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Losing Muscle with GLP-1 RAs? There May be a Drug for That
NEW ORLEANS — Medications in development would preserve muscle mass and augment fat loss when used in combination with glucagon-like peptide 1 (GLP-1) receptor agonists taken for weight loss.
As drugs such as semaglutide (Wegovy) and the dual agonist glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 tirzepatide (Zepbound) are producing unprecedented degrees of weight loss in increasing numbers of people, concern has arisen about the proportion of the lost weight, approximately 30%-50%, that is beneficial lean body mass vs fat mass. While some loss of muscle mass is expected with any rapid overall weight loss, it’s not clear what long-term effect that may have on physical function, bone density, and longevity, particularly in older adults with sarcopenic obesity who are at risk for muscle atrophy and frailty.
Trials now underway will need to show improved function — not just increased muscle — and also establish safety, experts told this news organization.
One such agent is Veru Inc.’s oral selective androgen receptor modulator (SARM) enobosarm, currently in a phase 2b clinical trial for use with semaglutide in people who are at risk for muscle atrophy and weakness.
Also in a phase 2b trial for use with semaglutide is the antimyostatin intravenous agent bimagrumab. In July 2023, Eli Lilly purchased Versanis, the company that was developing that drug. Previous phase 2 data on bimagrumab alone vs placebo in people with obesity and type 2 diabetes showed improvement in muscle mass with greater fat loss but also produced a signal for pancreatitis requiring further evaluation.
Scholar Rock’s intravenous antimyostatin apitegromab is also now in a phase 2 trial and Biohaven Pharmaceuticals is expected to launch a phase 2 trial of its subcutaneous antimyostatin taldefgrobep alfa later this year.
Most of these and other similar agents have also been under investigation for use in one or more other muscle-losing conditions including spinal muscular atrophy, sarcopenia, and cancer.
“Wouldn’t it be nice if there was a drug that built up muscle mass?”
Data presented in two late-breaking posters at the annual meeting of the American Association of Clinical Endocrinology meeting held May 9-11, 2024, laid the groundwork for the subsequent phase 2 studies of enobosarm in combination with a GLP-1 RA. One showed increases in total lean mass and decreases in total fat mass with 3 mg enobosarm for 14 days compared with placebo in both healthy young men and older men (≥ 60 years), with the greatest benefit seen in the older men who had lower lean mass and higher fat mass at baseline.
The other was a post hoc analysis of a phase 3 clinical trial of 3 mg/d oral enobosarm for the treatment of muscle wasting in advanced lung cancer. Here, a subset of participants who were aged ≥ 60 years and had obesity also showed reductions in fat mass and preservation of lean body mass with the drug compared with placebo, leading to “high-quality weight loss.”
Endocrinologist Adrian Dobs, MD, professor of medicine and oncology at Johns Hopkins University Medical School, Baltimore, an investigator on both of the Veru-sponsored studies, told Medscape Medical News, “The wishful thinking about these drugs has been around for quite a while, particularly in the cancer population or ... in a frail population. The hope was, wouldn’t it be nice if there was a drug that built up muscle mass? Certainly, we know that going into the gym does that but looking for some medication had been the goal. The thought was this class of medication would have a muscle-building effect, an anabolic effect without an androgenic effect causing masculinization.”
The problem with those studies in terms of regulatory approval, Dr. Dobs said, was defining the endpoints. “The [US Food and Drug Administration] is very interested in functional status. You can show that there is an increase in muscle mass. But to take that leap and show that a person can walk upstairs, carry groceries, and be more functionally able is hard to prove.”
And she noted that bringing frail elderly people into clinical trials isn’t easy. But now, “this is an interesting new avenue of scientific pursuit, looking at this particular population that is losing weight due to GLP-1 [agonists]. Now we’re dealing with high numbers of patients who are easy to identify because they’re taking those medications.”
“We have to also focus on ‘first, do no harm’”
Asked to comment, Angela Fitch, MD, associate director of the Massachusetts General Hospital Weight Center, Boston, expressed caution. “We have to remember that it is not all about muscle mass. Maintaining muscle mass with weight loss is obviously important, but even today, with 30% of the weight loss coming from lean mass, which is not the same as muscle, there are huge benefits from fat loss, including cardiovascular and cancer risk reduction, increased life increased life expectancy, and diabetes remission.”
Moreover, Dr. Fitch pointed out, SARMs have been linked to increased cardiovascular events and blood clots.
“So, we have to also focus on ‘first, do no harm’. A lot of these muscle-promoting medications have been associated with increased risk of other things. So, it is going to take a lot of time and testing to be sure they are safe. While I am supportive of research to look into these risks vs benefits, we have to be mindful of the risks and recognize that in most cases of weight loss in people with obesity losing some lean mass is acceptable and the benefits of fat loss outweigh the risks of lean loss, especially if people are doing resistance exercise and maintaining strength.”
“Wherever the GLP-1s go, we go”
In an investor call held on May 8, 2024, Veru’s Chairman, CEO, and President Mitchell Steiner, MD, said that the current phase 2b study of enobosarm with semaglutide is only examining people aged ≥ 60 years to maximize the functional outcome benefit. But phase 3, he anticipates, will be “all comers, for sure. And then we’ll embed special populations.” The thinking, he said, is “Wherever the GLP-1s go, we go.”
Fitch has participated on advisory boards for Jenny Craig, Novo Nordisk, Eli Lily, Sidekick Health, and Vivus. Dobs had no disclosures beyond conducting research for Veru.
A version of this article appeared on Medscape.com.
NEW ORLEANS — Medications in development would preserve muscle mass and augment fat loss when used in combination with glucagon-like peptide 1 (GLP-1) receptor agonists taken for weight loss.
As drugs such as semaglutide (Wegovy) and the dual agonist glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 tirzepatide (Zepbound) are producing unprecedented degrees of weight loss in increasing numbers of people, concern has arisen about the proportion of the lost weight, approximately 30%-50%, that is beneficial lean body mass vs fat mass. While some loss of muscle mass is expected with any rapid overall weight loss, it’s not clear what long-term effect that may have on physical function, bone density, and longevity, particularly in older adults with sarcopenic obesity who are at risk for muscle atrophy and frailty.
Trials now underway will need to show improved function — not just increased muscle — and also establish safety, experts told this news organization.
One such agent is Veru Inc.’s oral selective androgen receptor modulator (SARM) enobosarm, currently in a phase 2b clinical trial for use with semaglutide in people who are at risk for muscle atrophy and weakness.
Also in a phase 2b trial for use with semaglutide is the antimyostatin intravenous agent bimagrumab. In July 2023, Eli Lilly purchased Versanis, the company that was developing that drug. Previous phase 2 data on bimagrumab alone vs placebo in people with obesity and type 2 diabetes showed improvement in muscle mass with greater fat loss but also produced a signal for pancreatitis requiring further evaluation.
Scholar Rock’s intravenous antimyostatin apitegromab is also now in a phase 2 trial and Biohaven Pharmaceuticals is expected to launch a phase 2 trial of its subcutaneous antimyostatin taldefgrobep alfa later this year.
Most of these and other similar agents have also been under investigation for use in one or more other muscle-losing conditions including spinal muscular atrophy, sarcopenia, and cancer.
“Wouldn’t it be nice if there was a drug that built up muscle mass?”
Data presented in two late-breaking posters at the annual meeting of the American Association of Clinical Endocrinology meeting held May 9-11, 2024, laid the groundwork for the subsequent phase 2 studies of enobosarm in combination with a GLP-1 RA. One showed increases in total lean mass and decreases in total fat mass with 3 mg enobosarm for 14 days compared with placebo in both healthy young men and older men (≥ 60 years), with the greatest benefit seen in the older men who had lower lean mass and higher fat mass at baseline.
The other was a post hoc analysis of a phase 3 clinical trial of 3 mg/d oral enobosarm for the treatment of muscle wasting in advanced lung cancer. Here, a subset of participants who were aged ≥ 60 years and had obesity also showed reductions in fat mass and preservation of lean body mass with the drug compared with placebo, leading to “high-quality weight loss.”
Endocrinologist Adrian Dobs, MD, professor of medicine and oncology at Johns Hopkins University Medical School, Baltimore, an investigator on both of the Veru-sponsored studies, told Medscape Medical News, “The wishful thinking about these drugs has been around for quite a while, particularly in the cancer population or ... in a frail population. The hope was, wouldn’t it be nice if there was a drug that built up muscle mass? Certainly, we know that going into the gym does that but looking for some medication had been the goal. The thought was this class of medication would have a muscle-building effect, an anabolic effect without an androgenic effect causing masculinization.”
The problem with those studies in terms of regulatory approval, Dr. Dobs said, was defining the endpoints. “The [US Food and Drug Administration] is very interested in functional status. You can show that there is an increase in muscle mass. But to take that leap and show that a person can walk upstairs, carry groceries, and be more functionally able is hard to prove.”
And she noted that bringing frail elderly people into clinical trials isn’t easy. But now, “this is an interesting new avenue of scientific pursuit, looking at this particular population that is losing weight due to GLP-1 [agonists]. Now we’re dealing with high numbers of patients who are easy to identify because they’re taking those medications.”
“We have to also focus on ‘first, do no harm’”
Asked to comment, Angela Fitch, MD, associate director of the Massachusetts General Hospital Weight Center, Boston, expressed caution. “We have to remember that it is not all about muscle mass. Maintaining muscle mass with weight loss is obviously important, but even today, with 30% of the weight loss coming from lean mass, which is not the same as muscle, there are huge benefits from fat loss, including cardiovascular and cancer risk reduction, increased life increased life expectancy, and diabetes remission.”
Moreover, Dr. Fitch pointed out, SARMs have been linked to increased cardiovascular events and blood clots.
“So, we have to also focus on ‘first, do no harm’. A lot of these muscle-promoting medications have been associated with increased risk of other things. So, it is going to take a lot of time and testing to be sure they are safe. While I am supportive of research to look into these risks vs benefits, we have to be mindful of the risks and recognize that in most cases of weight loss in people with obesity losing some lean mass is acceptable and the benefits of fat loss outweigh the risks of lean loss, especially if people are doing resistance exercise and maintaining strength.”
“Wherever the GLP-1s go, we go”
In an investor call held on May 8, 2024, Veru’s Chairman, CEO, and President Mitchell Steiner, MD, said that the current phase 2b study of enobosarm with semaglutide is only examining people aged ≥ 60 years to maximize the functional outcome benefit. But phase 3, he anticipates, will be “all comers, for sure. And then we’ll embed special populations.” The thinking, he said, is “Wherever the GLP-1s go, we go.”
Fitch has participated on advisory boards for Jenny Craig, Novo Nordisk, Eli Lily, Sidekick Health, and Vivus. Dobs had no disclosures beyond conducting research for Veru.
A version of this article appeared on Medscape.com.
NEW ORLEANS — Medications in development would preserve muscle mass and augment fat loss when used in combination with glucagon-like peptide 1 (GLP-1) receptor agonists taken for weight loss.
As drugs such as semaglutide (Wegovy) and the dual agonist glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 tirzepatide (Zepbound) are producing unprecedented degrees of weight loss in increasing numbers of people, concern has arisen about the proportion of the lost weight, approximately 30%-50%, that is beneficial lean body mass vs fat mass. While some loss of muscle mass is expected with any rapid overall weight loss, it’s not clear what long-term effect that may have on physical function, bone density, and longevity, particularly in older adults with sarcopenic obesity who are at risk for muscle atrophy and frailty.
Trials now underway will need to show improved function — not just increased muscle — and also establish safety, experts told this news organization.
One such agent is Veru Inc.’s oral selective androgen receptor modulator (SARM) enobosarm, currently in a phase 2b clinical trial for use with semaglutide in people who are at risk for muscle atrophy and weakness.
Also in a phase 2b trial for use with semaglutide is the antimyostatin intravenous agent bimagrumab. In July 2023, Eli Lilly purchased Versanis, the company that was developing that drug. Previous phase 2 data on bimagrumab alone vs placebo in people with obesity and type 2 diabetes showed improvement in muscle mass with greater fat loss but also produced a signal for pancreatitis requiring further evaluation.
Scholar Rock’s intravenous antimyostatin apitegromab is also now in a phase 2 trial and Biohaven Pharmaceuticals is expected to launch a phase 2 trial of its subcutaneous antimyostatin taldefgrobep alfa later this year.
Most of these and other similar agents have also been under investigation for use in one or more other muscle-losing conditions including spinal muscular atrophy, sarcopenia, and cancer.
“Wouldn’t it be nice if there was a drug that built up muscle mass?”
Data presented in two late-breaking posters at the annual meeting of the American Association of Clinical Endocrinology meeting held May 9-11, 2024, laid the groundwork for the subsequent phase 2 studies of enobosarm in combination with a GLP-1 RA. One showed increases in total lean mass and decreases in total fat mass with 3 mg enobosarm for 14 days compared with placebo in both healthy young men and older men (≥ 60 years), with the greatest benefit seen in the older men who had lower lean mass and higher fat mass at baseline.
The other was a post hoc analysis of a phase 3 clinical trial of 3 mg/d oral enobosarm for the treatment of muscle wasting in advanced lung cancer. Here, a subset of participants who were aged ≥ 60 years and had obesity also showed reductions in fat mass and preservation of lean body mass with the drug compared with placebo, leading to “high-quality weight loss.”
Endocrinologist Adrian Dobs, MD, professor of medicine and oncology at Johns Hopkins University Medical School, Baltimore, an investigator on both of the Veru-sponsored studies, told Medscape Medical News, “The wishful thinking about these drugs has been around for quite a while, particularly in the cancer population or ... in a frail population. The hope was, wouldn’t it be nice if there was a drug that built up muscle mass? Certainly, we know that going into the gym does that but looking for some medication had been the goal. The thought was this class of medication would have a muscle-building effect, an anabolic effect without an androgenic effect causing masculinization.”
The problem with those studies in terms of regulatory approval, Dr. Dobs said, was defining the endpoints. “The [US Food and Drug Administration] is very interested in functional status. You can show that there is an increase in muscle mass. But to take that leap and show that a person can walk upstairs, carry groceries, and be more functionally able is hard to prove.”
And she noted that bringing frail elderly people into clinical trials isn’t easy. But now, “this is an interesting new avenue of scientific pursuit, looking at this particular population that is losing weight due to GLP-1 [agonists]. Now we’re dealing with high numbers of patients who are easy to identify because they’re taking those medications.”
“We have to also focus on ‘first, do no harm’”
Asked to comment, Angela Fitch, MD, associate director of the Massachusetts General Hospital Weight Center, Boston, expressed caution. “We have to remember that it is not all about muscle mass. Maintaining muscle mass with weight loss is obviously important, but even today, with 30% of the weight loss coming from lean mass, which is not the same as muscle, there are huge benefits from fat loss, including cardiovascular and cancer risk reduction, increased life increased life expectancy, and diabetes remission.”
Moreover, Dr. Fitch pointed out, SARMs have been linked to increased cardiovascular events and blood clots.
“So, we have to also focus on ‘first, do no harm’. A lot of these muscle-promoting medications have been associated with increased risk of other things. So, it is going to take a lot of time and testing to be sure they are safe. While I am supportive of research to look into these risks vs benefits, we have to be mindful of the risks and recognize that in most cases of weight loss in people with obesity losing some lean mass is acceptable and the benefits of fat loss outweigh the risks of lean loss, especially if people are doing resistance exercise and maintaining strength.”
“Wherever the GLP-1s go, we go”
In an investor call held on May 8, 2024, Veru’s Chairman, CEO, and President Mitchell Steiner, MD, said that the current phase 2b study of enobosarm with semaglutide is only examining people aged ≥ 60 years to maximize the functional outcome benefit. But phase 3, he anticipates, will be “all comers, for sure. And then we’ll embed special populations.” The thinking, he said, is “Wherever the GLP-1s go, we go.”
Fitch has participated on advisory boards for Jenny Craig, Novo Nordisk, Eli Lily, Sidekick Health, and Vivus. Dobs had no disclosures beyond conducting research for Veru.
A version of this article appeared on Medscape.com.
FROM AACE 2024
AI-Assessed Bowel Prep Helps Ensure Successful Screening Colonoscopy
TOPLINE:
The adenoma missed rate (AMR), including lesions > 5 mm, was lower in patients whose precolonoscopy bowel preparation was deemed suitable using an artificial intelligence (AI)–guided assessment.
METHODOLOGY:
- Individuals with inappropriate bowel preparation before a colonoscopy face a higher lesion miss rate and may need to repeat the procedure.
- This prospective single-center study analyzed the screening colonoscopies of 393 individuals (mean age, 55 years; 50% men) using assessments made by endoscopists and AI.
- The AI-based method was the e-Boston Bowel Preparation Scale (e-BBPS), in which a score of 3 is the threshold to guarantee an adenoma detection rate of > 25%. Patients with an e-BBPS score of ≤ 3 or > 3 were considered by the AI as being qualified or unqualified, respectively.
- If the bowel preparation was considered adequate by the endoscopists and qualified by AI, individuals immediately underwent a repeat colonoscopy to assess for any missed lesions; otherwise, they underwent bowel recleansing before a repeat colonoscopy.
- The primary outcome was a > 5-mm AMR.
TAKEAWAY:
- The > 5-mm AMR was higher in individuals whose bowel preparation was deemed unqualified vs qualified by AI (35.71% vs 13.19%), particularly in the cecum (50.00% vs 25.00%), ascending colon (25.00% vs 9.09%), transverse colon (58.82% vs 14.71%), and descending colon (40.00% vs 21.43%).
- Similarly, any AMR (50.89% vs 20.79%), > 5-mm polyp miss rate (35.82% vs 19.48%), and any polyp miss rate (43.05% vs 25.51%) were higher in the unqualified AI vs qualified AI individuals.
- The rate of detection of adenomas > 5 mm (2.88% vs 11.25%) or any adenoma (15.97% vs 46.25%) was lower among the qualified AI vs unqualified AI individuals during the repeat colonoscopy.
- The e-BBPS also showed a high pairwise agreement with the analysis of expert endoscopists and moderate pairwise agreement with that of general endoscopists.
IN PRACTICE:
“The use of AI in bowel preparation assessment can relieve endoscopists’ workload, enabling them to concentrate more on detecting lesions during colonoscopy without being distracted by preparation evaluation, thus enhancing both efficiency and overall medical quality,” the authors wrote.
SOURCE:
The study, led by Liwen Yao, PhD, Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China, was published online in Gastrointestinal Endoscopy.
LIMITATIONS:
Limitations included the study’s lack of external validity, including Western populations. Different bowel preparation regimens were not compared; therefore, conclusions about their efficacy cannot be deduced. The use of AI in the assessment of bowel preparation may lead to ethical issues, such as increased colonoscopy costs due to the technology and whether patients are fully informed.
DISCLOSURES:
This study was funded by the Science and Technology Achievement Transformation Platform Construction Project of Ministry of Education and Public Health Research Project of Futian District, Shenzhen. The authors declared no conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
The adenoma missed rate (AMR), including lesions > 5 mm, was lower in patients whose precolonoscopy bowel preparation was deemed suitable using an artificial intelligence (AI)–guided assessment.
METHODOLOGY:
- Individuals with inappropriate bowel preparation before a colonoscopy face a higher lesion miss rate and may need to repeat the procedure.
- This prospective single-center study analyzed the screening colonoscopies of 393 individuals (mean age, 55 years; 50% men) using assessments made by endoscopists and AI.
- The AI-based method was the e-Boston Bowel Preparation Scale (e-BBPS), in which a score of 3 is the threshold to guarantee an adenoma detection rate of > 25%. Patients with an e-BBPS score of ≤ 3 or > 3 were considered by the AI as being qualified or unqualified, respectively.
- If the bowel preparation was considered adequate by the endoscopists and qualified by AI, individuals immediately underwent a repeat colonoscopy to assess for any missed lesions; otherwise, they underwent bowel recleansing before a repeat colonoscopy.
- The primary outcome was a > 5-mm AMR.
TAKEAWAY:
- The > 5-mm AMR was higher in individuals whose bowel preparation was deemed unqualified vs qualified by AI (35.71% vs 13.19%), particularly in the cecum (50.00% vs 25.00%), ascending colon (25.00% vs 9.09%), transverse colon (58.82% vs 14.71%), and descending colon (40.00% vs 21.43%).
- Similarly, any AMR (50.89% vs 20.79%), > 5-mm polyp miss rate (35.82% vs 19.48%), and any polyp miss rate (43.05% vs 25.51%) were higher in the unqualified AI vs qualified AI individuals.
- The rate of detection of adenomas > 5 mm (2.88% vs 11.25%) or any adenoma (15.97% vs 46.25%) was lower among the qualified AI vs unqualified AI individuals during the repeat colonoscopy.
- The e-BBPS also showed a high pairwise agreement with the analysis of expert endoscopists and moderate pairwise agreement with that of general endoscopists.
IN PRACTICE:
“The use of AI in bowel preparation assessment can relieve endoscopists’ workload, enabling them to concentrate more on detecting lesions during colonoscopy without being distracted by preparation evaluation, thus enhancing both efficiency and overall medical quality,” the authors wrote.
SOURCE:
The study, led by Liwen Yao, PhD, Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China, was published online in Gastrointestinal Endoscopy.
LIMITATIONS:
Limitations included the study’s lack of external validity, including Western populations. Different bowel preparation regimens were not compared; therefore, conclusions about their efficacy cannot be deduced. The use of AI in the assessment of bowel preparation may lead to ethical issues, such as increased colonoscopy costs due to the technology and whether patients are fully informed.
DISCLOSURES:
This study was funded by the Science and Technology Achievement Transformation Platform Construction Project of Ministry of Education and Public Health Research Project of Futian District, Shenzhen. The authors declared no conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
The adenoma missed rate (AMR), including lesions > 5 mm, was lower in patients whose precolonoscopy bowel preparation was deemed suitable using an artificial intelligence (AI)–guided assessment.
METHODOLOGY:
- Individuals with inappropriate bowel preparation before a colonoscopy face a higher lesion miss rate and may need to repeat the procedure.
- This prospective single-center study analyzed the screening colonoscopies of 393 individuals (mean age, 55 years; 50% men) using assessments made by endoscopists and AI.
- The AI-based method was the e-Boston Bowel Preparation Scale (e-BBPS), in which a score of 3 is the threshold to guarantee an adenoma detection rate of > 25%. Patients with an e-BBPS score of ≤ 3 or > 3 were considered by the AI as being qualified or unqualified, respectively.
- If the bowel preparation was considered adequate by the endoscopists and qualified by AI, individuals immediately underwent a repeat colonoscopy to assess for any missed lesions; otherwise, they underwent bowel recleansing before a repeat colonoscopy.
- The primary outcome was a > 5-mm AMR.
TAKEAWAY:
- The > 5-mm AMR was higher in individuals whose bowel preparation was deemed unqualified vs qualified by AI (35.71% vs 13.19%), particularly in the cecum (50.00% vs 25.00%), ascending colon (25.00% vs 9.09%), transverse colon (58.82% vs 14.71%), and descending colon (40.00% vs 21.43%).
- Similarly, any AMR (50.89% vs 20.79%), > 5-mm polyp miss rate (35.82% vs 19.48%), and any polyp miss rate (43.05% vs 25.51%) were higher in the unqualified AI vs qualified AI individuals.
- The rate of detection of adenomas > 5 mm (2.88% vs 11.25%) or any adenoma (15.97% vs 46.25%) was lower among the qualified AI vs unqualified AI individuals during the repeat colonoscopy.
- The e-BBPS also showed a high pairwise agreement with the analysis of expert endoscopists and moderate pairwise agreement with that of general endoscopists.
IN PRACTICE:
“The use of AI in bowel preparation assessment can relieve endoscopists’ workload, enabling them to concentrate more on detecting lesions during colonoscopy without being distracted by preparation evaluation, thus enhancing both efficiency and overall medical quality,” the authors wrote.
SOURCE:
The study, led by Liwen Yao, PhD, Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China, was published online in Gastrointestinal Endoscopy.
LIMITATIONS:
Limitations included the study’s lack of external validity, including Western populations. Different bowel preparation regimens were not compared; therefore, conclusions about their efficacy cannot be deduced. The use of AI in the assessment of bowel preparation may lead to ethical issues, such as increased colonoscopy costs due to the technology and whether patients are fully informed.
DISCLOSURES:
This study was funded by the Science and Technology Achievement Transformation Platform Construction Project of Ministry of Education and Public Health Research Project of Futian District, Shenzhen. The authors declared no conflicts of interest.
A version of this article first appeared on Medscape.com.
Recently Incarcerated Account for Nearly 20% of US Suicides
Nearly one-fifth of suicides in the United States occur in people who were incarcerated in the previous year, a new study showed.
An analysis of more than seven million recently incarcerated US adults revealed a nearly ninefold increased risk for suicide within 1 year after release and an almost sevenfold higher risk during the 2 years following release compared with nonincarcerated people.
The findings suggest that recent incarceration should be considered a risk factor for suicide, investigators said.
“Suicide prevention efforts should focus on people who have spent at least 1 night in jail in the past year,” investigator Ted R. Miller, PhD, of the Pacific Institute for Research and Evaluation, Beltsville, Maryland, and Curtin University School of Public Health, Silver Spring, Maryland, and colleagues wrote. “Health systems could develop infrastructure to identify these high-risk adults and provide community-based suicide screening and prevention.”
The study was published online on May 10, 2024, in JAMA Network Open.
To address the lack of data on suicide risk after recent incarceration, researchers used estimates from meta-analyses and jail census counts.
In 2019, a little more than seven million people (77% male), or 2.8% of the US adult population, were released from US jails at least once, typically after brief pretrial stays. Of those, 9121 died by suicide.
Compared with suicide risk in people who had never been incarcerated, risk was nearly nine times higher within 1 year of release (relative risk [RR], 8.95; 95% CI, 7.21-10.69) and nearly seven times higher during the second year after release (RR, 6.98; 95% CI, 4.21-9.76), researchers found.
Over a quarter (27%) of all adult suicides in the United States occurred in formerly incarcerated people within 2 years of jail release, and one fifth occurred within 1 year of release.
“The results suggest that better integration of suicide risk detection and prevention across health and criminal justice systems is critical to advancing population-level suicide-prevention efforts,” the authors wrote.
High volumes of jail admissions and discharges, short jail stays, and understaffing limit the capacity of many jails to coordinate care with outside health agencies, researchers acknowledged.
“The suicide rate after the return to the community after jail stay is higher than the suicide rate in jail, but local jails have limited capacity to coordinate postrelease health activities,” authors wrote. “Thus, a comprehensive approach to reducing the population-level US suicide rate would include health systems screening their subscribers or patients for recent arrest or police involvement and reaching out to those recently released to prevent suicide.”
In an accompanying editorial, Stuart A. Kinner, PhD, and Rohan Borschmann, PhD, both with the Melbourne School of Population and Global Health, University of Melbourne, Australia, noted that people who experience incarceration “are distinguished by complex health problems that necessitate coordinated, multisectoral care.”
“Miller and colleagues’ findings provide further evidence that incarceration serves as an important marker for disease vulnerability and risk,” Dr. Kinner and Borschmann wrote. “Yet, all too often, the health care provided to these individuals before, during, and after incarceration is underresourced, interrupted, and fragmented.”
Coordinating care for recently incarcerated individuals will require a coordinated effort by all stakeholders, including those in the criminal justice system, they argued.
“The systems that incarcerate 7.1 million people in the United States each year should not be given a get-out-of-jail-free card,” they wrote.
This study was supported by grants from the National Institutes of Mental Health (NIMH)/National Institutes of Health (NIH) and from the National Center for Health and Justice Integration for Suicide Prevention. Dr. Miller reported receiving grants from the NIMH/NIH with his employer as a subcontractor during the conduct of the study and a contract from government plaintiffs in Opioid Litigation: Epidemiology/Abatement Planning outside the submitted work. The other authors’ disclosures are listed on the original paper. Dr. Kinner and Borschmann declared no relevant financial relationships.
A version of this article appeared on Medscape.com.
Nearly one-fifth of suicides in the United States occur in people who were incarcerated in the previous year, a new study showed.
An analysis of more than seven million recently incarcerated US adults revealed a nearly ninefold increased risk for suicide within 1 year after release and an almost sevenfold higher risk during the 2 years following release compared with nonincarcerated people.
The findings suggest that recent incarceration should be considered a risk factor for suicide, investigators said.
“Suicide prevention efforts should focus on people who have spent at least 1 night in jail in the past year,” investigator Ted R. Miller, PhD, of the Pacific Institute for Research and Evaluation, Beltsville, Maryland, and Curtin University School of Public Health, Silver Spring, Maryland, and colleagues wrote. “Health systems could develop infrastructure to identify these high-risk adults and provide community-based suicide screening and prevention.”
The study was published online on May 10, 2024, in JAMA Network Open.
To address the lack of data on suicide risk after recent incarceration, researchers used estimates from meta-analyses and jail census counts.
In 2019, a little more than seven million people (77% male), or 2.8% of the US adult population, were released from US jails at least once, typically after brief pretrial stays. Of those, 9121 died by suicide.
Compared with suicide risk in people who had never been incarcerated, risk was nearly nine times higher within 1 year of release (relative risk [RR], 8.95; 95% CI, 7.21-10.69) and nearly seven times higher during the second year after release (RR, 6.98; 95% CI, 4.21-9.76), researchers found.
Over a quarter (27%) of all adult suicides in the United States occurred in formerly incarcerated people within 2 years of jail release, and one fifth occurred within 1 year of release.
“The results suggest that better integration of suicide risk detection and prevention across health and criminal justice systems is critical to advancing population-level suicide-prevention efforts,” the authors wrote.
High volumes of jail admissions and discharges, short jail stays, and understaffing limit the capacity of many jails to coordinate care with outside health agencies, researchers acknowledged.
“The suicide rate after the return to the community after jail stay is higher than the suicide rate in jail, but local jails have limited capacity to coordinate postrelease health activities,” authors wrote. “Thus, a comprehensive approach to reducing the population-level US suicide rate would include health systems screening their subscribers or patients for recent arrest or police involvement and reaching out to those recently released to prevent suicide.”
In an accompanying editorial, Stuart A. Kinner, PhD, and Rohan Borschmann, PhD, both with the Melbourne School of Population and Global Health, University of Melbourne, Australia, noted that people who experience incarceration “are distinguished by complex health problems that necessitate coordinated, multisectoral care.”
“Miller and colleagues’ findings provide further evidence that incarceration serves as an important marker for disease vulnerability and risk,” Dr. Kinner and Borschmann wrote. “Yet, all too often, the health care provided to these individuals before, during, and after incarceration is underresourced, interrupted, and fragmented.”
Coordinating care for recently incarcerated individuals will require a coordinated effort by all stakeholders, including those in the criminal justice system, they argued.
“The systems that incarcerate 7.1 million people in the United States each year should not be given a get-out-of-jail-free card,” they wrote.
This study was supported by grants from the National Institutes of Mental Health (NIMH)/National Institutes of Health (NIH) and from the National Center for Health and Justice Integration for Suicide Prevention. Dr. Miller reported receiving grants from the NIMH/NIH with his employer as a subcontractor during the conduct of the study and a contract from government plaintiffs in Opioid Litigation: Epidemiology/Abatement Planning outside the submitted work. The other authors’ disclosures are listed on the original paper. Dr. Kinner and Borschmann declared no relevant financial relationships.
A version of this article appeared on Medscape.com.
Nearly one-fifth of suicides in the United States occur in people who were incarcerated in the previous year, a new study showed.
An analysis of more than seven million recently incarcerated US adults revealed a nearly ninefold increased risk for suicide within 1 year after release and an almost sevenfold higher risk during the 2 years following release compared with nonincarcerated people.
The findings suggest that recent incarceration should be considered a risk factor for suicide, investigators said.
“Suicide prevention efforts should focus on people who have spent at least 1 night in jail in the past year,” investigator Ted R. Miller, PhD, of the Pacific Institute for Research and Evaluation, Beltsville, Maryland, and Curtin University School of Public Health, Silver Spring, Maryland, and colleagues wrote. “Health systems could develop infrastructure to identify these high-risk adults and provide community-based suicide screening and prevention.”
The study was published online on May 10, 2024, in JAMA Network Open.
To address the lack of data on suicide risk after recent incarceration, researchers used estimates from meta-analyses and jail census counts.
In 2019, a little more than seven million people (77% male), or 2.8% of the US adult population, were released from US jails at least once, typically after brief pretrial stays. Of those, 9121 died by suicide.
Compared with suicide risk in people who had never been incarcerated, risk was nearly nine times higher within 1 year of release (relative risk [RR], 8.95; 95% CI, 7.21-10.69) and nearly seven times higher during the second year after release (RR, 6.98; 95% CI, 4.21-9.76), researchers found.
Over a quarter (27%) of all adult suicides in the United States occurred in formerly incarcerated people within 2 years of jail release, and one fifth occurred within 1 year of release.
“The results suggest that better integration of suicide risk detection and prevention across health and criminal justice systems is critical to advancing population-level suicide-prevention efforts,” the authors wrote.
High volumes of jail admissions and discharges, short jail stays, and understaffing limit the capacity of many jails to coordinate care with outside health agencies, researchers acknowledged.
“The suicide rate after the return to the community after jail stay is higher than the suicide rate in jail, but local jails have limited capacity to coordinate postrelease health activities,” authors wrote. “Thus, a comprehensive approach to reducing the population-level US suicide rate would include health systems screening their subscribers or patients for recent arrest or police involvement and reaching out to those recently released to prevent suicide.”
In an accompanying editorial, Stuart A. Kinner, PhD, and Rohan Borschmann, PhD, both with the Melbourne School of Population and Global Health, University of Melbourne, Australia, noted that people who experience incarceration “are distinguished by complex health problems that necessitate coordinated, multisectoral care.”
“Miller and colleagues’ findings provide further evidence that incarceration serves as an important marker for disease vulnerability and risk,” Dr. Kinner and Borschmann wrote. “Yet, all too often, the health care provided to these individuals before, during, and after incarceration is underresourced, interrupted, and fragmented.”
Coordinating care for recently incarcerated individuals will require a coordinated effort by all stakeholders, including those in the criminal justice system, they argued.
“The systems that incarcerate 7.1 million people in the United States each year should not be given a get-out-of-jail-free card,” they wrote.
This study was supported by grants from the National Institutes of Mental Health (NIMH)/National Institutes of Health (NIH) and from the National Center for Health and Justice Integration for Suicide Prevention. Dr. Miller reported receiving grants from the NIMH/NIH with his employer as a subcontractor during the conduct of the study and a contract from government plaintiffs in Opioid Litigation: Epidemiology/Abatement Planning outside the submitted work. The other authors’ disclosures are listed on the original paper. Dr. Kinner and Borschmann declared no relevant financial relationships.
A version of this article appeared on Medscape.com.
Late-Night Eaters May Have Increased Risk for Colorectal Cancer
WASHINGTON — , according to the results of research presented at the annual Digestive Disease Week® (DDW).
Investigators in a new study questioned 664 people getting a colonoscopy to screen for cancer, and 42% said they were late eaters. This group was 46% more likely than non–late eaters to have an adenoma found during colonoscopy. An estimated 5% to 10% of them become cancerous over time.
“A lot of other studies are about what we eat but not when we eat,” said Edena Khoshaba, lead investigator and a medical student at Rush University Medical College in Chicago. “The common advice includes not eating red meat, eating more fruits and vegetables — which is great, of course — but we wanted to see if the timing affects us at all.”
Ms. Khoshaba and colleagues found it did. Late eaters were 5.5 times more likely to have three or more tubular adenomas compared to non–late eaters, even after adjusting for what people were eating. Tubular adenomas are the most common type of polyp found in the colon.
So, what’s the possible connection between late eating and the risk for colorectal cancer?
Resetting Your Internal Clock
Eating close to bedtime could be throwing off the body’s circadian rhythm. But in this case, it’s not the central circadian center located in the brain — the one that releases melatonin. Instead, late eating could disrupt the peripheral circadian rhythm, part of which is found in the GI tract. For example, if a person is eating late at night, the brain thinks it is nighttime while the gut thinks it is daytime, Ms. Khoshaba said in an interview.
This is an interesting study, said Amy Bragagnini, MS, RD, spokesperson for the Academy of Nutrition and Dietetics, when asked to comment on the research. “It is true that eating later at night can disrupt your circadian rhythm.”
“In addition, many of my patients have told me that when they do eat later at night, they don’t always make the healthiest food choices,” Ms. Bragagnini said. “Their late-night food choices are generally higher in added sugar and fat. This may cause them to consume far more calories than their body needs.” So, eating late at night can also lead to unwanted weight gain.
An unanswered question is if late eating is connected in any way at all to increasing rates of colorectal cancer seen in younger patients.
This was an observational study, and another possible limitation, Ms. Khoshaba said, is that people were asked to recall their diets over 24 hours, which may not always be accurate.
Some of the organisms in the gut have their own internal clocks that follow a daily rhythm, and what someone eat determines how many different kinds of these organisms are active, Ms. Bragagnini said.
“So, if your late-night eating consists of foods high in sugar and fat, you may be negatively impacting your microbiome.” she said.
The next step for Ms. Khoshaba and colleagues is a study examining the peripheral circadian rhythm, changes in the gut microbiome, and the risk for developing metabolic syndrome. Ms. Khoshaba and Ms. Bragagnini had no relevant disclosures.
A version of this article appeared on Medscape.com.
WASHINGTON — , according to the results of research presented at the annual Digestive Disease Week® (DDW).
Investigators in a new study questioned 664 people getting a colonoscopy to screen for cancer, and 42% said they were late eaters. This group was 46% more likely than non–late eaters to have an adenoma found during colonoscopy. An estimated 5% to 10% of them become cancerous over time.
“A lot of other studies are about what we eat but not when we eat,” said Edena Khoshaba, lead investigator and a medical student at Rush University Medical College in Chicago. “The common advice includes not eating red meat, eating more fruits and vegetables — which is great, of course — but we wanted to see if the timing affects us at all.”
Ms. Khoshaba and colleagues found it did. Late eaters were 5.5 times more likely to have three or more tubular adenomas compared to non–late eaters, even after adjusting for what people were eating. Tubular adenomas are the most common type of polyp found in the colon.
So, what’s the possible connection between late eating and the risk for colorectal cancer?
Resetting Your Internal Clock
Eating close to bedtime could be throwing off the body’s circadian rhythm. But in this case, it’s not the central circadian center located in the brain — the one that releases melatonin. Instead, late eating could disrupt the peripheral circadian rhythm, part of which is found in the GI tract. For example, if a person is eating late at night, the brain thinks it is nighttime while the gut thinks it is daytime, Ms. Khoshaba said in an interview.
This is an interesting study, said Amy Bragagnini, MS, RD, spokesperson for the Academy of Nutrition and Dietetics, when asked to comment on the research. “It is true that eating later at night can disrupt your circadian rhythm.”
“In addition, many of my patients have told me that when they do eat later at night, they don’t always make the healthiest food choices,” Ms. Bragagnini said. “Their late-night food choices are generally higher in added sugar and fat. This may cause them to consume far more calories than their body needs.” So, eating late at night can also lead to unwanted weight gain.
An unanswered question is if late eating is connected in any way at all to increasing rates of colorectal cancer seen in younger patients.
This was an observational study, and another possible limitation, Ms. Khoshaba said, is that people were asked to recall their diets over 24 hours, which may not always be accurate.
Some of the organisms in the gut have their own internal clocks that follow a daily rhythm, and what someone eat determines how many different kinds of these organisms are active, Ms. Bragagnini said.
“So, if your late-night eating consists of foods high in sugar and fat, you may be negatively impacting your microbiome.” she said.
The next step for Ms. Khoshaba and colleagues is a study examining the peripheral circadian rhythm, changes in the gut microbiome, and the risk for developing metabolic syndrome. Ms. Khoshaba and Ms. Bragagnini had no relevant disclosures.
A version of this article appeared on Medscape.com.
WASHINGTON — , according to the results of research presented at the annual Digestive Disease Week® (DDW).
Investigators in a new study questioned 664 people getting a colonoscopy to screen for cancer, and 42% said they were late eaters. This group was 46% more likely than non–late eaters to have an adenoma found during colonoscopy. An estimated 5% to 10% of them become cancerous over time.
“A lot of other studies are about what we eat but not when we eat,” said Edena Khoshaba, lead investigator and a medical student at Rush University Medical College in Chicago. “The common advice includes not eating red meat, eating more fruits and vegetables — which is great, of course — but we wanted to see if the timing affects us at all.”
Ms. Khoshaba and colleagues found it did. Late eaters were 5.5 times more likely to have three or more tubular adenomas compared to non–late eaters, even after adjusting for what people were eating. Tubular adenomas are the most common type of polyp found in the colon.
So, what’s the possible connection between late eating and the risk for colorectal cancer?
Resetting Your Internal Clock
Eating close to bedtime could be throwing off the body’s circadian rhythm. But in this case, it’s not the central circadian center located in the brain — the one that releases melatonin. Instead, late eating could disrupt the peripheral circadian rhythm, part of which is found in the GI tract. For example, if a person is eating late at night, the brain thinks it is nighttime while the gut thinks it is daytime, Ms. Khoshaba said in an interview.
This is an interesting study, said Amy Bragagnini, MS, RD, spokesperson for the Academy of Nutrition and Dietetics, when asked to comment on the research. “It is true that eating later at night can disrupt your circadian rhythm.”
“In addition, many of my patients have told me that when they do eat later at night, they don’t always make the healthiest food choices,” Ms. Bragagnini said. “Their late-night food choices are generally higher in added sugar and fat. This may cause them to consume far more calories than their body needs.” So, eating late at night can also lead to unwanted weight gain.
An unanswered question is if late eating is connected in any way at all to increasing rates of colorectal cancer seen in younger patients.
This was an observational study, and another possible limitation, Ms. Khoshaba said, is that people were asked to recall their diets over 24 hours, which may not always be accurate.
Some of the organisms in the gut have their own internal clocks that follow a daily rhythm, and what someone eat determines how many different kinds of these organisms are active, Ms. Bragagnini said.
“So, if your late-night eating consists of foods high in sugar and fat, you may be negatively impacting your microbiome.” she said.
The next step for Ms. Khoshaba and colleagues is a study examining the peripheral circadian rhythm, changes in the gut microbiome, and the risk for developing metabolic syndrome. Ms. Khoshaba and Ms. Bragagnini had no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM DDW 2024
Obesity and Cancer: Untangling a Complex Web
According to the Centers for Disease Control and Prevention (CDC), over 684,000 Americans are diagnosed with an “obesity-associated” cancer each year.
The incidence of many of these cancers has been rising in recent years, particularly among younger people — a trend that sits in contrast with the overall decline in cancers with no established relationship to excess weight, such as lung and skin cancers.
Is obesity the new smoking? Not exactly.
While about 42% of cancers — including common ones such as colorectal and postmenopausal breast cancers — are considered obesity-related, only about 8% of incident cancers are attributed to excess body weight. People often develop those diseases regardless of weight.
Although plenty of evidence points to excess body fat as a cancer risk factor, it’s unclear at what point excess weight has an effect. Is gaining weight later in life, for instance, better or worse for cancer risk than being overweight or obese from a young age?
There’s another glaring knowledge gap: Does losing weight at some point in adulthood change the picture? In other words, how many of those 684,000 diagnoses might have been prevented if people shed excess pounds?
When it comes to weight and cancer risk, “there’s a lot we don’t know,” said Jennifer W. Bea, PhD, associate professor, health promotion sciences, University of Arizona, Tucson.
A Consistent but Complicated Relationship
Given the growing incidence of obesity — which currently affects about 42% of US adults and 20% of children and teenagers — it’s no surprise that many studies have delved into the potential effects of excess weight on cancer rates.
Although virtually all the evidence comes from large cohort studies, leaving the cause-effect question open, certain associations keep showing up.
“What we know is that, consistently, a higher body mass index [BMI] — particularly in the obese category — leads to a higher risk of multiple cancers,” said Jeffrey A. Meyerhardt, MD, MPH, codirector, Colon and Rectal Cancer Center, Dana-Farber Cancer Institute, Boston.
In a widely cited report published in The New England Journal of Medicine in 2016, the International Agency for Research on Cancer (IARC) analyzed over 1000 epidemiologic studies on body fat and cancer. The agency pointed to over a dozen cancers, including some of the most common and deadly, linked to excess body weight.
That list includes esophageal adenocarcinoma and endometrial cancer — associated with the highest risk — along with kidney, liver, stomach (gastric cardia), pancreatic, colorectal, postmenopausal breast, gallbladder, ovarian, and thyroid cancers, plus multiple myeloma and meningioma. There’s also “limited” evidence linking excess weight to additional cancer types, including aggressive prostate cancer and certain head and neck cancers.
At the same time, Dr. Meyerhardt said, many of those same cancers are also associated with issues that lead to, or coexist with, overweight and obesity, including poor diet, lack of exercise, and metabolic conditions such as diabetes.
It’s a complicated web, and it’s likely, Dr. Meyerhardt said, that high BMI both directly affects cancer risk and is part of a “causal pathway” of other factors that do.
Regarding direct effects, preclinical research has pointed to multiple ways in which excess body fat could contribute to cancer, said Karen M. Basen-Engquist, PhD, MPH, professor, Division of Cancer Prevention and Population Services, The University of Texas MD Anderson Cancer Center, Houston.
One broad mechanism to help explain the obesity-cancer link is chronic systemic inflammation because excess fat tissue can raise levels of substances in the body, such as tumor necrosis factor alpha and interleukin 6, which fuel inflammation. Excess fat also contributes to hyperinsulinemia — too much insulin in the blood — which can help promote the growth and spread of tumor cells.
But the underlying reasons also appear to vary by cancer type, Dr. Basen-Engquist said. With hormonally driven cancer types, such as breast and endometrial, excess body fat may alter hormone levels in ways that spur tumor growth. Extra fat tissue may, for example, convert androgens into estrogens, which could help feed estrogen-dependent tumors.
That, Dr. Basen-Engquist noted, could be why excess weight is associated with postmenopausal, not premenopausal, breast cancer: Before menopause, body fat is a relatively minor contributor to estrogen levels but becomes more important after menopause.
How Big Is the Effect?
While more than a dozen cancers have been consistently linked to excess weight, the strength of those associations varies considerably.
Endometrial and esophageal cancers are two that stand out. In the 2016 IARC analysis, people with severe obesity had a seven-times greater risk for endometrial cancer and 4.8-times greater risk for esophageal adenocarcinoma vs people with a normal BMI.
With other cancers, the risk increases for those with severe obesity compared with a normal BMI were far more modest: 10% for ovarian cancer, 30% for colorectal cancer, and 80% for kidney and stomach cancers, for example. For postmenopausal breast cancer, every five-unit increase in BMI was associated with a 10% relative risk increase.
A 2018 study from the American Cancer Society, which attempted to estimate the proportion of cancers in the United States attributable to modifiable risk factors — including alcohol consumption, ultraviolet rays exposure, and physical inactivity — found that smoking accounted for the highest proportion of cancer cases by a wide margin (19%), but excess weight came in second (7.8%).
Again, weight appeared to play a bigger role in certain cancers than others: An estimated 60% of endometrial cancers were linked to excess weight, as were roughly one third of esophageal, kidney, and liver cancers. At the other end of the spectrum, just over 11% of breast, 5% of colorectal, and 4% of ovarian cancers were attributable to excess weight.
Even at the lower end, those rates could make a big difference on the population level, especially for groups with higher rates of obesity.
CDC data show that obesity-related cancers are rising among women younger than 50 years, most rapidly among Hispanic women, and some less common obesity-related cancers, such as stomach, thyroid and pancreatic, are also rising among Black individuals and Hispanic Americans.
Obesity may be one reason for growing cancer disparities, said Leah Ferrucci, PhD, MPH, assistant professor, epidemiology, Yale School of Public Health, New Haven, Connecticut. But, she added, the evidence is limited because Black individuals and Hispanic Americans are understudied.
When Do Extra Pounds Matter?
When it comes to cancer risk, at what point in life does excess weight, or weight gain, matter? Is the standard weight gain in middle age, for instance, as hazardous as being overweight or obese from a young age?
Some evidence suggests there’s no “safe” time for putting on excess pounds.
A recent meta-analysis concluded that weight gain at any point after age 18 years is associated with incremental increases in the risk for postmenopausal breast cancer. A 2023 study in JAMA Network Open found a similar pattern with colorectal and other gastrointestinal cancers: People who had sustained overweight or obesity from age 20 years through middle age faced an increased risk of developing those cancers after age 55 years.
The timing of weight gain didn’t seem to matter either. The same elevated risk held among people who were normal weight in their younger years but became overweight after age 55 years.
Those studies focused on later-onset disease. But, in recent years, experts have tracked a troubling rise in early-onset cancers — those diagnosed before age 50 years — particularly gastrointestinal cancers.
An obvious question, Dr. Meyerhardt said, is whether the growing prevalence of obesity among young people is partly to blame.
There’s some data to support that, he said. An analysis from the Nurses’ Health Study II found that women with obesity had double the risk for early-onset colorectal cancer as those with a normal BMI. And every 5-kg increase in weight after age 18 years was associated with a 9% increase in colorectal cancer risk.
But while obesity trends probably partly explain the rise in early-onset cancers, there is likely more to the story, Dr. Meyerhardt said.
“I think all of us who see an increasing number of patients under 50 with colorectal cancer know there’s a fair number who do not fit that [high BMI] profile,” he said. “There’s a fair number over 50 who don’t either.”
Does Weight Loss Help?
With all the evidence pointing to high BMI as a cancer risk factor, a logical conclusion is that weight loss should reduce that excess risk. However, Dr. Bea said, there’s actually little data to support that, and what exists comes from observational studies.
Some research has focused on people who had substantial weight loss after bariatric surgery, with encouraging results. A study published in JAMA found that among 5053 people who underwent bariatric surgery, 2.9% developed an obesity-related cancer over 10 years compared with 4.9% in the nonsurgery group.
Most people, however, aim for less dramatic weight loss, with the help of diet and exercise or sometimes medication. Some evidence shows that a modest degree of weight loss may lower the risks for postmenopausal breast and endometrial cancers.
A 2020 pooled analysis found, for instance, that among women aged ≥ 50 years, those who lost as little as 2.0-4.5 kg, or 4.4-10.0 pounds, and kept it off for 10 years had a lower risk for breast cancer than women whose weight remained stable. And losing more weight — 9 kg, or about 20 pounds, or more — was even better for lowering cancer risk.
But other research suggests the opposite. A recent analysis found that people who lost weight within the past 2 years through diet and exercise had a higher risk for a range of cancers compared with those who did not lose weight. Overall, though, the increased risk was quite low.
Whatever the research does, or doesn’t, show about weight and cancer risk, Dr. Basen-Engquist said, it’s important that risk factors, obesity and otherwise, aren’t “used as blame tools.”
“With obesity, behavior certainly plays into it,” she said. “But there are so many influences on our behavior that are socially determined.”
Both Dr. Basen-Engquist and Dr. Meyerhardt said it’s important for clinicians to consider the individual in front of them and for everyone to set realistic expectations.
People with obesity should not feel they have to become thin to be healthier, and no one has to leap from being sedentary to exercising several hours a week.
“We don’t want patients to feel that if they don’t get to a stated goal in a guideline, it’s all for naught,” Dr. Meyerhardt said.
A version of this article appeared on Medscape.com.
According to the Centers for Disease Control and Prevention (CDC), over 684,000 Americans are diagnosed with an “obesity-associated” cancer each year.
The incidence of many of these cancers has been rising in recent years, particularly among younger people — a trend that sits in contrast with the overall decline in cancers with no established relationship to excess weight, such as lung and skin cancers.
Is obesity the new smoking? Not exactly.
While about 42% of cancers — including common ones such as colorectal and postmenopausal breast cancers — are considered obesity-related, only about 8% of incident cancers are attributed to excess body weight. People often develop those diseases regardless of weight.
Although plenty of evidence points to excess body fat as a cancer risk factor, it’s unclear at what point excess weight has an effect. Is gaining weight later in life, for instance, better or worse for cancer risk than being overweight or obese from a young age?
There’s another glaring knowledge gap: Does losing weight at some point in adulthood change the picture? In other words, how many of those 684,000 diagnoses might have been prevented if people shed excess pounds?
When it comes to weight and cancer risk, “there’s a lot we don’t know,” said Jennifer W. Bea, PhD, associate professor, health promotion sciences, University of Arizona, Tucson.
A Consistent but Complicated Relationship
Given the growing incidence of obesity — which currently affects about 42% of US adults and 20% of children and teenagers — it’s no surprise that many studies have delved into the potential effects of excess weight on cancer rates.
Although virtually all the evidence comes from large cohort studies, leaving the cause-effect question open, certain associations keep showing up.
“What we know is that, consistently, a higher body mass index [BMI] — particularly in the obese category — leads to a higher risk of multiple cancers,” said Jeffrey A. Meyerhardt, MD, MPH, codirector, Colon and Rectal Cancer Center, Dana-Farber Cancer Institute, Boston.
In a widely cited report published in The New England Journal of Medicine in 2016, the International Agency for Research on Cancer (IARC) analyzed over 1000 epidemiologic studies on body fat and cancer. The agency pointed to over a dozen cancers, including some of the most common and deadly, linked to excess body weight.
That list includes esophageal adenocarcinoma and endometrial cancer — associated with the highest risk — along with kidney, liver, stomach (gastric cardia), pancreatic, colorectal, postmenopausal breast, gallbladder, ovarian, and thyroid cancers, plus multiple myeloma and meningioma. There’s also “limited” evidence linking excess weight to additional cancer types, including aggressive prostate cancer and certain head and neck cancers.
At the same time, Dr. Meyerhardt said, many of those same cancers are also associated with issues that lead to, or coexist with, overweight and obesity, including poor diet, lack of exercise, and metabolic conditions such as diabetes.
It’s a complicated web, and it’s likely, Dr. Meyerhardt said, that high BMI both directly affects cancer risk and is part of a “causal pathway” of other factors that do.
Regarding direct effects, preclinical research has pointed to multiple ways in which excess body fat could contribute to cancer, said Karen M. Basen-Engquist, PhD, MPH, professor, Division of Cancer Prevention and Population Services, The University of Texas MD Anderson Cancer Center, Houston.
One broad mechanism to help explain the obesity-cancer link is chronic systemic inflammation because excess fat tissue can raise levels of substances in the body, such as tumor necrosis factor alpha and interleukin 6, which fuel inflammation. Excess fat also contributes to hyperinsulinemia — too much insulin in the blood — which can help promote the growth and spread of tumor cells.
But the underlying reasons also appear to vary by cancer type, Dr. Basen-Engquist said. With hormonally driven cancer types, such as breast and endometrial, excess body fat may alter hormone levels in ways that spur tumor growth. Extra fat tissue may, for example, convert androgens into estrogens, which could help feed estrogen-dependent tumors.
That, Dr. Basen-Engquist noted, could be why excess weight is associated with postmenopausal, not premenopausal, breast cancer: Before menopause, body fat is a relatively minor contributor to estrogen levels but becomes more important after menopause.
How Big Is the Effect?
While more than a dozen cancers have been consistently linked to excess weight, the strength of those associations varies considerably.
Endometrial and esophageal cancers are two that stand out. In the 2016 IARC analysis, people with severe obesity had a seven-times greater risk for endometrial cancer and 4.8-times greater risk for esophageal adenocarcinoma vs people with a normal BMI.
With other cancers, the risk increases for those with severe obesity compared with a normal BMI were far more modest: 10% for ovarian cancer, 30% for colorectal cancer, and 80% for kidney and stomach cancers, for example. For postmenopausal breast cancer, every five-unit increase in BMI was associated with a 10% relative risk increase.
A 2018 study from the American Cancer Society, which attempted to estimate the proportion of cancers in the United States attributable to modifiable risk factors — including alcohol consumption, ultraviolet rays exposure, and physical inactivity — found that smoking accounted for the highest proportion of cancer cases by a wide margin (19%), but excess weight came in second (7.8%).
Again, weight appeared to play a bigger role in certain cancers than others: An estimated 60% of endometrial cancers were linked to excess weight, as were roughly one third of esophageal, kidney, and liver cancers. At the other end of the spectrum, just over 11% of breast, 5% of colorectal, and 4% of ovarian cancers were attributable to excess weight.
Even at the lower end, those rates could make a big difference on the population level, especially for groups with higher rates of obesity.
CDC data show that obesity-related cancers are rising among women younger than 50 years, most rapidly among Hispanic women, and some less common obesity-related cancers, such as stomach, thyroid and pancreatic, are also rising among Black individuals and Hispanic Americans.
Obesity may be one reason for growing cancer disparities, said Leah Ferrucci, PhD, MPH, assistant professor, epidemiology, Yale School of Public Health, New Haven, Connecticut. But, she added, the evidence is limited because Black individuals and Hispanic Americans are understudied.
When Do Extra Pounds Matter?
When it comes to cancer risk, at what point in life does excess weight, or weight gain, matter? Is the standard weight gain in middle age, for instance, as hazardous as being overweight or obese from a young age?
Some evidence suggests there’s no “safe” time for putting on excess pounds.
A recent meta-analysis concluded that weight gain at any point after age 18 years is associated with incremental increases in the risk for postmenopausal breast cancer. A 2023 study in JAMA Network Open found a similar pattern with colorectal and other gastrointestinal cancers: People who had sustained overweight or obesity from age 20 years through middle age faced an increased risk of developing those cancers after age 55 years.
The timing of weight gain didn’t seem to matter either. The same elevated risk held among people who were normal weight in their younger years but became overweight after age 55 years.
Those studies focused on later-onset disease. But, in recent years, experts have tracked a troubling rise in early-onset cancers — those diagnosed before age 50 years — particularly gastrointestinal cancers.
An obvious question, Dr. Meyerhardt said, is whether the growing prevalence of obesity among young people is partly to blame.
There’s some data to support that, he said. An analysis from the Nurses’ Health Study II found that women with obesity had double the risk for early-onset colorectal cancer as those with a normal BMI. And every 5-kg increase in weight after age 18 years was associated with a 9% increase in colorectal cancer risk.
But while obesity trends probably partly explain the rise in early-onset cancers, there is likely more to the story, Dr. Meyerhardt said.
“I think all of us who see an increasing number of patients under 50 with colorectal cancer know there’s a fair number who do not fit that [high BMI] profile,” he said. “There’s a fair number over 50 who don’t either.”
Does Weight Loss Help?
With all the evidence pointing to high BMI as a cancer risk factor, a logical conclusion is that weight loss should reduce that excess risk. However, Dr. Bea said, there’s actually little data to support that, and what exists comes from observational studies.
Some research has focused on people who had substantial weight loss after bariatric surgery, with encouraging results. A study published in JAMA found that among 5053 people who underwent bariatric surgery, 2.9% developed an obesity-related cancer over 10 years compared with 4.9% in the nonsurgery group.
Most people, however, aim for less dramatic weight loss, with the help of diet and exercise or sometimes medication. Some evidence shows that a modest degree of weight loss may lower the risks for postmenopausal breast and endometrial cancers.
A 2020 pooled analysis found, for instance, that among women aged ≥ 50 years, those who lost as little as 2.0-4.5 kg, or 4.4-10.0 pounds, and kept it off for 10 years had a lower risk for breast cancer than women whose weight remained stable. And losing more weight — 9 kg, or about 20 pounds, or more — was even better for lowering cancer risk.
But other research suggests the opposite. A recent analysis found that people who lost weight within the past 2 years through diet and exercise had a higher risk for a range of cancers compared with those who did not lose weight. Overall, though, the increased risk was quite low.
Whatever the research does, or doesn’t, show about weight and cancer risk, Dr. Basen-Engquist said, it’s important that risk factors, obesity and otherwise, aren’t “used as blame tools.”
“With obesity, behavior certainly plays into it,” she said. “But there are so many influences on our behavior that are socially determined.”
Both Dr. Basen-Engquist and Dr. Meyerhardt said it’s important for clinicians to consider the individual in front of them and for everyone to set realistic expectations.
People with obesity should not feel they have to become thin to be healthier, and no one has to leap from being sedentary to exercising several hours a week.
“We don’t want patients to feel that if they don’t get to a stated goal in a guideline, it’s all for naught,” Dr. Meyerhardt said.
A version of this article appeared on Medscape.com.
According to the Centers for Disease Control and Prevention (CDC), over 684,000 Americans are diagnosed with an “obesity-associated” cancer each year.
The incidence of many of these cancers has been rising in recent years, particularly among younger people — a trend that sits in contrast with the overall decline in cancers with no established relationship to excess weight, such as lung and skin cancers.
Is obesity the new smoking? Not exactly.
While about 42% of cancers — including common ones such as colorectal and postmenopausal breast cancers — are considered obesity-related, only about 8% of incident cancers are attributed to excess body weight. People often develop those diseases regardless of weight.
Although plenty of evidence points to excess body fat as a cancer risk factor, it’s unclear at what point excess weight has an effect. Is gaining weight later in life, for instance, better or worse for cancer risk than being overweight or obese from a young age?
There’s another glaring knowledge gap: Does losing weight at some point in adulthood change the picture? In other words, how many of those 684,000 diagnoses might have been prevented if people shed excess pounds?
When it comes to weight and cancer risk, “there’s a lot we don’t know,” said Jennifer W. Bea, PhD, associate professor, health promotion sciences, University of Arizona, Tucson.
A Consistent but Complicated Relationship
Given the growing incidence of obesity — which currently affects about 42% of US adults and 20% of children and teenagers — it’s no surprise that many studies have delved into the potential effects of excess weight on cancer rates.
Although virtually all the evidence comes from large cohort studies, leaving the cause-effect question open, certain associations keep showing up.
“What we know is that, consistently, a higher body mass index [BMI] — particularly in the obese category — leads to a higher risk of multiple cancers,” said Jeffrey A. Meyerhardt, MD, MPH, codirector, Colon and Rectal Cancer Center, Dana-Farber Cancer Institute, Boston.
In a widely cited report published in The New England Journal of Medicine in 2016, the International Agency for Research on Cancer (IARC) analyzed over 1000 epidemiologic studies on body fat and cancer. The agency pointed to over a dozen cancers, including some of the most common and deadly, linked to excess body weight.
That list includes esophageal adenocarcinoma and endometrial cancer — associated with the highest risk — along with kidney, liver, stomach (gastric cardia), pancreatic, colorectal, postmenopausal breast, gallbladder, ovarian, and thyroid cancers, plus multiple myeloma and meningioma. There’s also “limited” evidence linking excess weight to additional cancer types, including aggressive prostate cancer and certain head and neck cancers.
At the same time, Dr. Meyerhardt said, many of those same cancers are also associated with issues that lead to, or coexist with, overweight and obesity, including poor diet, lack of exercise, and metabolic conditions such as diabetes.
It’s a complicated web, and it’s likely, Dr. Meyerhardt said, that high BMI both directly affects cancer risk and is part of a “causal pathway” of other factors that do.
Regarding direct effects, preclinical research has pointed to multiple ways in which excess body fat could contribute to cancer, said Karen M. Basen-Engquist, PhD, MPH, professor, Division of Cancer Prevention and Population Services, The University of Texas MD Anderson Cancer Center, Houston.
One broad mechanism to help explain the obesity-cancer link is chronic systemic inflammation because excess fat tissue can raise levels of substances in the body, such as tumor necrosis factor alpha and interleukin 6, which fuel inflammation. Excess fat also contributes to hyperinsulinemia — too much insulin in the blood — which can help promote the growth and spread of tumor cells.
But the underlying reasons also appear to vary by cancer type, Dr. Basen-Engquist said. With hormonally driven cancer types, such as breast and endometrial, excess body fat may alter hormone levels in ways that spur tumor growth. Extra fat tissue may, for example, convert androgens into estrogens, which could help feed estrogen-dependent tumors.
That, Dr. Basen-Engquist noted, could be why excess weight is associated with postmenopausal, not premenopausal, breast cancer: Before menopause, body fat is a relatively minor contributor to estrogen levels but becomes more important after menopause.
How Big Is the Effect?
While more than a dozen cancers have been consistently linked to excess weight, the strength of those associations varies considerably.
Endometrial and esophageal cancers are two that stand out. In the 2016 IARC analysis, people with severe obesity had a seven-times greater risk for endometrial cancer and 4.8-times greater risk for esophageal adenocarcinoma vs people with a normal BMI.
With other cancers, the risk increases for those with severe obesity compared with a normal BMI were far more modest: 10% for ovarian cancer, 30% for colorectal cancer, and 80% for kidney and stomach cancers, for example. For postmenopausal breast cancer, every five-unit increase in BMI was associated with a 10% relative risk increase.
A 2018 study from the American Cancer Society, which attempted to estimate the proportion of cancers in the United States attributable to modifiable risk factors — including alcohol consumption, ultraviolet rays exposure, and physical inactivity — found that smoking accounted for the highest proportion of cancer cases by a wide margin (19%), but excess weight came in second (7.8%).
Again, weight appeared to play a bigger role in certain cancers than others: An estimated 60% of endometrial cancers were linked to excess weight, as were roughly one third of esophageal, kidney, and liver cancers. At the other end of the spectrum, just over 11% of breast, 5% of colorectal, and 4% of ovarian cancers were attributable to excess weight.
Even at the lower end, those rates could make a big difference on the population level, especially for groups with higher rates of obesity.
CDC data show that obesity-related cancers are rising among women younger than 50 years, most rapidly among Hispanic women, and some less common obesity-related cancers, such as stomach, thyroid and pancreatic, are also rising among Black individuals and Hispanic Americans.
Obesity may be one reason for growing cancer disparities, said Leah Ferrucci, PhD, MPH, assistant professor, epidemiology, Yale School of Public Health, New Haven, Connecticut. But, she added, the evidence is limited because Black individuals and Hispanic Americans are understudied.
When Do Extra Pounds Matter?
When it comes to cancer risk, at what point in life does excess weight, or weight gain, matter? Is the standard weight gain in middle age, for instance, as hazardous as being overweight or obese from a young age?
Some evidence suggests there’s no “safe” time for putting on excess pounds.
A recent meta-analysis concluded that weight gain at any point after age 18 years is associated with incremental increases in the risk for postmenopausal breast cancer. A 2023 study in JAMA Network Open found a similar pattern with colorectal and other gastrointestinal cancers: People who had sustained overweight or obesity from age 20 years through middle age faced an increased risk of developing those cancers after age 55 years.
The timing of weight gain didn’t seem to matter either. The same elevated risk held among people who were normal weight in their younger years but became overweight after age 55 years.
Those studies focused on later-onset disease. But, in recent years, experts have tracked a troubling rise in early-onset cancers — those diagnosed before age 50 years — particularly gastrointestinal cancers.
An obvious question, Dr. Meyerhardt said, is whether the growing prevalence of obesity among young people is partly to blame.
There’s some data to support that, he said. An analysis from the Nurses’ Health Study II found that women with obesity had double the risk for early-onset colorectal cancer as those with a normal BMI. And every 5-kg increase in weight after age 18 years was associated with a 9% increase in colorectal cancer risk.
But while obesity trends probably partly explain the rise in early-onset cancers, there is likely more to the story, Dr. Meyerhardt said.
“I think all of us who see an increasing number of patients under 50 with colorectal cancer know there’s a fair number who do not fit that [high BMI] profile,” he said. “There’s a fair number over 50 who don’t either.”
Does Weight Loss Help?
With all the evidence pointing to high BMI as a cancer risk factor, a logical conclusion is that weight loss should reduce that excess risk. However, Dr. Bea said, there’s actually little data to support that, and what exists comes from observational studies.
Some research has focused on people who had substantial weight loss after bariatric surgery, with encouraging results. A study published in JAMA found that among 5053 people who underwent bariatric surgery, 2.9% developed an obesity-related cancer over 10 years compared with 4.9% in the nonsurgery group.
Most people, however, aim for less dramatic weight loss, with the help of diet and exercise or sometimes medication. Some evidence shows that a modest degree of weight loss may lower the risks for postmenopausal breast and endometrial cancers.
A 2020 pooled analysis found, for instance, that among women aged ≥ 50 years, those who lost as little as 2.0-4.5 kg, or 4.4-10.0 pounds, and kept it off for 10 years had a lower risk for breast cancer than women whose weight remained stable. And losing more weight — 9 kg, or about 20 pounds, or more — was even better for lowering cancer risk.
But other research suggests the opposite. A recent analysis found that people who lost weight within the past 2 years through diet and exercise had a higher risk for a range of cancers compared with those who did not lose weight. Overall, though, the increased risk was quite low.
Whatever the research does, or doesn’t, show about weight and cancer risk, Dr. Basen-Engquist said, it’s important that risk factors, obesity and otherwise, aren’t “used as blame tools.”
“With obesity, behavior certainly plays into it,” she said. “But there are so many influences on our behavior that are socially determined.”
Both Dr. Basen-Engquist and Dr. Meyerhardt said it’s important for clinicians to consider the individual in front of them and for everyone to set realistic expectations.
People with obesity should not feel they have to become thin to be healthier, and no one has to leap from being sedentary to exercising several hours a week.
“We don’t want patients to feel that if they don’t get to a stated goal in a guideline, it’s all for naught,” Dr. Meyerhardt said.
A version of this article appeared on Medscape.com.
Failed IOL Promotes Poor Maternal and Fetal Outcomes for Mothers With Diabetes
Approximately one-quarter of mothers with diabetes failed induction of labor, and this failure was associated with a range of adverse outcomes for mothers and infants, based on data from more than 2,000 individuals.
Uncontrolled diabetes remains a risk factor for cesarean delivery, Ali Alhousseini, MD, of Corewell Health East, Dearborn, Michigan, and colleagues wrote in a study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
“Identifying and stratifying associated risk factors for failed induction of labor [IOL] may improve counseling and intrapartum care,” the researchers wrote in their abstract.
The researchers reviewed data from 2,172 mothers with diabetes who underwent IOL at a single university medical center between January 2013 and December 2021. They examined a range of maternal characteristics including age, ethnicity, gestational age, medical comorbidities, insulin administration, parity, and health insurance.
A total of 567 mothers with diabetes (26.1%) failed IOL and underwent cesarean delivery.
Overall, failed IOL was significantly associated with nulliparity (P = .0001), as well as preexisting diabetes compared with gestational diabetes, diabetes control with insulin, maternal essential hypertension, preeclampsia, and polyhydramnios (P = .001 for all). Other factors significantly associated with failed IOL included prenatal diagnosis of fetal growth restriction (P = .008), and placental abnormalities (P = .027).
Neonatal factors of weight, large for gestational age, head circumference, and height were not significantly associated with failed IOL (P > .05 for all).
As for neonatal outcomes, failed IOL was significantly associated with admission to neonatal intensive care unit, hyperbilirubinemia, and longer hospital stay (P = .001 for all). Failed IOL was significantly associated with lower 1-minute APGAR scores, but not with lower 5-minute APGAR scores, the researchers noted (P = .033 for 1-minute score). No association was noted between failed IOL and neonatal readmission, lower umbilical cord pH value, or maternal ethnicity.
The findings were limited by the retrospective design, but data analysis is ongoing, Dr. Alhousseini said. The researchers are continuing to assess the roles not only of optimal glucose control, but other maternal factors in improving maternal and neonatal outcomes, he said.
Data Add to Awareness of Risk Factors
The current study is important because of the increasing incidence of diabetes and the need to examine associated risk factors in pregnancy, Michael Richley, MD, a maternal fetal medicine physician at the University of Washington, Seattle, said in an interview. “The average age of onset of diabetes is becoming younger and type 2 diabetes in pregnancy is an increasingly common diagnosis,” said Dr. Richley, who was not involved in the study.
The increase in both maternal and neonatal adverse outcomes is expected given the risk factors identified in the study, said Dr. Richley. “The patients with diabetes also were sicker at baseline, with hypertensive disorders, growth restriction, and pregestational diabetes,” he noted.
The study findings support data from previous research, Dr. Richley said. The message to clinicians is that patients with diabetes not only have an increased risk of needing a cesarean delivery but also have an increased risk of poor outcomes if a cesarean delivery is needed, he said.
Although a prospective study would be useful to show causality as opposed to just an association, such a study is challenging in this patient population given the limitations of conducting research on labor and delivery, he said.
The study received no outside funding. The researchers and Dr. Richley had no financial conflicts to disclose.
Approximately one-quarter of mothers with diabetes failed induction of labor, and this failure was associated with a range of adverse outcomes for mothers and infants, based on data from more than 2,000 individuals.
Uncontrolled diabetes remains a risk factor for cesarean delivery, Ali Alhousseini, MD, of Corewell Health East, Dearborn, Michigan, and colleagues wrote in a study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
“Identifying and stratifying associated risk factors for failed induction of labor [IOL] may improve counseling and intrapartum care,” the researchers wrote in their abstract.
The researchers reviewed data from 2,172 mothers with diabetes who underwent IOL at a single university medical center between January 2013 and December 2021. They examined a range of maternal characteristics including age, ethnicity, gestational age, medical comorbidities, insulin administration, parity, and health insurance.
A total of 567 mothers with diabetes (26.1%) failed IOL and underwent cesarean delivery.
Overall, failed IOL was significantly associated with nulliparity (P = .0001), as well as preexisting diabetes compared with gestational diabetes, diabetes control with insulin, maternal essential hypertension, preeclampsia, and polyhydramnios (P = .001 for all). Other factors significantly associated with failed IOL included prenatal diagnosis of fetal growth restriction (P = .008), and placental abnormalities (P = .027).
Neonatal factors of weight, large for gestational age, head circumference, and height were not significantly associated with failed IOL (P > .05 for all).
As for neonatal outcomes, failed IOL was significantly associated with admission to neonatal intensive care unit, hyperbilirubinemia, and longer hospital stay (P = .001 for all). Failed IOL was significantly associated with lower 1-minute APGAR scores, but not with lower 5-minute APGAR scores, the researchers noted (P = .033 for 1-minute score). No association was noted between failed IOL and neonatal readmission, lower umbilical cord pH value, or maternal ethnicity.
The findings were limited by the retrospective design, but data analysis is ongoing, Dr. Alhousseini said. The researchers are continuing to assess the roles not only of optimal glucose control, but other maternal factors in improving maternal and neonatal outcomes, he said.
Data Add to Awareness of Risk Factors
The current study is important because of the increasing incidence of diabetes and the need to examine associated risk factors in pregnancy, Michael Richley, MD, a maternal fetal medicine physician at the University of Washington, Seattle, said in an interview. “The average age of onset of diabetes is becoming younger and type 2 diabetes in pregnancy is an increasingly common diagnosis,” said Dr. Richley, who was not involved in the study.
The increase in both maternal and neonatal adverse outcomes is expected given the risk factors identified in the study, said Dr. Richley. “The patients with diabetes also were sicker at baseline, with hypertensive disorders, growth restriction, and pregestational diabetes,” he noted.
The study findings support data from previous research, Dr. Richley said. The message to clinicians is that patients with diabetes not only have an increased risk of needing a cesarean delivery but also have an increased risk of poor outcomes if a cesarean delivery is needed, he said.
Although a prospective study would be useful to show causality as opposed to just an association, such a study is challenging in this patient population given the limitations of conducting research on labor and delivery, he said.
The study received no outside funding. The researchers and Dr. Richley had no financial conflicts to disclose.
Approximately one-quarter of mothers with diabetes failed induction of labor, and this failure was associated with a range of adverse outcomes for mothers and infants, based on data from more than 2,000 individuals.
Uncontrolled diabetes remains a risk factor for cesarean delivery, Ali Alhousseini, MD, of Corewell Health East, Dearborn, Michigan, and colleagues wrote in a study presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.
“Identifying and stratifying associated risk factors for failed induction of labor [IOL] may improve counseling and intrapartum care,” the researchers wrote in their abstract.
The researchers reviewed data from 2,172 mothers with diabetes who underwent IOL at a single university medical center between January 2013 and December 2021. They examined a range of maternal characteristics including age, ethnicity, gestational age, medical comorbidities, insulin administration, parity, and health insurance.
A total of 567 mothers with diabetes (26.1%) failed IOL and underwent cesarean delivery.
Overall, failed IOL was significantly associated with nulliparity (P = .0001), as well as preexisting diabetes compared with gestational diabetes, diabetes control with insulin, maternal essential hypertension, preeclampsia, and polyhydramnios (P = .001 for all). Other factors significantly associated with failed IOL included prenatal diagnosis of fetal growth restriction (P = .008), and placental abnormalities (P = .027).
Neonatal factors of weight, large for gestational age, head circumference, and height were not significantly associated with failed IOL (P > .05 for all).
As for neonatal outcomes, failed IOL was significantly associated with admission to neonatal intensive care unit, hyperbilirubinemia, and longer hospital stay (P = .001 for all). Failed IOL was significantly associated with lower 1-minute APGAR scores, but not with lower 5-minute APGAR scores, the researchers noted (P = .033 for 1-minute score). No association was noted between failed IOL and neonatal readmission, lower umbilical cord pH value, or maternal ethnicity.
The findings were limited by the retrospective design, but data analysis is ongoing, Dr. Alhousseini said. The researchers are continuing to assess the roles not only of optimal glucose control, but other maternal factors in improving maternal and neonatal outcomes, he said.
Data Add to Awareness of Risk Factors
The current study is important because of the increasing incidence of diabetes and the need to examine associated risk factors in pregnancy, Michael Richley, MD, a maternal fetal medicine physician at the University of Washington, Seattle, said in an interview. “The average age of onset of diabetes is becoming younger and type 2 diabetes in pregnancy is an increasingly common diagnosis,” said Dr. Richley, who was not involved in the study.
The increase in both maternal and neonatal adverse outcomes is expected given the risk factors identified in the study, said Dr. Richley. “The patients with diabetes also were sicker at baseline, with hypertensive disorders, growth restriction, and pregestational diabetes,” he noted.
The study findings support data from previous research, Dr. Richley said. The message to clinicians is that patients with diabetes not only have an increased risk of needing a cesarean delivery but also have an increased risk of poor outcomes if a cesarean delivery is needed, he said.
Although a prospective study would be useful to show causality as opposed to just an association, such a study is challenging in this patient population given the limitations of conducting research on labor and delivery, he said.
The study received no outside funding. The researchers and Dr. Richley had no financial conflicts to disclose.
FROM ACOG 2024
Parental e-Cigarette Use Linked to Atopic Dermatitis Risk in Children
TOPLINE:
METHODOLOGY:
- AD is one of the most common inflammatory conditions in children and is linked to environmental risk factors, such as exposure to secondhand smoke and prenatal exposure to tobacco.
- To address the effect of e-cigarettes use on children, researchers conducted a cross-sectional analysis of data from the 2014-2018 National Health Interview Survey, a nationally representative sample of the US population.
- The analysis included 48,637,111 individuals (mean age, 8.4 years), with 6,354,515 (13%) indicating a history of AD (mean age, 8 years).
TAKEAWAY:
- The prevalence of parental e-cigarette use was 18.0% among individuals with AD, compared with 14.4% among those without AD.
- This corresponded to a 24% higher risk for AD associated with parental e-cigarette use (adjusted odds ratio, 1.24; 95% CI, 1.08-1.42).
- The association between e-cigarette use and AD in children held regardless of parent’s sex.
IN PRACTICE:
“Our results suggest that parental e-cigarette use was associated with pediatric AD,” the authors concluded. They noted that the authors of a previous study that associated e-cigarette use with AD in adults postulated that the cause was “the inflammatory state created by” e-cigarettes.
SOURCE:
This study, led by Gun Min Youn, Department of Dermatology, Stanford University School of Medicine, Stanford, California, was published online in JAMA Dermatology.
LIMITATIONS:
The cross-sectional survey design limited the ability to draw causal inferences. Defining e-cigarette use as a single past instance could affect the strength of the findings. Only past-year e-cigarette use was considered. Furthermore, data on pediatric cigarette or e-cigarette use, a potential confounder, were unavailable.
DISCLOSURES:
The study did not disclose funding information. One author reported receiving consultation fees outside the submitted work. No other disclosures were reported.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- AD is one of the most common inflammatory conditions in children and is linked to environmental risk factors, such as exposure to secondhand smoke and prenatal exposure to tobacco.
- To address the effect of e-cigarettes use on children, researchers conducted a cross-sectional analysis of data from the 2014-2018 National Health Interview Survey, a nationally representative sample of the US population.
- The analysis included 48,637,111 individuals (mean age, 8.4 years), with 6,354,515 (13%) indicating a history of AD (mean age, 8 years).
TAKEAWAY:
- The prevalence of parental e-cigarette use was 18.0% among individuals with AD, compared with 14.4% among those without AD.
- This corresponded to a 24% higher risk for AD associated with parental e-cigarette use (adjusted odds ratio, 1.24; 95% CI, 1.08-1.42).
- The association between e-cigarette use and AD in children held regardless of parent’s sex.
IN PRACTICE:
“Our results suggest that parental e-cigarette use was associated with pediatric AD,” the authors concluded. They noted that the authors of a previous study that associated e-cigarette use with AD in adults postulated that the cause was “the inflammatory state created by” e-cigarettes.
SOURCE:
This study, led by Gun Min Youn, Department of Dermatology, Stanford University School of Medicine, Stanford, California, was published online in JAMA Dermatology.
LIMITATIONS:
The cross-sectional survey design limited the ability to draw causal inferences. Defining e-cigarette use as a single past instance could affect the strength of the findings. Only past-year e-cigarette use was considered. Furthermore, data on pediatric cigarette or e-cigarette use, a potential confounder, were unavailable.
DISCLOSURES:
The study did not disclose funding information. One author reported receiving consultation fees outside the submitted work. No other disclosures were reported.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- AD is one of the most common inflammatory conditions in children and is linked to environmental risk factors, such as exposure to secondhand smoke and prenatal exposure to tobacco.
- To address the effect of e-cigarettes use on children, researchers conducted a cross-sectional analysis of data from the 2014-2018 National Health Interview Survey, a nationally representative sample of the US population.
- The analysis included 48,637,111 individuals (mean age, 8.4 years), with 6,354,515 (13%) indicating a history of AD (mean age, 8 years).
TAKEAWAY:
- The prevalence of parental e-cigarette use was 18.0% among individuals with AD, compared with 14.4% among those without AD.
- This corresponded to a 24% higher risk for AD associated with parental e-cigarette use (adjusted odds ratio, 1.24; 95% CI, 1.08-1.42).
- The association between e-cigarette use and AD in children held regardless of parent’s sex.
IN PRACTICE:
“Our results suggest that parental e-cigarette use was associated with pediatric AD,” the authors concluded. They noted that the authors of a previous study that associated e-cigarette use with AD in adults postulated that the cause was “the inflammatory state created by” e-cigarettes.
SOURCE:
This study, led by Gun Min Youn, Department of Dermatology, Stanford University School of Medicine, Stanford, California, was published online in JAMA Dermatology.
LIMITATIONS:
The cross-sectional survey design limited the ability to draw causal inferences. Defining e-cigarette use as a single past instance could affect the strength of the findings. Only past-year e-cigarette use was considered. Furthermore, data on pediatric cigarette or e-cigarette use, a potential confounder, were unavailable.
DISCLOSURES:
The study did not disclose funding information. One author reported receiving consultation fees outside the submitted work. No other disclosures were reported.
A version of this article appeared on Medscape.com.
Cortisol Test Confirms HPA Axis Recovery from Steroid Use
TOPLINE:
An early serum cortisol concentration of > 237 nmol/L (> 8.6 μg/dL) has been validated as a safe and useful screening test with 100% specificity for predicting recovery of the hypothalamic-pituitary-adrenal (HPA) axis in patients on tapering regimes from long‐term chronic glucocorticoid therapy (CGT).
METHODOLOGY:
- A retrospective review of 250-µg Synacthen test (SST) results performed in patients on tapering CGT doses from a single-center rheumatology department over 12 months.
- A total of 60 SSTs were performed in 58 patients, all in the morning (7-12 AM) after withholding CGT for 48 hours.
- Peripheral blood was sampled for cortisol at baseline, 30 minutes, and 60 minutes.
- Adrenal insufficiency (AI) was defined as a peak serum cortisol concentration.
TAKEAWAY:
- The mean duration of CGT (all prednisolone) was 63 months, prescribed primarily for giant cell arteritis/polymyalgia rheumatica (48%) and inflammatory arthritis (18%), with a mean daily dose of 3.4 mg at the time of SST.
- With the investigators’ previously reported basal serum cortisol concentration of > 237 nmol/L (> 8.6 μg/dL) used to confirm an intact HPA axis, no patient with AI would have been missed, but 37 of 51 (73%) unnecessary SSTs in euadrenal patients would have been avoided.
- A basal serum cortisol concentration of > 227 nmol/L had a specificity of 100% for predicting passing the SST, while a basal serum cortisol concentration of ≤ 55 nmol/L had a 100% sensitivity for predicting failure.
- A mean daily prednisolone dosing at the time of SST in patients with AI was significantly higher than that with normal SSTs (5.7 vs 2.9 mg, respectively; P = .01).
IN PRACTICE:
“This offers a more rapid, convenient, and cost‐effective screening method for patients requiring biochemical assessment of the HPA axis with the potential for significant resource savings without any adverse impact on patient safety,” the authors wrote.
SOURCE:
The study was conducted by Ella Sharma, of the Department of Endocrinology, Royal Victoria Infirmary, Newcastle upon Tyne, UK, and colleagues and published online on May 19, 2024, as a letter in Clinical Endocrinology.
LIMITATIONS:
Not provided.
DISCLOSURES:
Not provided.
A version of this article appeared on Medscape.com.
TOPLINE:
An early serum cortisol concentration of > 237 nmol/L (> 8.6 μg/dL) has been validated as a safe and useful screening test with 100% specificity for predicting recovery of the hypothalamic-pituitary-adrenal (HPA) axis in patients on tapering regimes from long‐term chronic glucocorticoid therapy (CGT).
METHODOLOGY:
- A retrospective review of 250-µg Synacthen test (SST) results performed in patients on tapering CGT doses from a single-center rheumatology department over 12 months.
- A total of 60 SSTs were performed in 58 patients, all in the morning (7-12 AM) after withholding CGT for 48 hours.
- Peripheral blood was sampled for cortisol at baseline, 30 minutes, and 60 minutes.
- Adrenal insufficiency (AI) was defined as a peak serum cortisol concentration.
TAKEAWAY:
- The mean duration of CGT (all prednisolone) was 63 months, prescribed primarily for giant cell arteritis/polymyalgia rheumatica (48%) and inflammatory arthritis (18%), with a mean daily dose of 3.4 mg at the time of SST.
- With the investigators’ previously reported basal serum cortisol concentration of > 237 nmol/L (> 8.6 μg/dL) used to confirm an intact HPA axis, no patient with AI would have been missed, but 37 of 51 (73%) unnecessary SSTs in euadrenal patients would have been avoided.
- A basal serum cortisol concentration of > 227 nmol/L had a specificity of 100% for predicting passing the SST, while a basal serum cortisol concentration of ≤ 55 nmol/L had a 100% sensitivity for predicting failure.
- A mean daily prednisolone dosing at the time of SST in patients with AI was significantly higher than that with normal SSTs (5.7 vs 2.9 mg, respectively; P = .01).
IN PRACTICE:
“This offers a more rapid, convenient, and cost‐effective screening method for patients requiring biochemical assessment of the HPA axis with the potential for significant resource savings without any adverse impact on patient safety,” the authors wrote.
SOURCE:
The study was conducted by Ella Sharma, of the Department of Endocrinology, Royal Victoria Infirmary, Newcastle upon Tyne, UK, and colleagues and published online on May 19, 2024, as a letter in Clinical Endocrinology.
LIMITATIONS:
Not provided.
DISCLOSURES:
Not provided.
A version of this article appeared on Medscape.com.
TOPLINE:
An early serum cortisol concentration of > 237 nmol/L (> 8.6 μg/dL) has been validated as a safe and useful screening test with 100% specificity for predicting recovery of the hypothalamic-pituitary-adrenal (HPA) axis in patients on tapering regimes from long‐term chronic glucocorticoid therapy (CGT).
METHODOLOGY:
- A retrospective review of 250-µg Synacthen test (SST) results performed in patients on tapering CGT doses from a single-center rheumatology department over 12 months.
- A total of 60 SSTs were performed in 58 patients, all in the morning (7-12 AM) after withholding CGT for 48 hours.
- Peripheral blood was sampled for cortisol at baseline, 30 minutes, and 60 minutes.
- Adrenal insufficiency (AI) was defined as a peak serum cortisol concentration.
TAKEAWAY:
- The mean duration of CGT (all prednisolone) was 63 months, prescribed primarily for giant cell arteritis/polymyalgia rheumatica (48%) and inflammatory arthritis (18%), with a mean daily dose of 3.4 mg at the time of SST.
- With the investigators’ previously reported basal serum cortisol concentration of > 237 nmol/L (> 8.6 μg/dL) used to confirm an intact HPA axis, no patient with AI would have been missed, but 37 of 51 (73%) unnecessary SSTs in euadrenal patients would have been avoided.
- A basal serum cortisol concentration of > 227 nmol/L had a specificity of 100% for predicting passing the SST, while a basal serum cortisol concentration of ≤ 55 nmol/L had a 100% sensitivity for predicting failure.
- A mean daily prednisolone dosing at the time of SST in patients with AI was significantly higher than that with normal SSTs (5.7 vs 2.9 mg, respectively; P = .01).
IN PRACTICE:
“This offers a more rapid, convenient, and cost‐effective screening method for patients requiring biochemical assessment of the HPA axis with the potential for significant resource savings without any adverse impact on patient safety,” the authors wrote.
SOURCE:
The study was conducted by Ella Sharma, of the Department of Endocrinology, Royal Victoria Infirmary, Newcastle upon Tyne, UK, and colleagues and published online on May 19, 2024, as a letter in Clinical Endocrinology.
LIMITATIONS:
Not provided.
DISCLOSURES:
Not provided.
A version of this article appeared on Medscape.com.
Greater Awareness Urged for Important, Overlooked Neuropsychiatric Symptoms of Lupus
Neuropsychiatric symptoms, including nightmares and hallucinatory “daymares,” may be a more important aspect of systemic lupus erythematosus (SLE) than formerly recognized, according to a qualitative mixed methods study published in The Lancet Discovery Science’s eClinicalMedicine. The findings suggested these neuropsychiatric symptoms can sometimes present as prodromal and other times act as an early warning system for a forthcoming flare.
“For clinicians, the key point is to be aware that neurological and psychiatric symptoms are much more common in patients with lupus and other autoimmune systemic rheumatic diseases than previously thought,” lead author Melanie Sloan, PhD, of the Department of Public Health and Primary Care at the University of Cambridge in England, told this news organization.
“If clinicians — and some do already — could all ask about and document these symptoms for each patient, the usual progression of symptoms in a flare can then be monitored, and patients could be supported and treated at an earlier stage,” Dr. Sloan said. “Another key point is to consider systemic autoimmune diseases at an early stage if a patient presents with multiple seemingly unconnected symptoms, which often include both physical and mental health symptoms.”
Alfred Kim, MD, PhD, associate professor of medicine in rheumatology at Washington University School of Medicine in St. Louis, Missouri, noted the difficulty of determining what neuropsychiatric symptoms may be linked to lupus vs those occurring independently or as part of a different condition.
“There is some controversy about whether the neuropsychiatric manifestations that we have long attributed to lupus actually are due to lupus,” Dr. Kim told this news organization. Dr. Kim was part of a group that published a review on potential mechanisms underlying neuropsychiatric symptoms described by a committee of the American College of Rheumatology.
Since that committee’s findings, “we have long assumed that if we saw these symptoms, the best explanation was lupus,” Dr. Kim said. “The problem is that, in the real world, we can see many of these manifestations in patients with lupus that do not get better with lupus meds. This opens up the very real possibility that another etiology is at play.”
Dr. Kim noted that mood disorders such as depression and anxiety may be part of the neuropsychiatric SLE criteria, but they failed to correlate with overall lupus disease activity in a cohort he evaluated. That makes it hard to distinguish whether those neuropsychiatric symptoms can actually be attributed to lupus. “Probably the more accurate interpretation is that there may be certain symptoms, such as nightmares, that indicated a prodrome of lupus,” he said. “Whether these are actually lupus symptoms is debatable to me.”
There remains value in initiating discussions about these symptoms with patients, however, because the stigma associated with neuropsychiatric symptoms may prevent patients from bringing them up themselves.
“It is important to remember that many of these patients, in common with other chronic diseases, will often have had long and traumatic journeys to diagnosis,” including having been misdiagnosed with a psychiatric condition, Dr. Sloan said. “Many of the patients then lose trust in doctors and are reluctant to report symptoms that may lead to another misdiagnosis.”
Clinicians may also be reluctant to bring up these symptoms, but for different reasons. Their reluctance may stem from insufficient time to discuss the symptoms or not having the support available to help the patients with these particular problems, Dr. Sloan said. The invisible nature of these symptoms, which lack biomarkers, makes them harder to identify and makes listening to patients more important, she added.
Study Details
In planning for the study, the researchers first searched the existing literature for studies involving neuropsychiatric symptoms in patients with systemic autoimmune rheumatic diseases (SARDs). “The literature indicated frequent underreporting and misattributions of neuropsychiatric symptoms in SLE and other SARD patients, and clinician-patient discordance in neuropsychiatric symptom attribution,” the authors reported.
During 2022-2023, the researchers conducted two surveys, one with 676 adult patients with SLE and one with 400 clinicians, recruited through social media, online patient support groups, and professional networks. All patients self-reported an SLE diagnosis that the researchers did not independently confirm. The patients were predominantly White (80%) and female (94%), ranging in age from 18 to over 70, with most falling between ages 40 and 69. Most patients lived in the United Kingdom (76%) or Europe (15%).
The clinicians included 51% rheumatologists, 24% psychiatrists, 13% neurologists, 5% rheumatology nurses, 3% primary care physicians, and 7% other clinicians. Nearly half of the clinicians (45%) were from the United Kingdom, with others from the United States or Canada (16%), Europe (17%), Asia (9%), Latin America (8%), Australia or New Zealand (3%), or elsewhere (3%).
The patient surveys asked whether they had experienced any of the 29 neuropsychiatric symptoms. For the symptoms that patients had experienced at least three times in their lives, the survey asked when they first experienced the symptom in relation to their SLE onset or other SLE symptoms: Over a year before, within a year of (on either side), 1-4 years after, or more than 5 years after onset/other symptoms. “Other quantitative data included timings of disrupted dreaming sleep in relation to hallucinations for those patients reporting experiencing these,” the authors wrote.
The researchers also conducted video conference interviews with 50 clinicians, including 20 rheumatologists, and 69 interviews with patients who had a systemic autoimmune rheumatic disease, including 27 patients with SLE. Other conditions among those interviewed included inflammatory arthritis, vasculitis, Sjögren disease, systemic sclerosis, myositis, undifferentiated and mixed connective tissue diseases, and polymyalgia rheumatica. During interviews, the term “daymare” was used to discuss possible hallucinations.
Linking Neuropsychiatric Symptoms and Disease
Four themes emerged from the analysis of the surveys and interviews. First, despite many rheumatologists stating that it was an “established theory” that most neuropsychiatric symptoms related to SLE would initially present around the time of diagnosis or disease onset, the findings from patients and interviews with psychiatrists did not align with this theory. The first presentation of each neuropsychiatric symptom only occurred around the onset of other SLE symptoms, about one fifth to one third of the time. In fact, more than half of the patients with SLE who had experienced hallucinations or delusions/paranoia said they occurred more than a year after they first experienced their other SLE symptoms.
Patient experiences differed in terms of whether they believed their neuropsychiatric symptoms were directly related to their SLE or other rheumatic disease. Some did attribute the symptoms, such as hypomania, to their rheumatic illness, while others, such as a patient with major depression, did not see the two as linked.
A second theme focused on pattern recognition of neuropsychiatric symptoms and the onset of a disease flare. “For example, several patients described how they felt that some types of depressive symptoms were directly attributable to active inflammation due to its time of onset and differences in type and intensity compared to their more ‘reactive’ low mood that could be more attributable to a consequence of psychological distress,” the authors wrote. Another common report from patients was experiencing a sudden, intense fatigue that coincided with a flare and differed from other types of fatigue.
Some patients could recognize that a flare was coming because of familiar neuropsychiatric symptoms that acted like an “early warning system.” Often, however, these symptoms “were absent from current diagnostic guidelines and only rarely identified by clinician interviewees as related to SLE/NPSLE,” the authors found. “These neuropsychiatric prodromal symptoms were reported as sometimes preceding the more widely recognized SLE and other SARD symptoms such as joint pain, rashes, and other organ involvement.” These symptoms included sudden changes in mood (usually a lowering but sometimes mania), increased nightmares, a “feeling of unreality,” or increased sensory symptoms.
Other patients, on the other hand, had not considered a link between neuropsychiatric symptoms and their rheumatic disease until the interview, and many of the clinicians, aside from psychiatrists and nurses, said they had little time in clinic to gather information about symptom progression.
Nightmares and Daymares
A third theme centered on disrupted dreaming sleep, nightmares, and “daymares” as a prodromal symptom in particular. Some patients had already drawn a connection between an oncoming flare of their disease and these dreaming-related symptoms, while others had not considered a link until the interviews.
“Several SLE patients recounted flares consistently involving the segueing of increasingly vivid and distressing nightmares into distorted reality and daytime hallucinations,” the authors reported. Flare-related nightmares in particular “often involved being attacked, trapped, crushed, or falling.” Patients tended to be more forthcoming about hallucinatory experiences when the term “daymare” was used to describe them, and they often related to the idea of feeling “in-between asleep and awake.”
Only one of the rheumatologists interviewed had considered nightmares as potentially related to SLE flares, and several appeared skeptical about a link but planned to ask their patients about it. Most of the specialists interviewed, meanwhile, said they often discussed sleep disruption with patients.
“There was agreement that recognizing and eliciting these early flare symptoms may improve care and even reduce clinic times by averting flares at any earlier stage, although some rheumatologists were clear that limited appointment times meant that these symptoms would not be prioritized for discussion,” the authors wrote.
Though Dr. Kim acknowledged the possibility of nightmares as prodromal, he noted other ways in which nightmares may be indirectly linked to lupus. “Trauma is a major risk factor for lupus,” Dr. Kim said, with multiple studies showing childhood traumatic experiences and even posttraumatic stress disorder to be risk factors for lupus. “Whether nightmares represent a traumatic event or prior traumatic events is not clear to me, but one could hypothesize that this may be a manifestation of trauma,” Dr. Kim said.
In addition, nightmares represent a sleep disorder that can substantially reduce sleep quality, Dr. Kim said, and poor sleep is also associated with lupus. “One has to wonder whether disruptive dreaming sleep is one of several specific manifestations of poor sleep quality, which then increases the risk of lupus in those patients,” Dr. Kim said.
Misattribution of Neuropsychiatric Symptoms
The final theme to emerge from the findings was patients had been misdiagnosed with psychiatric or psychosomatic conditions shortly before getting their rheumatic disease diagnosis. One patient, for example, reported being diagnosed with borderline personality disorder just 6 months before the lupus diagnosis at age 19 and noticed that the symptoms of one “got under control” when the symptoms of the other did.
“Early misattributions of SARD symptoms to primary psychiatric or psychosomatic conditions were frequently reported to have delayed SARD diagnosis and led to future misattributions,” the authors reported. “Whilst some of these misdiagnoses likely reflect the widespread lack of knowledge and limited definitive tests for SLE, it is plausible that some early SLE neurological and/or psychiatric symptoms may represent a neuropsychiatric prodrome for SLE itself.”
Dr. Kim agreed that misattribution of symptoms to other diagnoses is common with lupus and a common reason for delays in diagnosis, even with symptoms that are not neuropsychiatric. The findings in this study broaden “the type of symptoms we need to put on our radar pre-diagnosis,” Dr. Kim said. “We just also have to be aware that these prodromal symptoms are not diagnostic for lupus, though.”
Dr. Sloan cited earlier work in recommending an “ABC” approach to improving clinician-patient relationships: “Availability is being accessible when patients need them, Belief is demonstrating belief and validating patient self-reports of symptoms, and Continuity is when the same clinician sees the same patient each clinic visit to build up a trusting relationship.” She noted the importance of asking about and normalizing the existence of these symptoms with rheumatic diseases.
The research was funded by The Lupus Trust. Three authors reported consultancy, speaker, or advisory fees from Alumis, Amgen, AstraZeneca, Eli Lilly, GlaxoSmithKline, Janssen, MGP, Novartis, Pfizer, Sanofi, UCB, Vifor, and/or Werfen Group. The other authors, including Dr. Sloan, had no industry-related disclosures. Dr. Kim reported research support from AstraZeneca, GlaxoSmithKline, and Novartis; speaking fees from Exagen Diagnostics and GlaxoSmithKline; and consulting fees from AbbVie, Amgen, ANI Pharmaceuticals, AstraZeneca, Atara Bio, Aurinia Pharmaceuticals, Cargo Therapeutics, Exagen Diagnostics, Hinge Bio, GlaxoSmithKline, Kypha, Miltenyi Biotec, Synthekine, and Tectonic Therapeutic.
A version of this article appeared on Medscape.com.
Neuropsychiatric symptoms, including nightmares and hallucinatory “daymares,” may be a more important aspect of systemic lupus erythematosus (SLE) than formerly recognized, according to a qualitative mixed methods study published in The Lancet Discovery Science’s eClinicalMedicine. The findings suggested these neuropsychiatric symptoms can sometimes present as prodromal and other times act as an early warning system for a forthcoming flare.
“For clinicians, the key point is to be aware that neurological and psychiatric symptoms are much more common in patients with lupus and other autoimmune systemic rheumatic diseases than previously thought,” lead author Melanie Sloan, PhD, of the Department of Public Health and Primary Care at the University of Cambridge in England, told this news organization.
“If clinicians — and some do already — could all ask about and document these symptoms for each patient, the usual progression of symptoms in a flare can then be monitored, and patients could be supported and treated at an earlier stage,” Dr. Sloan said. “Another key point is to consider systemic autoimmune diseases at an early stage if a patient presents with multiple seemingly unconnected symptoms, which often include both physical and mental health symptoms.”
Alfred Kim, MD, PhD, associate professor of medicine in rheumatology at Washington University School of Medicine in St. Louis, Missouri, noted the difficulty of determining what neuropsychiatric symptoms may be linked to lupus vs those occurring independently or as part of a different condition.
“There is some controversy about whether the neuropsychiatric manifestations that we have long attributed to lupus actually are due to lupus,” Dr. Kim told this news organization. Dr. Kim was part of a group that published a review on potential mechanisms underlying neuropsychiatric symptoms described by a committee of the American College of Rheumatology.
Since that committee’s findings, “we have long assumed that if we saw these symptoms, the best explanation was lupus,” Dr. Kim said. “The problem is that, in the real world, we can see many of these manifestations in patients with lupus that do not get better with lupus meds. This opens up the very real possibility that another etiology is at play.”
Dr. Kim noted that mood disorders such as depression and anxiety may be part of the neuropsychiatric SLE criteria, but they failed to correlate with overall lupus disease activity in a cohort he evaluated. That makes it hard to distinguish whether those neuropsychiatric symptoms can actually be attributed to lupus. “Probably the more accurate interpretation is that there may be certain symptoms, such as nightmares, that indicated a prodrome of lupus,” he said. “Whether these are actually lupus symptoms is debatable to me.”
There remains value in initiating discussions about these symptoms with patients, however, because the stigma associated with neuropsychiatric symptoms may prevent patients from bringing them up themselves.
“It is important to remember that many of these patients, in common with other chronic diseases, will often have had long and traumatic journeys to diagnosis,” including having been misdiagnosed with a psychiatric condition, Dr. Sloan said. “Many of the patients then lose trust in doctors and are reluctant to report symptoms that may lead to another misdiagnosis.”
Clinicians may also be reluctant to bring up these symptoms, but for different reasons. Their reluctance may stem from insufficient time to discuss the symptoms or not having the support available to help the patients with these particular problems, Dr. Sloan said. The invisible nature of these symptoms, which lack biomarkers, makes them harder to identify and makes listening to patients more important, she added.
Study Details
In planning for the study, the researchers first searched the existing literature for studies involving neuropsychiatric symptoms in patients with systemic autoimmune rheumatic diseases (SARDs). “The literature indicated frequent underreporting and misattributions of neuropsychiatric symptoms in SLE and other SARD patients, and clinician-patient discordance in neuropsychiatric symptom attribution,” the authors reported.
During 2022-2023, the researchers conducted two surveys, one with 676 adult patients with SLE and one with 400 clinicians, recruited through social media, online patient support groups, and professional networks. All patients self-reported an SLE diagnosis that the researchers did not independently confirm. The patients were predominantly White (80%) and female (94%), ranging in age from 18 to over 70, with most falling between ages 40 and 69. Most patients lived in the United Kingdom (76%) or Europe (15%).
The clinicians included 51% rheumatologists, 24% psychiatrists, 13% neurologists, 5% rheumatology nurses, 3% primary care physicians, and 7% other clinicians. Nearly half of the clinicians (45%) were from the United Kingdom, with others from the United States or Canada (16%), Europe (17%), Asia (9%), Latin America (8%), Australia or New Zealand (3%), or elsewhere (3%).
The patient surveys asked whether they had experienced any of the 29 neuropsychiatric symptoms. For the symptoms that patients had experienced at least three times in their lives, the survey asked when they first experienced the symptom in relation to their SLE onset or other SLE symptoms: Over a year before, within a year of (on either side), 1-4 years after, or more than 5 years after onset/other symptoms. “Other quantitative data included timings of disrupted dreaming sleep in relation to hallucinations for those patients reporting experiencing these,” the authors wrote.
The researchers also conducted video conference interviews with 50 clinicians, including 20 rheumatologists, and 69 interviews with patients who had a systemic autoimmune rheumatic disease, including 27 patients with SLE. Other conditions among those interviewed included inflammatory arthritis, vasculitis, Sjögren disease, systemic sclerosis, myositis, undifferentiated and mixed connective tissue diseases, and polymyalgia rheumatica. During interviews, the term “daymare” was used to discuss possible hallucinations.
Linking Neuropsychiatric Symptoms and Disease
Four themes emerged from the analysis of the surveys and interviews. First, despite many rheumatologists stating that it was an “established theory” that most neuropsychiatric symptoms related to SLE would initially present around the time of diagnosis or disease onset, the findings from patients and interviews with psychiatrists did not align with this theory. The first presentation of each neuropsychiatric symptom only occurred around the onset of other SLE symptoms, about one fifth to one third of the time. In fact, more than half of the patients with SLE who had experienced hallucinations or delusions/paranoia said they occurred more than a year after they first experienced their other SLE symptoms.
Patient experiences differed in terms of whether they believed their neuropsychiatric symptoms were directly related to their SLE or other rheumatic disease. Some did attribute the symptoms, such as hypomania, to their rheumatic illness, while others, such as a patient with major depression, did not see the two as linked.
A second theme focused on pattern recognition of neuropsychiatric symptoms and the onset of a disease flare. “For example, several patients described how they felt that some types of depressive symptoms were directly attributable to active inflammation due to its time of onset and differences in type and intensity compared to their more ‘reactive’ low mood that could be more attributable to a consequence of psychological distress,” the authors wrote. Another common report from patients was experiencing a sudden, intense fatigue that coincided with a flare and differed from other types of fatigue.
Some patients could recognize that a flare was coming because of familiar neuropsychiatric symptoms that acted like an “early warning system.” Often, however, these symptoms “were absent from current diagnostic guidelines and only rarely identified by clinician interviewees as related to SLE/NPSLE,” the authors found. “These neuropsychiatric prodromal symptoms were reported as sometimes preceding the more widely recognized SLE and other SARD symptoms such as joint pain, rashes, and other organ involvement.” These symptoms included sudden changes in mood (usually a lowering but sometimes mania), increased nightmares, a “feeling of unreality,” or increased sensory symptoms.
Other patients, on the other hand, had not considered a link between neuropsychiatric symptoms and their rheumatic disease until the interview, and many of the clinicians, aside from psychiatrists and nurses, said they had little time in clinic to gather information about symptom progression.
Nightmares and Daymares
A third theme centered on disrupted dreaming sleep, nightmares, and “daymares” as a prodromal symptom in particular. Some patients had already drawn a connection between an oncoming flare of their disease and these dreaming-related symptoms, while others had not considered a link until the interviews.
“Several SLE patients recounted flares consistently involving the segueing of increasingly vivid and distressing nightmares into distorted reality and daytime hallucinations,” the authors reported. Flare-related nightmares in particular “often involved being attacked, trapped, crushed, or falling.” Patients tended to be more forthcoming about hallucinatory experiences when the term “daymare” was used to describe them, and they often related to the idea of feeling “in-between asleep and awake.”
Only one of the rheumatologists interviewed had considered nightmares as potentially related to SLE flares, and several appeared skeptical about a link but planned to ask their patients about it. Most of the specialists interviewed, meanwhile, said they often discussed sleep disruption with patients.
“There was agreement that recognizing and eliciting these early flare symptoms may improve care and even reduce clinic times by averting flares at any earlier stage, although some rheumatologists were clear that limited appointment times meant that these symptoms would not be prioritized for discussion,” the authors wrote.
Though Dr. Kim acknowledged the possibility of nightmares as prodromal, he noted other ways in which nightmares may be indirectly linked to lupus. “Trauma is a major risk factor for lupus,” Dr. Kim said, with multiple studies showing childhood traumatic experiences and even posttraumatic stress disorder to be risk factors for lupus. “Whether nightmares represent a traumatic event or prior traumatic events is not clear to me, but one could hypothesize that this may be a manifestation of trauma,” Dr. Kim said.
In addition, nightmares represent a sleep disorder that can substantially reduce sleep quality, Dr. Kim said, and poor sleep is also associated with lupus. “One has to wonder whether disruptive dreaming sleep is one of several specific manifestations of poor sleep quality, which then increases the risk of lupus in those patients,” Dr. Kim said.
Misattribution of Neuropsychiatric Symptoms
The final theme to emerge from the findings was patients had been misdiagnosed with psychiatric or psychosomatic conditions shortly before getting their rheumatic disease diagnosis. One patient, for example, reported being diagnosed with borderline personality disorder just 6 months before the lupus diagnosis at age 19 and noticed that the symptoms of one “got under control” when the symptoms of the other did.
“Early misattributions of SARD symptoms to primary psychiatric or psychosomatic conditions were frequently reported to have delayed SARD diagnosis and led to future misattributions,” the authors reported. “Whilst some of these misdiagnoses likely reflect the widespread lack of knowledge and limited definitive tests for SLE, it is plausible that some early SLE neurological and/or psychiatric symptoms may represent a neuropsychiatric prodrome for SLE itself.”
Dr. Kim agreed that misattribution of symptoms to other diagnoses is common with lupus and a common reason for delays in diagnosis, even with symptoms that are not neuropsychiatric. The findings in this study broaden “the type of symptoms we need to put on our radar pre-diagnosis,” Dr. Kim said. “We just also have to be aware that these prodromal symptoms are not diagnostic for lupus, though.”
Dr. Sloan cited earlier work in recommending an “ABC” approach to improving clinician-patient relationships: “Availability is being accessible when patients need them, Belief is demonstrating belief and validating patient self-reports of symptoms, and Continuity is when the same clinician sees the same patient each clinic visit to build up a trusting relationship.” She noted the importance of asking about and normalizing the existence of these symptoms with rheumatic diseases.
The research was funded by The Lupus Trust. Three authors reported consultancy, speaker, or advisory fees from Alumis, Amgen, AstraZeneca, Eli Lilly, GlaxoSmithKline, Janssen, MGP, Novartis, Pfizer, Sanofi, UCB, Vifor, and/or Werfen Group. The other authors, including Dr. Sloan, had no industry-related disclosures. Dr. Kim reported research support from AstraZeneca, GlaxoSmithKline, and Novartis; speaking fees from Exagen Diagnostics and GlaxoSmithKline; and consulting fees from AbbVie, Amgen, ANI Pharmaceuticals, AstraZeneca, Atara Bio, Aurinia Pharmaceuticals, Cargo Therapeutics, Exagen Diagnostics, Hinge Bio, GlaxoSmithKline, Kypha, Miltenyi Biotec, Synthekine, and Tectonic Therapeutic.
A version of this article appeared on Medscape.com.
Neuropsychiatric symptoms, including nightmares and hallucinatory “daymares,” may be a more important aspect of systemic lupus erythematosus (SLE) than formerly recognized, according to a qualitative mixed methods study published in The Lancet Discovery Science’s eClinicalMedicine. The findings suggested these neuropsychiatric symptoms can sometimes present as prodromal and other times act as an early warning system for a forthcoming flare.
“For clinicians, the key point is to be aware that neurological and psychiatric symptoms are much more common in patients with lupus and other autoimmune systemic rheumatic diseases than previously thought,” lead author Melanie Sloan, PhD, of the Department of Public Health and Primary Care at the University of Cambridge in England, told this news organization.
“If clinicians — and some do already — could all ask about and document these symptoms for each patient, the usual progression of symptoms in a flare can then be monitored, and patients could be supported and treated at an earlier stage,” Dr. Sloan said. “Another key point is to consider systemic autoimmune diseases at an early stage if a patient presents with multiple seemingly unconnected symptoms, which often include both physical and mental health symptoms.”
Alfred Kim, MD, PhD, associate professor of medicine in rheumatology at Washington University School of Medicine in St. Louis, Missouri, noted the difficulty of determining what neuropsychiatric symptoms may be linked to lupus vs those occurring independently or as part of a different condition.
“There is some controversy about whether the neuropsychiatric manifestations that we have long attributed to lupus actually are due to lupus,” Dr. Kim told this news organization. Dr. Kim was part of a group that published a review on potential mechanisms underlying neuropsychiatric symptoms described by a committee of the American College of Rheumatology.
Since that committee’s findings, “we have long assumed that if we saw these symptoms, the best explanation was lupus,” Dr. Kim said. “The problem is that, in the real world, we can see many of these manifestations in patients with lupus that do not get better with lupus meds. This opens up the very real possibility that another etiology is at play.”
Dr. Kim noted that mood disorders such as depression and anxiety may be part of the neuropsychiatric SLE criteria, but they failed to correlate with overall lupus disease activity in a cohort he evaluated. That makes it hard to distinguish whether those neuropsychiatric symptoms can actually be attributed to lupus. “Probably the more accurate interpretation is that there may be certain symptoms, such as nightmares, that indicated a prodrome of lupus,” he said. “Whether these are actually lupus symptoms is debatable to me.”
There remains value in initiating discussions about these symptoms with patients, however, because the stigma associated with neuropsychiatric symptoms may prevent patients from bringing them up themselves.
“It is important to remember that many of these patients, in common with other chronic diseases, will often have had long and traumatic journeys to diagnosis,” including having been misdiagnosed with a psychiatric condition, Dr. Sloan said. “Many of the patients then lose trust in doctors and are reluctant to report symptoms that may lead to another misdiagnosis.”
Clinicians may also be reluctant to bring up these symptoms, but for different reasons. Their reluctance may stem from insufficient time to discuss the symptoms or not having the support available to help the patients with these particular problems, Dr. Sloan said. The invisible nature of these symptoms, which lack biomarkers, makes them harder to identify and makes listening to patients more important, she added.
Study Details
In planning for the study, the researchers first searched the existing literature for studies involving neuropsychiatric symptoms in patients with systemic autoimmune rheumatic diseases (SARDs). “The literature indicated frequent underreporting and misattributions of neuropsychiatric symptoms in SLE and other SARD patients, and clinician-patient discordance in neuropsychiatric symptom attribution,” the authors reported.
During 2022-2023, the researchers conducted two surveys, one with 676 adult patients with SLE and one with 400 clinicians, recruited through social media, online patient support groups, and professional networks. All patients self-reported an SLE diagnosis that the researchers did not independently confirm. The patients were predominantly White (80%) and female (94%), ranging in age from 18 to over 70, with most falling between ages 40 and 69. Most patients lived in the United Kingdom (76%) or Europe (15%).
The clinicians included 51% rheumatologists, 24% psychiatrists, 13% neurologists, 5% rheumatology nurses, 3% primary care physicians, and 7% other clinicians. Nearly half of the clinicians (45%) were from the United Kingdom, with others from the United States or Canada (16%), Europe (17%), Asia (9%), Latin America (8%), Australia or New Zealand (3%), or elsewhere (3%).
The patient surveys asked whether they had experienced any of the 29 neuropsychiatric symptoms. For the symptoms that patients had experienced at least three times in their lives, the survey asked when they first experienced the symptom in relation to their SLE onset or other SLE symptoms: Over a year before, within a year of (on either side), 1-4 years after, or more than 5 years after onset/other symptoms. “Other quantitative data included timings of disrupted dreaming sleep in relation to hallucinations for those patients reporting experiencing these,” the authors wrote.
The researchers also conducted video conference interviews with 50 clinicians, including 20 rheumatologists, and 69 interviews with patients who had a systemic autoimmune rheumatic disease, including 27 patients with SLE. Other conditions among those interviewed included inflammatory arthritis, vasculitis, Sjögren disease, systemic sclerosis, myositis, undifferentiated and mixed connective tissue diseases, and polymyalgia rheumatica. During interviews, the term “daymare” was used to discuss possible hallucinations.
Linking Neuropsychiatric Symptoms and Disease
Four themes emerged from the analysis of the surveys and interviews. First, despite many rheumatologists stating that it was an “established theory” that most neuropsychiatric symptoms related to SLE would initially present around the time of diagnosis or disease onset, the findings from patients and interviews with psychiatrists did not align with this theory. The first presentation of each neuropsychiatric symptom only occurred around the onset of other SLE symptoms, about one fifth to one third of the time. In fact, more than half of the patients with SLE who had experienced hallucinations or delusions/paranoia said they occurred more than a year after they first experienced their other SLE symptoms.
Patient experiences differed in terms of whether they believed their neuropsychiatric symptoms were directly related to their SLE or other rheumatic disease. Some did attribute the symptoms, such as hypomania, to their rheumatic illness, while others, such as a patient with major depression, did not see the two as linked.
A second theme focused on pattern recognition of neuropsychiatric symptoms and the onset of a disease flare. “For example, several patients described how they felt that some types of depressive symptoms were directly attributable to active inflammation due to its time of onset and differences in type and intensity compared to their more ‘reactive’ low mood that could be more attributable to a consequence of psychological distress,” the authors wrote. Another common report from patients was experiencing a sudden, intense fatigue that coincided with a flare and differed from other types of fatigue.
Some patients could recognize that a flare was coming because of familiar neuropsychiatric symptoms that acted like an “early warning system.” Often, however, these symptoms “were absent from current diagnostic guidelines and only rarely identified by clinician interviewees as related to SLE/NPSLE,” the authors found. “These neuropsychiatric prodromal symptoms were reported as sometimes preceding the more widely recognized SLE and other SARD symptoms such as joint pain, rashes, and other organ involvement.” These symptoms included sudden changes in mood (usually a lowering but sometimes mania), increased nightmares, a “feeling of unreality,” or increased sensory symptoms.
Other patients, on the other hand, had not considered a link between neuropsychiatric symptoms and their rheumatic disease until the interview, and many of the clinicians, aside from psychiatrists and nurses, said they had little time in clinic to gather information about symptom progression.
Nightmares and Daymares
A third theme centered on disrupted dreaming sleep, nightmares, and “daymares” as a prodromal symptom in particular. Some patients had already drawn a connection between an oncoming flare of their disease and these dreaming-related symptoms, while others had not considered a link until the interviews.
“Several SLE patients recounted flares consistently involving the segueing of increasingly vivid and distressing nightmares into distorted reality and daytime hallucinations,” the authors reported. Flare-related nightmares in particular “often involved being attacked, trapped, crushed, or falling.” Patients tended to be more forthcoming about hallucinatory experiences when the term “daymare” was used to describe them, and they often related to the idea of feeling “in-between asleep and awake.”
Only one of the rheumatologists interviewed had considered nightmares as potentially related to SLE flares, and several appeared skeptical about a link but planned to ask their patients about it. Most of the specialists interviewed, meanwhile, said they often discussed sleep disruption with patients.
“There was agreement that recognizing and eliciting these early flare symptoms may improve care and even reduce clinic times by averting flares at any earlier stage, although some rheumatologists were clear that limited appointment times meant that these symptoms would not be prioritized for discussion,” the authors wrote.
Though Dr. Kim acknowledged the possibility of nightmares as prodromal, he noted other ways in which nightmares may be indirectly linked to lupus. “Trauma is a major risk factor for lupus,” Dr. Kim said, with multiple studies showing childhood traumatic experiences and even posttraumatic stress disorder to be risk factors for lupus. “Whether nightmares represent a traumatic event or prior traumatic events is not clear to me, but one could hypothesize that this may be a manifestation of trauma,” Dr. Kim said.
In addition, nightmares represent a sleep disorder that can substantially reduce sleep quality, Dr. Kim said, and poor sleep is also associated with lupus. “One has to wonder whether disruptive dreaming sleep is one of several specific manifestations of poor sleep quality, which then increases the risk of lupus in those patients,” Dr. Kim said.
Misattribution of Neuropsychiatric Symptoms
The final theme to emerge from the findings was patients had been misdiagnosed with psychiatric or psychosomatic conditions shortly before getting their rheumatic disease diagnosis. One patient, for example, reported being diagnosed with borderline personality disorder just 6 months before the lupus diagnosis at age 19 and noticed that the symptoms of one “got under control” when the symptoms of the other did.
“Early misattributions of SARD symptoms to primary psychiatric or psychosomatic conditions were frequently reported to have delayed SARD diagnosis and led to future misattributions,” the authors reported. “Whilst some of these misdiagnoses likely reflect the widespread lack of knowledge and limited definitive tests for SLE, it is plausible that some early SLE neurological and/or psychiatric symptoms may represent a neuropsychiatric prodrome for SLE itself.”
Dr. Kim agreed that misattribution of symptoms to other diagnoses is common with lupus and a common reason for delays in diagnosis, even with symptoms that are not neuropsychiatric. The findings in this study broaden “the type of symptoms we need to put on our radar pre-diagnosis,” Dr. Kim said. “We just also have to be aware that these prodromal symptoms are not diagnostic for lupus, though.”
Dr. Sloan cited earlier work in recommending an “ABC” approach to improving clinician-patient relationships: “Availability is being accessible when patients need them, Belief is demonstrating belief and validating patient self-reports of symptoms, and Continuity is when the same clinician sees the same patient each clinic visit to build up a trusting relationship.” She noted the importance of asking about and normalizing the existence of these symptoms with rheumatic diseases.
The research was funded by The Lupus Trust. Three authors reported consultancy, speaker, or advisory fees from Alumis, Amgen, AstraZeneca, Eli Lilly, GlaxoSmithKline, Janssen, MGP, Novartis, Pfizer, Sanofi, UCB, Vifor, and/or Werfen Group. The other authors, including Dr. Sloan, had no industry-related disclosures. Dr. Kim reported research support from AstraZeneca, GlaxoSmithKline, and Novartis; speaking fees from Exagen Diagnostics and GlaxoSmithKline; and consulting fees from AbbVie, Amgen, ANI Pharmaceuticals, AstraZeneca, Atara Bio, Aurinia Pharmaceuticals, Cargo Therapeutics, Exagen Diagnostics, Hinge Bio, GlaxoSmithKline, Kypha, Miltenyi Biotec, Synthekine, and Tectonic Therapeutic.
A version of this article appeared on Medscape.com.
FROM ECLINICALMEDICINE
Maternal Buprenorphine Affects Fetal Breathing
Measures of fetal breathing movement were lower in fetuses of pregnant patients who received buprenorphine, compared with controls, based on data from 177 individuals.
The findings were presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists by Caroline Bulger, MD, of East Tennessee State University, Johnson City.
Pregnant patients with opioid-use disorder in the community surrounding Johnson City receive medication-assisted therapy with buprenorphine during the prenatal period, Dr. Bulger and colleagues wrote in their abstract. The current prenatal program for substance use disorder was established in 2016 based on patient requests for assistance in lowering their buprenorphine dosages during pregnancy, said senior author Martin E. Olsen, MD, also of East Tennessee State University, in an interview.
“Buprenorphine medication–assisted treatment in pregnancy is associated with long-term effects on childhood development such as smaller neonatal brains, decreased school performance, and low birth weight;” however, data on the fetal effects of buprenorphine are limited, said Dr. Olsen.
The current study was conducted to evaluate a short-term finding of the fetal effects of buprenorphine, Dr. Olsen said.
“This study was performed after obstetric sonographers at our institution noted that biophysical profile [BPP] ultrasound assessments of the fetuses of mothers on buprenorphine took longer than for other patients,” said Dr. Olsen.
The researchers conducted a retrospective chart review of 131 patients who received buprenorphine and 46 who were followed for chronic hypertension and served as high-risk controls. Patients were seen at a single institution between July 1, 2016, and June 30, 2020.
The researchers hypothesized that BPP of fetuses in patients receiving buprenorphine might be different from controls because of the effects of buprenorphine.
Overall, patients who received buprenorphine were more likely to have a fetal breathing score of zero than those who underwent a BPP for hypertension. A significant relationship emerged between buprenorphine dosage and breathing motion assessment; patients on high-dose buprenorphine were more likely than patients on low doses to have values of zero on fetal breathing motion assessment, and a chi-squared test yielded a P value of .04269.
The takeaway for clinical practice is that clinicians performing BPP ultrasounds on buprenorphine-exposed fetuses can expect that these assessments may take longer on average than assessments of other high-risk patients, said Dr. Olsen. “Additional assessment after a low BPP score is still indicated for these fetuses just as in other high-risk pregnancies,” he said.
The study was limited primarily by the retrospective design, Dr. Olsen said.
Although current treatment guidelines do not emphasize the effects of maternal buprenorphine use on fetal development, these findings support previous research showing effects of buprenorphine on fetal brain structure, the researchers wrote in their abstract. Looking ahead, “We recommend additional study on the maternal buprenorphine medication–assisted treatment dose effects for fetal and neonatal development with attention to such factors as head circumference, birth weight, achievement of developmental milestones, and school performance,” Dr. Olsen said.
“We and others have shown that the lowest effective dose of buprenorphine can lower neonatal abstinence syndrome/neonatal opioid withdrawal syndrome rates,” but data showing an impact of lowest effective dose management on long-term complications of fetal buprenorphine exposure are lacking, he noted.
The study received no outside funding. The researchers had no financial conflicts to disclose.
Measures of fetal breathing movement were lower in fetuses of pregnant patients who received buprenorphine, compared with controls, based on data from 177 individuals.
The findings were presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists by Caroline Bulger, MD, of East Tennessee State University, Johnson City.
Pregnant patients with opioid-use disorder in the community surrounding Johnson City receive medication-assisted therapy with buprenorphine during the prenatal period, Dr. Bulger and colleagues wrote in their abstract. The current prenatal program for substance use disorder was established in 2016 based on patient requests for assistance in lowering their buprenorphine dosages during pregnancy, said senior author Martin E. Olsen, MD, also of East Tennessee State University, in an interview.
“Buprenorphine medication–assisted treatment in pregnancy is associated with long-term effects on childhood development such as smaller neonatal brains, decreased school performance, and low birth weight;” however, data on the fetal effects of buprenorphine are limited, said Dr. Olsen.
The current study was conducted to evaluate a short-term finding of the fetal effects of buprenorphine, Dr. Olsen said.
“This study was performed after obstetric sonographers at our institution noted that biophysical profile [BPP] ultrasound assessments of the fetuses of mothers on buprenorphine took longer than for other patients,” said Dr. Olsen.
The researchers conducted a retrospective chart review of 131 patients who received buprenorphine and 46 who were followed for chronic hypertension and served as high-risk controls. Patients were seen at a single institution between July 1, 2016, and June 30, 2020.
The researchers hypothesized that BPP of fetuses in patients receiving buprenorphine might be different from controls because of the effects of buprenorphine.
Overall, patients who received buprenorphine were more likely to have a fetal breathing score of zero than those who underwent a BPP for hypertension. A significant relationship emerged between buprenorphine dosage and breathing motion assessment; patients on high-dose buprenorphine were more likely than patients on low doses to have values of zero on fetal breathing motion assessment, and a chi-squared test yielded a P value of .04269.
The takeaway for clinical practice is that clinicians performing BPP ultrasounds on buprenorphine-exposed fetuses can expect that these assessments may take longer on average than assessments of other high-risk patients, said Dr. Olsen. “Additional assessment after a low BPP score is still indicated for these fetuses just as in other high-risk pregnancies,” he said.
The study was limited primarily by the retrospective design, Dr. Olsen said.
Although current treatment guidelines do not emphasize the effects of maternal buprenorphine use on fetal development, these findings support previous research showing effects of buprenorphine on fetal brain structure, the researchers wrote in their abstract. Looking ahead, “We recommend additional study on the maternal buprenorphine medication–assisted treatment dose effects for fetal and neonatal development with attention to such factors as head circumference, birth weight, achievement of developmental milestones, and school performance,” Dr. Olsen said.
“We and others have shown that the lowest effective dose of buprenorphine can lower neonatal abstinence syndrome/neonatal opioid withdrawal syndrome rates,” but data showing an impact of lowest effective dose management on long-term complications of fetal buprenorphine exposure are lacking, he noted.
The study received no outside funding. The researchers had no financial conflicts to disclose.
Measures of fetal breathing movement were lower in fetuses of pregnant patients who received buprenorphine, compared with controls, based on data from 177 individuals.
The findings were presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists by Caroline Bulger, MD, of East Tennessee State University, Johnson City.
Pregnant patients with opioid-use disorder in the community surrounding Johnson City receive medication-assisted therapy with buprenorphine during the prenatal period, Dr. Bulger and colleagues wrote in their abstract. The current prenatal program for substance use disorder was established in 2016 based on patient requests for assistance in lowering their buprenorphine dosages during pregnancy, said senior author Martin E. Olsen, MD, also of East Tennessee State University, in an interview.
“Buprenorphine medication–assisted treatment in pregnancy is associated with long-term effects on childhood development such as smaller neonatal brains, decreased school performance, and low birth weight;” however, data on the fetal effects of buprenorphine are limited, said Dr. Olsen.
The current study was conducted to evaluate a short-term finding of the fetal effects of buprenorphine, Dr. Olsen said.
“This study was performed after obstetric sonographers at our institution noted that biophysical profile [BPP] ultrasound assessments of the fetuses of mothers on buprenorphine took longer than for other patients,” said Dr. Olsen.
The researchers conducted a retrospective chart review of 131 patients who received buprenorphine and 46 who were followed for chronic hypertension and served as high-risk controls. Patients were seen at a single institution between July 1, 2016, and June 30, 2020.
The researchers hypothesized that BPP of fetuses in patients receiving buprenorphine might be different from controls because of the effects of buprenorphine.
Overall, patients who received buprenorphine were more likely to have a fetal breathing score of zero than those who underwent a BPP for hypertension. A significant relationship emerged between buprenorphine dosage and breathing motion assessment; patients on high-dose buprenorphine were more likely than patients on low doses to have values of zero on fetal breathing motion assessment, and a chi-squared test yielded a P value of .04269.
The takeaway for clinical practice is that clinicians performing BPP ultrasounds on buprenorphine-exposed fetuses can expect that these assessments may take longer on average than assessments of other high-risk patients, said Dr. Olsen. “Additional assessment after a low BPP score is still indicated for these fetuses just as in other high-risk pregnancies,” he said.
The study was limited primarily by the retrospective design, Dr. Olsen said.
Although current treatment guidelines do not emphasize the effects of maternal buprenorphine use on fetal development, these findings support previous research showing effects of buprenorphine on fetal brain structure, the researchers wrote in their abstract. Looking ahead, “We recommend additional study on the maternal buprenorphine medication–assisted treatment dose effects for fetal and neonatal development with attention to such factors as head circumference, birth weight, achievement of developmental milestones, and school performance,” Dr. Olsen said.
“We and others have shown that the lowest effective dose of buprenorphine can lower neonatal abstinence syndrome/neonatal opioid withdrawal syndrome rates,” but data showing an impact of lowest effective dose management on long-term complications of fetal buprenorphine exposure are lacking, he noted.
The study received no outside funding. The researchers had no financial conflicts to disclose.
ACOG 2024