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Novel PET tracer for perfusion imaging: What’s the potential?
The emerging advantages of PET myocardial perfusion imaging (MPI) for coronary artery disease (CAD) diagnosis and assessment of cardiovascular event risk has prompted growing use of this technology as an alternative to the more commonly used single photon–emission CT (SPECT) MPI.
The advantages of PET MPI include better diagnostic performance and shorter acquisition times. , including consistent, high-quality images and low radiation exposure. It also allows quantification of myocardial blood flow, and it has “strong prognostic power.”
Tracer availability
Despite these advantages, that position paper and subsequent studies note that PET MPI has been underutilized in the United States, largely owing to issues with the available tracers, which have characteristics that limit widespread use in the clinic.
Rubidium, arguably the most commonly used tracer for PET MPI, is not available in unit dosing and so can be expensive for low-volume centers, plus it also requires an on-site generator, Michael Salerno, MD, PhD, a member of the American College of Cardiology’s Imaging Council and section chief of cardiovascular imaging, Stanford (Calif.) University, told this news organization.
N-ammonia, the other U.S. Food and Drug Administration–approved tracer, is available in unit dosing, but its short half-life means that centers need an onsite cyclotron, Dr. Salerno said.
For cardiac perfusion imaging and myocardial blood flow (MBF) quantification, 15O-water is considered the gold standard, although it’s not approved by the FDA. This tracer also requires an on-site cyclotron and “is challenging to use,” Dr. Salerno said. Use has been largely restricted to research purposes, though efforts are underway to widen its availability.
Enter flurpiridaz F-18 (GE Healthcare), a novel PET MPI tracer labeled with fluorine-18. Its longer half-life – similar to that of fluorodeoxyglucose, a tracer used to detect various cancers – could broaden the number of sites that could perform perfusion PET studies, Dr. Salerno said.
“Flurpiridaz also is supposed to have a more linear relationship between flow and tracer uptake, which could improve the ability to perform quantification of perfusion,” he noted. “It also offers the ability to do exercise PET, which is impossible for rubidium and challenging for ammonia, given its 11-minute half-life.”
Flurpiridaz status
The FDA requires two phase-3 studies that show safety and sufficient diagnostic performance before it will approve a new tracer. The first required study, published in the Journal of the American College of Cardiology, showed that the tracer’s sensitivity for detection of greater than or equal to 50% stenosis by ICA was significantly higher than SPECT; however, the specificity did not meet the prespecified noninferiority criterion.
The second FDA-required study, published online recently, also in the Journal of the American College of Cardiology, was designed differently from the first in that only patients with suspected – not known – CAD were enrolled. The primary efficacy endpoint was sensitivity and specificity of flurpiridaz PET for overall detection of CAD, rather than comparing it to SPECT MPI (which became a secondary endpoint). PET and SPECT studies were both performed before invasive coronary angiography to minimize referral bias; SPECT studies included cadmium zinc telluride cameras.
In that study, which included 578 patients (mean age, 64; 32.5% women) from 48 centers in the United States, Canada, and Europe, flurpiridaz met the efficacy endpoints: Its sensitivity and specificity were significantly higher than the prespecified threshold value by two of the three readers; its sensitivity was higher than SPECT (80.3% vs. 68.7%); and its specificity was noninferior (63.8% vs. 61.7%).
PET areas under the receiver-operating characteristic curves were higher than SPECT in the overall population and in women and obese patients, at half the radiation dose of SPECT.
“Cardiac PET MPI is positioned to serve as the leading modality for the functional evaluation of suspected and known CAD,” Jamieson M. Bourque, MD, MHS, medical director of nuclear cardiology, echocardiography, and the Stress Laboratory, University of Virginia, Charlottesville, wrote in an editorial accompanying the second study . “18F-flurpiridaz will facilitate this upward progression with beneficial tracer characteristics that will increase access and availability, enable exercise stress, and optimize MBF quantification.”
At this point, FDA approval of flurpiridaz is expected sometime in 2024, said James E. Udelson, MD, principal investigator of the recent study, chief of the division of cardiology, and director of the Nuclear Cardiology Laboratory at Tufts University School of Medicine, Boston.
Learning curve
Flurpiridaz comes with “a really interesting and important” learning curve, Dr. Udelson said. “The images are really crisp, and they look very different from what most people are used to. The GE folks are going to have to make sure that the American Society of Nuclear Cardiology and other professional societies are tuned in to help in the education part, because it’s not an easy, automatic switch. Very good image readers can adapt, but it’s not just one day you do one, then switch to the other.”
A “somewhat apt” analogy would be the difference between an echocardiogram and an MRI, he explained. “The MRI is much crisper. You’re seeing edges more crisply. You’re seeing the difference between a thicker and a thinner segment of the wall more crisply, and that’s actually real. You can’t say the thinner segment is abnormal; it’s just that you’re seeing it better. So, with this tracer, normal differences in the thickness of a wall can almost look like a defect if you’re not used to knowing that’s the new normal.”
The expected approval of flurpiridaz “will be a win for cardiac PET, broadening the range of sites that could perform PET,” Dr. Salerno commented. “However, it is worth cautioning that all of the prior data with PET using different agents does not necessarily equate to the same performance with the new agent, given that the performance seems to be lower than that shown in prior PET studies using other agents.”
Dr. Salerno would like to see additional studies comparing flurpiridaz with rubidium or ammonia, as well as studies performing quantification with flurpiridaz, “which theoretically should have some advantages,” he said.
Dr. Udelson noted that MedTrace, a company in Denmark, is working on a radiolabeled water tracer based on 15-O-water that is just starting a pivotal trial. Dr. Udelson is a consultant to the company and is a steering committee member for the pivotal trial.
For now, “the big take-home is that there are a lot of ways these days to test people for CAD,” he said. “As the types of things we can do to test people expand, individuals and centers need to make sure they focus on providing any new service, however they do it, with really superb quality and experience.”
“You don’t just do something new because it’s new,” he added. “It has to be done really well. If you do the new thing badly, you’re not going to get better information.”
Dr. Udelson is a consultant and advisory board member for GE Healthcare, a consultant to MedTrace, and a steering committee member for MedTrace’s pivotal trial. Dr. Bourque has served on a GE Healthcare advisory board for amyloid imaging. Dr. Salerno reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The emerging advantages of PET myocardial perfusion imaging (MPI) for coronary artery disease (CAD) diagnosis and assessment of cardiovascular event risk has prompted growing use of this technology as an alternative to the more commonly used single photon–emission CT (SPECT) MPI.
The advantages of PET MPI include better diagnostic performance and shorter acquisition times. , including consistent, high-quality images and low radiation exposure. It also allows quantification of myocardial blood flow, and it has “strong prognostic power.”
Tracer availability
Despite these advantages, that position paper and subsequent studies note that PET MPI has been underutilized in the United States, largely owing to issues with the available tracers, which have characteristics that limit widespread use in the clinic.
Rubidium, arguably the most commonly used tracer for PET MPI, is not available in unit dosing and so can be expensive for low-volume centers, plus it also requires an on-site generator, Michael Salerno, MD, PhD, a member of the American College of Cardiology’s Imaging Council and section chief of cardiovascular imaging, Stanford (Calif.) University, told this news organization.
N-ammonia, the other U.S. Food and Drug Administration–approved tracer, is available in unit dosing, but its short half-life means that centers need an onsite cyclotron, Dr. Salerno said.
For cardiac perfusion imaging and myocardial blood flow (MBF) quantification, 15O-water is considered the gold standard, although it’s not approved by the FDA. This tracer also requires an on-site cyclotron and “is challenging to use,” Dr. Salerno said. Use has been largely restricted to research purposes, though efforts are underway to widen its availability.
Enter flurpiridaz F-18 (GE Healthcare), a novel PET MPI tracer labeled with fluorine-18. Its longer half-life – similar to that of fluorodeoxyglucose, a tracer used to detect various cancers – could broaden the number of sites that could perform perfusion PET studies, Dr. Salerno said.
“Flurpiridaz also is supposed to have a more linear relationship between flow and tracer uptake, which could improve the ability to perform quantification of perfusion,” he noted. “It also offers the ability to do exercise PET, which is impossible for rubidium and challenging for ammonia, given its 11-minute half-life.”
Flurpiridaz status
The FDA requires two phase-3 studies that show safety and sufficient diagnostic performance before it will approve a new tracer. The first required study, published in the Journal of the American College of Cardiology, showed that the tracer’s sensitivity for detection of greater than or equal to 50% stenosis by ICA was significantly higher than SPECT; however, the specificity did not meet the prespecified noninferiority criterion.
The second FDA-required study, published online recently, also in the Journal of the American College of Cardiology, was designed differently from the first in that only patients with suspected – not known – CAD were enrolled. The primary efficacy endpoint was sensitivity and specificity of flurpiridaz PET for overall detection of CAD, rather than comparing it to SPECT MPI (which became a secondary endpoint). PET and SPECT studies were both performed before invasive coronary angiography to minimize referral bias; SPECT studies included cadmium zinc telluride cameras.
In that study, which included 578 patients (mean age, 64; 32.5% women) from 48 centers in the United States, Canada, and Europe, flurpiridaz met the efficacy endpoints: Its sensitivity and specificity were significantly higher than the prespecified threshold value by two of the three readers; its sensitivity was higher than SPECT (80.3% vs. 68.7%); and its specificity was noninferior (63.8% vs. 61.7%).
PET areas under the receiver-operating characteristic curves were higher than SPECT in the overall population and in women and obese patients, at half the radiation dose of SPECT.
“Cardiac PET MPI is positioned to serve as the leading modality for the functional evaluation of suspected and known CAD,” Jamieson M. Bourque, MD, MHS, medical director of nuclear cardiology, echocardiography, and the Stress Laboratory, University of Virginia, Charlottesville, wrote in an editorial accompanying the second study . “18F-flurpiridaz will facilitate this upward progression with beneficial tracer characteristics that will increase access and availability, enable exercise stress, and optimize MBF quantification.”
At this point, FDA approval of flurpiridaz is expected sometime in 2024, said James E. Udelson, MD, principal investigator of the recent study, chief of the division of cardiology, and director of the Nuclear Cardiology Laboratory at Tufts University School of Medicine, Boston.
Learning curve
Flurpiridaz comes with “a really interesting and important” learning curve, Dr. Udelson said. “The images are really crisp, and they look very different from what most people are used to. The GE folks are going to have to make sure that the American Society of Nuclear Cardiology and other professional societies are tuned in to help in the education part, because it’s not an easy, automatic switch. Very good image readers can adapt, but it’s not just one day you do one, then switch to the other.”
A “somewhat apt” analogy would be the difference between an echocardiogram and an MRI, he explained. “The MRI is much crisper. You’re seeing edges more crisply. You’re seeing the difference between a thicker and a thinner segment of the wall more crisply, and that’s actually real. You can’t say the thinner segment is abnormal; it’s just that you’re seeing it better. So, with this tracer, normal differences in the thickness of a wall can almost look like a defect if you’re not used to knowing that’s the new normal.”
The expected approval of flurpiridaz “will be a win for cardiac PET, broadening the range of sites that could perform PET,” Dr. Salerno commented. “However, it is worth cautioning that all of the prior data with PET using different agents does not necessarily equate to the same performance with the new agent, given that the performance seems to be lower than that shown in prior PET studies using other agents.”
Dr. Salerno would like to see additional studies comparing flurpiridaz with rubidium or ammonia, as well as studies performing quantification with flurpiridaz, “which theoretically should have some advantages,” he said.
Dr. Udelson noted that MedTrace, a company in Denmark, is working on a radiolabeled water tracer based on 15-O-water that is just starting a pivotal trial. Dr. Udelson is a consultant to the company and is a steering committee member for the pivotal trial.
For now, “the big take-home is that there are a lot of ways these days to test people for CAD,” he said. “As the types of things we can do to test people expand, individuals and centers need to make sure they focus on providing any new service, however they do it, with really superb quality and experience.”
“You don’t just do something new because it’s new,” he added. “It has to be done really well. If you do the new thing badly, you’re not going to get better information.”
Dr. Udelson is a consultant and advisory board member for GE Healthcare, a consultant to MedTrace, and a steering committee member for MedTrace’s pivotal trial. Dr. Bourque has served on a GE Healthcare advisory board for amyloid imaging. Dr. Salerno reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The emerging advantages of PET myocardial perfusion imaging (MPI) for coronary artery disease (CAD) diagnosis and assessment of cardiovascular event risk has prompted growing use of this technology as an alternative to the more commonly used single photon–emission CT (SPECT) MPI.
The advantages of PET MPI include better diagnostic performance and shorter acquisition times. , including consistent, high-quality images and low radiation exposure. It also allows quantification of myocardial blood flow, and it has “strong prognostic power.”
Tracer availability
Despite these advantages, that position paper and subsequent studies note that PET MPI has been underutilized in the United States, largely owing to issues with the available tracers, which have characteristics that limit widespread use in the clinic.
Rubidium, arguably the most commonly used tracer for PET MPI, is not available in unit dosing and so can be expensive for low-volume centers, plus it also requires an on-site generator, Michael Salerno, MD, PhD, a member of the American College of Cardiology’s Imaging Council and section chief of cardiovascular imaging, Stanford (Calif.) University, told this news organization.
N-ammonia, the other U.S. Food and Drug Administration–approved tracer, is available in unit dosing, but its short half-life means that centers need an onsite cyclotron, Dr. Salerno said.
For cardiac perfusion imaging and myocardial blood flow (MBF) quantification, 15O-water is considered the gold standard, although it’s not approved by the FDA. This tracer also requires an on-site cyclotron and “is challenging to use,” Dr. Salerno said. Use has been largely restricted to research purposes, though efforts are underway to widen its availability.
Enter flurpiridaz F-18 (GE Healthcare), a novel PET MPI tracer labeled with fluorine-18. Its longer half-life – similar to that of fluorodeoxyglucose, a tracer used to detect various cancers – could broaden the number of sites that could perform perfusion PET studies, Dr. Salerno said.
“Flurpiridaz also is supposed to have a more linear relationship between flow and tracer uptake, which could improve the ability to perform quantification of perfusion,” he noted. “It also offers the ability to do exercise PET, which is impossible for rubidium and challenging for ammonia, given its 11-minute half-life.”
Flurpiridaz status
The FDA requires two phase-3 studies that show safety and sufficient diagnostic performance before it will approve a new tracer. The first required study, published in the Journal of the American College of Cardiology, showed that the tracer’s sensitivity for detection of greater than or equal to 50% stenosis by ICA was significantly higher than SPECT; however, the specificity did not meet the prespecified noninferiority criterion.
The second FDA-required study, published online recently, also in the Journal of the American College of Cardiology, was designed differently from the first in that only patients with suspected – not known – CAD were enrolled. The primary efficacy endpoint was sensitivity and specificity of flurpiridaz PET for overall detection of CAD, rather than comparing it to SPECT MPI (which became a secondary endpoint). PET and SPECT studies were both performed before invasive coronary angiography to minimize referral bias; SPECT studies included cadmium zinc telluride cameras.
In that study, which included 578 patients (mean age, 64; 32.5% women) from 48 centers in the United States, Canada, and Europe, flurpiridaz met the efficacy endpoints: Its sensitivity and specificity were significantly higher than the prespecified threshold value by two of the three readers; its sensitivity was higher than SPECT (80.3% vs. 68.7%); and its specificity was noninferior (63.8% vs. 61.7%).
PET areas under the receiver-operating characteristic curves were higher than SPECT in the overall population and in women and obese patients, at half the radiation dose of SPECT.
“Cardiac PET MPI is positioned to serve as the leading modality for the functional evaluation of suspected and known CAD,” Jamieson M. Bourque, MD, MHS, medical director of nuclear cardiology, echocardiography, and the Stress Laboratory, University of Virginia, Charlottesville, wrote in an editorial accompanying the second study . “18F-flurpiridaz will facilitate this upward progression with beneficial tracer characteristics that will increase access and availability, enable exercise stress, and optimize MBF quantification.”
At this point, FDA approval of flurpiridaz is expected sometime in 2024, said James E. Udelson, MD, principal investigator of the recent study, chief of the division of cardiology, and director of the Nuclear Cardiology Laboratory at Tufts University School of Medicine, Boston.
Learning curve
Flurpiridaz comes with “a really interesting and important” learning curve, Dr. Udelson said. “The images are really crisp, and they look very different from what most people are used to. The GE folks are going to have to make sure that the American Society of Nuclear Cardiology and other professional societies are tuned in to help in the education part, because it’s not an easy, automatic switch. Very good image readers can adapt, but it’s not just one day you do one, then switch to the other.”
A “somewhat apt” analogy would be the difference between an echocardiogram and an MRI, he explained. “The MRI is much crisper. You’re seeing edges more crisply. You’re seeing the difference between a thicker and a thinner segment of the wall more crisply, and that’s actually real. You can’t say the thinner segment is abnormal; it’s just that you’re seeing it better. So, with this tracer, normal differences in the thickness of a wall can almost look like a defect if you’re not used to knowing that’s the new normal.”
The expected approval of flurpiridaz “will be a win for cardiac PET, broadening the range of sites that could perform PET,” Dr. Salerno commented. “However, it is worth cautioning that all of the prior data with PET using different agents does not necessarily equate to the same performance with the new agent, given that the performance seems to be lower than that shown in prior PET studies using other agents.”
Dr. Salerno would like to see additional studies comparing flurpiridaz with rubidium or ammonia, as well as studies performing quantification with flurpiridaz, “which theoretically should have some advantages,” he said.
Dr. Udelson noted that MedTrace, a company in Denmark, is working on a radiolabeled water tracer based on 15-O-water that is just starting a pivotal trial. Dr. Udelson is a consultant to the company and is a steering committee member for the pivotal trial.
For now, “the big take-home is that there are a lot of ways these days to test people for CAD,” he said. “As the types of things we can do to test people expand, individuals and centers need to make sure they focus on providing any new service, however they do it, with really superb quality and experience.”
“You don’t just do something new because it’s new,” he added. “It has to be done really well. If you do the new thing badly, you’re not going to get better information.”
Dr. Udelson is a consultant and advisory board member for GE Healthcare, a consultant to MedTrace, and a steering committee member for MedTrace’s pivotal trial. Dr. Bourque has served on a GE Healthcare advisory board for amyloid imaging. Dr. Salerno reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AI detects hidden, potentially curable pancreatic cancers
TOPLINE:
new research suggests.
METHODOLOGY:
- The researchers utilized a diverse dataset of 3,014 CT scans: 1,105 diagnostic CT scans with pancreatic ductal adenocarcinoma (PDA) and 1,909 control CT scans.
- Of the total, 696 diagnostic CT scans with PDA and 1,080 control CT scans were used as an AI model training subset, and 409 CT scans with PDA and 829 control CT scans were used as an intramural hold-out test subset.
- The model was also tested on a simulated cohort that evaluated the risk for PDA in new-onset diabetes; multicenter public datasets (194 CT scans with PDA and 80 controls); and a cohort of 100 prediagnostic CT scans, incidentally acquired 3-36 months prior to PDA being diagnosed, and 134 controls.
TAKEAWAY:
- The model correctly classified 360 CT scans with PDA (88%) and 783 control CT scans (94%) in the intramural test subset. The mean accuracy was 0.92, the area under the receiver operating characteristic curve was 0.97, sensitivity was 0.88, and specificity was 0.95.
- On heat maps, activation areas overlapped with the tumor in 350 of 360 CT scans (97%).
- Performance was high across tumor stages, with sensitivities of 0.80, 0.87, 0.95, and 1.0 on T1 through T4 stages, respectively. Performance was comparable for hypodense versus isodense tumors (sensitivity of 0.90 vs. 0.82, respectively), patient demographics, CT slice thicknesses, and vendors.
- Findings were generalizable on both the simulated cohort (accuracy, 0.95; area under the ROC curve, 0.97) and public datasets (accuracy, 0.86; AUROC, 0.9).
- Occult PDA was detected on prediagnostic CT scans at a median 475 days before clinical diagnosis. Accuracy was 0.84, AUROC was 0.91, sensitivity was 0.75, and specificity was 0.9.
IN PRACTICE:
“Artificial intelligence model could mitigate the inadequacies of imaging and the diagnostic errors in interpretation, which often contribute to delayed diagnosis of pancreas cancer. In combination with emerging blood-based biomarkers, such a model could be evaluated to screen for sporadic cancer in ongoing trials of high-risk cohorts such as the Early Detection Initiative (NCT04662879).”
SOURCE:
Panagiotis Korfiatis, PhD, of Mayo Clinic, Rochester, Minn., led the study, which was published online in Gastroenterology.
LIMITATIONS:
The retrospective design is prone to selection bias. Results are presented dichotomously as either cancer or control. These are preliminary insights, and prospective clinical trials that incorporate epidemiological risk factors and emerging blood-based biomarkers are needed to further evaluate the model’s performance.
DISCLOSURES:
The research was supported by the National Cancer Institute, the Centene Charitable Foundation, and the Champions for Hope Pancreatic Cancer Research Program of the Funk Zitiello Foundation. One author received an institutional research grant from Sofie Biosciences and Clovis Oncology, is on the BlueStar Genomics advisory board (ad hoc), and is a consultant for Bayer Healthcare, Candel Therapeutics, and UWorld. The remaining authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
TOPLINE:
new research suggests.
METHODOLOGY:
- The researchers utilized a diverse dataset of 3,014 CT scans: 1,105 diagnostic CT scans with pancreatic ductal adenocarcinoma (PDA) and 1,909 control CT scans.
- Of the total, 696 diagnostic CT scans with PDA and 1,080 control CT scans were used as an AI model training subset, and 409 CT scans with PDA and 829 control CT scans were used as an intramural hold-out test subset.
- The model was also tested on a simulated cohort that evaluated the risk for PDA in new-onset diabetes; multicenter public datasets (194 CT scans with PDA and 80 controls); and a cohort of 100 prediagnostic CT scans, incidentally acquired 3-36 months prior to PDA being diagnosed, and 134 controls.
TAKEAWAY:
- The model correctly classified 360 CT scans with PDA (88%) and 783 control CT scans (94%) in the intramural test subset. The mean accuracy was 0.92, the area under the receiver operating characteristic curve was 0.97, sensitivity was 0.88, and specificity was 0.95.
- On heat maps, activation areas overlapped with the tumor in 350 of 360 CT scans (97%).
- Performance was high across tumor stages, with sensitivities of 0.80, 0.87, 0.95, and 1.0 on T1 through T4 stages, respectively. Performance was comparable for hypodense versus isodense tumors (sensitivity of 0.90 vs. 0.82, respectively), patient demographics, CT slice thicknesses, and vendors.
- Findings were generalizable on both the simulated cohort (accuracy, 0.95; area under the ROC curve, 0.97) and public datasets (accuracy, 0.86; AUROC, 0.9).
- Occult PDA was detected on prediagnostic CT scans at a median 475 days before clinical diagnosis. Accuracy was 0.84, AUROC was 0.91, sensitivity was 0.75, and specificity was 0.9.
IN PRACTICE:
“Artificial intelligence model could mitigate the inadequacies of imaging and the diagnostic errors in interpretation, which often contribute to delayed diagnosis of pancreas cancer. In combination with emerging blood-based biomarkers, such a model could be evaluated to screen for sporadic cancer in ongoing trials of high-risk cohorts such as the Early Detection Initiative (NCT04662879).”
SOURCE:
Panagiotis Korfiatis, PhD, of Mayo Clinic, Rochester, Minn., led the study, which was published online in Gastroenterology.
LIMITATIONS:
The retrospective design is prone to selection bias. Results are presented dichotomously as either cancer or control. These are preliminary insights, and prospective clinical trials that incorporate epidemiological risk factors and emerging blood-based biomarkers are needed to further evaluate the model’s performance.
DISCLOSURES:
The research was supported by the National Cancer Institute, the Centene Charitable Foundation, and the Champions for Hope Pancreatic Cancer Research Program of the Funk Zitiello Foundation. One author received an institutional research grant from Sofie Biosciences and Clovis Oncology, is on the BlueStar Genomics advisory board (ad hoc), and is a consultant for Bayer Healthcare, Candel Therapeutics, and UWorld. The remaining authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
TOPLINE:
new research suggests.
METHODOLOGY:
- The researchers utilized a diverse dataset of 3,014 CT scans: 1,105 diagnostic CT scans with pancreatic ductal adenocarcinoma (PDA) and 1,909 control CT scans.
- Of the total, 696 diagnostic CT scans with PDA and 1,080 control CT scans were used as an AI model training subset, and 409 CT scans with PDA and 829 control CT scans were used as an intramural hold-out test subset.
- The model was also tested on a simulated cohort that evaluated the risk for PDA in new-onset diabetes; multicenter public datasets (194 CT scans with PDA and 80 controls); and a cohort of 100 prediagnostic CT scans, incidentally acquired 3-36 months prior to PDA being diagnosed, and 134 controls.
TAKEAWAY:
- The model correctly classified 360 CT scans with PDA (88%) and 783 control CT scans (94%) in the intramural test subset. The mean accuracy was 0.92, the area under the receiver operating characteristic curve was 0.97, sensitivity was 0.88, and specificity was 0.95.
- On heat maps, activation areas overlapped with the tumor in 350 of 360 CT scans (97%).
- Performance was high across tumor stages, with sensitivities of 0.80, 0.87, 0.95, and 1.0 on T1 through T4 stages, respectively. Performance was comparable for hypodense versus isodense tumors (sensitivity of 0.90 vs. 0.82, respectively), patient demographics, CT slice thicknesses, and vendors.
- Findings were generalizable on both the simulated cohort (accuracy, 0.95; area under the ROC curve, 0.97) and public datasets (accuracy, 0.86; AUROC, 0.9).
- Occult PDA was detected on prediagnostic CT scans at a median 475 days before clinical diagnosis. Accuracy was 0.84, AUROC was 0.91, sensitivity was 0.75, and specificity was 0.9.
IN PRACTICE:
“Artificial intelligence model could mitigate the inadequacies of imaging and the diagnostic errors in interpretation, which often contribute to delayed diagnosis of pancreas cancer. In combination with emerging blood-based biomarkers, such a model could be evaluated to screen for sporadic cancer in ongoing trials of high-risk cohorts such as the Early Detection Initiative (NCT04662879).”
SOURCE:
Panagiotis Korfiatis, PhD, of Mayo Clinic, Rochester, Minn., led the study, which was published online in Gastroenterology.
LIMITATIONS:
The retrospective design is prone to selection bias. Results are presented dichotomously as either cancer or control. These are preliminary insights, and prospective clinical trials that incorporate epidemiological risk factors and emerging blood-based biomarkers are needed to further evaluate the model’s performance.
DISCLOSURES:
The research was supported by the National Cancer Institute, the Centene Charitable Foundation, and the Champions for Hope Pancreatic Cancer Research Program of the Funk Zitiello Foundation. One author received an institutional research grant from Sofie Biosciences and Clovis Oncology, is on the BlueStar Genomics advisory board (ad hoc), and is a consultant for Bayer Healthcare, Candel Therapeutics, and UWorld. The remaining authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Paxlovid tied to benefits in high-risk patients with COVID
In a cohort study from British Columbia that included nearly 7,000 patients with COVID-19, nirmatrelvir-ritonavir was associated with a 2.5% reduction in risk for death or emergency hospitalization in clinically extremely vulnerable (CEV) patients who were severely immunocompromised. No significant benefit was observed in patients who were not immunocompromised.
“This finding could help substantially limit unnecessary use of nirmatrelvir and ritonavir in older, otherwise healthy individuals,” lead author Colin R. Dormuth, ScD, associate professor of anesthesiology, pharmacology, and therapeutics at the University of British Columbia, Vancouver, told this news organization. “Another finding that was surprising and might help place the role of nirmatrelvir and ritonavir in context is that even in severely immunocompromised individuals who did not take [the drug], the risk of death or hospitalization with COVID-19 was less than 4% in our study population.”
The study was published online in JAMA Network Open.
Who benefits?
The investigators analyzed medical records for 6,866 patients in British Columbia (median age, 70 years; 57% women) who presented between Feb. 1, 2022, and Feb. 3, 2023. Eligible patients belonged to one of four higher-risk groups who received priority for COVID-19 vaccination.
Two groups included CEV patients who were severely (CEV1) or moderately (CEV2) immunocompromised. The CEV3 group was not immunocompromised but had medical conditions associated with a high risk for complications from COVID-19. A fourth expanded eligibility (EXEL) group included higher-risk patients who were not in one of the other groups, such as unvaccinated patients older than age 70 years.
The investigators matched treated patients to untreated patients in the same vulnerability group according to age, sex, and month of infection. The primary outcome was death from any cause or emergency hospitalization with COVID-19 within 28 days.
Treatment with nirmatrelvir-ritonavir was associated with statistically significant relative reductions in the primary outcome, compared with no treatment, for patients in the CEV1 (risk difference, −2.5%) and CEV2 (RD, −1.7%) groups. In the CEV3 group, the RD of −1.3% was not statistically significant. In the EXEL group, treatment was associated with a higher risk for the primary outcome (RD, 1.0%), but the result was not statistically significant.
The results were “robust across sex and older vs. younger age,” the authors note. “No reduction in the primary outcome was observed in lower-risk individuals, including those aged 70 years or older without serious comorbidities.”
The combination of nirmatrelvir-ritonavir was approved for use in Canada based on interim efficacy and safety data from the Evaluation of Inhibition for COVID-19 in High-Risk Patients (EPIC-HR) trial, said Dr. Dormuth.
British Columbia’s eligibility criteria for nirmatrelvir-ritonavir coverage differ substantially from the criteria for participants in the EPIC-HR trial, he noted. Those patients were unvaccinated, had no natural immunity from a previous COVID-19 infection, and were infected with COVID-19 variants that were different from those now circulating. The current study was prompted by the need to look at a broader population of individuals in British Columbia with varying risks of complications from COVID-19 infection.
Before the study, a common view was that patients aged 70 and older would benefit from the drug, said Dr. Dormuth. “Our study, which accounted for medical conditions related to an individual’s vulnerability to complications, showed that older age on its own was not a reason to use nirmatrelvir and ritonavir once relevant medical conditions were taken into consideration.”
The researchers are working on a study to identify with greater specificity which comorbid conditions are most associated with nirmatrelvir-ritonavir effectiveness, he added. “It could be that a relatively small number of conditions can be used to identify most individuals who would benefit from the drug.”
‘Signal toward benefit’
Commenting on the findings for this news organization, Abhijit Duggal, MD, vice chair of critical care at the Cleveland Clinic, who was not involved in this study, said, “I’m always very wary when we look at observational data and we start saying the effectiveness is not really as high as was seen in other studies. We are seeing an effect with all these studies that seems to be in the right direction.
“Having said that,” he added, “is the effect going to be potentially more in patients at higher risk? Absolutely. I think these postmarket studies are really showing that after vaccination, if someone does get infected, this is a secondary option available to us that can prevent progression of the disease, which would likely be more severe in immunocompromised patients.”
Dr. Duggal was a coinvestigator on a recent study of more than 68,000 patients that showed that nirmatrelvir-ritonavir or molnupiravir was associated with reductions in mortality and hospitalization in nonhospitalized patients infected with the Omicron variant, regardless of age, race and ethnicity, virus strain, vaccination status, previous infection status, or coexisting conditions.
“In all groups, there was a signal toward benefit,” said Dr. Duggal. “These studies tell us that these drugs do remain valid options. But their use needs to be discussed on a case-by-case basis with patients we feel are deteriorating or at a higher risk because of underlying disease processes.”
The study was supported by funding from the British Columbia Ministry of Health. Dr. Dormuth and Dr. Duggal report no relevant financial relationships.
A version of this article appeared on Medscape.com.
In a cohort study from British Columbia that included nearly 7,000 patients with COVID-19, nirmatrelvir-ritonavir was associated with a 2.5% reduction in risk for death or emergency hospitalization in clinically extremely vulnerable (CEV) patients who were severely immunocompromised. No significant benefit was observed in patients who were not immunocompromised.
“This finding could help substantially limit unnecessary use of nirmatrelvir and ritonavir in older, otherwise healthy individuals,” lead author Colin R. Dormuth, ScD, associate professor of anesthesiology, pharmacology, and therapeutics at the University of British Columbia, Vancouver, told this news organization. “Another finding that was surprising and might help place the role of nirmatrelvir and ritonavir in context is that even in severely immunocompromised individuals who did not take [the drug], the risk of death or hospitalization with COVID-19 was less than 4% in our study population.”
The study was published online in JAMA Network Open.
Who benefits?
The investigators analyzed medical records for 6,866 patients in British Columbia (median age, 70 years; 57% women) who presented between Feb. 1, 2022, and Feb. 3, 2023. Eligible patients belonged to one of four higher-risk groups who received priority for COVID-19 vaccination.
Two groups included CEV patients who were severely (CEV1) or moderately (CEV2) immunocompromised. The CEV3 group was not immunocompromised but had medical conditions associated with a high risk for complications from COVID-19. A fourth expanded eligibility (EXEL) group included higher-risk patients who were not in one of the other groups, such as unvaccinated patients older than age 70 years.
The investigators matched treated patients to untreated patients in the same vulnerability group according to age, sex, and month of infection. The primary outcome was death from any cause or emergency hospitalization with COVID-19 within 28 days.
Treatment with nirmatrelvir-ritonavir was associated with statistically significant relative reductions in the primary outcome, compared with no treatment, for patients in the CEV1 (risk difference, −2.5%) and CEV2 (RD, −1.7%) groups. In the CEV3 group, the RD of −1.3% was not statistically significant. In the EXEL group, treatment was associated with a higher risk for the primary outcome (RD, 1.0%), but the result was not statistically significant.
The results were “robust across sex and older vs. younger age,” the authors note. “No reduction in the primary outcome was observed in lower-risk individuals, including those aged 70 years or older without serious comorbidities.”
The combination of nirmatrelvir-ritonavir was approved for use in Canada based on interim efficacy and safety data from the Evaluation of Inhibition for COVID-19 in High-Risk Patients (EPIC-HR) trial, said Dr. Dormuth.
British Columbia’s eligibility criteria for nirmatrelvir-ritonavir coverage differ substantially from the criteria for participants in the EPIC-HR trial, he noted. Those patients were unvaccinated, had no natural immunity from a previous COVID-19 infection, and were infected with COVID-19 variants that were different from those now circulating. The current study was prompted by the need to look at a broader population of individuals in British Columbia with varying risks of complications from COVID-19 infection.
Before the study, a common view was that patients aged 70 and older would benefit from the drug, said Dr. Dormuth. “Our study, which accounted for medical conditions related to an individual’s vulnerability to complications, showed that older age on its own was not a reason to use nirmatrelvir and ritonavir once relevant medical conditions were taken into consideration.”
The researchers are working on a study to identify with greater specificity which comorbid conditions are most associated with nirmatrelvir-ritonavir effectiveness, he added. “It could be that a relatively small number of conditions can be used to identify most individuals who would benefit from the drug.”
‘Signal toward benefit’
Commenting on the findings for this news organization, Abhijit Duggal, MD, vice chair of critical care at the Cleveland Clinic, who was not involved in this study, said, “I’m always very wary when we look at observational data and we start saying the effectiveness is not really as high as was seen in other studies. We are seeing an effect with all these studies that seems to be in the right direction.
“Having said that,” he added, “is the effect going to be potentially more in patients at higher risk? Absolutely. I think these postmarket studies are really showing that after vaccination, if someone does get infected, this is a secondary option available to us that can prevent progression of the disease, which would likely be more severe in immunocompromised patients.”
Dr. Duggal was a coinvestigator on a recent study of more than 68,000 patients that showed that nirmatrelvir-ritonavir or molnupiravir was associated with reductions in mortality and hospitalization in nonhospitalized patients infected with the Omicron variant, regardless of age, race and ethnicity, virus strain, vaccination status, previous infection status, or coexisting conditions.
“In all groups, there was a signal toward benefit,” said Dr. Duggal. “These studies tell us that these drugs do remain valid options. But their use needs to be discussed on a case-by-case basis with patients we feel are deteriorating or at a higher risk because of underlying disease processes.”
The study was supported by funding from the British Columbia Ministry of Health. Dr. Dormuth and Dr. Duggal report no relevant financial relationships.
A version of this article appeared on Medscape.com.
In a cohort study from British Columbia that included nearly 7,000 patients with COVID-19, nirmatrelvir-ritonavir was associated with a 2.5% reduction in risk for death or emergency hospitalization in clinically extremely vulnerable (CEV) patients who were severely immunocompromised. No significant benefit was observed in patients who were not immunocompromised.
“This finding could help substantially limit unnecessary use of nirmatrelvir and ritonavir in older, otherwise healthy individuals,” lead author Colin R. Dormuth, ScD, associate professor of anesthesiology, pharmacology, and therapeutics at the University of British Columbia, Vancouver, told this news organization. “Another finding that was surprising and might help place the role of nirmatrelvir and ritonavir in context is that even in severely immunocompromised individuals who did not take [the drug], the risk of death or hospitalization with COVID-19 was less than 4% in our study population.”
The study was published online in JAMA Network Open.
Who benefits?
The investigators analyzed medical records for 6,866 patients in British Columbia (median age, 70 years; 57% women) who presented between Feb. 1, 2022, and Feb. 3, 2023. Eligible patients belonged to one of four higher-risk groups who received priority for COVID-19 vaccination.
Two groups included CEV patients who were severely (CEV1) or moderately (CEV2) immunocompromised. The CEV3 group was not immunocompromised but had medical conditions associated with a high risk for complications from COVID-19. A fourth expanded eligibility (EXEL) group included higher-risk patients who were not in one of the other groups, such as unvaccinated patients older than age 70 years.
The investigators matched treated patients to untreated patients in the same vulnerability group according to age, sex, and month of infection. The primary outcome was death from any cause or emergency hospitalization with COVID-19 within 28 days.
Treatment with nirmatrelvir-ritonavir was associated with statistically significant relative reductions in the primary outcome, compared with no treatment, for patients in the CEV1 (risk difference, −2.5%) and CEV2 (RD, −1.7%) groups. In the CEV3 group, the RD of −1.3% was not statistically significant. In the EXEL group, treatment was associated with a higher risk for the primary outcome (RD, 1.0%), but the result was not statistically significant.
The results were “robust across sex and older vs. younger age,” the authors note. “No reduction in the primary outcome was observed in lower-risk individuals, including those aged 70 years or older without serious comorbidities.”
The combination of nirmatrelvir-ritonavir was approved for use in Canada based on interim efficacy and safety data from the Evaluation of Inhibition for COVID-19 in High-Risk Patients (EPIC-HR) trial, said Dr. Dormuth.
British Columbia’s eligibility criteria for nirmatrelvir-ritonavir coverage differ substantially from the criteria for participants in the EPIC-HR trial, he noted. Those patients were unvaccinated, had no natural immunity from a previous COVID-19 infection, and were infected with COVID-19 variants that were different from those now circulating. The current study was prompted by the need to look at a broader population of individuals in British Columbia with varying risks of complications from COVID-19 infection.
Before the study, a common view was that patients aged 70 and older would benefit from the drug, said Dr. Dormuth. “Our study, which accounted for medical conditions related to an individual’s vulnerability to complications, showed that older age on its own was not a reason to use nirmatrelvir and ritonavir once relevant medical conditions were taken into consideration.”
The researchers are working on a study to identify with greater specificity which comorbid conditions are most associated with nirmatrelvir-ritonavir effectiveness, he added. “It could be that a relatively small number of conditions can be used to identify most individuals who would benefit from the drug.”
‘Signal toward benefit’
Commenting on the findings for this news organization, Abhijit Duggal, MD, vice chair of critical care at the Cleveland Clinic, who was not involved in this study, said, “I’m always very wary when we look at observational data and we start saying the effectiveness is not really as high as was seen in other studies. We are seeing an effect with all these studies that seems to be in the right direction.
“Having said that,” he added, “is the effect going to be potentially more in patients at higher risk? Absolutely. I think these postmarket studies are really showing that after vaccination, if someone does get infected, this is a secondary option available to us that can prevent progression of the disease, which would likely be more severe in immunocompromised patients.”
Dr. Duggal was a coinvestigator on a recent study of more than 68,000 patients that showed that nirmatrelvir-ritonavir or molnupiravir was associated with reductions in mortality and hospitalization in nonhospitalized patients infected with the Omicron variant, regardless of age, race and ethnicity, virus strain, vaccination status, previous infection status, or coexisting conditions.
“In all groups, there was a signal toward benefit,” said Dr. Duggal. “These studies tell us that these drugs do remain valid options. But their use needs to be discussed on a case-by-case basis with patients we feel are deteriorating or at a higher risk because of underlying disease processes.”
The study was supported by funding from the British Columbia Ministry of Health. Dr. Dormuth and Dr. Duggal report no relevant financial relationships.
A version of this article appeared on Medscape.com.
AHA updates CPR guidelines on cardiac arrest after poisoning
The update reflects treatment advances and new knowledge, including the use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) for patients whose condition is refractory to poison antidotes and other therapies.
The new guidelines are designed primarily for North American health care professionals who treat adults and children who are critically ill because of poisoning, including intentional and unintentional drug overdose, chemical exposure, and drug-drug interactions, the authors note.
Published online in Circulation, the update was endorsed by the American Academy of Pediatrics.
‘Nearly miraculous’
“It’s been 13 years since the poisoning treatment guidelines had a comprehensive update,” lead author Eric J. Lavonas, MD, professor of emergency medicine at Denver Health and the Rocky Mountain Poison and Drug Center, Colo., told this news organization. “In that time, we’ve learned a lot about how to best use antidotes and other treatments to save the most critically poisoned patients.”
Highlighting a few key points from the update, he said, “For those rare situations when antidotes aren’t enough, the new guidelines include the use of heart-lung machines (VA-ECMO) for patients with beta-blocker, calcium channel blocker, or sodium channel blocker poisoning causing cardiogenic shock.”
Furthermore, he said, “High-dose insulin treatment for patients with beta-blocker and calcium channel blocker poisoning [also recommended in the update] has really become mainstream. The doses are up to 10 times higher than the amount used to treat diabetic emergencies.
“Some excellent science has shown that giving IV lipid emulsion can save the life of someone with an accidental overdose of local anesthetic medications, particularly bupivacaine,” he added. “The result is sometimes nearly miraculous.
“But when this treatment is extended to poisoning from other medications, it often doesn’t work as well, and in some situations may make things worse,” he said. “The issue may be that giving lipids increases absorption of drug from the stomach and intestines, which can be dangerous when the patient took an overdose of pills.”
Low level of evidence
The guidelines were compiled by the Critical Poisoning Writing Group, which includes experts from emergency medicine, pediatrics, medical toxicology, pharmacology, critical care, emergency medical services, education, research, and nursing. Group members were appointed by the AHA Emergency Cardiovascular Care Science Subcommittee and were approved by the AHA Manuscript Oversight Committee.
First and foremost, the group recommends timely consultation with a medical toxicologist, a clinical toxicologist, or a regional poison center to facilitate rapid, effective therapy, because treatment of cardiac arrest and toxicity from poisoning often requires treatments that most clinicians don’t use frequently.
Other key points include the following:
- Naloxone administration may reverse respiratory arrest due to opioid overdose, preventing progression to cardiac arrest.
- Give high-dose insulin therapy early in the treatment of patients with beta-blocker and calcium channel blocker poisoning, Dr. Lavonas noted.
- Standard advanced life support plus sodium bicarbonate is appropriate for life-threatening dysrhythmias caused by cocaine or other sodium channel blockers.
- If cyanide poisoning is suspected, clinicians should not wait for confirmatory testing; treatment should begin immediately with hydroxocobalamin (preferred) or sodium nitrite plus sodium thiosulfate.
- Digoxin-specific immune antibody fragments can reverse life-threatening dysrhythmias from digoxin poisoning.
- Use of 20% intravenous lipid emulsion can be efficacious in the resuscitation of life-threatening local anesthetic toxicity, especially from bupivacaine, Dr. Lavonas indicated.
- Sedation is recommended for patients with severe agitation from sympathomimetic poisoning to manage hyperthermia and acidosis, prevent rhabdomyolysis and injury, and allow evaluation for other life-threatening conditions.
- Although flumazenil reverses central nervous system and respiratory depression from benzodiazepine poisoning, risks and contraindications, provided in the guidelines, limit its use.
- VA-ECMO can be lifesaving for patients with cardiogenic shock or dysrhythmias that are refractory to other treatments.
“Unfortunately, despite improvements in the design and funding support for resuscitation research, the overall certainty of the evidence base for resuscitation science and management of critical poisoning is low,” the group acknowledges.
Of the 73 guideline recommendations, only 2 are supported by level A evidence; 3 are supported by level B-randomized evidence, 12 by level B-nonrandomized evidence, and the rest by level C evidence.
“Accordingly, the strength of recommendations is weaker than optimal,” they write. “Clinical trials in resuscitation and the management of critical poisoning are sorely needed.”
‘Don’t go it alone!’
“Most critical poisonings are pretty uncommon, and each patient is different,” Dr. Lavonas said. “Even in the emergency department or ICU, most physicians will treat a patient who is critically ill with any given poison less than once a year. The antidotes and medication doses needed to effectively treat these patients are often very different than everyday medical practice.
“Don’t try to go it alone!” he urges. “Poisoning cases are complex, and the treatments work best when they are implemented quickly and assertively. A toxicologist can help sort through complex situations and get effective treatment started without delay.”
Every certified poison center has a medical toxicologist or clinical toxicologist on call 24/7 to give advice to physicians and hospitals about patients who are critically ill after being poisoned, he added. “Everyone in the U.S. has access to a poison center by calling one number: 1-800-222-1222.”
Dr. Lavonas has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
The update reflects treatment advances and new knowledge, including the use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) for patients whose condition is refractory to poison antidotes and other therapies.
The new guidelines are designed primarily for North American health care professionals who treat adults and children who are critically ill because of poisoning, including intentional and unintentional drug overdose, chemical exposure, and drug-drug interactions, the authors note.
Published online in Circulation, the update was endorsed by the American Academy of Pediatrics.
‘Nearly miraculous’
“It’s been 13 years since the poisoning treatment guidelines had a comprehensive update,” lead author Eric J. Lavonas, MD, professor of emergency medicine at Denver Health and the Rocky Mountain Poison and Drug Center, Colo., told this news organization. “In that time, we’ve learned a lot about how to best use antidotes and other treatments to save the most critically poisoned patients.”
Highlighting a few key points from the update, he said, “For those rare situations when antidotes aren’t enough, the new guidelines include the use of heart-lung machines (VA-ECMO) for patients with beta-blocker, calcium channel blocker, or sodium channel blocker poisoning causing cardiogenic shock.”
Furthermore, he said, “High-dose insulin treatment for patients with beta-blocker and calcium channel blocker poisoning [also recommended in the update] has really become mainstream. The doses are up to 10 times higher than the amount used to treat diabetic emergencies.
“Some excellent science has shown that giving IV lipid emulsion can save the life of someone with an accidental overdose of local anesthetic medications, particularly bupivacaine,” he added. “The result is sometimes nearly miraculous.
“But when this treatment is extended to poisoning from other medications, it often doesn’t work as well, and in some situations may make things worse,” he said. “The issue may be that giving lipids increases absorption of drug from the stomach and intestines, which can be dangerous when the patient took an overdose of pills.”
Low level of evidence
The guidelines were compiled by the Critical Poisoning Writing Group, which includes experts from emergency medicine, pediatrics, medical toxicology, pharmacology, critical care, emergency medical services, education, research, and nursing. Group members were appointed by the AHA Emergency Cardiovascular Care Science Subcommittee and were approved by the AHA Manuscript Oversight Committee.
First and foremost, the group recommends timely consultation with a medical toxicologist, a clinical toxicologist, or a regional poison center to facilitate rapid, effective therapy, because treatment of cardiac arrest and toxicity from poisoning often requires treatments that most clinicians don’t use frequently.
Other key points include the following:
- Naloxone administration may reverse respiratory arrest due to opioid overdose, preventing progression to cardiac arrest.
- Give high-dose insulin therapy early in the treatment of patients with beta-blocker and calcium channel blocker poisoning, Dr. Lavonas noted.
- Standard advanced life support plus sodium bicarbonate is appropriate for life-threatening dysrhythmias caused by cocaine or other sodium channel blockers.
- If cyanide poisoning is suspected, clinicians should not wait for confirmatory testing; treatment should begin immediately with hydroxocobalamin (preferred) or sodium nitrite plus sodium thiosulfate.
- Digoxin-specific immune antibody fragments can reverse life-threatening dysrhythmias from digoxin poisoning.
- Use of 20% intravenous lipid emulsion can be efficacious in the resuscitation of life-threatening local anesthetic toxicity, especially from bupivacaine, Dr. Lavonas indicated.
- Sedation is recommended for patients with severe agitation from sympathomimetic poisoning to manage hyperthermia and acidosis, prevent rhabdomyolysis and injury, and allow evaluation for other life-threatening conditions.
- Although flumazenil reverses central nervous system and respiratory depression from benzodiazepine poisoning, risks and contraindications, provided in the guidelines, limit its use.
- VA-ECMO can be lifesaving for patients with cardiogenic shock or dysrhythmias that are refractory to other treatments.
“Unfortunately, despite improvements in the design and funding support for resuscitation research, the overall certainty of the evidence base for resuscitation science and management of critical poisoning is low,” the group acknowledges.
Of the 73 guideline recommendations, only 2 are supported by level A evidence; 3 are supported by level B-randomized evidence, 12 by level B-nonrandomized evidence, and the rest by level C evidence.
“Accordingly, the strength of recommendations is weaker than optimal,” they write. “Clinical trials in resuscitation and the management of critical poisoning are sorely needed.”
‘Don’t go it alone!’
“Most critical poisonings are pretty uncommon, and each patient is different,” Dr. Lavonas said. “Even in the emergency department or ICU, most physicians will treat a patient who is critically ill with any given poison less than once a year. The antidotes and medication doses needed to effectively treat these patients are often very different than everyday medical practice.
“Don’t try to go it alone!” he urges. “Poisoning cases are complex, and the treatments work best when they are implemented quickly and assertively. A toxicologist can help sort through complex situations and get effective treatment started without delay.”
Every certified poison center has a medical toxicologist or clinical toxicologist on call 24/7 to give advice to physicians and hospitals about patients who are critically ill after being poisoned, he added. “Everyone in the U.S. has access to a poison center by calling one number: 1-800-222-1222.”
Dr. Lavonas has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
The update reflects treatment advances and new knowledge, including the use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) for patients whose condition is refractory to poison antidotes and other therapies.
The new guidelines are designed primarily for North American health care professionals who treat adults and children who are critically ill because of poisoning, including intentional and unintentional drug overdose, chemical exposure, and drug-drug interactions, the authors note.
Published online in Circulation, the update was endorsed by the American Academy of Pediatrics.
‘Nearly miraculous’
“It’s been 13 years since the poisoning treatment guidelines had a comprehensive update,” lead author Eric J. Lavonas, MD, professor of emergency medicine at Denver Health and the Rocky Mountain Poison and Drug Center, Colo., told this news organization. “In that time, we’ve learned a lot about how to best use antidotes and other treatments to save the most critically poisoned patients.”
Highlighting a few key points from the update, he said, “For those rare situations when antidotes aren’t enough, the new guidelines include the use of heart-lung machines (VA-ECMO) for patients with beta-blocker, calcium channel blocker, or sodium channel blocker poisoning causing cardiogenic shock.”
Furthermore, he said, “High-dose insulin treatment for patients with beta-blocker and calcium channel blocker poisoning [also recommended in the update] has really become mainstream. The doses are up to 10 times higher than the amount used to treat diabetic emergencies.
“Some excellent science has shown that giving IV lipid emulsion can save the life of someone with an accidental overdose of local anesthetic medications, particularly bupivacaine,” he added. “The result is sometimes nearly miraculous.
“But when this treatment is extended to poisoning from other medications, it often doesn’t work as well, and in some situations may make things worse,” he said. “The issue may be that giving lipids increases absorption of drug from the stomach and intestines, which can be dangerous when the patient took an overdose of pills.”
Low level of evidence
The guidelines were compiled by the Critical Poisoning Writing Group, which includes experts from emergency medicine, pediatrics, medical toxicology, pharmacology, critical care, emergency medical services, education, research, and nursing. Group members were appointed by the AHA Emergency Cardiovascular Care Science Subcommittee and were approved by the AHA Manuscript Oversight Committee.
First and foremost, the group recommends timely consultation with a medical toxicologist, a clinical toxicologist, or a regional poison center to facilitate rapid, effective therapy, because treatment of cardiac arrest and toxicity from poisoning often requires treatments that most clinicians don’t use frequently.
Other key points include the following:
- Naloxone administration may reverse respiratory arrest due to opioid overdose, preventing progression to cardiac arrest.
- Give high-dose insulin therapy early in the treatment of patients with beta-blocker and calcium channel blocker poisoning, Dr. Lavonas noted.
- Standard advanced life support plus sodium bicarbonate is appropriate for life-threatening dysrhythmias caused by cocaine or other sodium channel blockers.
- If cyanide poisoning is suspected, clinicians should not wait for confirmatory testing; treatment should begin immediately with hydroxocobalamin (preferred) or sodium nitrite plus sodium thiosulfate.
- Digoxin-specific immune antibody fragments can reverse life-threatening dysrhythmias from digoxin poisoning.
- Use of 20% intravenous lipid emulsion can be efficacious in the resuscitation of life-threatening local anesthetic toxicity, especially from bupivacaine, Dr. Lavonas indicated.
- Sedation is recommended for patients with severe agitation from sympathomimetic poisoning to manage hyperthermia and acidosis, prevent rhabdomyolysis and injury, and allow evaluation for other life-threatening conditions.
- Although flumazenil reverses central nervous system and respiratory depression from benzodiazepine poisoning, risks and contraindications, provided in the guidelines, limit its use.
- VA-ECMO can be lifesaving for patients with cardiogenic shock or dysrhythmias that are refractory to other treatments.
“Unfortunately, despite improvements in the design and funding support for resuscitation research, the overall certainty of the evidence base for resuscitation science and management of critical poisoning is low,” the group acknowledges.
Of the 73 guideline recommendations, only 2 are supported by level A evidence; 3 are supported by level B-randomized evidence, 12 by level B-nonrandomized evidence, and the rest by level C evidence.
“Accordingly, the strength of recommendations is weaker than optimal,” they write. “Clinical trials in resuscitation and the management of critical poisoning are sorely needed.”
‘Don’t go it alone!’
“Most critical poisonings are pretty uncommon, and each patient is different,” Dr. Lavonas said. “Even in the emergency department or ICU, most physicians will treat a patient who is critically ill with any given poison less than once a year. The antidotes and medication doses needed to effectively treat these patients are often very different than everyday medical practice.
“Don’t try to go it alone!” he urges. “Poisoning cases are complex, and the treatments work best when they are implemented quickly and assertively. A toxicologist can help sort through complex situations and get effective treatment started without delay.”
Every certified poison center has a medical toxicologist or clinical toxicologist on call 24/7 to give advice to physicians and hospitals about patients who are critically ill after being poisoned, he added. “Everyone in the U.S. has access to a poison center by calling one number: 1-800-222-1222.”
Dr. Lavonas has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
New biomarker tests could reduce need for liver biopsy
(NASH, now known as metabolic dysfunction–associated steatohepatitis or MASH), laying the groundwork for noninvasive alternatives to liver biopsy, new research suggests.
The blood-based tests could expand diagnostic options at health care facilities and facilitate enrollment in NASH clinical trials, which now require a biopsy for inclusion.
“The current study meets a key milestone for qualification of the biomarker panels studied for identification of at-risk NASH,” Arun Sanyal, MD, of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University, Richmond, told this news organization.
“It sets the stage for further validation of these outcomes,” he said. “These data will inform development of full qualification plans for these biomarker panels that will be submitted to the U.S. Food and Drug Administration. Once these are accepted by the FDA, the final steps toward qualification can be initiated.”
The study, published online in Nature Medicine, was conducted as part of the Foundation for the National Institutes of Health – Biomarkers Consortium’s Noninvasive Biomarkers of Metabolic Liver Disease (FNIH-NIMBLE), a multistakeholder project to support regulatory approval of NASH-related biomarkers.
Multiple biomarkers move forward
The investigators evaluated the diagnostic performance of five blood-based panels in an observational cohort derived from the NASH Clinical Research Network study, which included 4,094 participants; 2,479 individuals were excluded from the current study because of age, lack of samples, or lack of evaluable liver biopsies.
The remaining 1,073 patients (mean age, 52.5 years; 62% women) represented the full spectrum of nonalcoholic fatty liver disease (NAFLD, now known as metabolic dysfunction–associated steatotic liver disease or MASLD). In total, 225 individuals had NAFLD, 835 had NASH, and 13 had cirrhosis with an indeterminate NAFLD phenotype.
Those without fibrosis were younger and had mainly fatty liver, not steatohepatitis. They also had a lower NAFLD activity score, compared with those with stage 2 or higher fibrosis.
The study population for one of the five tests, FibroMeter VCTE, was a smaller subset (n = 396) of the larger population, with baseline features similar to the larger cohort.
The biomarker panels were intended to diagnose at-risk NASH (NIS4), presence of NASH (OWLiver), or fibrosis stages greater than 2, greater than 3, or 4 (enhanced liver fibrosis [ELF] test, PROC3, and FibroMeter VCTE). At-risk NASH was defined by the presence of NASH, high histologic activity, and fibrosis stage greater than or equal to 2.
The performance metric was an area under the receiver operating characteristic curve (AUROC) greater than or equal to 0.7 and superiority over alanine aminotransferase (ALT) for disease activity and the FIB-4 test for fibrosis severity.
Multiple biomarkers met the required metrics. For example, NIS4 had an AUROC of 0.81 for at-risk NASH. AUROCs for the ELF test (for clinically significant fibrosis, ≥ stage 2), PROC3 (advanced fibrosis, ≥ stage 3), and FibroMeter VCTE (cirrhosis, stage 4) were all greater than or equal to 0.8.
For all fibrosis endpoints, ELF and FibroMeter VCTE also outperformed FIB-4.
“The current study was a first step to determine if the biomarker panels not only identified the relevant phenotypes based on their intended use but also if they were superior to some commonly used clinical laboratory tools, such as ALT and FIB-4,” the authors write. “These will serve as criteria, to be finalized with feedback from the FDA, to move the panels with the most promising performance metrics to the final qualification steps.”
“Individual developers of specific biomarker panels will need to determine their strategy; that is, have separate rule-in and rule-out cutoffs or a single optimized cutoff as they [formulate] the full qualification plans,” Dr. Sanyal noted. “Also, it may be necessary to validate these cutoffs and performance in independent cohorts reflecting the populations where these are planned to be used.”
“We hope that by 2025, the first wave of biomarkers will have enough data to support approval for diagnostic purposes, and the data for prognostic biomarkers will follow within 1-2 years after that,” Dr. Sanyal added.
Are practice changes ahead?
“Findings from this study and subsequent planned studies have the potential to redefine our approach to MASH and fibrosis diagnosis and staging, both in clinical practice and as part of clinical trials for the multiple new therapeutics being evaluated for MASLD/MASH,” Tatyana Kushner, MD, gastroenterologist/hepatologist and associate professor of medicine in the Division of Liver Diseases at the Icahn School of Medicine at Mount Sinai, New York City, told this news organization.
Dr. Kushner noted that the study population “may not represent the diverse population affected by MASH in the United States, or even the clinical trial population.” The cohort was predominantly White, with relatively low representation from people of Hispanic ethnicity, who are known to have a higher prevalence of MASH.
“Furthermore, the study population was specifically curated to have representative numbers across liver disease/fibrosis stages, and this may have biased the results,” she added.
In addition, other MASH-related biomarkers were developed after the current study started, including the FAST, Agile, and ADAPT scores, she said. “After validation of the biomarkers in this study, it will also be important to see how this newer wave of biomarkers performs.”
“If subsequent efforts validate the current findings, and there is buy-in from all of the stakeholders, including the FDA, NIH, industry, and academic leaders, this can truly lead to practice-changing approaches to the clinical management and study of MASLD/MASH,” Dr. Kushner concluded.
The study was partially funded by the National Institute of Diabetes and Digestive and Kidney Diseases and a grant from the National Center for Advancing Translational Sciences. The NIMBLE project is sponsored by the FNIH and is a public-private partnership supported by numerous entities. Support was also provided by the Global Liver Institute and FDA. Dr. Sanyal has disclosed financial relationships with multiple companies. He recused himself from the analysis and interpretation of NIS4. Dr. Kushner has declared being an adviser for Gilead, AbbVie, Eiger, and Bausch, and receiving research support from Gilead. None are MASH/NASH-related.
A version of this article first appeared on Medscape.com.
(NASH, now known as metabolic dysfunction–associated steatohepatitis or MASH), laying the groundwork for noninvasive alternatives to liver biopsy, new research suggests.
The blood-based tests could expand diagnostic options at health care facilities and facilitate enrollment in NASH clinical trials, which now require a biopsy for inclusion.
“The current study meets a key milestone for qualification of the biomarker panels studied for identification of at-risk NASH,” Arun Sanyal, MD, of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University, Richmond, told this news organization.
“It sets the stage for further validation of these outcomes,” he said. “These data will inform development of full qualification plans for these biomarker panels that will be submitted to the U.S. Food and Drug Administration. Once these are accepted by the FDA, the final steps toward qualification can be initiated.”
The study, published online in Nature Medicine, was conducted as part of the Foundation for the National Institutes of Health – Biomarkers Consortium’s Noninvasive Biomarkers of Metabolic Liver Disease (FNIH-NIMBLE), a multistakeholder project to support regulatory approval of NASH-related biomarkers.
Multiple biomarkers move forward
The investigators evaluated the diagnostic performance of five blood-based panels in an observational cohort derived from the NASH Clinical Research Network study, which included 4,094 participants; 2,479 individuals were excluded from the current study because of age, lack of samples, or lack of evaluable liver biopsies.
The remaining 1,073 patients (mean age, 52.5 years; 62% women) represented the full spectrum of nonalcoholic fatty liver disease (NAFLD, now known as metabolic dysfunction–associated steatotic liver disease or MASLD). In total, 225 individuals had NAFLD, 835 had NASH, and 13 had cirrhosis with an indeterminate NAFLD phenotype.
Those without fibrosis were younger and had mainly fatty liver, not steatohepatitis. They also had a lower NAFLD activity score, compared with those with stage 2 or higher fibrosis.
The study population for one of the five tests, FibroMeter VCTE, was a smaller subset (n = 396) of the larger population, with baseline features similar to the larger cohort.
The biomarker panels were intended to diagnose at-risk NASH (NIS4), presence of NASH (OWLiver), or fibrosis stages greater than 2, greater than 3, or 4 (enhanced liver fibrosis [ELF] test, PROC3, and FibroMeter VCTE). At-risk NASH was defined by the presence of NASH, high histologic activity, and fibrosis stage greater than or equal to 2.
The performance metric was an area under the receiver operating characteristic curve (AUROC) greater than or equal to 0.7 and superiority over alanine aminotransferase (ALT) for disease activity and the FIB-4 test for fibrosis severity.
Multiple biomarkers met the required metrics. For example, NIS4 had an AUROC of 0.81 for at-risk NASH. AUROCs for the ELF test (for clinically significant fibrosis, ≥ stage 2), PROC3 (advanced fibrosis, ≥ stage 3), and FibroMeter VCTE (cirrhosis, stage 4) were all greater than or equal to 0.8.
For all fibrosis endpoints, ELF and FibroMeter VCTE also outperformed FIB-4.
“The current study was a first step to determine if the biomarker panels not only identified the relevant phenotypes based on their intended use but also if they were superior to some commonly used clinical laboratory tools, such as ALT and FIB-4,” the authors write. “These will serve as criteria, to be finalized with feedback from the FDA, to move the panels with the most promising performance metrics to the final qualification steps.”
“Individual developers of specific biomarker panels will need to determine their strategy; that is, have separate rule-in and rule-out cutoffs or a single optimized cutoff as they [formulate] the full qualification plans,” Dr. Sanyal noted. “Also, it may be necessary to validate these cutoffs and performance in independent cohorts reflecting the populations where these are planned to be used.”
“We hope that by 2025, the first wave of biomarkers will have enough data to support approval for diagnostic purposes, and the data for prognostic biomarkers will follow within 1-2 years after that,” Dr. Sanyal added.
Are practice changes ahead?
“Findings from this study and subsequent planned studies have the potential to redefine our approach to MASH and fibrosis diagnosis and staging, both in clinical practice and as part of clinical trials for the multiple new therapeutics being evaluated for MASLD/MASH,” Tatyana Kushner, MD, gastroenterologist/hepatologist and associate professor of medicine in the Division of Liver Diseases at the Icahn School of Medicine at Mount Sinai, New York City, told this news organization.
Dr. Kushner noted that the study population “may not represent the diverse population affected by MASH in the United States, or even the clinical trial population.” The cohort was predominantly White, with relatively low representation from people of Hispanic ethnicity, who are known to have a higher prevalence of MASH.
“Furthermore, the study population was specifically curated to have representative numbers across liver disease/fibrosis stages, and this may have biased the results,” she added.
In addition, other MASH-related biomarkers were developed after the current study started, including the FAST, Agile, and ADAPT scores, she said. “After validation of the biomarkers in this study, it will also be important to see how this newer wave of biomarkers performs.”
“If subsequent efforts validate the current findings, and there is buy-in from all of the stakeholders, including the FDA, NIH, industry, and academic leaders, this can truly lead to practice-changing approaches to the clinical management and study of MASLD/MASH,” Dr. Kushner concluded.
The study was partially funded by the National Institute of Diabetes and Digestive and Kidney Diseases and a grant from the National Center for Advancing Translational Sciences. The NIMBLE project is sponsored by the FNIH and is a public-private partnership supported by numerous entities. Support was also provided by the Global Liver Institute and FDA. Dr. Sanyal has disclosed financial relationships with multiple companies. He recused himself from the analysis and interpretation of NIS4. Dr. Kushner has declared being an adviser for Gilead, AbbVie, Eiger, and Bausch, and receiving research support from Gilead. None are MASH/NASH-related.
A version of this article first appeared on Medscape.com.
(NASH, now known as metabolic dysfunction–associated steatohepatitis or MASH), laying the groundwork for noninvasive alternatives to liver biopsy, new research suggests.
The blood-based tests could expand diagnostic options at health care facilities and facilitate enrollment in NASH clinical trials, which now require a biopsy for inclusion.
“The current study meets a key milestone for qualification of the biomarker panels studied for identification of at-risk NASH,” Arun Sanyal, MD, of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University, Richmond, told this news organization.
“It sets the stage for further validation of these outcomes,” he said. “These data will inform development of full qualification plans for these biomarker panels that will be submitted to the U.S. Food and Drug Administration. Once these are accepted by the FDA, the final steps toward qualification can be initiated.”
The study, published online in Nature Medicine, was conducted as part of the Foundation for the National Institutes of Health – Biomarkers Consortium’s Noninvasive Biomarkers of Metabolic Liver Disease (FNIH-NIMBLE), a multistakeholder project to support regulatory approval of NASH-related biomarkers.
Multiple biomarkers move forward
The investigators evaluated the diagnostic performance of five blood-based panels in an observational cohort derived from the NASH Clinical Research Network study, which included 4,094 participants; 2,479 individuals were excluded from the current study because of age, lack of samples, or lack of evaluable liver biopsies.
The remaining 1,073 patients (mean age, 52.5 years; 62% women) represented the full spectrum of nonalcoholic fatty liver disease (NAFLD, now known as metabolic dysfunction–associated steatotic liver disease or MASLD). In total, 225 individuals had NAFLD, 835 had NASH, and 13 had cirrhosis with an indeterminate NAFLD phenotype.
Those without fibrosis were younger and had mainly fatty liver, not steatohepatitis. They also had a lower NAFLD activity score, compared with those with stage 2 or higher fibrosis.
The study population for one of the five tests, FibroMeter VCTE, was a smaller subset (n = 396) of the larger population, with baseline features similar to the larger cohort.
The biomarker panels were intended to diagnose at-risk NASH (NIS4), presence of NASH (OWLiver), or fibrosis stages greater than 2, greater than 3, or 4 (enhanced liver fibrosis [ELF] test, PROC3, and FibroMeter VCTE). At-risk NASH was defined by the presence of NASH, high histologic activity, and fibrosis stage greater than or equal to 2.
The performance metric was an area under the receiver operating characteristic curve (AUROC) greater than or equal to 0.7 and superiority over alanine aminotransferase (ALT) for disease activity and the FIB-4 test for fibrosis severity.
Multiple biomarkers met the required metrics. For example, NIS4 had an AUROC of 0.81 for at-risk NASH. AUROCs for the ELF test (for clinically significant fibrosis, ≥ stage 2), PROC3 (advanced fibrosis, ≥ stage 3), and FibroMeter VCTE (cirrhosis, stage 4) were all greater than or equal to 0.8.
For all fibrosis endpoints, ELF and FibroMeter VCTE also outperformed FIB-4.
“The current study was a first step to determine if the biomarker panels not only identified the relevant phenotypes based on their intended use but also if they were superior to some commonly used clinical laboratory tools, such as ALT and FIB-4,” the authors write. “These will serve as criteria, to be finalized with feedback from the FDA, to move the panels with the most promising performance metrics to the final qualification steps.”
“Individual developers of specific biomarker panels will need to determine their strategy; that is, have separate rule-in and rule-out cutoffs or a single optimized cutoff as they [formulate] the full qualification plans,” Dr. Sanyal noted. “Also, it may be necessary to validate these cutoffs and performance in independent cohorts reflecting the populations where these are planned to be used.”
“We hope that by 2025, the first wave of biomarkers will have enough data to support approval for diagnostic purposes, and the data for prognostic biomarkers will follow within 1-2 years after that,” Dr. Sanyal added.
Are practice changes ahead?
“Findings from this study and subsequent planned studies have the potential to redefine our approach to MASH and fibrosis diagnosis and staging, both in clinical practice and as part of clinical trials for the multiple new therapeutics being evaluated for MASLD/MASH,” Tatyana Kushner, MD, gastroenterologist/hepatologist and associate professor of medicine in the Division of Liver Diseases at the Icahn School of Medicine at Mount Sinai, New York City, told this news organization.
Dr. Kushner noted that the study population “may not represent the diverse population affected by MASH in the United States, or even the clinical trial population.” The cohort was predominantly White, with relatively low representation from people of Hispanic ethnicity, who are known to have a higher prevalence of MASH.
“Furthermore, the study population was specifically curated to have representative numbers across liver disease/fibrosis stages, and this may have biased the results,” she added.
In addition, other MASH-related biomarkers were developed after the current study started, including the FAST, Agile, and ADAPT scores, she said. “After validation of the biomarkers in this study, it will also be important to see how this newer wave of biomarkers performs.”
“If subsequent efforts validate the current findings, and there is buy-in from all of the stakeholders, including the FDA, NIH, industry, and academic leaders, this can truly lead to practice-changing approaches to the clinical management and study of MASLD/MASH,” Dr. Kushner concluded.
The study was partially funded by the National Institute of Diabetes and Digestive and Kidney Diseases and a grant from the National Center for Advancing Translational Sciences. The NIMBLE project is sponsored by the FNIH and is a public-private partnership supported by numerous entities. Support was also provided by the Global Liver Institute and FDA. Dr. Sanyal has disclosed financial relationships with multiple companies. He recused himself from the analysis and interpretation of NIS4. Dr. Kushner has declared being an adviser for Gilead, AbbVie, Eiger, and Bausch, and receiving research support from Gilead. None are MASH/NASH-related.
A version of this article first appeared on Medscape.com.
FROM NATURE MEDICINE
Endoscopic monitoring may not be needed for nonerosive GERD
Patients with confirmed nonerosive gastroesophageal reflux disease (GERD) are not at greater risk for esophageal cancer compared with the general population and are unlikely to need additional endoscopic monitoring for cancer, new research suggests.
By contrast, patients with erosive disease had more than double the incidence of esophageal cancer.
“We expected a less-strong association with cancer among patients with nonerosive GERD compared to those with erosive GERD, [and] the results do make sense in view of the fact that the nonerosive GERD patients had normal esophageal mucosa at endoscopy,” Jesper Lagergren, MD, PhD, of Karolinska Institutet, Stockholm, told this news organization.
The findings “suggest that in patients with GERD, a normal endoscopy indicates that the risk of cancer development in the esophagus is low,” he said. “If future research confirms our results, no monitoring would be needed for patients with known nonerosive GERD.”
However, a related editorial suggests there may be other reasons to endoscopically monitor patients with nonerosive GERD.
The study was published online in the BMJ, as was the editorial.
Erosive GERD raises risk
To assess the incidence rate of esophageal cancer among patients with nonerosive GERD compared with the general population, the investigators analyzed records from 486,556 patients in hospital and specialized outpatient centers in Denmark, Finland, and Sweden who underwent endoscopy from 1987 to 2019.
A total of 285,811 patients were included in the nonerosive GERD cohort, and 200,745 were included in a validation cohort of patients with erosive GERD.
Nonerosive GERD was defined by the absence of esophagitis and any other esophageal disorder at endoscopy. Erosive GERD was defined by esophagitis at endoscopy.
The incidence rate of esophageal cancer was assessed for up to 31 years of follow-up, with the median being 6.3 years.
In the nonerosive GERD cohort, 228 patients developed esophageal cancer during nearly 2.1 million person-years of follow-up. The incidence rate was 11 per 100,000 person-years, similar to that of the general population (standardized incidence ratio, 1.04) and did not increase with longer follow-up.
In the erosive GERD cohort, 542 patients developed esophageal cancer over almost 1.8 million person-years. This corresponded to an incidence rate of 31 per 100,000 person-years, or an increased overall standardized incidence ratio of 2.36, which became more pronounced with longer follow-up.
“This finding suggests that endoscopically confirmed non-erosive [GERD] does not require additional endoscopic monitoring for esophageal adenocarcinoma,” the authors concluded.
‘Dynamic’ progression
In a related editorial, Jerry Zhou, PhD, and Vincent Ho, MD, both of Western Sydney University, Penrith, New South Wales, Australia, wrote that the finding that patients with nonerosive disease do not have to undergo additional endoscopic evaluations for cancer is in line with previous research.
However, they added, “the more pressing rationale for reevaluating these patients would be the potential for progression to conditions such as erosive reflux disease or Barrett’s esophagus.” Longitudinal studies have shown that GERD progression is dynamic, and so the development of erosive disease after nonerosive disease is feasible.
“Widespread use of proton-pump inhibitors complicates our understanding” of GERD progression, they noted. Although study participants were advised not to take antireflux medications in the weeks prior to their endoscopy, “uncertainties about previous treatments remain due to the study’s design.” Some participants without erosive disease at baseline may have had it in the past.
Dr. Zhou and Dr. Ho also postulated that rather than being a progressive disease, nonerosive and erosive GERD might be two distinct conditions with different features and underpinnings.
Although valuable, the study “prompts reflection on the limitations of relying on the absence of esophageal erosions as the sole diagnostic criterion for non-erosive disease. The changing progression of gastroesophageal reflux disease, the complex influence of proton pump inhibitors, and the potential for a range of underlying pathophysiological causes requires a more comprehensive diagnostic perspective,” they concluded.
Dr. Lagergren said that his group plans to assess whether treatment of nonerosive GERD should be different from erosive GERD.
The study was funded by the Swedish Research Council, Swedish Cancer Society, and Nordic Cancer Union. No competing interests were declared.
A version of this article appeared on Medscape.com.
Patients with confirmed nonerosive gastroesophageal reflux disease (GERD) are not at greater risk for esophageal cancer compared with the general population and are unlikely to need additional endoscopic monitoring for cancer, new research suggests.
By contrast, patients with erosive disease had more than double the incidence of esophageal cancer.
“We expected a less-strong association with cancer among patients with nonerosive GERD compared to those with erosive GERD, [and] the results do make sense in view of the fact that the nonerosive GERD patients had normal esophageal mucosa at endoscopy,” Jesper Lagergren, MD, PhD, of Karolinska Institutet, Stockholm, told this news organization.
The findings “suggest that in patients with GERD, a normal endoscopy indicates that the risk of cancer development in the esophagus is low,” he said. “If future research confirms our results, no monitoring would be needed for patients with known nonerosive GERD.”
However, a related editorial suggests there may be other reasons to endoscopically monitor patients with nonerosive GERD.
The study was published online in the BMJ, as was the editorial.
Erosive GERD raises risk
To assess the incidence rate of esophageal cancer among patients with nonerosive GERD compared with the general population, the investigators analyzed records from 486,556 patients in hospital and specialized outpatient centers in Denmark, Finland, and Sweden who underwent endoscopy from 1987 to 2019.
A total of 285,811 patients were included in the nonerosive GERD cohort, and 200,745 were included in a validation cohort of patients with erosive GERD.
Nonerosive GERD was defined by the absence of esophagitis and any other esophageal disorder at endoscopy. Erosive GERD was defined by esophagitis at endoscopy.
The incidence rate of esophageal cancer was assessed for up to 31 years of follow-up, with the median being 6.3 years.
In the nonerosive GERD cohort, 228 patients developed esophageal cancer during nearly 2.1 million person-years of follow-up. The incidence rate was 11 per 100,000 person-years, similar to that of the general population (standardized incidence ratio, 1.04) and did not increase with longer follow-up.
In the erosive GERD cohort, 542 patients developed esophageal cancer over almost 1.8 million person-years. This corresponded to an incidence rate of 31 per 100,000 person-years, or an increased overall standardized incidence ratio of 2.36, which became more pronounced with longer follow-up.
“This finding suggests that endoscopically confirmed non-erosive [GERD] does not require additional endoscopic monitoring for esophageal adenocarcinoma,” the authors concluded.
‘Dynamic’ progression
In a related editorial, Jerry Zhou, PhD, and Vincent Ho, MD, both of Western Sydney University, Penrith, New South Wales, Australia, wrote that the finding that patients with nonerosive disease do not have to undergo additional endoscopic evaluations for cancer is in line with previous research.
However, they added, “the more pressing rationale for reevaluating these patients would be the potential for progression to conditions such as erosive reflux disease or Barrett’s esophagus.” Longitudinal studies have shown that GERD progression is dynamic, and so the development of erosive disease after nonerosive disease is feasible.
“Widespread use of proton-pump inhibitors complicates our understanding” of GERD progression, they noted. Although study participants were advised not to take antireflux medications in the weeks prior to their endoscopy, “uncertainties about previous treatments remain due to the study’s design.” Some participants without erosive disease at baseline may have had it in the past.
Dr. Zhou and Dr. Ho also postulated that rather than being a progressive disease, nonerosive and erosive GERD might be two distinct conditions with different features and underpinnings.
Although valuable, the study “prompts reflection on the limitations of relying on the absence of esophageal erosions as the sole diagnostic criterion for non-erosive disease. The changing progression of gastroesophageal reflux disease, the complex influence of proton pump inhibitors, and the potential for a range of underlying pathophysiological causes requires a more comprehensive diagnostic perspective,” they concluded.
Dr. Lagergren said that his group plans to assess whether treatment of nonerosive GERD should be different from erosive GERD.
The study was funded by the Swedish Research Council, Swedish Cancer Society, and Nordic Cancer Union. No competing interests were declared.
A version of this article appeared on Medscape.com.
Patients with confirmed nonerosive gastroesophageal reflux disease (GERD) are not at greater risk for esophageal cancer compared with the general population and are unlikely to need additional endoscopic monitoring for cancer, new research suggests.
By contrast, patients with erosive disease had more than double the incidence of esophageal cancer.
“We expected a less-strong association with cancer among patients with nonerosive GERD compared to those with erosive GERD, [and] the results do make sense in view of the fact that the nonerosive GERD patients had normal esophageal mucosa at endoscopy,” Jesper Lagergren, MD, PhD, of Karolinska Institutet, Stockholm, told this news organization.
The findings “suggest that in patients with GERD, a normal endoscopy indicates that the risk of cancer development in the esophagus is low,” he said. “If future research confirms our results, no monitoring would be needed for patients with known nonerosive GERD.”
However, a related editorial suggests there may be other reasons to endoscopically monitor patients with nonerosive GERD.
The study was published online in the BMJ, as was the editorial.
Erosive GERD raises risk
To assess the incidence rate of esophageal cancer among patients with nonerosive GERD compared with the general population, the investigators analyzed records from 486,556 patients in hospital and specialized outpatient centers in Denmark, Finland, and Sweden who underwent endoscopy from 1987 to 2019.
A total of 285,811 patients were included in the nonerosive GERD cohort, and 200,745 were included in a validation cohort of patients with erosive GERD.
Nonerosive GERD was defined by the absence of esophagitis and any other esophageal disorder at endoscopy. Erosive GERD was defined by esophagitis at endoscopy.
The incidence rate of esophageal cancer was assessed for up to 31 years of follow-up, with the median being 6.3 years.
In the nonerosive GERD cohort, 228 patients developed esophageal cancer during nearly 2.1 million person-years of follow-up. The incidence rate was 11 per 100,000 person-years, similar to that of the general population (standardized incidence ratio, 1.04) and did not increase with longer follow-up.
In the erosive GERD cohort, 542 patients developed esophageal cancer over almost 1.8 million person-years. This corresponded to an incidence rate of 31 per 100,000 person-years, or an increased overall standardized incidence ratio of 2.36, which became more pronounced with longer follow-up.
“This finding suggests that endoscopically confirmed non-erosive [GERD] does not require additional endoscopic monitoring for esophageal adenocarcinoma,” the authors concluded.
‘Dynamic’ progression
In a related editorial, Jerry Zhou, PhD, and Vincent Ho, MD, both of Western Sydney University, Penrith, New South Wales, Australia, wrote that the finding that patients with nonerosive disease do not have to undergo additional endoscopic evaluations for cancer is in line with previous research.
However, they added, “the more pressing rationale for reevaluating these patients would be the potential for progression to conditions such as erosive reflux disease or Barrett’s esophagus.” Longitudinal studies have shown that GERD progression is dynamic, and so the development of erosive disease after nonerosive disease is feasible.
“Widespread use of proton-pump inhibitors complicates our understanding” of GERD progression, they noted. Although study participants were advised not to take antireflux medications in the weeks prior to their endoscopy, “uncertainties about previous treatments remain due to the study’s design.” Some participants without erosive disease at baseline may have had it in the past.
Dr. Zhou and Dr. Ho also postulated that rather than being a progressive disease, nonerosive and erosive GERD might be two distinct conditions with different features and underpinnings.
Although valuable, the study “prompts reflection on the limitations of relying on the absence of esophageal erosions as the sole diagnostic criterion for non-erosive disease. The changing progression of gastroesophageal reflux disease, the complex influence of proton pump inhibitors, and the potential for a range of underlying pathophysiological causes requires a more comprehensive diagnostic perspective,” they concluded.
Dr. Lagergren said that his group plans to assess whether treatment of nonerosive GERD should be different from erosive GERD.
The study was funded by the Swedish Research Council, Swedish Cancer Society, and Nordic Cancer Union. No competing interests were declared.
A version of this article appeared on Medscape.com.
No need to restrict hep C DAA therapy based on alcohol use
TOPLINE:
Alcohol use at any level, including alcohol use disorder (AUD), is not associated with decreased odds of a sustained virologic response (SVR) to direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection. Therefore, DAA therapy should not be withheld from patients who consume alcohol.
METHODOLOGY:
- The researchers examined electronic health records for 69,229 patients (mean age, 63 years; 97% men; 50% non-Hispanic White) who started DAA therapy through the Department of Veterans Affairs between 2014 and 2018.
- Alcohol use categories were abstinent without history of AUD, abstinent with history of AUD, lower-risk consumption, moderate-risk consumption, and high-risk consumption or AUD.
- The primary outcome was SVR, which was defined as undetectable HCV RNA for 12 weeks to 6 months after completion of DAA treatment.
TAKEAWAY:
- Close to half (46.6%) of patients were abstinent without AUD, 13.3% were abstinent with AUD, 19.4% had lower-risk consumption, 4.5% had moderate-risk consumption, and 16.2% had high-risk consumption or AUD.
- Overall, 94.4% of those who started on DAA treatment achieved SVR.
- After adjustment, there was no evidence that any alcohol category was significantly associated with decreased odds of achieving SVR. The odds ratios were 1.09 for abstinent without AUD history, 0.92 for abstinent with AUD history, 0.96 for moderate-risk consumption, and 0.95 for high-risk consumption or AUD.
- SVR did not differ by baseline stage of hepatic fibrosis, as measured by Fibrosis-4 score of 3.25 or less versus greater than 3.25.
IN PRACTICE:
“Achieving SVR has been shown to be associated with reduced risk of post-SVR outcomes, including hepatocellular carcinoma, liver-related mortality, and all-cause mortality. Our findings suggest that DAA therapy should be provided and reimbursed despite alcohol consumption or history of AUD. Restricting access to DAA therapy according to alcohol consumption or AUD creates an unnecessary barrier to patients accessing DAA therapy and challenges HCV elimination goals,” the investigators wrote.
SOURCE:
Emily J. Cartwright, MD, of Emory University, Atlanta, led the study, which was published online in JAMA Network Open.
LIMITATIONS:
The study was observational and subject to potential residual confounding. To define SVR, HCV RNA was measured 6 months after DAA treatment ended, which may have resulted in a misclassification of patients who experienced viral relapse. Most participants were men born between 1945 and 1965, and the results may not be generalizable to women and/or older and younger patients.
DISCLOSURES:
The study was supported by grants from the National Institute on Alcohol Abuse and Alcoholism. Dr. Cartwright reported no disclosures. Two coauthors disclosed fees from pharmaceutical companies outside the submitted work.
A version of this article first appeared on Medscape.com.
TOPLINE:
Alcohol use at any level, including alcohol use disorder (AUD), is not associated with decreased odds of a sustained virologic response (SVR) to direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection. Therefore, DAA therapy should not be withheld from patients who consume alcohol.
METHODOLOGY:
- The researchers examined electronic health records for 69,229 patients (mean age, 63 years; 97% men; 50% non-Hispanic White) who started DAA therapy through the Department of Veterans Affairs between 2014 and 2018.
- Alcohol use categories were abstinent without history of AUD, abstinent with history of AUD, lower-risk consumption, moderate-risk consumption, and high-risk consumption or AUD.
- The primary outcome was SVR, which was defined as undetectable HCV RNA for 12 weeks to 6 months after completion of DAA treatment.
TAKEAWAY:
- Close to half (46.6%) of patients were abstinent without AUD, 13.3% were abstinent with AUD, 19.4% had lower-risk consumption, 4.5% had moderate-risk consumption, and 16.2% had high-risk consumption or AUD.
- Overall, 94.4% of those who started on DAA treatment achieved SVR.
- After adjustment, there was no evidence that any alcohol category was significantly associated with decreased odds of achieving SVR. The odds ratios were 1.09 for abstinent without AUD history, 0.92 for abstinent with AUD history, 0.96 for moderate-risk consumption, and 0.95 for high-risk consumption or AUD.
- SVR did not differ by baseline stage of hepatic fibrosis, as measured by Fibrosis-4 score of 3.25 or less versus greater than 3.25.
IN PRACTICE:
“Achieving SVR has been shown to be associated with reduced risk of post-SVR outcomes, including hepatocellular carcinoma, liver-related mortality, and all-cause mortality. Our findings suggest that DAA therapy should be provided and reimbursed despite alcohol consumption or history of AUD. Restricting access to DAA therapy according to alcohol consumption or AUD creates an unnecessary barrier to patients accessing DAA therapy and challenges HCV elimination goals,” the investigators wrote.
SOURCE:
Emily J. Cartwright, MD, of Emory University, Atlanta, led the study, which was published online in JAMA Network Open.
LIMITATIONS:
The study was observational and subject to potential residual confounding. To define SVR, HCV RNA was measured 6 months after DAA treatment ended, which may have resulted in a misclassification of patients who experienced viral relapse. Most participants were men born between 1945 and 1965, and the results may not be generalizable to women and/or older and younger patients.
DISCLOSURES:
The study was supported by grants from the National Institute on Alcohol Abuse and Alcoholism. Dr. Cartwright reported no disclosures. Two coauthors disclosed fees from pharmaceutical companies outside the submitted work.
A version of this article first appeared on Medscape.com.
TOPLINE:
Alcohol use at any level, including alcohol use disorder (AUD), is not associated with decreased odds of a sustained virologic response (SVR) to direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection. Therefore, DAA therapy should not be withheld from patients who consume alcohol.
METHODOLOGY:
- The researchers examined electronic health records for 69,229 patients (mean age, 63 years; 97% men; 50% non-Hispanic White) who started DAA therapy through the Department of Veterans Affairs between 2014 and 2018.
- Alcohol use categories were abstinent without history of AUD, abstinent with history of AUD, lower-risk consumption, moderate-risk consumption, and high-risk consumption or AUD.
- The primary outcome was SVR, which was defined as undetectable HCV RNA for 12 weeks to 6 months after completion of DAA treatment.
TAKEAWAY:
- Close to half (46.6%) of patients were abstinent without AUD, 13.3% were abstinent with AUD, 19.4% had lower-risk consumption, 4.5% had moderate-risk consumption, and 16.2% had high-risk consumption or AUD.
- Overall, 94.4% of those who started on DAA treatment achieved SVR.
- After adjustment, there was no evidence that any alcohol category was significantly associated with decreased odds of achieving SVR. The odds ratios were 1.09 for abstinent without AUD history, 0.92 for abstinent with AUD history, 0.96 for moderate-risk consumption, and 0.95 for high-risk consumption or AUD.
- SVR did not differ by baseline stage of hepatic fibrosis, as measured by Fibrosis-4 score of 3.25 or less versus greater than 3.25.
IN PRACTICE:
“Achieving SVR has been shown to be associated with reduced risk of post-SVR outcomes, including hepatocellular carcinoma, liver-related mortality, and all-cause mortality. Our findings suggest that DAA therapy should be provided and reimbursed despite alcohol consumption or history of AUD. Restricting access to DAA therapy according to alcohol consumption or AUD creates an unnecessary barrier to patients accessing DAA therapy and challenges HCV elimination goals,” the investigators wrote.
SOURCE:
Emily J. Cartwright, MD, of Emory University, Atlanta, led the study, which was published online in JAMA Network Open.
LIMITATIONS:
The study was observational and subject to potential residual confounding. To define SVR, HCV RNA was measured 6 months after DAA treatment ended, which may have resulted in a misclassification of patients who experienced viral relapse. Most participants were men born between 1945 and 1965, and the results may not be generalizable to women and/or older and younger patients.
DISCLOSURES:
The study was supported by grants from the National Institute on Alcohol Abuse and Alcoholism. Dr. Cartwright reported no disclosures. Two coauthors disclosed fees from pharmaceutical companies outside the submitted work.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
No benefit of EC/IC bypass versus meds in large-artery stroke
in the latest randomized trial comparing the two interventions.
However, subgroup analyses suggest a potential benefit of surgery for certain patients, such as those with MCA vs. ICA occlusion, mean transit time greater than 6 seconds, or regional blood flow of 0.8 or less.
“We were disappointed by the results,” Liqun Jiao, MD, of the National Center for Neurological Disorders in Beijing, told this news organization. “We were expecting to demonstrate a benefit from EC-IC bypass surgery over medical treatment alone in symptomatic patients with ICA or MCA occlusion and hemodynamic insufficiency, per our original hypothesis.”
Although the study showed improved efficacy and safety for the surgical procedure, he said, “The progress of medical treatment is even better.”
The study was published online in JAMA.
Subgroup analyses promising
Previous randomized clinical trials, including the EC/IC Bypass Study and the Carotid Occlusion Surgery Study (COSS), showed no benefit in stroke prevention for patients with atherosclerotic occlusion of the ICA or MCA.
However, in light of improvements over the years in surgical techniques and patient selection, the authors conducted the Carotid and Middle Cerebral Artery Occlusion Surgery Study (CMOSS), a multicenter, randomized, open-label trial comparing EC-IC bypass surgery plus medical therapy, consisting of antiplatelet therapy and control of stroke risk factors, with medical therapy alone in symptomatic patients with ICA or MCA occlusion and hemodynamic insufficiency, with refined patient and operator selection.
A total of 324 patients (median age, 52.7 years; 79% men) in 13 centers in China were included; 309 patients (95%) completed the study.
The primary outcome was a composite of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years after randomization.
Secondary outcomes included, among others, any stroke or death within 2 years and fatal stroke within 2 years.
No significant difference was found for the primary outcome between the surgical group (8.6%) and the medical group (12.3%).
The 30-day risk of stroke or death was 6.2% in the surgery group, versus 1.8% (3/163) for the medical group. The risk of ipsilateral ischemic stroke beyond 30 days through 2 years was 2%, versus 10.3% – nonsignificant differences.
Furthermore, none of the prespecified secondary endpoints showed a significant difference, including any stroke or death within 2 years (9.9% vs. 15.3%; hazard ratio, 0.69) and fatal stroke within 2 years (2% vs. none).
Despite the findings, “We are encouraged by the subgroup analysis and the trend of long-term outcomes,” Dr. Jiao said. “We will continue to finish 5-10 years of follow-up to see whether the benefit of bypass surgery can be identified.”
The team has also launched the CMOSS-2 trial with a refined study design based on the results of subgroup analysis of the CMOSS study.
CMOSS-2 is recruiting patients with symptomatic chronic occlusion of the MCA and severe hemodynamic insufficiency in 13 sites in China. The primary outcome is ischemic stroke in the territory of the target artery within 24 months after randomization.
Can’t exclude benefit
Thomas Jeerakathil, MD, a professor at the University of Alberta and Northern Stroke Lead, Cardiovascular and Stroke Strategic Clinical Network, Alberta Health Services, Edmonton, commented on the study for this news organization. Like the authors, he said, “I don’t consider this study to definitively exclude the benefit of EC/IC bypass. More studies are required.”
Dr. Jeerakathil would like to see a study of a higher-risk group based on both clinical and hemodynamic blood flow criteria. In the current study, he said, “The trial group overall may not have been at high enough stroke risk to justify the up-front risks of the EC-IC bypass procedure.”
In addition, “The analysis method of Cox proportional hazards regression for the primary outcome did not fit the data when the perioperative period was combined with the period beyond 30 days,” he noted. “The researchers were open about this and did pivot and included a post hoc relative risk-based analysis, but the validity of their primary analysis is questionable.”
Furthermore, the study was “somewhat underpowered with a relatively small sample size and had the potential to miss clinically significant differences between groups,” he said. “It would be good to see a longer follow-up period of at least 5 years added to this trial and used in future trials, rather than 2 years.”
“Lastly,” he said, “it’s difficult to ignore the reduction in recurrent stroke events over the 30-day to 2-year time period associated with EC-IC bypass (from 10.3% down to 2%). This reduction alone shows the procedure has some potential to prevent stroke and would argue for more trials.”
EC-IC could be considered for patients who have failed other medical therapies and have more substantial evidence of compromised blood flow to the brain than those in the CMOSS trial, he noted, as many of these patients have few other options. “In our center and many other centers, the approach to EC-IC bypass is probably much more selective than used in the trial.”
Dr. Jeerakathil concluded, “Clinicians should be cautious about offering the procedure to patients with just mildly delayed blood flow in the hemisphere affected by the occluded artery and those who have not yet failed maximal medical therapy.”
But Seemant Chaturvedi, MD, and J. Marc Simard, MD, PhD, both of the University of Maryland, Baltimore, are not as optimistic about the potential for EC-IC.
Writing in a related editorial, they conclude that the results with EC-IC bypass surgery in randomized trials “remain unimpressive. Until a better understanding of the unique hemodynamic features of the brain is achieved, it will be difficult for neurosurgeons to continue offering this procedure to patients with ICA or MCA occlusion. Intensive, multifaceted medical therapy remains the first-line treatment for [these] patients.”
The study was supported by a research grant from the National Health Commission of the People’s Republic of China. Dr. Jiao, Dr. Jeerakathil, Dr. Chaturvedi, and Dr. Simard reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
in the latest randomized trial comparing the two interventions.
However, subgroup analyses suggest a potential benefit of surgery for certain patients, such as those with MCA vs. ICA occlusion, mean transit time greater than 6 seconds, or regional blood flow of 0.8 or less.
“We were disappointed by the results,” Liqun Jiao, MD, of the National Center for Neurological Disorders in Beijing, told this news organization. “We were expecting to demonstrate a benefit from EC-IC bypass surgery over medical treatment alone in symptomatic patients with ICA or MCA occlusion and hemodynamic insufficiency, per our original hypothesis.”
Although the study showed improved efficacy and safety for the surgical procedure, he said, “The progress of medical treatment is even better.”
The study was published online in JAMA.
Subgroup analyses promising
Previous randomized clinical trials, including the EC/IC Bypass Study and the Carotid Occlusion Surgery Study (COSS), showed no benefit in stroke prevention for patients with atherosclerotic occlusion of the ICA or MCA.
However, in light of improvements over the years in surgical techniques and patient selection, the authors conducted the Carotid and Middle Cerebral Artery Occlusion Surgery Study (CMOSS), a multicenter, randomized, open-label trial comparing EC-IC bypass surgery plus medical therapy, consisting of antiplatelet therapy and control of stroke risk factors, with medical therapy alone in symptomatic patients with ICA or MCA occlusion and hemodynamic insufficiency, with refined patient and operator selection.
A total of 324 patients (median age, 52.7 years; 79% men) in 13 centers in China were included; 309 patients (95%) completed the study.
The primary outcome was a composite of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years after randomization.
Secondary outcomes included, among others, any stroke or death within 2 years and fatal stroke within 2 years.
No significant difference was found for the primary outcome between the surgical group (8.6%) and the medical group (12.3%).
The 30-day risk of stroke or death was 6.2% in the surgery group, versus 1.8% (3/163) for the medical group. The risk of ipsilateral ischemic stroke beyond 30 days through 2 years was 2%, versus 10.3% – nonsignificant differences.
Furthermore, none of the prespecified secondary endpoints showed a significant difference, including any stroke or death within 2 years (9.9% vs. 15.3%; hazard ratio, 0.69) and fatal stroke within 2 years (2% vs. none).
Despite the findings, “We are encouraged by the subgroup analysis and the trend of long-term outcomes,” Dr. Jiao said. “We will continue to finish 5-10 years of follow-up to see whether the benefit of bypass surgery can be identified.”
The team has also launched the CMOSS-2 trial with a refined study design based on the results of subgroup analysis of the CMOSS study.
CMOSS-2 is recruiting patients with symptomatic chronic occlusion of the MCA and severe hemodynamic insufficiency in 13 sites in China. The primary outcome is ischemic stroke in the territory of the target artery within 24 months after randomization.
Can’t exclude benefit
Thomas Jeerakathil, MD, a professor at the University of Alberta and Northern Stroke Lead, Cardiovascular and Stroke Strategic Clinical Network, Alberta Health Services, Edmonton, commented on the study for this news organization. Like the authors, he said, “I don’t consider this study to definitively exclude the benefit of EC/IC bypass. More studies are required.”
Dr. Jeerakathil would like to see a study of a higher-risk group based on both clinical and hemodynamic blood flow criteria. In the current study, he said, “The trial group overall may not have been at high enough stroke risk to justify the up-front risks of the EC-IC bypass procedure.”
In addition, “The analysis method of Cox proportional hazards regression for the primary outcome did not fit the data when the perioperative period was combined with the period beyond 30 days,” he noted. “The researchers were open about this and did pivot and included a post hoc relative risk-based analysis, but the validity of their primary analysis is questionable.”
Furthermore, the study was “somewhat underpowered with a relatively small sample size and had the potential to miss clinically significant differences between groups,” he said. “It would be good to see a longer follow-up period of at least 5 years added to this trial and used in future trials, rather than 2 years.”
“Lastly,” he said, “it’s difficult to ignore the reduction in recurrent stroke events over the 30-day to 2-year time period associated with EC-IC bypass (from 10.3% down to 2%). This reduction alone shows the procedure has some potential to prevent stroke and would argue for more trials.”
EC-IC could be considered for patients who have failed other medical therapies and have more substantial evidence of compromised blood flow to the brain than those in the CMOSS trial, he noted, as many of these patients have few other options. “In our center and many other centers, the approach to EC-IC bypass is probably much more selective than used in the trial.”
Dr. Jeerakathil concluded, “Clinicians should be cautious about offering the procedure to patients with just mildly delayed blood flow in the hemisphere affected by the occluded artery and those who have not yet failed maximal medical therapy.”
But Seemant Chaturvedi, MD, and J. Marc Simard, MD, PhD, both of the University of Maryland, Baltimore, are not as optimistic about the potential for EC-IC.
Writing in a related editorial, they conclude that the results with EC-IC bypass surgery in randomized trials “remain unimpressive. Until a better understanding of the unique hemodynamic features of the brain is achieved, it will be difficult for neurosurgeons to continue offering this procedure to patients with ICA or MCA occlusion. Intensive, multifaceted medical therapy remains the first-line treatment for [these] patients.”
The study was supported by a research grant from the National Health Commission of the People’s Republic of China. Dr. Jiao, Dr. Jeerakathil, Dr. Chaturvedi, and Dr. Simard reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
in the latest randomized trial comparing the two interventions.
However, subgroup analyses suggest a potential benefit of surgery for certain patients, such as those with MCA vs. ICA occlusion, mean transit time greater than 6 seconds, or regional blood flow of 0.8 or less.
“We were disappointed by the results,” Liqun Jiao, MD, of the National Center for Neurological Disorders in Beijing, told this news organization. “We were expecting to demonstrate a benefit from EC-IC bypass surgery over medical treatment alone in symptomatic patients with ICA or MCA occlusion and hemodynamic insufficiency, per our original hypothesis.”
Although the study showed improved efficacy and safety for the surgical procedure, he said, “The progress of medical treatment is even better.”
The study was published online in JAMA.
Subgroup analyses promising
Previous randomized clinical trials, including the EC/IC Bypass Study and the Carotid Occlusion Surgery Study (COSS), showed no benefit in stroke prevention for patients with atherosclerotic occlusion of the ICA or MCA.
However, in light of improvements over the years in surgical techniques and patient selection, the authors conducted the Carotid and Middle Cerebral Artery Occlusion Surgery Study (CMOSS), a multicenter, randomized, open-label trial comparing EC-IC bypass surgery plus medical therapy, consisting of antiplatelet therapy and control of stroke risk factors, with medical therapy alone in symptomatic patients with ICA or MCA occlusion and hemodynamic insufficiency, with refined patient and operator selection.
A total of 324 patients (median age, 52.7 years; 79% men) in 13 centers in China were included; 309 patients (95%) completed the study.
The primary outcome was a composite of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years after randomization.
Secondary outcomes included, among others, any stroke or death within 2 years and fatal stroke within 2 years.
No significant difference was found for the primary outcome between the surgical group (8.6%) and the medical group (12.3%).
The 30-day risk of stroke or death was 6.2% in the surgery group, versus 1.8% (3/163) for the medical group. The risk of ipsilateral ischemic stroke beyond 30 days through 2 years was 2%, versus 10.3% – nonsignificant differences.
Furthermore, none of the prespecified secondary endpoints showed a significant difference, including any stroke or death within 2 years (9.9% vs. 15.3%; hazard ratio, 0.69) and fatal stroke within 2 years (2% vs. none).
Despite the findings, “We are encouraged by the subgroup analysis and the trend of long-term outcomes,” Dr. Jiao said. “We will continue to finish 5-10 years of follow-up to see whether the benefit of bypass surgery can be identified.”
The team has also launched the CMOSS-2 trial with a refined study design based on the results of subgroup analysis of the CMOSS study.
CMOSS-2 is recruiting patients with symptomatic chronic occlusion of the MCA and severe hemodynamic insufficiency in 13 sites in China. The primary outcome is ischemic stroke in the territory of the target artery within 24 months after randomization.
Can’t exclude benefit
Thomas Jeerakathil, MD, a professor at the University of Alberta and Northern Stroke Lead, Cardiovascular and Stroke Strategic Clinical Network, Alberta Health Services, Edmonton, commented on the study for this news organization. Like the authors, he said, “I don’t consider this study to definitively exclude the benefit of EC/IC bypass. More studies are required.”
Dr. Jeerakathil would like to see a study of a higher-risk group based on both clinical and hemodynamic blood flow criteria. In the current study, he said, “The trial group overall may not have been at high enough stroke risk to justify the up-front risks of the EC-IC bypass procedure.”
In addition, “The analysis method of Cox proportional hazards regression for the primary outcome did not fit the data when the perioperative period was combined with the period beyond 30 days,” he noted. “The researchers were open about this and did pivot and included a post hoc relative risk-based analysis, but the validity of their primary analysis is questionable.”
Furthermore, the study was “somewhat underpowered with a relatively small sample size and had the potential to miss clinically significant differences between groups,” he said. “It would be good to see a longer follow-up period of at least 5 years added to this trial and used in future trials, rather than 2 years.”
“Lastly,” he said, “it’s difficult to ignore the reduction in recurrent stroke events over the 30-day to 2-year time period associated with EC-IC bypass (from 10.3% down to 2%). This reduction alone shows the procedure has some potential to prevent stroke and would argue for more trials.”
EC-IC could be considered for patients who have failed other medical therapies and have more substantial evidence of compromised blood flow to the brain than those in the CMOSS trial, he noted, as many of these patients have few other options. “In our center and many other centers, the approach to EC-IC bypass is probably much more selective than used in the trial.”
Dr. Jeerakathil concluded, “Clinicians should be cautious about offering the procedure to patients with just mildly delayed blood flow in the hemisphere affected by the occluded artery and those who have not yet failed maximal medical therapy.”
But Seemant Chaturvedi, MD, and J. Marc Simard, MD, PhD, both of the University of Maryland, Baltimore, are not as optimistic about the potential for EC-IC.
Writing in a related editorial, they conclude that the results with EC-IC bypass surgery in randomized trials “remain unimpressive. Until a better understanding of the unique hemodynamic features of the brain is achieved, it will be difficult for neurosurgeons to continue offering this procedure to patients with ICA or MCA occlusion. Intensive, multifaceted medical therapy remains the first-line treatment for [these] patients.”
The study was supported by a research grant from the National Health Commission of the People’s Republic of China. Dr. Jiao, Dr. Jeerakathil, Dr. Chaturvedi, and Dr. Simard reported no conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM JAMA
No-biopsy approach to celiac disease diagnosis safe for some
TOPLINE:
For adults with suspected celiac disease who do not have immunoglobulin A (IgA) deficiency, diagnostic bowel biopsy can most likely be avoided if the serum antitissue transglutaminase IgA (tTG-IgA) level is high.
METHODOLOGY:
- Researchers evaluated the reliability of serum tests for diagnosing celiac disease, as defined by duodenal villous atrophy (Marsh type 3 or Corazza-Villanacci grade B).
- The main study cohort included 436 adults with suspected celiac disease who did not have IgA deficiency and who were not on a gluten-free diet (mean age, 40 years; 68% women). The patients were referred by 14 centers across four continents to undergo local endoscopic duodenal biopsy.
- Local serum tTG-IgA was measured with 14 test brands. Concentration was expressed as a multiple of each test’s upper limit of normal (ULN). Tests were defined as positive when they exceeded one times the ULN.
- Histology was assessed by the local pathologist, and discordant cases were reevaluated by a central pathologist.
TAKEAWAY:
- Positive serum tTG-IgA was detected in 363 (83%) participants; negative serum tTG-IgA was detected in 73 (17%).
- After local review, 341 of the participants with positive serum tTG-IgA had positive histology (true positives) and 22 had negative histology (false positives).
- Of the 73 participants with negative serum tTG-IgA, 66 had negative histology (true negatives) and 7 had positive histology (false negatives).
- Central reevaluation of duodenal histology was performed in 29 discordant cases, resulting in 348 true positive cases, 15 false positive cases, 66 true negative cases, and 7 false negative cases – the equivalent of a positive predictive value of 95.9%, a negative predictive value of 90.4%, a sensitivity of 98%, and a specificity of 81.5%.
- The positive predictive value of local serum tTG-IgA increased when the serologic threshold was defined at increasing multiples of the ULN. The test correctly diagnosed duodenal villous atrophy in 97.5% of patients with serum tTG-IgA concentrations greater than 10 times the ULN.
IN PRACTICE:
“The results of this multicentre prospective study indicate that a no-biopsy approach for the diagnosis of coeliac disease is safe and reliable in adult patients without IgA deficiency and with serum tTG-IgA greater than the assay-specific upper limit of normal,” the authors write. “We found no evidence that important comorbidities would be missed by adopting a no-biopsy strategy.”
SOURCE:
The study was led by Carolina Ciacci, Centre for Coeliac Disease, AOU San Giovanni Di Dio e Ruggi d’Aragona, Salerno, Italy, and was published online in The Lancet Gastroenterology and Hepatology.
LIMITATIONS:
Limitations include a lack of data on IgA-deficient participants, a low number of participants in some subgroup analyses, a lack of data for many ethnic groups, limited follow-up information, limited assessments in the central laboratory, and high pretest probability of celiac disease (low number of participants without duodenal villous atrophy).
DISCLOSURES:
The study had no specific funding. One coauthor is an employee of Werfen. The other authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
TOPLINE:
For adults with suspected celiac disease who do not have immunoglobulin A (IgA) deficiency, diagnostic bowel biopsy can most likely be avoided if the serum antitissue transglutaminase IgA (tTG-IgA) level is high.
METHODOLOGY:
- Researchers evaluated the reliability of serum tests for diagnosing celiac disease, as defined by duodenal villous atrophy (Marsh type 3 or Corazza-Villanacci grade B).
- The main study cohort included 436 adults with suspected celiac disease who did not have IgA deficiency and who were not on a gluten-free diet (mean age, 40 years; 68% women). The patients were referred by 14 centers across four continents to undergo local endoscopic duodenal biopsy.
- Local serum tTG-IgA was measured with 14 test brands. Concentration was expressed as a multiple of each test’s upper limit of normal (ULN). Tests were defined as positive when they exceeded one times the ULN.
- Histology was assessed by the local pathologist, and discordant cases were reevaluated by a central pathologist.
TAKEAWAY:
- Positive serum tTG-IgA was detected in 363 (83%) participants; negative serum tTG-IgA was detected in 73 (17%).
- After local review, 341 of the participants with positive serum tTG-IgA had positive histology (true positives) and 22 had negative histology (false positives).
- Of the 73 participants with negative serum tTG-IgA, 66 had negative histology (true negatives) and 7 had positive histology (false negatives).
- Central reevaluation of duodenal histology was performed in 29 discordant cases, resulting in 348 true positive cases, 15 false positive cases, 66 true negative cases, and 7 false negative cases – the equivalent of a positive predictive value of 95.9%, a negative predictive value of 90.4%, a sensitivity of 98%, and a specificity of 81.5%.
- The positive predictive value of local serum tTG-IgA increased when the serologic threshold was defined at increasing multiples of the ULN. The test correctly diagnosed duodenal villous atrophy in 97.5% of patients with serum tTG-IgA concentrations greater than 10 times the ULN.
IN PRACTICE:
“The results of this multicentre prospective study indicate that a no-biopsy approach for the diagnosis of coeliac disease is safe and reliable in adult patients without IgA deficiency and with serum tTG-IgA greater than the assay-specific upper limit of normal,” the authors write. “We found no evidence that important comorbidities would be missed by adopting a no-biopsy strategy.”
SOURCE:
The study was led by Carolina Ciacci, Centre for Coeliac Disease, AOU San Giovanni Di Dio e Ruggi d’Aragona, Salerno, Italy, and was published online in The Lancet Gastroenterology and Hepatology.
LIMITATIONS:
Limitations include a lack of data on IgA-deficient participants, a low number of participants in some subgroup analyses, a lack of data for many ethnic groups, limited follow-up information, limited assessments in the central laboratory, and high pretest probability of celiac disease (low number of participants without duodenal villous atrophy).
DISCLOSURES:
The study had no specific funding. One coauthor is an employee of Werfen. The other authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
TOPLINE:
For adults with suspected celiac disease who do not have immunoglobulin A (IgA) deficiency, diagnostic bowel biopsy can most likely be avoided if the serum antitissue transglutaminase IgA (tTG-IgA) level is high.
METHODOLOGY:
- Researchers evaluated the reliability of serum tests for diagnosing celiac disease, as defined by duodenal villous atrophy (Marsh type 3 or Corazza-Villanacci grade B).
- The main study cohort included 436 adults with suspected celiac disease who did not have IgA deficiency and who were not on a gluten-free diet (mean age, 40 years; 68% women). The patients were referred by 14 centers across four continents to undergo local endoscopic duodenal biopsy.
- Local serum tTG-IgA was measured with 14 test brands. Concentration was expressed as a multiple of each test’s upper limit of normal (ULN). Tests were defined as positive when they exceeded one times the ULN.
- Histology was assessed by the local pathologist, and discordant cases were reevaluated by a central pathologist.
TAKEAWAY:
- Positive serum tTG-IgA was detected in 363 (83%) participants; negative serum tTG-IgA was detected in 73 (17%).
- After local review, 341 of the participants with positive serum tTG-IgA had positive histology (true positives) and 22 had negative histology (false positives).
- Of the 73 participants with negative serum tTG-IgA, 66 had negative histology (true negatives) and 7 had positive histology (false negatives).
- Central reevaluation of duodenal histology was performed in 29 discordant cases, resulting in 348 true positive cases, 15 false positive cases, 66 true negative cases, and 7 false negative cases – the equivalent of a positive predictive value of 95.9%, a negative predictive value of 90.4%, a sensitivity of 98%, and a specificity of 81.5%.
- The positive predictive value of local serum tTG-IgA increased when the serologic threshold was defined at increasing multiples of the ULN. The test correctly diagnosed duodenal villous atrophy in 97.5% of patients with serum tTG-IgA concentrations greater than 10 times the ULN.
IN PRACTICE:
“The results of this multicentre prospective study indicate that a no-biopsy approach for the diagnosis of coeliac disease is safe and reliable in adult patients without IgA deficiency and with serum tTG-IgA greater than the assay-specific upper limit of normal,” the authors write. “We found no evidence that important comorbidities would be missed by adopting a no-biopsy strategy.”
SOURCE:
The study was led by Carolina Ciacci, Centre for Coeliac Disease, AOU San Giovanni Di Dio e Ruggi d’Aragona, Salerno, Italy, and was published online in The Lancet Gastroenterology and Hepatology.
LIMITATIONS:
Limitations include a lack of data on IgA-deficient participants, a low number of participants in some subgroup analyses, a lack of data for many ethnic groups, limited follow-up information, limited assessments in the central laboratory, and high pretest probability of celiac disease (low number of participants without duodenal villous atrophy).
DISCLOSURES:
The study had no specific funding. One coauthor is an employee of Werfen. The other authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Fish oil labels make health claims, despite lack of data
Overall, about 74% of more than 2,800 supplements that were examined had labels that made at least one health claim, and only 19% included a U.S. Food and Drug Administration–reviewed qualified health claim (QHC).
The authors say “additional regulation” of the claims may be needed to prevent consumer misinformation. Notably, 20% of adults older than 60 years take fish oil supplements for heart health despite the fact that multiple randomized trials show no cardiovascular benefit.
“Based on what I’ve seen personally in the grocery store and pharmacy, I was not surprised to find such high rates of health claims on fish oil supplements,” lead author Joanna Assadourian, BSA, of UT Southwestern Medical Center, Dallas, said in an interview. “What was surprising, though, was just how broad the types of claims being made were – from heart and brain health to joint health, eye health, and immune function.”
Principal author Ann Marie Navar, MD, PhD, also of UT Southwestern, added, “As a preventive cardiologist, I tell my patients that if they are taking fish oil to try to avoid heart disease, then they can stop taking it because it’s not helping them. Their money would be better spent on something that will actually prevent a heart attack, like more fresh vegetables, their blood pressure or cholesterol medication, or a gym membership.”
The study was published online in JAMA Cardiology.
‘Vague statements’
To evaluate health claims made on fish oil supplement labels in the United States and to examine doses of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in commonly available formulations, the investigators analyzed labels on supplements obtained from the National Institutes of Health Dietary Supplement Label Database.
The main outcomes were the frequency and types of health claims made on the labels, including use of an FDA-reviewed QHC versus a structure/function claim and the organ system referenced, as well as the total daily doses in combined EPA and DHA supplements from leading manufacturers and retailers.
QHCs are statements regarding a supplement’s or food’s potential to treatment or prevent disease. Such claims undergo evidence review by the FDA and include qualifying language that reflects lack of scientific consensus or uncertainty.
An example: “Consuming EPA and DHA combined may reduce the risk of CHD [coronary heart disease] by lowering blood pressure. However, FDA has concluded that the evidence is inconsistent and inconclusive. One serving of [name of the food or dietary supplement] provides [ ] gram(s) of EPA and DHA.”
By contrast, structure/function claims “describe the role of a nutrient or dietary ingredient intended to affect the structure or function in humans” but do not state that the supplement prevents, treats, or cures any disease. Such a claim “does not require any mitigating language regarding potential scientific uncertainty of the statement.”
Structure/function claims commonly state that the supplement “maintains,” “supports,” or “promotes” the function of certain organs. Examples are “promotes heart health” and “supports heart, mind and mood.”
Among 2,819 fish oil supplements, 2,082 (73.9%) made at least one health claim. Of these, only 399 (19.2%) used a QHC; the rest made only structure/function claims. In addition to heart-health claims, many fish oil supplements also have labels that make claims implying benefit to other organ systems, such as brain/mental health, joint health, and eye health – despite a lack of data from randomized clinical trials that support benefit.
The dose analysis of 255 fish oil supplements across 16 major brands found “substantial variability” in the daily dose of EPA (median interquartile range, 340 [135-647] mg/d), DHA (median IQR, 270 [140-500] mg/d), and total EPA+DHA (median IQR, 600 [300-1,100] mg/d).
Twenty-four (9.4%) of the supplements contained a daily dose of 2 g or more EPA+DHA.
“Significant heterogeneity exists in the daily dose of EPA+DHA in available supplements, leading to potential variability in safety and efficacy between supplements,” the authors conclude. “Increasing regulation of dietary supplement labeling may be needed to prevent consumer misinformation.”
Dr. Navar added, “We now need to understand what consumers are taking away from vague statements like ‘promotes brain health’ or ‘supports joint function’ – and test what language we can use to accurately describe the state of the science around fish oil and heart health.”
Enthusiasm vs. evidence
“I agree with these concerns and think that the enthusiasm for these supplements outpaces the evidence from rigorous randomized clinical trials,” JoAnn E. Manson, MD, MPH, DrPH, chief of the Division of Preventive Medicine at Brigham and Women’s Hospital, Boston, said in an interview. “Results of the observational studies have tended to be much more favorable than the randomized clinical trials.
“The labels can be very misleading to the general public,” she noted. “People are confronted with a dizzying array of dietary supplements, many of which include structure/function claims that require minimal, if any, evidence of efficacy. Clinicians should emphasize with patients that a dietary supplement will never be a substitute for a heart-healthy diet and that many supplements are not helpful for people who already follow a healthy diet,” she said.
The VITAL trial, for which Dr. Manson was principal investigator, showed that supplementation with n-3 fatty acids did not lead to a lower incidence of major cardiovascular events or cancer, compared with placebo.
A subgroup analysis showed that 1 g/d conferred a 20% reduction in major events only for participants who ate less than 1.5 servings of fish per week, Dr. Manson said.
Regarding supplement labels, clinicians should recommend that patients look for a U.S. Pharmacopoeia seal or a seal from the National Science Foundation or ConsumerLab, she advised. These seals ensure that the product has been audited for purity and consistency of content and that the dose in the capsule is consistent with what is on the label.
Dr. Manson also would like to see labels explain that most of the products have not been reviewed by the FDA. “Many members of the general public are misled by these labels into thinking that they’re going to receive health benefits. They’re spending a lot of money on supplements that likely provide no benefit and may even be associated with increased risks.”
No funding for the study was reported. Dr. Navar has received grants from BMS, Esperion, Amgen, and Janssen and personal fees from AstraZeneca, Boehringer Ingelheim, Bayer, BMS, Esperion, Janssen, Eli Lilly, Merck, Silence Therapeutics, Novo Nordisk, Novartis, New Amsterdam, and Pfizer outside the submitted work and serves as deputy editor for equity, diversity, and inclusion at JAMA Cardiology.
A version of this article first appeared on Medscape.com.
Overall, about 74% of more than 2,800 supplements that were examined had labels that made at least one health claim, and only 19% included a U.S. Food and Drug Administration–reviewed qualified health claim (QHC).
The authors say “additional regulation” of the claims may be needed to prevent consumer misinformation. Notably, 20% of adults older than 60 years take fish oil supplements for heart health despite the fact that multiple randomized trials show no cardiovascular benefit.
“Based on what I’ve seen personally in the grocery store and pharmacy, I was not surprised to find such high rates of health claims on fish oil supplements,” lead author Joanna Assadourian, BSA, of UT Southwestern Medical Center, Dallas, said in an interview. “What was surprising, though, was just how broad the types of claims being made were – from heart and brain health to joint health, eye health, and immune function.”
Principal author Ann Marie Navar, MD, PhD, also of UT Southwestern, added, “As a preventive cardiologist, I tell my patients that if they are taking fish oil to try to avoid heart disease, then they can stop taking it because it’s not helping them. Their money would be better spent on something that will actually prevent a heart attack, like more fresh vegetables, their blood pressure or cholesterol medication, or a gym membership.”
The study was published online in JAMA Cardiology.
‘Vague statements’
To evaluate health claims made on fish oil supplement labels in the United States and to examine doses of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in commonly available formulations, the investigators analyzed labels on supplements obtained from the National Institutes of Health Dietary Supplement Label Database.
The main outcomes were the frequency and types of health claims made on the labels, including use of an FDA-reviewed QHC versus a structure/function claim and the organ system referenced, as well as the total daily doses in combined EPA and DHA supplements from leading manufacturers and retailers.
QHCs are statements regarding a supplement’s or food’s potential to treatment or prevent disease. Such claims undergo evidence review by the FDA and include qualifying language that reflects lack of scientific consensus or uncertainty.
An example: “Consuming EPA and DHA combined may reduce the risk of CHD [coronary heart disease] by lowering blood pressure. However, FDA has concluded that the evidence is inconsistent and inconclusive. One serving of [name of the food or dietary supplement] provides [ ] gram(s) of EPA and DHA.”
By contrast, structure/function claims “describe the role of a nutrient or dietary ingredient intended to affect the structure or function in humans” but do not state that the supplement prevents, treats, or cures any disease. Such a claim “does not require any mitigating language regarding potential scientific uncertainty of the statement.”
Structure/function claims commonly state that the supplement “maintains,” “supports,” or “promotes” the function of certain organs. Examples are “promotes heart health” and “supports heart, mind and mood.”
Among 2,819 fish oil supplements, 2,082 (73.9%) made at least one health claim. Of these, only 399 (19.2%) used a QHC; the rest made only structure/function claims. In addition to heart-health claims, many fish oil supplements also have labels that make claims implying benefit to other organ systems, such as brain/mental health, joint health, and eye health – despite a lack of data from randomized clinical trials that support benefit.
The dose analysis of 255 fish oil supplements across 16 major brands found “substantial variability” in the daily dose of EPA (median interquartile range, 340 [135-647] mg/d), DHA (median IQR, 270 [140-500] mg/d), and total EPA+DHA (median IQR, 600 [300-1,100] mg/d).
Twenty-four (9.4%) of the supplements contained a daily dose of 2 g or more EPA+DHA.
“Significant heterogeneity exists in the daily dose of EPA+DHA in available supplements, leading to potential variability in safety and efficacy between supplements,” the authors conclude. “Increasing regulation of dietary supplement labeling may be needed to prevent consumer misinformation.”
Dr. Navar added, “We now need to understand what consumers are taking away from vague statements like ‘promotes brain health’ or ‘supports joint function’ – and test what language we can use to accurately describe the state of the science around fish oil and heart health.”
Enthusiasm vs. evidence
“I agree with these concerns and think that the enthusiasm for these supplements outpaces the evidence from rigorous randomized clinical trials,” JoAnn E. Manson, MD, MPH, DrPH, chief of the Division of Preventive Medicine at Brigham and Women’s Hospital, Boston, said in an interview. “Results of the observational studies have tended to be much more favorable than the randomized clinical trials.
“The labels can be very misleading to the general public,” she noted. “People are confronted with a dizzying array of dietary supplements, many of which include structure/function claims that require minimal, if any, evidence of efficacy. Clinicians should emphasize with patients that a dietary supplement will never be a substitute for a heart-healthy diet and that many supplements are not helpful for people who already follow a healthy diet,” she said.
The VITAL trial, for which Dr. Manson was principal investigator, showed that supplementation with n-3 fatty acids did not lead to a lower incidence of major cardiovascular events or cancer, compared with placebo.
A subgroup analysis showed that 1 g/d conferred a 20% reduction in major events only for participants who ate less than 1.5 servings of fish per week, Dr. Manson said.
Regarding supplement labels, clinicians should recommend that patients look for a U.S. Pharmacopoeia seal or a seal from the National Science Foundation or ConsumerLab, she advised. These seals ensure that the product has been audited for purity and consistency of content and that the dose in the capsule is consistent with what is on the label.
Dr. Manson also would like to see labels explain that most of the products have not been reviewed by the FDA. “Many members of the general public are misled by these labels into thinking that they’re going to receive health benefits. They’re spending a lot of money on supplements that likely provide no benefit and may even be associated with increased risks.”
No funding for the study was reported. Dr. Navar has received grants from BMS, Esperion, Amgen, and Janssen and personal fees from AstraZeneca, Boehringer Ingelheim, Bayer, BMS, Esperion, Janssen, Eli Lilly, Merck, Silence Therapeutics, Novo Nordisk, Novartis, New Amsterdam, and Pfizer outside the submitted work and serves as deputy editor for equity, diversity, and inclusion at JAMA Cardiology.
A version of this article first appeared on Medscape.com.
Overall, about 74% of more than 2,800 supplements that were examined had labels that made at least one health claim, and only 19% included a U.S. Food and Drug Administration–reviewed qualified health claim (QHC).
The authors say “additional regulation” of the claims may be needed to prevent consumer misinformation. Notably, 20% of adults older than 60 years take fish oil supplements for heart health despite the fact that multiple randomized trials show no cardiovascular benefit.
“Based on what I’ve seen personally in the grocery store and pharmacy, I was not surprised to find such high rates of health claims on fish oil supplements,” lead author Joanna Assadourian, BSA, of UT Southwestern Medical Center, Dallas, said in an interview. “What was surprising, though, was just how broad the types of claims being made were – from heart and brain health to joint health, eye health, and immune function.”
Principal author Ann Marie Navar, MD, PhD, also of UT Southwestern, added, “As a preventive cardiologist, I tell my patients that if they are taking fish oil to try to avoid heart disease, then they can stop taking it because it’s not helping them. Their money would be better spent on something that will actually prevent a heart attack, like more fresh vegetables, their blood pressure or cholesterol medication, or a gym membership.”
The study was published online in JAMA Cardiology.
‘Vague statements’
To evaluate health claims made on fish oil supplement labels in the United States and to examine doses of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in commonly available formulations, the investigators analyzed labels on supplements obtained from the National Institutes of Health Dietary Supplement Label Database.
The main outcomes were the frequency and types of health claims made on the labels, including use of an FDA-reviewed QHC versus a structure/function claim and the organ system referenced, as well as the total daily doses in combined EPA and DHA supplements from leading manufacturers and retailers.
QHCs are statements regarding a supplement’s or food’s potential to treatment or prevent disease. Such claims undergo evidence review by the FDA and include qualifying language that reflects lack of scientific consensus or uncertainty.
An example: “Consuming EPA and DHA combined may reduce the risk of CHD [coronary heart disease] by lowering blood pressure. However, FDA has concluded that the evidence is inconsistent and inconclusive. One serving of [name of the food or dietary supplement] provides [ ] gram(s) of EPA and DHA.”
By contrast, structure/function claims “describe the role of a nutrient or dietary ingredient intended to affect the structure or function in humans” but do not state that the supplement prevents, treats, or cures any disease. Such a claim “does not require any mitigating language regarding potential scientific uncertainty of the statement.”
Structure/function claims commonly state that the supplement “maintains,” “supports,” or “promotes” the function of certain organs. Examples are “promotes heart health” and “supports heart, mind and mood.”
Among 2,819 fish oil supplements, 2,082 (73.9%) made at least one health claim. Of these, only 399 (19.2%) used a QHC; the rest made only structure/function claims. In addition to heart-health claims, many fish oil supplements also have labels that make claims implying benefit to other organ systems, such as brain/mental health, joint health, and eye health – despite a lack of data from randomized clinical trials that support benefit.
The dose analysis of 255 fish oil supplements across 16 major brands found “substantial variability” in the daily dose of EPA (median interquartile range, 340 [135-647] mg/d), DHA (median IQR, 270 [140-500] mg/d), and total EPA+DHA (median IQR, 600 [300-1,100] mg/d).
Twenty-four (9.4%) of the supplements contained a daily dose of 2 g or more EPA+DHA.
“Significant heterogeneity exists in the daily dose of EPA+DHA in available supplements, leading to potential variability in safety and efficacy between supplements,” the authors conclude. “Increasing regulation of dietary supplement labeling may be needed to prevent consumer misinformation.”
Dr. Navar added, “We now need to understand what consumers are taking away from vague statements like ‘promotes brain health’ or ‘supports joint function’ – and test what language we can use to accurately describe the state of the science around fish oil and heart health.”
Enthusiasm vs. evidence
“I agree with these concerns and think that the enthusiasm for these supplements outpaces the evidence from rigorous randomized clinical trials,” JoAnn E. Manson, MD, MPH, DrPH, chief of the Division of Preventive Medicine at Brigham and Women’s Hospital, Boston, said in an interview. “Results of the observational studies have tended to be much more favorable than the randomized clinical trials.
“The labels can be very misleading to the general public,” she noted. “People are confronted with a dizzying array of dietary supplements, many of which include structure/function claims that require minimal, if any, evidence of efficacy. Clinicians should emphasize with patients that a dietary supplement will never be a substitute for a heart-healthy diet and that many supplements are not helpful for people who already follow a healthy diet,” she said.
The VITAL trial, for which Dr. Manson was principal investigator, showed that supplementation with n-3 fatty acids did not lead to a lower incidence of major cardiovascular events or cancer, compared with placebo.
A subgroup analysis showed that 1 g/d conferred a 20% reduction in major events only for participants who ate less than 1.5 servings of fish per week, Dr. Manson said.
Regarding supplement labels, clinicians should recommend that patients look for a U.S. Pharmacopoeia seal or a seal from the National Science Foundation or ConsumerLab, she advised. These seals ensure that the product has been audited for purity and consistency of content and that the dose in the capsule is consistent with what is on the label.
Dr. Manson also would like to see labels explain that most of the products have not been reviewed by the FDA. “Many members of the general public are misled by these labels into thinking that they’re going to receive health benefits. They’re spending a lot of money on supplements that likely provide no benefit and may even be associated with increased risks.”
No funding for the study was reported. Dr. Navar has received grants from BMS, Esperion, Amgen, and Janssen and personal fees from AstraZeneca, Boehringer Ingelheim, Bayer, BMS, Esperion, Janssen, Eli Lilly, Merck, Silence Therapeutics, Novo Nordisk, Novartis, New Amsterdam, and Pfizer outside the submitted work and serves as deputy editor for equity, diversity, and inclusion at JAMA Cardiology.
A version of this article first appeared on Medscape.com.
FROM JAMA CARDIOLOGY