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Cognitive benefit of highly touted MIND diet questioned
in healthy adults at risk for dementia, results of a new randomized trial show.
Given the strong base of evidence from observational studies that demonstrate the benefits of the MIND diet on cognitive decline, Alzheimer’s disease (AD), and neuropathologic changes such as reduced beta amyloid and tau associated with AD, the study’s results were “unexpected,” study investigator Lisa L. Barnes, PhD, with the Rush Alzheimer’s Disease Center, Chicago, said in an interview.
“One possibility is the trial may not have been long enough to see an effect. It’s also possible that participants in the control diet group benefited just as much as those in the MIND diet group because they also improved their diets to focus on weight loss,” Dr. Barnes said.
“Although we did not see a specific effect of the MIND diet, people in both groups improved their cognitive function, suggesting that a healthy diet in general is good for cognitive function,” she added.
The findings were presented at the annual Alzheimer’s Association International Conference and simultaneously published online in the New England Journal of Medicine.
Randomized trial
A hybrid of the Dietary Approaches to Stop Hypertension (DASH) and Mediterranean diet, the MIND diet includes foods and nutrients that have been putatively associated with a decreased risk of dementia.
To further investigate, the researchers conducted a randomized trial that included 604 older adults without cognitive impairment who had a family history of dementia, a body mass index greater than 25, and a suboptimal diet determined via a 14-item questionnaire.
For 3 years, 301 were randomly assigned to follow the MIND-diet with mild calorie restriction and 303 to follow a control diet with mild calorie restriction only. All participants received counseling to help them adhere to their assigned diet, plus support to promote weight loss of 3%-5% by year 3.
The primary endpoint was the change from baseline in global cognition and in specific cognitive domains through year 3. Cognition was assessed with an established battery of 12 publicly available cognitive function tests.
The secondary endpoint was the change from baseline in MRI-derived measures of brain characteristics in a nonrandom sample of participants.
“We had good adherence to the assigned diets and both groups lost weight, on average about 5 kilograms in both groups,” Dr. Barnes noted in her presentation.
From baseline through 3 years, small improvements in global cognition scores were observed in both groups, with increases of 0.205 standardized units in the MIND-diet group versus 0.170 standardized units in the control-diet group.
However, in intention-to-treat analysis, the mean change in score did not differ significantly between groups, with an estimated mean difference at the end of the trial of 0.035 standardized units (P = .23).
At the trial’s conclusion, there were also no between-group differences in change in white-matter hyperintensities, hippocampal volumes, and total gray- and white-matter volumes on MRI.
Dr. Barnes noted that the trial was limited to well-educated, older adults, mostly of European descent. Other limitations include the small sample size of those who received MRI and follow-up that was shorter than a typical observational study.
Dr. Barnes noted that this is a single study and that there needs to be more randomized trials of the MIND diet that, as with the observational research, follow participants for a longer period of time.
More to brain health than diet
Reached for comment, Majid Fotuhi, MD, PhD, adjunct professor of neuroscience at George Washington University, Washington, noted that participants who enroll in clinical trials that focus on diet become more aware of their eating habits and shift toward a healthier diet.
“This may explain the reason why both groups of participants in this study improved,” said Dr. Fotuhi, medical director of NeuroGrow Brain Fitness Center, McLean, Va.
However, he believes that better brain health requires a multipronged approach.
“In order to see significant results, people need to improve their diet, become physically fit, sleep well, reduce their stress, engage in cognitively challenging activities, and develop a positive mind set,” said Dr. Fotuhi.
“Interventions that target only one of these goals may not produce results that are as remarkable as multimodal programs, which target all of these goals,” Dr. Fotuhi said.
Dr. Fotuhi developed a multidimensional “brain fitness program” that has shown to provide multiple benefits for individuals with memory loss, attention deficit hyperactivity disorder, and post-concussion syndrome.
“Having provided our 12-week program for thousands of patients in the past 10 years, I have noticed a synergistic effect in patients who incorporate all of these changes in their day-to-day life and maintain it over time. They often become sharper and feel better overall,” Dr. Fotuhi told this news organization.
The study was supported by the National Institute on Aging. Disclosures for study authors are listed with the original article. Dr. Fotuhi has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
in healthy adults at risk for dementia, results of a new randomized trial show.
Given the strong base of evidence from observational studies that demonstrate the benefits of the MIND diet on cognitive decline, Alzheimer’s disease (AD), and neuropathologic changes such as reduced beta amyloid and tau associated with AD, the study’s results were “unexpected,” study investigator Lisa L. Barnes, PhD, with the Rush Alzheimer’s Disease Center, Chicago, said in an interview.
“One possibility is the trial may not have been long enough to see an effect. It’s also possible that participants in the control diet group benefited just as much as those in the MIND diet group because they also improved their diets to focus on weight loss,” Dr. Barnes said.
“Although we did not see a specific effect of the MIND diet, people in both groups improved their cognitive function, suggesting that a healthy diet in general is good for cognitive function,” she added.
The findings were presented at the annual Alzheimer’s Association International Conference and simultaneously published online in the New England Journal of Medicine.
Randomized trial
A hybrid of the Dietary Approaches to Stop Hypertension (DASH) and Mediterranean diet, the MIND diet includes foods and nutrients that have been putatively associated with a decreased risk of dementia.
To further investigate, the researchers conducted a randomized trial that included 604 older adults without cognitive impairment who had a family history of dementia, a body mass index greater than 25, and a suboptimal diet determined via a 14-item questionnaire.
For 3 years, 301 were randomly assigned to follow the MIND-diet with mild calorie restriction and 303 to follow a control diet with mild calorie restriction only. All participants received counseling to help them adhere to their assigned diet, plus support to promote weight loss of 3%-5% by year 3.
The primary endpoint was the change from baseline in global cognition and in specific cognitive domains through year 3. Cognition was assessed with an established battery of 12 publicly available cognitive function tests.
The secondary endpoint was the change from baseline in MRI-derived measures of brain characteristics in a nonrandom sample of participants.
“We had good adherence to the assigned diets and both groups lost weight, on average about 5 kilograms in both groups,” Dr. Barnes noted in her presentation.
From baseline through 3 years, small improvements in global cognition scores were observed in both groups, with increases of 0.205 standardized units in the MIND-diet group versus 0.170 standardized units in the control-diet group.
However, in intention-to-treat analysis, the mean change in score did not differ significantly between groups, with an estimated mean difference at the end of the trial of 0.035 standardized units (P = .23).
At the trial’s conclusion, there were also no between-group differences in change in white-matter hyperintensities, hippocampal volumes, and total gray- and white-matter volumes on MRI.
Dr. Barnes noted that the trial was limited to well-educated, older adults, mostly of European descent. Other limitations include the small sample size of those who received MRI and follow-up that was shorter than a typical observational study.
Dr. Barnes noted that this is a single study and that there needs to be more randomized trials of the MIND diet that, as with the observational research, follow participants for a longer period of time.
More to brain health than diet
Reached for comment, Majid Fotuhi, MD, PhD, adjunct professor of neuroscience at George Washington University, Washington, noted that participants who enroll in clinical trials that focus on diet become more aware of their eating habits and shift toward a healthier diet.
“This may explain the reason why both groups of participants in this study improved,” said Dr. Fotuhi, medical director of NeuroGrow Brain Fitness Center, McLean, Va.
However, he believes that better brain health requires a multipronged approach.
“In order to see significant results, people need to improve their diet, become physically fit, sleep well, reduce their stress, engage in cognitively challenging activities, and develop a positive mind set,” said Dr. Fotuhi.
“Interventions that target only one of these goals may not produce results that are as remarkable as multimodal programs, which target all of these goals,” Dr. Fotuhi said.
Dr. Fotuhi developed a multidimensional “brain fitness program” that has shown to provide multiple benefits for individuals with memory loss, attention deficit hyperactivity disorder, and post-concussion syndrome.
“Having provided our 12-week program for thousands of patients in the past 10 years, I have noticed a synergistic effect in patients who incorporate all of these changes in their day-to-day life and maintain it over time. They often become sharper and feel better overall,” Dr. Fotuhi told this news organization.
The study was supported by the National Institute on Aging. Disclosures for study authors are listed with the original article. Dr. Fotuhi has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
in healthy adults at risk for dementia, results of a new randomized trial show.
Given the strong base of evidence from observational studies that demonstrate the benefits of the MIND diet on cognitive decline, Alzheimer’s disease (AD), and neuropathologic changes such as reduced beta amyloid and tau associated with AD, the study’s results were “unexpected,” study investigator Lisa L. Barnes, PhD, with the Rush Alzheimer’s Disease Center, Chicago, said in an interview.
“One possibility is the trial may not have been long enough to see an effect. It’s also possible that participants in the control diet group benefited just as much as those in the MIND diet group because they also improved their diets to focus on weight loss,” Dr. Barnes said.
“Although we did not see a specific effect of the MIND diet, people in both groups improved their cognitive function, suggesting that a healthy diet in general is good for cognitive function,” she added.
The findings were presented at the annual Alzheimer’s Association International Conference and simultaneously published online in the New England Journal of Medicine.
Randomized trial
A hybrid of the Dietary Approaches to Stop Hypertension (DASH) and Mediterranean diet, the MIND diet includes foods and nutrients that have been putatively associated with a decreased risk of dementia.
To further investigate, the researchers conducted a randomized trial that included 604 older adults without cognitive impairment who had a family history of dementia, a body mass index greater than 25, and a suboptimal diet determined via a 14-item questionnaire.
For 3 years, 301 were randomly assigned to follow the MIND-diet with mild calorie restriction and 303 to follow a control diet with mild calorie restriction only. All participants received counseling to help them adhere to their assigned diet, plus support to promote weight loss of 3%-5% by year 3.
The primary endpoint was the change from baseline in global cognition and in specific cognitive domains through year 3. Cognition was assessed with an established battery of 12 publicly available cognitive function tests.
The secondary endpoint was the change from baseline in MRI-derived measures of brain characteristics in a nonrandom sample of participants.
“We had good adherence to the assigned diets and both groups lost weight, on average about 5 kilograms in both groups,” Dr. Barnes noted in her presentation.
From baseline through 3 years, small improvements in global cognition scores were observed in both groups, with increases of 0.205 standardized units in the MIND-diet group versus 0.170 standardized units in the control-diet group.
However, in intention-to-treat analysis, the mean change in score did not differ significantly between groups, with an estimated mean difference at the end of the trial of 0.035 standardized units (P = .23).
At the trial’s conclusion, there were also no between-group differences in change in white-matter hyperintensities, hippocampal volumes, and total gray- and white-matter volumes on MRI.
Dr. Barnes noted that the trial was limited to well-educated, older adults, mostly of European descent. Other limitations include the small sample size of those who received MRI and follow-up that was shorter than a typical observational study.
Dr. Barnes noted that this is a single study and that there needs to be more randomized trials of the MIND diet that, as with the observational research, follow participants for a longer period of time.
More to brain health than diet
Reached for comment, Majid Fotuhi, MD, PhD, adjunct professor of neuroscience at George Washington University, Washington, noted that participants who enroll in clinical trials that focus on diet become more aware of their eating habits and shift toward a healthier diet.
“This may explain the reason why both groups of participants in this study improved,” said Dr. Fotuhi, medical director of NeuroGrow Brain Fitness Center, McLean, Va.
However, he believes that better brain health requires a multipronged approach.
“In order to see significant results, people need to improve their diet, become physically fit, sleep well, reduce their stress, engage in cognitively challenging activities, and develop a positive mind set,” said Dr. Fotuhi.
“Interventions that target only one of these goals may not produce results that are as remarkable as multimodal programs, which target all of these goals,” Dr. Fotuhi said.
Dr. Fotuhi developed a multidimensional “brain fitness program” that has shown to provide multiple benefits for individuals with memory loss, attention deficit hyperactivity disorder, and post-concussion syndrome.
“Having provided our 12-week program for thousands of patients in the past 10 years, I have noticed a synergistic effect in patients who incorporate all of these changes in their day-to-day life and maintain it over time. They often become sharper and feel better overall,” Dr. Fotuhi told this news organization.
The study was supported by the National Institute on Aging. Disclosures for study authors are listed with the original article. Dr. Fotuhi has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AAIC 2023
Omega-3s and AFib: No added risk from eating fish but high-dose supplement questions persist
Regular consumption of fish and other foods rich in omega-3 fatty acids (FA) won’t raise an individual’s risk for developing atrial fibrillation (AFib), suggests a meta-analysis of population-based studies.
The finding may alleviate recent concerns about higher-dose omega-3 FA supplement intake in clinical-trial patients at elevated cardiovascular (CV) risk, researchers say.
Indeed, across the 17 cohort studies in the meta-analysis, risk for incident AFib was unaffected by elevated circulating and adipose tissue levels of eicosapentaenoic acid (EPA) from dietary intake. Moreover, the risk appeared to drop significantly with such levels of docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and EPA plus DHA.
The signals of AFib risk associated with high-dose omega-3 FA in supplements or prescription form in some clinical trials “may not necessarily be generalizable to lower-dose habitual dietary omega-3 intakes,” concludes the study’s report published in the Journal of the American College of Cardiology.
Other recent research suggests that any elevated AFib risk from omega-3 FA intake is dose-related and may be associated with omega-3 FA supplement or medication intake in high doses, such as 4 g/day.
“Coupled with the more consistent benefits of these fatty acids in the prevention of adverse coronary events, our study suggests that current dietary guidelines recommending fish/omega-3 fatty acid consumption should be maintained,” conclude the authors of the report, led by Frank Qian, MD, MPH, Harvard T.H. Chan School of Public Health and Beth Israel Deaconess Medical Center, Boston.
The current study is “important in showing that physiologic levels of omega-3s that would accumulate through diet don’t seem to increase the risk of arrhythmia,” preventive cardiologist Sean Heffron, MD, NYU Langone Health and Grossman School of Medicine, told this news organization.
“It also lends credence to the fact that the increased risk is specific to the high dose supplementation, because that’s the only instance in which we’ve seen increased atrial fibrillation in association with omega-3s,” said Dr. Heffron, who wasn’t involved in the meta-analysis.
An accompanying editorial agrees. “Based on present evidence, moderate dietary intake of fish and seafood is unlikely to achieve sufficiently high levels of omega-3-FAs in blood or tissue that would result in increased AFib risk as observed in clinical trials of fish oil supplements and high-dose prescriptions,” write Christie Ballantyne, MD, and Xiaoming Jia, MD, Baylor College of Medicine, Houston.
Therefore, they conclude, “fish should continue to be an important part of the menu of a heart-healthy diet.”
The meta-analysis comprised 54,799 participants from 21 countries worldwide in 17 prospective cohort studies that yielded data on incident AFib, in which there were 7,720 cases of the arrhythmia over a median follow-up of 13 years. It looked at associations between such cases and levels of omega-3 FA in blood and adipose tissue samples.
In multivariable analysis, EPA levels were not associated with incident AFib, with a hazard ratio of 1.00 (95% confidence interval, 0.95-1.05) per interquintile range, which the report describes as the difference between the 90th and 10th percentiles.
In contrast, levels of DPA, DHA, and EPA plus DHA were all associated with reduced AFib incidence at interquintile-range HRs of 0.89 (95% CI, 0.83-0.95) for DPA, 0.90 (95% CI, 0.85-0.96) for DHA and 0.93 (95% CI, 0.87-0.99) for EPA and DHA combined.
“We found little evidence that the associations significantly varied by age, sex, or global region, or across the various lipid compartments,” the report states. “Moreover, the relationship between omega-3 fatty acids and AFib did not significantly differ among individuals at higher CV risk.”
The authors observe that the prevalence of omega-3 FA supplement use in the cohorts was very low, suggesting that the omega-3 FA biomarker levels largely reflected habitual dietary intake.
Most of the meta-analysis population were free of CV disease or at relatively low CV risk, they write, and “it is conceivable that the effects of omega-3 fatty acids on atrial arrhythmias may differ in those with existing CV disease versus without.”
However, they note, in a prespecified subgroup analysis of participants mirroring the REDUCE-IT cohort of people with established CV disease or at elevated CV risk, no association with incident AFib was observed for EPA and inverse associations emerged for DPA, DHA, and EPA plus DHA.
In their editorial, Dr. Ballantyne and Dr. Jia say the meta-analysis “represents the largest epidemiological study assessing laboratory-measured omega-3 fatty acid concentrations and AFib risk in the general population.”
But significant heterogeneity across the studies and their populations is a major limitation of the analysis, they write, and made for differences in protocols, sample preparation, outcomes ascertainment, follow-up time, and other variables.
“Despite a rigorous approach to harmonize the data across cohorts and adjusting for multiple confounders,” note Dr. Ballantyne and Dr. Jia, “observational studies always have potential for residual confounders.”
The findings support fish consumption as heart-healthy, they write, but “clinicians should be aware of and discuss with patients the risks versus benefits when prescribing high-dose omega-3 FA therapies.”
The Fatty Acid Research Institute retrospectively provided a small honorarium to a subset of the analysts who participated in this study, but it had no role in its design, analysis, manuscript writing, or decision to submit for publication, the report states. Dr. Ballantyne received grant/research support through his institution from Akcea, Amgen, Arrowhead, Esperion, Ionis, Merck, Novartis, and Regeneron, as well as consulting fees from Alnylam Pharmaceuticals, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Esperion, Genentech, Gilead, Matinas BioPharma, Merck, New Amsterdam, Novartis, Pfizer, and Regeneron. Dr. Heffron and Dr. Jia have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Regular consumption of fish and other foods rich in omega-3 fatty acids (FA) won’t raise an individual’s risk for developing atrial fibrillation (AFib), suggests a meta-analysis of population-based studies.
The finding may alleviate recent concerns about higher-dose omega-3 FA supplement intake in clinical-trial patients at elevated cardiovascular (CV) risk, researchers say.
Indeed, across the 17 cohort studies in the meta-analysis, risk for incident AFib was unaffected by elevated circulating and adipose tissue levels of eicosapentaenoic acid (EPA) from dietary intake. Moreover, the risk appeared to drop significantly with such levels of docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and EPA plus DHA.
The signals of AFib risk associated with high-dose omega-3 FA in supplements or prescription form in some clinical trials “may not necessarily be generalizable to lower-dose habitual dietary omega-3 intakes,” concludes the study’s report published in the Journal of the American College of Cardiology.
Other recent research suggests that any elevated AFib risk from omega-3 FA intake is dose-related and may be associated with omega-3 FA supplement or medication intake in high doses, such as 4 g/day.
“Coupled with the more consistent benefits of these fatty acids in the prevention of adverse coronary events, our study suggests that current dietary guidelines recommending fish/omega-3 fatty acid consumption should be maintained,” conclude the authors of the report, led by Frank Qian, MD, MPH, Harvard T.H. Chan School of Public Health and Beth Israel Deaconess Medical Center, Boston.
The current study is “important in showing that physiologic levels of omega-3s that would accumulate through diet don’t seem to increase the risk of arrhythmia,” preventive cardiologist Sean Heffron, MD, NYU Langone Health and Grossman School of Medicine, told this news organization.
“It also lends credence to the fact that the increased risk is specific to the high dose supplementation, because that’s the only instance in which we’ve seen increased atrial fibrillation in association with omega-3s,” said Dr. Heffron, who wasn’t involved in the meta-analysis.
An accompanying editorial agrees. “Based on present evidence, moderate dietary intake of fish and seafood is unlikely to achieve sufficiently high levels of omega-3-FAs in blood or tissue that would result in increased AFib risk as observed in clinical trials of fish oil supplements and high-dose prescriptions,” write Christie Ballantyne, MD, and Xiaoming Jia, MD, Baylor College of Medicine, Houston.
Therefore, they conclude, “fish should continue to be an important part of the menu of a heart-healthy diet.”
The meta-analysis comprised 54,799 participants from 21 countries worldwide in 17 prospective cohort studies that yielded data on incident AFib, in which there were 7,720 cases of the arrhythmia over a median follow-up of 13 years. It looked at associations between such cases and levels of omega-3 FA in blood and adipose tissue samples.
In multivariable analysis, EPA levels were not associated with incident AFib, with a hazard ratio of 1.00 (95% confidence interval, 0.95-1.05) per interquintile range, which the report describes as the difference between the 90th and 10th percentiles.
In contrast, levels of DPA, DHA, and EPA plus DHA were all associated with reduced AFib incidence at interquintile-range HRs of 0.89 (95% CI, 0.83-0.95) for DPA, 0.90 (95% CI, 0.85-0.96) for DHA and 0.93 (95% CI, 0.87-0.99) for EPA and DHA combined.
“We found little evidence that the associations significantly varied by age, sex, or global region, or across the various lipid compartments,” the report states. “Moreover, the relationship between omega-3 fatty acids and AFib did not significantly differ among individuals at higher CV risk.”
The authors observe that the prevalence of omega-3 FA supplement use in the cohorts was very low, suggesting that the omega-3 FA biomarker levels largely reflected habitual dietary intake.
Most of the meta-analysis population were free of CV disease or at relatively low CV risk, they write, and “it is conceivable that the effects of omega-3 fatty acids on atrial arrhythmias may differ in those with existing CV disease versus without.”
However, they note, in a prespecified subgroup analysis of participants mirroring the REDUCE-IT cohort of people with established CV disease or at elevated CV risk, no association with incident AFib was observed for EPA and inverse associations emerged for DPA, DHA, and EPA plus DHA.
In their editorial, Dr. Ballantyne and Dr. Jia say the meta-analysis “represents the largest epidemiological study assessing laboratory-measured omega-3 fatty acid concentrations and AFib risk in the general population.”
But significant heterogeneity across the studies and their populations is a major limitation of the analysis, they write, and made for differences in protocols, sample preparation, outcomes ascertainment, follow-up time, and other variables.
“Despite a rigorous approach to harmonize the data across cohorts and adjusting for multiple confounders,” note Dr. Ballantyne and Dr. Jia, “observational studies always have potential for residual confounders.”
The findings support fish consumption as heart-healthy, they write, but “clinicians should be aware of and discuss with patients the risks versus benefits when prescribing high-dose omega-3 FA therapies.”
The Fatty Acid Research Institute retrospectively provided a small honorarium to a subset of the analysts who participated in this study, but it had no role in its design, analysis, manuscript writing, or decision to submit for publication, the report states. Dr. Ballantyne received grant/research support through his institution from Akcea, Amgen, Arrowhead, Esperion, Ionis, Merck, Novartis, and Regeneron, as well as consulting fees from Alnylam Pharmaceuticals, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Esperion, Genentech, Gilead, Matinas BioPharma, Merck, New Amsterdam, Novartis, Pfizer, and Regeneron. Dr. Heffron and Dr. Jia have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Regular consumption of fish and other foods rich in omega-3 fatty acids (FA) won’t raise an individual’s risk for developing atrial fibrillation (AFib), suggests a meta-analysis of population-based studies.
The finding may alleviate recent concerns about higher-dose omega-3 FA supplement intake in clinical-trial patients at elevated cardiovascular (CV) risk, researchers say.
Indeed, across the 17 cohort studies in the meta-analysis, risk for incident AFib was unaffected by elevated circulating and adipose tissue levels of eicosapentaenoic acid (EPA) from dietary intake. Moreover, the risk appeared to drop significantly with such levels of docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and EPA plus DHA.
The signals of AFib risk associated with high-dose omega-3 FA in supplements or prescription form in some clinical trials “may not necessarily be generalizable to lower-dose habitual dietary omega-3 intakes,” concludes the study’s report published in the Journal of the American College of Cardiology.
Other recent research suggests that any elevated AFib risk from omega-3 FA intake is dose-related and may be associated with omega-3 FA supplement or medication intake in high doses, such as 4 g/day.
“Coupled with the more consistent benefits of these fatty acids in the prevention of adverse coronary events, our study suggests that current dietary guidelines recommending fish/omega-3 fatty acid consumption should be maintained,” conclude the authors of the report, led by Frank Qian, MD, MPH, Harvard T.H. Chan School of Public Health and Beth Israel Deaconess Medical Center, Boston.
The current study is “important in showing that physiologic levels of omega-3s that would accumulate through diet don’t seem to increase the risk of arrhythmia,” preventive cardiologist Sean Heffron, MD, NYU Langone Health and Grossman School of Medicine, told this news organization.
“It also lends credence to the fact that the increased risk is specific to the high dose supplementation, because that’s the only instance in which we’ve seen increased atrial fibrillation in association with omega-3s,” said Dr. Heffron, who wasn’t involved in the meta-analysis.
An accompanying editorial agrees. “Based on present evidence, moderate dietary intake of fish and seafood is unlikely to achieve sufficiently high levels of omega-3-FAs in blood or tissue that would result in increased AFib risk as observed in clinical trials of fish oil supplements and high-dose prescriptions,” write Christie Ballantyne, MD, and Xiaoming Jia, MD, Baylor College of Medicine, Houston.
Therefore, they conclude, “fish should continue to be an important part of the menu of a heart-healthy diet.”
The meta-analysis comprised 54,799 participants from 21 countries worldwide in 17 prospective cohort studies that yielded data on incident AFib, in which there were 7,720 cases of the arrhythmia over a median follow-up of 13 years. It looked at associations between such cases and levels of omega-3 FA in blood and adipose tissue samples.
In multivariable analysis, EPA levels were not associated with incident AFib, with a hazard ratio of 1.00 (95% confidence interval, 0.95-1.05) per interquintile range, which the report describes as the difference between the 90th and 10th percentiles.
In contrast, levels of DPA, DHA, and EPA plus DHA were all associated with reduced AFib incidence at interquintile-range HRs of 0.89 (95% CI, 0.83-0.95) for DPA, 0.90 (95% CI, 0.85-0.96) for DHA and 0.93 (95% CI, 0.87-0.99) for EPA and DHA combined.
“We found little evidence that the associations significantly varied by age, sex, or global region, or across the various lipid compartments,” the report states. “Moreover, the relationship between omega-3 fatty acids and AFib did not significantly differ among individuals at higher CV risk.”
The authors observe that the prevalence of omega-3 FA supplement use in the cohorts was very low, suggesting that the omega-3 FA biomarker levels largely reflected habitual dietary intake.
Most of the meta-analysis population were free of CV disease or at relatively low CV risk, they write, and “it is conceivable that the effects of omega-3 fatty acids on atrial arrhythmias may differ in those with existing CV disease versus without.”
However, they note, in a prespecified subgroup analysis of participants mirroring the REDUCE-IT cohort of people with established CV disease or at elevated CV risk, no association with incident AFib was observed for EPA and inverse associations emerged for DPA, DHA, and EPA plus DHA.
In their editorial, Dr. Ballantyne and Dr. Jia say the meta-analysis “represents the largest epidemiological study assessing laboratory-measured omega-3 fatty acid concentrations and AFib risk in the general population.”
But significant heterogeneity across the studies and their populations is a major limitation of the analysis, they write, and made for differences in protocols, sample preparation, outcomes ascertainment, follow-up time, and other variables.
“Despite a rigorous approach to harmonize the data across cohorts and adjusting for multiple confounders,” note Dr. Ballantyne and Dr. Jia, “observational studies always have potential for residual confounders.”
The findings support fish consumption as heart-healthy, they write, but “clinicians should be aware of and discuss with patients the risks versus benefits when prescribing high-dose omega-3 FA therapies.”
The Fatty Acid Research Institute retrospectively provided a small honorarium to a subset of the analysts who participated in this study, but it had no role in its design, analysis, manuscript writing, or decision to submit for publication, the report states. Dr. Ballantyne received grant/research support through his institution from Akcea, Amgen, Arrowhead, Esperion, Ionis, Merck, Novartis, and Regeneron, as well as consulting fees from Alnylam Pharmaceuticals, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Esperion, Genentech, Gilead, Matinas BioPharma, Merck, New Amsterdam, Novartis, Pfizer, and Regeneron. Dr. Heffron and Dr. Jia have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Chronic constipation linked to cognitive decline
Compared with individuals who have a bowel movement once daily, adults with constipation who have a bowel movement every 3 days or more had significantly worse cognition that was commensurate with an additional 3 years of chronological cognitive aging, the investigators found.
“We should watch for symptoms of abnormal intestinal function, especially constipation, in older individuals, as these symptoms may hint at a higher risk of cognitive decline in the future,” study investigator Chaoran Ma, MD, PhD, former research fellow at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and current assistant professor at the University of Massachusetts Amherst, said in an interview.
The findings were presented at the Alzheimer’s Association International Conference.
Prevent constipation, improve brain health?
It’s estimated that 16% of the world’s population suffers from constipation. The problem is more common in older adults, owing to age-related factors such as a lack of dietary fiber and exercise and the use of constipating drugs to treat other medical conditions.
Chronic constipation – defined as having bowel movements every 3 days or more – has been associated with long-term health problems, such as inflammation, hormonal imbalances, anxiety, and depression.
However, few studies have investigated variations in intestinal motility and cognitive function.
“Our study provides first-of-its-kind evidence that examined a wide spectrum of bowel movement frequency, especially an analysis of the more frequent end, in relation to cognitive function,” Dr. Ma said.
The analysis involved data from 112,753 women and men from the Nurses’ Health Study (aged 30-55 years), the Nurses’ Health Study II (aged 25-42), and the Health Professionals Follow-up Study (aged 40-75).
Data on participants’ bowel movement frequency was collected between 2012 and 2013, and self-assessments of cognitive function were obtained from 2014 to 2017. A subgroup of 12,696 participants completed a standard neuropsychological test battery for objective cognitive assessment between 2014 and 2018.
The results show that bowel movement frequency was associated with overall objective cognitive function and learning and working memory in an inverse J-shape dose-response manner (both P for nonlinearity < .05).
Compared with adults who had one bowel movement daily, those who only had a bowel movement every 3 or more days had significantly worse cognition, equivalent to 3 years of additional aging (95% confidence interval, 1.2-4.7).
The researchers also observed similar J-shape dose-response relationships of bowel movement frequency with the odds of subjective cognitive decline and the likelihood of having more subjective cognitive complaints over time.
Compared with once-daily bowel movements, having bowel movements every 3 or more days was associated with a greater likelihood of subjective cognitive decline (odds ratio, 1.73; 95% CI, 1.60-1.86).
These relationships were generally consistent across the three cohorts and subgroups.
“These results stress the importance of clinicians discussing gut health, especially constipation, with their older patients,” senior investigator Dong Wang, MD, ScD, with Harvard Medical School and Brigham and Women’s Hospital, said in a conference statement.
“Interventions for preventing constipation and improving gut health include adopting healthy diets enriched with high-fiber and high-polyphenol foods such as fruits, vegetables, and whole grains; taking fiber supplementation; drinking plenty of water every day; and having regular physical activity,” Dr. Wang added.
The researchers also explored the role of the gut microbiome in the association between bowel movement frequency and cognitive function in a subgroup of 515 women and men.
They found that bowel movement frequency and subjective cognition were significantly associated with the overall variation of the gut microbiome (both P < .005) and specific microbial species.
“This research adds further evidence for a link between the microbiome and gastrointestinal function with cognitive function,” Dr. Ma said in an interview.
Interconnected systems
Commenting on the study in a conference statement, Heather M. Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, noted that “our body systems are all interconnected. When one system is malfunctioning, it impacts other systems. When that dysfunction isn’t addressed, it can create a waterfall of consequences for the rest of the body.”
Dr. Snyder cautioned, however, that “there are a lot of unanswered questions about the connection between the health of our digestive system and our long-term cognitive function. Answering these questions may uncover novel therapeutic and risk-reduction approaches for Alzheimer’s and other dementias.”
In an interview, Percy Griffin, PhD, director of scientific engagement at the Alzheimer’s Association, noted that the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk, is evaluating the impact of behavioral interventions on the gut-brain axis.
“We want to better understand how engaging in healthier habits can impact microorganisms in the gut and how changes in gut bacteria relate to brain health,” Dr. Griffin said.
The study was funded by the National Institutes of Health. Dr. Ma, Dr. Wang, Dr. Snyder, and Dr. Griffin have no relevant disclosures.
A version of this article first appeared on Medscape.com.
Compared with individuals who have a bowel movement once daily, adults with constipation who have a bowel movement every 3 days or more had significantly worse cognition that was commensurate with an additional 3 years of chronological cognitive aging, the investigators found.
“We should watch for symptoms of abnormal intestinal function, especially constipation, in older individuals, as these symptoms may hint at a higher risk of cognitive decline in the future,” study investigator Chaoran Ma, MD, PhD, former research fellow at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and current assistant professor at the University of Massachusetts Amherst, said in an interview.
The findings were presented at the Alzheimer’s Association International Conference.
Prevent constipation, improve brain health?
It’s estimated that 16% of the world’s population suffers from constipation. The problem is more common in older adults, owing to age-related factors such as a lack of dietary fiber and exercise and the use of constipating drugs to treat other medical conditions.
Chronic constipation – defined as having bowel movements every 3 days or more – has been associated with long-term health problems, such as inflammation, hormonal imbalances, anxiety, and depression.
However, few studies have investigated variations in intestinal motility and cognitive function.
“Our study provides first-of-its-kind evidence that examined a wide spectrum of bowel movement frequency, especially an analysis of the more frequent end, in relation to cognitive function,” Dr. Ma said.
The analysis involved data from 112,753 women and men from the Nurses’ Health Study (aged 30-55 years), the Nurses’ Health Study II (aged 25-42), and the Health Professionals Follow-up Study (aged 40-75).
Data on participants’ bowel movement frequency was collected between 2012 and 2013, and self-assessments of cognitive function were obtained from 2014 to 2017. A subgroup of 12,696 participants completed a standard neuropsychological test battery for objective cognitive assessment between 2014 and 2018.
The results show that bowel movement frequency was associated with overall objective cognitive function and learning and working memory in an inverse J-shape dose-response manner (both P for nonlinearity < .05).
Compared with adults who had one bowel movement daily, those who only had a bowel movement every 3 or more days had significantly worse cognition, equivalent to 3 years of additional aging (95% confidence interval, 1.2-4.7).
The researchers also observed similar J-shape dose-response relationships of bowel movement frequency with the odds of subjective cognitive decline and the likelihood of having more subjective cognitive complaints over time.
Compared with once-daily bowel movements, having bowel movements every 3 or more days was associated with a greater likelihood of subjective cognitive decline (odds ratio, 1.73; 95% CI, 1.60-1.86).
These relationships were generally consistent across the three cohorts and subgroups.
“These results stress the importance of clinicians discussing gut health, especially constipation, with their older patients,” senior investigator Dong Wang, MD, ScD, with Harvard Medical School and Brigham and Women’s Hospital, said in a conference statement.
“Interventions for preventing constipation and improving gut health include adopting healthy diets enriched with high-fiber and high-polyphenol foods such as fruits, vegetables, and whole grains; taking fiber supplementation; drinking plenty of water every day; and having regular physical activity,” Dr. Wang added.
The researchers also explored the role of the gut microbiome in the association between bowel movement frequency and cognitive function in a subgroup of 515 women and men.
They found that bowel movement frequency and subjective cognition were significantly associated with the overall variation of the gut microbiome (both P < .005) and specific microbial species.
“This research adds further evidence for a link between the microbiome and gastrointestinal function with cognitive function,” Dr. Ma said in an interview.
Interconnected systems
Commenting on the study in a conference statement, Heather M. Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, noted that “our body systems are all interconnected. When one system is malfunctioning, it impacts other systems. When that dysfunction isn’t addressed, it can create a waterfall of consequences for the rest of the body.”
Dr. Snyder cautioned, however, that “there are a lot of unanswered questions about the connection between the health of our digestive system and our long-term cognitive function. Answering these questions may uncover novel therapeutic and risk-reduction approaches for Alzheimer’s and other dementias.”
In an interview, Percy Griffin, PhD, director of scientific engagement at the Alzheimer’s Association, noted that the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk, is evaluating the impact of behavioral interventions on the gut-brain axis.
“We want to better understand how engaging in healthier habits can impact microorganisms in the gut and how changes in gut bacteria relate to brain health,” Dr. Griffin said.
The study was funded by the National Institutes of Health. Dr. Ma, Dr. Wang, Dr. Snyder, and Dr. Griffin have no relevant disclosures.
A version of this article first appeared on Medscape.com.
Compared with individuals who have a bowel movement once daily, adults with constipation who have a bowel movement every 3 days or more had significantly worse cognition that was commensurate with an additional 3 years of chronological cognitive aging, the investigators found.
“We should watch for symptoms of abnormal intestinal function, especially constipation, in older individuals, as these symptoms may hint at a higher risk of cognitive decline in the future,” study investigator Chaoran Ma, MD, PhD, former research fellow at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and current assistant professor at the University of Massachusetts Amherst, said in an interview.
The findings were presented at the Alzheimer’s Association International Conference.
Prevent constipation, improve brain health?
It’s estimated that 16% of the world’s population suffers from constipation. The problem is more common in older adults, owing to age-related factors such as a lack of dietary fiber and exercise and the use of constipating drugs to treat other medical conditions.
Chronic constipation – defined as having bowel movements every 3 days or more – has been associated with long-term health problems, such as inflammation, hormonal imbalances, anxiety, and depression.
However, few studies have investigated variations in intestinal motility and cognitive function.
“Our study provides first-of-its-kind evidence that examined a wide spectrum of bowel movement frequency, especially an analysis of the more frequent end, in relation to cognitive function,” Dr. Ma said.
The analysis involved data from 112,753 women and men from the Nurses’ Health Study (aged 30-55 years), the Nurses’ Health Study II (aged 25-42), and the Health Professionals Follow-up Study (aged 40-75).
Data on participants’ bowel movement frequency was collected between 2012 and 2013, and self-assessments of cognitive function were obtained from 2014 to 2017. A subgroup of 12,696 participants completed a standard neuropsychological test battery for objective cognitive assessment between 2014 and 2018.
The results show that bowel movement frequency was associated with overall objective cognitive function and learning and working memory in an inverse J-shape dose-response manner (both P for nonlinearity < .05).
Compared with adults who had one bowel movement daily, those who only had a bowel movement every 3 or more days had significantly worse cognition, equivalent to 3 years of additional aging (95% confidence interval, 1.2-4.7).
The researchers also observed similar J-shape dose-response relationships of bowel movement frequency with the odds of subjective cognitive decline and the likelihood of having more subjective cognitive complaints over time.
Compared with once-daily bowel movements, having bowel movements every 3 or more days was associated with a greater likelihood of subjective cognitive decline (odds ratio, 1.73; 95% CI, 1.60-1.86).
These relationships were generally consistent across the three cohorts and subgroups.
“These results stress the importance of clinicians discussing gut health, especially constipation, with their older patients,” senior investigator Dong Wang, MD, ScD, with Harvard Medical School and Brigham and Women’s Hospital, said in a conference statement.
“Interventions for preventing constipation and improving gut health include adopting healthy diets enriched with high-fiber and high-polyphenol foods such as fruits, vegetables, and whole grains; taking fiber supplementation; drinking plenty of water every day; and having regular physical activity,” Dr. Wang added.
The researchers also explored the role of the gut microbiome in the association between bowel movement frequency and cognitive function in a subgroup of 515 women and men.
They found that bowel movement frequency and subjective cognition were significantly associated with the overall variation of the gut microbiome (both P < .005) and specific microbial species.
“This research adds further evidence for a link between the microbiome and gastrointestinal function with cognitive function,” Dr. Ma said in an interview.
Interconnected systems
Commenting on the study in a conference statement, Heather M. Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, noted that “our body systems are all interconnected. When one system is malfunctioning, it impacts other systems. When that dysfunction isn’t addressed, it can create a waterfall of consequences for the rest of the body.”
Dr. Snyder cautioned, however, that “there are a lot of unanswered questions about the connection between the health of our digestive system and our long-term cognitive function. Answering these questions may uncover novel therapeutic and risk-reduction approaches for Alzheimer’s and other dementias.”
In an interview, Percy Griffin, PhD, director of scientific engagement at the Alzheimer’s Association, noted that the U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk, is evaluating the impact of behavioral interventions on the gut-brain axis.
“We want to better understand how engaging in healthier habits can impact microorganisms in the gut and how changes in gut bacteria relate to brain health,” Dr. Griffin said.
The study was funded by the National Institutes of Health. Dr. Ma, Dr. Wang, Dr. Snyder, and Dr. Griffin have no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM AAIC 2023
A risk for adverse events in cancer meds cleared renally
TOPLINE:
For patients receiving renally cleared cancer medications, therapeutic drug levels are higher and adverse events were more frequent for those whose cystatin C–based estimated glomerular filtration rate (eGFR) was more than 30% lower than their serum creatinine–based eGFR, a recent study suggests.
METHODOLOGY:
- The cohort study included 1,869 adult patients with cancer who had simultaneous serum creatinine–based eGFR (eGFRcr) and cystatin C–based eGFR (eGFRcys) measured.
- The primary exposure was eGFR discordance, defined as an eGFRcys > 30% lower than the eGFRcr.
- The primary outcome was risk of medication-related adverse events associated with vancomycin, trimethoprim-sulfamethoxazole, baclofen, or digoxin.
TAKEAWAYS:
- , including supratherapeutic vancomycin levels (24% vs. 9% of patients), trimethoprim-sulfamethoxazole–related hyperkalemia (22% vs. 12%), baclofen toxic effect (26% vs. 0%), and high digoxin levels (29% vs. 0%).
- Even after adjusting for age, sex, race and ethnicity, baseline comorbidities, laboratory studies, and medication use, patients with an eGFRcys more than 30% lower than the eGFRcr had a significantly increased risk of 30-day mortality (adjusted hazard ratio, 1.98).
- These patients were more likely to experience medication-related adverse events, including supratherapeutic vancomycin levels (24% vs. 9% of patients), trimethoprim-sulfamethoxazole–related hyperkalemia (22% vs. 12%), baclofen toxic effect (26% vs. 0%), and high digoxin levels (29% vs. 0%).
Even after adjusting for age, sex, race and ethnicity, baseline comorbidities, laboratory studies, and medication use, patients with an eGFRcys more than 30% lower than the eGFRcr had a significantly increased risk of 30-day mortality (adjusted hazard ratio, 1.98).
IN PRACTICE:
“We found a considerably higher rate of supratherapeutic drug levels and [adverse events] associated with select renally cleared medications and increased risk of death in patients with an eGFRcys that was more than 30% lower than the eGFRcr, compared with patients with a concordant eGFR or those whose eGFRcys was more than 30% higher than the eGFRcr,” the authors reported.
SOURCE:
This study, led by Paul Hanna, MD, with Massachusetts General Hospital, Boston, was published online in JAMA Network Open.
LIMITATIONS:
The study likely overestimated the rate of eGFR discordance and used a one-time assessment of serum creatinine and cystatin C, which may not reflect a steady state at the time of measurement.
DISCLOSURES:
The authors report no relevant financial relationships. The study reported no specific funding.
A version of this article first appeared on Medscape.com.
TOPLINE:
For patients receiving renally cleared cancer medications, therapeutic drug levels are higher and adverse events were more frequent for those whose cystatin C–based estimated glomerular filtration rate (eGFR) was more than 30% lower than their serum creatinine–based eGFR, a recent study suggests.
METHODOLOGY:
- The cohort study included 1,869 adult patients with cancer who had simultaneous serum creatinine–based eGFR (eGFRcr) and cystatin C–based eGFR (eGFRcys) measured.
- The primary exposure was eGFR discordance, defined as an eGFRcys > 30% lower than the eGFRcr.
- The primary outcome was risk of medication-related adverse events associated with vancomycin, trimethoprim-sulfamethoxazole, baclofen, or digoxin.
TAKEAWAYS:
- , including supratherapeutic vancomycin levels (24% vs. 9% of patients), trimethoprim-sulfamethoxazole–related hyperkalemia (22% vs. 12%), baclofen toxic effect (26% vs. 0%), and high digoxin levels (29% vs. 0%).
- Even after adjusting for age, sex, race and ethnicity, baseline comorbidities, laboratory studies, and medication use, patients with an eGFRcys more than 30% lower than the eGFRcr had a significantly increased risk of 30-day mortality (adjusted hazard ratio, 1.98).
- These patients were more likely to experience medication-related adverse events, including supratherapeutic vancomycin levels (24% vs. 9% of patients), trimethoprim-sulfamethoxazole–related hyperkalemia (22% vs. 12%), baclofen toxic effect (26% vs. 0%), and high digoxin levels (29% vs. 0%).
Even after adjusting for age, sex, race and ethnicity, baseline comorbidities, laboratory studies, and medication use, patients with an eGFRcys more than 30% lower than the eGFRcr had a significantly increased risk of 30-day mortality (adjusted hazard ratio, 1.98).
IN PRACTICE:
“We found a considerably higher rate of supratherapeutic drug levels and [adverse events] associated with select renally cleared medications and increased risk of death in patients with an eGFRcys that was more than 30% lower than the eGFRcr, compared with patients with a concordant eGFR or those whose eGFRcys was more than 30% higher than the eGFRcr,” the authors reported.
SOURCE:
This study, led by Paul Hanna, MD, with Massachusetts General Hospital, Boston, was published online in JAMA Network Open.
LIMITATIONS:
The study likely overestimated the rate of eGFR discordance and used a one-time assessment of serum creatinine and cystatin C, which may not reflect a steady state at the time of measurement.
DISCLOSURES:
The authors report no relevant financial relationships. The study reported no specific funding.
A version of this article first appeared on Medscape.com.
TOPLINE:
For patients receiving renally cleared cancer medications, therapeutic drug levels are higher and adverse events were more frequent for those whose cystatin C–based estimated glomerular filtration rate (eGFR) was more than 30% lower than their serum creatinine–based eGFR, a recent study suggests.
METHODOLOGY:
- The cohort study included 1,869 adult patients with cancer who had simultaneous serum creatinine–based eGFR (eGFRcr) and cystatin C–based eGFR (eGFRcys) measured.
- The primary exposure was eGFR discordance, defined as an eGFRcys > 30% lower than the eGFRcr.
- The primary outcome was risk of medication-related adverse events associated with vancomycin, trimethoprim-sulfamethoxazole, baclofen, or digoxin.
TAKEAWAYS:
- , including supratherapeutic vancomycin levels (24% vs. 9% of patients), trimethoprim-sulfamethoxazole–related hyperkalemia (22% vs. 12%), baclofen toxic effect (26% vs. 0%), and high digoxin levels (29% vs. 0%).
- Even after adjusting for age, sex, race and ethnicity, baseline comorbidities, laboratory studies, and medication use, patients with an eGFRcys more than 30% lower than the eGFRcr had a significantly increased risk of 30-day mortality (adjusted hazard ratio, 1.98).
- These patients were more likely to experience medication-related adverse events, including supratherapeutic vancomycin levels (24% vs. 9% of patients), trimethoprim-sulfamethoxazole–related hyperkalemia (22% vs. 12%), baclofen toxic effect (26% vs. 0%), and high digoxin levels (29% vs. 0%).
Even after adjusting for age, sex, race and ethnicity, baseline comorbidities, laboratory studies, and medication use, patients with an eGFRcys more than 30% lower than the eGFRcr had a significantly increased risk of 30-day mortality (adjusted hazard ratio, 1.98).
IN PRACTICE:
“We found a considerably higher rate of supratherapeutic drug levels and [adverse events] associated with select renally cleared medications and increased risk of death in patients with an eGFRcys that was more than 30% lower than the eGFRcr, compared with patients with a concordant eGFR or those whose eGFRcys was more than 30% higher than the eGFRcr,” the authors reported.
SOURCE:
This study, led by Paul Hanna, MD, with Massachusetts General Hospital, Boston, was published online in JAMA Network Open.
LIMITATIONS:
The study likely overestimated the rate of eGFR discordance and used a one-time assessment of serum creatinine and cystatin C, which may not reflect a steady state at the time of measurement.
DISCLOSURES:
The authors report no relevant financial relationships. The study reported no specific funding.
A version of this article first appeared on Medscape.com.
Opioid initiation in dementia tied to an 11-fold increased risk of death
Opioid initiation for older adults with dementia is linked to a significantly increased risk of death, especially in the first 2 weeks, when the risk is elevated 11-fold, new research shows.
“We expected that opioids would be associated with an increased risk of death, but we are surprised by the magnitude,” study investigator Christina Jensen-Dahm, MD, PhD, with the Danish Dementia Research Centre, Copenhagen University Hospital, Rigshospitalet, Denmark, told this news organization.
“It’s important that physicians carefully evaluate the risk and benefits if considering initiating an opioid, and this is particularly important in elderly with dementia,” Dr. Jensen-Dahm added.
The findings were presented at the Alzheimer’s Association International Conference.
Risky business
Using Danish nationwide registries, the researchers analyzed data on all 75,471 adults in Denmark who were aged 65 and older and had been diagnosed with dementia between 2008 and 2018. A total of 31,619 individuals (42%) filled a prescription for an opioid. These “exposed” individuals were matched to 63,235 unexposed individuals.
Among the exposed group, 10,474 (33%) died within 180 days after starting opioid therapy, compared with 3,980 (6.4%) in the unexposed group.
After adjusting for potential differences between groups, new use of an opioid was associated with a greater than fourfold excess mortality risk (adjusted hazard ratio, 4.16; 95% confidence interval, 4.00-4.33).
New use of a strong opioid – defined as morphine, oxycodone, ketobemidone, hydromorphone, pethidine, buprenorphine, and fentanyl – was associated with a greater than sixfold increase in mortality risk (aHR, 6.42; 95% CI, 6.08-6.79).
Among those who used fentanyl patches as their first opioid, 65% died within the first 180 days, compared with 6.7% in the unexposed – an eightfold increased mortality risk (aHR, 8.04; 95% CI, 7.01-9.22).
For all opioids, the risk was greatest in the first 14 days, with a nearly 11-fold increased risk of mortality (aHR, 10.8; 95% CI, 9.74-11.99). However, there remained a twofold increase in risk after taking opioids for 90 days (aHR, 2.32; 95% CI, 2.17-2.48).
“Opioids are associated with severe and well-known side effects, such as sedation, confusion, respiratory depression, falls, and in the most severe cases, death. In the general population, opioids have been associated with an increased risk of death, and similar to ours, greatest in the first 14 days,” said Dr. Jensen-Dahm.
Need to weigh risks, benefits
Commenting on the study, Percy Griffin, PhD, director of scientific engagement at the Alzheimer’s Association, told this news organization that the use of strong opioids has “increased considerably over the past decade among older people with dementia. Opioid therapy should only be considered for pain if the benefits are anticipated to outweigh the risks in individuals who are living with dementia.”
“Opioids are very powerful drugs, and while we need to see additional research in more diverse populations, these initial findings indicate they may put older adults with dementia at much higher risk of death,” Nicole Purcell, DO, neurologist and senior director of clinical practice at the Alzheimer’s Association, added in a conference statement.
“Pain should not go undiagnosed or untreated, in particular in people living with dementia, who may not be able to effectively articulate the location and severity of the pain,” Dr. Purcell added.
These new findings further emphasize the need for discussion between patient, family, and physician. Decisions about prescribing pain medication should be thought through carefully, and if used, there needs to be careful monitoring of the patient, said Dr. Purcell.
The study was supported by a grant from the Capital Region of Denmark. Dr. Jensen-Dahm, Dr. Griffin, and Dr. Purcell have no relevant disclosures.
A version of this article first appeared on Medscape.com.
Opioid initiation for older adults with dementia is linked to a significantly increased risk of death, especially in the first 2 weeks, when the risk is elevated 11-fold, new research shows.
“We expected that opioids would be associated with an increased risk of death, but we are surprised by the magnitude,” study investigator Christina Jensen-Dahm, MD, PhD, with the Danish Dementia Research Centre, Copenhagen University Hospital, Rigshospitalet, Denmark, told this news organization.
“It’s important that physicians carefully evaluate the risk and benefits if considering initiating an opioid, and this is particularly important in elderly with dementia,” Dr. Jensen-Dahm added.
The findings were presented at the Alzheimer’s Association International Conference.
Risky business
Using Danish nationwide registries, the researchers analyzed data on all 75,471 adults in Denmark who were aged 65 and older and had been diagnosed with dementia between 2008 and 2018. A total of 31,619 individuals (42%) filled a prescription for an opioid. These “exposed” individuals were matched to 63,235 unexposed individuals.
Among the exposed group, 10,474 (33%) died within 180 days after starting opioid therapy, compared with 3,980 (6.4%) in the unexposed group.
After adjusting for potential differences between groups, new use of an opioid was associated with a greater than fourfold excess mortality risk (adjusted hazard ratio, 4.16; 95% confidence interval, 4.00-4.33).
New use of a strong opioid – defined as morphine, oxycodone, ketobemidone, hydromorphone, pethidine, buprenorphine, and fentanyl – was associated with a greater than sixfold increase in mortality risk (aHR, 6.42; 95% CI, 6.08-6.79).
Among those who used fentanyl patches as their first opioid, 65% died within the first 180 days, compared with 6.7% in the unexposed – an eightfold increased mortality risk (aHR, 8.04; 95% CI, 7.01-9.22).
For all opioids, the risk was greatest in the first 14 days, with a nearly 11-fold increased risk of mortality (aHR, 10.8; 95% CI, 9.74-11.99). However, there remained a twofold increase in risk after taking opioids for 90 days (aHR, 2.32; 95% CI, 2.17-2.48).
“Opioids are associated with severe and well-known side effects, such as sedation, confusion, respiratory depression, falls, and in the most severe cases, death. In the general population, opioids have been associated with an increased risk of death, and similar to ours, greatest in the first 14 days,” said Dr. Jensen-Dahm.
Need to weigh risks, benefits
Commenting on the study, Percy Griffin, PhD, director of scientific engagement at the Alzheimer’s Association, told this news organization that the use of strong opioids has “increased considerably over the past decade among older people with dementia. Opioid therapy should only be considered for pain if the benefits are anticipated to outweigh the risks in individuals who are living with dementia.”
“Opioids are very powerful drugs, and while we need to see additional research in more diverse populations, these initial findings indicate they may put older adults with dementia at much higher risk of death,” Nicole Purcell, DO, neurologist and senior director of clinical practice at the Alzheimer’s Association, added in a conference statement.
“Pain should not go undiagnosed or untreated, in particular in people living with dementia, who may not be able to effectively articulate the location and severity of the pain,” Dr. Purcell added.
These new findings further emphasize the need for discussion between patient, family, and physician. Decisions about prescribing pain medication should be thought through carefully, and if used, there needs to be careful monitoring of the patient, said Dr. Purcell.
The study was supported by a grant from the Capital Region of Denmark. Dr. Jensen-Dahm, Dr. Griffin, and Dr. Purcell have no relevant disclosures.
A version of this article first appeared on Medscape.com.
Opioid initiation for older adults with dementia is linked to a significantly increased risk of death, especially in the first 2 weeks, when the risk is elevated 11-fold, new research shows.
“We expected that opioids would be associated with an increased risk of death, but we are surprised by the magnitude,” study investigator Christina Jensen-Dahm, MD, PhD, with the Danish Dementia Research Centre, Copenhagen University Hospital, Rigshospitalet, Denmark, told this news organization.
“It’s important that physicians carefully evaluate the risk and benefits if considering initiating an opioid, and this is particularly important in elderly with dementia,” Dr. Jensen-Dahm added.
The findings were presented at the Alzheimer’s Association International Conference.
Risky business
Using Danish nationwide registries, the researchers analyzed data on all 75,471 adults in Denmark who were aged 65 and older and had been diagnosed with dementia between 2008 and 2018. A total of 31,619 individuals (42%) filled a prescription for an opioid. These “exposed” individuals were matched to 63,235 unexposed individuals.
Among the exposed group, 10,474 (33%) died within 180 days after starting opioid therapy, compared with 3,980 (6.4%) in the unexposed group.
After adjusting for potential differences between groups, new use of an opioid was associated with a greater than fourfold excess mortality risk (adjusted hazard ratio, 4.16; 95% confidence interval, 4.00-4.33).
New use of a strong opioid – defined as morphine, oxycodone, ketobemidone, hydromorphone, pethidine, buprenorphine, and fentanyl – was associated with a greater than sixfold increase in mortality risk (aHR, 6.42; 95% CI, 6.08-6.79).
Among those who used fentanyl patches as their first opioid, 65% died within the first 180 days, compared with 6.7% in the unexposed – an eightfold increased mortality risk (aHR, 8.04; 95% CI, 7.01-9.22).
For all opioids, the risk was greatest in the first 14 days, with a nearly 11-fold increased risk of mortality (aHR, 10.8; 95% CI, 9.74-11.99). However, there remained a twofold increase in risk after taking opioids for 90 days (aHR, 2.32; 95% CI, 2.17-2.48).
“Opioids are associated with severe and well-known side effects, such as sedation, confusion, respiratory depression, falls, and in the most severe cases, death. In the general population, opioids have been associated with an increased risk of death, and similar to ours, greatest in the first 14 days,” said Dr. Jensen-Dahm.
Need to weigh risks, benefits
Commenting on the study, Percy Griffin, PhD, director of scientific engagement at the Alzheimer’s Association, told this news organization that the use of strong opioids has “increased considerably over the past decade among older people with dementia. Opioid therapy should only be considered for pain if the benefits are anticipated to outweigh the risks in individuals who are living with dementia.”
“Opioids are very powerful drugs, and while we need to see additional research in more diverse populations, these initial findings indicate they may put older adults with dementia at much higher risk of death,” Nicole Purcell, DO, neurologist and senior director of clinical practice at the Alzheimer’s Association, added in a conference statement.
“Pain should not go undiagnosed or untreated, in particular in people living with dementia, who may not be able to effectively articulate the location and severity of the pain,” Dr. Purcell added.
These new findings further emphasize the need for discussion between patient, family, and physician. Decisions about prescribing pain medication should be thought through carefully, and if used, there needs to be careful monitoring of the patient, said Dr. Purcell.
The study was supported by a grant from the Capital Region of Denmark. Dr. Jensen-Dahm, Dr. Griffin, and Dr. Purcell have no relevant disclosures.
A version of this article first appeared on Medscape.com.
From AAIC 2023
‘Brain fitness program’ may aid memory loss, concussion, ADHD
new research shows.
The program, which consists of targeted cognitive training and EEG-based neurofeedback, coupled with meditation and diet/lifestyle coaching, led to improvements in memory, attention, mood, alertness, and sleep.
The program promotes “neuroplasticity and was equally effective for patients with all three conditions,” program creator Majid Fotuhi, MD, PhD, said in an interview.
Patients with mild to moderate cognitive symptoms often see “remarkable” results within 3 months of consistently following the program, said Dr. Fotuhi, adjunct professor of neuroscience at George Washington University, Washington, and medical director of NeuroGrow Brain Fitness Center, McLean, Va.
“It actually makes intuitive sense that a healthier and stronger brain would function better and that patients of all ages with various cognitive or emotional symptoms would all benefit from improving the biology of their brain,” Dr. Fotuhi added.
The study was published online in the Journal of Alzheimer’s Disease Reports.
Personalized program
The findings are based on 223 children and adults who completed the 12-week NeuroGrow Brain Fitness Program (NeuroGrow BFP), including 71 with ADHD, 88 with PCS, and 64 with memory loss, defined as diagnosed mild cognitive impairment or subjective cognitive decline.
As part of the program, participants undergo a complete neurocognitive evaluation, including tests for verbal memory, complex attention, processing speed, executive functioning, and the Neurocognitive Index.
They also complete questionnaires regarding sleep, mood, diet, exercise, and anxiety/depression, and they undergo quantitative EEG at the beginning and end of the program.
A comparison of before and after neurocognitive test scores showed that all three patient subgroups experienced statistically significant improvements on most measures, the study team reports.
After completing the program, 60%-90% of patients scored higher on cognitive tests and reported having fewer cognitive, sleep, and emotional symptoms.
In all subgroups, the most significant improvement was observed in executive functioning.
“These preliminary findings appear to show that multimodal interventions which are known to increase neuroplasticity in the brain, when personalized, can have benefits for patients with cognitive symptoms from a variety of neurological conditions,” the investigators wrote.
The study’s strengths include a large, community-based sample of patients of different ages who had disruptive symptoms and abnormalities as determined using objective cognitive tests whose progress was monitored by objective and subjective measures.
The chief limitation is the lack of a control or placebo group.
“Though it is difficult to find a comparable group of patients with the exact same profile of cognitive deficits and brain-related symptoms, studying a larger group of patients – and comparing them with a wait-list group – may make it possible to do a more definitive assessment of the NeuroGrow BFP,” the researchers noted.
Dr. Fotuhi said the “secret to the success” of the program is that it involves a full assessment of all cognitive and neurobehavioral symptoms for each patient. This allows for individualized and targeted interventions for specific concerns and symptoms.
He said there is a need to recognize that patients who present to a neurology practice with a single complaint, such as a problem with memory or attention, often have other problems, such as anxiety/depression, stress, insomnia, sedentary lifestyle, obesity, diabetes, sleep apnea, or alcohol overuse.
“Each of these factors can affect their cognitive abilities and need a multimodal set of interventions in order to see full resolution of their cognitive symptoms,” Dr. Fotuhi said.
He has created a series of educational videos to demonstrate the program’s benefits.
The self-pay cost for the NeuroGrow BFP assessment and treatment sessions is approximately $7,000.
Dr. Fotuhi said all of the interventions included in the program are readily available at low cost.
He suggested that health care professionals who lack time or staff for conducting a comprehensive neurocognitive assessment for their patients can provide them with a copy of the Brain Health Index.
“Patients can then be instructed to work on the individual components of their brain health on their own – and measure their brain health index on a weekly basis,” Dr. Fotuhi said. “Private practices or academic centers can use the detailed information I have provided in my paper to develop their own brain fitness program.”
Not ready for prime time
Commenting on the study, Percy Griffin, PhD, director of scientific engagement for the Alzheimer’s Association, noted that “nonpharmacologic interventions can help alleviate some of the symptoms associated with dementia.
“The current study investigates nonpharmacologic interventions in a small number of patients with ADHD, postconcussion syndrome, or memory loss. The researchers found improvements on most measures following the brain rehabilitation program.
“While this is interesting, more work is needed in larger, more diverse cohorts before these programs can be applied broadly. Nonpharmacologic interventions are a helpful tool that need to be studied further in future studies,” Dr. Griffin added.
Funding for the study was provided by the NeuroGrow Brain Fitness Center. Dr. Fotuhi, the owner of NeuroGrow, was involved in data analysis, writing, editing, approval, and decision to publish. Dr. Griffin reported no disclosures.
A version of this article appeared on Medscape.com.
new research shows.
The program, which consists of targeted cognitive training and EEG-based neurofeedback, coupled with meditation and diet/lifestyle coaching, led to improvements in memory, attention, mood, alertness, and sleep.
The program promotes “neuroplasticity and was equally effective for patients with all three conditions,” program creator Majid Fotuhi, MD, PhD, said in an interview.
Patients with mild to moderate cognitive symptoms often see “remarkable” results within 3 months of consistently following the program, said Dr. Fotuhi, adjunct professor of neuroscience at George Washington University, Washington, and medical director of NeuroGrow Brain Fitness Center, McLean, Va.
“It actually makes intuitive sense that a healthier and stronger brain would function better and that patients of all ages with various cognitive or emotional symptoms would all benefit from improving the biology of their brain,” Dr. Fotuhi added.
The study was published online in the Journal of Alzheimer’s Disease Reports.
Personalized program
The findings are based on 223 children and adults who completed the 12-week NeuroGrow Brain Fitness Program (NeuroGrow BFP), including 71 with ADHD, 88 with PCS, and 64 with memory loss, defined as diagnosed mild cognitive impairment or subjective cognitive decline.
As part of the program, participants undergo a complete neurocognitive evaluation, including tests for verbal memory, complex attention, processing speed, executive functioning, and the Neurocognitive Index.
They also complete questionnaires regarding sleep, mood, diet, exercise, and anxiety/depression, and they undergo quantitative EEG at the beginning and end of the program.
A comparison of before and after neurocognitive test scores showed that all three patient subgroups experienced statistically significant improvements on most measures, the study team reports.
After completing the program, 60%-90% of patients scored higher on cognitive tests and reported having fewer cognitive, sleep, and emotional symptoms.
In all subgroups, the most significant improvement was observed in executive functioning.
“These preliminary findings appear to show that multimodal interventions which are known to increase neuroplasticity in the brain, when personalized, can have benefits for patients with cognitive symptoms from a variety of neurological conditions,” the investigators wrote.
The study’s strengths include a large, community-based sample of patients of different ages who had disruptive symptoms and abnormalities as determined using objective cognitive tests whose progress was monitored by objective and subjective measures.
The chief limitation is the lack of a control or placebo group.
“Though it is difficult to find a comparable group of patients with the exact same profile of cognitive deficits and brain-related symptoms, studying a larger group of patients – and comparing them with a wait-list group – may make it possible to do a more definitive assessment of the NeuroGrow BFP,” the researchers noted.
Dr. Fotuhi said the “secret to the success” of the program is that it involves a full assessment of all cognitive and neurobehavioral symptoms for each patient. This allows for individualized and targeted interventions for specific concerns and symptoms.
He said there is a need to recognize that patients who present to a neurology practice with a single complaint, such as a problem with memory or attention, often have other problems, such as anxiety/depression, stress, insomnia, sedentary lifestyle, obesity, diabetes, sleep apnea, or alcohol overuse.
“Each of these factors can affect their cognitive abilities and need a multimodal set of interventions in order to see full resolution of their cognitive symptoms,” Dr. Fotuhi said.
He has created a series of educational videos to demonstrate the program’s benefits.
The self-pay cost for the NeuroGrow BFP assessment and treatment sessions is approximately $7,000.
Dr. Fotuhi said all of the interventions included in the program are readily available at low cost.
He suggested that health care professionals who lack time or staff for conducting a comprehensive neurocognitive assessment for their patients can provide them with a copy of the Brain Health Index.
“Patients can then be instructed to work on the individual components of their brain health on their own – and measure their brain health index on a weekly basis,” Dr. Fotuhi said. “Private practices or academic centers can use the detailed information I have provided in my paper to develop their own brain fitness program.”
Not ready for prime time
Commenting on the study, Percy Griffin, PhD, director of scientific engagement for the Alzheimer’s Association, noted that “nonpharmacologic interventions can help alleviate some of the symptoms associated with dementia.
“The current study investigates nonpharmacologic interventions in a small number of patients with ADHD, postconcussion syndrome, or memory loss. The researchers found improvements on most measures following the brain rehabilitation program.
“While this is interesting, more work is needed in larger, more diverse cohorts before these programs can be applied broadly. Nonpharmacologic interventions are a helpful tool that need to be studied further in future studies,” Dr. Griffin added.
Funding for the study was provided by the NeuroGrow Brain Fitness Center. Dr. Fotuhi, the owner of NeuroGrow, was involved in data analysis, writing, editing, approval, and decision to publish. Dr. Griffin reported no disclosures.
A version of this article appeared on Medscape.com.
new research shows.
The program, which consists of targeted cognitive training and EEG-based neurofeedback, coupled with meditation and diet/lifestyle coaching, led to improvements in memory, attention, mood, alertness, and sleep.
The program promotes “neuroplasticity and was equally effective for patients with all three conditions,” program creator Majid Fotuhi, MD, PhD, said in an interview.
Patients with mild to moderate cognitive symptoms often see “remarkable” results within 3 months of consistently following the program, said Dr. Fotuhi, adjunct professor of neuroscience at George Washington University, Washington, and medical director of NeuroGrow Brain Fitness Center, McLean, Va.
“It actually makes intuitive sense that a healthier and stronger brain would function better and that patients of all ages with various cognitive or emotional symptoms would all benefit from improving the biology of their brain,” Dr. Fotuhi added.
The study was published online in the Journal of Alzheimer’s Disease Reports.
Personalized program
The findings are based on 223 children and adults who completed the 12-week NeuroGrow Brain Fitness Program (NeuroGrow BFP), including 71 with ADHD, 88 with PCS, and 64 with memory loss, defined as diagnosed mild cognitive impairment or subjective cognitive decline.
As part of the program, participants undergo a complete neurocognitive evaluation, including tests for verbal memory, complex attention, processing speed, executive functioning, and the Neurocognitive Index.
They also complete questionnaires regarding sleep, mood, diet, exercise, and anxiety/depression, and they undergo quantitative EEG at the beginning and end of the program.
A comparison of before and after neurocognitive test scores showed that all three patient subgroups experienced statistically significant improvements on most measures, the study team reports.
After completing the program, 60%-90% of patients scored higher on cognitive tests and reported having fewer cognitive, sleep, and emotional symptoms.
In all subgroups, the most significant improvement was observed in executive functioning.
“These preliminary findings appear to show that multimodal interventions which are known to increase neuroplasticity in the brain, when personalized, can have benefits for patients with cognitive symptoms from a variety of neurological conditions,” the investigators wrote.
The study’s strengths include a large, community-based sample of patients of different ages who had disruptive symptoms and abnormalities as determined using objective cognitive tests whose progress was monitored by objective and subjective measures.
The chief limitation is the lack of a control or placebo group.
“Though it is difficult to find a comparable group of patients with the exact same profile of cognitive deficits and brain-related symptoms, studying a larger group of patients – and comparing them with a wait-list group – may make it possible to do a more definitive assessment of the NeuroGrow BFP,” the researchers noted.
Dr. Fotuhi said the “secret to the success” of the program is that it involves a full assessment of all cognitive and neurobehavioral symptoms for each patient. This allows for individualized and targeted interventions for specific concerns and symptoms.
He said there is a need to recognize that patients who present to a neurology practice with a single complaint, such as a problem with memory or attention, often have other problems, such as anxiety/depression, stress, insomnia, sedentary lifestyle, obesity, diabetes, sleep apnea, or alcohol overuse.
“Each of these factors can affect their cognitive abilities and need a multimodal set of interventions in order to see full resolution of their cognitive symptoms,” Dr. Fotuhi said.
He has created a series of educational videos to demonstrate the program’s benefits.
The self-pay cost for the NeuroGrow BFP assessment and treatment sessions is approximately $7,000.
Dr. Fotuhi said all of the interventions included in the program are readily available at low cost.
He suggested that health care professionals who lack time or staff for conducting a comprehensive neurocognitive assessment for their patients can provide them with a copy of the Brain Health Index.
“Patients can then be instructed to work on the individual components of their brain health on their own – and measure their brain health index on a weekly basis,” Dr. Fotuhi said. “Private practices or academic centers can use the detailed information I have provided in my paper to develop their own brain fitness program.”
Not ready for prime time
Commenting on the study, Percy Griffin, PhD, director of scientific engagement for the Alzheimer’s Association, noted that “nonpharmacologic interventions can help alleviate some of the symptoms associated with dementia.
“The current study investigates nonpharmacologic interventions in a small number of patients with ADHD, postconcussion syndrome, or memory loss. The researchers found improvements on most measures following the brain rehabilitation program.
“While this is interesting, more work is needed in larger, more diverse cohorts before these programs can be applied broadly. Nonpharmacologic interventions are a helpful tool that need to be studied further in future studies,” Dr. Griffin added.
Funding for the study was provided by the NeuroGrow Brain Fitness Center. Dr. Fotuhi, the owner of NeuroGrow, was involved in data analysis, writing, editing, approval, and decision to publish. Dr. Griffin reported no disclosures.
A version of this article appeared on Medscape.com.
FROM THE JOURNAL OF ALZHEIMER’S DISEASE REPORTS
Immunotherapy stewardship could save tens of millions a year
Implementing stewardship strategies for immune checkpoint inhibitor (ICI) therapy, including personalized weight-based dosing, dose rounding, and pharmacy-level vial sharing, could generate savings of as much as $74 million each year for the Veterans Health Administration (VHA), a new analysis suggests.
That $74 million in savings would translate to nearly 14% less spent on ICI therapy annually.
first author Alex Bryant, MD, University of Michigan, Ann Arbor, said in an interview.
The study was published in Health Affairs.
ICI therapy is used in about 40 unique cancer indications and, in 2020, accounted for more than $6 billion in Medicare Part B spending.
Two of the most prescribed ICIs – pembrolizumab and nivolumab – initially received their U.S. approval at personalized weight-based doses. But at the request of the manufacturers, the Food and Drug Administration approved “one-size-fits-all” flat doses, despite a lack of data to support this strategy compared with weight-based dosing.
With a fixed dose strategy, “patients with cancer not only tend to get too high a dose of the drug, but costs go up significantly,” Daniel Goldstein, MD, a medical oncologist at the Rabin Medical Center, Petah Tikva, Israel, told this news organization last year. “Why should we give a higher dose with the same efficacy when that dose will cost significantly more and has the potential to increase adverse events?”
To compare the cost of a weight-based vs. fixed-dose strategy, Dr. Bryant and colleagues conducted a simulation analysis under four stewardship scenarios, using data from the VHA and Medicare drug prices. Strategy one looked at weight-based dosing; strategy two combined weight-based dosing and dose rounding but not single-use vial sharing; strategy three used weight-based dosing and single-use vial sharing but not dose rounding; and strategy four, the most aggressive, combined all three.
ICIs in the VHA national formulary included pembrolizumab, nivolumab, atezolizumab, durvalumab, and cemiplimab-rwlc.
Using an algorithm to extract data, the team identified 49,851 administration events in 8,276 unique patients in 2021 – just over half were pembrolizumab, nearly 23% were nivolumab, and the remaining 26% largely included atezolizumab (12.1%) and durvalumab (11.9%).
The team found that the VHA spends roughly $537 million annually on ICIs. But implementing the stewardship measures that combined weight-based dosing, dose rounding, and vial sharing could save the VHA $74 million, or about 14%, annually on ICIs.
Most of the savings came from dosing changes to pembrolizumab and nivolumab, with greater savings achieved by combining more stewardship strategies. For instance, using strategy one (weight-based dosing alone) could lead to annual pembrolizumab savings of $14 million. Adding dose rounding (strategy two) could reduce pembrolizumab spending by $24 million. And using strategy four, with an unlimited window for vial sharing, could mean annual savings of nearly $60 million.
“Our results should prompt cost-conscious systems and payers to ask whether the amounts of drugs they’re providing to patients and how they go about making those doses are the most cost-effective approaches,” said corresponding author Garth W. Strohbehn, MD, of the University of Michigan and the VA Ann Arbor Healthcare System.
Dr. Strohbehn said the prospect of adopting these strategies hinges on several factors, with financial incentives at the prescriber and medical center level likely being the most influential.
“In fee-for-service systems, reimbursement scales with the amount of drug administered, so there can be a financial disincentive to decreasing overall drug usage,” Dr. Strohbehn explained.
“Conversely, integrated systems such as Kaiser Permanente or the VHA and large self-insured employers are incentivized to contain costs and take great care of patients, so they may be more inclined to promote these strategies,” he added.
However, Adam C. Powell, PhD, president, Payer+Provider Syndicate, who wasn’t involved in the analysis, cautioned that such a shift may come with unintended consequences.
The Infrastructure, Investment, and Jobs Act of 2021 let the Centers for Medicare and Medicaid Services seek reimbursement for discarded drugs – in effect, changing the reimbursement model for medications. That led pharmaceutical manufacturers to respond in kind by changing the dosing model, Dr. Powell said.
“Drugs that previously had personalized weight-based dosing were moved to uniform flat dosing, eliminating the potential for the manufacturer to have to issue a reimbursement if the patient’s personalized dose fell short of the amount in the single-use vial,” Dr. Powell added.
If there is a substantial migration to weight-based dosing, “it is possible that pharmaceutical manufacturers will rethink their dosing and pricing models, just as happened previously,” he cautioned.
However, these strategies could also provide relief for another escalating issue: drug shortages. Especially in the current moment, having a stewardship mindset, “might be helpful in navigating drug shortages,” Dr. Strohbehn said.
This research had no commercial funding. Dr. Bryant, Dr. Strohbehn, and Dr. Powell report no relevant financial relationships.
A version of this article appeared on Medscape.com.
Implementing stewardship strategies for immune checkpoint inhibitor (ICI) therapy, including personalized weight-based dosing, dose rounding, and pharmacy-level vial sharing, could generate savings of as much as $74 million each year for the Veterans Health Administration (VHA), a new analysis suggests.
That $74 million in savings would translate to nearly 14% less spent on ICI therapy annually.
first author Alex Bryant, MD, University of Michigan, Ann Arbor, said in an interview.
The study was published in Health Affairs.
ICI therapy is used in about 40 unique cancer indications and, in 2020, accounted for more than $6 billion in Medicare Part B spending.
Two of the most prescribed ICIs – pembrolizumab and nivolumab – initially received their U.S. approval at personalized weight-based doses. But at the request of the manufacturers, the Food and Drug Administration approved “one-size-fits-all” flat doses, despite a lack of data to support this strategy compared with weight-based dosing.
With a fixed dose strategy, “patients with cancer not only tend to get too high a dose of the drug, but costs go up significantly,” Daniel Goldstein, MD, a medical oncologist at the Rabin Medical Center, Petah Tikva, Israel, told this news organization last year. “Why should we give a higher dose with the same efficacy when that dose will cost significantly more and has the potential to increase adverse events?”
To compare the cost of a weight-based vs. fixed-dose strategy, Dr. Bryant and colleagues conducted a simulation analysis under four stewardship scenarios, using data from the VHA and Medicare drug prices. Strategy one looked at weight-based dosing; strategy two combined weight-based dosing and dose rounding but not single-use vial sharing; strategy three used weight-based dosing and single-use vial sharing but not dose rounding; and strategy four, the most aggressive, combined all three.
ICIs in the VHA national formulary included pembrolizumab, nivolumab, atezolizumab, durvalumab, and cemiplimab-rwlc.
Using an algorithm to extract data, the team identified 49,851 administration events in 8,276 unique patients in 2021 – just over half were pembrolizumab, nearly 23% were nivolumab, and the remaining 26% largely included atezolizumab (12.1%) and durvalumab (11.9%).
The team found that the VHA spends roughly $537 million annually on ICIs. But implementing the stewardship measures that combined weight-based dosing, dose rounding, and vial sharing could save the VHA $74 million, or about 14%, annually on ICIs.
Most of the savings came from dosing changes to pembrolizumab and nivolumab, with greater savings achieved by combining more stewardship strategies. For instance, using strategy one (weight-based dosing alone) could lead to annual pembrolizumab savings of $14 million. Adding dose rounding (strategy two) could reduce pembrolizumab spending by $24 million. And using strategy four, with an unlimited window for vial sharing, could mean annual savings of nearly $60 million.
“Our results should prompt cost-conscious systems and payers to ask whether the amounts of drugs they’re providing to patients and how they go about making those doses are the most cost-effective approaches,” said corresponding author Garth W. Strohbehn, MD, of the University of Michigan and the VA Ann Arbor Healthcare System.
Dr. Strohbehn said the prospect of adopting these strategies hinges on several factors, with financial incentives at the prescriber and medical center level likely being the most influential.
“In fee-for-service systems, reimbursement scales with the amount of drug administered, so there can be a financial disincentive to decreasing overall drug usage,” Dr. Strohbehn explained.
“Conversely, integrated systems such as Kaiser Permanente or the VHA and large self-insured employers are incentivized to contain costs and take great care of patients, so they may be more inclined to promote these strategies,” he added.
However, Adam C. Powell, PhD, president, Payer+Provider Syndicate, who wasn’t involved in the analysis, cautioned that such a shift may come with unintended consequences.
The Infrastructure, Investment, and Jobs Act of 2021 let the Centers for Medicare and Medicaid Services seek reimbursement for discarded drugs – in effect, changing the reimbursement model for medications. That led pharmaceutical manufacturers to respond in kind by changing the dosing model, Dr. Powell said.
“Drugs that previously had personalized weight-based dosing were moved to uniform flat dosing, eliminating the potential for the manufacturer to have to issue a reimbursement if the patient’s personalized dose fell short of the amount in the single-use vial,” Dr. Powell added.
If there is a substantial migration to weight-based dosing, “it is possible that pharmaceutical manufacturers will rethink their dosing and pricing models, just as happened previously,” he cautioned.
However, these strategies could also provide relief for another escalating issue: drug shortages. Especially in the current moment, having a stewardship mindset, “might be helpful in navigating drug shortages,” Dr. Strohbehn said.
This research had no commercial funding. Dr. Bryant, Dr. Strohbehn, and Dr. Powell report no relevant financial relationships.
A version of this article appeared on Medscape.com.
Implementing stewardship strategies for immune checkpoint inhibitor (ICI) therapy, including personalized weight-based dosing, dose rounding, and pharmacy-level vial sharing, could generate savings of as much as $74 million each year for the Veterans Health Administration (VHA), a new analysis suggests.
That $74 million in savings would translate to nearly 14% less spent on ICI therapy annually.
first author Alex Bryant, MD, University of Michigan, Ann Arbor, said in an interview.
The study was published in Health Affairs.
ICI therapy is used in about 40 unique cancer indications and, in 2020, accounted for more than $6 billion in Medicare Part B spending.
Two of the most prescribed ICIs – pembrolizumab and nivolumab – initially received their U.S. approval at personalized weight-based doses. But at the request of the manufacturers, the Food and Drug Administration approved “one-size-fits-all” flat doses, despite a lack of data to support this strategy compared with weight-based dosing.
With a fixed dose strategy, “patients with cancer not only tend to get too high a dose of the drug, but costs go up significantly,” Daniel Goldstein, MD, a medical oncologist at the Rabin Medical Center, Petah Tikva, Israel, told this news organization last year. “Why should we give a higher dose with the same efficacy when that dose will cost significantly more and has the potential to increase adverse events?”
To compare the cost of a weight-based vs. fixed-dose strategy, Dr. Bryant and colleagues conducted a simulation analysis under four stewardship scenarios, using data from the VHA and Medicare drug prices. Strategy one looked at weight-based dosing; strategy two combined weight-based dosing and dose rounding but not single-use vial sharing; strategy three used weight-based dosing and single-use vial sharing but not dose rounding; and strategy four, the most aggressive, combined all three.
ICIs in the VHA national formulary included pembrolizumab, nivolumab, atezolizumab, durvalumab, and cemiplimab-rwlc.
Using an algorithm to extract data, the team identified 49,851 administration events in 8,276 unique patients in 2021 – just over half were pembrolizumab, nearly 23% were nivolumab, and the remaining 26% largely included atezolizumab (12.1%) and durvalumab (11.9%).
The team found that the VHA spends roughly $537 million annually on ICIs. But implementing the stewardship measures that combined weight-based dosing, dose rounding, and vial sharing could save the VHA $74 million, or about 14%, annually on ICIs.
Most of the savings came from dosing changes to pembrolizumab and nivolumab, with greater savings achieved by combining more stewardship strategies. For instance, using strategy one (weight-based dosing alone) could lead to annual pembrolizumab savings of $14 million. Adding dose rounding (strategy two) could reduce pembrolizumab spending by $24 million. And using strategy four, with an unlimited window for vial sharing, could mean annual savings of nearly $60 million.
“Our results should prompt cost-conscious systems and payers to ask whether the amounts of drugs they’re providing to patients and how they go about making those doses are the most cost-effective approaches,” said corresponding author Garth W. Strohbehn, MD, of the University of Michigan and the VA Ann Arbor Healthcare System.
Dr. Strohbehn said the prospect of adopting these strategies hinges on several factors, with financial incentives at the prescriber and medical center level likely being the most influential.
“In fee-for-service systems, reimbursement scales with the amount of drug administered, so there can be a financial disincentive to decreasing overall drug usage,” Dr. Strohbehn explained.
“Conversely, integrated systems such as Kaiser Permanente or the VHA and large self-insured employers are incentivized to contain costs and take great care of patients, so they may be more inclined to promote these strategies,” he added.
However, Adam C. Powell, PhD, president, Payer+Provider Syndicate, who wasn’t involved in the analysis, cautioned that such a shift may come with unintended consequences.
The Infrastructure, Investment, and Jobs Act of 2021 let the Centers for Medicare and Medicaid Services seek reimbursement for discarded drugs – in effect, changing the reimbursement model for medications. That led pharmaceutical manufacturers to respond in kind by changing the dosing model, Dr. Powell said.
“Drugs that previously had personalized weight-based dosing were moved to uniform flat dosing, eliminating the potential for the manufacturer to have to issue a reimbursement if the patient’s personalized dose fell short of the amount in the single-use vial,” Dr. Powell added.
If there is a substantial migration to weight-based dosing, “it is possible that pharmaceutical manufacturers will rethink their dosing and pricing models, just as happened previously,” he cautioned.
However, these strategies could also provide relief for another escalating issue: drug shortages. Especially in the current moment, having a stewardship mindset, “might be helpful in navigating drug shortages,” Dr. Strohbehn said.
This research had no commercial funding. Dr. Bryant, Dr. Strohbehn, and Dr. Powell report no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM HEALTH AFFAIRS
Fatigue after breast cancer radiotherapy: Who’s most at risk?
Topline
Many patients with breast cancer who receive radiotherapy can still experience fatigue years after treatment; risk factors, including pain, insomnia, depression, baseline fatigue, and endocrine therapy were associated with long-term fatigue, new data show.
Methodology
- Overall, 1,443 patients with breast cancer from the REQUITE study responded to the Multidimensional Fatigue Inventory 20 (MFI-20) tool to assess five dimensions of fatigue: general, physical, and mental fatigue as well as reduced activity and motivation.
- Patients from France, Spain, Germany, Italy, the United Kingdom, and United States were assessed for characteristics, including age, body mass index (BMI), smoking, depression, pain, insomnia, fatigue, and therapy type, at baseline and at 24 months.
- Investigators identified factors associated with fatigue at 2 years post-radiotherapy among a total of 664 patients without chemotherapy and 324 with chemotherapy.
- General fatigue trajectories were classified as low, moderate, high, or decreasing.
Takeaways
- In general, levels of fatigue increased significantly from baseline to the end of radiotherapy for all fatigue dimensions (P < .05) and returned close to baseline levels after 1-2 years.
- About 24% of patients had high general fatigue trajectories and 25% had moderate, while 46% had low and 5% had decreasing fatigue trajectories.
- Factors such as age, BMI, global health status, insomnia, pain, dyspnea, depression, and baseline fatigue were each associated with multiple fatigue dimensions at 2 years; for instance, fatigue at baseline was associated with all five MFI-20 dimensions at 2 years regardless of chemotherapy status.
- Those with a combination of factors such as pain, insomnia, depression, younger age, and endocrine therapy were especially likely to develop high fatigue early and have it persist years after treatment.
In practice
the authors concluded.
Source
The study was led by Juan C. Rosas, with the German Cancer Research Center, Heidelberg. It was published online July 5 in the International Journal of Cancer.
Limitations
About one-quarter of patients did not complete the 2-year follow-up. Some variables identified in the literature as possible fatigue predictors such as socioeconomic status, physical activity, and social support were not included.
Disclosures
The study had no commercial funding. The authors reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Topline
Many patients with breast cancer who receive radiotherapy can still experience fatigue years after treatment; risk factors, including pain, insomnia, depression, baseline fatigue, and endocrine therapy were associated with long-term fatigue, new data show.
Methodology
- Overall, 1,443 patients with breast cancer from the REQUITE study responded to the Multidimensional Fatigue Inventory 20 (MFI-20) tool to assess five dimensions of fatigue: general, physical, and mental fatigue as well as reduced activity and motivation.
- Patients from France, Spain, Germany, Italy, the United Kingdom, and United States were assessed for characteristics, including age, body mass index (BMI), smoking, depression, pain, insomnia, fatigue, and therapy type, at baseline and at 24 months.
- Investigators identified factors associated with fatigue at 2 years post-radiotherapy among a total of 664 patients without chemotherapy and 324 with chemotherapy.
- General fatigue trajectories were classified as low, moderate, high, or decreasing.
Takeaways
- In general, levels of fatigue increased significantly from baseline to the end of radiotherapy for all fatigue dimensions (P < .05) and returned close to baseline levels after 1-2 years.
- About 24% of patients had high general fatigue trajectories and 25% had moderate, while 46% had low and 5% had decreasing fatigue trajectories.
- Factors such as age, BMI, global health status, insomnia, pain, dyspnea, depression, and baseline fatigue were each associated with multiple fatigue dimensions at 2 years; for instance, fatigue at baseline was associated with all five MFI-20 dimensions at 2 years regardless of chemotherapy status.
- Those with a combination of factors such as pain, insomnia, depression, younger age, and endocrine therapy were especially likely to develop high fatigue early and have it persist years after treatment.
In practice
the authors concluded.
Source
The study was led by Juan C. Rosas, with the German Cancer Research Center, Heidelberg. It was published online July 5 in the International Journal of Cancer.
Limitations
About one-quarter of patients did not complete the 2-year follow-up. Some variables identified in the literature as possible fatigue predictors such as socioeconomic status, physical activity, and social support were not included.
Disclosures
The study had no commercial funding. The authors reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Topline
Many patients with breast cancer who receive radiotherapy can still experience fatigue years after treatment; risk factors, including pain, insomnia, depression, baseline fatigue, and endocrine therapy were associated with long-term fatigue, new data show.
Methodology
- Overall, 1,443 patients with breast cancer from the REQUITE study responded to the Multidimensional Fatigue Inventory 20 (MFI-20) tool to assess five dimensions of fatigue: general, physical, and mental fatigue as well as reduced activity and motivation.
- Patients from France, Spain, Germany, Italy, the United Kingdom, and United States were assessed for characteristics, including age, body mass index (BMI), smoking, depression, pain, insomnia, fatigue, and therapy type, at baseline and at 24 months.
- Investigators identified factors associated with fatigue at 2 years post-radiotherapy among a total of 664 patients without chemotherapy and 324 with chemotherapy.
- General fatigue trajectories were classified as low, moderate, high, or decreasing.
Takeaways
- In general, levels of fatigue increased significantly from baseline to the end of radiotherapy for all fatigue dimensions (P < .05) and returned close to baseline levels after 1-2 years.
- About 24% of patients had high general fatigue trajectories and 25% had moderate, while 46% had low and 5% had decreasing fatigue trajectories.
- Factors such as age, BMI, global health status, insomnia, pain, dyspnea, depression, and baseline fatigue were each associated with multiple fatigue dimensions at 2 years; for instance, fatigue at baseline was associated with all five MFI-20 dimensions at 2 years regardless of chemotherapy status.
- Those with a combination of factors such as pain, insomnia, depression, younger age, and endocrine therapy were especially likely to develop high fatigue early and have it persist years after treatment.
In practice
the authors concluded.
Source
The study was led by Juan C. Rosas, with the German Cancer Research Center, Heidelberg. It was published online July 5 in the International Journal of Cancer.
Limitations
About one-quarter of patients did not complete the 2-year follow-up. Some variables identified in the literature as possible fatigue predictors such as socioeconomic status, physical activity, and social support were not included.
Disclosures
The study had no commercial funding. The authors reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Metachronous CRC risk after colonoscopy for positive FIT
TOPLINE:
a study suggests.
,
METHODOLOGY:
- Investigators conducted a retrospective analysis of 253,833 colonoscopies performed after FIT-positive screens in a Dutch CRC screening program.
- A Cox regression analysis assessed the association between the findings at baseline colonoscopy and metachronous CRC risk.
- Investigators categorized patients into subgroups based on removed polyp subtypes and used groups without polyps as a reference.
- High-risk subgroups included those with high-risk serrated polyps, which were defined as a serrated polyp of at least 10 mm, sessile serrated lesions with dysplasia, or traditional serrated adenomas, as well as high-risk adenomas, which were defined as an adenoma of at least 10 mm or containing high-grade dysplasia.
TAKEAWAY:
- Over a median follow-up of 36 months, 504 metachronous CRCs were identified.
- Individuals with high-risk serrated polyps without co-occurring high-risk adenomas had an increased risk for metachronous CRC (hazard ratio, 1.70).
- The highest risk was seen in individuals with both high-risk serrated polyps and high-risk adenomas (HR, 2.0), as well as those with villous adenomas (HR, 2.07).
- Individuals with only high-risk adenomas did not show a significantly increased risk for metachronous CRC (HR, 1.22).
IN PRACTICE:
“Our results suggest that individuals with high-risk serrated polyps might comprise the higher CRC risk in the first years after colonoscopy. Results of this study could contribute to establish more restrictive polyp surveillance guidelines in a quality-assured setting,” the authors wrote.
SOURCE:
The study was led by David E. F. W. M. van Toledo, MD, department of gastroenterology and hepatology, Amsterdam University Medical Centers. It was published online July 5, 2023, in eClinicalMedicine. The study received no funding.
LIMITATIONS:
The relatively short median follow-up time of 3 years may limit the assessment of long-term metachronous CRC risk. The study population consisted of FIT-positive individuals, which may introduce selection bias. The incidence of metachronous CRC in the study was lower compared with other studies, potentially affecting the risk estimates. The limited number of cases in some subgroups may result in unreliable risk estimations.
DISCLOSURES:
Dr. van Toledo declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
TOPLINE:
a study suggests.
,
METHODOLOGY:
- Investigators conducted a retrospective analysis of 253,833 colonoscopies performed after FIT-positive screens in a Dutch CRC screening program.
- A Cox regression analysis assessed the association between the findings at baseline colonoscopy and metachronous CRC risk.
- Investigators categorized patients into subgroups based on removed polyp subtypes and used groups without polyps as a reference.
- High-risk subgroups included those with high-risk serrated polyps, which were defined as a serrated polyp of at least 10 mm, sessile serrated lesions with dysplasia, or traditional serrated adenomas, as well as high-risk adenomas, which were defined as an adenoma of at least 10 mm or containing high-grade dysplasia.
TAKEAWAY:
- Over a median follow-up of 36 months, 504 metachronous CRCs were identified.
- Individuals with high-risk serrated polyps without co-occurring high-risk adenomas had an increased risk for metachronous CRC (hazard ratio, 1.70).
- The highest risk was seen in individuals with both high-risk serrated polyps and high-risk adenomas (HR, 2.0), as well as those with villous adenomas (HR, 2.07).
- Individuals with only high-risk adenomas did not show a significantly increased risk for metachronous CRC (HR, 1.22).
IN PRACTICE:
“Our results suggest that individuals with high-risk serrated polyps might comprise the higher CRC risk in the first years after colonoscopy. Results of this study could contribute to establish more restrictive polyp surveillance guidelines in a quality-assured setting,” the authors wrote.
SOURCE:
The study was led by David E. F. W. M. van Toledo, MD, department of gastroenterology and hepatology, Amsterdam University Medical Centers. It was published online July 5, 2023, in eClinicalMedicine. The study received no funding.
LIMITATIONS:
The relatively short median follow-up time of 3 years may limit the assessment of long-term metachronous CRC risk. The study population consisted of FIT-positive individuals, which may introduce selection bias. The incidence of metachronous CRC in the study was lower compared with other studies, potentially affecting the risk estimates. The limited number of cases in some subgroups may result in unreliable risk estimations.
DISCLOSURES:
Dr. van Toledo declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
TOPLINE:
a study suggests.
,
METHODOLOGY:
- Investigators conducted a retrospective analysis of 253,833 colonoscopies performed after FIT-positive screens in a Dutch CRC screening program.
- A Cox regression analysis assessed the association between the findings at baseline colonoscopy and metachronous CRC risk.
- Investigators categorized patients into subgroups based on removed polyp subtypes and used groups without polyps as a reference.
- High-risk subgroups included those with high-risk serrated polyps, which were defined as a serrated polyp of at least 10 mm, sessile serrated lesions with dysplasia, or traditional serrated adenomas, as well as high-risk adenomas, which were defined as an adenoma of at least 10 mm or containing high-grade dysplasia.
TAKEAWAY:
- Over a median follow-up of 36 months, 504 metachronous CRCs were identified.
- Individuals with high-risk serrated polyps without co-occurring high-risk adenomas had an increased risk for metachronous CRC (hazard ratio, 1.70).
- The highest risk was seen in individuals with both high-risk serrated polyps and high-risk adenomas (HR, 2.0), as well as those with villous adenomas (HR, 2.07).
- Individuals with only high-risk adenomas did not show a significantly increased risk for metachronous CRC (HR, 1.22).
IN PRACTICE:
“Our results suggest that individuals with high-risk serrated polyps might comprise the higher CRC risk in the first years after colonoscopy. Results of this study could contribute to establish more restrictive polyp surveillance guidelines in a quality-assured setting,” the authors wrote.
SOURCE:
The study was led by David E. F. W. M. van Toledo, MD, department of gastroenterology and hepatology, Amsterdam University Medical Centers. It was published online July 5, 2023, in eClinicalMedicine. The study received no funding.
LIMITATIONS:
The relatively short median follow-up time of 3 years may limit the assessment of long-term metachronous CRC risk. The study population consisted of FIT-positive individuals, which may introduce selection bias. The incidence of metachronous CRC in the study was lower compared with other studies, potentially affecting the risk estimates. The limited number of cases in some subgroups may result in unreliable risk estimations.
DISCLOSURES:
Dr. van Toledo declared no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Liquid biopsy shows big promise in oropharyngeal cancer
In a retrospective observational cohort study, a commercially available blood test used to evaluate tumor tissue–modified viral-HPV DNA demonstrated 100% specificity for both diagnosis of oropharyngeal cancer and surveillance for recurrence. Sensitivity was 91.5% for correctly identifying patients who have the disease and 88.4% for surveillance.
“A positive result appeared to confirm the presence of disease, [but] approximately 1 in 10 negative results in patients with pathologically confirmed HPV-associated oropharyngeal squamous cell carcinoma were falsely negative,” lead investigator Rocco Ferrandino, MD, with Mount Sinai, New York, said in an interview.
“Therefore, further workup should still be pursued when clinical suspicion for HPV-associated oropharynx cancer is high,” Dr. Ferrandino said.
The study was published online, in JAMA Otolaryngology–Head and Neck Surgery, to coincide with presentation at the annual meeting of the American Head and Neck Society in Montreal.
‘Remarkable promise’
The diagnosis of HPV-associated oropharyngeal cancer currently relies on a tissue-based biopsy of the primary site or a regional lymph node; however, there has been growing interest in the potential of liquid biopsy for diagnosis and surveillance.
The commercially available assay that was evaluated in the study uses a distinct method to identify and quantify a tumor-associated or tumor-modified pattern of DNA fragments that significantly increases the specificity for identifying an HPV-associated malignant tumor. However, evaluation of the assay has been limited to small cohort studies and clinical trials.
In the current study, Dr. Ferrandino and colleagues evaluated the performance of the assay used during routine clinical practice at their high-volume institution over a period of nearly 3 years.
The study included 163 patients in the diagnostic cohort and 290 in the surveillance cohort. In the diagnostic cohort, 152 had HPV-associated oropharyngeal cancer, and 11 had HPV-negative oropharyngeal cancer. The sensitivity of the assay in pretreatment diagnosis was 91.5% (139 of 152 tests), and the specificity was 100% (11 of 11 tests).
In the surveillance cohort of 290 patients, 591 tests were evaluated. A total of 23 patients developed pathologically confirmed recurrences over a median follow-up of 40.5 months. The assay demonstrated sensitivity of 88.4% (38 of 43 tests) and specificity of 100% (548 of 548 tests) in detecting recurrences.
The median lead time from positive test to pathologic confirmation was 47 days.
“The lead time provided by positive assay results may allow a window of opportunity for salvage treatment or for the application of adjuvant systemic therapy,” Dr. Ferrandino and colleagues explain.
“While these results are exciting and may support adjunctive use of circulating tumor DNA testing for diagnosis and surveillance, we really need more prospective and multicenter studies to validate these findings,” Dr. Ferrandino said in an interview.
In an accompanying commentary, Miriam Lango, MD, department of head and neck surgery, the University of Texas MD Anderson Cancer Center, Houston, said she agrees that a prospective clinical validation study is needed.
“Nevertheless, the use of this technology shows remarkable promise to transform the ability to identify and follow patients with HPV-related disease. Testing is likely to be increasingly used in routine clinical care, as it is commercially available,” Dr. Lango writes.
Still, she noted, “It is incumbent on us to establish evidence for strong and detailed surveillance guidelines to share among the cancer community.”
The study had no specific funding. Dr. Ferrandino and Dr. Lango have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a retrospective observational cohort study, a commercially available blood test used to evaluate tumor tissue–modified viral-HPV DNA demonstrated 100% specificity for both diagnosis of oropharyngeal cancer and surveillance for recurrence. Sensitivity was 91.5% for correctly identifying patients who have the disease and 88.4% for surveillance.
“A positive result appeared to confirm the presence of disease, [but] approximately 1 in 10 negative results in patients with pathologically confirmed HPV-associated oropharyngeal squamous cell carcinoma were falsely negative,” lead investigator Rocco Ferrandino, MD, with Mount Sinai, New York, said in an interview.
“Therefore, further workup should still be pursued when clinical suspicion for HPV-associated oropharynx cancer is high,” Dr. Ferrandino said.
The study was published online, in JAMA Otolaryngology–Head and Neck Surgery, to coincide with presentation at the annual meeting of the American Head and Neck Society in Montreal.
‘Remarkable promise’
The diagnosis of HPV-associated oropharyngeal cancer currently relies on a tissue-based biopsy of the primary site or a regional lymph node; however, there has been growing interest in the potential of liquid biopsy for diagnosis and surveillance.
The commercially available assay that was evaluated in the study uses a distinct method to identify and quantify a tumor-associated or tumor-modified pattern of DNA fragments that significantly increases the specificity for identifying an HPV-associated malignant tumor. However, evaluation of the assay has been limited to small cohort studies and clinical trials.
In the current study, Dr. Ferrandino and colleagues evaluated the performance of the assay used during routine clinical practice at their high-volume institution over a period of nearly 3 years.
The study included 163 patients in the diagnostic cohort and 290 in the surveillance cohort. In the diagnostic cohort, 152 had HPV-associated oropharyngeal cancer, and 11 had HPV-negative oropharyngeal cancer. The sensitivity of the assay in pretreatment diagnosis was 91.5% (139 of 152 tests), and the specificity was 100% (11 of 11 tests).
In the surveillance cohort of 290 patients, 591 tests were evaluated. A total of 23 patients developed pathologically confirmed recurrences over a median follow-up of 40.5 months. The assay demonstrated sensitivity of 88.4% (38 of 43 tests) and specificity of 100% (548 of 548 tests) in detecting recurrences.
The median lead time from positive test to pathologic confirmation was 47 days.
“The lead time provided by positive assay results may allow a window of opportunity for salvage treatment or for the application of adjuvant systemic therapy,” Dr. Ferrandino and colleagues explain.
“While these results are exciting and may support adjunctive use of circulating tumor DNA testing for diagnosis and surveillance, we really need more prospective and multicenter studies to validate these findings,” Dr. Ferrandino said in an interview.
In an accompanying commentary, Miriam Lango, MD, department of head and neck surgery, the University of Texas MD Anderson Cancer Center, Houston, said she agrees that a prospective clinical validation study is needed.
“Nevertheless, the use of this technology shows remarkable promise to transform the ability to identify and follow patients with HPV-related disease. Testing is likely to be increasingly used in routine clinical care, as it is commercially available,” Dr. Lango writes.
Still, she noted, “It is incumbent on us to establish evidence for strong and detailed surveillance guidelines to share among the cancer community.”
The study had no specific funding. Dr. Ferrandino and Dr. Lango have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a retrospective observational cohort study, a commercially available blood test used to evaluate tumor tissue–modified viral-HPV DNA demonstrated 100% specificity for both diagnosis of oropharyngeal cancer and surveillance for recurrence. Sensitivity was 91.5% for correctly identifying patients who have the disease and 88.4% for surveillance.
“A positive result appeared to confirm the presence of disease, [but] approximately 1 in 10 negative results in patients with pathologically confirmed HPV-associated oropharyngeal squamous cell carcinoma were falsely negative,” lead investigator Rocco Ferrandino, MD, with Mount Sinai, New York, said in an interview.
“Therefore, further workup should still be pursued when clinical suspicion for HPV-associated oropharynx cancer is high,” Dr. Ferrandino said.
The study was published online, in JAMA Otolaryngology–Head and Neck Surgery, to coincide with presentation at the annual meeting of the American Head and Neck Society in Montreal.
‘Remarkable promise’
The diagnosis of HPV-associated oropharyngeal cancer currently relies on a tissue-based biopsy of the primary site or a regional lymph node; however, there has been growing interest in the potential of liquid biopsy for diagnosis and surveillance.
The commercially available assay that was evaluated in the study uses a distinct method to identify and quantify a tumor-associated or tumor-modified pattern of DNA fragments that significantly increases the specificity for identifying an HPV-associated malignant tumor. However, evaluation of the assay has been limited to small cohort studies and clinical trials.
In the current study, Dr. Ferrandino and colleagues evaluated the performance of the assay used during routine clinical practice at their high-volume institution over a period of nearly 3 years.
The study included 163 patients in the diagnostic cohort and 290 in the surveillance cohort. In the diagnostic cohort, 152 had HPV-associated oropharyngeal cancer, and 11 had HPV-negative oropharyngeal cancer. The sensitivity of the assay in pretreatment diagnosis was 91.5% (139 of 152 tests), and the specificity was 100% (11 of 11 tests).
In the surveillance cohort of 290 patients, 591 tests were evaluated. A total of 23 patients developed pathologically confirmed recurrences over a median follow-up of 40.5 months. The assay demonstrated sensitivity of 88.4% (38 of 43 tests) and specificity of 100% (548 of 548 tests) in detecting recurrences.
The median lead time from positive test to pathologic confirmation was 47 days.
“The lead time provided by positive assay results may allow a window of opportunity for salvage treatment or for the application of adjuvant systemic therapy,” Dr. Ferrandino and colleagues explain.
“While these results are exciting and may support adjunctive use of circulating tumor DNA testing for diagnosis and surveillance, we really need more prospective and multicenter studies to validate these findings,” Dr. Ferrandino said in an interview.
In an accompanying commentary, Miriam Lango, MD, department of head and neck surgery, the University of Texas MD Anderson Cancer Center, Houston, said she agrees that a prospective clinical validation study is needed.
“Nevertheless, the use of this technology shows remarkable promise to transform the ability to identify and follow patients with HPV-related disease. Testing is likely to be increasingly used in routine clinical care, as it is commercially available,” Dr. Lango writes.
Still, she noted, “It is incumbent on us to establish evidence for strong and detailed surveillance guidelines to share among the cancer community.”
The study had no specific funding. Dr. Ferrandino and Dr. Lango have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA OTOLARYNGOLOGY–HEAD AND NECK SURGERY