Preventive Care

MRI-invisible prostate lesions. It sounds like the stuff of science fiction and fantasy, a creation from the minds of H.G. Wells, who wrote The Invisible Man, or J.K. Rowling, who authored the Harry Potter series.

But MRI-invisible prostate lesions are real. And what these lesions may, or may not, indicate is the subject of intense debate.

MRI plays an increasingly important role in detecting and diagnosing prostate cancer, staging prostate cancer as well as monitoring disease progression. However, on occasion, a puzzling phenomenon arises. Certain prostate lesions that appear when pathologists examine biopsied tissue samples under a microscope are not visible on MRI. The prostate tissue will, instead, appear normal to a radiologist’s eye.

Why are certain lesions invisible with MRI? And is it dangerous for patients if these lesions are not detected? 

Some experts believe these MRI-invisible lesions are nothing to worry about.

If the clinician can’t see the cancer on MRI, then it simply isn’t a threat, according to Mark Emberton, MD, a pioneer in prostate MRIs and director of interventional oncology at University College London, England.

Laurence Klotz, MD, of the University of Toronto, Ontario, Canada, agreed, noting that “invisible cancers are clinically insignificant and don’t require systematic biopsies.”

Emberton and Klotz compared MRI-invisible lesions to grade group 1 prostate cancer (Gleason score ≤ 6) — the least aggressive category that indicates the cancer that is not likely to spread or kill. For patients on active surveillance, those with MRI-invisible cancers do drastically better than those with visible cancers, Klotz explained.

But other experts in the field are skeptical that MRI-invisible lesions are truly innocuous.

Although statistically an MRI-visible prostate lesion indicates a more aggressive tumor, that is not always the case for every individual, said Brian Helfand, MD, PhD, chief of urology at NorthShore University Health System, Evanston, Illinois.

MRIs can lead to false negatives in about 10%-20% of patients who have clinically significant prostate cancer, though estimates vary.

In one analysis, 16% of men with no suspicious lesions on MRI had clinically significant prostate cancer identified after undergoing a systematic biopsy. Another analysis found that about 35% of MRI-invisible prostate cancers identified via biopsy were clinically significant.

Other studies, however, have indicated that negative MRI results accurately indicate patients at low risk of developing clinically significant cancers. A recent JAMA Oncology analysis, for instance, found that only seven of 233 men (3%) with negative MRI results at baseline who completed 3 years of monitoring were diagnosed with clinically significant prostate cancer.

When a patient has an MRI-invisible prostate tumor, there are a couple of reasons the MRI may not be picking it up, said urologic oncologist Alexander Putnam Cole, MD, assistant professor of surgery, Harvard Medical School, Boston, Massachusetts. “One is that the cancer is aggressive but just very small,” said Cole.

“Another possibility is that the cancer looks very similar to background prostate tissue, which is something that you might expect if you think about more of a low-grade cancer,” he explained.

The experience level of the radiologist interpreting the MRI can also play into the accuracy of the reading.

But Cole agreed that “in general, MRI visibility is associated with molecular and histologic features of progression and aggressiveness and non-visible cancers are less likely to have aggressive features.”

The genomic profiles of MRI-visible and -invisible cancers bear this out.

According to Todd Morgan, MD, chief of urologic oncology at Michigan Medicine, University of Michigan, Ann Arbor, the gene expression in visible disease tends to be linked to more aggressive prostate tumors whereas gene expression in invisible disease does not.

In one analysis, for instance, researchers found that four genes — PHYHD1, CENPF, ALDH2, and GDF15 — associated with worse progression-free survival and metastasis-free survival in prostate cancer also predicted MRI visibility.

“Genes that are associated with visibility are essentially the same genes that are associated with aggressive cancers,” Klotz said.

 

Next Steps After Negative MRI Result

What do MRI-invisible lesions mean for patient care? If, for instance, a patient has elevated PSA levels but a normal MRI, is a targeted or systematic biopsy warranted?

The overarching message, according to Klotz, is that “you don’t need to find them.” Klotz noted, however, that patients with a negative MRI result should still be followed with periodic repeat imaging.

Several trials support this approach of using MRI to decide who needs a biopsy and delaying a biopsy in men with normal MRIs.

The recent JAMA Oncology analysis found that, among men with negative MRI results, 86% avoided a biopsy over 3 years, with clinically significant prostate cancer detected in only 4% of men across the study period — four in the initial diagnostic phase and seven in the 3-year monitoring phase. However, during the initial diagnostic phase, more than half the men with positive MRI findings had clinically significant prostate cancer detected.

Another recent study found that patients with negative MRI results were much less likely to upgrade to higher Gleason scores over time. Among 522 patients who underwent a systematic and targeted biopsy within 18 months of their grade group 1 designation, 9.2% with negative MRI findings had tumors reclassified as grade group 2 or higher vs 27% with positive MRI findings, and 2.3% with negative MRI findings had tumors reclassified as grade group 3 or higher vs 7.8% with positive MRI findings.

These data suggest that men with grade group 1 cancer and negative MRI result “may be able to avoid confirmatory biopsies until a routine surveillance biopsy in 2-3 years,” according to study author Christian Pavlovich, MD, professor of urologic oncology at the Johns Hopkins University School of Medicine, Baltimore.

Cole used MRI findings to triage who gets a biopsy. When a biopsy is warranted, “I usually recommend adding in some systematic sampling of the other side to assess for nonvisible cancers,” he noted.

Sampling prostate tissue outside the target area “adds maybe 1-2 minutes to the procedure and doesn’t drastically increase the morbidity or risks,” Cole said. It also can help “confirm there is cancer in the MRI target and also confirm there is no cancer in the nonvisible areas.” 

According to Klotz, if imaging demonstrates progression, patients should receive a biopsy — in most cases, a targeted biopsy only. And, Klotz noted, skipping routine prostate biopsies in men with negative MRI results can save thousands of men from these procedures, which carry risks for infections and sepsis.

Looking beyond Gleason scores for risk prediction, MRI “visibility is a very powerful risk stratifier,” he said.

A version of this article appeared on Medscape.com.

MRI-invisible prostate lesions. It sounds like the stuff of science fiction and fantasy, a creation from the minds of H.G. Wells, who wrote The Invisible Man, or J.K. Rowling, who authored the Harry Potter series.

But MRI-invisible prostate lesions are real. And what these lesions may, or may not, indicate is the subject of intense debate.

MRI plays an increasingly important role in detecting and diagnosing prostate cancer, staging prostate cancer as well as monitoring disease progression. However, on occasion, a puzzling phenomenon arises. Certain prostate lesions that appear when pathologists examine biopsied tissue samples under a microscope are not visible on MRI. The prostate tissue will, instead, appear normal to a radiologist’s eye.

Why are certain lesions invisible with MRI? And is it dangerous for patients if these lesions are not detected? 

Some experts believe these MRI-invisible lesions are nothing to worry about.

If the clinician can’t see the cancer on MRI, then it simply isn’t a threat, according to Mark Emberton, MD, a pioneer in prostate MRIs and director of interventional oncology at University College London, England.

Laurence Klotz, MD, of the University of Toronto, Ontario, Canada, agreed, noting that “invisible cancers are clinically insignificant and don’t require systematic biopsies.”

Emberton and Klotz compared MRI-invisible lesions to grade group 1 prostate cancer (Gleason score ≤ 6) — the least aggressive category that indicates the cancer that is not likely to spread or kill. For patients on active surveillance, those with MRI-invisible cancers do drastically better than those with visible cancers, Klotz explained.

But other experts in the field are skeptical that MRI-invisible lesions are truly innocuous.

Although statistically an MRI-visible prostate lesion indicates a more aggressive tumor, that is not always the case for every individual, said Brian Helfand, MD, PhD, chief of urology at NorthShore University Health System, Evanston, Illinois.

MRIs can lead to false negatives in about 10%-20% of patients who have clinically significant prostate cancer, though estimates vary.

In one analysis, 16% of men with no suspicious lesions on MRI had clinically significant prostate cancer identified after undergoing a systematic biopsy. Another analysis found that about 35% of MRI-invisible prostate cancers identified via biopsy were clinically significant.

Other studies, however, have indicated that negative MRI results accurately indicate patients at low risk of developing clinically significant cancers. A recent JAMA Oncology analysis, for instance, found that only seven of 233 men (3%) with negative MRI results at baseline who completed 3 years of monitoring were diagnosed with clinically significant prostate cancer.

When a patient has an MRI-invisible prostate tumor, there are a couple of reasons the MRI may not be picking it up, said urologic oncologist Alexander Putnam Cole, MD, assistant professor of surgery, Harvard Medical School, Boston, Massachusetts. “One is that the cancer is aggressive but just very small,” said Cole.

“Another possibility is that the cancer looks very similar to background prostate tissue, which is something that you might expect if you think about more of a low-grade cancer,” he explained.

The experience level of the radiologist interpreting the MRI can also play into the accuracy of the reading.

But Cole agreed that “in general, MRI visibility is associated with molecular and histologic features of progression and aggressiveness and non-visible cancers are less likely to have aggressive features.”

The genomic profiles of MRI-visible and -invisible cancers bear this out.

According to Todd Morgan, MD, chief of urologic oncology at Michigan Medicine, University of Michigan, Ann Arbor, the gene expression in visible disease tends to be linked to more aggressive prostate tumors whereas gene expression in invisible disease does not.

In one analysis, for instance, researchers found that four genes — PHYHD1, CENPF, ALDH2, and GDF15 — associated with worse progression-free survival and metastasis-free survival in prostate cancer also predicted MRI visibility.

“Genes that are associated with visibility are essentially the same genes that are associated with aggressive cancers,” Klotz said.

 

Next Steps After Negative MRI Result

What do MRI-invisible lesions mean for patient care? If, for instance, a patient has elevated PSA levels but a normal MRI, is a targeted or systematic biopsy warranted?

The overarching message, according to Klotz, is that “you don’t need to find them.” Klotz noted, however, that patients with a negative MRI result should still be followed with periodic repeat imaging.

Several trials support this approach of using MRI to decide who needs a biopsy and delaying a biopsy in men with normal MRIs.

The recent JAMA Oncology analysis found that, among men with negative MRI results, 86% avoided a biopsy over 3 years, with clinically significant prostate cancer detected in only 4% of men across the study period — four in the initial diagnostic phase and seven in the 3-year monitoring phase. However, during the initial diagnostic phase, more than half the men with positive MRI findings had clinically significant prostate cancer detected.

Another recent study found that patients with negative MRI results were much less likely to upgrade to higher Gleason scores over time. Among 522 patients who underwent a systematic and targeted biopsy within 18 months of their grade group 1 designation, 9.2% with negative MRI findings had tumors reclassified as grade group 2 or higher vs 27% with positive MRI findings, and 2.3% with negative MRI findings had tumors reclassified as grade group 3 or higher vs 7.8% with positive MRI findings.

These data suggest that men with grade group 1 cancer and negative MRI result “may be able to avoid confirmatory biopsies until a routine surveillance biopsy in 2-3 years,” according to study author Christian Pavlovich, MD, professor of urologic oncology at the Johns Hopkins University School of Medicine, Baltimore.

Cole used MRI findings to triage who gets a biopsy. When a biopsy is warranted, “I usually recommend adding in some systematic sampling of the other side to assess for nonvisible cancers,” he noted.

Sampling prostate tissue outside the target area “adds maybe 1-2 minutes to the procedure and doesn’t drastically increase the morbidity or risks,” Cole said. It also can help “confirm there is cancer in the MRI target and also confirm there is no cancer in the nonvisible areas.” 

According to Klotz, if imaging demonstrates progression, patients should receive a biopsy — in most cases, a targeted biopsy only. And, Klotz noted, skipping routine prostate biopsies in men with negative MRI results can save thousands of men from these procedures, which carry risks for infections and sepsis.

Looking beyond Gleason scores for risk prediction, MRI “visibility is a very powerful risk stratifier,” he said.

A version of this article appeared on Medscape.com.

MRI-invisible prostate lesions. It sounds like the stuff of science fiction and fantasy, a creation from the minds of H.G. Wells, who wrote The Invisible Man, or J.K. Rowling, who authored the Harry Potter series.

But MRI-invisible prostate lesions are real. And what these lesions may, or may not, indicate is the subject of intense debate.

MRI plays an increasingly important role in detecting and diagnosing prostate cancer, staging prostate cancer as well as monitoring disease progression. However, on occasion, a puzzling phenomenon arises. Certain prostate lesions that appear when pathologists examine biopsied tissue samples under a microscope are not visible on MRI. The prostate tissue will, instead, appear normal to a radiologist’s eye.

Why are certain lesions invisible with MRI? And is it dangerous for patients if these lesions are not detected? 

Some experts believe these MRI-invisible lesions are nothing to worry about.

If the clinician can’t see the cancer on MRI, then it simply isn’t a threat, according to Mark Emberton, MD, a pioneer in prostate MRIs and director of interventional oncology at University College London, England.

Laurence Klotz, MD, of the University of Toronto, Ontario, Canada, agreed, noting that “invisible cancers are clinically insignificant and don’t require systematic biopsies.”

Emberton and Klotz compared MRI-invisible lesions to grade group 1 prostate cancer (Gleason score ≤ 6) — the least aggressive category that indicates the cancer that is not likely to spread or kill. For patients on active surveillance, those with MRI-invisible cancers do drastically better than those with visible cancers, Klotz explained.

But other experts in the field are skeptical that MRI-invisible lesions are truly innocuous.

Although statistically an MRI-visible prostate lesion indicates a more aggressive tumor, that is not always the case for every individual, said Brian Helfand, MD, PhD, chief of urology at NorthShore University Health System, Evanston, Illinois.

MRIs can lead to false negatives in about 10%-20% of patients who have clinically significant prostate cancer, though estimates vary.

In one analysis, 16% of men with no suspicious lesions on MRI had clinically significant prostate cancer identified after undergoing a systematic biopsy. Another analysis found that about 35% of MRI-invisible prostate cancers identified via biopsy were clinically significant.

Other studies, however, have indicated that negative MRI results accurately indicate patients at low risk of developing clinically significant cancers. A recent JAMA Oncology analysis, for instance, found that only seven of 233 men (3%) with negative MRI results at baseline who completed 3 years of monitoring were diagnosed with clinically significant prostate cancer.

When a patient has an MRI-invisible prostate tumor, there are a couple of reasons the MRI may not be picking it up, said urologic oncologist Alexander Putnam Cole, MD, assistant professor of surgery, Harvard Medical School, Boston, Massachusetts. “One is that the cancer is aggressive but just very small,” said Cole.

“Another possibility is that the cancer looks very similar to background prostate tissue, which is something that you might expect if you think about more of a low-grade cancer,” he explained.

The experience level of the radiologist interpreting the MRI can also play into the accuracy of the reading.

But Cole agreed that “in general, MRI visibility is associated with molecular and histologic features of progression and aggressiveness and non-visible cancers are less likely to have aggressive features.”

The genomic profiles of MRI-visible and -invisible cancers bear this out.

According to Todd Morgan, MD, chief of urologic oncology at Michigan Medicine, University of Michigan, Ann Arbor, the gene expression in visible disease tends to be linked to more aggressive prostate tumors whereas gene expression in invisible disease does not.

In one analysis, for instance, researchers found that four genes — PHYHD1, CENPF, ALDH2, and GDF15 — associated with worse progression-free survival and metastasis-free survival in prostate cancer also predicted MRI visibility.

“Genes that are associated with visibility are essentially the same genes that are associated with aggressive cancers,” Klotz said.

 

Next Steps After Negative MRI Result

What do MRI-invisible lesions mean for patient care? If, for instance, a patient has elevated PSA levels but a normal MRI, is a targeted or systematic biopsy warranted?

The overarching message, according to Klotz, is that “you don’t need to find them.” Klotz noted, however, that patients with a negative MRI result should still be followed with periodic repeat imaging.

Several trials support this approach of using MRI to decide who needs a biopsy and delaying a biopsy in men with normal MRIs.

The recent JAMA Oncology analysis found that, among men with negative MRI results, 86% avoided a biopsy over 3 years, with clinically significant prostate cancer detected in only 4% of men across the study period — four in the initial diagnostic phase and seven in the 3-year monitoring phase. However, during the initial diagnostic phase, more than half the men with positive MRI findings had clinically significant prostate cancer detected.

Another recent study found that patients with negative MRI results were much less likely to upgrade to higher Gleason scores over time. Among 522 patients who underwent a systematic and targeted biopsy within 18 months of their grade group 1 designation, 9.2% with negative MRI findings had tumors reclassified as grade group 2 or higher vs 27% with positive MRI findings, and 2.3% with negative MRI findings had tumors reclassified as grade group 3 or higher vs 7.8% with positive MRI findings.

These data suggest that men with grade group 1 cancer and negative MRI result “may be able to avoid confirmatory biopsies until a routine surveillance biopsy in 2-3 years,” according to study author Christian Pavlovich, MD, professor of urologic oncology at the Johns Hopkins University School of Medicine, Baltimore.

Cole used MRI findings to triage who gets a biopsy. When a biopsy is warranted, “I usually recommend adding in some systematic sampling of the other side to assess for nonvisible cancers,” he noted.

Sampling prostate tissue outside the target area “adds maybe 1-2 minutes to the procedure and doesn’t drastically increase the morbidity or risks,” Cole said. It also can help “confirm there is cancer in the MRI target and also confirm there is no cancer in the nonvisible areas.” 

According to Klotz, if imaging demonstrates progression, patients should receive a biopsy — in most cases, a targeted biopsy only. And, Klotz noted, skipping routine prostate biopsies in men with negative MRI results can save thousands of men from these procedures, which carry risks for infections and sepsis.

Looking beyond Gleason scores for risk prediction, MRI “visibility is a very powerful risk stratifier,” he said.

A version of this article appeared on Medscape.com.

A new light therapy device could be a game-changer for millions at risk of vision loss. The Food and Drug Administration (FDA) has approved a first-of-its-kind treatment for dry age-related macular degeneration (AMD), a leading cause of blindness in adults over 55.

Developed by LumiThera, the device showed promising results in a clinical trial, marking it as the first effective therapy for AMD. Approved under the FDA’s “De Novo” process, the treatment offers hope where no similar options existed.

The LumiThera study, done at 10 retinal centers in the United States, assessed the safety and effectiveness of the system on the eyes of 100 people over a 24-month period. The data collected during the trial was then analyzed over a 13-month period. 

The trial found that LumiThera’s Valeda Light Delivery System significantly reduced the risk of vision loss and the start of geographic atrophy in dry AMD. More than 58% of the people studied reported improvements in their sight after the therapy. 

Geographic atrophy is a treacherous hallmark of late-stage dry AMD, in which cells in the center of the eye’s retina — called the macula — die, which can cause severe vision loss in advanced forms of the disease.

LumiThera’s system is the first treatment authorized by the FDA for vision loss from dry AMD. AMD is a leading cause of irreversible blindness or vision loss in people over 60. Around 20 million people in the United States have AMD, with dry AMD accounting for 90% of diagnosed cases. It’s considered “dry” because it doesn’t involve the growth of abnormal blood vessels, the way the “wet” form of AMD does.

The percentage of people with dry AMD who lose their vision depends on how severe the disease is and whether it becomes the wet form, which is more severe than the dry form. The wet form is marked by blood vessels leaking into the macula and the loss of central vision. Around 10%-15% of dry AMD cases become the wet form. 

During a presentation in 2024 at a meeting of the American Society of Retina Specialists, Eleonora Lad, MD, PhD, vice chair of ophthalmology clinical research at Duke University Medical Center, said the treatment — known as “photobiomodulation” (PBM) — is the first to deliver “meaningful effects” in dry AMD.

But how does PBM work, and what specifically improved in the eyes of the people in the study to help combat the disease?

 

Specific Wavelengths of Light Improve Cellular Function

Until now, taking nutritional supplements (vitamin C, vitamin E, lutein, zeaxanthin, zinc, and copper) was among the most common ways of treating dry AMD. The efficacy with this combo of nutritional supplements was established by the Age-Related Eye Disease Study 2 (AREDS2). The supplements help lower the risk of advanced dry AMD and wet AMD. 

There are also recently approved eye injections for dry AMD, such as the drugs Syfovre and Izervay, to treat later stages of the disease. But while both Syfovre and Izervay can slow the progression of geographic atrophy by about 14%-20%, patients receiving either drug have a higher risk of getting wet AMD, and the treatments are invasive. The drugs must be injected directly into the middle of the eye around once per month. 

PBM works by delivering specific wavelengths of light to the retina that help cells in retinal tissue, increasing energy production by mitochondria in eye cells, decreasing inflammation, and increasing nutrients and oxygen for cells. This improves cell survival in dry AMD and could slow the disease or stop it from reaching later stages.

Several eye disorders may be partly caused by oxidative stress and impaired mitochondrial function. The wavelength of light used in PBM stimulates an enzyme in eye cells that is key to healthy cellular function and vision. 

Research has shown that PBM prevents oxidative stress, which damages retinal pigment epithelial cells and could lead to AMD.

 

More Study Is Needed

PBM has been around for decades and has been promoted as a treatment for dementia, smoking cessation, spinal cord injury, and wound healing, along with AMD. 

“Google photobiomodulation or light therapy, and you’ll find it’s supposed to fix everything ... people try to sell it for everything, and that’s because they own the equipment, and they’re looking to recoup their costs,” said Jason M. Miller, MD, PhD, a retinal disease specialist at the Kellogg Eye Center at the University of Michigan School of Medicine, Ann Arbor.

He said more rigorous and larger trials are need before PBM therapy should gain wider FDA approval.

The FDA’s De Novo approval process is for medical devices that have designs that are unlike others already on the market. To get full approval from the FDA, a new drug or device must be assessed in a clinical trial that involves more people than the 100 or so that LumiThera used in its trial. For example, phase 3 trials for drugs usually involve 1,000-3,000 people.

Syfovre’s phase 3 clinical trials involved 1,258 patients. 

Research has shown that perceptions of visual acuity could also color the study results in a way that distorts the actual effectiveness of treatment, the way the placebo effect works. Some people in studies may simply think their vision is improving because they know they’re getting treatment. 

In a 2022 study, researchers showed that people in a trial who were given a placebo with the expectation the treatment would work reported a more favorable response to treatment than those who received a “nocebo” they were told wouldn’t work. 

The sensitivity of response to the placebo/nocebo treatments were shown to rely on the expectations caused by the experiment, and the study’s findings provided evidence that “both ocular accommodation and stereoacuity can be influenced by manipulating expectations and belief about the efficacy of an inert treatment.”

“The placebo effect in medicine is just rampant. It accounts for, in some trials, 30%-40% of an effect. ... I would have a hard time buying this device right now. I don’t want to say it’s ineffective, I just want more data,” said Miller.

A version of this article appeared on WebMD.com.

A new light therapy device could be a game-changer for millions at risk of vision loss. The Food and Drug Administration (FDA) has approved a first-of-its-kind treatment for dry age-related macular degeneration (AMD), a leading cause of blindness in adults over 55.

Developed by LumiThera, the device showed promising results in a clinical trial, marking it as the first effective therapy for AMD. Approved under the FDA’s “De Novo” process, the treatment offers hope where no similar options existed.

The LumiThera study, done at 10 retinal centers in the United States, assessed the safety and effectiveness of the system on the eyes of 100 people over a 24-month period. The data collected during the trial was then analyzed over a 13-month period. 

The trial found that LumiThera’s Valeda Light Delivery System significantly reduced the risk of vision loss and the start of geographic atrophy in dry AMD. More than 58% of the people studied reported improvements in their sight after the therapy. 

Geographic atrophy is a treacherous hallmark of late-stage dry AMD, in which cells in the center of the eye’s retina — called the macula — die, which can cause severe vision loss in advanced forms of the disease.

LumiThera’s system is the first treatment authorized by the FDA for vision loss from dry AMD. AMD is a leading cause of irreversible blindness or vision loss in people over 60. Around 20 million people in the United States have AMD, with dry AMD accounting for 90% of diagnosed cases. It’s considered “dry” because it doesn’t involve the growth of abnormal blood vessels, the way the “wet” form of AMD does.

The percentage of people with dry AMD who lose their vision depends on how severe the disease is and whether it becomes the wet form, which is more severe than the dry form. The wet form is marked by blood vessels leaking into the macula and the loss of central vision. Around 10%-15% of dry AMD cases become the wet form. 

During a presentation in 2024 at a meeting of the American Society of Retina Specialists, Eleonora Lad, MD, PhD, vice chair of ophthalmology clinical research at Duke University Medical Center, said the treatment — known as “photobiomodulation” (PBM) — is the first to deliver “meaningful effects” in dry AMD.

But how does PBM work, and what specifically improved in the eyes of the people in the study to help combat the disease?

 

Specific Wavelengths of Light Improve Cellular Function

Until now, taking nutritional supplements (vitamin C, vitamin E, lutein, zeaxanthin, zinc, and copper) was among the most common ways of treating dry AMD. The efficacy with this combo of nutritional supplements was established by the Age-Related Eye Disease Study 2 (AREDS2). The supplements help lower the risk of advanced dry AMD and wet AMD. 

There are also recently approved eye injections for dry AMD, such as the drugs Syfovre and Izervay, to treat later stages of the disease. But while both Syfovre and Izervay can slow the progression of geographic atrophy by about 14%-20%, patients receiving either drug have a higher risk of getting wet AMD, and the treatments are invasive. The drugs must be injected directly into the middle of the eye around once per month. 

PBM works by delivering specific wavelengths of light to the retina that help cells in retinal tissue, increasing energy production by mitochondria in eye cells, decreasing inflammation, and increasing nutrients and oxygen for cells. This improves cell survival in dry AMD and could slow the disease or stop it from reaching later stages.

Several eye disorders may be partly caused by oxidative stress and impaired mitochondrial function. The wavelength of light used in PBM stimulates an enzyme in eye cells that is key to healthy cellular function and vision. 

Research has shown that PBM prevents oxidative stress, which damages retinal pigment epithelial cells and could lead to AMD.

 

More Study Is Needed

PBM has been around for decades and has been promoted as a treatment for dementia, smoking cessation, spinal cord injury, and wound healing, along with AMD. 

“Google photobiomodulation or light therapy, and you’ll find it’s supposed to fix everything ... people try to sell it for everything, and that’s because they own the equipment, and they’re looking to recoup their costs,” said Jason M. Miller, MD, PhD, a retinal disease specialist at the Kellogg Eye Center at the University of Michigan School of Medicine, Ann Arbor.

He said more rigorous and larger trials are need before PBM therapy should gain wider FDA approval.

The FDA’s De Novo approval process is for medical devices that have designs that are unlike others already on the market. To get full approval from the FDA, a new drug or device must be assessed in a clinical trial that involves more people than the 100 or so that LumiThera used in its trial. For example, phase 3 trials for drugs usually involve 1,000-3,000 people.

Syfovre’s phase 3 clinical trials involved 1,258 patients. 

Research has shown that perceptions of visual acuity could also color the study results in a way that distorts the actual effectiveness of treatment, the way the placebo effect works. Some people in studies may simply think their vision is improving because they know they’re getting treatment. 

In a 2022 study, researchers showed that people in a trial who were given a placebo with the expectation the treatment would work reported a more favorable response to treatment than those who received a “nocebo” they were told wouldn’t work. 

The sensitivity of response to the placebo/nocebo treatments were shown to rely on the expectations caused by the experiment, and the study’s findings provided evidence that “both ocular accommodation and stereoacuity can be influenced by manipulating expectations and belief about the efficacy of an inert treatment.”

“The placebo effect in medicine is just rampant. It accounts for, in some trials, 30%-40% of an effect. ... I would have a hard time buying this device right now. I don’t want to say it’s ineffective, I just want more data,” said Miller.

A version of this article appeared on WebMD.com.

A new light therapy device could be a game-changer for millions at risk of vision loss. The Food and Drug Administration (FDA) has approved a first-of-its-kind treatment for dry age-related macular degeneration (AMD), a leading cause of blindness in adults over 55.

Developed by LumiThera, the device showed promising results in a clinical trial, marking it as the first effective therapy for AMD. Approved under the FDA’s “De Novo” process, the treatment offers hope where no similar options existed.

The LumiThera study, done at 10 retinal centers in the United States, assessed the safety and effectiveness of the system on the eyes of 100 people over a 24-month period. The data collected during the trial was then analyzed over a 13-month period. 

The trial found that LumiThera’s Valeda Light Delivery System significantly reduced the risk of vision loss and the start of geographic atrophy in dry AMD. More than 58% of the people studied reported improvements in their sight after the therapy. 

Geographic atrophy is a treacherous hallmark of late-stage dry AMD, in which cells in the center of the eye’s retina — called the macula — die, which can cause severe vision loss in advanced forms of the disease.

LumiThera’s system is the first treatment authorized by the FDA for vision loss from dry AMD. AMD is a leading cause of irreversible blindness or vision loss in people over 60. Around 20 million people in the United States have AMD, with dry AMD accounting for 90% of diagnosed cases. It’s considered “dry” because it doesn’t involve the growth of abnormal blood vessels, the way the “wet” form of AMD does.

The percentage of people with dry AMD who lose their vision depends on how severe the disease is and whether it becomes the wet form, which is more severe than the dry form. The wet form is marked by blood vessels leaking into the macula and the loss of central vision. Around 10%-15% of dry AMD cases become the wet form. 

During a presentation in 2024 at a meeting of the American Society of Retina Specialists, Eleonora Lad, MD, PhD, vice chair of ophthalmology clinical research at Duke University Medical Center, said the treatment — known as “photobiomodulation” (PBM) — is the first to deliver “meaningful effects” in dry AMD.

But how does PBM work, and what specifically improved in the eyes of the people in the study to help combat the disease?

 

Specific Wavelengths of Light Improve Cellular Function

Until now, taking nutritional supplements (vitamin C, vitamin E, lutein, zeaxanthin, zinc, and copper) was among the most common ways of treating dry AMD. The efficacy with this combo of nutritional supplements was established by the Age-Related Eye Disease Study 2 (AREDS2). The supplements help lower the risk of advanced dry AMD and wet AMD. 

There are also recently approved eye injections for dry AMD, such as the drugs Syfovre and Izervay, to treat later stages of the disease. But while both Syfovre and Izervay can slow the progression of geographic atrophy by about 14%-20%, patients receiving either drug have a higher risk of getting wet AMD, and the treatments are invasive. The drugs must be injected directly into the middle of the eye around once per month. 

PBM works by delivering specific wavelengths of light to the retina that help cells in retinal tissue, increasing energy production by mitochondria in eye cells, decreasing inflammation, and increasing nutrients and oxygen for cells. This improves cell survival in dry AMD and could slow the disease or stop it from reaching later stages.

Several eye disorders may be partly caused by oxidative stress and impaired mitochondrial function. The wavelength of light used in PBM stimulates an enzyme in eye cells that is key to healthy cellular function and vision. 

Research has shown that PBM prevents oxidative stress, which damages retinal pigment epithelial cells and could lead to AMD.

 

More Study Is Needed

PBM has been around for decades and has been promoted as a treatment for dementia, smoking cessation, spinal cord injury, and wound healing, along with AMD. 

“Google photobiomodulation or light therapy, and you’ll find it’s supposed to fix everything ... people try to sell it for everything, and that’s because they own the equipment, and they’re looking to recoup their costs,” said Jason M. Miller, MD, PhD, a retinal disease specialist at the Kellogg Eye Center at the University of Michigan School of Medicine, Ann Arbor.

He said more rigorous and larger trials are need before PBM therapy should gain wider FDA approval.

The FDA’s De Novo approval process is for medical devices that have designs that are unlike others already on the market. To get full approval from the FDA, a new drug or device must be assessed in a clinical trial that involves more people than the 100 or so that LumiThera used in its trial. For example, phase 3 trials for drugs usually involve 1,000-3,000 people.

Syfovre’s phase 3 clinical trials involved 1,258 patients. 

Research has shown that perceptions of visual acuity could also color the study results in a way that distorts the actual effectiveness of treatment, the way the placebo effect works. Some people in studies may simply think their vision is improving because they know they’re getting treatment. 

In a 2022 study, researchers showed that people in a trial who were given a placebo with the expectation the treatment would work reported a more favorable response to treatment than those who received a “nocebo” they were told wouldn’t work. 

The sensitivity of response to the placebo/nocebo treatments were shown to rely on the expectations caused by the experiment, and the study’s findings provided evidence that “both ocular accommodation and stereoacuity can be influenced by manipulating expectations and belief about the efficacy of an inert treatment.”

“The placebo effect in medicine is just rampant. It accounts for, in some trials, 30%-40% of an effect. ... I would have a hard time buying this device right now. I don’t want to say it’s ineffective, I just want more data,” said Miller.

A version of this article appeared on WebMD.com.

TOPLINE:

The cardiovascular benefits observed with intensive blood pressure (BP) control in patients with hypertension and elevated cardiovascular risk from the Systolic Blood Pressure Intervention Trial (SPRINT) can be largely replicated in real-world settings among patients with chronic kidney disease (CKD), highlighting the advantages of adopting intensive BP targets.
 

METHODOLOGY:

• The SPRINT showed that an intensive systolic BP goal < 120 mm Hg reduced mortality, cardiovascular events, and mild cognitive impairment in patients with hypertension and elevated cardiovascular risk, including in patients with CKD.
• Researchers conducted a comparative effectiveness study to determine if the beneficial and adverse effects of intensive vs standard BP control observed in SPRINT were replicable in patients with CKD and hypertension in clinical practice.
• They identified 85,938 patients (mean age, 75.7 years; 95.0% men) and 13,983 patients (mean age, 77.4 years; 38.4% men) from the Veterans Health Administration (VHA) and Kaiser Permanente of Southern California (KPSC) databases, respectively.
• The treatment effect was estimated by combining baseline covariate, treatment, and outcome data of participants from the SPRINT with covariate data from the VHA and KPSC databases.
• The primary outcomes included major cardiovascular events, all-cause death, cognitive impairment, CKD progression, and adverse events at 4 years.

TAKEAWAY:

• Compared with SPRINT participants, those in the VHA and KPSC databases were older, had less prevalent cardiovascular disease, higher albuminuria, and used more statins.
• The benefits of intensive vs standard BP control on major cardiovascular events, all-cause mortality, and certain adverse events (hypotension, syncope, bradycardia, acute kidney injury, and electrolyte abnormality) were transferable from the trial to the VHA and KPSC populations.
• The treatment effect of intensive BP management on CKD progression was transportable to the KPSC population but not to the VHA population. However, the trial’s impact on cognitive outcomes, such as dementia, was not transportable to either the VHA or KPSC populations.
• On the absolute scale, intensive vs standard BP treatment showed greater cardiovascular benefits and fewer safety concerns in the VHA and KPSC populations than in the SPRINT.

IN PRACTICE:

“This example highlights the potential for transportability methods to provide insights that can bridge evidence gaps and inform the application of novel therapies to patients with CKD who are treated in everyday practice,” the authors wrote.
 

SOURCE:

This study was led by Manjula Kurella Tamura, MD, MPH, Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Palo Alto, California. It was published online on January 7, 2025, in JAMA Network Open.
 

LIMITATIONS:

Transportability analyses could not account for characteristics that were not well-documented in electronic health records, such as limited life expectancy. The study was conducted before the widespread use of sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and nonsteroidal mineralocorticoid receptor antagonists, making it unclear whether intensive BP treatment would result in similar benefits with current pharmacotherapy regimens. Eligibility for this study was based on BP measurements in routine practice, which tend to be more variable than those collected in research settings.
 

DISCLOSURES:

This study was supported by grants from the National Institutes of Health. Some authors disclosed serving as a consultant and receiving grants, personal fees, and consulting fees from pharmaceutical companies and other sources.
 

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

TOPLINE:

The cardiovascular benefits observed with intensive blood pressure (BP) control in patients with hypertension and elevated cardiovascular risk from the Systolic Blood Pressure Intervention Trial (SPRINT) can be largely replicated in real-world settings among patients with chronic kidney disease (CKD), highlighting the advantages of adopting intensive BP targets.
 

METHODOLOGY:

• The SPRINT showed that an intensive systolic BP goal < 120 mm Hg reduced mortality, cardiovascular events, and mild cognitive impairment in patients with hypertension and elevated cardiovascular risk, including in patients with CKD.
• Researchers conducted a comparative effectiveness study to determine if the beneficial and adverse effects of intensive vs standard BP control observed in SPRINT were replicable in patients with CKD and hypertension in clinical practice.
• They identified 85,938 patients (mean age, 75.7 years; 95.0% men) and 13,983 patients (mean age, 77.4 years; 38.4% men) from the Veterans Health Administration (VHA) and Kaiser Permanente of Southern California (KPSC) databases, respectively.
• The treatment effect was estimated by combining baseline covariate, treatment, and outcome data of participants from the SPRINT with covariate data from the VHA and KPSC databases.
• The primary outcomes included major cardiovascular events, all-cause death, cognitive impairment, CKD progression, and adverse events at 4 years.

TAKEAWAY:

• Compared with SPRINT participants, those in the VHA and KPSC databases were older, had less prevalent cardiovascular disease, higher albuminuria, and used more statins.
• The benefits of intensive vs standard BP control on major cardiovascular events, all-cause mortality, and certain adverse events (hypotension, syncope, bradycardia, acute kidney injury, and electrolyte abnormality) were transferable from the trial to the VHA and KPSC populations.
• The treatment effect of intensive BP management on CKD progression was transportable to the KPSC population but not to the VHA population. However, the trial’s impact on cognitive outcomes, such as dementia, was not transportable to either the VHA or KPSC populations.
• On the absolute scale, intensive vs standard BP treatment showed greater cardiovascular benefits and fewer safety concerns in the VHA and KPSC populations than in the SPRINT.

IN PRACTICE:

“This example highlights the potential for transportability methods to provide insights that can bridge evidence gaps and inform the application of novel therapies to patients with CKD who are treated in everyday practice,” the authors wrote.
 

SOURCE:

This study was led by Manjula Kurella Tamura, MD, MPH, Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Palo Alto, California. It was published online on January 7, 2025, in JAMA Network Open.
 

LIMITATIONS:

Transportability analyses could not account for characteristics that were not well-documented in electronic health records, such as limited life expectancy. The study was conducted before the widespread use of sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and nonsteroidal mineralocorticoid receptor antagonists, making it unclear whether intensive BP treatment would result in similar benefits with current pharmacotherapy regimens. Eligibility for this study was based on BP measurements in routine practice, which tend to be more variable than those collected in research settings.
 

DISCLOSURES:

This study was supported by grants from the National Institutes of Health. Some authors disclosed serving as a consultant and receiving grants, personal fees, and consulting fees from pharmaceutical companies and other sources.
 

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

TOPLINE:

The cardiovascular benefits observed with intensive blood pressure (BP) control in patients with hypertension and elevated cardiovascular risk from the Systolic Blood Pressure Intervention Trial (SPRINT) can be largely replicated in real-world settings among patients with chronic kidney disease (CKD), highlighting the advantages of adopting intensive BP targets.
 

METHODOLOGY:

• The SPRINT showed that an intensive systolic BP goal < 120 mm Hg reduced mortality, cardiovascular events, and mild cognitive impairment in patients with hypertension and elevated cardiovascular risk, including in patients with CKD.
• Researchers conducted a comparative effectiveness study to determine if the beneficial and adverse effects of intensive vs standard BP control observed in SPRINT were replicable in patients with CKD and hypertension in clinical practice.
• They identified 85,938 patients (mean age, 75.7 years; 95.0% men) and 13,983 patients (mean age, 77.4 years; 38.4% men) from the Veterans Health Administration (VHA) and Kaiser Permanente of Southern California (KPSC) databases, respectively.
• The treatment effect was estimated by combining baseline covariate, treatment, and outcome data of participants from the SPRINT with covariate data from the VHA and KPSC databases.
• The primary outcomes included major cardiovascular events, all-cause death, cognitive impairment, CKD progression, and adverse events at 4 years.

TAKEAWAY:

• Compared with SPRINT participants, those in the VHA and KPSC databases were older, had less prevalent cardiovascular disease, higher albuminuria, and used more statins.
• The benefits of intensive vs standard BP control on major cardiovascular events, all-cause mortality, and certain adverse events (hypotension, syncope, bradycardia, acute kidney injury, and electrolyte abnormality) were transferable from the trial to the VHA and KPSC populations.
• The treatment effect of intensive BP management on CKD progression was transportable to the KPSC population but not to the VHA population. However, the trial’s impact on cognitive outcomes, such as dementia, was not transportable to either the VHA or KPSC populations.
• On the absolute scale, intensive vs standard BP treatment showed greater cardiovascular benefits and fewer safety concerns in the VHA and KPSC populations than in the SPRINT.

IN PRACTICE:

“This example highlights the potential for transportability methods to provide insights that can bridge evidence gaps and inform the application of novel therapies to patients with CKD who are treated in everyday practice,” the authors wrote.
 

SOURCE:

This study was led by Manjula Kurella Tamura, MD, MPH, Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Palo Alto, California. It was published online on January 7, 2025, in JAMA Network Open.
 

LIMITATIONS:

Transportability analyses could not account for characteristics that were not well-documented in electronic health records, such as limited life expectancy. The study was conducted before the widespread use of sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and nonsteroidal mineralocorticoid receptor antagonists, making it unclear whether intensive BP treatment would result in similar benefits with current pharmacotherapy regimens. Eligibility for this study was based on BP measurements in routine practice, which tend to be more variable than those collected in research settings.
 

DISCLOSURES:

This study was supported by grants from the National Institutes of Health. Some authors disclosed serving as a consultant and receiving grants, personal fees, and consulting fees from pharmaceutical companies and other sources.
 

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

TOPLINE:

Patients with rectal cancer managed by watch and wait and subsequent local regrowth have a higher risk for distant metastases than those undergoing immediate surgery. The new study highlights the importance of timely surgical intervention to improve distant metastases–free survival rates.

METHODOLOGY:

• Organ preservation has become an attractive alternative to surgery for patients with rectal cancer who achieve a clinical complete response after neoadjuvant therapy, with the risk for local regrowth after initial clinical complete response being around 25%-30%.
• The new study aimed to compare the risk for distant metastases between patients with local regrowth after watch and wait and patients with near-complete pathologic response managed by total mesorectal excision.
• A total of 508 patients with local regrowth were included from the International Watch & Wait Database, and 893 patients with near-complete pathologic response were included from the Spanish Rectal Cancer Project.
• The primary endpoint was distant metastases–free survival at 3 years from the decision to watch and wait or total mesorectal excision, and the secondary endpoints included possible risk factors associated with distant metastases.

TAKEAWAY:

• Patients with local regrowth had a significantly higher rate of distant metastases (rate, 22.8% vs 10.2%; P ≤.001) than those with near-complete pathologic response managed by total mesorectal excision.
• Distant metastases–free survival at 3 years was significantly worse for patients with local regrowth (rate, 75% vs 87%; P < .001).
• Independent risk factors for distant metastases included local regrowth (vs total mesorectal excision at reassessment; P = .001), ypT3-4 status (P = .016), and ypN+ status (P = .001) at the time of surgery.
• Patients with local regrowth had worse distant metastases–free survival across all pathologic stages than those managed by total mesorectal excision.

IN PRACTICE:

“Patients with local regrowth appear to have a higher risk for subsequent distant metastases development than patients with near-complete pathologic response managed by total mesorectal excision at restaging irrespective of final pathology,” the authors wrote.

SOURCE:

This study was led by Laura M. Fernandez, MD, of the Champalimaud Foundation in Lisbon, Portugal. It was published online in Journal of Clinical Oncology.

LIMITATIONS:

This study’s limitations included the heterogeneity in defining clinical complete response and the decision to watch and wait across different institutions. The majority of patients did not receive total neoadjuvant therapy regimens, which may have affected the generalizability of the findings. The study had a considerable amount of follow-up losses, which could have introduced bias.

DISCLOSURES:

This study was supported by the European Society of Surgical Oncology, the Champalimaud Foundation, the Bas Mulder Award, the Alpe d’HuZes Foundation, the Dutch Cancer Society, the European Research Council Advanced Grant, and the National Institute of Health and Research Manchester Biomedical Research Centre. Fernandez disclosed receiving grants from Johnson & Johnson. Additional disclosures are noted in the original article.

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

TOPLINE:

Patients with rectal cancer managed by watch and wait and subsequent local regrowth have a higher risk for distant metastases than those undergoing immediate surgery. The new study highlights the importance of timely surgical intervention to improve distant metastases–free survival rates.

METHODOLOGY:

• Organ preservation has become an attractive alternative to surgery for patients with rectal cancer who achieve a clinical complete response after neoadjuvant therapy, with the risk for local regrowth after initial clinical complete response being around 25%-30%.
• The new study aimed to compare the risk for distant metastases between patients with local regrowth after watch and wait and patients with near-complete pathologic response managed by total mesorectal excision.
• A total of 508 patients with local regrowth were included from the International Watch & Wait Database, and 893 patients with near-complete pathologic response were included from the Spanish Rectal Cancer Project.
• The primary endpoint was distant metastases–free survival at 3 years from the decision to watch and wait or total mesorectal excision, and the secondary endpoints included possible risk factors associated with distant metastases.

TAKEAWAY:

• Patients with local regrowth had a significantly higher rate of distant metastases (rate, 22.8% vs 10.2%; P ≤.001) than those with near-complete pathologic response managed by total mesorectal excision.
• Distant metastases–free survival at 3 years was significantly worse for patients with local regrowth (rate, 75% vs 87%; P < .001).
• Independent risk factors for distant metastases included local regrowth (vs total mesorectal excision at reassessment; P = .001), ypT3-4 status (P = .016), and ypN+ status (P = .001) at the time of surgery.
• Patients with local regrowth had worse distant metastases–free survival across all pathologic stages than those managed by total mesorectal excision.

IN PRACTICE:

“Patients with local regrowth appear to have a higher risk for subsequent distant metastases development than patients with near-complete pathologic response managed by total mesorectal excision at restaging irrespective of final pathology,” the authors wrote.

SOURCE:

This study was led by Laura M. Fernandez, MD, of the Champalimaud Foundation in Lisbon, Portugal. It was published online in Journal of Clinical Oncology.

LIMITATIONS:

This study’s limitations included the heterogeneity in defining clinical complete response and the decision to watch and wait across different institutions. The majority of patients did not receive total neoadjuvant therapy regimens, which may have affected the generalizability of the findings. The study had a considerable amount of follow-up losses, which could have introduced bias.

DISCLOSURES:

This study was supported by the European Society of Surgical Oncology, the Champalimaud Foundation, the Bas Mulder Award, the Alpe d’HuZes Foundation, the Dutch Cancer Society, the European Research Council Advanced Grant, and the National Institute of Health and Research Manchester Biomedical Research Centre. Fernandez disclosed receiving grants from Johnson & Johnson. Additional disclosures are noted in the original article.

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

TOPLINE:

Patients with rectal cancer managed by watch and wait and subsequent local regrowth have a higher risk for distant metastases than those undergoing immediate surgery. The new study highlights the importance of timely surgical intervention to improve distant metastases–free survival rates.

METHODOLOGY:

• Organ preservation has become an attractive alternative to surgery for patients with rectal cancer who achieve a clinical complete response after neoadjuvant therapy, with the risk for local regrowth after initial clinical complete response being around 25%-30%.
• The new study aimed to compare the risk for distant metastases between patients with local regrowth after watch and wait and patients with near-complete pathologic response managed by total mesorectal excision.
• A total of 508 patients with local regrowth were included from the International Watch & Wait Database, and 893 patients with near-complete pathologic response were included from the Spanish Rectal Cancer Project.
• The primary endpoint was distant metastases–free survival at 3 years from the decision to watch and wait or total mesorectal excision, and the secondary endpoints included possible risk factors associated with distant metastases.

TAKEAWAY:

• Patients with local regrowth had a significantly higher rate of distant metastases (rate, 22.8% vs 10.2%; P ≤.001) than those with near-complete pathologic response managed by total mesorectal excision.
• Distant metastases–free survival at 3 years was significantly worse for patients with local regrowth (rate, 75% vs 87%; P < .001).
• Independent risk factors for distant metastases included local regrowth (vs total mesorectal excision at reassessment; P = .001), ypT3-4 status (P = .016), and ypN+ status (P = .001) at the time of surgery.
• Patients with local regrowth had worse distant metastases–free survival across all pathologic stages than those managed by total mesorectal excision.

IN PRACTICE:

“Patients with local regrowth appear to have a higher risk for subsequent distant metastases development than patients with near-complete pathologic response managed by total mesorectal excision at restaging irrespective of final pathology,” the authors wrote.

SOURCE:

This study was led by Laura M. Fernandez, MD, of the Champalimaud Foundation in Lisbon, Portugal. It was published online in Journal of Clinical Oncology.

LIMITATIONS:

This study’s limitations included the heterogeneity in defining clinical complete response and the decision to watch and wait across different institutions. The majority of patients did not receive total neoadjuvant therapy regimens, which may have affected the generalizability of the findings. The study had a considerable amount of follow-up losses, which could have introduced bias.

DISCLOSURES:

This study was supported by the European Society of Surgical Oncology, the Champalimaud Foundation, the Bas Mulder Award, the Alpe d’HuZes Foundation, the Dutch Cancer Society, the European Research Council Advanced Grant, and the National Institute of Health and Research Manchester Biomedical Research Centre. Fernandez disclosed receiving grants from Johnson & Johnson. Additional disclosures are noted in the original article.

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

TOPLINE:

Among 57,086 older adults, new gabapentin users demonstrated lower fall-related healthcare visits than duloxetine users, with a weighted cumulative incidence of 84.44 vs 158.21 per 1000 person-years at 180 days. Incident gabapentin use showed a 48% lower hazard of falls at 6-month follow-up, with no increase in severe fall-related events.
 

METHODOLOGY:

• Researchers conducted a new user, active comparator cohort study using IBM MarketScan Research Databases from January 2014 to December 2021.
• Analysis included 57,086 adults aged 65 years or older with postherpetic neuralgia, diabetic neuropathy, or fibromyalgia, excluding those with depression, anxiety, seizures, or cancer in the prior 365 days.
• The primary outcome measured the hazard of experiencing any fall-related visit in the 6 months after initiating gabapentin or duloxetine until treatment discontinuation.
• Secondary outcomes examined severe fall-related events, including falls with hip fractures or emergency department visits/hospitalizations associated with falls.

TAKEAWAY:

• The analytic cohort included 52,152 gabapentin users and 4934 duloxetine users, with a median follow-up duration of 30 days (interquartile range, 30-90 days).
• Weighted cumulative incidence of fall-related visits per 1000 person-years at 30, 90, and 180 days was 103.60, 90.44, and 84.44 for gabapentin users vs 203.43, 177.73, and 158.21 for duloxetine users.
• At 6-month follow-up, incident gabapentin users demonstrated lower hazard of falls (hazard ratio, 0.52; 95% CI, 0.43-0.64), with no difference in hazards of severe falls.
• Results remained consistent across sensitivity and subgroup analyses.

IN PRACTICE:

“One bioplausible explanation for our results is that gabapentin is a highly titratable medication and many in our cohort started on low doses. Alternatively, duloxetine is usually titrated only once or twice. Thus, although it may be that gabapentin is simply safer than duloxetine from a falls perspective, it may also be likely that we are measuring specific clinical scenarios, the peri-initiation and titration period, in which gabapentin may be less likely to cause falls than duloxetine,” the authors wrote.
 

SOURCE:

The study was led by Alexander Chaitoff, MD, MPH, Department of Internal Medicine, University of Michigan School of Medicine in Ann Arbor, and Center for Healthcare Delivery Sciences, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School in Boston. It was published online in Annals of Internal Medicine.
 

LIMITATIONS:

Despite the design aimed at limiting confounding effects, the observational nature of the study introduces potential bias. Claims data may undercount falls for which patients do not seek care, though this limitation likely affects both medication groups equally. The commercial claims database includes only Medicare supplemental insurance beneficiaries, potentially limiting generalizability. Regional variations in prescribing patterns could not be accounted for in the analysis.
 

DISCLOSURES:

No funding was provided for this study.
 

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

TOPLINE:

Among 57,086 older adults, new gabapentin users demonstrated lower fall-related healthcare visits than duloxetine users, with a weighted cumulative incidence of 84.44 vs 158.21 per 1000 person-years at 180 days. Incident gabapentin use showed a 48% lower hazard of falls at 6-month follow-up, with no increase in severe fall-related events.
 

METHODOLOGY:

• Researchers conducted a new user, active comparator cohort study using IBM MarketScan Research Databases from January 2014 to December 2021.
• Analysis included 57,086 adults aged 65 years or older with postherpetic neuralgia, diabetic neuropathy, or fibromyalgia, excluding those with depression, anxiety, seizures, or cancer in the prior 365 days.
• The primary outcome measured the hazard of experiencing any fall-related visit in the 6 months after initiating gabapentin or duloxetine until treatment discontinuation.
• Secondary outcomes examined severe fall-related events, including falls with hip fractures or emergency department visits/hospitalizations associated with falls.

TAKEAWAY:

• The analytic cohort included 52,152 gabapentin users and 4934 duloxetine users, with a median follow-up duration of 30 days (interquartile range, 30-90 days).
• Weighted cumulative incidence of fall-related visits per 1000 person-years at 30, 90, and 180 days was 103.60, 90.44, and 84.44 for gabapentin users vs 203.43, 177.73, and 158.21 for duloxetine users.
• At 6-month follow-up, incident gabapentin users demonstrated lower hazard of falls (hazard ratio, 0.52; 95% CI, 0.43-0.64), with no difference in hazards of severe falls.
• Results remained consistent across sensitivity and subgroup analyses.

IN PRACTICE:

“One bioplausible explanation for our results is that gabapentin is a highly titratable medication and many in our cohort started on low doses. Alternatively, duloxetine is usually titrated only once or twice. Thus, although it may be that gabapentin is simply safer than duloxetine from a falls perspective, it may also be likely that we are measuring specific clinical scenarios, the peri-initiation and titration period, in which gabapentin may be less likely to cause falls than duloxetine,” the authors wrote.
 

SOURCE:

The study was led by Alexander Chaitoff, MD, MPH, Department of Internal Medicine, University of Michigan School of Medicine in Ann Arbor, and Center for Healthcare Delivery Sciences, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School in Boston. It was published online in Annals of Internal Medicine.
 

LIMITATIONS:

Despite the design aimed at limiting confounding effects, the observational nature of the study introduces potential bias. Claims data may undercount falls for which patients do not seek care, though this limitation likely affects both medication groups equally. The commercial claims database includes only Medicare supplemental insurance beneficiaries, potentially limiting generalizability. Regional variations in prescribing patterns could not be accounted for in the analysis.
 

DISCLOSURES:

No funding was provided for this study.
 

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

TOPLINE:

Among 57,086 older adults, new gabapentin users demonstrated lower fall-related healthcare visits than duloxetine users, with a weighted cumulative incidence of 84.44 vs 158.21 per 1000 person-years at 180 days. Incident gabapentin use showed a 48% lower hazard of falls at 6-month follow-up, with no increase in severe fall-related events.
 

METHODOLOGY:

• Researchers conducted a new user, active comparator cohort study using IBM MarketScan Research Databases from January 2014 to December 2021.
• Analysis included 57,086 adults aged 65 years or older with postherpetic neuralgia, diabetic neuropathy, or fibromyalgia, excluding those with depression, anxiety, seizures, or cancer in the prior 365 days.
• The primary outcome measured the hazard of experiencing any fall-related visit in the 6 months after initiating gabapentin or duloxetine until treatment discontinuation.
• Secondary outcomes examined severe fall-related events, including falls with hip fractures or emergency department visits/hospitalizations associated with falls.

TAKEAWAY:

• The analytic cohort included 52,152 gabapentin users and 4934 duloxetine users, with a median follow-up duration of 30 days (interquartile range, 30-90 days).
• Weighted cumulative incidence of fall-related visits per 1000 person-years at 30, 90, and 180 days was 103.60, 90.44, and 84.44 for gabapentin users vs 203.43, 177.73, and 158.21 for duloxetine users.
• At 6-month follow-up, incident gabapentin users demonstrated lower hazard of falls (hazard ratio, 0.52; 95% CI, 0.43-0.64), with no difference in hazards of severe falls.
• Results remained consistent across sensitivity and subgroup analyses.

IN PRACTICE:

“One bioplausible explanation for our results is that gabapentin is a highly titratable medication and many in our cohort started on low doses. Alternatively, duloxetine is usually titrated only once or twice. Thus, although it may be that gabapentin is simply safer than duloxetine from a falls perspective, it may also be likely that we are measuring specific clinical scenarios, the peri-initiation and titration period, in which gabapentin may be less likely to cause falls than duloxetine,” the authors wrote.
 

SOURCE:

The study was led by Alexander Chaitoff, MD, MPH, Department of Internal Medicine, University of Michigan School of Medicine in Ann Arbor, and Center for Healthcare Delivery Sciences, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School in Boston. It was published online in Annals of Internal Medicine.
 

LIMITATIONS:

Despite the design aimed at limiting confounding effects, the observational nature of the study introduces potential bias. Claims data may undercount falls for which patients do not seek care, though this limitation likely affects both medication groups equally. The commercial claims database includes only Medicare supplemental insurance beneficiaries, potentially limiting generalizability. Regional variations in prescribing patterns could not be accounted for in the analysis.
 

DISCLOSURES:

No funding was provided for this study.
 

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

For millennia in medicine, alcohol, particularly red wine, carried a health halo; in small doses, it has historically been thought to have cardioprotective benefits. Michael Farkouh, MD, a professor of cardiology at Cedars-Sinai, estimates half the physicians still accept people having a drink or two a day. “That is still in practice, though the numbers are reducing,” he said.

But Farkouh no longer drinks alcohol, a position he has come to after getting more involved in research into the substance and his realization that many of the studies touting alcohol’s health benefits were flawed.

Today, alcohol sits alongside asbestos and tobacco as class 1 carcinogens. According to the World Health Organization, it has no known safe ingestible amount. In 2018, a blockbuster report in The Lancet found no amount of any kind of alcohol improves health. In early January, US Surgeon General Vivek Murthy called for adding cancer warnings to alcohol labels.

But the way doctors drink is far from black and white. For physicians, drinking habits are tied up in personal values, professional understanding of a substance with a confusing research history, and the fact alcohol is deeply ingrained in the social fabric of society — and in medicine. As thinking on alcohol shifts, this news organization spoke with physicians about their own drinking habits, how they counsel patients on it, and alcohol’s place in a field that works to keep people healthy.

 

Cultural Currency

From the days of Hippocrates, who believed alcohol could cure virtually every ailment, alcohol has held a large role in medicine. Through much of the 19th century, patent remedies like Hamlin’s Wizard Oil and the Seven Sutherland Sisters Hair Grower, contained alcohol — sometimes in concentrations exceeding 50%.

The first American Pharmacopoeia, published in 1820, even contained nine wine-based medicines. Throughout the second half of the 19th century, physicians largely debated alcohol’s role in medicine. However, a 1922 poll of members of the American Medical Association found that physicians were still using alcohol as a medicine for everything from heart attacks to animal bites.

Today, alcohol’s presence in medicine is, in some ways, representative of a realized cognitive dissonance.

“In my mind, alcohol has completely lost any illusion of benefit. It is a poison to almost every single organ in our body. Yet I’m currently engaged in a duel of being a physician who drinks in moderation and constantly judging myself for it,” said Tyra Fainstad, MD, an internist and an associate professor at CU Medicine in Denver.

Fainstad said every academic national conference she has attended has had a reception with multiple cash bars — and professional recruitment dinners regularly include at least the offering of alcohol. Private hospitals often have open bars at events.

“Drinking has historically been a way that people unwind, even in medicine,” said addiction psychiatrist Alexis Ritvo, MD. Ritvo — who said she drinks occasionally but much less than she used to after paying attention to how alcohol makes her feel and the harm alcohol can cause — noted that some occasions where alcohol is present socially in medicine don’t bother her. Alcohol is even an option at the addiction psychiatry conference, where attendees can exchange tickets for drinks. But last year, the event provided separate bars for alcoholic and nonalcoholic drinks.

“Our life is full of things that are contradictory or at odds,” Ritvo said. “We want things to either be wrong or right, appropriate or inappropriate, but just like all things, everything’s pretty nuanced.”

But there are examples of alcohol being a part of an event that are downright inappropriate, such as when she attended a fundraiser for a recovery facility that had an open bar.

Farkouh said alcohol at events can exclude others. (He recommends that instead of calling a social gathering “going out for drinks,” someone might say, “We’re getting together.”) He drinks mocktails or nonalcoholic beer at work events where alcohol is served.

Brian Dwinnell, MD, associate dean of student life at CU Medicine, said alcohol can quickly become the focus of an event — something he noticed at an annual kickball game between first- and second-year students that has historically served beer.

In recent years, school leadership has removed alcohol from his institution’s match day celebration and the kickball game. “Initially, there was some pushback from students,” he said of making these events dry, “but now, it’s just sort of accepted, and the events have been just as great as they were when we did provide alcohol.”

 

How Doctors Drink

Physicians may have a greater understanding of alcohol’s health harms. Still, they don’t necessarily drink less because of it, and whether they should becomes a question not just of health but also of the standards to which society holds medical professionals.

Data suggest physicians tend to drink at rates similar to those among the general population. A recent Medscape Medical News survey found nearly 60% of physicians have started drinking less.

Dwinnell said he is a long-time “wine connoisseur” and drinks on occasion. But he admitted that while he thinks about the health implications of alcohol more — and he has nixed it from various events for medical students — he does not believe his drinking habits have changed much.

Navya Mysore, MD, a family physician in New York City, said she has become interested in wine over the past few years, even taking classes to learn more about it. “I like understanding how it’s made, the regions it’s from, and how to pair it with food,” she said. Mysore admits she drank a little more than usual throughout the pandemic, yet today, she said her relationship with alcohol in moderation is related to family, community, and connection.

Fainstad, who drinks socially, said: “I think there’s an immeasurable quality to the social ritual of it. I think for better or worse — probably for worse — for many generations, alcohol has been a part of many meaningful traditions and rituals that we hold.”

Farkouh was quick to underscore the importance of social connection, and that alcohol reduces stress for some people. “I don’t want to take that away from people,” he said. But he also stated the importance of finding other ways to find social fulfillment and enjoyment — and said it’s essential for societal norms to shift to reflect this.

With emerging data, alcohol’s image in society is shifting. Ireland recently became the first country to pass regulation requiring all alcohol sold there to come with a cancer warning. All the clinicians interviewed for this article spoke about the increased acceptability of choosing not to drink for whatever reason.

In the context of alcohol, Dwinnell often asks his students, “What if you were out at a restaurant and you saw your mother’s surgeon there and they were intoxicated? Are you going to feel comfortable with that individual operating on your mother tomorrow or any time?” He added: “Physicians are held to a higher professional standard than those in other fields — and they should be. This is a high-stakes business.”

Dwinnell’s hypothetical question to students is a good one, albeit perhaps not always a fair one. “It’s important for people to realize that physicians are humans,” Mysore said. “We are people, we have lives, and we may choose to have habits that are not necessarily the healthiest for us.”

Fainstad said there’s no shame in medical professionals drinking on occasion. “You can’t be held accountable for something you don’t know about,” she said, acknowledging the known harms of alcohol and that there is still more to learn. But she does wonder how doctors who drank might be perceived in years to come. “I can imagine in a couple of decades, people could say, ‘Even doctors used to have a glass of wine with dinner.’”

 

‘Physicians Should Tighten Their Stances on Alcohol’

The 2020-2025 Dietary Guidelines suggest limiting intake to two alcoholic drinks or less daily for men and one drink or less for women or to choose not to drink. Farkouh said he skews toward the latter, encouraging patients to drink as little as possible or nothing at all. “If you take a holistic approach, physicians should tighten their stances on alcohol,” he said.

Ultimately, he said a randomized trial is warranted to address the risk for cardiovascular disease, in particular.

Of course, physicians vary in how they discuss the topic with patients.

Mysore said she regularly educates patients about pour size and ways to swap out alcoholic drinks with nonalcoholic ones. Outside of cases of addiction, she favors the idea of moderation. “I don’t really subscribe to all-or-nothing mindsets. If there’s something that you enjoy having as a part of your life, I don’t think there’s any reason why you need to eliminate it,” she said. “You just need to figure out what moderation looks like for you.”

Ritvo favors motivational interviewing and tries to understand someone’s relationship with alcohol.

Fainstad provides the Dietary Guidelines’ cutoffs to patients and educates them on the poisonous nature of the substance.

Clearer guidance from large governing bodies — potential changes around alcohol in the 2025-230 revision of the US Dietary Guidelines or cancer warnings on booze sold in the United States — are coming and could help streamline messaging.

And although he speaks with urgency about alcohol’s dangers, Farkouh emphasized the need for a judgment-free and patient-centered approach to conversations around drinking: “People have grown up with alcohol being acceptable, and it’s going to take time to change that.”

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

For millennia in medicine, alcohol, particularly red wine, carried a health halo; in small doses, it has historically been thought to have cardioprotective benefits. Michael Farkouh, MD, a professor of cardiology at Cedars-Sinai, estimates half the physicians still accept people having a drink or two a day. “That is still in practice, though the numbers are reducing,” he said.

But Farkouh no longer drinks alcohol, a position he has come to after getting more involved in research into the substance and his realization that many of the studies touting alcohol’s health benefits were flawed.

Today, alcohol sits alongside asbestos and tobacco as class 1 carcinogens. According to the World Health Organization, it has no known safe ingestible amount. In 2018, a blockbuster report in The Lancet found no amount of any kind of alcohol improves health. In early January, US Surgeon General Vivek Murthy called for adding cancer warnings to alcohol labels.

But the way doctors drink is far from black and white. For physicians, drinking habits are tied up in personal values, professional understanding of a substance with a confusing research history, and the fact alcohol is deeply ingrained in the social fabric of society — and in medicine. As thinking on alcohol shifts, this news organization spoke with physicians about their own drinking habits, how they counsel patients on it, and alcohol’s place in a field that works to keep people healthy.

 

Cultural Currency

From the days of Hippocrates, who believed alcohol could cure virtually every ailment, alcohol has held a large role in medicine. Through much of the 19th century, patent remedies like Hamlin’s Wizard Oil and the Seven Sutherland Sisters Hair Grower, contained alcohol — sometimes in concentrations exceeding 50%.

The first American Pharmacopoeia, published in 1820, even contained nine wine-based medicines. Throughout the second half of the 19th century, physicians largely debated alcohol’s role in medicine. However, a 1922 poll of members of the American Medical Association found that physicians were still using alcohol as a medicine for everything from heart attacks to animal bites.

Today, alcohol’s presence in medicine is, in some ways, representative of a realized cognitive dissonance.

“In my mind, alcohol has completely lost any illusion of benefit. It is a poison to almost every single organ in our body. Yet I’m currently engaged in a duel of being a physician who drinks in moderation and constantly judging myself for it,” said Tyra Fainstad, MD, an internist and an associate professor at CU Medicine in Denver.

Fainstad said every academic national conference she has attended has had a reception with multiple cash bars — and professional recruitment dinners regularly include at least the offering of alcohol. Private hospitals often have open bars at events.

“Drinking has historically been a way that people unwind, even in medicine,” said addiction psychiatrist Alexis Ritvo, MD. Ritvo — who said she drinks occasionally but much less than she used to after paying attention to how alcohol makes her feel and the harm alcohol can cause — noted that some occasions where alcohol is present socially in medicine don’t bother her. Alcohol is even an option at the addiction psychiatry conference, where attendees can exchange tickets for drinks. But last year, the event provided separate bars for alcoholic and nonalcoholic drinks.

“Our life is full of things that are contradictory or at odds,” Ritvo said. “We want things to either be wrong or right, appropriate or inappropriate, but just like all things, everything’s pretty nuanced.”

But there are examples of alcohol being a part of an event that are downright inappropriate, such as when she attended a fundraiser for a recovery facility that had an open bar.

Farkouh said alcohol at events can exclude others. (He recommends that instead of calling a social gathering “going out for drinks,” someone might say, “We’re getting together.”) He drinks mocktails or nonalcoholic beer at work events where alcohol is served.

Brian Dwinnell, MD, associate dean of student life at CU Medicine, said alcohol can quickly become the focus of an event — something he noticed at an annual kickball game between first- and second-year students that has historically served beer.

In recent years, school leadership has removed alcohol from his institution’s match day celebration and the kickball game. “Initially, there was some pushback from students,” he said of making these events dry, “but now, it’s just sort of accepted, and the events have been just as great as they were when we did provide alcohol.”

 

How Doctors Drink

Physicians may have a greater understanding of alcohol’s health harms. Still, they don’t necessarily drink less because of it, and whether they should becomes a question not just of health but also of the standards to which society holds medical professionals.

Data suggest physicians tend to drink at rates similar to those among the general population. A recent Medscape Medical News survey found nearly 60% of physicians have started drinking less.

Dwinnell said he is a long-time “wine connoisseur” and drinks on occasion. But he admitted that while he thinks about the health implications of alcohol more — and he has nixed it from various events for medical students — he does not believe his drinking habits have changed much.

Navya Mysore, MD, a family physician in New York City, said she has become interested in wine over the past few years, even taking classes to learn more about it. “I like understanding how it’s made, the regions it’s from, and how to pair it with food,” she said. Mysore admits she drank a little more than usual throughout the pandemic, yet today, she said her relationship with alcohol in moderation is related to family, community, and connection.

Fainstad, who drinks socially, said: “I think there’s an immeasurable quality to the social ritual of it. I think for better or worse — probably for worse — for many generations, alcohol has been a part of many meaningful traditions and rituals that we hold.”

Farkouh was quick to underscore the importance of social connection, and that alcohol reduces stress for some people. “I don’t want to take that away from people,” he said. But he also stated the importance of finding other ways to find social fulfillment and enjoyment — and said it’s essential for societal norms to shift to reflect this.

With emerging data, alcohol’s image in society is shifting. Ireland recently became the first country to pass regulation requiring all alcohol sold there to come with a cancer warning. All the clinicians interviewed for this article spoke about the increased acceptability of choosing not to drink for whatever reason.

In the context of alcohol, Dwinnell often asks his students, “What if you were out at a restaurant and you saw your mother’s surgeon there and they were intoxicated? Are you going to feel comfortable with that individual operating on your mother tomorrow or any time?” He added: “Physicians are held to a higher professional standard than those in other fields — and they should be. This is a high-stakes business.”

Dwinnell’s hypothetical question to students is a good one, albeit perhaps not always a fair one. “It’s important for people to realize that physicians are humans,” Mysore said. “We are people, we have lives, and we may choose to have habits that are not necessarily the healthiest for us.”

Fainstad said there’s no shame in medical professionals drinking on occasion. “You can’t be held accountable for something you don’t know about,” she said, acknowledging the known harms of alcohol and that there is still more to learn. But she does wonder how doctors who drank might be perceived in years to come. “I can imagine in a couple of decades, people could say, ‘Even doctors used to have a glass of wine with dinner.’”

 

‘Physicians Should Tighten Their Stances on Alcohol’

The 2020-2025 Dietary Guidelines suggest limiting intake to two alcoholic drinks or less daily for men and one drink or less for women or to choose not to drink. Farkouh said he skews toward the latter, encouraging patients to drink as little as possible or nothing at all. “If you take a holistic approach, physicians should tighten their stances on alcohol,” he said.

Ultimately, he said a randomized trial is warranted to address the risk for cardiovascular disease, in particular.

Of course, physicians vary in how they discuss the topic with patients.

Mysore said she regularly educates patients about pour size and ways to swap out alcoholic drinks with nonalcoholic ones. Outside of cases of addiction, she favors the idea of moderation. “I don’t really subscribe to all-or-nothing mindsets. If there’s something that you enjoy having as a part of your life, I don’t think there’s any reason why you need to eliminate it,” she said. “You just need to figure out what moderation looks like for you.”

Ritvo favors motivational interviewing and tries to understand someone’s relationship with alcohol.

Fainstad provides the Dietary Guidelines’ cutoffs to patients and educates them on the poisonous nature of the substance.

Clearer guidance from large governing bodies — potential changes around alcohol in the 2025-230 revision of the US Dietary Guidelines or cancer warnings on booze sold in the United States — are coming and could help streamline messaging.

And although he speaks with urgency about alcohol’s dangers, Farkouh emphasized the need for a judgment-free and patient-centered approach to conversations around drinking: “People have grown up with alcohol being acceptable, and it’s going to take time to change that.”

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

For millennia in medicine, alcohol, particularly red wine, carried a health halo; in small doses, it has historically been thought to have cardioprotective benefits. Michael Farkouh, MD, a professor of cardiology at Cedars-Sinai, estimates half the physicians still accept people having a drink or two a day. “That is still in practice, though the numbers are reducing,” he said.

But Farkouh no longer drinks alcohol, a position he has come to after getting more involved in research into the substance and his realization that many of the studies touting alcohol’s health benefits were flawed.

Today, alcohol sits alongside asbestos and tobacco as class 1 carcinogens. According to the World Health Organization, it has no known safe ingestible amount. In 2018, a blockbuster report in The Lancet found no amount of any kind of alcohol improves health. In early January, US Surgeon General Vivek Murthy called for adding cancer warnings to alcohol labels.

But the way doctors drink is far from black and white. For physicians, drinking habits are tied up in personal values, professional understanding of a substance with a confusing research history, and the fact alcohol is deeply ingrained in the social fabric of society — and in medicine. As thinking on alcohol shifts, this news organization spoke with physicians about their own drinking habits, how they counsel patients on it, and alcohol’s place in a field that works to keep people healthy.

 

Cultural Currency

From the days of Hippocrates, who believed alcohol could cure virtually every ailment, alcohol has held a large role in medicine. Through much of the 19th century, patent remedies like Hamlin’s Wizard Oil and the Seven Sutherland Sisters Hair Grower, contained alcohol — sometimes in concentrations exceeding 50%.

The first American Pharmacopoeia, published in 1820, even contained nine wine-based medicines. Throughout the second half of the 19th century, physicians largely debated alcohol’s role in medicine. However, a 1922 poll of members of the American Medical Association found that physicians were still using alcohol as a medicine for everything from heart attacks to animal bites.

Today, alcohol’s presence in medicine is, in some ways, representative of a realized cognitive dissonance.

“In my mind, alcohol has completely lost any illusion of benefit. It is a poison to almost every single organ in our body. Yet I’m currently engaged in a duel of being a physician who drinks in moderation and constantly judging myself for it,” said Tyra Fainstad, MD, an internist and an associate professor at CU Medicine in Denver.

Fainstad said every academic national conference she has attended has had a reception with multiple cash bars — and professional recruitment dinners regularly include at least the offering of alcohol. Private hospitals often have open bars at events.

“Drinking has historically been a way that people unwind, even in medicine,” said addiction psychiatrist Alexis Ritvo, MD. Ritvo — who said she drinks occasionally but much less than she used to after paying attention to how alcohol makes her feel and the harm alcohol can cause — noted that some occasions where alcohol is present socially in medicine don’t bother her. Alcohol is even an option at the addiction psychiatry conference, where attendees can exchange tickets for drinks. But last year, the event provided separate bars for alcoholic and nonalcoholic drinks.

“Our life is full of things that are contradictory or at odds,” Ritvo said. “We want things to either be wrong or right, appropriate or inappropriate, but just like all things, everything’s pretty nuanced.”

But there are examples of alcohol being a part of an event that are downright inappropriate, such as when she attended a fundraiser for a recovery facility that had an open bar.

Farkouh said alcohol at events can exclude others. (He recommends that instead of calling a social gathering “going out for drinks,” someone might say, “We’re getting together.”) He drinks mocktails or nonalcoholic beer at work events where alcohol is served.

Brian Dwinnell, MD, associate dean of student life at CU Medicine, said alcohol can quickly become the focus of an event — something he noticed at an annual kickball game between first- and second-year students that has historically served beer.

In recent years, school leadership has removed alcohol from his institution’s match day celebration and the kickball game. “Initially, there was some pushback from students,” he said of making these events dry, “but now, it’s just sort of accepted, and the events have been just as great as they were when we did provide alcohol.”

 

How Doctors Drink

Physicians may have a greater understanding of alcohol’s health harms. Still, they don’t necessarily drink less because of it, and whether they should becomes a question not just of health but also of the standards to which society holds medical professionals.

Data suggest physicians tend to drink at rates similar to those among the general population. A recent Medscape Medical News survey found nearly 60% of physicians have started drinking less.

Dwinnell said he is a long-time “wine connoisseur” and drinks on occasion. But he admitted that while he thinks about the health implications of alcohol more — and he has nixed it from various events for medical students — he does not believe his drinking habits have changed much.

Navya Mysore, MD, a family physician in New York City, said she has become interested in wine over the past few years, even taking classes to learn more about it. “I like understanding how it’s made, the regions it’s from, and how to pair it with food,” she said. Mysore admits she drank a little more than usual throughout the pandemic, yet today, she said her relationship with alcohol in moderation is related to family, community, and connection.

Fainstad, who drinks socially, said: “I think there’s an immeasurable quality to the social ritual of it. I think for better or worse — probably for worse — for many generations, alcohol has been a part of many meaningful traditions and rituals that we hold.”

Farkouh was quick to underscore the importance of social connection, and that alcohol reduces stress for some people. “I don’t want to take that away from people,” he said. But he also stated the importance of finding other ways to find social fulfillment and enjoyment — and said it’s essential for societal norms to shift to reflect this.

With emerging data, alcohol’s image in society is shifting. Ireland recently became the first country to pass regulation requiring all alcohol sold there to come with a cancer warning. All the clinicians interviewed for this article spoke about the increased acceptability of choosing not to drink for whatever reason.

In the context of alcohol, Dwinnell often asks his students, “What if you were out at a restaurant and you saw your mother’s surgeon there and they were intoxicated? Are you going to feel comfortable with that individual operating on your mother tomorrow or any time?” He added: “Physicians are held to a higher professional standard than those in other fields — and they should be. This is a high-stakes business.”

Dwinnell’s hypothetical question to students is a good one, albeit perhaps not always a fair one. “It’s important for people to realize that physicians are humans,” Mysore said. “We are people, we have lives, and we may choose to have habits that are not necessarily the healthiest for us.”

Fainstad said there’s no shame in medical professionals drinking on occasion. “You can’t be held accountable for something you don’t know about,” she said, acknowledging the known harms of alcohol and that there is still more to learn. But she does wonder how doctors who drank might be perceived in years to come. “I can imagine in a couple of decades, people could say, ‘Even doctors used to have a glass of wine with dinner.’”

 

‘Physicians Should Tighten Their Stances on Alcohol’

The 2020-2025 Dietary Guidelines suggest limiting intake to two alcoholic drinks or less daily for men and one drink or less for women or to choose not to drink. Farkouh said he skews toward the latter, encouraging patients to drink as little as possible or nothing at all. “If you take a holistic approach, physicians should tighten their stances on alcohol,” he said.

Ultimately, he said a randomized trial is warranted to address the risk for cardiovascular disease, in particular.

Of course, physicians vary in how they discuss the topic with patients.

Mysore said she regularly educates patients about pour size and ways to swap out alcoholic drinks with nonalcoholic ones. Outside of cases of addiction, she favors the idea of moderation. “I don’t really subscribe to all-or-nothing mindsets. If there’s something that you enjoy having as a part of your life, I don’t think there’s any reason why you need to eliminate it,” she said. “You just need to figure out what moderation looks like for you.”

Ritvo favors motivational interviewing and tries to understand someone’s relationship with alcohol.

Fainstad provides the Dietary Guidelines’ cutoffs to patients and educates them on the poisonous nature of the substance.

Clearer guidance from large governing bodies — potential changes around alcohol in the 2025-230 revision of the US Dietary Guidelines or cancer warnings on booze sold in the United States — are coming and could help streamline messaging.

And although he speaks with urgency about alcohol’s dangers, Farkouh emphasized the need for a judgment-free and patient-centered approach to conversations around drinking: “People have grown up with alcohol being acceptable, and it’s going to take time to change that.”

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

TOPLINE: 

Prostate-specific membrane antigen (PSMA)–PET detected metastatic disease in 46% of patients with high-risk prostate cancer previously classified as nonmetastatic by conventional imaging. Results were positive in 84% of patients, with polymetastatic disease found in 24% of cases.

METHODOLOGY:

• Recurrent nonmetastatic hormone-sensitive prostate cancer is characterized by increasing prostate-specific antigen (PSA) levels while naive or responsive to androgen deprivation therapy, without evidence of metastasis on conventional imaging.
• A post hoc, retrospective, cross-sectional analysis included 182 patients from four prospective studies conducted from September 2016 to September 2021, with participants having recurrent prostate cancer after radical prostatectomy, definitive radiotherapy, or salvage radiotherapy.
• Inclusion criteria encompassed PSA levels > 1.0 ng/mL after radical prostatectomy and salvage radiotherapy or > 2.0 ng/mL above nadir after definitive radiotherapy, PSA doubling time ≤ 9 months, and serum testosterone ≥ 150 ng/dL.
• Researchers at the University of California, Los Angeles, performed Gallium-68-PSMA-11 PET/CT imaging with a median injection of 5.0 mCi and uptake time of 61 minutes, with 98% of patients receiving CT contrast.

TAKEAWAY:

• PSMA-PET findings were positive in 80% of patients after radical prostatectomy, 92% after definitive radiotherapy, 85% after radical prostatectomy and salvage radiotherapy, and 84% overall (153 of 182 patients).
• Distant metastatic disease was detected in 34% of patients after radical prostatectomy, 56% after definitive radiotherapy, 60% after radical prostatectomy and salvage radiotherapy, and 46% overall.
• Polymetastatic disease (≥ 5 lesions) was identified in 19% of patients after radical prostatectomy, 36% after definitive radiotherapy, 23% after radical prostatectomy and salvage radiotherapy, and 24% overall.
• According to the authors, these findings suggest that patients’ high-risk nonmetastatic hormone-sensitive prostate cancers are understaged by conventional imaging.

IN PRACTICE:

“In a cohort of patients with high-risk hormone-sensitive prostate cancer without evidence of metastatic disease by conventional imaging, PSMA-PET results were positive in 84% of patients, detected M1 disease stage in 46% of patients, and found polymetastatic disease in 24% of patients. ... The results challenge the interpretation of previous studies, such as the EMBARK trial, and support the evolving role of PSMA-PET for patient selection in clinical and trial interventions in prostate cancer,” the authors of the new paper wrote. “Further studies are needed to assess its independent prognostic value and use for treatment guidance.”

SOURCE:

This study was led by Adrien Holzgreve, MD, and Wesley R. Armstrong, BS, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles. It was published online on January 3 in JAMA Network Open.

LIMITATIONS:

The analysis included significantly fewer patients treated with combined radical prostatectomy and salvage radiotherapy than the original EMBARK trial (29% vs 49%). Patients in this study had a lower median PSA doubling time and serum PSA level at enrollment than those in the EMBARK study. The retrospective nature of this study precluded systematic baseline imaging that would be standard for clinical trial enrollment. Additionally, while PSMA-PET offers the best diagnostic accuracy for prostate cancer staging, it can produce false-positive findings, particularly in bone metastases, with a positive predictive value of 0.84% in biochemical recurrence.

DISCLOSURES:

Holzgreve reported receiving personal fees from ABX advanced biochemical compounds outside the submitted work. This study was supported by grants from the Deutsche Forschungsgemeinschaft, the Prostate Cancer Foundation, and the Society of Nuclear Medicine and Molecular Imaging. Additional disclosures are noted in the original article.

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

TOPLINE: 

Prostate-specific membrane antigen (PSMA)–PET detected metastatic disease in 46% of patients with high-risk prostate cancer previously classified as nonmetastatic by conventional imaging. Results were positive in 84% of patients, with polymetastatic disease found in 24% of cases.

METHODOLOGY:

• Recurrent nonmetastatic hormone-sensitive prostate cancer is characterized by increasing prostate-specific antigen (PSA) levels while naive or responsive to androgen deprivation therapy, without evidence of metastasis on conventional imaging.
• A post hoc, retrospective, cross-sectional analysis included 182 patients from four prospective studies conducted from September 2016 to September 2021, with participants having recurrent prostate cancer after radical prostatectomy, definitive radiotherapy, or salvage radiotherapy.
• Inclusion criteria encompassed PSA levels > 1.0 ng/mL after radical prostatectomy and salvage radiotherapy or > 2.0 ng/mL above nadir after definitive radiotherapy, PSA doubling time ≤ 9 months, and serum testosterone ≥ 150 ng/dL.
• Researchers at the University of California, Los Angeles, performed Gallium-68-PSMA-11 PET/CT imaging with a median injection of 5.0 mCi and uptake time of 61 minutes, with 98% of patients receiving CT contrast.

TAKEAWAY:

• PSMA-PET findings were positive in 80% of patients after radical prostatectomy, 92% after definitive radiotherapy, 85% after radical prostatectomy and salvage radiotherapy, and 84% overall (153 of 182 patients).
• Distant metastatic disease was detected in 34% of patients after radical prostatectomy, 56% after definitive radiotherapy, 60% after radical prostatectomy and salvage radiotherapy, and 46% overall.
• Polymetastatic disease (≥ 5 lesions) was identified in 19% of patients after radical prostatectomy, 36% after definitive radiotherapy, 23% after radical prostatectomy and salvage radiotherapy, and 24% overall.
• According to the authors, these findings suggest that patients’ high-risk nonmetastatic hormone-sensitive prostate cancers are understaged by conventional imaging.

IN PRACTICE:

“In a cohort of patients with high-risk hormone-sensitive prostate cancer without evidence of metastatic disease by conventional imaging, PSMA-PET results were positive in 84% of patients, detected M1 disease stage in 46% of patients, and found polymetastatic disease in 24% of patients. ... The results challenge the interpretation of previous studies, such as the EMBARK trial, and support the evolving role of PSMA-PET for patient selection in clinical and trial interventions in prostate cancer,” the authors of the new paper wrote. “Further studies are needed to assess its independent prognostic value and use for treatment guidance.”

SOURCE:

This study was led by Adrien Holzgreve, MD, and Wesley R. Armstrong, BS, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles. It was published online on January 3 in JAMA Network Open.

LIMITATIONS:

The analysis included significantly fewer patients treated with combined radical prostatectomy and salvage radiotherapy than the original EMBARK trial (29% vs 49%). Patients in this study had a lower median PSA doubling time and serum PSA level at enrollment than those in the EMBARK study. The retrospective nature of this study precluded systematic baseline imaging that would be standard for clinical trial enrollment. Additionally, while PSMA-PET offers the best diagnostic accuracy for prostate cancer staging, it can produce false-positive findings, particularly in bone metastases, with a positive predictive value of 0.84% in biochemical recurrence.

DISCLOSURES:

Holzgreve reported receiving personal fees from ABX advanced biochemical compounds outside the submitted work. This study was supported by grants from the Deutsche Forschungsgemeinschaft, the Prostate Cancer Foundation, and the Society of Nuclear Medicine and Molecular Imaging. Additional disclosures are noted in the original article.

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

TOPLINE: 

Prostate-specific membrane antigen (PSMA)–PET detected metastatic disease in 46% of patients with high-risk prostate cancer previously classified as nonmetastatic by conventional imaging. Results were positive in 84% of patients, with polymetastatic disease found in 24% of cases.

METHODOLOGY:

• Recurrent nonmetastatic hormone-sensitive prostate cancer is characterized by increasing prostate-specific antigen (PSA) levels while naive or responsive to androgen deprivation therapy, without evidence of metastasis on conventional imaging.
• A post hoc, retrospective, cross-sectional analysis included 182 patients from four prospective studies conducted from September 2016 to September 2021, with participants having recurrent prostate cancer after radical prostatectomy, definitive radiotherapy, or salvage radiotherapy.
• Inclusion criteria encompassed PSA levels > 1.0 ng/mL after radical prostatectomy and salvage radiotherapy or > 2.0 ng/mL above nadir after definitive radiotherapy, PSA doubling time ≤ 9 months, and serum testosterone ≥ 150 ng/dL.
• Researchers at the University of California, Los Angeles, performed Gallium-68-PSMA-11 PET/CT imaging with a median injection of 5.0 mCi and uptake time of 61 minutes, with 98% of patients receiving CT contrast.

TAKEAWAY:

• PSMA-PET findings were positive in 80% of patients after radical prostatectomy, 92% after definitive radiotherapy, 85% after radical prostatectomy and salvage radiotherapy, and 84% overall (153 of 182 patients).
• Distant metastatic disease was detected in 34% of patients after radical prostatectomy, 56% after definitive radiotherapy, 60% after radical prostatectomy and salvage radiotherapy, and 46% overall.
• Polymetastatic disease (≥ 5 lesions) was identified in 19% of patients after radical prostatectomy, 36% after definitive radiotherapy, 23% after radical prostatectomy and salvage radiotherapy, and 24% overall.
• According to the authors, these findings suggest that patients’ high-risk nonmetastatic hormone-sensitive prostate cancers are understaged by conventional imaging.

IN PRACTICE:

“In a cohort of patients with high-risk hormone-sensitive prostate cancer without evidence of metastatic disease by conventional imaging, PSMA-PET results were positive in 84% of patients, detected M1 disease stage in 46% of patients, and found polymetastatic disease in 24% of patients. ... The results challenge the interpretation of previous studies, such as the EMBARK trial, and support the evolving role of PSMA-PET for patient selection in clinical and trial interventions in prostate cancer,” the authors of the new paper wrote. “Further studies are needed to assess its independent prognostic value and use for treatment guidance.”

SOURCE:

This study was led by Adrien Holzgreve, MD, and Wesley R. Armstrong, BS, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles. It was published online on January 3 in JAMA Network Open.

LIMITATIONS:

The analysis included significantly fewer patients treated with combined radical prostatectomy and salvage radiotherapy than the original EMBARK trial (29% vs 49%). Patients in this study had a lower median PSA doubling time and serum PSA level at enrollment than those in the EMBARK study. The retrospective nature of this study precluded systematic baseline imaging that would be standard for clinical trial enrollment. Additionally, while PSMA-PET offers the best diagnostic accuracy for prostate cancer staging, it can produce false-positive findings, particularly in bone metastases, with a positive predictive value of 0.84% in biochemical recurrence.

DISCLOSURES:

Holzgreve reported receiving personal fees from ABX advanced biochemical compounds outside the submitted work. This study was supported by grants from the Deutsche Forschungsgemeinschaft, the Prostate Cancer Foundation, and the Society of Nuclear Medicine and Molecular Imaging. Additional disclosures are noted in the original article.

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

TOPLINE:

Combined exposure to dioxins and dioxin-like polychlorinated biphenyls (DL-PCBs) is significantly associated with an increased risk for obesity in adults, with 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD) showing the greatest contribution.

METHODOLOGY:

• Recent evidence has shown that environmental contaminants, particularly dioxins and dioxin-like polychlorinated biphenyls, may be linked to an increased risk for obesity as endocrine-disrupting chemicals.
• Researchers evaluated the relationship between mixed exposure to nine types of dioxins and DL-PCBs and obesity or obesity indices in 852 adults using data from the National Health and Nutrition Examination Survey from 2003 to 2004.
• They chose nine chemicals for analysis: 1,2,3,4,6,7,8-HpCDD; 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin (OCDD); 3,3’,4,4’,5-pentachlorodibenzofuran (PnCB); PCB28; PCB66; PCB74; PCB105; PCB118; and PCB156.
• General and abdominal obesity were present in 34% and 53.9% of participants, respectively.
• Multiple statistical approaches were employed to evaluate the association of exposures to dioxins and DL-PCBs with obesity. Mediation analysis was performed to assess the potential role of A1c in this association.

TAKEAWAY:

• Multivariable logistic regression analysis found that a single exposure to higher concentrations of 1,2,3,4,6,7,8-HpCDD; 1,2,3,4,6,7,8,9-OCDD; 3,3’,4,4’,5-PnCB; PCB74; PCB105; and PCB118 was associated with an increased risk for general and abdominal obesity (P for trend < .001 for all). A stratified analysis by sex found that except for PCB28, PCB66, PCB74, and PCB156, all chemicals were linked to increased general and abdominal obesity risk in both men and women.
• Combined exposure to dioxins and DL-PCBs was positively associated with the risk for obesity, with 1,2,3,4,6,7,8-HpCDD showing the greatest contribution.
• When considering obesity indices, 1,2,3,4,6,7,8,9-OCDD; 1,2,3,4,6,7,8-HpCDD; 3,3’,4,4’,5-PnCB; PCB74; PCB105; and PCB118 were significantly associated with body mass index and waist circumference.
• A1c levels significantly mediated the association between mixed exposure to dioxins and DL-PCBs and obesity (P < .05), with mediation proportions of 6.94% for general obesity and 5.21% for abdominal obesity.

IN PRACTICE:

“Our findings suggested that dioxins and DL-PCBs may be independent risk factors for obesity,” the authors wrote. “The hazards of dioxins on obesity should be emphasized, and additional studies are desirable to elucidate the potential mechanisms for dioxins on obesity in adults.”

SOURCE:

This study, led by Zhao-Xing Gao, Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University and Center for Big Data and Population Health of IHM, both in Hefei, China, was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The cross-sectional nature of this study prevented the establishment of causal relationships between dioxins or DL-PCBs and obesity. This study relied on a small sample. Replacing chemical concentrations below the limit of detection with fixed values may have introduced bias.

DISCLOSURES:

This study was funded by grants from the National Natural Science Foundation of China, Research Fund of Anhui Institute of Translational Medicine, and Research Fund of Center for Big Data and Population Health of IHM. The authors declared no conflicts of interest.

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

TOPLINE:

Combined exposure to dioxins and dioxin-like polychlorinated biphenyls (DL-PCBs) is significantly associated with an increased risk for obesity in adults, with 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD) showing the greatest contribution.

METHODOLOGY:

• Recent evidence has shown that environmental contaminants, particularly dioxins and dioxin-like polychlorinated biphenyls, may be linked to an increased risk for obesity as endocrine-disrupting chemicals.
• Researchers evaluated the relationship between mixed exposure to nine types of dioxins and DL-PCBs and obesity or obesity indices in 852 adults using data from the National Health and Nutrition Examination Survey from 2003 to 2004.
• They chose nine chemicals for analysis: 1,2,3,4,6,7,8-HpCDD; 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin (OCDD); 3,3’,4,4’,5-pentachlorodibenzofuran (PnCB); PCB28; PCB66; PCB74; PCB105; PCB118; and PCB156.
• General and abdominal obesity were present in 34% and 53.9% of participants, respectively.
• Multiple statistical approaches were employed to evaluate the association of exposures to dioxins and DL-PCBs with obesity. Mediation analysis was performed to assess the potential role of A1c in this association.

TAKEAWAY:

• Multivariable logistic regression analysis found that a single exposure to higher concentrations of 1,2,3,4,6,7,8-HpCDD; 1,2,3,4,6,7,8,9-OCDD; 3,3’,4,4’,5-PnCB; PCB74; PCB105; and PCB118 was associated with an increased risk for general and abdominal obesity (P for trend < .001 for all). A stratified analysis by sex found that except for PCB28, PCB66, PCB74, and PCB156, all chemicals were linked to increased general and abdominal obesity risk in both men and women.
• Combined exposure to dioxins and DL-PCBs was positively associated with the risk for obesity, with 1,2,3,4,6,7,8-HpCDD showing the greatest contribution.
• When considering obesity indices, 1,2,3,4,6,7,8,9-OCDD; 1,2,3,4,6,7,8-HpCDD; 3,3’,4,4’,5-PnCB; PCB74; PCB105; and PCB118 were significantly associated with body mass index and waist circumference.
• A1c levels significantly mediated the association between mixed exposure to dioxins and DL-PCBs and obesity (P < .05), with mediation proportions of 6.94% for general obesity and 5.21% for abdominal obesity.

IN PRACTICE:

“Our findings suggested that dioxins and DL-PCBs may be independent risk factors for obesity,” the authors wrote. “The hazards of dioxins on obesity should be emphasized, and additional studies are desirable to elucidate the potential mechanisms for dioxins on obesity in adults.”

SOURCE:

This study, led by Zhao-Xing Gao, Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University and Center for Big Data and Population Health of IHM, both in Hefei, China, was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The cross-sectional nature of this study prevented the establishment of causal relationships between dioxins or DL-PCBs and obesity. This study relied on a small sample. Replacing chemical concentrations below the limit of detection with fixed values may have introduced bias.

DISCLOSURES:

This study was funded by grants from the National Natural Science Foundation of China, Research Fund of Anhui Institute of Translational Medicine, and Research Fund of Center for Big Data and Population Health of IHM. The authors declared no conflicts of interest.

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

TOPLINE:

Combined exposure to dioxins and dioxin-like polychlorinated biphenyls (DL-PCBs) is significantly associated with an increased risk for obesity in adults, with 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD) showing the greatest contribution.

METHODOLOGY:

• Recent evidence has shown that environmental contaminants, particularly dioxins and dioxin-like polychlorinated biphenyls, may be linked to an increased risk for obesity as endocrine-disrupting chemicals.
• Researchers evaluated the relationship between mixed exposure to nine types of dioxins and DL-PCBs and obesity or obesity indices in 852 adults using data from the National Health and Nutrition Examination Survey from 2003 to 2004.
• They chose nine chemicals for analysis: 1,2,3,4,6,7,8-HpCDD; 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin (OCDD); 3,3’,4,4’,5-pentachlorodibenzofuran (PnCB); PCB28; PCB66; PCB74; PCB105; PCB118; and PCB156.
• General and abdominal obesity were present in 34% and 53.9% of participants, respectively.
• Multiple statistical approaches were employed to evaluate the association of exposures to dioxins and DL-PCBs with obesity. Mediation analysis was performed to assess the potential role of A1c in this association.

TAKEAWAY:

• Multivariable logistic regression analysis found that a single exposure to higher concentrations of 1,2,3,4,6,7,8-HpCDD; 1,2,3,4,6,7,8,9-OCDD; 3,3’,4,4’,5-PnCB; PCB74; PCB105; and PCB118 was associated with an increased risk for general and abdominal obesity (P for trend < .001 for all). A stratified analysis by sex found that except for PCB28, PCB66, PCB74, and PCB156, all chemicals were linked to increased general and abdominal obesity risk in both men and women.
• Combined exposure to dioxins and DL-PCBs was positively associated with the risk for obesity, with 1,2,3,4,6,7,8-HpCDD showing the greatest contribution.
• When considering obesity indices, 1,2,3,4,6,7,8,9-OCDD; 1,2,3,4,6,7,8-HpCDD; 3,3’,4,4’,5-PnCB; PCB74; PCB105; and PCB118 were significantly associated with body mass index and waist circumference.
• A1c levels significantly mediated the association between mixed exposure to dioxins and DL-PCBs and obesity (P < .05), with mediation proportions of 6.94% for general obesity and 5.21% for abdominal obesity.

IN PRACTICE:

“Our findings suggested that dioxins and DL-PCBs may be independent risk factors for obesity,” the authors wrote. “The hazards of dioxins on obesity should be emphasized, and additional studies are desirable to elucidate the potential mechanisms for dioxins on obesity in adults.”

SOURCE:

This study, led by Zhao-Xing Gao, Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University and Center for Big Data and Population Health of IHM, both in Hefei, China, was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The cross-sectional nature of this study prevented the establishment of causal relationships between dioxins or DL-PCBs and obesity. This study relied on a small sample. Replacing chemical concentrations below the limit of detection with fixed values may have introduced bias.

DISCLOSURES:

This study was funded by grants from the National Natural Science Foundation of China, Research Fund of Anhui Institute of Translational Medicine, and Research Fund of Center for Big Data and Population Health of IHM. The authors declared no conflicts of interest.

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

TOPLINE:

Higher levels of environmental metals in urine are associated with poorer cognitive performance and an increased risk for dementia, new research suggests.

METHODOLOGY:

• This multicenter prospective cohort study included 6303 participants from six US study centers from 2000 to 2002, with follow-up through 2018.
• Participants were aged 45-84 years (median age at baseline, 60 years; 52% women) and were free of diagnosed cardiovascular disease.
• Researchers measured urinary levels of arsenic, cadmium, cobalt, copper, lead, manganese, tungsten, uranium, and zinc.
• Neuropsychological assessments included the Digit Symbol Coding, Cognitive Abilities Screening Instrument, and Digit Span tests.
• The median follow-up duration was 11.7 years for participants with dementia and 16.8 years for those without; 559 cases of dementia were identified during the study.

TAKEAWAY:

• Lower Digit Symbol Coding scores were associated with higher urinary concentrations of arsenic (mean difference [MD] in score per interquartile range [IQR] increase, –0.03), cobalt (MD per IQR increase, –0.05), copper (MD per IQR increase, –0.05), uranium (MD per IQR increase, –0.04), and zinc (MD per IQR increase, –0.03).
• Effects for cobalt, uranium, and zinc were stronger in apolipoprotein epsilon 4 allele (APOE4) carriers vs noncarriers.
• Higher urinary levels of copper were associated with lower Digit Span scores (MD, –0.043) and elevated levels of copper (MD, –0.028) and zinc (MD, –0.024) were associated with lower global cognitive scores.
• Individuals with urinary levels of the nine-metal mixture at the 95th percentile had a 71% higher risk for dementia compared to those with levels at the 25th percentile, with the risk more pronounced in APOE4 carriers than in noncarriers (MD, –0.30 vs –0.10, respectively).

IN PRACTICE:

“We found an inverse association of essential and nonessential metals in urine, both individually and as a mixture, with the speed of mental operations, as well as a positive association of urinary metal levels with dementia risk. As metal exposure and levels in the body are modifiable, these findings could inform early screening and precision interventions for dementia prevention based on individuals’ metal exposure and genetic profiles,” the investigators wrote.

 

SOURCE:

The study was led by Arce Domingo-Relloso, PhD, Columbia University Mailman School of Public Health, New York City. It was published online in JAMA Network Open.

 

LIMITATIONS:

Data may have been missed for patients with dementia who were never hospitalized, died, or were lost to follow-up. The dementia diagnosis included nonspecific International Classification of Diseases codes, potentially leading to false-positive reports. In addition, the sample size was not sufficient to evaluate the associations between metal exposure and cognitive test scores for carriers of two APOE4 alleles.

 

DISCLOSURES:

The study was supported by the National Heart, Lung, and Blood Institute. Several authors reported receiving grants from the National Institutes of Health and consulting fees, editorial stipends, teaching fees, or unrelated grant funding from various sources, which are fully listed in the original article.

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

TOPLINE:

Higher levels of environmental metals in urine are associated with poorer cognitive performance and an increased risk for dementia, new research suggests.

METHODOLOGY:

• This multicenter prospective cohort study included 6303 participants from six US study centers from 2000 to 2002, with follow-up through 2018.
• Participants were aged 45-84 years (median age at baseline, 60 years; 52% women) and were free of diagnosed cardiovascular disease.
• Researchers measured urinary levels of arsenic, cadmium, cobalt, copper, lead, manganese, tungsten, uranium, and zinc.
• Neuropsychological assessments included the Digit Symbol Coding, Cognitive Abilities Screening Instrument, and Digit Span tests.
• The median follow-up duration was 11.7 years for participants with dementia and 16.8 years for those without; 559 cases of dementia were identified during the study.

TAKEAWAY:

• Lower Digit Symbol Coding scores were associated with higher urinary concentrations of arsenic (mean difference [MD] in score per interquartile range [IQR] increase, –0.03), cobalt (MD per IQR increase, –0.05), copper (MD per IQR increase, –0.05), uranium (MD per IQR increase, –0.04), and zinc (MD per IQR increase, –0.03).
• Effects for cobalt, uranium, and zinc were stronger in apolipoprotein epsilon 4 allele (APOE4) carriers vs noncarriers.
• Higher urinary levels of copper were associated with lower Digit Span scores (MD, –0.043) and elevated levels of copper (MD, –0.028) and zinc (MD, –0.024) were associated with lower global cognitive scores.
• Individuals with urinary levels of the nine-metal mixture at the 95th percentile had a 71% higher risk for dementia compared to those with levels at the 25th percentile, with the risk more pronounced in APOE4 carriers than in noncarriers (MD, –0.30 vs –0.10, respectively).

IN PRACTICE:

“We found an inverse association of essential and nonessential metals in urine, both individually and as a mixture, with the speed of mental operations, as well as a positive association of urinary metal levels with dementia risk. As metal exposure and levels in the body are modifiable, these findings could inform early screening and precision interventions for dementia prevention based on individuals’ metal exposure and genetic profiles,” the investigators wrote.

 

SOURCE:

The study was led by Arce Domingo-Relloso, PhD, Columbia University Mailman School of Public Health, New York City. It was published online in JAMA Network Open.

 

LIMITATIONS:

Data may have been missed for patients with dementia who were never hospitalized, died, or were lost to follow-up. The dementia diagnosis included nonspecific International Classification of Diseases codes, potentially leading to false-positive reports. In addition, the sample size was not sufficient to evaluate the associations between metal exposure and cognitive test scores for carriers of two APOE4 alleles.

 

DISCLOSURES:

The study was supported by the National Heart, Lung, and Blood Institute. Several authors reported receiving grants from the National Institutes of Health and consulting fees, editorial stipends, teaching fees, or unrelated grant funding from various sources, which are fully listed in the original article.

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

TOPLINE:

Higher levels of environmental metals in urine are associated with poorer cognitive performance and an increased risk for dementia, new research suggests.

METHODOLOGY:

• This multicenter prospective cohort study included 6303 participants from six US study centers from 2000 to 2002, with follow-up through 2018.
• Participants were aged 45-84 years (median age at baseline, 60 years; 52% women) and were free of diagnosed cardiovascular disease.
• Researchers measured urinary levels of arsenic, cadmium, cobalt, copper, lead, manganese, tungsten, uranium, and zinc.
• Neuropsychological assessments included the Digit Symbol Coding, Cognitive Abilities Screening Instrument, and Digit Span tests.
• The median follow-up duration was 11.7 years for participants with dementia and 16.8 years for those without; 559 cases of dementia were identified during the study.

TAKEAWAY:

• Lower Digit Symbol Coding scores were associated with higher urinary concentrations of arsenic (mean difference [MD] in score per interquartile range [IQR] increase, –0.03), cobalt (MD per IQR increase, –0.05), copper (MD per IQR increase, –0.05), uranium (MD per IQR increase, –0.04), and zinc (MD per IQR increase, –0.03).
• Effects for cobalt, uranium, and zinc were stronger in apolipoprotein epsilon 4 allele (APOE4) carriers vs noncarriers.
• Higher urinary levels of copper were associated with lower Digit Span scores (MD, –0.043) and elevated levels of copper (MD, –0.028) and zinc (MD, –0.024) were associated with lower global cognitive scores.
• Individuals with urinary levels of the nine-metal mixture at the 95th percentile had a 71% higher risk for dementia compared to those with levels at the 25th percentile, with the risk more pronounced in APOE4 carriers than in noncarriers (MD, –0.30 vs –0.10, respectively).

IN PRACTICE:

“We found an inverse association of essential and nonessential metals in urine, both individually and as a mixture, with the speed of mental operations, as well as a positive association of urinary metal levels with dementia risk. As metal exposure and levels in the body are modifiable, these findings could inform early screening and precision interventions for dementia prevention based on individuals’ metal exposure and genetic profiles,” the investigators wrote.

 

SOURCE:

The study was led by Arce Domingo-Relloso, PhD, Columbia University Mailman School of Public Health, New York City. It was published online in JAMA Network Open.

 

LIMITATIONS:

Data may have been missed for patients with dementia who were never hospitalized, died, or were lost to follow-up. The dementia diagnosis included nonspecific International Classification of Diseases codes, potentially leading to false-positive reports. In addition, the sample size was not sufficient to evaluate the associations between metal exposure and cognitive test scores for carriers of two APOE4 alleles.

 

DISCLOSURES:

The study was supported by the National Heart, Lung, and Blood Institute. Several authors reported receiving grants from the National Institutes of Health and consulting fees, editorial stipends, teaching fees, or unrelated grant funding from various sources, which are fully listed in the original article.

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

An individual’s estimated risk of having a heart attack or stroke in the next 10 years is widely used to guide preventative medication prescriptions with statins or antihypertensive drugs in those who have not yet had such an event.

To estimate that risk, doctors use equations that include different risk factors, such as age, cholesterol levels, and blood pressure. The current equations, known as the pooled cohort equations, are considered to be outdated as they were developed in 2013 based on population data from the 1960s and 70s. A new set of risk equations — known as the PREVENT equations — were developed by the American Heart Association (AHA) in 2023, and are based on a more contemporary population. It is anticipated that AHA will recommend these new risk equations be used in clinical practice in the next primary prevention guidelines.

But could these new risk equations do more harm than good?

Two recent studies found that applying the PREVENT risk equations to the US population results in a much lower overall level of risk compared with the pooled cohort equations. And, if the current threshold for starting statin treatment — which is an estimated 7.5% risk of having a heart attack or stroke in the next 10 years — is kept the same, this would result in many fewer patients being eligible for statin treatment.

As cardiovascular risk is also used to guide antihypertensive treatment, the new risk equations would also result in fewer people with borderline high blood pressure being eligible for those medications.

This has raised concerns in the medical community, where there is a widespread view that many more people would benefit from primary prevention treatment, and that anything that may cause fewer people to receive these medications would be harmful. 

“I believe the new equations more accurately predict the risk of the current US population, but we need to be aware of what effect that may have on use of statins,” said Tim Anderson, MD, who studies healthcare delivery at the University of Pittsburgh in Pennsylvania and is lead author of one of the studies evaluating the equations.

Anderson told this news organization that the pooled cohort equations have long been viewed as problematic. 

“Because these equations were based on cohorts from the 1960s and 70s, it is believed they overestimate the current population’s risk of MI and stroke as the burden of disease has shifted in the intervening 50-60 years,” he said.

 

Current Equations Overestimate Risk

The new equations are based on more recent, representative, and diverse cohorts that capture a wider spectrum of the population in terms of race, ethnicity, and socioeconomic status. They also include factors that are now known to be relevant to cardiovascular risk, such as chronic kidney disease.

Anderson compared how the two sets of equations estimated risk of cardiovascular disease in the next 10 years in the US population using the NHANES survey — a large nationally representative survey conducted between 2017 and 2020. 

He found that the pooled cohort equations estimated the population average 10-year risk of cardiovascular disease to be about 8%, but the PREVENT equations estimated it at just over 4%.

“The new equations estimate that the middle-aged US population have almost half the level of risk of MI and stroke over next 10 years compared with the equations used currently. So, we will substantially change risk estimates if the new equations are introduced into practice,” Anderson said. 

The study found that, if the PREVENT equations are adopted in the next set of primary prevention guidelines and the current threshold of a 7.5% risk of having an MI or stroke in the next 10 years is maintained as the starting point for statin treatment, then 17.3 million adults who were previously recommended primary prevention statin therapy would no longer be eligible.

A second, similar study, conducted by a different team of US researchers, estimated that using PREVENT would decrease the number of US adults receiving or recommended for statin therapy by 14.3 million and antihypertensive therapy by 2.62 million.

The researchers, led by James A. Diao, MD, from Harvard Medical School, Boston, Massachusetts, also suggested that over 10 years, reductions in treatment eligibility could result in an estimated 107,000 additional MI or stroke events.

Anderson points out that using the new equations would not affect the highest-risk patients. “They are still going to be high risk whichever equations are used. If you smoke a pack of cigarettes a day, have very high blood pressure or cholesterol and are older, then you are high risk. That part hasn’t changed. These people will qualify for statin treatment many times over with both sets of guidelines,” he said. 

Rather it will be the large population at moderate risk of cardiovascular disease that will be affected, with far fewer of these individuals likely to get statins.

“If you are on the fence about whether to take a statin or not and you’re currently just on the threshold where they might be recommended then these new equations could mean that you’ll be less likely to be offered them,” he said. “Using the new equations may result in a delay of a couple of years to have that conversation.”

 

A Red Flag

Steve Nissen, MD, a cardiologist at the Cleveland Clinic in Ohio, is not a fan of cardiovascular risk equations in general. He points out that less than half of those currently eligible for statins are actually treated. And he believes the studies suggesting fewer people will be eligible with the new risk equations raise a red flag on whether they should be used.

“Anything that may result in fewer people being treated is a huge problem,” he told this news organization. “We have abundant evidence that we should be treating more people, not fewer people. Every study we have done has shown benefit with statins.”

The risk calculators were initially developed to limit use of statins and other medications to high-risk patients, he said, but now that we know more about safety of these drugs, it’s clear that the risks are almost nonexistent. 

“We really need something else to guide the prescription of statins,” said Nissen.

Nissen suggests the risk calculators and guidelines have resulted in undertreatment of the population because they lack nuance and put too much emphasis on age. We should be more interested in reducing the lifetime risk of cardiovascular events, he said. “Calculators don’t do a good job of that. Their time horizons are too short. Young people with a family history of cardiovascular disease may have a low 10-year risk on a risk calculator but their lifetime risk is elevated, and as such, they should be considered for statin treatment. We need to find a more nuanced approach to understanding the lifetime risk of individuals,” he said. 

Nissen said risk calculators can be useful in high-risk patients to help demonstrate their need for treatment. “I can show them the calculator and that they have a 20% chance of an event — that can help convince them to take a statin.” 

But at the lower end of the risk scale, “all it does is keep patients who should be getting treatment from having that treatment.”

Nissen said changing the risk calculator won’t affect how he treats patients. “I use judgment to decide who to treat based on scientific literature and the patient in front of me. We will engage in a discussion and make a shared decision on what is the best course of action. Calculators will never be a substitute for medical judgment,” he said.

 

Equations Don’t Decide

Sadiya Khan, MD, a cardiologist at Northwestern University, Evanston, Illinois, and lead author of the PREVENT equations, told this news organization that it is important to put this discussion into context.

“The two recent papers do a good job of describing differences in predictive risk between the two sets of equations but that’s where they stop,” she said. “The translation from that to the decision on who should or should not be on statins or other medications is a step too far.”

Clinical guidelines will need to be updated to take the PREVENT equations into account, as Khan argued in a JAMA editorial. So it is not clear whether the current 7.5% 10-year risk figure will remain the threshold to start treatment. Khan anticipates the guidelines committee will have to re-evaluate that threshold.

“The 7.5% risk threshold was advised in the 2013 guidelines, based on what we knew then about the balance between benefit and harm and with the knowledge that the risk equations overestimated risk,” she said. “We now have a lot more data on the safety of statin therapy. We see this frequently in preventive care. Treatments often becomes more widespread in time and use expands into lower-risk patients.”

She also pointed out that the current primary prevention guidelines encourage consideration of other factors, not just predictive risk scores, when thinking about starting statins, including very high LDL cholesterol, family history, and apo B and Lp(a) levels.

“The recommendation on who would qualify for statin therapy is not based on one number,” she said. “It is based on many considerations, including both qualitative and quantitative factors, and discussions between the patient and the doctor. It is not a straightforward yes or no based on a 7.5% risk threshold.”

The equations, she said, should only be viewed as the first step in the process, and she said she agrees with Nissen that when applying the equations, doctors need to use additional data from each individual patient to make a judgment. “Equations do not decide who gets treated. Clinical practice guidelines do that.” 

Khan also agreed with Nissen that more effort is needed to identify longer term cardiovascular risk in younger people, and so the PREVENT equations include 30-year risk estimates.

“I totally agree that we need to start earlier in having these prevention conversations. The PREVENT model starts at age 30 which is 10 years earlier than the pooled cohort equations and they add a 30-year time horizon as well as the 10-year period for these discussions on predicted risk estimates,” she said. “We need to make sure we are not missing risk in young adults just because we are waiting for them to get into some arbitrary age category.”

Khan says she believes that, used correctly, the new equations will not limit access to statins or other cardiovascular treatments. “Because they are a more accurate reflection of risk in the contemporary population, the new PREVENT equations should identify the correct patients to be treated, within the confines of knowing that no risk prediction equation is perfect,” she said. “And if everything else is considered as well, not just the numbers in the risk equations, it shouldn’t result in fewer patients being treated.”

Anderson reported receiving grants from the American Heart Association, the American College of Cardiology, and the US Deprescribing Research Network. Nissen is leading a development program for a nonprescription low dose of rosuvastatin. He is also involved in trials of a new cholesterol lowering drug, obicetrapib, and on trials on drugs that lower Lp(a). Khan reported receiving grants from the American Heart Association and National Heart, Lung, and Blood Institute.

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

An individual’s estimated risk of having a heart attack or stroke in the next 10 years is widely used to guide preventative medication prescriptions with statins or antihypertensive drugs in those who have not yet had such an event.

To estimate that risk, doctors use equations that include different risk factors, such as age, cholesterol levels, and blood pressure. The current equations, known as the pooled cohort equations, are considered to be outdated as they were developed in 2013 based on population data from the 1960s and 70s. A new set of risk equations — known as the PREVENT equations — were developed by the American Heart Association (AHA) in 2023, and are based on a more contemporary population. It is anticipated that AHA will recommend these new risk equations be used in clinical practice in the next primary prevention guidelines.

But could these new risk equations do more harm than good?

Two recent studies found that applying the PREVENT risk equations to the US population results in a much lower overall level of risk compared with the pooled cohort equations. And, if the current threshold for starting statin treatment — which is an estimated 7.5% risk of having a heart attack or stroke in the next 10 years — is kept the same, this would result in many fewer patients being eligible for statin treatment.

As cardiovascular risk is also used to guide antihypertensive treatment, the new risk equations would also result in fewer people with borderline high blood pressure being eligible for those medications.

This has raised concerns in the medical community, where there is a widespread view that many more people would benefit from primary prevention treatment, and that anything that may cause fewer people to receive these medications would be harmful. 

“I believe the new equations more accurately predict the risk of the current US population, but we need to be aware of what effect that may have on use of statins,” said Tim Anderson, MD, who studies healthcare delivery at the University of Pittsburgh in Pennsylvania and is lead author of one of the studies evaluating the equations.

Anderson told this news organization that the pooled cohort equations have long been viewed as problematic. 

“Because these equations were based on cohorts from the 1960s and 70s, it is believed they overestimate the current population’s risk of MI and stroke as the burden of disease has shifted in the intervening 50-60 years,” he said.

 

Current Equations Overestimate Risk

The new equations are based on more recent, representative, and diverse cohorts that capture a wider spectrum of the population in terms of race, ethnicity, and socioeconomic status. They also include factors that are now known to be relevant to cardiovascular risk, such as chronic kidney disease.

Anderson compared how the two sets of equations estimated risk of cardiovascular disease in the next 10 years in the US population using the NHANES survey — a large nationally representative survey conducted between 2017 and 2020. 

He found that the pooled cohort equations estimated the population average 10-year risk of cardiovascular disease to be about 8%, but the PREVENT equations estimated it at just over 4%.

“The new equations estimate that the middle-aged US population have almost half the level of risk of MI and stroke over next 10 years compared with the equations used currently. So, we will substantially change risk estimates if the new equations are introduced into practice,” Anderson said. 

The study found that, if the PREVENT equations are adopted in the next set of primary prevention guidelines and the current threshold of a 7.5% risk of having an MI or stroke in the next 10 years is maintained as the starting point for statin treatment, then 17.3 million adults who were previously recommended primary prevention statin therapy would no longer be eligible.

A second, similar study, conducted by a different team of US researchers, estimated that using PREVENT would decrease the number of US adults receiving or recommended for statin therapy by 14.3 million and antihypertensive therapy by 2.62 million.

The researchers, led by James A. Diao, MD, from Harvard Medical School, Boston, Massachusetts, also suggested that over 10 years, reductions in treatment eligibility could result in an estimated 107,000 additional MI or stroke events.

Anderson points out that using the new equations would not affect the highest-risk patients. “They are still going to be high risk whichever equations are used. If you smoke a pack of cigarettes a day, have very high blood pressure or cholesterol and are older, then you are high risk. That part hasn’t changed. These people will qualify for statin treatment many times over with both sets of guidelines,” he said. 

Rather it will be the large population at moderate risk of cardiovascular disease that will be affected, with far fewer of these individuals likely to get statins.

“If you are on the fence about whether to take a statin or not and you’re currently just on the threshold where they might be recommended then these new equations could mean that you’ll be less likely to be offered them,” he said. “Using the new equations may result in a delay of a couple of years to have that conversation.”

 

A Red Flag

Steve Nissen, MD, a cardiologist at the Cleveland Clinic in Ohio, is not a fan of cardiovascular risk equations in general. He points out that less than half of those currently eligible for statins are actually treated. And he believes the studies suggesting fewer people will be eligible with the new risk equations raise a red flag on whether they should be used.

“Anything that may result in fewer people being treated is a huge problem,” he told this news organization. “We have abundant evidence that we should be treating more people, not fewer people. Every study we have done has shown benefit with statins.”

The risk calculators were initially developed to limit use of statins and other medications to high-risk patients, he said, but now that we know more about safety of these drugs, it’s clear that the risks are almost nonexistent. 

“We really need something else to guide the prescription of statins,” said Nissen.

Nissen suggests the risk calculators and guidelines have resulted in undertreatment of the population because they lack nuance and put too much emphasis on age. We should be more interested in reducing the lifetime risk of cardiovascular events, he said. “Calculators don’t do a good job of that. Their time horizons are too short. Young people with a family history of cardiovascular disease may have a low 10-year risk on a risk calculator but their lifetime risk is elevated, and as such, they should be considered for statin treatment. We need to find a more nuanced approach to understanding the lifetime risk of individuals,” he said. 

Nissen said risk calculators can be useful in high-risk patients to help demonstrate their need for treatment. “I can show them the calculator and that they have a 20% chance of an event — that can help convince them to take a statin.” 

But at the lower end of the risk scale, “all it does is keep patients who should be getting treatment from having that treatment.”

Nissen said changing the risk calculator won’t affect how he treats patients. “I use judgment to decide who to treat based on scientific literature and the patient in front of me. We will engage in a discussion and make a shared decision on what is the best course of action. Calculators will never be a substitute for medical judgment,” he said.

 

Equations Don’t Decide

Sadiya Khan, MD, a cardiologist at Northwestern University, Evanston, Illinois, and lead author of the PREVENT equations, told this news organization that it is important to put this discussion into context.

“The two recent papers do a good job of describing differences in predictive risk between the two sets of equations but that’s where they stop,” she said. “The translation from that to the decision on who should or should not be on statins or other medications is a step too far.”

Clinical guidelines will need to be updated to take the PREVENT equations into account, as Khan argued in a JAMA editorial. So it is not clear whether the current 7.5% 10-year risk figure will remain the threshold to start treatment. Khan anticipates the guidelines committee will have to re-evaluate that threshold.

“The 7.5% risk threshold was advised in the 2013 guidelines, based on what we knew then about the balance between benefit and harm and with the knowledge that the risk equations overestimated risk,” she said. “We now have a lot more data on the safety of statin therapy. We see this frequently in preventive care. Treatments often becomes more widespread in time and use expands into lower-risk patients.”

She also pointed out that the current primary prevention guidelines encourage consideration of other factors, not just predictive risk scores, when thinking about starting statins, including very high LDL cholesterol, family history, and apo B and Lp(a) levels.

“The recommendation on who would qualify for statin therapy is not based on one number,” she said. “It is based on many considerations, including both qualitative and quantitative factors, and discussions between the patient and the doctor. It is not a straightforward yes or no based on a 7.5% risk threshold.”

The equations, she said, should only be viewed as the first step in the process, and she said she agrees with Nissen that when applying the equations, doctors need to use additional data from each individual patient to make a judgment. “Equations do not decide who gets treated. Clinical practice guidelines do that.” 

Khan also agreed with Nissen that more effort is needed to identify longer term cardiovascular risk in younger people, and so the PREVENT equations include 30-year risk estimates.

“I totally agree that we need to start earlier in having these prevention conversations. The PREVENT model starts at age 30 which is 10 years earlier than the pooled cohort equations and they add a 30-year time horizon as well as the 10-year period for these discussions on predicted risk estimates,” she said. “We need to make sure we are not missing risk in young adults just because we are waiting for them to get into some arbitrary age category.”

Khan says she believes that, used correctly, the new equations will not limit access to statins or other cardiovascular treatments. “Because they are a more accurate reflection of risk in the contemporary population, the new PREVENT equations should identify the correct patients to be treated, within the confines of knowing that no risk prediction equation is perfect,” she said. “And if everything else is considered as well, not just the numbers in the risk equations, it shouldn’t result in fewer patients being treated.”

Anderson reported receiving grants from the American Heart Association, the American College of Cardiology, and the US Deprescribing Research Network. Nissen is leading a development program for a nonprescription low dose of rosuvastatin. He is also involved in trials of a new cholesterol lowering drug, obicetrapib, and on trials on drugs that lower Lp(a). Khan reported receiving grants from the American Heart Association and National Heart, Lung, and Blood Institute.

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

An individual’s estimated risk of having a heart attack or stroke in the next 10 years is widely used to guide preventative medication prescriptions with statins or antihypertensive drugs in those who have not yet had such an event.

To estimate that risk, doctors use equations that include different risk factors, such as age, cholesterol levels, and blood pressure. The current equations, known as the pooled cohort equations, are considered to be outdated as they were developed in 2013 based on population data from the 1960s and 70s. A new set of risk equations — known as the PREVENT equations — were developed by the American Heart Association (AHA) in 2023, and are based on a more contemporary population. It is anticipated that AHA will recommend these new risk equations be used in clinical practice in the next primary prevention guidelines.

But could these new risk equations do more harm than good?

Two recent studies found that applying the PREVENT risk equations to the US population results in a much lower overall level of risk compared with the pooled cohort equations. And, if the current threshold for starting statin treatment — which is an estimated 7.5% risk of having a heart attack or stroke in the next 10 years — is kept the same, this would result in many fewer patients being eligible for statin treatment.

As cardiovascular risk is also used to guide antihypertensive treatment, the new risk equations would also result in fewer people with borderline high blood pressure being eligible for those medications.

This has raised concerns in the medical community, where there is a widespread view that many more people would benefit from primary prevention treatment, and that anything that may cause fewer people to receive these medications would be harmful. 

“I believe the new equations more accurately predict the risk of the current US population, but we need to be aware of what effect that may have on use of statins,” said Tim Anderson, MD, who studies healthcare delivery at the University of Pittsburgh in Pennsylvania and is lead author of one of the studies evaluating the equations.

Anderson told this news organization that the pooled cohort equations have long been viewed as problematic. 

“Because these equations were based on cohorts from the 1960s and 70s, it is believed they overestimate the current population’s risk of MI and stroke as the burden of disease has shifted in the intervening 50-60 years,” he said.

 

Current Equations Overestimate Risk

The new equations are based on more recent, representative, and diverse cohorts that capture a wider spectrum of the population in terms of race, ethnicity, and socioeconomic status. They also include factors that are now known to be relevant to cardiovascular risk, such as chronic kidney disease.

Anderson compared how the two sets of equations estimated risk of cardiovascular disease in the next 10 years in the US population using the NHANES survey — a large nationally representative survey conducted between 2017 and 2020. 

He found that the pooled cohort equations estimated the population average 10-year risk of cardiovascular disease to be about 8%, but the PREVENT equations estimated it at just over 4%.

“The new equations estimate that the middle-aged US population have almost half the level of risk of MI and stroke over next 10 years compared with the equations used currently. So, we will substantially change risk estimates if the new equations are introduced into practice,” Anderson said. 

The study found that, if the PREVENT equations are adopted in the next set of primary prevention guidelines and the current threshold of a 7.5% risk of having an MI or stroke in the next 10 years is maintained as the starting point for statin treatment, then 17.3 million adults who were previously recommended primary prevention statin therapy would no longer be eligible.

A second, similar study, conducted by a different team of US researchers, estimated that using PREVENT would decrease the number of US adults receiving or recommended for statin therapy by 14.3 million and antihypertensive therapy by 2.62 million.

The researchers, led by James A. Diao, MD, from Harvard Medical School, Boston, Massachusetts, also suggested that over 10 years, reductions in treatment eligibility could result in an estimated 107,000 additional MI or stroke events.

Anderson points out that using the new equations would not affect the highest-risk patients. “They are still going to be high risk whichever equations are used. If you smoke a pack of cigarettes a day, have very high blood pressure or cholesterol and are older, then you are high risk. That part hasn’t changed. These people will qualify for statin treatment many times over with both sets of guidelines,” he said. 

Rather it will be the large population at moderate risk of cardiovascular disease that will be affected, with far fewer of these individuals likely to get statins.

“If you are on the fence about whether to take a statin or not and you’re currently just on the threshold where they might be recommended then these new equations could mean that you’ll be less likely to be offered them,” he said. “Using the new equations may result in a delay of a couple of years to have that conversation.”

 

A Red Flag

Steve Nissen, MD, a cardiologist at the Cleveland Clinic in Ohio, is not a fan of cardiovascular risk equations in general. He points out that less than half of those currently eligible for statins are actually treated. And he believes the studies suggesting fewer people will be eligible with the new risk equations raise a red flag on whether they should be used.

“Anything that may result in fewer people being treated is a huge problem,” he told this news organization. “We have abundant evidence that we should be treating more people, not fewer people. Every study we have done has shown benefit with statins.”

The risk calculators were initially developed to limit use of statins and other medications to high-risk patients, he said, but now that we know more about safety of these drugs, it’s clear that the risks are almost nonexistent. 

“We really need something else to guide the prescription of statins,” said Nissen.

Nissen suggests the risk calculators and guidelines have resulted in undertreatment of the population because they lack nuance and put too much emphasis on age. We should be more interested in reducing the lifetime risk of cardiovascular events, he said. “Calculators don’t do a good job of that. Their time horizons are too short. Young people with a family history of cardiovascular disease may have a low 10-year risk on a risk calculator but their lifetime risk is elevated, and as such, they should be considered for statin treatment. We need to find a more nuanced approach to understanding the lifetime risk of individuals,” he said. 

Nissen said risk calculators can be useful in high-risk patients to help demonstrate their need for treatment. “I can show them the calculator and that they have a 20% chance of an event — that can help convince them to take a statin.” 

But at the lower end of the risk scale, “all it does is keep patients who should be getting treatment from having that treatment.”

Nissen said changing the risk calculator won’t affect how he treats patients. “I use judgment to decide who to treat based on scientific literature and the patient in front of me. We will engage in a discussion and make a shared decision on what is the best course of action. Calculators will never be a substitute for medical judgment,” he said.

 

Equations Don’t Decide

Sadiya Khan, MD, a cardiologist at Northwestern University, Evanston, Illinois, and lead author of the PREVENT equations, told this news organization that it is important to put this discussion into context.

“The two recent papers do a good job of describing differences in predictive risk between the two sets of equations but that’s where they stop,” she said. “The translation from that to the decision on who should or should not be on statins or other medications is a step too far.”

Clinical guidelines will need to be updated to take the PREVENT equations into account, as Khan argued in a JAMA editorial. So it is not clear whether the current 7.5% 10-year risk figure will remain the threshold to start treatment. Khan anticipates the guidelines committee will have to re-evaluate that threshold.

“The 7.5% risk threshold was advised in the 2013 guidelines, based on what we knew then about the balance between benefit and harm and with the knowledge that the risk equations overestimated risk,” she said. “We now have a lot more data on the safety of statin therapy. We see this frequently in preventive care. Treatments often becomes more widespread in time and use expands into lower-risk patients.”

She also pointed out that the current primary prevention guidelines encourage consideration of other factors, not just predictive risk scores, when thinking about starting statins, including very high LDL cholesterol, family history, and apo B and Lp(a) levels.

“The recommendation on who would qualify for statin therapy is not based on one number,” she said. “It is based on many considerations, including both qualitative and quantitative factors, and discussions between the patient and the doctor. It is not a straightforward yes or no based on a 7.5% risk threshold.”

The equations, she said, should only be viewed as the first step in the process, and she said she agrees with Nissen that when applying the equations, doctors need to use additional data from each individual patient to make a judgment. “Equations do not decide who gets treated. Clinical practice guidelines do that.” 

Khan also agreed with Nissen that more effort is needed to identify longer term cardiovascular risk in younger people, and so the PREVENT equations include 30-year risk estimates.

“I totally agree that we need to start earlier in having these prevention conversations. The PREVENT model starts at age 30 which is 10 years earlier than the pooled cohort equations and they add a 30-year time horizon as well as the 10-year period for these discussions on predicted risk estimates,” she said. “We need to make sure we are not missing risk in young adults just because we are waiting for them to get into some arbitrary age category.”

Khan says she believes that, used correctly, the new equations will not limit access to statins or other cardiovascular treatments. “Because they are a more accurate reflection of risk in the contemporary population, the new PREVENT equations should identify the correct patients to be treated, within the confines of knowing that no risk prediction equation is perfect,” she said. “And if everything else is considered as well, not just the numbers in the risk equations, it shouldn’t result in fewer patients being treated.”

Anderson reported receiving grants from the American Heart Association, the American College of Cardiology, and the US Deprescribing Research Network. Nissen is leading a development program for a nonprescription low dose of rosuvastatin. He is also involved in trials of a new cholesterol lowering drug, obicetrapib, and on trials on drugs that lower Lp(a). Khan reported receiving grants from the American Heart Association and National Heart, Lung, and Blood Institute.

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