Clinical Endocrinology News

The quality and credibility of scientific publications have received increasing scrutiny. Findings from studies by Maria Ángeles Oviedo-García, PhD, from the Department of Business and Marketing at the University of Seville in Spain, highlight growing concerns about the integrity of published research. Insights from the journal Science and the US blog Retraction Watch reveal similar concerns regarding research integrity.

Artificial Intelligence (AI) Spurs Low-Quality Submissions

According to a report in Science, journals are inundated with low-quality contributions such as letters and comments generated by AI. Daniel Prevedello, MD, editor in chief of Neurosurgical Review, announced that the journal would temporarily stop accepting these submissions because of their poor quality.

Neurosurgical Review is not the only journal to experience low-quality submissions. In the journal Oral Oncology Reports (Elsevier), comments comprised 70% of the content, whereas in the International Journal of Surgery Open (Wolters Kluwer), they accounted for nearly half. In Neurosurgical Review, letters, comments, and editorials made up 58% of the total content from January to October 2024, compared with only 9% in the previous year.

This trend benefits authors by allowing them to inflate their publication lists with quickly produced contributions that bypass peer review. Publishers may also profit, as many charge fees to publish comments. Additionally, universities and research institutions find this type of content generation useful as more publications can enhance their reputation.

 

Concerns Over Peer Reviews

The troubling behavior described by Oviedo-García in the journal Scientometrics raises further doubts. An analysis of 263 peer reviews from 37 journals revealed that reviewers often used identical or very similar phrases in their evaluations, regardless of the content. In one case, the reviewer used the same wording in 52 reviews. This suggests that some reviewers read the studies that they are supposed to evaluate only superficially. Such practices can lead to valueless reviews and jeopardize the integrity of scientific literature. “Some other researchers will probably base their future research on these fake reports, which is frightening, especially when it comes to health and medicine,” Oviedo-García stated.

She suspects that the reviewers may have relied on templates to produce their reports quickly. This allowed them to list this work on their resumes for potential career advantages. Some reviewers have reportedly even “requested” the authors of the studies they reviewed to cite their own scientific work.

 

AI Complicates Peer Review

The process of research and publication has become increasingly challenging in recent years, and more standard and predatory journals allow anyone to publish their work for a fee. Roger W. Byard, MD, PhD, from the University of Adelaide in Australia, explained this trend in the journal Forensic Science, Medicine and Pathology. AI is increasingly being used to generate articles. At international conferences, experts have highlighted claims that AI can complete papers in just a few weeks and dissertations in less than a year. According to the authors of a letter in Critical Care, generative AI is infiltrating the peer review process.

Moreover, the peer review process can be bypassed by publishing research findings on online platforms (eg, preprint servers). Another issue is that some publications have hundreds of authors who can extend their publication list in this manner, even if their contribution to the publication is ambiguous or not substantial.

In a guest article for the Laborjournal, Ulrich Dirnagl, MD, PhD, from the Charité — Universitätsmedizin Berlin in Germany, emphasized that the scientific papers have become so complex that two or three experts often cannot thoroughly assess everything presented. The review process is time-consuming and can take several days for reviewers. Currently, very few people have time, especially because it is an unpaid and anonymous task. Dirnagl stated, “the self-correction of science no longer works as it claims.”

The old Russian saying ‘Dowjerjaj, no prowjerjaj: Trust, but verify’  remains a timeless recommendation that is likely to stay relevant for years to come.

This story was translated from Univadis Germany 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.

The quality and credibility of scientific publications have received increasing scrutiny. Findings from studies by Maria Ángeles Oviedo-García, PhD, from the Department of Business and Marketing at the University of Seville in Spain, highlight growing concerns about the integrity of published research. Insights from the journal Science and the US blog Retraction Watch reveal similar concerns regarding research integrity.

Artificial Intelligence (AI) Spurs Low-Quality Submissions

According to a report in Science, journals are inundated with low-quality contributions such as letters and comments generated by AI. Daniel Prevedello, MD, editor in chief of Neurosurgical Review, announced that the journal would temporarily stop accepting these submissions because of their poor quality.

Neurosurgical Review is not the only journal to experience low-quality submissions. In the journal Oral Oncology Reports (Elsevier), comments comprised 70% of the content, whereas in the International Journal of Surgery Open (Wolters Kluwer), they accounted for nearly half. In Neurosurgical Review, letters, comments, and editorials made up 58% of the total content from January to October 2024, compared with only 9% in the previous year.

This trend benefits authors by allowing them to inflate their publication lists with quickly produced contributions that bypass peer review. Publishers may also profit, as many charge fees to publish comments. Additionally, universities and research institutions find this type of content generation useful as more publications can enhance their reputation.

 

Concerns Over Peer Reviews

The troubling behavior described by Oviedo-García in the journal Scientometrics raises further doubts. An analysis of 263 peer reviews from 37 journals revealed that reviewers often used identical or very similar phrases in their evaluations, regardless of the content. In one case, the reviewer used the same wording in 52 reviews. This suggests that some reviewers read the studies that they are supposed to evaluate only superficially. Such practices can lead to valueless reviews and jeopardize the integrity of scientific literature. “Some other researchers will probably base their future research on these fake reports, which is frightening, especially when it comes to health and medicine,” Oviedo-García stated.

She suspects that the reviewers may have relied on templates to produce their reports quickly. This allowed them to list this work on their resumes for potential career advantages. Some reviewers have reportedly even “requested” the authors of the studies they reviewed to cite their own scientific work.

 

AI Complicates Peer Review

The process of research and publication has become increasingly challenging in recent years, and more standard and predatory journals allow anyone to publish their work for a fee. Roger W. Byard, MD, PhD, from the University of Adelaide in Australia, explained this trend in the journal Forensic Science, Medicine and Pathology. AI is increasingly being used to generate articles. At international conferences, experts have highlighted claims that AI can complete papers in just a few weeks and dissertations in less than a year. According to the authors of a letter in Critical Care, generative AI is infiltrating the peer review process.

Moreover, the peer review process can be bypassed by publishing research findings on online platforms (eg, preprint servers). Another issue is that some publications have hundreds of authors who can extend their publication list in this manner, even if their contribution to the publication is ambiguous or not substantial.

In a guest article for the Laborjournal, Ulrich Dirnagl, MD, PhD, from the Charité — Universitätsmedizin Berlin in Germany, emphasized that the scientific papers have become so complex that two or three experts often cannot thoroughly assess everything presented. The review process is time-consuming and can take several days for reviewers. Currently, very few people have time, especially because it is an unpaid and anonymous task. Dirnagl stated, “the self-correction of science no longer works as it claims.”

The old Russian saying ‘Dowjerjaj, no prowjerjaj: Trust, but verify’  remains a timeless recommendation that is likely to stay relevant for years to come.

This story was translated from Univadis Germany 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.

The quality and credibility of scientific publications have received increasing scrutiny. Findings from studies by Maria Ángeles Oviedo-García, PhD, from the Department of Business and Marketing at the University of Seville in Spain, highlight growing concerns about the integrity of published research. Insights from the journal Science and the US blog Retraction Watch reveal similar concerns regarding research integrity.

Artificial Intelligence (AI) Spurs Low-Quality Submissions

According to a report in Science, journals are inundated with low-quality contributions such as letters and comments generated by AI. Daniel Prevedello, MD, editor in chief of Neurosurgical Review, announced that the journal would temporarily stop accepting these submissions because of their poor quality.

Neurosurgical Review is not the only journal to experience low-quality submissions. In the journal Oral Oncology Reports (Elsevier), comments comprised 70% of the content, whereas in the International Journal of Surgery Open (Wolters Kluwer), they accounted for nearly half. In Neurosurgical Review, letters, comments, and editorials made up 58% of the total content from January to October 2024, compared with only 9% in the previous year.

This trend benefits authors by allowing them to inflate their publication lists with quickly produced contributions that bypass peer review. Publishers may also profit, as many charge fees to publish comments. Additionally, universities and research institutions find this type of content generation useful as more publications can enhance their reputation.

 

Concerns Over Peer Reviews

The troubling behavior described by Oviedo-García in the journal Scientometrics raises further doubts. An analysis of 263 peer reviews from 37 journals revealed that reviewers often used identical or very similar phrases in their evaluations, regardless of the content. In one case, the reviewer used the same wording in 52 reviews. This suggests that some reviewers read the studies that they are supposed to evaluate only superficially. Such practices can lead to valueless reviews and jeopardize the integrity of scientific literature. “Some other researchers will probably base their future research on these fake reports, which is frightening, especially when it comes to health and medicine,” Oviedo-García stated.

She suspects that the reviewers may have relied on templates to produce their reports quickly. This allowed them to list this work on their resumes for potential career advantages. Some reviewers have reportedly even “requested” the authors of the studies they reviewed to cite their own scientific work.

 

AI Complicates Peer Review

The process of research and publication has become increasingly challenging in recent years, and more standard and predatory journals allow anyone to publish their work for a fee. Roger W. Byard, MD, PhD, from the University of Adelaide in Australia, explained this trend in the journal Forensic Science, Medicine and Pathology. AI is increasingly being used to generate articles. At international conferences, experts have highlighted claims that AI can complete papers in just a few weeks and dissertations in less than a year. According to the authors of a letter in Critical Care, generative AI is infiltrating the peer review process.

Moreover, the peer review process can be bypassed by publishing research findings on online platforms (eg, preprint servers). Another issue is that some publications have hundreds of authors who can extend their publication list in this manner, even if their contribution to the publication is ambiguous or not substantial.

In a guest article for the Laborjournal, Ulrich Dirnagl, MD, PhD, from the Charité — Universitätsmedizin Berlin in Germany, emphasized that the scientific papers have become so complex that two or three experts often cannot thoroughly assess everything presented. The review process is time-consuming and can take several days for reviewers. Currently, very few people have time, especially because it is an unpaid and anonymous task. Dirnagl stated, “the self-correction of science no longer works as it claims.”

The old Russian saying ‘Dowjerjaj, no prowjerjaj: Trust, but verify’  remains a timeless recommendation that is likely to stay relevant for years to come.

This story was translated from Univadis Germany 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.

Tina is a lovely 67-year-old woman who was recently found to be an APOE gene carrier (a gene associated with increased risk of developing Alzheimer’s disease as well as an earlier age of disease onset), with diffused amyloid protein deposition her brain. 

Her neuropsychiatric testing was consistent with mild cognitive impairment. Although Tina is not a doctor herself, her entire family consists of doctors, and she came to me under their advisement to consider semaglutide (Ozempic) for early Alzheimer’s disease prevention. 

This would usually be simple, but in Tina’s case, there was a complicating factor: At 5’ and 90 pounds, she was already considerably underweight and was at risk of becoming severely undernourished. 

To understand the potential role for glucagon-like peptide-1 (GLP-1) receptor agonists such as Ozempic in prevention, a quick primer on Alzheimer’s Disease is necessary.

The exact cause of Alzheimer’s disease remains elusive, but it is probably due to a combination of factors, including:

• Buildup of abnormal amyloid and tau proteins around brain cells
• Brain shrinkage, with subsequent damage to blood vessels and mitochondria, and inflammation
• Genetic predisposition
• Lifestyle factors, including obesity, high blood pressure, high cholesterol, and diabetes.

GLP-1 receptor agonists can cross the blood-brain barrier and bind to GLP-1 receptors expressed by neurons. Once in the brain, they can reduce inflammation and improve functioning of the neurons. In early rodent trials, GLP-1 receptor agonists led to reduced amyloid and tau aggregation, downregulation of inflammation, and improved memory.

In 2021, multiple studies showed that liraglutide, an early GLP-1 receptor agonist, improved cognitive function and MRI volume in patients with Alzheimer’s disease. 

A study recently published in Alzheimer’s & Dementia analyzed data from 1 million people with type 2 diabetes and no prior Alzheimer’s disease diagnosis. The authors compared Alzheimer’s disease occurrence in patients taking various diabetes medications, including insulin, metformin, and GLP-1 receptor agonists. The study found that participants taking semaglutide had up to a 70% reduction in Alzheimer’s risk. The results were consistent across gender, age, and weight.

Given the reassuring safety profile of GLP-1 receptor agonists and lack of other effective treatment or prophylaxis for Alzheimer’s disease, I agreed to start her on dulaglutide (Trulicity). My rationale was twofold:

1. In studies, dulaglutide has the highest uptake in the brain tissue at 68%. By contrast, there is virtually zero uptake in brain tissue for semaglutide (Ozempic/Wegovy) and tirzepatide (Mounjaro/Zepbound). Because this class of drugs exert their effects in the brain tissue, I wanted to give her a GLP-1 receptor agonist with a high percent uptake.

2. Trulicity has a minimal effect on weight loss compared with the newer-generation GLP-1 receptor agonists. Even so, I connected Tina to my dietitian to ensure that she would receive a high-protein, high-calorie diet.

Tina has now been taking Trulicity for 6 months. Although it is certainly too early to draw firm conclusions about the efficacy of her treatment, she is not experiencing any weight loss and is cognitively stable, according to her neurologist. 

The EVOKE and EVOKE+ phase 3 trials are currently underway to evaluate the efficacy of semaglutide to treat mild cognitive impairment and early Alzheimer’s in amyloid-positive patients. Results are expected in 2025, but in the meantime, I feel comforted knowing that Tina is receiving a potentially beneficial and definitively low-risk treatment. 

 

Dr Messer, Clinical Assistant Professor, Mount Sinai School of Medicine; Associate Professor, Hofstra School of Medicine, New York, NY, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Tina is a lovely 67-year-old woman who was recently found to be an APOE gene carrier (a gene associated with increased risk of developing Alzheimer’s disease as well as an earlier age of disease onset), with diffused amyloid protein deposition her brain. 

Her neuropsychiatric testing was consistent with mild cognitive impairment. Although Tina is not a doctor herself, her entire family consists of doctors, and she came to me under their advisement to consider semaglutide (Ozempic) for early Alzheimer’s disease prevention. 

This would usually be simple, but in Tina’s case, there was a complicating factor: At 5’ and 90 pounds, she was already considerably underweight and was at risk of becoming severely undernourished. 

To understand the potential role for glucagon-like peptide-1 (GLP-1) receptor agonists such as Ozempic in prevention, a quick primer on Alzheimer’s Disease is necessary.

The exact cause of Alzheimer’s disease remains elusive, but it is probably due to a combination of factors, including:

• Buildup of abnormal amyloid and tau proteins around brain cells
• Brain shrinkage, with subsequent damage to blood vessels and mitochondria, and inflammation
• Genetic predisposition
• Lifestyle factors, including obesity, high blood pressure, high cholesterol, and diabetes.

GLP-1 receptor agonists can cross the blood-brain barrier and bind to GLP-1 receptors expressed by neurons. Once in the brain, they can reduce inflammation and improve functioning of the neurons. In early rodent trials, GLP-1 receptor agonists led to reduced amyloid and tau aggregation, downregulation of inflammation, and improved memory.

In 2021, multiple studies showed that liraglutide, an early GLP-1 receptor agonist, improved cognitive function and MRI volume in patients with Alzheimer’s disease. 

A study recently published in Alzheimer’s & Dementia analyzed data from 1 million people with type 2 diabetes and no prior Alzheimer’s disease diagnosis. The authors compared Alzheimer’s disease occurrence in patients taking various diabetes medications, including insulin, metformin, and GLP-1 receptor agonists. The study found that participants taking semaglutide had up to a 70% reduction in Alzheimer’s risk. The results were consistent across gender, age, and weight.

Given the reassuring safety profile of GLP-1 receptor agonists and lack of other effective treatment or prophylaxis for Alzheimer’s disease, I agreed to start her on dulaglutide (Trulicity). My rationale was twofold:

1. In studies, dulaglutide has the highest uptake in the brain tissue at 68%. By contrast, there is virtually zero uptake in brain tissue for semaglutide (Ozempic/Wegovy) and tirzepatide (Mounjaro/Zepbound). Because this class of drugs exert their effects in the brain tissue, I wanted to give her a GLP-1 receptor agonist with a high percent uptake.

2. Trulicity has a minimal effect on weight loss compared with the newer-generation GLP-1 receptor agonists. Even so, I connected Tina to my dietitian to ensure that she would receive a high-protein, high-calorie diet.

Tina has now been taking Trulicity for 6 months. Although it is certainly too early to draw firm conclusions about the efficacy of her treatment, she is not experiencing any weight loss and is cognitively stable, according to her neurologist. 

The EVOKE and EVOKE+ phase 3 trials are currently underway to evaluate the efficacy of semaglutide to treat mild cognitive impairment and early Alzheimer’s in amyloid-positive patients. Results are expected in 2025, but in the meantime, I feel comforted knowing that Tina is receiving a potentially beneficial and definitively low-risk treatment. 

 

Dr Messer, Clinical Assistant Professor, Mount Sinai School of Medicine; Associate Professor, Hofstra School of Medicine, New York, NY, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Tina is a lovely 67-year-old woman who was recently found to be an APOE gene carrier (a gene associated with increased risk of developing Alzheimer’s disease as well as an earlier age of disease onset), with diffused amyloid protein deposition her brain. 

Her neuropsychiatric testing was consistent with mild cognitive impairment. Although Tina is not a doctor herself, her entire family consists of doctors, and she came to me under their advisement to consider semaglutide (Ozempic) for early Alzheimer’s disease prevention. 

This would usually be simple, but in Tina’s case, there was a complicating factor: At 5’ and 90 pounds, she was already considerably underweight and was at risk of becoming severely undernourished. 

To understand the potential role for glucagon-like peptide-1 (GLP-1) receptor agonists such as Ozempic in prevention, a quick primer on Alzheimer’s Disease is necessary.

The exact cause of Alzheimer’s disease remains elusive, but it is probably due to a combination of factors, including:

• Buildup of abnormal amyloid and tau proteins around brain cells
• Brain shrinkage, with subsequent damage to blood vessels and mitochondria, and inflammation
• Genetic predisposition
• Lifestyle factors, including obesity, high blood pressure, high cholesterol, and diabetes.

GLP-1 receptor agonists can cross the blood-brain barrier and bind to GLP-1 receptors expressed by neurons. Once in the brain, they can reduce inflammation and improve functioning of the neurons. In early rodent trials, GLP-1 receptor agonists led to reduced amyloid and tau aggregation, downregulation of inflammation, and improved memory.

In 2021, multiple studies showed that liraglutide, an early GLP-1 receptor agonist, improved cognitive function and MRI volume in patients with Alzheimer’s disease. 

A study recently published in Alzheimer’s & Dementia analyzed data from 1 million people with type 2 diabetes and no prior Alzheimer’s disease diagnosis. The authors compared Alzheimer’s disease occurrence in patients taking various diabetes medications, including insulin, metformin, and GLP-1 receptor agonists. The study found that participants taking semaglutide had up to a 70% reduction in Alzheimer’s risk. The results were consistent across gender, age, and weight.

Given the reassuring safety profile of GLP-1 receptor agonists and lack of other effective treatment or prophylaxis for Alzheimer’s disease, I agreed to start her on dulaglutide (Trulicity). My rationale was twofold:

1. In studies, dulaglutide has the highest uptake in the brain tissue at 68%. By contrast, there is virtually zero uptake in brain tissue for semaglutide (Ozempic/Wegovy) and tirzepatide (Mounjaro/Zepbound). Because this class of drugs exert their effects in the brain tissue, I wanted to give her a GLP-1 receptor agonist with a high percent uptake.

2. Trulicity has a minimal effect on weight loss compared with the newer-generation GLP-1 receptor agonists. Even so, I connected Tina to my dietitian to ensure that she would receive a high-protein, high-calorie diet.

Tina has now been taking Trulicity for 6 months. Although it is certainly too early to draw firm conclusions about the efficacy of her treatment, she is not experiencing any weight loss and is cognitively stable, according to her neurologist. 

The EVOKE and EVOKE+ phase 3 trials are currently underway to evaluate the efficacy of semaglutide to treat mild cognitive impairment and early Alzheimer’s in amyloid-positive patients. Results are expected in 2025, but in the meantime, I feel comforted knowing that Tina is receiving a potentially beneficial and definitively low-risk treatment. 

 

Dr Messer, Clinical Assistant Professor, Mount Sinai School of Medicine; Associate Professor, Hofstra School of Medicine, New York, NY, has disclosed no relevant financial relationships.

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.

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.

TOPLINE:

Among older adults with type 2 diabetes (T2D), the use of antidiabetes medications declined in the last year before death, with notable shifts from metformin and sulfonylureas toward insulin therapy.

METHODOLOGY:

Current recommendations emphasize a more liberal approach to glycemic control in people with a high burden of comorbidities and shorter life expectancy, but little is known about the changes and discontinuation patterns of diabetes medications among older adults near the end of life.

Researchers conducted an observational cohort study to assess the prescribing trends of antidiabetes medications in the final year of life among 975,407 community-dwelling Medicare beneficiaries with T2D (mean age at death, 80.9 years; 54.3% women) who died between January 2015 and December 2019.

All medication classes available during the study period were considered, including short-acting and long-acting insulins, metformin, sulfonylureas, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and other medications.

Analysis included temporal trends in prescribing antidiabetes medications, stratified by frailty using a validated claims-based frailty index, with scores ≥ 0.30 indicating higher frailty.

Antidiabetes medication fills were assessed within 1 year before death, examining changes across three time periods: 12 to 8 months, 8 to 4 months, and 4 to 0 months before death.

TAKEAWAY:

The proportion of older patients receiving antidiabetes medications increased slightly from 71.4% in 2015 to 72.9% in 2019, with metformin showing the largest increase from 40.7% to 46.5% (standardized mean difference [SMD], −0.12) and sulfonylureas showing the largest decrease from 37.0% to 31.8% (SMD, 0.11).

The use of newer diabetes medications with cardiovascular benefits, such as GLP-1 receptor agonists and SGLT2 inhibitors, remained less common but showed increasing trends over time.

The use of any antidiabetes medication decreased from 66.1% in the 9 to 12 months before death to 60.8% in the last 4 months of life (P < .01), primarily due to the reduced use of metformin and sulfonylureas.

The use of both short-acting and long-acting insulin agents increased toward the end of life (from 28.0% to 32.9% and from 41.2% to 43.9%, respectively; both P < .001) , particularly among frailer individuals.

IN PRACTICE:

“[The study] findings underscore important implications for diabetes management in patients nearing the end of life. With ~70% of patients with T2D using at least one antidiabetes medication, there is a need to consider further de-escalation or deprescribing in this vulnerable population,” the authors wrote.

SOURCE:

The study was led by Alexander Kutz, MD, MPH, MSc, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, and was published online in Diabetes Care.

LIMITATIONS:

The study lacked details on the reasons for changes in medication patterns, making it unclear whether these changes were due to clinical guidelines or to reduce adverse events. Moreover, the study could not capture transitions or substitutions between medications, information on the dosage data, and causes of death.

DISCLOSURES:

This study was supported by the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School. Some authors reported receiving personal fees or research grants from the National Institutes of Health and other institutions and a few pharmaceutical companies. One author reported acting as a principal investigator and receiving a research grant from Boehringer-Ingelheim, unrelated to the work.

 

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 older adults with type 2 diabetes (T2D), the use of antidiabetes medications declined in the last year before death, with notable shifts from metformin and sulfonylureas toward insulin therapy.

METHODOLOGY:

Current recommendations emphasize a more liberal approach to glycemic control in people with a high burden of comorbidities and shorter life expectancy, but little is known about the changes and discontinuation patterns of diabetes medications among older adults near the end of life.

Researchers conducted an observational cohort study to assess the prescribing trends of antidiabetes medications in the final year of life among 975,407 community-dwelling Medicare beneficiaries with T2D (mean age at death, 80.9 years; 54.3% women) who died between January 2015 and December 2019.

All medication classes available during the study period were considered, including short-acting and long-acting insulins, metformin, sulfonylureas, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and other medications.

Analysis included temporal trends in prescribing antidiabetes medications, stratified by frailty using a validated claims-based frailty index, with scores ≥ 0.30 indicating higher frailty.

Antidiabetes medication fills were assessed within 1 year before death, examining changes across three time periods: 12 to 8 months, 8 to 4 months, and 4 to 0 months before death.

TAKEAWAY:

The proportion of older patients receiving antidiabetes medications increased slightly from 71.4% in 2015 to 72.9% in 2019, with metformin showing the largest increase from 40.7% to 46.5% (standardized mean difference [SMD], −0.12) and sulfonylureas showing the largest decrease from 37.0% to 31.8% (SMD, 0.11).

The use of newer diabetes medications with cardiovascular benefits, such as GLP-1 receptor agonists and SGLT2 inhibitors, remained less common but showed increasing trends over time.

The use of any antidiabetes medication decreased from 66.1% in the 9 to 12 months before death to 60.8% in the last 4 months of life (P < .01), primarily due to the reduced use of metformin and sulfonylureas.

The use of both short-acting and long-acting insulin agents increased toward the end of life (from 28.0% to 32.9% and from 41.2% to 43.9%, respectively; both P < .001) , particularly among frailer individuals.

IN PRACTICE:

“[The study] findings underscore important implications for diabetes management in patients nearing the end of life. With ~70% of patients with T2D using at least one antidiabetes medication, there is a need to consider further de-escalation or deprescribing in this vulnerable population,” the authors wrote.

SOURCE:

The study was led by Alexander Kutz, MD, MPH, MSc, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, and was published online in Diabetes Care.

LIMITATIONS:

The study lacked details on the reasons for changes in medication patterns, making it unclear whether these changes were due to clinical guidelines or to reduce adverse events. Moreover, the study could not capture transitions or substitutions between medications, information on the dosage data, and causes of death.

DISCLOSURES:

This study was supported by the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School. Some authors reported receiving personal fees or research grants from the National Institutes of Health and other institutions and a few pharmaceutical companies. One author reported acting as a principal investigator and receiving a research grant from Boehringer-Ingelheim, unrelated to the work.

 

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 older adults with type 2 diabetes (T2D), the use of antidiabetes medications declined in the last year before death, with notable shifts from metformin and sulfonylureas toward insulin therapy.

METHODOLOGY:

Current recommendations emphasize a more liberal approach to glycemic control in people with a high burden of comorbidities and shorter life expectancy, but little is known about the changes and discontinuation patterns of diabetes medications among older adults near the end of life.

Researchers conducted an observational cohort study to assess the prescribing trends of antidiabetes medications in the final year of life among 975,407 community-dwelling Medicare beneficiaries with T2D (mean age at death, 80.9 years; 54.3% women) who died between January 2015 and December 2019.

All medication classes available during the study period were considered, including short-acting and long-acting insulins, metformin, sulfonylureas, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and other medications.

Analysis included temporal trends in prescribing antidiabetes medications, stratified by frailty using a validated claims-based frailty index, with scores ≥ 0.30 indicating higher frailty.

Antidiabetes medication fills were assessed within 1 year before death, examining changes across three time periods: 12 to 8 months, 8 to 4 months, and 4 to 0 months before death.

TAKEAWAY:

The proportion of older patients receiving antidiabetes medications increased slightly from 71.4% in 2015 to 72.9% in 2019, with metformin showing the largest increase from 40.7% to 46.5% (standardized mean difference [SMD], −0.12) and sulfonylureas showing the largest decrease from 37.0% to 31.8% (SMD, 0.11).

The use of newer diabetes medications with cardiovascular benefits, such as GLP-1 receptor agonists and SGLT2 inhibitors, remained less common but showed increasing trends over time.

The use of any antidiabetes medication decreased from 66.1% in the 9 to 12 months before death to 60.8% in the last 4 months of life (P < .01), primarily due to the reduced use of metformin and sulfonylureas.

The use of both short-acting and long-acting insulin agents increased toward the end of life (from 28.0% to 32.9% and from 41.2% to 43.9%, respectively; both P < .001) , particularly among frailer individuals.

IN PRACTICE:

“[The study] findings underscore important implications for diabetes management in patients nearing the end of life. With ~70% of patients with T2D using at least one antidiabetes medication, there is a need to consider further de-escalation or deprescribing in this vulnerable population,” the authors wrote.

SOURCE:

The study was led by Alexander Kutz, MD, MPH, MSc, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, and was published online in Diabetes Care.

LIMITATIONS:

The study lacked details on the reasons for changes in medication patterns, making it unclear whether these changes were due to clinical guidelines or to reduce adverse events. Moreover, the study could not capture transitions or substitutions between medications, information on the dosage data, and causes of death.

DISCLOSURES:

This study was supported by the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School. Some authors reported receiving personal fees or research grants from the National Institutes of Health and other institutions and a few pharmaceutical companies. One author reported acting as a principal investigator and receiving a research grant from Boehringer-Ingelheim, unrelated to the work.

 

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:

Daily treatment with 1200 mg of choline alfoscerate for 12 months shows a modest yet significant improvement in cognitive function and physical health in older patients with type 2 diabetes (T2D) and early signs of cognitive decline. 
 

METHODOLOGY:

• Prior studies have demonstrated the efficacy of choline alfoscerate, a phospholipid metabolite naturally found in the brain, in improving cognitive function in patients with neurodegenerative conditions, but its use in patients with T2D remains unexplored.
• Researchers at a hospital in Korea enrolled patients aged over 60 years with T2D and mild cognitive impairment (assessed by Mini-Mental State Examination [MMSE] scores of 25-28), who were randomly assigned to receive either 1200 mg/d choline alfoscerate or placebo for 12 months.
• The primary efficacy endpoint was the change in the total MMSE score from baseline to month 6; secondary efficacy endpoints included changes in cognitive performance and quality of life, measured by the 36-Item Short Form Health Survey, at 6 and 12 months.

TAKEAWAY:

• Thirty-six patients (average age, 71.8 years; 25% men) with an average diabetes duration of 12.1 years were randomized to receive choline alfoscerate (n = 18) or placebo (n = 18).
• At 6 months, there was modest but nonsignificant improvement in MMSE score with choline alfoscerate vs placebo (P = .059).
• After 12 months, the choline alfoscerate group showed an increase in the MMSE score from 26.2 to 27.1, whereas the placebo group showed a slight decline from 26.6 to 25.8, which represented a significant improvement for the treatment arm (P < .001).
• Physical health scores were significantly superior in the choline alfoscerate group vs the placebo group at 6 months (P = .014), with similar observations at 12 months (P = .039).
• No serious adverse events were reported in either group.

IN PRACTICE:

“Choline alfoscerate could be considered an anticipated therapeutic option to preserve cognitive function and subsequently physical health in elderly patients with diabetes and mild cognitive impairment,” the authors wrote.
 

SOURCE:

The study was led by Minji Sohn, PhD, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea, and published online in Diabetes, Obesity and Metabolism.
 

LIMITATIONS:

The study population primarily comprised non–insulin-dependent patients with controlled glycemia and minimal comorbidities, which may have limited the applicability of the results to a broader population. The small sample size may have contributed to the lack of statistical significance in some outcomes. Moreover, the 12-month study duration may have not been sufficient to investigate the long-term effects of choline alfoscerate.
 

DISCLOSURES:

This study was funded by Daewoong Pharmaceutical through subcontracting with Seoul National University Bundang Hospital. The authors declared no competing interests.
 

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:

Daily treatment with 1200 mg of choline alfoscerate for 12 months shows a modest yet significant improvement in cognitive function and physical health in older patients with type 2 diabetes (T2D) and early signs of cognitive decline. 
 

METHODOLOGY:

• Prior studies have demonstrated the efficacy of choline alfoscerate, a phospholipid metabolite naturally found in the brain, in improving cognitive function in patients with neurodegenerative conditions, but its use in patients with T2D remains unexplored.
• Researchers at a hospital in Korea enrolled patients aged over 60 years with T2D and mild cognitive impairment (assessed by Mini-Mental State Examination [MMSE] scores of 25-28), who were randomly assigned to receive either 1200 mg/d choline alfoscerate or placebo for 12 months.
• The primary efficacy endpoint was the change in the total MMSE score from baseline to month 6; secondary efficacy endpoints included changes in cognitive performance and quality of life, measured by the 36-Item Short Form Health Survey, at 6 and 12 months.

TAKEAWAY:

• Thirty-six patients (average age, 71.8 years; 25% men) with an average diabetes duration of 12.1 years were randomized to receive choline alfoscerate (n = 18) or placebo (n = 18).
• At 6 months, there was modest but nonsignificant improvement in MMSE score with choline alfoscerate vs placebo (P = .059).
• After 12 months, the choline alfoscerate group showed an increase in the MMSE score from 26.2 to 27.1, whereas the placebo group showed a slight decline from 26.6 to 25.8, which represented a significant improvement for the treatment arm (P < .001).
• Physical health scores were significantly superior in the choline alfoscerate group vs the placebo group at 6 months (P = .014), with similar observations at 12 months (P = .039).
• No serious adverse events were reported in either group.

IN PRACTICE:

“Choline alfoscerate could be considered an anticipated therapeutic option to preserve cognitive function and subsequently physical health in elderly patients with diabetes and mild cognitive impairment,” the authors wrote.
 

SOURCE:

The study was led by Minji Sohn, PhD, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea, and published online in Diabetes, Obesity and Metabolism.
 

LIMITATIONS:

The study population primarily comprised non–insulin-dependent patients with controlled glycemia and minimal comorbidities, which may have limited the applicability of the results to a broader population. The small sample size may have contributed to the lack of statistical significance in some outcomes. Moreover, the 12-month study duration may have not been sufficient to investigate the long-term effects of choline alfoscerate.
 

DISCLOSURES:

This study was funded by Daewoong Pharmaceutical through subcontracting with Seoul National University Bundang Hospital. The authors declared no competing interests.
 

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:

Daily treatment with 1200 mg of choline alfoscerate for 12 months shows a modest yet significant improvement in cognitive function and physical health in older patients with type 2 diabetes (T2D) and early signs of cognitive decline. 
 

METHODOLOGY:

• Prior studies have demonstrated the efficacy of choline alfoscerate, a phospholipid metabolite naturally found in the brain, in improving cognitive function in patients with neurodegenerative conditions, but its use in patients with T2D remains unexplored.
• Researchers at a hospital in Korea enrolled patients aged over 60 years with T2D and mild cognitive impairment (assessed by Mini-Mental State Examination [MMSE] scores of 25-28), who were randomly assigned to receive either 1200 mg/d choline alfoscerate or placebo for 12 months.
• The primary efficacy endpoint was the change in the total MMSE score from baseline to month 6; secondary efficacy endpoints included changes in cognitive performance and quality of life, measured by the 36-Item Short Form Health Survey, at 6 and 12 months.

TAKEAWAY:

• Thirty-six patients (average age, 71.8 years; 25% men) with an average diabetes duration of 12.1 years were randomized to receive choline alfoscerate (n = 18) or placebo (n = 18).
• At 6 months, there was modest but nonsignificant improvement in MMSE score with choline alfoscerate vs placebo (P = .059).
• After 12 months, the choline alfoscerate group showed an increase in the MMSE score from 26.2 to 27.1, whereas the placebo group showed a slight decline from 26.6 to 25.8, which represented a significant improvement for the treatment arm (P < .001).
• Physical health scores were significantly superior in the choline alfoscerate group vs the placebo group at 6 months (P = .014), with similar observations at 12 months (P = .039).
• No serious adverse events were reported in either group.

IN PRACTICE:

“Choline alfoscerate could be considered an anticipated therapeutic option to preserve cognitive function and subsequently physical health in elderly patients with diabetes and mild cognitive impairment,” the authors wrote.
 

SOURCE:

The study was led by Minji Sohn, PhD, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea, and published online in Diabetes, Obesity and Metabolism.
 

LIMITATIONS:

The study population primarily comprised non–insulin-dependent patients with controlled glycemia and minimal comorbidities, which may have limited the applicability of the results to a broader population. The small sample size may have contributed to the lack of statistical significance in some outcomes. Moreover, the 12-month study duration may have not been sufficient to investigate the long-term effects of choline alfoscerate.
 

DISCLOSURES:

This study was funded by Daewoong Pharmaceutical through subcontracting with Seoul National University Bundang Hospital. The authors declared no competing interests.
 

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.

A systematic review of 26 randomized controlled trials (RCTs) finds that, among glucagon-like peptide 1 (GLP-1) receptor agonists and co-agonists on the market or still being investigated, the experimental drug retatrutide (Eli Lilly) produces the greatest weight loss.

The review, conducted by researchers at McGill University, Montreal, Quebec, Canada, examined three commercially available medications in the class and nine that have not yet received regulatory approval.

In healthy adults with overweight or obesity who did not have diabetes, the highest mean reductions in relative and absolute body weight were achieved with once-weekly triple glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 and glucagon receptor agonist retatrutide, followed by the dual GIP/GLP-1 agonist tirzepatide (Eli Lilly) and lastly by the GLP-1 agonist semaglutide (Novo Nordisk), according to the authors.

The use of all the GLP-1s or co-agonist medications “led to decreased body mass index (BMI), waist circumference, SBP (systolic blood pressure), and DBP (diastolic blood pressure),” wrote the authors in Annals of Internal Medicine. All the medications had a similar safety profile.

The researchers did not find any head-to-head studies, so instead examined the results from 26 RCTs that enrolled more than 15,000 patients. Only trials with a treatment duration of at least 16 weeks were included, to ensure that patients had at least a month of a fixed dose.

Not surprisingly, the review found that, except for semaglutide, trials with “dual and triple agonists generally reported numerically greater mean weight losses than single GLP-1 agonists.”

They caution, however, against drawing conclusions about comparative efficacy, as the populations, control groups, and contexts of the various studies might not be directly comparable. All the trial enrollees also received lifestyle modification along with drug therapy or placebo, but the interventions and protocols varied across the studies.

The authors found that individuals on retatrutide (12-mg once-weekly injection) lost 22% of body weight from baseline after 48 weeks. Tirzepatide (15 mg once-weekly injection) recipients lost almost 18% of body weight after 72 weeks, while those on semaglutide (2.4-mg once-weekly injection) lost about 14% after 68 weeks. Both tirzepatide and semaglutide are commercially available.

Patients taking liraglutide (3-mg once-daily injection), also on the market, lost up to 6% of body weight after 26 weeks.

The authors also examined studies of investigational agents and reported that the greatest loss, aside from retatrutide, was with the dual glucagon/GLP-1 agonists survodutide (Boehringer Ingelheim; 6%-15%) and mazdutide (Innovent Biologics; 7%-11%).

Orforglipron (Eli Lilly), a once-daily pill, produced weight loss of 9%-15%, depending on the dose.

The study found that four investigational drugs did not produce as much weight loss: Beinaglutide (0.2-mg injection three times daily, 6%), efpeglenatide (4- to 8-mg injection once weekly, about 7%), exenatide (10-mcg injection twice daily, 5-kg change in weight), and noiiglutide (once-daily injection, 9%).

The most common adverse events for all GLP-1s were gastrointestinal (GI), such as nausea, diarrhea, constipation, and vomiting. Across all agents, 60%-80% of patients taking the medications experienced a GI adverse event, although most were transient, according to the authors. A total of 6%-26% of patients discontinued treatment as a result of a side effect.

The authors said that no serious GI disorders, such as bowel obstruction or gastroparesis, were reported in any of the 26 trials.

The review also shows that it is likely that GLP-1s would have to be used chronically to have the greatest effect, said the authors. They noted that they found that trials “with longer treatment durations demonstrate similar weight loss results to those with shorter follow-up, reinforcing the idea that continuous treatment may be required.”

One coauthor reported receiving payments or honoraria from Boehringer Ingelheim, Eli Lilly, Janssen Pharmaceuticals, and Novo Nordisk. The study was carried out independently without any grant or other funding.

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

A systematic review of 26 randomized controlled trials (RCTs) finds that, among glucagon-like peptide 1 (GLP-1) receptor agonists and co-agonists on the market or still being investigated, the experimental drug retatrutide (Eli Lilly) produces the greatest weight loss.

The review, conducted by researchers at McGill University, Montreal, Quebec, Canada, examined three commercially available medications in the class and nine that have not yet received regulatory approval.

In healthy adults with overweight or obesity who did not have diabetes, the highest mean reductions in relative and absolute body weight were achieved with once-weekly triple glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 and glucagon receptor agonist retatrutide, followed by the dual GIP/GLP-1 agonist tirzepatide (Eli Lilly) and lastly by the GLP-1 agonist semaglutide (Novo Nordisk), according to the authors.

The use of all the GLP-1s or co-agonist medications “led to decreased body mass index (BMI), waist circumference, SBP (systolic blood pressure), and DBP (diastolic blood pressure),” wrote the authors in Annals of Internal Medicine. All the medications had a similar safety profile.

The researchers did not find any head-to-head studies, so instead examined the results from 26 RCTs that enrolled more than 15,000 patients. Only trials with a treatment duration of at least 16 weeks were included, to ensure that patients had at least a month of a fixed dose.

Not surprisingly, the review found that, except for semaglutide, trials with “dual and triple agonists generally reported numerically greater mean weight losses than single GLP-1 agonists.”

They caution, however, against drawing conclusions about comparative efficacy, as the populations, control groups, and contexts of the various studies might not be directly comparable. All the trial enrollees also received lifestyle modification along with drug therapy or placebo, but the interventions and protocols varied across the studies.

The authors found that individuals on retatrutide (12-mg once-weekly injection) lost 22% of body weight from baseline after 48 weeks. Tirzepatide (15 mg once-weekly injection) recipients lost almost 18% of body weight after 72 weeks, while those on semaglutide (2.4-mg once-weekly injection) lost about 14% after 68 weeks. Both tirzepatide and semaglutide are commercially available.

Patients taking liraglutide (3-mg once-daily injection), also on the market, lost up to 6% of body weight after 26 weeks.

The authors also examined studies of investigational agents and reported that the greatest loss, aside from retatrutide, was with the dual glucagon/GLP-1 agonists survodutide (Boehringer Ingelheim; 6%-15%) and mazdutide (Innovent Biologics; 7%-11%).

Orforglipron (Eli Lilly), a once-daily pill, produced weight loss of 9%-15%, depending on the dose.

The study found that four investigational drugs did not produce as much weight loss: Beinaglutide (0.2-mg injection three times daily, 6%), efpeglenatide (4- to 8-mg injection once weekly, about 7%), exenatide (10-mcg injection twice daily, 5-kg change in weight), and noiiglutide (once-daily injection, 9%).

The most common adverse events for all GLP-1s were gastrointestinal (GI), such as nausea, diarrhea, constipation, and vomiting. Across all agents, 60%-80% of patients taking the medications experienced a GI adverse event, although most were transient, according to the authors. A total of 6%-26% of patients discontinued treatment as a result of a side effect.

The authors said that no serious GI disorders, such as bowel obstruction or gastroparesis, were reported in any of the 26 trials.

The review also shows that it is likely that GLP-1s would have to be used chronically to have the greatest effect, said the authors. They noted that they found that trials “with longer treatment durations demonstrate similar weight loss results to those with shorter follow-up, reinforcing the idea that continuous treatment may be required.”

One coauthor reported receiving payments or honoraria from Boehringer Ingelheim, Eli Lilly, Janssen Pharmaceuticals, and Novo Nordisk. The study was carried out independently without any grant or other funding.

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

A systematic review of 26 randomized controlled trials (RCTs) finds that, among glucagon-like peptide 1 (GLP-1) receptor agonists and co-agonists on the market or still being investigated, the experimental drug retatrutide (Eli Lilly) produces the greatest weight loss.

The review, conducted by researchers at McGill University, Montreal, Quebec, Canada, examined three commercially available medications in the class and nine that have not yet received regulatory approval.

In healthy adults with overweight or obesity who did not have diabetes, the highest mean reductions in relative and absolute body weight were achieved with once-weekly triple glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 and glucagon receptor agonist retatrutide, followed by the dual GIP/GLP-1 agonist tirzepatide (Eli Lilly) and lastly by the GLP-1 agonist semaglutide (Novo Nordisk), according to the authors.

The use of all the GLP-1s or co-agonist medications “led to decreased body mass index (BMI), waist circumference, SBP (systolic blood pressure), and DBP (diastolic blood pressure),” wrote the authors in Annals of Internal Medicine. All the medications had a similar safety profile.

The researchers did not find any head-to-head studies, so instead examined the results from 26 RCTs that enrolled more than 15,000 patients. Only trials with a treatment duration of at least 16 weeks were included, to ensure that patients had at least a month of a fixed dose.

Not surprisingly, the review found that, except for semaglutide, trials with “dual and triple agonists generally reported numerically greater mean weight losses than single GLP-1 agonists.”

They caution, however, against drawing conclusions about comparative efficacy, as the populations, control groups, and contexts of the various studies might not be directly comparable. All the trial enrollees also received lifestyle modification along with drug therapy or placebo, but the interventions and protocols varied across the studies.

The authors found that individuals on retatrutide (12-mg once-weekly injection) lost 22% of body weight from baseline after 48 weeks. Tirzepatide (15 mg once-weekly injection) recipients lost almost 18% of body weight after 72 weeks, while those on semaglutide (2.4-mg once-weekly injection) lost about 14% after 68 weeks. Both tirzepatide and semaglutide are commercially available.

Patients taking liraglutide (3-mg once-daily injection), also on the market, lost up to 6% of body weight after 26 weeks.

The authors also examined studies of investigational agents and reported that the greatest loss, aside from retatrutide, was with the dual glucagon/GLP-1 agonists survodutide (Boehringer Ingelheim; 6%-15%) and mazdutide (Innovent Biologics; 7%-11%).

Orforglipron (Eli Lilly), a once-daily pill, produced weight loss of 9%-15%, depending on the dose.

The study found that four investigational drugs did not produce as much weight loss: Beinaglutide (0.2-mg injection three times daily, 6%), efpeglenatide (4- to 8-mg injection once weekly, about 7%), exenatide (10-mcg injection twice daily, 5-kg change in weight), and noiiglutide (once-daily injection, 9%).

The most common adverse events for all GLP-1s were gastrointestinal (GI), such as nausea, diarrhea, constipation, and vomiting. Across all agents, 60%-80% of patients taking the medications experienced a GI adverse event, although most were transient, according to the authors. A total of 6%-26% of patients discontinued treatment as a result of a side effect.

The authors said that no serious GI disorders, such as bowel obstruction or gastroparesis, were reported in any of the 26 trials.

The review also shows that it is likely that GLP-1s would have to be used chronically to have the greatest effect, said the authors. They noted that they found that trials “with longer treatment durations demonstrate similar weight loss results to those with shorter follow-up, reinforcing the idea that continuous treatment may be required.”

One coauthor reported receiving payments or honoraria from Boehringer Ingelheim, Eli Lilly, Janssen Pharmaceuticals, and Novo Nordisk. The study was carried out independently without any grant or other funding.

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

Could an artificial intelligence (AI)–driven tool that mines medical records for suspected cases of osteoporosis be so successful that it becomes a potential liability? Yes, according to Christopher White, PhD, executive director of Maridulu Budyari Gumal, the Sydney Partnership for Health, Education, Research, and Enterprise, a research translation center in Liverpool, Australia.

In a thought-provoking presentation at the Endocrine Society’s AI in Healthcare Virtual Summit, White described the results after his fracture liaison team at Prince of Wales Hospital in Randwick, Australia, tried to plug the “osteoporosis treatment gap” by mining medical records to identify patients with the disorder.

 

‘Be Careful What You Wish For’

White and colleagues developed a robust standalone database over 20 years that informed fracture risk among patients with osteoporosis in Sydney. The database included all relevant clinical information, as well as bone density measurements, on about 30,000 patients and could be interrogated for randomized controlled trial recruitment.

However, a “crisis” occurred around 2011, when the team received a recruitment request for the first head-to-head comparison of alendronate with romosozumab. “We had numerous postmenopausal women in the age range with the required bone density, but we hadn’t captured the severity of their vertebral fracture or how many they actually had,” White told the this news organization. For recruitment into the study, participants must have had at least two moderate or severe vertebral fractures or a proximal vertebral fracture that was sustained between 3 and 24 months before recruitment.

White turned to his hospital’s mainframe, which had coding data and time intervals for patients who were admitted with vertebral or hip fractures. He calculated how many patients who met the study criteria had been discharged and how many of those he thought he’d be able to capture through the mainframe. He was confident he would have enough, but he was wrong. He underrecruited and could not participate in the trial.

Determined not to wind up in a similar situation in the future, he investigated and found that other centers were struggling with similar problems. This led to a collaboration with four investigators who were using AI and Advanced Encryption Standard (AES) coding to identify patients at risk for osteoporotic fractures. White, meanwhile, had developed a natural language processing tool called XRAIT that also identified patients at fracture risk. A study comparing the two electronic search programs, which screen medical records for fractures, found that both reliably identified patients who had had a fracture. White and his colleagues concluded that hybrid tools combining XRAIT and AES would likely improve the identification of patients with osteoporosis who would require follow-up or might participate in future trials.

Those patients were not being identified sooner for multiple reasons, White explained. Sometimes, the radiologist would report osteoporosis, but it wouldn’t get coded. Or, in the emergency department, a patient with a fracture would be treated and then sent home, and the possibility of osteoporosis wasn’t reported.

“As we went deeper and deeper with our tools into the medical record, we found more and more patients who hadn’t been coded or reported but who actually had osteoporosis,” White said. “It was incredibly prevalent.”

But the number of patients identified was more than the hospital could comfortably handle.

Ironically, he added, “To my relief and probably not to the benefit of the patients, there was a system upgrade of the radiology reporting system, which was incompatible with the natural language processing technology that I had installed. The AI was turned off at that point, but I had a look over the edge and into the mine pit.”

“The lesson learned,” White told this news organization, is “If you mine the medical record for unidentified patients before you know what to do with the output, you create a medico-legal minefield. You need to be careful what you wish for with technology, because it may actually come true.”

 

Grappling With the Treatment Gap

An (over)abundance of patients is likely contributing to the “osteoporosis treatment gap” that Australia’s fracture liaison services, which handle many of these patients, are grappling with. One recent meta-analysis showed that not all eligible patients are treated and that not all patients who are treated actually start treatment. Another study showed that only a minority of patients — anywhere between 20% and 40% — who start are still persisting at about 3 years, White said.

Various types of fracture liaison services exist, he noted. The model that has been shown to best promote adherence is the one requiring clinicians to “identify, educate [usually, the primary care physician], evaluate, start treatment, continue treatment, and follow-up at 12 months for to confirm that there is adherence.”

What’s happening now, he said, is that the technology is identifying a high number of vertebral crush fractures, and there’s no education or evaluation. “The radiologist just refers the patient to a primary care physician and hopes for the best. AI isn’t contributing to solving the treatment gap problem; it’s amplifying it. It’s ahead of the ability of organizations to accommodate the findings.”

Solutions, he said, would require support at the top of health systems and organizations, and funding to proceed; data surveys concentrating on vertical integration of the medical record to follow patients wherever they are — eg, hospital, primary care — in their health journeys; a workflow with synchronous diagnosis and treatment planning, delivery, monitoring, and payment; and clinical and community champions advocating and “leading the charge in health tech.”

Furthermore, he advised, organizations need to be “very, very careful with safety and security — that is, managing the digital risks.”

“Oscar Wilde said there are two tragedies in life: One is not getting what one wants, and the other is getting it,” White concluded. “In my career, we’ve moved on from not knowing how to treat osteoporosis to knowing how to treat it. And that is both an asset and a liability.”

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

Could an artificial intelligence (AI)–driven tool that mines medical records for suspected cases of osteoporosis be so successful that it becomes a potential liability? Yes, according to Christopher White, PhD, executive director of Maridulu Budyari Gumal, the Sydney Partnership for Health, Education, Research, and Enterprise, a research translation center in Liverpool, Australia.

In a thought-provoking presentation at the Endocrine Society’s AI in Healthcare Virtual Summit, White described the results after his fracture liaison team at Prince of Wales Hospital in Randwick, Australia, tried to plug the “osteoporosis treatment gap” by mining medical records to identify patients with the disorder.

 

‘Be Careful What You Wish For’

White and colleagues developed a robust standalone database over 20 years that informed fracture risk among patients with osteoporosis in Sydney. The database included all relevant clinical information, as well as bone density measurements, on about 30,000 patients and could be interrogated for randomized controlled trial recruitment.

However, a “crisis” occurred around 2011, when the team received a recruitment request for the first head-to-head comparison of alendronate with romosozumab. “We had numerous postmenopausal women in the age range with the required bone density, but we hadn’t captured the severity of their vertebral fracture or how many they actually had,” White told the this news organization. For recruitment into the study, participants must have had at least two moderate or severe vertebral fractures or a proximal vertebral fracture that was sustained between 3 and 24 months before recruitment.

White turned to his hospital’s mainframe, which had coding data and time intervals for patients who were admitted with vertebral or hip fractures. He calculated how many patients who met the study criteria had been discharged and how many of those he thought he’d be able to capture through the mainframe. He was confident he would have enough, but he was wrong. He underrecruited and could not participate in the trial.

Determined not to wind up in a similar situation in the future, he investigated and found that other centers were struggling with similar problems. This led to a collaboration with four investigators who were using AI and Advanced Encryption Standard (AES) coding to identify patients at risk for osteoporotic fractures. White, meanwhile, had developed a natural language processing tool called XRAIT that also identified patients at fracture risk. A study comparing the two electronic search programs, which screen medical records for fractures, found that both reliably identified patients who had had a fracture. White and his colleagues concluded that hybrid tools combining XRAIT and AES would likely improve the identification of patients with osteoporosis who would require follow-up or might participate in future trials.

Those patients were not being identified sooner for multiple reasons, White explained. Sometimes, the radiologist would report osteoporosis, but it wouldn’t get coded. Or, in the emergency department, a patient with a fracture would be treated and then sent home, and the possibility of osteoporosis wasn’t reported.

“As we went deeper and deeper with our tools into the medical record, we found more and more patients who hadn’t been coded or reported but who actually had osteoporosis,” White said. “It was incredibly prevalent.”

But the number of patients identified was more than the hospital could comfortably handle.

Ironically, he added, “To my relief and probably not to the benefit of the patients, there was a system upgrade of the radiology reporting system, which was incompatible with the natural language processing technology that I had installed. The AI was turned off at that point, but I had a look over the edge and into the mine pit.”

“The lesson learned,” White told this news organization, is “If you mine the medical record for unidentified patients before you know what to do with the output, you create a medico-legal minefield. You need to be careful what you wish for with technology, because it may actually come true.”

 

Grappling With the Treatment Gap

An (over)abundance of patients is likely contributing to the “osteoporosis treatment gap” that Australia’s fracture liaison services, which handle many of these patients, are grappling with. One recent meta-analysis showed that not all eligible patients are treated and that not all patients who are treated actually start treatment. Another study showed that only a minority of patients — anywhere between 20% and 40% — who start are still persisting at about 3 years, White said.

Various types of fracture liaison services exist, he noted. The model that has been shown to best promote adherence is the one requiring clinicians to “identify, educate [usually, the primary care physician], evaluate, start treatment, continue treatment, and follow-up at 12 months for to confirm that there is adherence.”

What’s happening now, he said, is that the technology is identifying a high number of vertebral crush fractures, and there’s no education or evaluation. “The radiologist just refers the patient to a primary care physician and hopes for the best. AI isn’t contributing to solving the treatment gap problem; it’s amplifying it. It’s ahead of the ability of organizations to accommodate the findings.”

Solutions, he said, would require support at the top of health systems and organizations, and funding to proceed; data surveys concentrating on vertical integration of the medical record to follow patients wherever they are — eg, hospital, primary care — in their health journeys; a workflow with synchronous diagnosis and treatment planning, delivery, monitoring, and payment; and clinical and community champions advocating and “leading the charge in health tech.”

Furthermore, he advised, organizations need to be “very, very careful with safety and security — that is, managing the digital risks.”

“Oscar Wilde said there are two tragedies in life: One is not getting what one wants, and the other is getting it,” White concluded. “In my career, we’ve moved on from not knowing how to treat osteoporosis to knowing how to treat it. And that is both an asset and a liability.”

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

Could an artificial intelligence (AI)–driven tool that mines medical records for suspected cases of osteoporosis be so successful that it becomes a potential liability? Yes, according to Christopher White, PhD, executive director of Maridulu Budyari Gumal, the Sydney Partnership for Health, Education, Research, and Enterprise, a research translation center in Liverpool, Australia.

In a thought-provoking presentation at the Endocrine Society’s AI in Healthcare Virtual Summit, White described the results after his fracture liaison team at Prince of Wales Hospital in Randwick, Australia, tried to plug the “osteoporosis treatment gap” by mining medical records to identify patients with the disorder.

 

‘Be Careful What You Wish For’

White and colleagues developed a robust standalone database over 20 years that informed fracture risk among patients with osteoporosis in Sydney. The database included all relevant clinical information, as well as bone density measurements, on about 30,000 patients and could be interrogated for randomized controlled trial recruitment.

However, a “crisis” occurred around 2011, when the team received a recruitment request for the first head-to-head comparison of alendronate with romosozumab. “We had numerous postmenopausal women in the age range with the required bone density, but we hadn’t captured the severity of their vertebral fracture or how many they actually had,” White told the this news organization. For recruitment into the study, participants must have had at least two moderate or severe vertebral fractures or a proximal vertebral fracture that was sustained between 3 and 24 months before recruitment.

White turned to his hospital’s mainframe, which had coding data and time intervals for patients who were admitted with vertebral or hip fractures. He calculated how many patients who met the study criteria had been discharged and how many of those he thought he’d be able to capture through the mainframe. He was confident he would have enough, but he was wrong. He underrecruited and could not participate in the trial.

Determined not to wind up in a similar situation in the future, he investigated and found that other centers were struggling with similar problems. This led to a collaboration with four investigators who were using AI and Advanced Encryption Standard (AES) coding to identify patients at risk for osteoporotic fractures. White, meanwhile, had developed a natural language processing tool called XRAIT that also identified patients at fracture risk. A study comparing the two electronic search programs, which screen medical records for fractures, found that both reliably identified patients who had had a fracture. White and his colleagues concluded that hybrid tools combining XRAIT and AES would likely improve the identification of patients with osteoporosis who would require follow-up or might participate in future trials.

Those patients were not being identified sooner for multiple reasons, White explained. Sometimes, the radiologist would report osteoporosis, but it wouldn’t get coded. Or, in the emergency department, a patient with a fracture would be treated and then sent home, and the possibility of osteoporosis wasn’t reported.

“As we went deeper and deeper with our tools into the medical record, we found more and more patients who hadn’t been coded or reported but who actually had osteoporosis,” White said. “It was incredibly prevalent.”

But the number of patients identified was more than the hospital could comfortably handle.

Ironically, he added, “To my relief and probably not to the benefit of the patients, there was a system upgrade of the radiology reporting system, which was incompatible with the natural language processing technology that I had installed. The AI was turned off at that point, but I had a look over the edge and into the mine pit.”

“The lesson learned,” White told this news organization, is “If you mine the medical record for unidentified patients before you know what to do with the output, you create a medico-legal minefield. You need to be careful what you wish for with technology, because it may actually come true.”

 

Grappling With the Treatment Gap

An (over)abundance of patients is likely contributing to the “osteoporosis treatment gap” that Australia’s fracture liaison services, which handle many of these patients, are grappling with. One recent meta-analysis showed that not all eligible patients are treated and that not all patients who are treated actually start treatment. Another study showed that only a minority of patients — anywhere between 20% and 40% — who start are still persisting at about 3 years, White said.

Various types of fracture liaison services exist, he noted. The model that has been shown to best promote adherence is the one requiring clinicians to “identify, educate [usually, the primary care physician], evaluate, start treatment, continue treatment, and follow-up at 12 months for to confirm that there is adherence.”

What’s happening now, he said, is that the technology is identifying a high number of vertebral crush fractures, and there’s no education or evaluation. “The radiologist just refers the patient to a primary care physician and hopes for the best. AI isn’t contributing to solving the treatment gap problem; it’s amplifying it. It’s ahead of the ability of organizations to accommodate the findings.”

Solutions, he said, would require support at the top of health systems and organizations, and funding to proceed; data surveys concentrating on vertical integration of the medical record to follow patients wherever they are — eg, hospital, primary care — in their health journeys; a workflow with synchronous diagnosis and treatment planning, delivery, monitoring, and payment; and clinical and community champions advocating and “leading the charge in health tech.”

Furthermore, he advised, organizations need to be “very, very careful with safety and security — that is, managing the digital risks.”

“Oscar Wilde said there are two tragedies in life: One is not getting what one wants, and the other is getting it,” White concluded. “In my career, we’ve moved on from not knowing how to treat osteoporosis to knowing how to treat it. And that is both an asset and a liability.”

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

The woman, in severe pain from hip and knee osteoarthritis, was confined to a wheelchair and had been told that would likely be for life. To qualify for hip replacement surgery, she needed to lose 100 pounds, a seemingly impossible goal. But she wanted to try.

“We tried a couple of medicines — oral medicines off-label — topiramate, phentermine,” said Leslie Golden, MD, MPH, DABM, a family medicine physician and obesity medicine specialist in Watertown, Wisconsin, 42 miles northeast of Madison.

They weren’t enough. But then Golden turned to glucagon-like peptide 1 (GLP-1) receptor agonists, and they delivered.

“She did lose a significant amount of weight and was able to get the hip replacement,” said Golden.

It took a couple of years. However, seeing her walk into her office, rather than wheel in, “is still one of the joys of my practice,” Golden said. “She’s so grateful. She felt everyone else had written her off.”

As she told Golden: “If I fell and broke my leg today, they would take me to surgery without concern.”

Because her hip replacement was viewed as a nonemergency procedure, the accepted threshold for elective safe surgery was a body mass index (BMI) < 40. That BMI cutoff can vary from provider to provider and medical facility to medical facility but is often required for other surgeries as well, including kidney and lung transplants, gender-affirming surgery, bariatric surgery, hernia surgery, and in vitro fertilization procedures.

Golden is at the forefront of a growing trend — obesity medicine physicians collaborating with surgeons to prescribe the more effective GLP-1s and get surgery candidates to the starting line. She worked with Rajit Chakravarty, MD, an adult reconstructive surgeon who practices in Watertown and nearby Madison, to oversee the weight loss.

 

High BMIs & Surgery Issues

High BMIs have long been linked with postsurgery complications, poor wound healing, and other issues, although some research now is questioning some of those associations. Even so, surgeons have long stressed weight loss for their patients with obesity before orthopedic and other procedures.

These days, surgeons are more likely to need to have that talk. In the last decade, the age-adjusted prevalence of severe obesity — a BMI of ≥ 40 — has increased from 7.7% to 9.7% of US adults. The number of joint replacements is also rising — more than 700,000 total knee arthroplasty (TKA) and more than 450,000 total hip arthroplasty (THA), according to the American Academy of Orthopaedic Surgeons. As the population ages, those numbers are expected to increase.

 

Making the GLP-1 Choice

GLP-1s aren’t the only choice, of course. But they’re often more effective, as Golden found, than other medications. And when his patients with obesity are offered bariatric surgery or GLP-1s, “people definitely want to avoid the bariatric surgery,” Chakravarty said.

With the Food and Drug Administration (FDA) approval of semaglutide (Wegovy) in June 2021 for chronic weight management and then tirzepatide (Zepbound) in November 2023, interest has boomed, he said, among his surgery candidates with a high BMI.

The FDA approved Wegovy based on clinical trials, including one in which participants lost an average of 12.4% of initial body weight compared with those on placebo. It approved Zepbound based on clinical trials, including one in which those on Zepbound lost an average of 18% of their body weight, compared with those on placebo.

The wheelchair-bound woman, now 65, began with a BMI of 63, Golden said. She negotiated a cutoff of 45 with the surgeon and got the go-ahead. Currently, her BMI is 36 as she stayed on the medications.

Beyond the benefit of GLP-1s helping patients meet the BMI cutoff, some research finds fewer postoperative infections and readmissions with their use. This study found the medications did lower both, and another found reduced readmissions and complications.

 

Growing Partnerships, Increasing Success

Helping patients lose weight isn’t just about lowering the BMI, Chakravarty pointed out. The aim is to improve nutritional health — to teach patients how to eat healthfully for their needs, in turn improving other health barometers. Referring them to an obesity medicine physician helps to meet those goals.

When Daniel Wiznia, MD, a Yale Medicine orthopedic surgeon and codirector of the Avascular Necrosis Program, has a patient who must delay a TKA or THA until they meet a BMI cutoff, he refers that patient to the Yale Medicine Center for Weight Management, New Haven, Connecticut, to learn about weight loss, including the options of anti-obesity medications or bariatric surgery.

Taking the GLP-1s can be a game changer, according to Wiznia and John Morton, MD, MPH, FACS, FASMBS, Yale’s medical director of Bariatric Surgery and professor and vice chair of surgery, who is a physician-director of the center. The program includes other options, such as bariatric surgery, and emphasizes diet and other lifestyle measures. GLP-1s give about a 15% weight loss, Morton said, compared with bariatric surgery providing up to 30%.

Sarah Stombaugh, MD, a family medicine and obesity medicine physician in Charlottesville, Virginia, often gets referrals from two orthopedic surgeons in her community. One recent patient in her early 60s had a BMI of 43.2, too high to qualify for the TKA she needed. On GLP-1s, the initial goal was to decrease a weight of 244 to 225, bringing the BMI to 39.9. The woman did that, then kept losing before her surgery was scheduled, getting to a weight of 210 or a BMI of 37 and staying there for 3 months before the surgery.

She had the TKA, and 5 months out, she is doing well, Stombaugh said. “We do medical weight loss primarily with the GLP-1s because they’re simply the best, the most effective,” Stombaugh said. She does occasionally use oral medications such as naltrexone/bupropion (Contrave).

Stombaugh sees the collaborating trend as still evolving. When she attends obesity medicine conferences, not all her colleagues report they are partnering with surgeons. But she predicts the practice will increase, saying the popularization of what she terms the more effective GLP-1 medications Wegovy and Zepbound is driving it. Partnering with the surgeon requires a conversation at the beginning, when the referral is made, about goals. After that, she sees her patient monthly and sends progress notes to the surgeon.

Golden collaborates with three orthopedic groups in her area, primarily for knee and hip surgeries, but has also helped patients meet the BMI cutoff before spine-related surgeries. She is helping a lung transplant patient now. She has seen several patients who must meet BMI requirements before starting in vitro fertilization, due to the need for conscious sedation for egg retrieval. She has had a few patients who had to meet a BMI cutoff for nonemergency hernia repair.

 

Insurance Issues

Insurance remains an issue for the pricey medications. “Only about a third of patients are routinely covered with insurance,” Morton said.

However, it’s improving, he said. Golden also finds about a third of private payers cover the medication but tries to use manufacturers’ coupons to help defray the costs (from about $1000 or $1400 to about $500 a month). She has sometimes gotten enough samples to get patients to their BMI goal

Morton consulted for Novo Nordisk, Eli Lilly, Olympus, Teleflex, and Johnson & Johnson.

A version of this article appeared on Medscape.com.

The woman, in severe pain from hip and knee osteoarthritis, was confined to a wheelchair and had been told that would likely be for life. To qualify for hip replacement surgery, she needed to lose 100 pounds, a seemingly impossible goal. But she wanted to try.

“We tried a couple of medicines — oral medicines off-label — topiramate, phentermine,” said Leslie Golden, MD, MPH, DABM, a family medicine physician and obesity medicine specialist in Watertown, Wisconsin, 42 miles northeast of Madison.

They weren’t enough. But then Golden turned to glucagon-like peptide 1 (GLP-1) receptor agonists, and they delivered.

“She did lose a significant amount of weight and was able to get the hip replacement,” said Golden.

It took a couple of years. However, seeing her walk into her office, rather than wheel in, “is still one of the joys of my practice,” Golden said. “She’s so grateful. She felt everyone else had written her off.”

As she told Golden: “If I fell and broke my leg today, they would take me to surgery without concern.”

Because her hip replacement was viewed as a nonemergency procedure, the accepted threshold for elective safe surgery was a body mass index (BMI) < 40. That BMI cutoff can vary from provider to provider and medical facility to medical facility but is often required for other surgeries as well, including kidney and lung transplants, gender-affirming surgery, bariatric surgery, hernia surgery, and in vitro fertilization procedures.

Golden is at the forefront of a growing trend — obesity medicine physicians collaborating with surgeons to prescribe the more effective GLP-1s and get surgery candidates to the starting line. She worked with Rajit Chakravarty, MD, an adult reconstructive surgeon who practices in Watertown and nearby Madison, to oversee the weight loss.

 

High BMIs & Surgery Issues

High BMIs have long been linked with postsurgery complications, poor wound healing, and other issues, although some research now is questioning some of those associations. Even so, surgeons have long stressed weight loss for their patients with obesity before orthopedic and other procedures.

These days, surgeons are more likely to need to have that talk. In the last decade, the age-adjusted prevalence of severe obesity — a BMI of ≥ 40 — has increased from 7.7% to 9.7% of US adults. The number of joint replacements is also rising — more than 700,000 total knee arthroplasty (TKA) and more than 450,000 total hip arthroplasty (THA), according to the American Academy of Orthopaedic Surgeons. As the population ages, those numbers are expected to increase.

 

Making the GLP-1 Choice

GLP-1s aren’t the only choice, of course. But they’re often more effective, as Golden found, than other medications. And when his patients with obesity are offered bariatric surgery or GLP-1s, “people definitely want to avoid the bariatric surgery,” Chakravarty said.

With the Food and Drug Administration (FDA) approval of semaglutide (Wegovy) in June 2021 for chronic weight management and then tirzepatide (Zepbound) in November 2023, interest has boomed, he said, among his surgery candidates with a high BMI.

The FDA approved Wegovy based on clinical trials, including one in which participants lost an average of 12.4% of initial body weight compared with those on placebo. It approved Zepbound based on clinical trials, including one in which those on Zepbound lost an average of 18% of their body weight, compared with those on placebo.

The wheelchair-bound woman, now 65, began with a BMI of 63, Golden said. She negotiated a cutoff of 45 with the surgeon and got the go-ahead. Currently, her BMI is 36 as she stayed on the medications.

Beyond the benefit of GLP-1s helping patients meet the BMI cutoff, some research finds fewer postoperative infections and readmissions with their use. This study found the medications did lower both, and another found reduced readmissions and complications.

 

Growing Partnerships, Increasing Success

Helping patients lose weight isn’t just about lowering the BMI, Chakravarty pointed out. The aim is to improve nutritional health — to teach patients how to eat healthfully for their needs, in turn improving other health barometers. Referring them to an obesity medicine physician helps to meet those goals.

When Daniel Wiznia, MD, a Yale Medicine orthopedic surgeon and codirector of the Avascular Necrosis Program, has a patient who must delay a TKA or THA until they meet a BMI cutoff, he refers that patient to the Yale Medicine Center for Weight Management, New Haven, Connecticut, to learn about weight loss, including the options of anti-obesity medications or bariatric surgery.

Taking the GLP-1s can be a game changer, according to Wiznia and John Morton, MD, MPH, FACS, FASMBS, Yale’s medical director of Bariatric Surgery and professor and vice chair of surgery, who is a physician-director of the center. The program includes other options, such as bariatric surgery, and emphasizes diet and other lifestyle measures. GLP-1s give about a 15% weight loss, Morton said, compared with bariatric surgery providing up to 30%.

Sarah Stombaugh, MD, a family medicine and obesity medicine physician in Charlottesville, Virginia, often gets referrals from two orthopedic surgeons in her community. One recent patient in her early 60s had a BMI of 43.2, too high to qualify for the TKA she needed. On GLP-1s, the initial goal was to decrease a weight of 244 to 225, bringing the BMI to 39.9. The woman did that, then kept losing before her surgery was scheduled, getting to a weight of 210 or a BMI of 37 and staying there for 3 months before the surgery.

She had the TKA, and 5 months out, she is doing well, Stombaugh said. “We do medical weight loss primarily with the GLP-1s because they’re simply the best, the most effective,” Stombaugh said. She does occasionally use oral medications such as naltrexone/bupropion (Contrave).

Stombaugh sees the collaborating trend as still evolving. When she attends obesity medicine conferences, not all her colleagues report they are partnering with surgeons. But she predicts the practice will increase, saying the popularization of what she terms the more effective GLP-1 medications Wegovy and Zepbound is driving it. Partnering with the surgeon requires a conversation at the beginning, when the referral is made, about goals. After that, she sees her patient monthly and sends progress notes to the surgeon.

Golden collaborates with three orthopedic groups in her area, primarily for knee and hip surgeries, but has also helped patients meet the BMI cutoff before spine-related surgeries. She is helping a lung transplant patient now. She has seen several patients who must meet BMI requirements before starting in vitro fertilization, due to the need for conscious sedation for egg retrieval. She has had a few patients who had to meet a BMI cutoff for nonemergency hernia repair.

 

Insurance Issues

Insurance remains an issue for the pricey medications. “Only about a third of patients are routinely covered with insurance,” Morton said.

However, it’s improving, he said. Golden also finds about a third of private payers cover the medication but tries to use manufacturers’ coupons to help defray the costs (from about $1000 or $1400 to about $500 a month). She has sometimes gotten enough samples to get patients to their BMI goal

Morton consulted for Novo Nordisk, Eli Lilly, Olympus, Teleflex, and Johnson & Johnson.

A version of this article appeared on Medscape.com.

The woman, in severe pain from hip and knee osteoarthritis, was confined to a wheelchair and had been told that would likely be for life. To qualify for hip replacement surgery, she needed to lose 100 pounds, a seemingly impossible goal. But she wanted to try.

“We tried a couple of medicines — oral medicines off-label — topiramate, phentermine,” said Leslie Golden, MD, MPH, DABM, a family medicine physician and obesity medicine specialist in Watertown, Wisconsin, 42 miles northeast of Madison.

They weren’t enough. But then Golden turned to glucagon-like peptide 1 (GLP-1) receptor agonists, and they delivered.

“She did lose a significant amount of weight and was able to get the hip replacement,” said Golden.

It took a couple of years. However, seeing her walk into her office, rather than wheel in, “is still one of the joys of my practice,” Golden said. “She’s so grateful. She felt everyone else had written her off.”

As she told Golden: “If I fell and broke my leg today, they would take me to surgery without concern.”

Because her hip replacement was viewed as a nonemergency procedure, the accepted threshold for elective safe surgery was a body mass index (BMI) < 40. That BMI cutoff can vary from provider to provider and medical facility to medical facility but is often required for other surgeries as well, including kidney and lung transplants, gender-affirming surgery, bariatric surgery, hernia surgery, and in vitro fertilization procedures.

Golden is at the forefront of a growing trend — obesity medicine physicians collaborating with surgeons to prescribe the more effective GLP-1s and get surgery candidates to the starting line. She worked with Rajit Chakravarty, MD, an adult reconstructive surgeon who practices in Watertown and nearby Madison, to oversee the weight loss.

 

High BMIs & Surgery Issues

High BMIs have long been linked with postsurgery complications, poor wound healing, and other issues, although some research now is questioning some of those associations. Even so, surgeons have long stressed weight loss for their patients with obesity before orthopedic and other procedures.

These days, surgeons are more likely to need to have that talk. In the last decade, the age-adjusted prevalence of severe obesity — a BMI of ≥ 40 — has increased from 7.7% to 9.7% of US adults. The number of joint replacements is also rising — more than 700,000 total knee arthroplasty (TKA) and more than 450,000 total hip arthroplasty (THA), according to the American Academy of Orthopaedic Surgeons. As the population ages, those numbers are expected to increase.

 

Making the GLP-1 Choice

GLP-1s aren’t the only choice, of course. But they’re often more effective, as Golden found, than other medications. And when his patients with obesity are offered bariatric surgery or GLP-1s, “people definitely want to avoid the bariatric surgery,” Chakravarty said.

With the Food and Drug Administration (FDA) approval of semaglutide (Wegovy) in June 2021 for chronic weight management and then tirzepatide (Zepbound) in November 2023, interest has boomed, he said, among his surgery candidates with a high BMI.

The FDA approved Wegovy based on clinical trials, including one in which participants lost an average of 12.4% of initial body weight compared with those on placebo. It approved Zepbound based on clinical trials, including one in which those on Zepbound lost an average of 18% of their body weight, compared with those on placebo.

The wheelchair-bound woman, now 65, began with a BMI of 63, Golden said. She negotiated a cutoff of 45 with the surgeon and got the go-ahead. Currently, her BMI is 36 as she stayed on the medications.

Beyond the benefit of GLP-1s helping patients meet the BMI cutoff, some research finds fewer postoperative infections and readmissions with their use. This study found the medications did lower both, and another found reduced readmissions and complications.

 

Growing Partnerships, Increasing Success

Helping patients lose weight isn’t just about lowering the BMI, Chakravarty pointed out. The aim is to improve nutritional health — to teach patients how to eat healthfully for their needs, in turn improving other health barometers. Referring them to an obesity medicine physician helps to meet those goals.

When Daniel Wiznia, MD, a Yale Medicine orthopedic surgeon and codirector of the Avascular Necrosis Program, has a patient who must delay a TKA or THA until they meet a BMI cutoff, he refers that patient to the Yale Medicine Center for Weight Management, New Haven, Connecticut, to learn about weight loss, including the options of anti-obesity medications or bariatric surgery.

Taking the GLP-1s can be a game changer, according to Wiznia and John Morton, MD, MPH, FACS, FASMBS, Yale’s medical director of Bariatric Surgery and professor and vice chair of surgery, who is a physician-director of the center. The program includes other options, such as bariatric surgery, and emphasizes diet and other lifestyle measures. GLP-1s give about a 15% weight loss, Morton said, compared with bariatric surgery providing up to 30%.

Sarah Stombaugh, MD, a family medicine and obesity medicine physician in Charlottesville, Virginia, often gets referrals from two orthopedic surgeons in her community. One recent patient in her early 60s had a BMI of 43.2, too high to qualify for the TKA she needed. On GLP-1s, the initial goal was to decrease a weight of 244 to 225, bringing the BMI to 39.9. The woman did that, then kept losing before her surgery was scheduled, getting to a weight of 210 or a BMI of 37 and staying there for 3 months before the surgery.

She had the TKA, and 5 months out, she is doing well, Stombaugh said. “We do medical weight loss primarily with the GLP-1s because they’re simply the best, the most effective,” Stombaugh said. She does occasionally use oral medications such as naltrexone/bupropion (Contrave).

Stombaugh sees the collaborating trend as still evolving. When she attends obesity medicine conferences, not all her colleagues report they are partnering with surgeons. But she predicts the practice will increase, saying the popularization of what she terms the more effective GLP-1 medications Wegovy and Zepbound is driving it. Partnering with the surgeon requires a conversation at the beginning, when the referral is made, about goals. After that, she sees her patient monthly and sends progress notes to the surgeon.

Golden collaborates with three orthopedic groups in her area, primarily for knee and hip surgeries, but has also helped patients meet the BMI cutoff before spine-related surgeries. She is helping a lung transplant patient now. She has seen several patients who must meet BMI requirements before starting in vitro fertilization, due to the need for conscious sedation for egg retrieval. She has had a few patients who had to meet a BMI cutoff for nonemergency hernia repair.

 

Insurance Issues

Insurance remains an issue for the pricey medications. “Only about a third of patients are routinely covered with insurance,” Morton said.

However, it’s improving, he said. Golden also finds about a third of private payers cover the medication but tries to use manufacturers’ coupons to help defray the costs (from about $1000 or $1400 to about $500 a month). She has sometimes gotten enough samples to get patients to their BMI goal

Morton consulted for Novo Nordisk, Eli Lilly, Olympus, Teleflex, and Johnson & Johnson.

A version of this article appeared on Medscape.com.

TOPLINE:

Aerobic exercise shows a linear relationship with weight loss, with 30 minutes of weekly exercise linked to reduced body weight, waist circumference, and body fat in adults who were overweight or had obesity.

METHODOLOGY:

• Researchers conducted a meta-analysis of randomized clinical trials to investigate the association of varying intensities and durations of aerobic exercise with adiposity measures in adults with obesity or who were overweight.
• Overall, 116 randomized clinical trials that spanned across North America, Asia, Europe, Australia, South America, and Africa and involved 6880 adults (mean age, 46 years; 61% women) were included.
• The trials were required to have intervention durations of at least 8 weeks; all trials used supervised aerobic exercise, such as walking or running, while the control groups remained sedentary or continued usual activities.
• The intensity of exercise was defined as: Light (40%-55% maximum heart rate), moderate (55%-70% maximum heart rate), and vigorous (70%-90% maximum heart rate).
• The primary outcomes were body weight changes and adverse events; the secondary outcomes included changes in waist circumference, quality-of-life scores, and reduction in medications like antihypertensives.

TAKEAWAY:

• Every 30 minutes of aerobic exercise per week was associated with a 1.14 lb reduction in body weight (certainty of evidence, moderate).
• Every 30 minutes of aerobic exercise per week was also associated with lower waist circumference (mean difference, −0.56 cm; 95% CI, –0.67 to –0.45), body fat percentage (mean difference, –0.37%; 95% CI, –0.43 to –0.31), and body fat mass (mean difference, –0.20 kg; 95% CI, –0.32 to –0.08), along with reduced visceral and subcutaneous adipose tissue.
• A dose-response meta-analysis revealed that body fat percentage improved most significantly with 150 minutes of aerobic exercise per week, while body weight and waist circumference decreased linearly with increasing duration of aerobic exercise at 300 min/wk at different intensities.
• Adverse events with aerobic exercise were mostly mild or moderate musculoskeletal symptoms.

IN PRACTICE:

“Point-specific estimates for different aerobic exercise duration and intensity can help patients and healthcare professionals select the optimal aerobic exercise duration and intensity according to their weight loss goals,” the authors wrote.

 

SOURCE:

The study was led by Ahmad Jayedi, PhD, of the Department of Epidemiology and Biostatistics in the School of Public Health at the Imperial College London in England. It was published online on December 26, 2024, in JAMA Network Open.

 

LIMITATIONS:

High heterogeneity was present in the data. Only one trial included measures of health-related quality of life, and two studies included measures of medication use. Dietary habits and smoking status of participants were not included in studies, so any potential effects were not risk adjusted for.

 

DISCLOSURES:

No funding sources were reported. The authors reported no relevant 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:

Aerobic exercise shows a linear relationship with weight loss, with 30 minutes of weekly exercise linked to reduced body weight, waist circumference, and body fat in adults who were overweight or had obesity.

METHODOLOGY:

• Researchers conducted a meta-analysis of randomized clinical trials to investigate the association of varying intensities and durations of aerobic exercise with adiposity measures in adults with obesity or who were overweight.
• Overall, 116 randomized clinical trials that spanned across North America, Asia, Europe, Australia, South America, and Africa and involved 6880 adults (mean age, 46 years; 61% women) were included.
• The trials were required to have intervention durations of at least 8 weeks; all trials used supervised aerobic exercise, such as walking or running, while the control groups remained sedentary or continued usual activities.
• The intensity of exercise was defined as: Light (40%-55% maximum heart rate), moderate (55%-70% maximum heart rate), and vigorous (70%-90% maximum heart rate).
• The primary outcomes were body weight changes and adverse events; the secondary outcomes included changes in waist circumference, quality-of-life scores, and reduction in medications like antihypertensives.

TAKEAWAY:

• Every 30 minutes of aerobic exercise per week was associated with a 1.14 lb reduction in body weight (certainty of evidence, moderate).
• Every 30 minutes of aerobic exercise per week was also associated with lower waist circumference (mean difference, −0.56 cm; 95% CI, –0.67 to –0.45), body fat percentage (mean difference, –0.37%; 95% CI, –0.43 to –0.31), and body fat mass (mean difference, –0.20 kg; 95% CI, –0.32 to –0.08), along with reduced visceral and subcutaneous adipose tissue.
• A dose-response meta-analysis revealed that body fat percentage improved most significantly with 150 minutes of aerobic exercise per week, while body weight and waist circumference decreased linearly with increasing duration of aerobic exercise at 300 min/wk at different intensities.
• Adverse events with aerobic exercise were mostly mild or moderate musculoskeletal symptoms.

IN PRACTICE:

“Point-specific estimates for different aerobic exercise duration and intensity can help patients and healthcare professionals select the optimal aerobic exercise duration and intensity according to their weight loss goals,” the authors wrote.

 

SOURCE:

The study was led by Ahmad Jayedi, PhD, of the Department of Epidemiology and Biostatistics in the School of Public Health at the Imperial College London in England. It was published online on December 26, 2024, in JAMA Network Open.

 

LIMITATIONS:

High heterogeneity was present in the data. Only one trial included measures of health-related quality of life, and two studies included measures of medication use. Dietary habits and smoking status of participants were not included in studies, so any potential effects were not risk adjusted for.

 

DISCLOSURES:

No funding sources were reported. The authors reported no relevant 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:

Aerobic exercise shows a linear relationship with weight loss, with 30 minutes of weekly exercise linked to reduced body weight, waist circumference, and body fat in adults who were overweight or had obesity.

METHODOLOGY:

• Researchers conducted a meta-analysis of randomized clinical trials to investigate the association of varying intensities and durations of aerobic exercise with adiposity measures in adults with obesity or who were overweight.
• Overall, 116 randomized clinical trials that spanned across North America, Asia, Europe, Australia, South America, and Africa and involved 6880 adults (mean age, 46 years; 61% women) were included.
• The trials were required to have intervention durations of at least 8 weeks; all trials used supervised aerobic exercise, such as walking or running, while the control groups remained sedentary or continued usual activities.
• The intensity of exercise was defined as: Light (40%-55% maximum heart rate), moderate (55%-70% maximum heart rate), and vigorous (70%-90% maximum heart rate).
• The primary outcomes were body weight changes and adverse events; the secondary outcomes included changes in waist circumference, quality-of-life scores, and reduction in medications like antihypertensives.

TAKEAWAY:

• Every 30 minutes of aerobic exercise per week was associated with a 1.14 lb reduction in body weight (certainty of evidence, moderate).
• Every 30 minutes of aerobic exercise per week was also associated with lower waist circumference (mean difference, −0.56 cm; 95% CI, –0.67 to –0.45), body fat percentage (mean difference, –0.37%; 95% CI, –0.43 to –0.31), and body fat mass (mean difference, –0.20 kg; 95% CI, –0.32 to –0.08), along with reduced visceral and subcutaneous adipose tissue.
• A dose-response meta-analysis revealed that body fat percentage improved most significantly with 150 minutes of aerobic exercise per week, while body weight and waist circumference decreased linearly with increasing duration of aerobic exercise at 300 min/wk at different intensities.
• Adverse events with aerobic exercise were mostly mild or moderate musculoskeletal symptoms.

IN PRACTICE:

“Point-specific estimates for different aerobic exercise duration and intensity can help patients and healthcare professionals select the optimal aerobic exercise duration and intensity according to their weight loss goals,” the authors wrote.

 

SOURCE:

The study was led by Ahmad Jayedi, PhD, of the Department of Epidemiology and Biostatistics in the School of Public Health at the Imperial College London in England. It was published online on December 26, 2024, in JAMA Network Open.

 

LIMITATIONS:

High heterogeneity was present in the data. Only one trial included measures of health-related quality of life, and two studies included measures of medication use. Dietary habits and smoking status of participants were not included in studies, so any potential effects were not risk adjusted for.

 

DISCLOSURES:

No funding sources were reported. The authors reported no relevant 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.

Recently, a 40-year-old woman took to Facebook to announce that she had died.

Rachel Davies, of Wales, wrote: “If you’re reading this, then it means I’m no longer here. What a life I’ve had, and surprisingly, since cancer entered my life. When I look through my photos, I’ve done and seen so much since cancer, and probably some of my best memories are from this period. In so many ways, I have to thank it for learning how to live fully. What I wish is that everyone can experience the same but without needing cancer. Get out there, experience life fully, and wear that dress!!! I’m so sad to leave my family and friends, I wish I never had to go. I’m so grateful to have had Charlie young so that I’ve watched him grow into the man he is today. I’m unbelievably proud of him. I am thankful I had the opportunity to have Kacey and Jacob in my life. Lastly, I was blessed to meet the love of my life, my husband, and my best friend. I have no regrets, I have had a wonderful life. So to all of you, don’t be sad I’ve gone. Live your life and live it well. Love, Rachel x.”

 

I didn’t know Ms. Davies, but am likely among many who wish I had. In a terrible situation she kept trying.

She had HER2 metastatic breast cancer, which can respond to the drug Enhertu (trastuzumab). Unfortunately, she never had the chance, because it wasn’t available to her in Wales. In the United Kingdom it’s available only in Scotland.

I’m not saying it was a cure. Statistically, it likely would have bought her another 6 months of family time. But that’s still another half year.

I’m not blaming the Welsh NHS, though they made the decision not to cover it because of cost. The jobs of such committees is a thankless one, trying to decide where the limited money goes — vaccines for many children that are proven to lessen morbidity and mortality over the course of a lifetime, or to add 6 months to the lives of comparatively fewer women with HER2 metastatic breast cancer.

I’m not blaming the company that makes Enhertu, though it was the cost that kept her from getting it. Bringing a drug to market, with all the labs and clinical research behind it, ain’t cheap. If the company can’t keep the lights on they’re not going to able to develop future pharmaceuticals to help others, though I do wonder if a better price could have been negotiated. (I’m not trying to justify the salaries of insurance CEOs — don’t even get me started on those.)

Money is always limited, and human suffering is infinite. Every health care organization, public or private, has to face that simple fact. There is no right place to draw the line, so we use the greatest good for the greatest many as our best guess.

In her last post, though, Ms. Davies didn’t dwell on any of this. She reflected on her joys and blessings, and encouraged others to live life fully. Things we should all focus on.

In a world that often seems to have gone mad, it’s good to keep in mind that there is more good than bad out there. 

Thank you, Ms. Davies, for the reminder.

Allan M. Block, MD, has a solo neurology practice in Scottsdale, Arizona.

Recently, a 40-year-old woman took to Facebook to announce that she had died.

Rachel Davies, of Wales, wrote: “If you’re reading this, then it means I’m no longer here. What a life I’ve had, and surprisingly, since cancer entered my life. When I look through my photos, I’ve done and seen so much since cancer, and probably some of my best memories are from this period. In so many ways, I have to thank it for learning how to live fully. What I wish is that everyone can experience the same but without needing cancer. Get out there, experience life fully, and wear that dress!!! I’m so sad to leave my family and friends, I wish I never had to go. I’m so grateful to have had Charlie young so that I’ve watched him grow into the man he is today. I’m unbelievably proud of him. I am thankful I had the opportunity to have Kacey and Jacob in my life. Lastly, I was blessed to meet the love of my life, my husband, and my best friend. I have no regrets, I have had a wonderful life. So to all of you, don’t be sad I’ve gone. Live your life and live it well. Love, Rachel x.”

 

I didn’t know Ms. Davies, but am likely among many who wish I had. In a terrible situation she kept trying.

She had HER2 metastatic breast cancer, which can respond to the drug Enhertu (trastuzumab). Unfortunately, she never had the chance, because it wasn’t available to her in Wales. In the United Kingdom it’s available only in Scotland.

I’m not saying it was a cure. Statistically, it likely would have bought her another 6 months of family time. But that’s still another half year.

I’m not blaming the Welsh NHS, though they made the decision not to cover it because of cost. The jobs of such committees is a thankless one, trying to decide where the limited money goes — vaccines for many children that are proven to lessen morbidity and mortality over the course of a lifetime, or to add 6 months to the lives of comparatively fewer women with HER2 metastatic breast cancer.

I’m not blaming the company that makes Enhertu, though it was the cost that kept her from getting it. Bringing a drug to market, with all the labs and clinical research behind it, ain’t cheap. If the company can’t keep the lights on they’re not going to able to develop future pharmaceuticals to help others, though I do wonder if a better price could have been negotiated. (I’m not trying to justify the salaries of insurance CEOs — don’t even get me started on those.)

Money is always limited, and human suffering is infinite. Every health care organization, public or private, has to face that simple fact. There is no right place to draw the line, so we use the greatest good for the greatest many as our best guess.

In her last post, though, Ms. Davies didn’t dwell on any of this. She reflected on her joys and blessings, and encouraged others to live life fully. Things we should all focus on.

In a world that often seems to have gone mad, it’s good to keep in mind that there is more good than bad out there. 

Thank you, Ms. Davies, for the reminder.

Allan M. Block, MD, has a solo neurology practice in Scottsdale, Arizona.

Recently, a 40-year-old woman took to Facebook to announce that she had died.

Rachel Davies, of Wales, wrote: “If you’re reading this, then it means I’m no longer here. What a life I’ve had, and surprisingly, since cancer entered my life. When I look through my photos, I’ve done and seen so much since cancer, and probably some of my best memories are from this period. In so many ways, I have to thank it for learning how to live fully. What I wish is that everyone can experience the same but without needing cancer. Get out there, experience life fully, and wear that dress!!! I’m so sad to leave my family and friends, I wish I never had to go. I’m so grateful to have had Charlie young so that I’ve watched him grow into the man he is today. I’m unbelievably proud of him. I am thankful I had the opportunity to have Kacey and Jacob in my life. Lastly, I was blessed to meet the love of my life, my husband, and my best friend. I have no regrets, I have had a wonderful life. So to all of you, don’t be sad I’ve gone. Live your life and live it well. Love, Rachel x.”

 

I didn’t know Ms. Davies, but am likely among many who wish I had. In a terrible situation she kept trying.

She had HER2 metastatic breast cancer, which can respond to the drug Enhertu (trastuzumab). Unfortunately, she never had the chance, because it wasn’t available to her in Wales. In the United Kingdom it’s available only in Scotland.

I’m not saying it was a cure. Statistically, it likely would have bought her another 6 months of family time. But that’s still another half year.

I’m not blaming the Welsh NHS, though they made the decision not to cover it because of cost. The jobs of such committees is a thankless one, trying to decide where the limited money goes — vaccines for many children that are proven to lessen morbidity and mortality over the course of a lifetime, or to add 6 months to the lives of comparatively fewer women with HER2 metastatic breast cancer.

I’m not blaming the company that makes Enhertu, though it was the cost that kept her from getting it. Bringing a drug to market, with all the labs and clinical research behind it, ain’t cheap. If the company can’t keep the lights on they’re not going to able to develop future pharmaceuticals to help others, though I do wonder if a better price could have been negotiated. (I’m not trying to justify the salaries of insurance CEOs — don’t even get me started on those.)

Money is always limited, and human suffering is infinite. Every health care organization, public or private, has to face that simple fact. There is no right place to draw the line, so we use the greatest good for the greatest many as our best guess.

In her last post, though, Ms. Davies didn’t dwell on any of this. She reflected on her joys and blessings, and encouraged others to live life fully. Things we should all focus on.

In a world that often seems to have gone mad, it’s good to keep in mind that there is more good than bad out there. 

Thank you, Ms. Davies, for the reminder.

Allan M. Block, MD, has a solo neurology practice in Scottsdale, Arizona.