartilage transplants, drilling holes to stimulate new growth, or total joint replacements – all of which require lengthy rehab – are the only options. 

But that may be about to change.

Dr. Wiley and his colleagues at Duke recently reported that they’d developed the first gel-based cartilage substitute even stronger and more durable than the real thing.

By attaching their hydrogel to a titanium backing to help stick it in place, they hope to repair damaged cartilage “much like a dentist fills a cavity” long before surgery is necessary.

They too have partnered with industry to bring their hydrogel to market – starting with knees.

“Ultimately, the goal is to do any joint – hips, ankles, fingers, and toes,” Dr. Wiley said. 

At the University of Toronto, chemist Karina Carneiro, PhD, and dentist Christopher McCulloch, DDS, are also thinking big.

In a recent paper in Proceedings of the National Academy of Sciences, they describe a hydrogel, designed by Dr. Carneiro and made of DNA, that can be injected, migrate to a defect in bone – an irreparable break, hole from surgery, or jawbone withered by age – and fill in the gap like putty. But not only does it patch the hole, it prompts the bone to regenerate. 

In rats with holes in their skulls due to surgery, they found that the treatment did not work as well as the existing gold standard for repairing holes in bone – grafting bone from elsewhere in the body. But it did work.

“These are very early days for DNA hydrogels,” cautioned Dr. McCulloch, a study coauthor and professor in the Faculty of Dentistry, noting that it will likely be a decade or more before such technology could be available to patients. “But there is the potential that DNA hydrogel could someday grow bone without having to have highly invasive surgical procedures. That’s a significant advancement.”
 

A sci-fi future

Perhaps the wildest, and weirdest, potential applications of hydrogels come in the realm of human-machine interaction.

Numerous companies are already dabbling in neural prosthetic or brain computer interfaces that might someday, for instance, let someone who is paralyzed and can’t speak write on a laptop using their thoughts.

The spoon-in-the-Jell-O problem has been a major stumbling block.

But Dr. Tringides, who recently earned her PhD in biophysics from Harvard, is working on it.

She and her team have developed a seaweed-based hydrogel loaded with tiny flecks of nanomaterials that can not only meld nicely into squishy brain tissue but also conduct electricity.

Within a decade, she says, this could replace the clunky platinum metal discs used for electrocorticography – recording electrical activity in the brain to identify where seizures start or doing precise brain surgery.

In 30 to 50 years? Let your imagination run wild.

“I’m a skeptic. I like to take research step by step,” she said. “But things are definitely progressing in an interesting direction.”
 

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

Imagine a day when a simple injection prompts a broken bone to heal. When tiny, ingestible devices linger in the body, unnoticed, tracking our health or delivering life-saving medications. When brain and heart implants mesh with flesh so seamlessly that the body thinks they’ve been there all along.

These are the dreams of materials scientists who have toiled for decades to mimic the complex architecture of the human body in hopes of replacing broken parts or treating disease.

The problem, say bioengineers, is that most replacement and corrective parts – from prosthetics to pacemakers – are made of hard, dry, lifeless materials, like metal or plastic, while biological tissue is soft, wet, and living. 

The body knows the difference and tends to reject imitations.

Enter hydrogels, three-dimensional networks of molecules swollen with – by definition – water. 

First described in 1960 by creators of soft contact lenses, these weird, shape-shifting substances are able to morph from liquid to solid to a squishy in-between. (Early, simple uses include hair gel or Jell-O.). Slow to gain attention, growing to just 1,000 studies published by 1982, they’ve become the subject of intense study recently, with 100,000 papers published by 2020, and 3,800 already this year alone.

As chemists, biologists, and engineers begin to work more with one another and with medical doctors, the burgeoning hydrogel field is poised to transform the way we take medication and treat worn-out joints and pave the way for a seemingly sci-fi future in which organs, including brains, can interact directly with machines.

“We are, essentially, hydrogels,” said Benjamin Wiley, PhD, a chemistry professor at Duke University in Durham, N.C. “As people develop new hydrogels that more closely match the tissues in our body, we’ll be able to treat a whole host of ailments we couldn’t treat before.”
 

From contact lenses to brain implants

Put simply, a hydrogel is like a mesh bag of water. 

The mesh is made of polymers, or spaghetti-like strands of molecules, stitched together in a repeating pattern and swollen with H₂O, much like the way 3D matrixes in our body surround, support, and give structure to our cells and tissues.

“Imagine a soccer net, with all of these long fibers woven together to create the net,” said Eric Appel, PhD, associate professor of materials science and engineering at Stanford (Calif.) University.

While the broader category of “gels” could be filled with anything, including chemical solvents, water is the key ingredient that sets hydrogels apart, making them ideal for, as some scientists put it, “merging humans and machines.”

Human bones are about 25% water, while muscles hover around 70% and the brain is 85%. The precious liquid plays a host of critical roles, from shuttling nutrients in and waste out to helping cells talk to each other. 

Lab-made hydrogels can be loaded with cargo (like a ball in the net), including cells or drugs that help mimic some of those functions.

Hydrogels are soft and pliable like flesh. So, if used in implants, they may be less likely to damage surrounding tissue.

“Think about a metal spoon in your bowl of pudding. As you’re shaking the bowl, the spoon doesn’t stay in place, and you get scarring around the spoon,” said Christina Tringides, PhD, a materials scientist who studies neural engineering. That, she says, is exactly what happens to brain implants when patients breathe or move. “It’s a mechanical mismatch. But with hydrogels, you could get perfect mechanical matching.”

Hydrogels also tend to be nontoxic, so the immune system may be less likely to attack them as foreign bodies.

All this has made hydrogels the new darling of the bioengineering world. 

“There has been an absolute explosion of interest in these materials,” Dr. Appel said.
 

Smarter drug delivery and ingestible electronics

Early versions of hydrogels were thick and gooey, making it hard to get them inside the body.

“Think of a block of Jell-O. You couldn’t inject something like that,” Dr. Appel said.

But Dr. Appel, whose lab develops new drug delivery systems, has been tinkering with gel formulas for years in hopes that these high-tech globs could someday ferry timed-release drugs to just the right spot in the body.

His new hydrogels start as fully formed gels (which help preserve the drug contents) inside a syringe. But once the plunger is pushed, they magically shape-shift to a liquid thin enough to flow easily through a standard needle. Upon exit, they immediately reform into gels, protecting the inherent cargo from degrading.

This could be a game changer at a time when many cutting-edge drugs – think Humira for arthritis or Ozempic for type 2 diabetes – are made of quickly degrading proteins too large and complex to simply jam into a pill. Instead, they must be injected, often frequently.

“Because the gel takes months to dissolve, it slowly delivers the drug over time,” Dr. Appel said. “You could conceivably go from a shot once a week to once every 4 months.”

Such slow-release hydrogels could make vaccines last longer, in turn teaching the body to better resist emerging virus variants, and deliver tumor-busting therapies more precisely, said Dr. Appel, who has formed a startup and hopes to fast-track the first hydrogel drug delivery system to clinical trials within a few years.

Meanwhile, another team at the Massachusetts Institute of Technology has taken a different approach, developing a standard-sized ingestible hydrogel pill that swells up like a puffer fish in the stomach, lasting a month and slowly releasing drugs all the while. To remove the pill, a patient simply drinks a salt-based solution that shrivels the ping-pong ball–sized device so it can be passed out of the body.

In a paper in Nature Communications, the scientists showed the puffer fish pill could also be loaded with tiny cameras or monitors to track conditions like ulcers or cancer.

“The dream is to have a Jell-O-like smart pill that, once swallowed, stays in the stomach and monitors the patient’s health,” said Xuanhe Zhao, PhD, a researcher on the project and associate professor of mechanical engineering at MIT.
 

Building joints and regrowing bones

Since the 1970s, researchers have mulled using hydrogels to replace human cartilage, a remarkably strong and flexible tissue made of about 90% water but able to withstand the weight of a car on an area about the size of a coin.

Until recently, those efforts have largely failed. Meaning when knee cartilage wears down, things like cartilage transplants, drilling holes to stimulate new growth, or total joint replacements – all of which require lengthy rehab – are the only options. 

But that may be about to change.

Dr. Wiley and his colleagues at Duke recently reported that they’d developed the first gel-based cartilage substitute even stronger and more durable than the real thing.

By attaching their hydrogel to a titanium backing to help stick it in place, they hope to repair damaged cartilage “much like a dentist fills a cavity” long before surgery is necessary.

They too have partnered with industry to bring their hydrogel to market – starting with knees.

“Ultimately, the goal is to do any joint – hips, ankles, fingers, and toes,” Dr. Wiley said. 

At the University of Toronto, chemist Karina Carneiro, PhD, and dentist Christopher McCulloch, DDS, are also thinking big.

In a recent paper in Proceedings of the National Academy of Sciences, they describe a hydrogel, designed by Dr. Carneiro and made of DNA, that can be injected, migrate to a defect in bone – an irreparable break, hole from surgery, or jawbone withered by age – and fill in the gap like putty. But not only does it patch the hole, it prompts the bone to regenerate. 

In rats with holes in their skulls due to surgery, they found that the treatment did not work as well as the existing gold standard for repairing holes in bone – grafting bone from elsewhere in the body. But it did work.

“These are very early days for DNA hydrogels,” cautioned Dr. McCulloch, a study coauthor and professor in the Faculty of Dentistry, noting that it will likely be a decade or more before such technology could be available to patients. “But there is the potential that DNA hydrogel could someday grow bone without having to have highly invasive surgical procedures. That’s a significant advancement.”
 

A sci-fi future

Perhaps the wildest, and weirdest, potential applications of hydrogels come in the realm of human-machine interaction.

Numerous companies are already dabbling in neural prosthetic or brain computer interfaces that might someday, for instance, let someone who is paralyzed and can’t speak write on a laptop using their thoughts.

The spoon-in-the-Jell-O problem has been a major stumbling block.

But Dr. Tringides, who recently earned her PhD in biophysics from Harvard, is working on it.

She and her team have developed a seaweed-based hydrogel loaded with tiny flecks of nanomaterials that can not only meld nicely into squishy brain tissue but also conduct electricity.

Within a decade, she says, this could replace the clunky platinum metal discs used for electrocorticography – recording electrical activity in the brain to identify where seizures start or doing precise brain surgery.

In 30 to 50 years? Let your imagination run wild.

“I’m a skeptic. I like to take research step by step,” she said. “But things are definitely progressing in an interesting direction.”
 

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

BALTIMORE – The off-label prescribing of compounded, bioidentical hormone therapy – in pills, creams, or pellets – for symptoms of perimenopause or menopause can put physicians at legal risk because the products lack scientific backing, according to an expert at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists (ACOG).

Clinicians write an estimated 26 to 33 million prescriptions for compounded bioidentical hormone therapy (cBHT) every year, and almost 41% of menopausal women who need treatment try cBHT during their lives. But these drugs lack the approval for this indication from the Food and Drug Administration.

“There is a public perception that this is natural, safer, and anti-aging,” said Robert Kauffman, MD, a professor of obstetrics and gynecology and assistant dean for research at Texas Tech University Health Sciences Center in Amarillo.

Following the 2002 Women’s Health Initiative report showing a link between hormone therapy (HT) and an increase in the incidence of breast cancer, medical schools have slowed or paused instructing trainees on the traditional treatment, Dr. Kauffman said. The association was later determined to be spurious: HT is not associated with a risk for all-cause mortality or deaths from cardiovascular disease or cancer. However, HT still is largely ignored by younger physicians, Dr. Kauffman said, because of unsubstantiated “dangers” such as heart attack, stroke, and deep vein thrombosis.

The lack of education on HT for medical school students and residents has “opened the door to unsubstantiated marketing claims and practices” for cBHT, Dr. Kauffman said. “Hence, the use of compounded bioidentical hormone therapy has increased” as clinicians look for alternatives.

Groups including ACOG, the North American Menopause Society (NAMS), and the U.S. Preventive Services Task Force recommend against the use of Non–FDA-approved therapies such as cBHT, except for narrow indications. Dr. Kauffman said that drug manufacturers have not conducted randomized controlled trials or observational studies on cBHT in treating menopause.

He cited studies showing quality problems with the compounding process of these drugs, and wide variations in the amount of actual ingredients from product labels. One 2021 study published in Menopause comparing patients taking cBHT or FDA-approved HT found that side effects were significantly higher in the cBHT group (57.6% vs. 14.8%; P < .0001).

But manufacturers of cBHT claim that their products prevent cardiovascular disease and Alzheimer’s disease and decrease the risk for breast cancer and stroke – assertions that are at best unproven, according to Dr. Kauffman.

The National Academies of Sciences, Engineering, and Medicine in 2020 said that clinicians have a duty to inform patients of the insufficient evidence to support clinical use of cBHT and should prescribe the products only to patients with documented allergies to an active ingredient in an FDA-approved agent or who require an alternative dosage.

Patients may also have to pay much more out of pocket for cBHT products because they often are not covered by insurance. Generic HT products, meanwhile, are relatively inexpensive and typically are covered, he noted.

“We have to be careful to avoid financial harm to patients by prescribing things, which are much more expensive than those which are usually available,” Dr. Kauffman said.

Prescribing any non–FDA-approved product, especially when biosimilars are available, places physicians at legal risk, Dr. Kauffman said. Physicians who recommend cBHT should inform patients that the products are not FDA approved and carefully document this discussion in the patient’s electronic health record. State boards of medicine can sanction physicians for “coercion” for prescribing cBHT products without mentioning alternatives, he added.

JoAnn Pinkerton, MD, professor of obstetrics and gynecology at the University of Virginia, Charlottesville, and executive director emeritus of NAMS, who attended the session, praised Dr. Kauffman for providing a balanced and evidence-based overview of the subject.

University of Virginia Health System

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

BALTIMORE – The off-label prescribing of compounded, bioidentical hormone therapy – in pills, creams, or pellets – for symptoms of perimenopause or menopause can put physicians at legal risk because the products lack scientific backing, according to an expert at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists (ACOG).

Clinicians write an estimated 26 to 33 million prescriptions for compounded bioidentical hormone therapy (cBHT) every year, and almost 41% of menopausal women who need treatment try cBHT during their lives. But these drugs lack the approval for this indication from the Food and Drug Administration.

“There is a public perception that this is natural, safer, and anti-aging,” said Robert Kauffman, MD, a professor of obstetrics and gynecology and assistant dean for research at Texas Tech University Health Sciences Center in Amarillo.

Following the 2002 Women’s Health Initiative report showing a link between hormone therapy (HT) and an increase in the incidence of breast cancer, medical schools have slowed or paused instructing trainees on the traditional treatment, Dr. Kauffman said. The association was later determined to be spurious: HT is not associated with a risk for all-cause mortality or deaths from cardiovascular disease or cancer. However, HT still is largely ignored by younger physicians, Dr. Kauffman said, because of unsubstantiated “dangers” such as heart attack, stroke, and deep vein thrombosis.

The lack of education on HT for medical school students and residents has “opened the door to unsubstantiated marketing claims and practices” for cBHT, Dr. Kauffman said. “Hence, the use of compounded bioidentical hormone therapy has increased” as clinicians look for alternatives.

Groups including ACOG, the North American Menopause Society (NAMS), and the U.S. Preventive Services Task Force recommend against the use of Non–FDA-approved therapies such as cBHT, except for narrow indications. Dr. Kauffman said that drug manufacturers have not conducted randomized controlled trials or observational studies on cBHT in treating menopause.

He cited studies showing quality problems with the compounding process of these drugs, and wide variations in the amount of actual ingredients from product labels. One 2021 study published in Menopause comparing patients taking cBHT or FDA-approved HT found that side effects were significantly higher in the cBHT group (57.6% vs. 14.8%; P < .0001).

But manufacturers of cBHT claim that their products prevent cardiovascular disease and Alzheimer’s disease and decrease the risk for breast cancer and stroke – assertions that are at best unproven, according to Dr. Kauffman.

The National Academies of Sciences, Engineering, and Medicine in 2020 said that clinicians have a duty to inform patients of the insufficient evidence to support clinical use of cBHT and should prescribe the products only to patients with documented allergies to an active ingredient in an FDA-approved agent or who require an alternative dosage.

Patients may also have to pay much more out of pocket for cBHT products because they often are not covered by insurance. Generic HT products, meanwhile, are relatively inexpensive and typically are covered, he noted.

“We have to be careful to avoid financial harm to patients by prescribing things, which are much more expensive than those which are usually available,” Dr. Kauffman said.

Prescribing any non–FDA-approved product, especially when biosimilars are available, places physicians at legal risk, Dr. Kauffman said. Physicians who recommend cBHT should inform patients that the products are not FDA approved and carefully document this discussion in the patient’s electronic health record. State boards of medicine can sanction physicians for “coercion” for prescribing cBHT products without mentioning alternatives, he added.

JoAnn Pinkerton, MD, professor of obstetrics and gynecology at the University of Virginia, Charlottesville, and executive director emeritus of NAMS, who attended the session, praised Dr. Kauffman for providing a balanced and evidence-based overview of the subject.

University of Virginia Health System

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

BALTIMORE – The off-label prescribing of compounded, bioidentical hormone therapy – in pills, creams, or pellets – for symptoms of perimenopause or menopause can put physicians at legal risk because the products lack scientific backing, according to an expert at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists (ACOG).

Clinicians write an estimated 26 to 33 million prescriptions for compounded bioidentical hormone therapy (cBHT) every year, and almost 41% of menopausal women who need treatment try cBHT during their lives. But these drugs lack the approval for this indication from the Food and Drug Administration.

“There is a public perception that this is natural, safer, and anti-aging,” said Robert Kauffman, MD, a professor of obstetrics and gynecology and assistant dean for research at Texas Tech University Health Sciences Center in Amarillo.

Following the 2002 Women’s Health Initiative report showing a link between hormone therapy (HT) and an increase in the incidence of breast cancer, medical schools have slowed or paused instructing trainees on the traditional treatment, Dr. Kauffman said. The association was later determined to be spurious: HT is not associated with a risk for all-cause mortality or deaths from cardiovascular disease or cancer. However, HT still is largely ignored by younger physicians, Dr. Kauffman said, because of unsubstantiated “dangers” such as heart attack, stroke, and deep vein thrombosis.

The lack of education on HT for medical school students and residents has “opened the door to unsubstantiated marketing claims and practices” for cBHT, Dr. Kauffman said. “Hence, the use of compounded bioidentical hormone therapy has increased” as clinicians look for alternatives.

Groups including ACOG, the North American Menopause Society (NAMS), and the U.S. Preventive Services Task Force recommend against the use of Non–FDA-approved therapies such as cBHT, except for narrow indications. Dr. Kauffman said that drug manufacturers have not conducted randomized controlled trials or observational studies on cBHT in treating menopause.

He cited studies showing quality problems with the compounding process of these drugs, and wide variations in the amount of actual ingredients from product labels. One 2021 study published in Menopause comparing patients taking cBHT or FDA-approved HT found that side effects were significantly higher in the cBHT group (57.6% vs. 14.8%; P < .0001).

But manufacturers of cBHT claim that their products prevent cardiovascular disease and Alzheimer’s disease and decrease the risk for breast cancer and stroke – assertions that are at best unproven, according to Dr. Kauffman.

The National Academies of Sciences, Engineering, and Medicine in 2020 said that clinicians have a duty to inform patients of the insufficient evidence to support clinical use of cBHT and should prescribe the products only to patients with documented allergies to an active ingredient in an FDA-approved agent or who require an alternative dosage.

Patients may also have to pay much more out of pocket for cBHT products because they often are not covered by insurance. Generic HT products, meanwhile, are relatively inexpensive and typically are covered, he noted.

“We have to be careful to avoid financial harm to patients by prescribing things, which are much more expensive than those which are usually available,” Dr. Kauffman said.

Prescribing any non–FDA-approved product, especially when biosimilars are available, places physicians at legal risk, Dr. Kauffman said. Physicians who recommend cBHT should inform patients that the products are not FDA approved and carefully document this discussion in the patient’s electronic health record. State boards of medicine can sanction physicians for “coercion” for prescribing cBHT products without mentioning alternatives, he added.

JoAnn Pinkerton, MD, professor of obstetrics and gynecology at the University of Virginia, Charlottesville, and executive director emeritus of NAMS, who attended the session, praised Dr. Kauffman for providing a balanced and evidence-based overview of the subject.

University of Virginia Health System

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

Patients undergoing bariatric surgery for obesity showed significant declines in the use of lipid-lowering and antidiabetic medications up to 15 years after the procedure compared with patients with obesity who did not have such an operation. However, these declines didn’t extend to cardiovascular medication use.

“In this study, undergoing bariatric surgery was associated with a substantial and long-lasting reduction in the use of lipid-lowering and antidiabetic medications, compared with no surgery for obesity, while for cardiovascular medications this reduction was only transient,” the authors report in research published in JAMA Surgery.

“The results can aid in informed decision-making when considering bariatric surgery for patients with morbid obesity and inform patients and professionals about the expected long-term effects of medication use for obesity-related comorbidities,” they write.

The study “highlights the benefits of mandated databases that report metabolic bariatric surgery, obesity-related comorbidities, and medications,” writes Paulina Salminen, MD, in an accompanying editorial.

However, key limitations include a lack of weight data, which is important in light of previous studies showing that suboptimal weight loss after bariatric surgery is linked to a higher incidence of type 2 diabetes, dyslipidemia, and hypertension, note Dr. Salminen, of the department of digestive surgery, University Hospital, Turku, Finland, and colleagues.
 

Swedish, Finnish obesity data probed

When significant weight loss is achieved, bariatric surgery has been well documented to be associated with improvements in a variety of comorbidities, quality of life, and even life expectancy.

Key comorbidities shown to improve with the surgery include hyperlipidemia, cardiovascular disease, and type 2 diabetes.

However, data are lacking on the association between bariatric surgery and the use of medications for those conditions, particularly compared with people with obesity who don’t have bariatric surgery.

To investigate, first author Joonas H. Kauppila, MD, PhD, of Upper Gastrointestinal Surgery, Karolinska University Hospital, Stockholm, and colleagues conducted a population-based cohort study, evaluating data on 26,396 patients who underwent bariatric surgery with gastric bypass or sleeve gastrectomy in Sweden between 2005 and 2020 or Finland between 1995 and 2018.

Overall, 66.4% of patients were women and their median age was 50.

They were compared with five times as many matched controls with obesity who had not had bariatric surgery from the same population databases, representing a total of 131,980 patients who were matched based on age, country, sex, calendar year, and medication use.  

In terms of lipid-lowering medication, rates of use after bariatric surgery decreased from 20.3% at baseline to 12.9% after 2 years and bounced back somewhat to 17.6% after 15 years. Comparatively, in the no surgery group, baseline lipid-lowering medication use of 21.0% increased to 44.6% after 15 years, more than twice the rate of usage in the bariatric surgery group in the same period.

Antidiabetic medications were used by 27.7% of patients in the bariatric surgery group at baseline, with a drop to 10.0% after 2 years, followed by an increase to 23.5% after 15 years. In the no surgery group, the rate of antidiabetic medication use steadily increased from 27.7% at baseline to 54.2% after 15 years, which again was nearly double the rate of antidiabetic medication use in the bariatric surgery group at 15 years.

Meanwhile, cardiovascular medications were used by 60.2% of patients receiving bariatric surgery at baseline, with the rate decreasing to 43.2% after 2 years but increasing to 74.6% after 15 years. Among the nonbariatric surgery patients, use of cardiovascular medications increased from 54.4% at baseline to 83.3% after 15 years.
 

Causes?

As for the cause of the lack of any decline in use of cardiovascular medications versus other medications in the surgery patients, the authors speculate that the effect “may be related to aging and regain of weight over time after bariatric surgery, a phenomenon caused by hormonal, dietary, physical, and behavioral factors.”

“In contrast, as expected, a gradual increase in the use of all three medication groups was observed over time among the patients treated with no surgery for obesity,” they note.

The lower medication use with bariatric surgery can also translate to economic benefits, the authors add.

“Economically, the long-lasting reductions in medication use for hyperlipidemia, cardiovascular morbidity, and diabetes suggest that surgical treatment of morbid obesity may infer savings in medication expenses for patients, health care, and society,” they report.

“Future research may focus on subgroups that are most likely to benefit from bariatric surgery, including resolution and severity of comorbidities,” they continue.

In their editorial, Dr. Salminen and colleagues note that previous research has shown remission of dyslipidemia in up to 70% of patients after bariatric surgery that was independent of weight loss, which appears to support the sustained reduction in lipid-lowering medications following surgery observed in the current study, suggesting some benefits on lipids beyond weight loss.

Other limitations, however, include that the bariatric surgery group in the study was older and had more comorbidities than those in previous bariatric surgery studies.

“Future studies should assess this in a younger cohort with less disease at baseline and differentiation within cardiovascular disease regarding at least hypertension, ischemic heart disease, and heart failure,” the authors conclude.

The authors have reported no relevant financial relationships. Dr. Salminen has reported receiving grants from the Sigrid Jusélius Foundation, Academy of Finland, Government Research Grant Foundation, and the University of Turku (Finland).

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

Patients undergoing bariatric surgery for obesity showed significant declines in the use of lipid-lowering and antidiabetic medications up to 15 years after the procedure compared with patients with obesity who did not have such an operation. However, these declines didn’t extend to cardiovascular medication use.

“In this study, undergoing bariatric surgery was associated with a substantial and long-lasting reduction in the use of lipid-lowering and antidiabetic medications, compared with no surgery for obesity, while for cardiovascular medications this reduction was only transient,” the authors report in research published in JAMA Surgery.

“The results can aid in informed decision-making when considering bariatric surgery for patients with morbid obesity and inform patients and professionals about the expected long-term effects of medication use for obesity-related comorbidities,” they write.

The study “highlights the benefits of mandated databases that report metabolic bariatric surgery, obesity-related comorbidities, and medications,” writes Paulina Salminen, MD, in an accompanying editorial.

However, key limitations include a lack of weight data, which is important in light of previous studies showing that suboptimal weight loss after bariatric surgery is linked to a higher incidence of type 2 diabetes, dyslipidemia, and hypertension, note Dr. Salminen, of the department of digestive surgery, University Hospital, Turku, Finland, and colleagues.
 

Swedish, Finnish obesity data probed

When significant weight loss is achieved, bariatric surgery has been well documented to be associated with improvements in a variety of comorbidities, quality of life, and even life expectancy.

Key comorbidities shown to improve with the surgery include hyperlipidemia, cardiovascular disease, and type 2 diabetes.

However, data are lacking on the association between bariatric surgery and the use of medications for those conditions, particularly compared with people with obesity who don’t have bariatric surgery.

To investigate, first author Joonas H. Kauppila, MD, PhD, of Upper Gastrointestinal Surgery, Karolinska University Hospital, Stockholm, and colleagues conducted a population-based cohort study, evaluating data on 26,396 patients who underwent bariatric surgery with gastric bypass or sleeve gastrectomy in Sweden between 2005 and 2020 or Finland between 1995 and 2018.

Overall, 66.4% of patients were women and their median age was 50.

They were compared with five times as many matched controls with obesity who had not had bariatric surgery from the same population databases, representing a total of 131,980 patients who were matched based on age, country, sex, calendar year, and medication use.  

In terms of lipid-lowering medication, rates of use after bariatric surgery decreased from 20.3% at baseline to 12.9% after 2 years and bounced back somewhat to 17.6% after 15 years. Comparatively, in the no surgery group, baseline lipid-lowering medication use of 21.0% increased to 44.6% after 15 years, more than twice the rate of usage in the bariatric surgery group in the same period.

Antidiabetic medications were used by 27.7% of patients in the bariatric surgery group at baseline, with a drop to 10.0% after 2 years, followed by an increase to 23.5% after 15 years. In the no surgery group, the rate of antidiabetic medication use steadily increased from 27.7% at baseline to 54.2% after 15 years, which again was nearly double the rate of antidiabetic medication use in the bariatric surgery group at 15 years.

Meanwhile, cardiovascular medications were used by 60.2% of patients receiving bariatric surgery at baseline, with the rate decreasing to 43.2% after 2 years but increasing to 74.6% after 15 years. Among the nonbariatric surgery patients, use of cardiovascular medications increased from 54.4% at baseline to 83.3% after 15 years.
 

Causes?

As for the cause of the lack of any decline in use of cardiovascular medications versus other medications in the surgery patients, the authors speculate that the effect “may be related to aging and regain of weight over time after bariatric surgery, a phenomenon caused by hormonal, dietary, physical, and behavioral factors.”

“In contrast, as expected, a gradual increase in the use of all three medication groups was observed over time among the patients treated with no surgery for obesity,” they note.

The lower medication use with bariatric surgery can also translate to economic benefits, the authors add.

“Economically, the long-lasting reductions in medication use for hyperlipidemia, cardiovascular morbidity, and diabetes suggest that surgical treatment of morbid obesity may infer savings in medication expenses for patients, health care, and society,” they report.

“Future research may focus on subgroups that are most likely to benefit from bariatric surgery, including resolution and severity of comorbidities,” they continue.

In their editorial, Dr. Salminen and colleagues note that previous research has shown remission of dyslipidemia in up to 70% of patients after bariatric surgery that was independent of weight loss, which appears to support the sustained reduction in lipid-lowering medications following surgery observed in the current study, suggesting some benefits on lipids beyond weight loss.

Other limitations, however, include that the bariatric surgery group in the study was older and had more comorbidities than those in previous bariatric surgery studies.

“Future studies should assess this in a younger cohort with less disease at baseline and differentiation within cardiovascular disease regarding at least hypertension, ischemic heart disease, and heart failure,” the authors conclude.

The authors have reported no relevant financial relationships. Dr. Salminen has reported receiving grants from the Sigrid Jusélius Foundation, Academy of Finland, Government Research Grant Foundation, and the University of Turku (Finland).

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

Patients undergoing bariatric surgery for obesity showed significant declines in the use of lipid-lowering and antidiabetic medications up to 15 years after the procedure compared with patients with obesity who did not have such an operation. However, these declines didn’t extend to cardiovascular medication use.

“In this study, undergoing bariatric surgery was associated with a substantial and long-lasting reduction in the use of lipid-lowering and antidiabetic medications, compared with no surgery for obesity, while for cardiovascular medications this reduction was only transient,” the authors report in research published in JAMA Surgery.

“The results can aid in informed decision-making when considering bariatric surgery for patients with morbid obesity and inform patients and professionals about the expected long-term effects of medication use for obesity-related comorbidities,” they write.

The study “highlights the benefits of mandated databases that report metabolic bariatric surgery, obesity-related comorbidities, and medications,” writes Paulina Salminen, MD, in an accompanying editorial.

However, key limitations include a lack of weight data, which is important in light of previous studies showing that suboptimal weight loss after bariatric surgery is linked to a higher incidence of type 2 diabetes, dyslipidemia, and hypertension, note Dr. Salminen, of the department of digestive surgery, University Hospital, Turku, Finland, and colleagues.
 

Swedish, Finnish obesity data probed

When significant weight loss is achieved, bariatric surgery has been well documented to be associated with improvements in a variety of comorbidities, quality of life, and even life expectancy.

Key comorbidities shown to improve with the surgery include hyperlipidemia, cardiovascular disease, and type 2 diabetes.

However, data are lacking on the association between bariatric surgery and the use of medications for those conditions, particularly compared with people with obesity who don’t have bariatric surgery.

To investigate, first author Joonas H. Kauppila, MD, PhD, of Upper Gastrointestinal Surgery, Karolinska University Hospital, Stockholm, and colleagues conducted a population-based cohort study, evaluating data on 26,396 patients who underwent bariatric surgery with gastric bypass or sleeve gastrectomy in Sweden between 2005 and 2020 or Finland between 1995 and 2018.

Overall, 66.4% of patients were women and their median age was 50.

They were compared with five times as many matched controls with obesity who had not had bariatric surgery from the same population databases, representing a total of 131,980 patients who were matched based on age, country, sex, calendar year, and medication use.  

In terms of lipid-lowering medication, rates of use after bariatric surgery decreased from 20.3% at baseline to 12.9% after 2 years and bounced back somewhat to 17.6% after 15 years. Comparatively, in the no surgery group, baseline lipid-lowering medication use of 21.0% increased to 44.6% after 15 years, more than twice the rate of usage in the bariatric surgery group in the same period.

Antidiabetic medications were used by 27.7% of patients in the bariatric surgery group at baseline, with a drop to 10.0% after 2 years, followed by an increase to 23.5% after 15 years. In the no surgery group, the rate of antidiabetic medication use steadily increased from 27.7% at baseline to 54.2% after 15 years, which again was nearly double the rate of antidiabetic medication use in the bariatric surgery group at 15 years.

Meanwhile, cardiovascular medications were used by 60.2% of patients receiving bariatric surgery at baseline, with the rate decreasing to 43.2% after 2 years but increasing to 74.6% after 15 years. Among the nonbariatric surgery patients, use of cardiovascular medications increased from 54.4% at baseline to 83.3% after 15 years.
 

Causes?

As for the cause of the lack of any decline in use of cardiovascular medications versus other medications in the surgery patients, the authors speculate that the effect “may be related to aging and regain of weight over time after bariatric surgery, a phenomenon caused by hormonal, dietary, physical, and behavioral factors.”

“In contrast, as expected, a gradual increase in the use of all three medication groups was observed over time among the patients treated with no surgery for obesity,” they note.

The lower medication use with bariatric surgery can also translate to economic benefits, the authors add.

“Economically, the long-lasting reductions in medication use for hyperlipidemia, cardiovascular morbidity, and diabetes suggest that surgical treatment of morbid obesity may infer savings in medication expenses for patients, health care, and society,” they report.

“Future research may focus on subgroups that are most likely to benefit from bariatric surgery, including resolution and severity of comorbidities,” they continue.

In their editorial, Dr. Salminen and colleagues note that previous research has shown remission of dyslipidemia in up to 70% of patients after bariatric surgery that was independent of weight loss, which appears to support the sustained reduction in lipid-lowering medications following surgery observed in the current study, suggesting some benefits on lipids beyond weight loss.

Other limitations, however, include that the bariatric surgery group in the study was older and had more comorbidities than those in previous bariatric surgery studies.

“Future studies should assess this in a younger cohort with less disease at baseline and differentiation within cardiovascular disease regarding at least hypertension, ischemic heart disease, and heart failure,” the authors conclude.

The authors have reported no relevant financial relationships. Dr. Salminen has reported receiving grants from the Sigrid Jusélius Foundation, Academy of Finland, Government Research Grant Foundation, and the University of Turku (Finland).

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

People who develop type 2 diabetes before age 60 years are at threefold greater risk for dementia compared with those who don’t develop diabetes, new findings suggest.

Moreover, the new data from the prospective Atherosclerosis Risk in Communities (ARIC) cohort also suggest that the previously identified increased risk for dementia among people with prediabetes appears to be entirely explained by the subset who go on to develop type 2 diabetes.

“Our findings suggest that preventing prediabetes progression, especially in younger individuals, may be an important way to reduce the dementia burden,” wrote PhD student Jiaqi Hu of Johns Hopkins University, Baltimore, and colleagues. Their article was  published online in Diabetologia.

The result builds on previous findings linking dysglycemia and cognitive decline, the study’s lead author, Elizabeth Selvin, PhD, of the Bloomberg School of Public Health at Johns Hopkins, said in an interview.  

“Our prior work in the ARIC study suggests that improving glucose control could help prevent dementia in later life,” she said.  

Johns Hopkins University

Other studies have also linked higher A1c levels and diabetes in midlife to increased rates of cognitive decline. In addition, Dr. Selvin noted, “There is growing evidence that focusing on vascular health, especially focusing on diabetes and blood pressure, in midlife can stave off dementia in later life.”

This new study is the first to examine the effect of diabetes in the relationship between prediabetes and dementia, as well as the age of diabetes onset on subsequent dementia.
 

Prediabetes linked to dementia via diabetes development

Of the 11,656 ARIC participants without diabetes at baseline during 1990-1992 (age 46-70 years), 20.0% had prediabetes (defined as A1c 5.7%-6.4% or 39-46 mmol/mol). During a median follow-up of 15.9 years, 3,143 participants developed diabetes. The proportions of patients who developed diabetes were 44.6% among those with prediabetes at baseline versus 22.5% of those without.

Dementia developed in 2,247 participants over a median follow-up of 24.7 years. The cumulative incidence of dementia was 23.9% among those who developed diabetes versus 20.5% among those who did not.

After adjustment for demographics and for the Alzheimer’s disease–linked apolipoprotein E (APOE) gene, prediabetes was significantly associated with incident dementia (hazard ratio [HR], 1.19). However, significance disappeared after adjustment for incident diabetes (HR, 1.09), the researchers reported.  
 

Younger age at diabetes diagnosis raises dementia risk  

Age at diabetes diagnosis made a difference in dementia risk. With adjustments for lifestyle, demographic, and clinical factors, those diagnosed with diabetes before age 60 years had a nearly threefold increased risk for dementia compared with those who never developed diabetes (HR, 2.92; P < .001).

The dementia risk was also significantly increased, although to a lesser degree, among those aged 60-69 years at diabetes diagnosis (HR, 1.73; P < .001) and age 70-79 years at diabetes diagnosis (HR, 1.23; P < .001). The relationship was not significant for those aged 80 years and older (HR, 1.13).  

“Prevention efforts in people with diabetes diagnosed younger than 65 years should be a high priority,” the authors urged.

Taken together, the data suggest that prolonged exposure to hyperglycemia plays a major role in dementia development.

“Putative mechanisms include acute and chronic hyperglycemia, glucose toxicity, insulin resistance, and microvascular dysfunction of the central nervous system. ... Glucose toxicity and microvascular dysfunction are associated with increased inflammatory and oxidative stress, leading to increased blood–brain permeability,” the researchers wrote.

Dr. Selvin said that her group is pursuing further work in this area using continuous glucose monitoring. “We plan to look at ... how glycemic control and different patterns of glucose in older adults may be linked to cognitive decline and other neurocognitive outcomes.”

The researchers reported no relevant financial relationships. Dr. Selvin has reported being on the advisory board for Diabetologia; she had no role in peer review of the manuscript.

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

People who develop type 2 diabetes before age 60 years are at threefold greater risk for dementia compared with those who don’t develop diabetes, new findings suggest.

Moreover, the new data from the prospective Atherosclerosis Risk in Communities (ARIC) cohort also suggest that the previously identified increased risk for dementia among people with prediabetes appears to be entirely explained by the subset who go on to develop type 2 diabetes.

“Our findings suggest that preventing prediabetes progression, especially in younger individuals, may be an important way to reduce the dementia burden,” wrote PhD student Jiaqi Hu of Johns Hopkins University, Baltimore, and colleagues. Their article was  published online in Diabetologia.

The result builds on previous findings linking dysglycemia and cognitive decline, the study’s lead author, Elizabeth Selvin, PhD, of the Bloomberg School of Public Health at Johns Hopkins, said in an interview.  

“Our prior work in the ARIC study suggests that improving glucose control could help prevent dementia in later life,” she said.  

Johns Hopkins University

Other studies have also linked higher A1c levels and diabetes in midlife to increased rates of cognitive decline. In addition, Dr. Selvin noted, “There is growing evidence that focusing on vascular health, especially focusing on diabetes and blood pressure, in midlife can stave off dementia in later life.”

This new study is the first to examine the effect of diabetes in the relationship between prediabetes and dementia, as well as the age of diabetes onset on subsequent dementia.
 

Prediabetes linked to dementia via diabetes development

Of the 11,656 ARIC participants without diabetes at baseline during 1990-1992 (age 46-70 years), 20.0% had prediabetes (defined as A1c 5.7%-6.4% or 39-46 mmol/mol). During a median follow-up of 15.9 years, 3,143 participants developed diabetes. The proportions of patients who developed diabetes were 44.6% among those with prediabetes at baseline versus 22.5% of those without.

Dementia developed in 2,247 participants over a median follow-up of 24.7 years. The cumulative incidence of dementia was 23.9% among those who developed diabetes versus 20.5% among those who did not.

After adjustment for demographics and for the Alzheimer’s disease–linked apolipoprotein E (APOE) gene, prediabetes was significantly associated with incident dementia (hazard ratio [HR], 1.19). However, significance disappeared after adjustment for incident diabetes (HR, 1.09), the researchers reported.  
 

Younger age at diabetes diagnosis raises dementia risk  

Age at diabetes diagnosis made a difference in dementia risk. With adjustments for lifestyle, demographic, and clinical factors, those diagnosed with diabetes before age 60 years had a nearly threefold increased risk for dementia compared with those who never developed diabetes (HR, 2.92; P < .001).

The dementia risk was also significantly increased, although to a lesser degree, among those aged 60-69 years at diabetes diagnosis (HR, 1.73; P < .001) and age 70-79 years at diabetes diagnosis (HR, 1.23; P < .001). The relationship was not significant for those aged 80 years and older (HR, 1.13).  

“Prevention efforts in people with diabetes diagnosed younger than 65 years should be a high priority,” the authors urged.

Taken together, the data suggest that prolonged exposure to hyperglycemia plays a major role in dementia development.

“Putative mechanisms include acute and chronic hyperglycemia, glucose toxicity, insulin resistance, and microvascular dysfunction of the central nervous system. ... Glucose toxicity and microvascular dysfunction are associated with increased inflammatory and oxidative stress, leading to increased blood–brain permeability,” the researchers wrote.

Dr. Selvin said that her group is pursuing further work in this area using continuous glucose monitoring. “We plan to look at ... how glycemic control and different patterns of glucose in older adults may be linked to cognitive decline and other neurocognitive outcomes.”

The researchers reported no relevant financial relationships. Dr. Selvin has reported being on the advisory board for Diabetologia; she had no role in peer review of the manuscript.

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

People who develop type 2 diabetes before age 60 years are at threefold greater risk for dementia compared with those who don’t develop diabetes, new findings suggest.

Moreover, the new data from the prospective Atherosclerosis Risk in Communities (ARIC) cohort also suggest that the previously identified increased risk for dementia among people with prediabetes appears to be entirely explained by the subset who go on to develop type 2 diabetes.

“Our findings suggest that preventing prediabetes progression, especially in younger individuals, may be an important way to reduce the dementia burden,” wrote PhD student Jiaqi Hu of Johns Hopkins University, Baltimore, and colleagues. Their article was  published online in Diabetologia.

The result builds on previous findings linking dysglycemia and cognitive decline, the study’s lead author, Elizabeth Selvin, PhD, of the Bloomberg School of Public Health at Johns Hopkins, said in an interview.  

“Our prior work in the ARIC study suggests that improving glucose control could help prevent dementia in later life,” she said.  

Johns Hopkins University

Other studies have also linked higher A1c levels and diabetes in midlife to increased rates of cognitive decline. In addition, Dr. Selvin noted, “There is growing evidence that focusing on vascular health, especially focusing on diabetes and blood pressure, in midlife can stave off dementia in later life.”

This new study is the first to examine the effect of diabetes in the relationship between prediabetes and dementia, as well as the age of diabetes onset on subsequent dementia.
 

Prediabetes linked to dementia via diabetes development

Of the 11,656 ARIC participants without diabetes at baseline during 1990-1992 (age 46-70 years), 20.0% had prediabetes (defined as A1c 5.7%-6.4% or 39-46 mmol/mol). During a median follow-up of 15.9 years, 3,143 participants developed diabetes. The proportions of patients who developed diabetes were 44.6% among those with prediabetes at baseline versus 22.5% of those without.

Dementia developed in 2,247 participants over a median follow-up of 24.7 years. The cumulative incidence of dementia was 23.9% among those who developed diabetes versus 20.5% among those who did not.

After adjustment for demographics and for the Alzheimer’s disease–linked apolipoprotein E (APOE) gene, prediabetes was significantly associated with incident dementia (hazard ratio [HR], 1.19). However, significance disappeared after adjustment for incident diabetes (HR, 1.09), the researchers reported.  
 

Younger age at diabetes diagnosis raises dementia risk  

Age at diabetes diagnosis made a difference in dementia risk. With adjustments for lifestyle, demographic, and clinical factors, those diagnosed with diabetes before age 60 years had a nearly threefold increased risk for dementia compared with those who never developed diabetes (HR, 2.92; P < .001).

The dementia risk was also significantly increased, although to a lesser degree, among those aged 60-69 years at diabetes diagnosis (HR, 1.73; P < .001) and age 70-79 years at diabetes diagnosis (HR, 1.23; P < .001). The relationship was not significant for those aged 80 years and older (HR, 1.13).  

“Prevention efforts in people with diabetes diagnosed younger than 65 years should be a high priority,” the authors urged.

Taken together, the data suggest that prolonged exposure to hyperglycemia plays a major role in dementia development.

“Putative mechanisms include acute and chronic hyperglycemia, glucose toxicity, insulin resistance, and microvascular dysfunction of the central nervous system. ... Glucose toxicity and microvascular dysfunction are associated with increased inflammatory and oxidative stress, leading to increased blood–brain permeability,” the researchers wrote.

Dr. Selvin said that her group is pursuing further work in this area using continuous glucose monitoring. “We plan to look at ... how glycemic control and different patterns of glucose in older adults may be linked to cognitive decline and other neurocognitive outcomes.”

The researchers reported no relevant financial relationships. Dr. Selvin has reported being on the advisory board for Diabetologia; she had no role in peer review of the manuscript.

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

BALTIMORE – Water-based personal vaginal lubricants can not only relieve vaginal dryness but also can improve dyspareunia and increase other measures of sexual satisfaction for women, according to research presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. In a secondary analysis also presented at the meeting, the lubricants were found not to alter the vaginal microbiome.

Using these types of lubricants during vaginal intercourse at least once a week over a 4-week period resulted in a statistically significant increase of over four points in the 36-point Female Sexual Function Index (FSFI), a self-reported measure of sexual functioning, for participants, said Michael Krychman, MD, executive director of the Southern California Center for Sexual Health and Survivorship Medicine, Newport Beach, the senior author of the study. Statistically significant improvements also were observed in individual areas such as sexual desire and arousal, orgasm, and satisfaction. Results of the study have been published in the Journal of Sexual Medicine.

Southern California Center for Sexual Health and Survivorship Medicine

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

BALTIMORE – Water-based personal vaginal lubricants can not only relieve vaginal dryness but also can improve dyspareunia and increase other measures of sexual satisfaction for women, according to research presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. In a secondary analysis also presented at the meeting, the lubricants were found not to alter the vaginal microbiome.

Using these types of lubricants during vaginal intercourse at least once a week over a 4-week period resulted in a statistically significant increase of over four points in the 36-point Female Sexual Function Index (FSFI), a self-reported measure of sexual functioning, for participants, said Michael Krychman, MD, executive director of the Southern California Center for Sexual Health and Survivorship Medicine, Newport Beach, the senior author of the study. Statistically significant improvements also were observed in individual areas such as sexual desire and arousal, orgasm, and satisfaction. Results of the study have been published in the Journal of Sexual Medicine.

Southern California Center for Sexual Health and Survivorship Medicine

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

BALTIMORE – Water-based personal vaginal lubricants can not only relieve vaginal dryness but also can improve dyspareunia and increase other measures of sexual satisfaction for women, according to research presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. In a secondary analysis also presented at the meeting, the lubricants were found not to alter the vaginal microbiome.

Using these types of lubricants during vaginal intercourse at least once a week over a 4-week period resulted in a statistically significant increase of over four points in the 36-point Female Sexual Function Index (FSFI), a self-reported measure of sexual functioning, for participants, said Michael Krychman, MD, executive director of the Southern California Center for Sexual Health and Survivorship Medicine, Newport Beach, the senior author of the study. Statistically significant improvements also were observed in individual areas such as sexual desire and arousal, orgasm, and satisfaction. Results of the study have been published in the Journal of Sexual Medicine.

Southern California Center for Sexual Health and Survivorship Medicine

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

Should people be concerned about possible hair loss when taking Wegovy, Ozempic, or Mounjaro for weight loss (where the latter two drugs are being used off label) – as was recently claimed by some people on social media and reported in news stories?
 

The consensus among dermatologists and endocrinologists is no.

It’s up to the individual to weigh the benefits of treating obesity against the risks of the therapy, including the low risk of developing temporary hair loss, says one expert.
 

Wegovy, Ozempic, and Mounjaro

Of these three newer medications, only the glucagonlike peptide–1 (GLP-1) receptor agonist semaglutide (Wegovy) is approved by the Food and Drug Administration (since June 2021) for weight management – specifically for people with either obesity (body mass index ≥ 30 kg/m²) or overweight (BMI ≥ 27) plus at least one weight-related comorbidity such as hypertension, type 2 diabetes, and high cholesterol – with a dosage up to a 2.4-mg weekly injection.

When there was a short supply of Wegovy soon after it became available, some people turned to the same drug – semaglutide, but marketed as Ozempic for type 2 diabetes, which is titrated up to a 2-mg weekly injection. Still others opted for tirzepatide (Mounjaro), a dual GLP-1 agonist and glucose-dependent insulinotropic polypeptide (GIP) agonist. Tirzepatide is approved for type 2 diabetes in the United States but is not yet approved for weight loss.

Wegovy shortages continue to be reported.

Alopecia (hair loss) was an uncommon side effect in the clinical trials of these medications; of interest, it was more common after bariatric surgery.

In clinical trials, 3% of patients receiving Wegovy (a 2.4-mg/wk injection) versus 1% of patients receiving placebo reported alopecia. Hair loss was not reported as a side effect in clinical trials of Ozempic (a 2-mg/wk injection) for type 2 diabetes. In a clinical trial of tirzepatide for weight loss in obesity, 5.7% of patients taking the highest dose (a 15-mg once-weekly injection) reported alopecia vs 1% of those who got a placebo.

In contrast, a review of 18 mostly observational studies reported that 57% of patients had hair loss after bariatric surgery.
 

Is it the drug or the rapid weight loss?

None of the experts consulted for this article had seen patients who came to them about hair loss while taking these drugs for weight loss.

“I have not seen patients complaining of hair loss from these medications, but perhaps it is just a matter of time,” said Lynne J. Goldberg, MD, a professor of dermatology and pathology and laboratory medicine, at Boston University, and director of the hair clinic at Boston Medical Center.

“Some of my patients lose hair when they lose weight, generally as a result of the weight loss itself and not as a side effect of these medications,” said Katharine H. Saunders, MD, an obesity medicine physician, cofounder of Intellihealth, and an assistant professor of medicine at Weill Cornell Medicine, New York.

“Hair loss from rapid weight loss is very common [and] not necessarily a side effect of the medication itself but more as a result of how quickly the weight loss occurs,” echoed Susan Massick, MD, associate professor of dermatology, Ohio State University, and a dermatologist at Ohio State’s Wexner Medical Center, both in Columbus.

USC Westside Center for Diabetes

“Hair loss is tricky,” observed Anne Peters, MD, director of clinical diabetes programs at the University of Southern California, Los Angeles. “Losing weight and/or changing your diet causes hair loss. Stress can cause hair loss. So, it is hard to separate weight loss from medication effect.”
 

Telogen effluvium (stress shedding) with rapid weight loss

The hair loss seems to be associated with rapid weight loss, the experts agreed.

“It is rare, but we can see patients who have a period of diffuse hair loss, called telogen effluvium, or ‘stress shedding’ with rapid weight loss,” said Michael A. Weintraub, MD, an endocrinologist at NYU Langone Health, New York.

This hair loss occurs in relation to either physical (surgery, pregnancy, illness) or emotional stress, added Dr. Weintraub, who is an assistant professor at NYU Grossman School of Medicine.

Hair loss caused by rapid weight loss could be caused by an antiobesity medication, but it could also occur with other obesity treatments, such as bariatric surgery or drastic dietary changes, he said. The hair shedding is typically short lived and reversible.

About 80%-85% of hair is in the anagen (growth) phase, about 5% is in a transitional (catagen) phase, and the rest is in telogen (resting, or shedding) phase, Dr. Massick explained. In telogen effluvium, hairs that are normally in the growth phase get suddenly shifted to telogen phase and are shed rapidly.

“Telogen effluvium can be caused by rapid weight loss, major surgery, severe COVID infection, high fever, or death in the family,” she noted. “You will not go bald with telogen effluvium, but you might find that you may lose a good volume of hair,” much more than the normal loss of up to 100 hairs a day.

“I counsel my patients about the possibility of losing hair before they undergo bariatric surgery,” Dr. Saunders said. “Generally, the health benefits of weight loss and weight maintenance outweigh the risk of temporary hair loss.”

Nutritional deficiencies and malnutrition can contribute to hair loss as well, and iron deficiency is sometimes a culprit, she added.

“If someone is worried” about hair loss associated with weight loss, “they should see their doctor,” Dr. Peters said. “If they are on thyroid hormone, in particular, the levels should be retested after weight loss.”

Hair loss appears more common after bariatric surgery than with antiobesity medications,” Dr. Weintraub observed, and it is unclear whether this is because the weight loss is more dramatic after surgery and thus a greater stressor, or whether it is caused by nutrient deficiency or a different mechanism entirely.

“Unlike certain forms of bariatric surgery, which can lead to malabsorption (e.g., Roux-en-Y gastric bypass), medications such as GLP-1 agonists and GLP-1/GIP dual agonists do not cause malabsorption,” Dr. Weintraub noted. “So nutritional deficiencies are less likely to be the cause of new hair loss in those taking antiobesity medications than [in] someone who underwent bariatric surgery.”

Iron and vitamin D deficiencies are the most common nutritional deficiencies that can cause hair loss, he noted.
 

Slow and steady weight loss rather than rapid

“I would suggest that patients try to keep the weight loss slow and steady, rather than rapid,” Dr. Goldberg said, “and follow any vitamin/mineral supplementation plan that they are given. Patients with bariatric surgery have nutritional guidance and a supplementation plan.”

“Follow a well-balanced dietary strategy with ample protein, vegetables, and some fruit,” Dr. Saunders said. Health care providers should monitor lab tests to check for and treat vitamin deficiencies, and registered dietitians can be crucial to ensure proper nutrition. She advises patients: “Find coping strategies to reduce stress and get enough sleep. If iron levels are low, start an iron supplement under your provider’s supervision.”

“Some of my patients swear by biotin supplements, prenatal vitamins or ‘hair, skin, and nails’ vitamins,” she added. If hair loss doesn’t stop, a dermatologist can look for other contributors and discuss strategies for hair restoration.

Individuals who undergo bariatric surgery require lifelong vitamin supplementation and yearly (or more frequent) lab testing, she noted.

“With, for example, bariatric surgery or any type of diet change you want to make sure you still maintain a balanced diet, whether its calories, protein, iron, zinc, vitamins (vitamin D for example),” Dr. Massick echoed.

Similarly, Dr. Peters advised: “I would say to maintain a normal healthy diet even if eating less. Exercise. Do all those healthy things. Taking a daily multivitamin isn’t a bad idea. Talk with a nutritionist. Use the appetite suppression of the medication to combine with healthy eating.”

“If someone is having new hair loss, they should see their clinician to evaluate for all possible causes,” Dr. Weintraub said. “Their provider can evaluate for underlying causes like thyroid dysfunction, iron deficiency, and vitamin D deficiency.”

However, if a patient’s pattern of hair loss is not diffuse but occurs in patches, this has an entirely different set of etiologies probably unrelated to antiobesity medication and should be evaluated.

Working with a nutritionist to ensure that patients have sufficient protein and micronutrient intake can lower the risk of developing hair loss and other complications, Dr. Weintraub said. “This is particularly important for certain forms of bariatric surgery such as Roux-en-Y gastric bypass, since that can lead to malabsorption of specific vitamins and minerals that need to be periodically measured and supplemented.”

In individuals starting an antiobesity medication, beginning a daily multivitamin has little harm, he added, and can ensure they are getting essential minerals and vitamins. However, no studies have specifically investigated this yet.

“Ultimately, it’s important to weigh the benefits of antiobesity medications against the potential risks, as we do with any medical intervention,” according to Dr. Weintraub.

“The purpose of treating obesity,” he stressed, “is to reduce the risk of heart disease, stroke, and multiple types of cancers. It’s up to the individual to weigh these benefits against the risks of the treatment, including the low risk of developing temporary hair loss.”

Dr. Peters writes a column for Medscape and disclosed that she served as a consultant for Blue Circle Health, Vertex, and Abbott Diabetes Care; received a research grant from Abbott Diabetes Care; and received stock options from Teladoc and Omada Health. Dr. Goldberg, Dr. Saunders, Dr. Massick, and Dr. Weintraub declared no relevant financial relationships.

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

Should people be concerned about possible hair loss when taking Wegovy, Ozempic, or Mounjaro for weight loss (where the latter two drugs are being used off label) – as was recently claimed by some people on social media and reported in news stories?
 

The consensus among dermatologists and endocrinologists is no.

It’s up to the individual to weigh the benefits of treating obesity against the risks of the therapy, including the low risk of developing temporary hair loss, says one expert.
 

Wegovy, Ozempic, and Mounjaro

Of these three newer medications, only the glucagonlike peptide–1 (GLP-1) receptor agonist semaglutide (Wegovy) is approved by the Food and Drug Administration (since June 2021) for weight management – specifically for people with either obesity (body mass index ≥ 30 kg/m²) or overweight (BMI ≥ 27) plus at least one weight-related comorbidity such as hypertension, type 2 diabetes, and high cholesterol – with a dosage up to a 2.4-mg weekly injection.

When there was a short supply of Wegovy soon after it became available, some people turned to the same drug – semaglutide, but marketed as Ozempic for type 2 diabetes, which is titrated up to a 2-mg weekly injection. Still others opted for tirzepatide (Mounjaro), a dual GLP-1 agonist and glucose-dependent insulinotropic polypeptide (GIP) agonist. Tirzepatide is approved for type 2 diabetes in the United States but is not yet approved for weight loss.

Wegovy shortages continue to be reported.

Alopecia (hair loss) was an uncommon side effect in the clinical trials of these medications; of interest, it was more common after bariatric surgery.

In clinical trials, 3% of patients receiving Wegovy (a 2.4-mg/wk injection) versus 1% of patients receiving placebo reported alopecia. Hair loss was not reported as a side effect in clinical trials of Ozempic (a 2-mg/wk injection) for type 2 diabetes. In a clinical trial of tirzepatide for weight loss in obesity, 5.7% of patients taking the highest dose (a 15-mg once-weekly injection) reported alopecia vs 1% of those who got a placebo.

In contrast, a review of 18 mostly observational studies reported that 57% of patients had hair loss after bariatric surgery.
 

Is it the drug or the rapid weight loss?

None of the experts consulted for this article had seen patients who came to them about hair loss while taking these drugs for weight loss.

“I have not seen patients complaining of hair loss from these medications, but perhaps it is just a matter of time,” said Lynne J. Goldberg, MD, a professor of dermatology and pathology and laboratory medicine, at Boston University, and director of the hair clinic at Boston Medical Center.

“Some of my patients lose hair when they lose weight, generally as a result of the weight loss itself and not as a side effect of these medications,” said Katharine H. Saunders, MD, an obesity medicine physician, cofounder of Intellihealth, and an assistant professor of medicine at Weill Cornell Medicine, New York.

“Hair loss from rapid weight loss is very common [and] not necessarily a side effect of the medication itself but more as a result of how quickly the weight loss occurs,” echoed Susan Massick, MD, associate professor of dermatology, Ohio State University, and a dermatologist at Ohio State’s Wexner Medical Center, both in Columbus.

USC Westside Center for Diabetes

“Hair loss is tricky,” observed Anne Peters, MD, director of clinical diabetes programs at the University of Southern California, Los Angeles. “Losing weight and/or changing your diet causes hair loss. Stress can cause hair loss. So, it is hard to separate weight loss from medication effect.”
 

Telogen effluvium (stress shedding) with rapid weight loss

The hair loss seems to be associated with rapid weight loss, the experts agreed.

“It is rare, but we can see patients who have a period of diffuse hair loss, called telogen effluvium, or ‘stress shedding’ with rapid weight loss,” said Michael A. Weintraub, MD, an endocrinologist at NYU Langone Health, New York.

This hair loss occurs in relation to either physical (surgery, pregnancy, illness) or emotional stress, added Dr. Weintraub, who is an assistant professor at NYU Grossman School of Medicine.

Hair loss caused by rapid weight loss could be caused by an antiobesity medication, but it could also occur with other obesity treatments, such as bariatric surgery or drastic dietary changes, he said. The hair shedding is typically short lived and reversible.

About 80%-85% of hair is in the anagen (growth) phase, about 5% is in a transitional (catagen) phase, and the rest is in telogen (resting, or shedding) phase, Dr. Massick explained. In telogen effluvium, hairs that are normally in the growth phase get suddenly shifted to telogen phase and are shed rapidly.

“Telogen effluvium can be caused by rapid weight loss, major surgery, severe COVID infection, high fever, or death in the family,” she noted. “You will not go bald with telogen effluvium, but you might find that you may lose a good volume of hair,” much more than the normal loss of up to 100 hairs a day.

“I counsel my patients about the possibility of losing hair before they undergo bariatric surgery,” Dr. Saunders said. “Generally, the health benefits of weight loss and weight maintenance outweigh the risk of temporary hair loss.”

Nutritional deficiencies and malnutrition can contribute to hair loss as well, and iron deficiency is sometimes a culprit, she added.

“If someone is worried” about hair loss associated with weight loss, “they should see their doctor,” Dr. Peters said. “If they are on thyroid hormone, in particular, the levels should be retested after weight loss.”

Hair loss appears more common after bariatric surgery than with antiobesity medications,” Dr. Weintraub observed, and it is unclear whether this is because the weight loss is more dramatic after surgery and thus a greater stressor, or whether it is caused by nutrient deficiency or a different mechanism entirely.

“Unlike certain forms of bariatric surgery, which can lead to malabsorption (e.g., Roux-en-Y gastric bypass), medications such as GLP-1 agonists and GLP-1/GIP dual agonists do not cause malabsorption,” Dr. Weintraub noted. “So nutritional deficiencies are less likely to be the cause of new hair loss in those taking antiobesity medications than [in] someone who underwent bariatric surgery.”

Iron and vitamin D deficiencies are the most common nutritional deficiencies that can cause hair loss, he noted.
 

Slow and steady weight loss rather than rapid

“I would suggest that patients try to keep the weight loss slow and steady, rather than rapid,” Dr. Goldberg said, “and follow any vitamin/mineral supplementation plan that they are given. Patients with bariatric surgery have nutritional guidance and a supplementation plan.”

“Follow a well-balanced dietary strategy with ample protein, vegetables, and some fruit,” Dr. Saunders said. Health care providers should monitor lab tests to check for and treat vitamin deficiencies, and registered dietitians can be crucial to ensure proper nutrition. She advises patients: “Find coping strategies to reduce stress and get enough sleep. If iron levels are low, start an iron supplement under your provider’s supervision.”

“Some of my patients swear by biotin supplements, prenatal vitamins or ‘hair, skin, and nails’ vitamins,” she added. If hair loss doesn’t stop, a dermatologist can look for other contributors and discuss strategies for hair restoration.

Individuals who undergo bariatric surgery require lifelong vitamin supplementation and yearly (or more frequent) lab testing, she noted.

“With, for example, bariatric surgery or any type of diet change you want to make sure you still maintain a balanced diet, whether its calories, protein, iron, zinc, vitamins (vitamin D for example),” Dr. Massick echoed.

Similarly, Dr. Peters advised: “I would say to maintain a normal healthy diet even if eating less. Exercise. Do all those healthy things. Taking a daily multivitamin isn’t a bad idea. Talk with a nutritionist. Use the appetite suppression of the medication to combine with healthy eating.”

“If someone is having new hair loss, they should see their clinician to evaluate for all possible causes,” Dr. Weintraub said. “Their provider can evaluate for underlying causes like thyroid dysfunction, iron deficiency, and vitamin D deficiency.”

However, if a patient’s pattern of hair loss is not diffuse but occurs in patches, this has an entirely different set of etiologies probably unrelated to antiobesity medication and should be evaluated.

Working with a nutritionist to ensure that patients have sufficient protein and micronutrient intake can lower the risk of developing hair loss and other complications, Dr. Weintraub said. “This is particularly important for certain forms of bariatric surgery such as Roux-en-Y gastric bypass, since that can lead to malabsorption of specific vitamins and minerals that need to be periodically measured and supplemented.”

In individuals starting an antiobesity medication, beginning a daily multivitamin has little harm, he added, and can ensure they are getting essential minerals and vitamins. However, no studies have specifically investigated this yet.

“Ultimately, it’s important to weigh the benefits of antiobesity medications against the potential risks, as we do with any medical intervention,” according to Dr. Weintraub.

“The purpose of treating obesity,” he stressed, “is to reduce the risk of heart disease, stroke, and multiple types of cancers. It’s up to the individual to weigh these benefits against the risks of the treatment, including the low risk of developing temporary hair loss.”

Dr. Peters writes a column for Medscape and disclosed that she served as a consultant for Blue Circle Health, Vertex, and Abbott Diabetes Care; received a research grant from Abbott Diabetes Care; and received stock options from Teladoc and Omada Health. Dr. Goldberg, Dr. Saunders, Dr. Massick, and Dr. Weintraub declared no relevant financial relationships.

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

Should people be concerned about possible hair loss when taking Wegovy, Ozempic, or Mounjaro for weight loss (where the latter two drugs are being used off label) – as was recently claimed by some people on social media and reported in news stories?
 

The consensus among dermatologists and endocrinologists is no.

It’s up to the individual to weigh the benefits of treating obesity against the risks of the therapy, including the low risk of developing temporary hair loss, says one expert.
 

Wegovy, Ozempic, and Mounjaro

Of these three newer medications, only the glucagonlike peptide–1 (GLP-1) receptor agonist semaglutide (Wegovy) is approved by the Food and Drug Administration (since June 2021) for weight management – specifically for people with either obesity (body mass index ≥ 30 kg/m²) or overweight (BMI ≥ 27) plus at least one weight-related comorbidity such as hypertension, type 2 diabetes, and high cholesterol – with a dosage up to a 2.4-mg weekly injection.

When there was a short supply of Wegovy soon after it became available, some people turned to the same drug – semaglutide, but marketed as Ozempic for type 2 diabetes, which is titrated up to a 2-mg weekly injection. Still others opted for tirzepatide (Mounjaro), a dual GLP-1 agonist and glucose-dependent insulinotropic polypeptide (GIP) agonist. Tirzepatide is approved for type 2 diabetes in the United States but is not yet approved for weight loss.

Wegovy shortages continue to be reported.

Alopecia (hair loss) was an uncommon side effect in the clinical trials of these medications; of interest, it was more common after bariatric surgery.

In clinical trials, 3% of patients receiving Wegovy (a 2.4-mg/wk injection) versus 1% of patients receiving placebo reported alopecia. Hair loss was not reported as a side effect in clinical trials of Ozempic (a 2-mg/wk injection) for type 2 diabetes. In a clinical trial of tirzepatide for weight loss in obesity, 5.7% of patients taking the highest dose (a 15-mg once-weekly injection) reported alopecia vs 1% of those who got a placebo.

In contrast, a review of 18 mostly observational studies reported that 57% of patients had hair loss after bariatric surgery.
 

Is it the drug or the rapid weight loss?

None of the experts consulted for this article had seen patients who came to them about hair loss while taking these drugs for weight loss.

“I have not seen patients complaining of hair loss from these medications, but perhaps it is just a matter of time,” said Lynne J. Goldberg, MD, a professor of dermatology and pathology and laboratory medicine, at Boston University, and director of the hair clinic at Boston Medical Center.

“Some of my patients lose hair when they lose weight, generally as a result of the weight loss itself and not as a side effect of these medications,” said Katharine H. Saunders, MD, an obesity medicine physician, cofounder of Intellihealth, and an assistant professor of medicine at Weill Cornell Medicine, New York.

“Hair loss from rapid weight loss is very common [and] not necessarily a side effect of the medication itself but more as a result of how quickly the weight loss occurs,” echoed Susan Massick, MD, associate professor of dermatology, Ohio State University, and a dermatologist at Ohio State’s Wexner Medical Center, both in Columbus.

USC Westside Center for Diabetes

“Hair loss is tricky,” observed Anne Peters, MD, director of clinical diabetes programs at the University of Southern California, Los Angeles. “Losing weight and/or changing your diet causes hair loss. Stress can cause hair loss. So, it is hard to separate weight loss from medication effect.”
 

Telogen effluvium (stress shedding) with rapid weight loss

The hair loss seems to be associated with rapid weight loss, the experts agreed.

“It is rare, but we can see patients who have a period of diffuse hair loss, called telogen effluvium, or ‘stress shedding’ with rapid weight loss,” said Michael A. Weintraub, MD, an endocrinologist at NYU Langone Health, New York.

This hair loss occurs in relation to either physical (surgery, pregnancy, illness) or emotional stress, added Dr. Weintraub, who is an assistant professor at NYU Grossman School of Medicine.

Hair loss caused by rapid weight loss could be caused by an antiobesity medication, but it could also occur with other obesity treatments, such as bariatric surgery or drastic dietary changes, he said. The hair shedding is typically short lived and reversible.

About 80%-85% of hair is in the anagen (growth) phase, about 5% is in a transitional (catagen) phase, and the rest is in telogen (resting, or shedding) phase, Dr. Massick explained. In telogen effluvium, hairs that are normally in the growth phase get suddenly shifted to telogen phase and are shed rapidly.

“Telogen effluvium can be caused by rapid weight loss, major surgery, severe COVID infection, high fever, or death in the family,” she noted. “You will not go bald with telogen effluvium, but you might find that you may lose a good volume of hair,” much more than the normal loss of up to 100 hairs a day.

“I counsel my patients about the possibility of losing hair before they undergo bariatric surgery,” Dr. Saunders said. “Generally, the health benefits of weight loss and weight maintenance outweigh the risk of temporary hair loss.”

Nutritional deficiencies and malnutrition can contribute to hair loss as well, and iron deficiency is sometimes a culprit, she added.

“If someone is worried” about hair loss associated with weight loss, “they should see their doctor,” Dr. Peters said. “If they are on thyroid hormone, in particular, the levels should be retested after weight loss.”

Hair loss appears more common after bariatric surgery than with antiobesity medications,” Dr. Weintraub observed, and it is unclear whether this is because the weight loss is more dramatic after surgery and thus a greater stressor, or whether it is caused by nutrient deficiency or a different mechanism entirely.

“Unlike certain forms of bariatric surgery, which can lead to malabsorption (e.g., Roux-en-Y gastric bypass), medications such as GLP-1 agonists and GLP-1/GIP dual agonists do not cause malabsorption,” Dr. Weintraub noted. “So nutritional deficiencies are less likely to be the cause of new hair loss in those taking antiobesity medications than [in] someone who underwent bariatric surgery.”

Iron and vitamin D deficiencies are the most common nutritional deficiencies that can cause hair loss, he noted.
 

Slow and steady weight loss rather than rapid

“I would suggest that patients try to keep the weight loss slow and steady, rather than rapid,” Dr. Goldberg said, “and follow any vitamin/mineral supplementation plan that they are given. Patients with bariatric surgery have nutritional guidance and a supplementation plan.”

“Follow a well-balanced dietary strategy with ample protein, vegetables, and some fruit,” Dr. Saunders said. Health care providers should monitor lab tests to check for and treat vitamin deficiencies, and registered dietitians can be crucial to ensure proper nutrition. She advises patients: “Find coping strategies to reduce stress and get enough sleep. If iron levels are low, start an iron supplement under your provider’s supervision.”

“Some of my patients swear by biotin supplements, prenatal vitamins or ‘hair, skin, and nails’ vitamins,” she added. If hair loss doesn’t stop, a dermatologist can look for other contributors and discuss strategies for hair restoration.

Individuals who undergo bariatric surgery require lifelong vitamin supplementation and yearly (or more frequent) lab testing, she noted.

“With, for example, bariatric surgery or any type of diet change you want to make sure you still maintain a balanced diet, whether its calories, protein, iron, zinc, vitamins (vitamin D for example),” Dr. Massick echoed.

Similarly, Dr. Peters advised: “I would say to maintain a normal healthy diet even if eating less. Exercise. Do all those healthy things. Taking a daily multivitamin isn’t a bad idea. Talk with a nutritionist. Use the appetite suppression of the medication to combine with healthy eating.”

“If someone is having new hair loss, they should see their clinician to evaluate for all possible causes,” Dr. Weintraub said. “Their provider can evaluate for underlying causes like thyroid dysfunction, iron deficiency, and vitamin D deficiency.”

However, if a patient’s pattern of hair loss is not diffuse but occurs in patches, this has an entirely different set of etiologies probably unrelated to antiobesity medication and should be evaluated.

Working with a nutritionist to ensure that patients have sufficient protein and micronutrient intake can lower the risk of developing hair loss and other complications, Dr. Weintraub said. “This is particularly important for certain forms of bariatric surgery such as Roux-en-Y gastric bypass, since that can lead to malabsorption of specific vitamins and minerals that need to be periodically measured and supplemented.”

In individuals starting an antiobesity medication, beginning a daily multivitamin has little harm, he added, and can ensure they are getting essential minerals and vitamins. However, no studies have specifically investigated this yet.

“Ultimately, it’s important to weigh the benefits of antiobesity medications against the potential risks, as we do with any medical intervention,” according to Dr. Weintraub.

“The purpose of treating obesity,” he stressed, “is to reduce the risk of heart disease, stroke, and multiple types of cancers. It’s up to the individual to weigh these benefits against the risks of the treatment, including the low risk of developing temporary hair loss.”

Dr. Peters writes a column for Medscape and disclosed that she served as a consultant for Blue Circle Health, Vertex, and Abbott Diabetes Care; received a research grant from Abbott Diabetes Care; and received stock options from Teladoc and Omada Health. Dr. Goldberg, Dr. Saunders, Dr. Massick, and Dr. Weintraub declared no relevant financial relationships.

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

DUBLIN – Changing the way food options and information is presented on food delivery apps, as well as default smaller portions, may encourage healthier selections, lowering the calorie intake by 4%-15%, show three new randomized trials from the United Kingdom.

The prominent positioning of low-calorie menu items, and restaurants with low-calorie main meals, on a food app emerged as the most promising approach to promote healthier eating, followed by preselecting smaller portions by default, and finally calorie labels, Anna Keleher, MPA, a behavioral scientist at Nesta, London, reported at the European Congress on Obesity (ECO) meeting.

“Many out-of-home meals have more calories than meals cooked in-home and using delivery apps is linked with a higher risk of becoming overweight or obese,” she remarked. “We’re interested in understanding more about delivery apps because they can be modified at scale easily and can reach millions of people with interventions to promote healthier and more nutritious options in these settings.”

Food delivery apps have surged in use in the United Kingdom with a 55% increase since 2015; examples include Uber Eats, Just Eat, and Deliveroo. “This trend is similar in the United States, with more and more consumers using delivery apps to buy food,” said Ms. Keleher, a senior adviser at the Behavioral Insights Team, New York. 

Emma Boyland, PhD, an obesity psychologist from Liverpool (England) University, said: “Apps are an increasingly popular way for people to buy food and the virtual food environment is becoming as prominent as the physical food environment in how we go about obtaining meals.”

She highlighted the need to understand more about how food apps change the way we purchase and eat, but noted that “the work presented today” showed that “moving the position of food choices and information, as well as the brand name and imagery, influences what people end up buying and consuming.

“I think there’s a place for interventions that challenge these things and improve dietary health,” said Dr. Boyland, who chaired the session during which Ms. Keleher presented her results. “However, as we’ve seen with calorie labeling, they don’t always have the biggest effect on their own, so as is often the case, we need to take multiple actions, incorporating all the elements of the environment to make a meaningful difference.”
 

Three trials changing displays on simulated food delivery apps

“Delivery apps could reach millions of people and help us select healthier food options, and yet there is very little research looking at what works to promote healthier and more nutritious options in these settings,” Filippo Bianchi, MD, a colleague working with Ms. Keleher, said in a press release issued by ECO.

So the research team carried out a proof-of-concept testing of health-promoting interventions by developing a simulated food delivery app and asking 23,783 adults who typically use such services to choose a meal for themselves as if it were a real-life food delivery order.

“As a first step, we developed a simulated online food delivery platform to generate evidence on the effectiveness of our interventions,” Ms. Keleher explained, noting that the simulated platform included 21 restaurants and almost 600 food and drink items to choose from.

The research evaluated 14 interventions across three randomized controlled trials, displaying various food-ordering options that promoted lower-calorie options against a control. The trials investigated default choices (promoting the selection of small portion sizes through defaults, n = 6,000); positioning (promoting the selection of less calorie-dense options through positioning, n = 9,003); and labeling (promoting the selection of less calorific options through calorie labels, n = 8,780).

The primary outcome was the total number of calories in the basket at checkout. The results were adjusted for potentially confounding factors, such as body mass index, age, gender, and income.

For the trial that promoted smaller portions by default, “all of our interventions significantly reduced calorie purchases, with each additional intervention element increasing the effect sizes, which ranged from a 6% to 13% reduction in calories [–5.5% to –12.5% kcal/order; P < .05],” reported Ms. Keleher.

The second trial varied the position of both items on the menu and the order of restaurants – effectively, lower-calorie menu options were more prominent, and restaurant options with lower-calorie main meals were placed at the top of the restaurant selection page.

Ms. Keleher noted that there have been some concerns about whether this strategy would negatively affect restaurant business, so the research team counteracted this by also incorporating an option where low-calorie but high-price options were placed near the top of the display to promote healthier options but without loss of income for participating restaurants. This last intervention with low-calorie/high-price options placed near the top also led to reduced calorie intake.

“This showed that promoting low-calorie options does not necessarily mean damaging business revenue,” she said. “We hope that the industry can evolve to meet the widely recognized needs of society and consumers.”

Repositioning restaurants emerged as more effective than repositioning foods on the menu, while all interventions significantly reduced calorie purchases. “Effect sizes ranged from 6% to 15% reductions in calories purchased per order [P < .05],” reported Ms. Keleher.

The last trial tested seven calorie labels: four that changed the font size and location of the label, two that added a switch on/off filter for calorie label display, and one that was a calorie summary at checkout.

“All these standard calorie labels directionally reduced the number of excess calories with two [options] reaching statistical significance. Five out of seven labels significantly reduced calorie purchases with effect sizes ranging from 4.3% to –7.8% kcal/order (P < .05),” reported Ms. Keleher.

“This research is important for policymakers so they can understand the best way for companies to display calorie labels and what to include in regulations and guidelines,” she summarized.
 

Qualitative think-aloud study explored views around food delivery apps

Another piece of research, the think-aloud study, by the same authors, was presented at ECO, and explored how best to enhance the effectiveness and acceptability of calorie labels in food delivery apps in consultation with 20 adult delivery app users in the United Kingdom.

Researchers tried to document the range of views people have about calorie labels, including variation both between people and within an individual.

“For example, on a weekend, people might not want to engage with calories at all because they are more concerned to treat themselves, whereas at a mid-week lunch that same person might really want the ability to check the calorie content of their food,” Ms. Keleher reported.

She said that considerations varied significantly between people such that they described different ways in which calorie labeling impacted their food-ordering experience.

“Some people felt labels supported their existing intentions, whereas others felt labels built their knowledge. Still others felt calorie labels were insufficient to support their health and wanted more information, such as on macronutrients,” said Ms. Keleher, quoting one participant: “There’s no situation in which I would look at [calories]. I look at nutrients. I prefer the traffic light system [color-coding salt, fat, and sugar content],” she relayed.   

The key recommendations based on the think-aloud study included providing a filter that allows users to switch calorie labels on and off; communicating recommended energy intake per meal (that is, 600 kcal) and not just per day (that is, 2,000 kcal); and avoiding framing calorie label messaging or formatting as judgmental (for example, red fonts).

“These studies provide encouraging proof-of-concept evidence that small tweaks in delivery apps could help many people to identify and select healthier foods. Testing similar initiatives with real restaurants and delivery apps will be important to assess the long-term impact of these interventions in the real world. Further research should also explore the best way to balance desired health impacts while minimizing effects on businesses and on cost-of-living concerns for consumers,” concluded Dr. Bianchi.
 

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

DUBLIN – Changing the way food options and information is presented on food delivery apps, as well as default smaller portions, may encourage healthier selections, lowering the calorie intake by 4%-15%, show three new randomized trials from the United Kingdom.

The prominent positioning of low-calorie menu items, and restaurants with low-calorie main meals, on a food app emerged as the most promising approach to promote healthier eating, followed by preselecting smaller portions by default, and finally calorie labels, Anna Keleher, MPA, a behavioral scientist at Nesta, London, reported at the European Congress on Obesity (ECO) meeting.

“Many out-of-home meals have more calories than meals cooked in-home and using delivery apps is linked with a higher risk of becoming overweight or obese,” she remarked. “We’re interested in understanding more about delivery apps because they can be modified at scale easily and can reach millions of people with interventions to promote healthier and more nutritious options in these settings.”

Food delivery apps have surged in use in the United Kingdom with a 55% increase since 2015; examples include Uber Eats, Just Eat, and Deliveroo. “This trend is similar in the United States, with more and more consumers using delivery apps to buy food,” said Ms. Keleher, a senior adviser at the Behavioral Insights Team, New York. 

Emma Boyland, PhD, an obesity psychologist from Liverpool (England) University, said: “Apps are an increasingly popular way for people to buy food and the virtual food environment is becoming as prominent as the physical food environment in how we go about obtaining meals.”

She highlighted the need to understand more about how food apps change the way we purchase and eat, but noted that “the work presented today” showed that “moving the position of food choices and information, as well as the brand name and imagery, influences what people end up buying and consuming.

“I think there’s a place for interventions that challenge these things and improve dietary health,” said Dr. Boyland, who chaired the session during which Ms. Keleher presented her results. “However, as we’ve seen with calorie labeling, they don’t always have the biggest effect on their own, so as is often the case, we need to take multiple actions, incorporating all the elements of the environment to make a meaningful difference.”
 

Three trials changing displays on simulated food delivery apps

“Delivery apps could reach millions of people and help us select healthier food options, and yet there is very little research looking at what works to promote healthier and more nutritious options in these settings,” Filippo Bianchi, MD, a colleague working with Ms. Keleher, said in a press release issued by ECO.

So the research team carried out a proof-of-concept testing of health-promoting interventions by developing a simulated food delivery app and asking 23,783 adults who typically use such services to choose a meal for themselves as if it were a real-life food delivery order.

“As a first step, we developed a simulated online food delivery platform to generate evidence on the effectiveness of our interventions,” Ms. Keleher explained, noting that the simulated platform included 21 restaurants and almost 600 food and drink items to choose from.

The research evaluated 14 interventions across three randomized controlled trials, displaying various food-ordering options that promoted lower-calorie options against a control. The trials investigated default choices (promoting the selection of small portion sizes through defaults, n = 6,000); positioning (promoting the selection of less calorie-dense options through positioning, n = 9,003); and labeling (promoting the selection of less calorific options through calorie labels, n = 8,780).

The primary outcome was the total number of calories in the basket at checkout. The results were adjusted for potentially confounding factors, such as body mass index, age, gender, and income.

For the trial that promoted smaller portions by default, “all of our interventions significantly reduced calorie purchases, with each additional intervention element increasing the effect sizes, which ranged from a 6% to 13% reduction in calories [–5.5% to –12.5% kcal/order; P < .05],” reported Ms. Keleher.

The second trial varied the position of both items on the menu and the order of restaurants – effectively, lower-calorie menu options were more prominent, and restaurant options with lower-calorie main meals were placed at the top of the restaurant selection page.

Ms. Keleher noted that there have been some concerns about whether this strategy would negatively affect restaurant business, so the research team counteracted this by also incorporating an option where low-calorie but high-price options were placed near the top of the display to promote healthier options but without loss of income for participating restaurants. This last intervention with low-calorie/high-price options placed near the top also led to reduced calorie intake.

“This showed that promoting low-calorie options does not necessarily mean damaging business revenue,” she said. “We hope that the industry can evolve to meet the widely recognized needs of society and consumers.”

Repositioning restaurants emerged as more effective than repositioning foods on the menu, while all interventions significantly reduced calorie purchases. “Effect sizes ranged from 6% to 15% reductions in calories purchased per order [P < .05],” reported Ms. Keleher.

The last trial tested seven calorie labels: four that changed the font size and location of the label, two that added a switch on/off filter for calorie label display, and one that was a calorie summary at checkout.

“All these standard calorie labels directionally reduced the number of excess calories with two [options] reaching statistical significance. Five out of seven labels significantly reduced calorie purchases with effect sizes ranging from 4.3% to –7.8% kcal/order (P < .05),” reported Ms. Keleher.

“This research is important for policymakers so they can understand the best way for companies to display calorie labels and what to include in regulations and guidelines,” she summarized.
 

Qualitative think-aloud study explored views around food delivery apps

Another piece of research, the think-aloud study, by the same authors, was presented at ECO, and explored how best to enhance the effectiveness and acceptability of calorie labels in food delivery apps in consultation with 20 adult delivery app users in the United Kingdom.

Researchers tried to document the range of views people have about calorie labels, including variation both between people and within an individual.

“For example, on a weekend, people might not want to engage with calories at all because they are more concerned to treat themselves, whereas at a mid-week lunch that same person might really want the ability to check the calorie content of their food,” Ms. Keleher reported.

She said that considerations varied significantly between people such that they described different ways in which calorie labeling impacted their food-ordering experience.

“Some people felt labels supported their existing intentions, whereas others felt labels built their knowledge. Still others felt calorie labels were insufficient to support their health and wanted more information, such as on macronutrients,” said Ms. Keleher, quoting one participant: “There’s no situation in which I would look at [calories]. I look at nutrients. I prefer the traffic light system [color-coding salt, fat, and sugar content],” she relayed.   

The key recommendations based on the think-aloud study included providing a filter that allows users to switch calorie labels on and off; communicating recommended energy intake per meal (that is, 600 kcal) and not just per day (that is, 2,000 kcal); and avoiding framing calorie label messaging or formatting as judgmental (for example, red fonts).

“These studies provide encouraging proof-of-concept evidence that small tweaks in delivery apps could help many people to identify and select healthier foods. Testing similar initiatives with real restaurants and delivery apps will be important to assess the long-term impact of these interventions in the real world. Further research should also explore the best way to balance desired health impacts while minimizing effects on businesses and on cost-of-living concerns for consumers,” concluded Dr. Bianchi.
 

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

DUBLIN – Changing the way food options and information is presented on food delivery apps, as well as default smaller portions, may encourage healthier selections, lowering the calorie intake by 4%-15%, show three new randomized trials from the United Kingdom.

The prominent positioning of low-calorie menu items, and restaurants with low-calorie main meals, on a food app emerged as the most promising approach to promote healthier eating, followed by preselecting smaller portions by default, and finally calorie labels, Anna Keleher, MPA, a behavioral scientist at Nesta, London, reported at the European Congress on Obesity (ECO) meeting.

“Many out-of-home meals have more calories than meals cooked in-home and using delivery apps is linked with a higher risk of becoming overweight or obese,” she remarked. “We’re interested in understanding more about delivery apps because they can be modified at scale easily and can reach millions of people with interventions to promote healthier and more nutritious options in these settings.”

Food delivery apps have surged in use in the United Kingdom with a 55% increase since 2015; examples include Uber Eats, Just Eat, and Deliveroo. “This trend is similar in the United States, with more and more consumers using delivery apps to buy food,” said Ms. Keleher, a senior adviser at the Behavioral Insights Team, New York. 

Emma Boyland, PhD, an obesity psychologist from Liverpool (England) University, said: “Apps are an increasingly popular way for people to buy food and the virtual food environment is becoming as prominent as the physical food environment in how we go about obtaining meals.”

She highlighted the need to understand more about how food apps change the way we purchase and eat, but noted that “the work presented today” showed that “moving the position of food choices and information, as well as the brand name and imagery, influences what people end up buying and consuming.

“I think there’s a place for interventions that challenge these things and improve dietary health,” said Dr. Boyland, who chaired the session during which Ms. Keleher presented her results. “However, as we’ve seen with calorie labeling, they don’t always have the biggest effect on their own, so as is often the case, we need to take multiple actions, incorporating all the elements of the environment to make a meaningful difference.”
 

Three trials changing displays on simulated food delivery apps

“Delivery apps could reach millions of people and help us select healthier food options, and yet there is very little research looking at what works to promote healthier and more nutritious options in these settings,” Filippo Bianchi, MD, a colleague working with Ms. Keleher, said in a press release issued by ECO.

So the research team carried out a proof-of-concept testing of health-promoting interventions by developing a simulated food delivery app and asking 23,783 adults who typically use such services to choose a meal for themselves as if it were a real-life food delivery order.

“As a first step, we developed a simulated online food delivery platform to generate evidence on the effectiveness of our interventions,” Ms. Keleher explained, noting that the simulated platform included 21 restaurants and almost 600 food and drink items to choose from.

The research evaluated 14 interventions across three randomized controlled trials, displaying various food-ordering options that promoted lower-calorie options against a control. The trials investigated default choices (promoting the selection of small portion sizes through defaults, n = 6,000); positioning (promoting the selection of less calorie-dense options through positioning, n = 9,003); and labeling (promoting the selection of less calorific options through calorie labels, n = 8,780).

The primary outcome was the total number of calories in the basket at checkout. The results were adjusted for potentially confounding factors, such as body mass index, age, gender, and income.

For the trial that promoted smaller portions by default, “all of our interventions significantly reduced calorie purchases, with each additional intervention element increasing the effect sizes, which ranged from a 6% to 13% reduction in calories [–5.5% to –12.5% kcal/order; P < .05],” reported Ms. Keleher.

The second trial varied the position of both items on the menu and the order of restaurants – effectively, lower-calorie menu options were more prominent, and restaurant options with lower-calorie main meals were placed at the top of the restaurant selection page.

Ms. Keleher noted that there have been some concerns about whether this strategy would negatively affect restaurant business, so the research team counteracted this by also incorporating an option where low-calorie but high-price options were placed near the top of the display to promote healthier options but without loss of income for participating restaurants. This last intervention with low-calorie/high-price options placed near the top also led to reduced calorie intake.

“This showed that promoting low-calorie options does not necessarily mean damaging business revenue,” she said. “We hope that the industry can evolve to meet the widely recognized needs of society and consumers.”

Repositioning restaurants emerged as more effective than repositioning foods on the menu, while all interventions significantly reduced calorie purchases. “Effect sizes ranged from 6% to 15% reductions in calories purchased per order [P < .05],” reported Ms. Keleher.

The last trial tested seven calorie labels: four that changed the font size and location of the label, two that added a switch on/off filter for calorie label display, and one that was a calorie summary at checkout.

“All these standard calorie labels directionally reduced the number of excess calories with two [options] reaching statistical significance. Five out of seven labels significantly reduced calorie purchases with effect sizes ranging from 4.3% to –7.8% kcal/order (P < .05),” reported Ms. Keleher.

“This research is important for policymakers so they can understand the best way for companies to display calorie labels and what to include in regulations and guidelines,” she summarized.
 

Qualitative think-aloud study explored views around food delivery apps

Another piece of research, the think-aloud study, by the same authors, was presented at ECO, and explored how best to enhance the effectiveness and acceptability of calorie labels in food delivery apps in consultation with 20 adult delivery app users in the United Kingdom.

Researchers tried to document the range of views people have about calorie labels, including variation both between people and within an individual.

“For example, on a weekend, people might not want to engage with calories at all because they are more concerned to treat themselves, whereas at a mid-week lunch that same person might really want the ability to check the calorie content of their food,” Ms. Keleher reported.

She said that considerations varied significantly between people such that they described different ways in which calorie labeling impacted their food-ordering experience.

“Some people felt labels supported their existing intentions, whereas others felt labels built their knowledge. Still others felt calorie labels were insufficient to support their health and wanted more information, such as on macronutrients,” said Ms. Keleher, quoting one participant: “There’s no situation in which I would look at [calories]. I look at nutrients. I prefer the traffic light system [color-coding salt, fat, and sugar content],” she relayed.   

The key recommendations based on the think-aloud study included providing a filter that allows users to switch calorie labels on and off; communicating recommended energy intake per meal (that is, 600 kcal) and not just per day (that is, 2,000 kcal); and avoiding framing calorie label messaging or formatting as judgmental (for example, red fonts).

“These studies provide encouraging proof-of-concept evidence that small tweaks in delivery apps could help many people to identify and select healthier foods. Testing similar initiatives with real restaurants and delivery apps will be important to assess the long-term impact of these interventions in the real world. Further research should also explore the best way to balance desired health impacts while minimizing effects on businesses and on cost-of-living concerns for consumers,” concluded Dr. Bianchi.
 

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

Twice-daily esmolol hydrochloride gel (Galnobax, NovaLead) appears to significantly improve closure of diabetic foot ulcers, particularly in patients with risk factors for impeded wound healing, say Indian researchers.
 

Esmolol is a short-acting beta-adrenergic receptor blocker that is currently approved by the Food and Drug Administration for cardiac indications such as short-term use for supraventricular tachycardia.

As a gel, esmolol hydrochloride is administered topically to stimulate wound healing via mechanisms such as the migration of keratinocytes, fibroblasts, and endothelial cells into wound tissue.

The current trial enrolled patients with type 1 or 2 diabetes, finding that, among 140 assessed, target ulcer closure within 12 weeks was more than twice as likely in those assigned esmolol gel plus standard of care than those given standard of care alone.

The impact of adding esmolol gel to standard of care was even greater in patients with a body mass index (BMI) over 25 kg/m² and in those who weighed more than 80 kg (176 lb).

“The use of esmolol in the treatment of diabetic foot ulcers in addition to standard of care may be an important addition to the endeavor of healing diabetic foot ulcers,” wrote Ashu Rastogi, MD, DM, department of endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India, and colleagues, in their article recently published in JAMA Network Open.

Dr. Rastogi first presented the findings at the 2022 annual meeting of the European Association for the Study of Diabetes. The results were well received, with one clinician describing them as “astounding.”

However, Andrew Boulton, MD, PhD, said in an interview that, although the final published data are “interesting,” they “need further confirmation” because “there are one or two unusual features” about the study. Dr. Boulton is a professor of medicine, division of diabetes, endocrinology & gastroenterology, at the University of Manchester (England).

He highlighted that the study was of “basically neuropathic ulcers, many of which were plantar and should be able to heal without any specific additional therapy.”

In addition, the inclusion criteria state that the ulcers could be below the malleoli or 5 cm above them, which Dr. Boulton explained is “very unusual and would therefore include some atypical and not truly diabetic ‘foot’ ulcers.”

And Frances Game, MBBCh, department of diabetes and endocrinology, University Hospitals of Derby (England) and Burton NHS Foundation Trust, added that there are questions about the study methodology.

She said in an interview that although it is a “fascinating study,” the main comparison group did not receive vehicle, or placebo, gel in addition to standard of care. “How were they blinded [to treatment]?”

The “biggest problem” with the study, however, is that the primary outcome was reported as a per-protocol endpoint, not as a standard intention-to-treat analysis, which allowed the researchers to exclude patients whose ulcers increased in size by over 30% on two consecutive visits.

“That kind of makes [esmolol gel] look better than it is because they’ve taken out the ones who got worse,” Dr. Game noted. However, the findings, while not conclusive, do warrant further study of esmolol gel.

The authors noted that diabetic foot ulcers are a severe complication of diabetes, with a prevalence of 1.3%-12.0% across various countries, And the complication contributes to patient morbidity and mortality, with a 5-year mortality that is substantially higher than that of many cancers.

Moreover, “even with the best therapy,” such as advanced moist wound therapy, bioengineered tissue or skin substitutes, peptides, growth factors, electric stimulation, and negative-pressure wound therapy, just 30% of wounds linked to diabetes heal and recurrence is as high as 70%.

Against this backdrop, topical esmolol 14% gel was shown in a phase 1/2 study to be associated with ulcer area reduction and earlier wound closure versus standard of care plus a control vehicle gel.

The current phase 3, randomized, controlled trial involved individuals aged 18-75 years with type 1 or type 2 diabetes and noninfected diabetic foot ulcers classified as grade 1A and 1C on the University of Texas Wound Classification System, which had been open for at least 6 weeks and had an area of 2-25 cm2.

Patients from 27 tertiary care centers across India were enrolled in 2018-2020. They were randomized in a 3:3:1 ratio to one of three groups: esmolol 14% gel plus standard of care, standard of care only, or vehicle plus standard of care.

The study lasted 25 weeks and included a 1-week screening phase, during which all patients received standard of care, a 12-week treatment phase, and a 12-week follow-up phase. The latter included a closure confirmation period of 4 weeks and an observation period of 8 weeks.

Patients were assessed once a week during the treatment phase, and then at weeks 14, 16, 20, and 24.

In all, 176 patients were enrolled. Participants were a mean age of 56.4 years and 69.3% were men. Average hemoglobin A1c was 8.6%. Mean diabetic foot ulcer area was 4.7 cm² and the average ulcer duration was 49.8 weeks.

The primary outcome was the proportion of patients who achieved target ulcer closure during the 12-week treatment phase and was assessed in 140 patients.

Overall, 60.3% of patients treated with esmolol gel plus standard of care achieved target ulcer closure versus 41.7% of those in the standard of care alone group (odds ratio, 2.13; P = .03).

The secondary outcome was the proportion of patients with target ulcer closure by the study end and was assessed in 120 patients.

In total, 77.2% of patients in the esmolol gel plus standard of care group met the secondary endpoint, compared with 55.6% of those receiving standard of care alone (OR, 1.72; P = .01).

Further analysis suggested the benefit seen with esmolol gel plus standard of care was greater in patients with a weight greater than 80 kg versus standard of care alone (OR, 4.04; P = .04), and in those with a BMI greater than 25 (OR, 2.72; P = .03).

Treatment-emergent adverse events were reported by 33 (18.8%) participants, with 12 events deemed serious. “However, none of the serious adverse events were considered as drug-related by the investigators,” concluded the researchers.

The study was partly funded by NovaLead Pharma and the Biotechnology Industry Research Assistance Council, New Delhi, set up by the Department of Biotechnology, Government of India. Dr. Rastogi reported no relevant financial relationships.

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

Twice-daily esmolol hydrochloride gel (Galnobax, NovaLead) appears to significantly improve closure of diabetic foot ulcers, particularly in patients with risk factors for impeded wound healing, say Indian researchers.
 

Esmolol is a short-acting beta-adrenergic receptor blocker that is currently approved by the Food and Drug Administration for cardiac indications such as short-term use for supraventricular tachycardia.

As a gel, esmolol hydrochloride is administered topically to stimulate wound healing via mechanisms such as the migration of keratinocytes, fibroblasts, and endothelial cells into wound tissue.

The current trial enrolled patients with type 1 or 2 diabetes, finding that, among 140 assessed, target ulcer closure within 12 weeks was more than twice as likely in those assigned esmolol gel plus standard of care than those given standard of care alone.

The impact of adding esmolol gel to standard of care was even greater in patients with a body mass index (BMI) over 25 kg/m² and in those who weighed more than 80 kg (176 lb).

“The use of esmolol in the treatment of diabetic foot ulcers in addition to standard of care may be an important addition to the endeavor of healing diabetic foot ulcers,” wrote Ashu Rastogi, MD, DM, department of endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India, and colleagues, in their article recently published in JAMA Network Open.

Dr. Rastogi first presented the findings at the 2022 annual meeting of the European Association for the Study of Diabetes. The results were well received, with one clinician describing them as “astounding.”

However, Andrew Boulton, MD, PhD, said in an interview that, although the final published data are “interesting,” they “need further confirmation” because “there are one or two unusual features” about the study. Dr. Boulton is a professor of medicine, division of diabetes, endocrinology & gastroenterology, at the University of Manchester (England).

He highlighted that the study was of “basically neuropathic ulcers, many of which were plantar and should be able to heal without any specific additional therapy.”

In addition, the inclusion criteria state that the ulcers could be below the malleoli or 5 cm above them, which Dr. Boulton explained is “very unusual and would therefore include some atypical and not truly diabetic ‘foot’ ulcers.”

And Frances Game, MBBCh, department of diabetes and endocrinology, University Hospitals of Derby (England) and Burton NHS Foundation Trust, added that there are questions about the study methodology.

She said in an interview that although it is a “fascinating study,” the main comparison group did not receive vehicle, or placebo, gel in addition to standard of care. “How were they blinded [to treatment]?”

The “biggest problem” with the study, however, is that the primary outcome was reported as a per-protocol endpoint, not as a standard intention-to-treat analysis, which allowed the researchers to exclude patients whose ulcers increased in size by over 30% on two consecutive visits.

“That kind of makes [esmolol gel] look better than it is because they’ve taken out the ones who got worse,” Dr. Game noted. However, the findings, while not conclusive, do warrant further study of esmolol gel.

The authors noted that diabetic foot ulcers are a severe complication of diabetes, with a prevalence of 1.3%-12.0% across various countries, And the complication contributes to patient morbidity and mortality, with a 5-year mortality that is substantially higher than that of many cancers.

Moreover, “even with the best therapy,” such as advanced moist wound therapy, bioengineered tissue or skin substitutes, peptides, growth factors, electric stimulation, and negative-pressure wound therapy, just 30% of wounds linked to diabetes heal and recurrence is as high as 70%.

Against this backdrop, topical esmolol 14% gel was shown in a phase 1/2 study to be associated with ulcer area reduction and earlier wound closure versus standard of care plus a control vehicle gel.

The current phase 3, randomized, controlled trial involved individuals aged 18-75 years with type 1 or type 2 diabetes and noninfected diabetic foot ulcers classified as grade 1A and 1C on the University of Texas Wound Classification System, which had been open for at least 6 weeks and had an area of 2-25 cm2.

Patients from 27 tertiary care centers across India were enrolled in 2018-2020. They were randomized in a 3:3:1 ratio to one of three groups: esmolol 14% gel plus standard of care, standard of care only, or vehicle plus standard of care.

The study lasted 25 weeks and included a 1-week screening phase, during which all patients received standard of care, a 12-week treatment phase, and a 12-week follow-up phase. The latter included a closure confirmation period of 4 weeks and an observation period of 8 weeks.

Patients were assessed once a week during the treatment phase, and then at weeks 14, 16, 20, and 24.

In all, 176 patients were enrolled. Participants were a mean age of 56.4 years and 69.3% were men. Average hemoglobin A1c was 8.6%. Mean diabetic foot ulcer area was 4.7 cm² and the average ulcer duration was 49.8 weeks.

The primary outcome was the proportion of patients who achieved target ulcer closure during the 12-week treatment phase and was assessed in 140 patients.

Overall, 60.3% of patients treated with esmolol gel plus standard of care achieved target ulcer closure versus 41.7% of those in the standard of care alone group (odds ratio, 2.13; P = .03).

The secondary outcome was the proportion of patients with target ulcer closure by the study end and was assessed in 120 patients.

In total, 77.2% of patients in the esmolol gel plus standard of care group met the secondary endpoint, compared with 55.6% of those receiving standard of care alone (OR, 1.72; P = .01).

Further analysis suggested the benefit seen with esmolol gel plus standard of care was greater in patients with a weight greater than 80 kg versus standard of care alone (OR, 4.04; P = .04), and in those with a BMI greater than 25 (OR, 2.72; P = .03).

Treatment-emergent adverse events were reported by 33 (18.8%) participants, with 12 events deemed serious. “However, none of the serious adverse events were considered as drug-related by the investigators,” concluded the researchers.

The study was partly funded by NovaLead Pharma and the Biotechnology Industry Research Assistance Council, New Delhi, set up by the Department of Biotechnology, Government of India. Dr. Rastogi reported no relevant financial relationships.

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

Twice-daily esmolol hydrochloride gel (Galnobax, NovaLead) appears to significantly improve closure of diabetic foot ulcers, particularly in patients with risk factors for impeded wound healing, say Indian researchers.
 

Esmolol is a short-acting beta-adrenergic receptor blocker that is currently approved by the Food and Drug Administration for cardiac indications such as short-term use for supraventricular tachycardia.

As a gel, esmolol hydrochloride is administered topically to stimulate wound healing via mechanisms such as the migration of keratinocytes, fibroblasts, and endothelial cells into wound tissue.

The current trial enrolled patients with type 1 or 2 diabetes, finding that, among 140 assessed, target ulcer closure within 12 weeks was more than twice as likely in those assigned esmolol gel plus standard of care than those given standard of care alone.

The impact of adding esmolol gel to standard of care was even greater in patients with a body mass index (BMI) over 25 kg/m² and in those who weighed more than 80 kg (176 lb).

“The use of esmolol in the treatment of diabetic foot ulcers in addition to standard of care may be an important addition to the endeavor of healing diabetic foot ulcers,” wrote Ashu Rastogi, MD, DM, department of endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India, and colleagues, in their article recently published in JAMA Network Open.

Dr. Rastogi first presented the findings at the 2022 annual meeting of the European Association for the Study of Diabetes. The results were well received, with one clinician describing them as “astounding.”

However, Andrew Boulton, MD, PhD, said in an interview that, although the final published data are “interesting,” they “need further confirmation” because “there are one or two unusual features” about the study. Dr. Boulton is a professor of medicine, division of diabetes, endocrinology & gastroenterology, at the University of Manchester (England).

He highlighted that the study was of “basically neuropathic ulcers, many of which were plantar and should be able to heal without any specific additional therapy.”

In addition, the inclusion criteria state that the ulcers could be below the malleoli or 5 cm above them, which Dr. Boulton explained is “very unusual and would therefore include some atypical and not truly diabetic ‘foot’ ulcers.”

And Frances Game, MBBCh, department of diabetes and endocrinology, University Hospitals of Derby (England) and Burton NHS Foundation Trust, added that there are questions about the study methodology.

She said in an interview that although it is a “fascinating study,” the main comparison group did not receive vehicle, or placebo, gel in addition to standard of care. “How were they blinded [to treatment]?”

The “biggest problem” with the study, however, is that the primary outcome was reported as a per-protocol endpoint, not as a standard intention-to-treat analysis, which allowed the researchers to exclude patients whose ulcers increased in size by over 30% on two consecutive visits.

“That kind of makes [esmolol gel] look better than it is because they’ve taken out the ones who got worse,” Dr. Game noted. However, the findings, while not conclusive, do warrant further study of esmolol gel.

The authors noted that diabetic foot ulcers are a severe complication of diabetes, with a prevalence of 1.3%-12.0% across various countries, And the complication contributes to patient morbidity and mortality, with a 5-year mortality that is substantially higher than that of many cancers.

Moreover, “even with the best therapy,” such as advanced moist wound therapy, bioengineered tissue or skin substitutes, peptides, growth factors, electric stimulation, and negative-pressure wound therapy, just 30% of wounds linked to diabetes heal and recurrence is as high as 70%.

Against this backdrop, topical esmolol 14% gel was shown in a phase 1/2 study to be associated with ulcer area reduction and earlier wound closure versus standard of care plus a control vehicle gel.

The current phase 3, randomized, controlled trial involved individuals aged 18-75 years with type 1 or type 2 diabetes and noninfected diabetic foot ulcers classified as grade 1A and 1C on the University of Texas Wound Classification System, which had been open for at least 6 weeks and had an area of 2-25 cm2.

Patients from 27 tertiary care centers across India were enrolled in 2018-2020. They were randomized in a 3:3:1 ratio to one of three groups: esmolol 14% gel plus standard of care, standard of care only, or vehicle plus standard of care.

The study lasted 25 weeks and included a 1-week screening phase, during which all patients received standard of care, a 12-week treatment phase, and a 12-week follow-up phase. The latter included a closure confirmation period of 4 weeks and an observation period of 8 weeks.

Patients were assessed once a week during the treatment phase, and then at weeks 14, 16, 20, and 24.

In all, 176 patients were enrolled. Participants were a mean age of 56.4 years and 69.3% were men. Average hemoglobin A1c was 8.6%. Mean diabetic foot ulcer area was 4.7 cm² and the average ulcer duration was 49.8 weeks.

The primary outcome was the proportion of patients who achieved target ulcer closure during the 12-week treatment phase and was assessed in 140 patients.

Overall, 60.3% of patients treated with esmolol gel plus standard of care achieved target ulcer closure versus 41.7% of those in the standard of care alone group (odds ratio, 2.13; P = .03).

The secondary outcome was the proportion of patients with target ulcer closure by the study end and was assessed in 120 patients.

In total, 77.2% of patients in the esmolol gel plus standard of care group met the secondary endpoint, compared with 55.6% of those receiving standard of care alone (OR, 1.72; P = .01).

Further analysis suggested the benefit seen with esmolol gel plus standard of care was greater in patients with a weight greater than 80 kg versus standard of care alone (OR, 4.04; P = .04), and in those with a BMI greater than 25 (OR, 2.72; P = .03).

Treatment-emergent adverse events were reported by 33 (18.8%) participants, with 12 events deemed serious. “However, none of the serious adverse events were considered as drug-related by the investigators,” concluded the researchers.

The study was partly funded by NovaLead Pharma and the Biotechnology Industry Research Assistance Council, New Delhi, set up by the Department of Biotechnology, Government of India. Dr. Rastogi reported no relevant financial relationships.

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

Screening for and treating chronic kidney disease (CKD) in all U.S. adults 35-75 years old is cost effective using a strategy that starts by measuring their urine albumin-creatinine ratio (UACR) followed by confirmatory tests and treatment of confirmed cases with current standard-care medications, according to an analysis published in the Annals of Internal Medicine.

This new evidence may prove important as the U.S. Preventive Services Task Force has begun revisiting its 2012 conclusion that “evidence is insufficient to assess the balance of benefits and harms of routine screening for chronic kidney disease in asymptomatic adults.”

A big difference between 2012 and today has been that sodium-glucose cotransporter 2 (SGLT2) inhibitors arrived on the scene as an important complement to well-established treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. SGLT2 inhibitors have been documented as safe and effective for slowing CKD progression regardless of a person’s diabetes status, and have “dramatically altered” first-line treatment of adults with CKD, wrote the authors of the new study.
 

‘Large population health gains’ from CKD screening

“Given the high prevalence of CKD, even among those without risk factors, low-cost screening combined with effective treatment using SGLT2 inhibitors represent value,” explained Marika M. Cusick, lead author of the report, a PhD student, and a health policy researcher at Stanford (Calif.) University. “Our results show large population health gains can be achieved through CKD screening,” she said in an interview.

“This is a well-designed cost-effectiveness analysis that, importantly, considers newer treatments shown to be effective for slowing progression of CKD. The overall findings are convincing,” commented Deidra C. Crews, MD, a nephrologist and professor at Johns Hopkins University in Baltimore who was not involved in the research.

Dr. Crews, who is also president-elect of the American Society of Nephrology noted that the findings “may be a conservative estimate of the cost-effectiveness of CKD screening in certain subgroups, particularly when considering profound racial, ethnic and socioeconomic disparities in survival and CKD progression.”

The USPSTF starts a relook

The new evidence of cost-effectiveness of routine CKD screening follows the USPSTF’s release in January 2023 of a draft research plan to reassess the potential role for CKD screening of asymptomatic adults in the United States, the first step on a potential path to a revised set of recommendations. Public comment on the draft plan closed in February, and based on the standard USPSTF development steps and time frames, a final recommendation statement could appear by early 2026.

Revisiting the prior USPSTF decision from 2012 received endorsement earlier in 2023 from the ASN. The organization issued a statement last January that cited “more than a decade of advocacy in support of more kidney health screening by ASN and other stakeholders dedicated to intervening earlier to slow or stop the progression of kidney diseases.”

A more detailed letter of support for CKD screening sent to top USPSTF officials followed in February 2023 from ASN president Michelle A. Josephson, MD, who said in part that “ASN believes that kidney care is at an inflection point. There are now far more novel therapeutics to slow the progression of CKD, evidence to support the impact of nonpharmacologic interventions on CKD, and an increased commitment in public health to confront disparities and their causes.”
 

USPSTF recommendation could make a difference

Dr. Josephson also cited the modest effect that CKD screening recommendations from other groups have had up to now.

“Although guidance from Kidney Disease Improving Global Outcomes and the National Kidney Foundation recommends CKD screening among patients with hypertension, only approximately 10% of individuals with hypertension receive yearly screening. Furthermore, American Diabetes Association guidelines recommend yearly CKD screening in patients with diabetes, but only 40%-50% of patients receive this.”

“USPSTF recommendations tend to reach clinicians in primary care settings, where screening for diseases most commonly occurs, much more than recommendations from professional or patient organizations,” Dr. Crews said in an interview. “USPSTF recommendations also often influence health policies that might financially incentivize clinicians and health systems to screen their patients.”

“We hope [the USPSTF] will be interested in including our results within the totality of evidence assessed in their review of CKD screening,” said Ms. Cusick.
 

Preventing hundreds of thousands dialysis cases

The Stanford researchers developed a decision analytic Markov cohort model of CKD progression in U.S. adults aged 35 years or older and fit their model to data from the National Health and Nutrition Examination Survey (NHANES). They found that implementing one-time screening and adding SGLT2 inhibitors to treatment of the 158 million U.S. adults 35-75 years old would prevent the need for kidney replacement therapy (dialysis or transplant) in approximately 398,000 people over their lifetimes, representing a 10% decrease in such cases, compared with the status quo. Screening every 10 or 5 years combined with SGLT2 inhibitors would prevent approximately 598,000 or 658,000 people, respectively, from requiring kidney replacement therapy, compared with not screening.

Analysis showed that one-time screening produced an incremental cost-effectiveness ratio of $86,300 per quality-adjusted life-year (QALY) gained when one-time screening occurred in adults when they reached 55 years old. Screening every 10 years until people became 75 years old cost $98,400 per QALY gained for this group when adults were 35 years old, and $89,800 per QALY gained when screening occurred at 65 years old. These QALY costs are less than “commonly used” U.S. thresholds for acceptable cost-effectiveness of $100,000-$150,000 per QALY gained, the authors said.

Ms. Cusick highlighted the advantages of population-level screening for all U.S. adults, including those who are asymptomatic, compared with focusing on adults with risk factors, such as hypertension or diabetes.

“While risk-based screening can be more cost effective in some settings, risk factors are not always known, especially in marginalized and disadvantaged populations. This may lead to disparities in the use of screening and downstream health outcomes that could be avoided through universal screening policies,” she explained.

The study received no commercial funding. Ms. Cusick had no disclosures. Dr. Crews has received research grants from Somatus. Dr. Josephson has been a consultant to Exosome Diagnostics, IMMUCOR, Labcorp, Otsuka, UBC, and Vera Therapeutics, and has an ownership interest in Seagen.

Screening for and treating chronic kidney disease (CKD) in all U.S. adults 35-75 years old is cost effective using a strategy that starts by measuring their urine albumin-creatinine ratio (UACR) followed by confirmatory tests and treatment of confirmed cases with current standard-care medications, according to an analysis published in the Annals of Internal Medicine.

This new evidence may prove important as the U.S. Preventive Services Task Force has begun revisiting its 2012 conclusion that “evidence is insufficient to assess the balance of benefits and harms of routine screening for chronic kidney disease in asymptomatic adults.”

A big difference between 2012 and today has been that sodium-glucose cotransporter 2 (SGLT2) inhibitors arrived on the scene as an important complement to well-established treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. SGLT2 inhibitors have been documented as safe and effective for slowing CKD progression regardless of a person’s diabetes status, and have “dramatically altered” first-line treatment of adults with CKD, wrote the authors of the new study.
 

‘Large population health gains’ from CKD screening

“Given the high prevalence of CKD, even among those without risk factors, low-cost screening combined with effective treatment using SGLT2 inhibitors represent value,” explained Marika M. Cusick, lead author of the report, a PhD student, and a health policy researcher at Stanford (Calif.) University. “Our results show large population health gains can be achieved through CKD screening,” she said in an interview.

“This is a well-designed cost-effectiveness analysis that, importantly, considers newer treatments shown to be effective for slowing progression of CKD. The overall findings are convincing,” commented Deidra C. Crews, MD, a nephrologist and professor at Johns Hopkins University in Baltimore who was not involved in the research.

Dr. Crews, who is also president-elect of the American Society of Nephrology noted that the findings “may be a conservative estimate of the cost-effectiveness of CKD screening in certain subgroups, particularly when considering profound racial, ethnic and socioeconomic disparities in survival and CKD progression.”

The USPSTF starts a relook

The new evidence of cost-effectiveness of routine CKD screening follows the USPSTF’s release in January 2023 of a draft research plan to reassess the potential role for CKD screening of asymptomatic adults in the United States, the first step on a potential path to a revised set of recommendations. Public comment on the draft plan closed in February, and based on the standard USPSTF development steps and time frames, a final recommendation statement could appear by early 2026.

Revisiting the prior USPSTF decision from 2012 received endorsement earlier in 2023 from the ASN. The organization issued a statement last January that cited “more than a decade of advocacy in support of more kidney health screening by ASN and other stakeholders dedicated to intervening earlier to slow or stop the progression of kidney diseases.”

A more detailed letter of support for CKD screening sent to top USPSTF officials followed in February 2023 from ASN president Michelle A. Josephson, MD, who said in part that “ASN believes that kidney care is at an inflection point. There are now far more novel therapeutics to slow the progression of CKD, evidence to support the impact of nonpharmacologic interventions on CKD, and an increased commitment in public health to confront disparities and their causes.”
 

USPSTF recommendation could make a difference

Dr. Josephson also cited the modest effect that CKD screening recommendations from other groups have had up to now.

“Although guidance from Kidney Disease Improving Global Outcomes and the National Kidney Foundation recommends CKD screening among patients with hypertension, only approximately 10% of individuals with hypertension receive yearly screening. Furthermore, American Diabetes Association guidelines recommend yearly CKD screening in patients with diabetes, but only 40%-50% of patients receive this.”

“USPSTF recommendations tend to reach clinicians in primary care settings, where screening for diseases most commonly occurs, much more than recommendations from professional or patient organizations,” Dr. Crews said in an interview. “USPSTF recommendations also often influence health policies that might financially incentivize clinicians and health systems to screen their patients.”

“We hope [the USPSTF] will be interested in including our results within the totality of evidence assessed in their review of CKD screening,” said Ms. Cusick.
 

Preventing hundreds of thousands dialysis cases

The Stanford researchers developed a decision analytic Markov cohort model of CKD progression in U.S. adults aged 35 years or older and fit their model to data from the National Health and Nutrition Examination Survey (NHANES). They found that implementing one-time screening and adding SGLT2 inhibitors to treatment of the 158 million U.S. adults 35-75 years old would prevent the need for kidney replacement therapy (dialysis or transplant) in approximately 398,000 people over their lifetimes, representing a 10% decrease in such cases, compared with the status quo. Screening every 10 or 5 years combined with SGLT2 inhibitors would prevent approximately 598,000 or 658,000 people, respectively, from requiring kidney replacement therapy, compared with not screening.

Analysis showed that one-time screening produced an incremental cost-effectiveness ratio of $86,300 per quality-adjusted life-year (QALY) gained when one-time screening occurred in adults when they reached 55 years old. Screening every 10 years until people became 75 years old cost $98,400 per QALY gained for this group when adults were 35 years old, and $89,800 per QALY gained when screening occurred at 65 years old. These QALY costs are less than “commonly used” U.S. thresholds for acceptable cost-effectiveness of $100,000-$150,000 per QALY gained, the authors said.

Ms. Cusick highlighted the advantages of population-level screening for all U.S. adults, including those who are asymptomatic, compared with focusing on adults with risk factors, such as hypertension or diabetes.

“While risk-based screening can be more cost effective in some settings, risk factors are not always known, especially in marginalized and disadvantaged populations. This may lead to disparities in the use of screening and downstream health outcomes that could be avoided through universal screening policies,” she explained.

The study received no commercial funding. Ms. Cusick had no disclosures. Dr. Crews has received research grants from Somatus. Dr. Josephson has been a consultant to Exosome Diagnostics, IMMUCOR, Labcorp, Otsuka, UBC, and Vera Therapeutics, and has an ownership interest in Seagen.

Screening for and treating chronic kidney disease (CKD) in all U.S. adults 35-75 years old is cost effective using a strategy that starts by measuring their urine albumin-creatinine ratio (UACR) followed by confirmatory tests and treatment of confirmed cases with current standard-care medications, according to an analysis published in the Annals of Internal Medicine.

This new evidence may prove important as the U.S. Preventive Services Task Force has begun revisiting its 2012 conclusion that “evidence is insufficient to assess the balance of benefits and harms of routine screening for chronic kidney disease in asymptomatic adults.”

A big difference between 2012 and today has been that sodium-glucose cotransporter 2 (SGLT2) inhibitors arrived on the scene as an important complement to well-established treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. SGLT2 inhibitors have been documented as safe and effective for slowing CKD progression regardless of a person’s diabetes status, and have “dramatically altered” first-line treatment of adults with CKD, wrote the authors of the new study.
 

‘Large population health gains’ from CKD screening

“Given the high prevalence of CKD, even among those without risk factors, low-cost screening combined with effective treatment using SGLT2 inhibitors represent value,” explained Marika M. Cusick, lead author of the report, a PhD student, and a health policy researcher at Stanford (Calif.) University. “Our results show large population health gains can be achieved through CKD screening,” she said in an interview.

“This is a well-designed cost-effectiveness analysis that, importantly, considers newer treatments shown to be effective for slowing progression of CKD. The overall findings are convincing,” commented Deidra C. Crews, MD, a nephrologist and professor at Johns Hopkins University in Baltimore who was not involved in the research.

Dr. Crews, who is also president-elect of the American Society of Nephrology noted that the findings “may be a conservative estimate of the cost-effectiveness of CKD screening in certain subgroups, particularly when considering profound racial, ethnic and socioeconomic disparities in survival and CKD progression.”

The USPSTF starts a relook

The new evidence of cost-effectiveness of routine CKD screening follows the USPSTF’s release in January 2023 of a draft research plan to reassess the potential role for CKD screening of asymptomatic adults in the United States, the first step on a potential path to a revised set of recommendations. Public comment on the draft plan closed in February, and based on the standard USPSTF development steps and time frames, a final recommendation statement could appear by early 2026.

Revisiting the prior USPSTF decision from 2012 received endorsement earlier in 2023 from the ASN. The organization issued a statement last January that cited “more than a decade of advocacy in support of more kidney health screening by ASN and other stakeholders dedicated to intervening earlier to slow or stop the progression of kidney diseases.”

A more detailed letter of support for CKD screening sent to top USPSTF officials followed in February 2023 from ASN president Michelle A. Josephson, MD, who said in part that “ASN believes that kidney care is at an inflection point. There are now far more novel therapeutics to slow the progression of CKD, evidence to support the impact of nonpharmacologic interventions on CKD, and an increased commitment in public health to confront disparities and their causes.”
 

USPSTF recommendation could make a difference

Dr. Josephson also cited the modest effect that CKD screening recommendations from other groups have had up to now.

“Although guidance from Kidney Disease Improving Global Outcomes and the National Kidney Foundation recommends CKD screening among patients with hypertension, only approximately 10% of individuals with hypertension receive yearly screening. Furthermore, American Diabetes Association guidelines recommend yearly CKD screening in patients with diabetes, but only 40%-50% of patients receive this.”

“USPSTF recommendations tend to reach clinicians in primary care settings, where screening for diseases most commonly occurs, much more than recommendations from professional or patient organizations,” Dr. Crews said in an interview. “USPSTF recommendations also often influence health policies that might financially incentivize clinicians and health systems to screen their patients.”

“We hope [the USPSTF] will be interested in including our results within the totality of evidence assessed in their review of CKD screening,” said Ms. Cusick.
 

Preventing hundreds of thousands dialysis cases

The Stanford researchers developed a decision analytic Markov cohort model of CKD progression in U.S. adults aged 35 years or older and fit their model to data from the National Health and Nutrition Examination Survey (NHANES). They found that implementing one-time screening and adding SGLT2 inhibitors to treatment of the 158 million U.S. adults 35-75 years old would prevent the need for kidney replacement therapy (dialysis or transplant) in approximately 398,000 people over their lifetimes, representing a 10% decrease in such cases, compared with the status quo. Screening every 10 or 5 years combined with SGLT2 inhibitors would prevent approximately 598,000 or 658,000 people, respectively, from requiring kidney replacement therapy, compared with not screening.

Analysis showed that one-time screening produced an incremental cost-effectiveness ratio of $86,300 per quality-adjusted life-year (QALY) gained when one-time screening occurred in adults when they reached 55 years old. Screening every 10 years until people became 75 years old cost $98,400 per QALY gained for this group when adults were 35 years old, and $89,800 per QALY gained when screening occurred at 65 years old. These QALY costs are less than “commonly used” U.S. thresholds for acceptable cost-effectiveness of $100,000-$150,000 per QALY gained, the authors said.

Ms. Cusick highlighted the advantages of population-level screening for all U.S. adults, including those who are asymptomatic, compared with focusing on adults with risk factors, such as hypertension or diabetes.

“While risk-based screening can be more cost effective in some settings, risk factors are not always known, especially in marginalized and disadvantaged populations. This may lead to disparities in the use of screening and downstream health outcomes that could be avoided through universal screening policies,” she explained.

The study received no commercial funding. Ms. Cusick had no disclosures. Dr. Crews has received research grants from Somatus. Dr. Josephson has been a consultant to Exosome Diagnostics, IMMUCOR, Labcorp, Otsuka, UBC, and Vera Therapeutics, and has an ownership interest in Seagen.