Federal Practitioner

Moderate to vigorous physical activity (MVPA) is a familiar and established approach to reducing cardiovascular (CV) risk, but it’s often believed that the exercise should be spread out across the week rather than concentrated within a couple of days.

A challenge to that view comes from an observational study of accelerometer-confirmed exercise in almost 90,000 people in their 60s. It suggests, among those who exercised at least 2.5 hours per week, similar CV-risk reductions in “weekend warriors” (WW) who focused their workouts on 1 or 2 days per week and those who spread their weekly exercise over more days.

Researchers compared three patterns of MVPA in their subjects who wore accelerometers on their wrists for 1 week. Active WW subjects obtained at least 2.5 hours of exercise weekly, with at least half the amount completed over 1-2 days; “active regular” subjects achieved that exercise level but not mostly during 1 or 2 days; and those who were “inactive” fell short of 2.5 hours of exercise during the week. The group used a median exercise threshold of 3 hours, 50 minutes in a separate analysis.

The “active” groups, compared with inactive subjects, achieved similar and significant reductions in risk for incident atrial fibrillation (AF), myocardial infarction (MI), stroke, and heart failure (HF) over a median follow-up of 6.3 years at both weekly exercise thresholds, the group reported.

“The take-home [message] is that efforts to optimize activity, even if concentrated within just a day or 2 each week, should be expected to result in improved cardiovascular risk profiles,” lead author Shaan Khurshid, MD, MPH, Massachusetts General Hospital, Boston, said in an interview.

The study was published online in JAMA.

The research “provides novel data on patterns of physical activity accumulation and the risk of developing cardiovascular diseases,” observed Peter Katzmarzyk, PhD, Pennington Biomedical Research Center, Baton Rouge, La., in an interview. He was not involved with the research. Its “marked strengths,” he noted, include a large sample population and “use of accelerometers to measure physical activity levels and patterns.”

Moreover, Dr. Katzmarzyk said, its findings are “important” for showing that physical activity “can be accumulated throughout the week in different ways, which opens up more options for busy people to get their physical activity in.”

Current guidelines from the World Health Organization and the American Heart Association recommend at least 150 minutes of MVPA weekly to lower risk for cardiovascular disease and death, but do not specify an optimal exercise time frame. The U.K. National Health Service recommends MVPA daily or spread evenly over perhaps 4-5 days.

“The weekend warrior pattern has been studied previously, but typically relying on self-reported data, which may be biased, or [in studies] too small to look at specific cardiovascular outcomes,” Dr. Khurshid explained.

In the UK Biobank database, he said, “We saw the opportunity to leverage the largest sample of measured activity to date” to address the question of whether exercise time pattern “affects specific major cardiovascular diseases differently,” Dr. Khurshid said

The primary analysis assessed exercise amount in a week based on the guideline-recommended threshold of at least 2.5 hours; a 3-hour, 50-minutes threshold was used in a secondary analysis. The group assessed multiple thresholds because optimal MVPS levels derived from wrist-based accelerometers are “unclear,” he said.

The sample consisted of 89,573 participants with a mean age 62; slightly more than half (56%) were women. Based on the weekly MVPA threshold of 2.5 hours , the WW, active regular, and inactive groups made up 42.2%, 24%, and 33.7% of the population, respectively.

Compared with the inactive group, the two active groups both showed significant risk reductions for the four clinical outcomes, to similar degrees, in multivariate analysis. The results were similar at the 230-minute weekly exercise threshold for incident AF, MI, and HF but not for stroke.

A version of this article appeared on Medscape.com.

Moderate to vigorous physical activity (MVPA) is a familiar and established approach to reducing cardiovascular (CV) risk, but it’s often believed that the exercise should be spread out across the week rather than concentrated within a couple of days.

A challenge to that view comes from an observational study of accelerometer-confirmed exercise in almost 90,000 people in their 60s. It suggests, among those who exercised at least 2.5 hours per week, similar CV-risk reductions in “weekend warriors” (WW) who focused their workouts on 1 or 2 days per week and those who spread their weekly exercise over more days.

Researchers compared three patterns of MVPA in their subjects who wore accelerometers on their wrists for 1 week. Active WW subjects obtained at least 2.5 hours of exercise weekly, with at least half the amount completed over 1-2 days; “active regular” subjects achieved that exercise level but not mostly during 1 or 2 days; and those who were “inactive” fell short of 2.5 hours of exercise during the week. The group used a median exercise threshold of 3 hours, 50 minutes in a separate analysis.

The “active” groups, compared with inactive subjects, achieved similar and significant reductions in risk for incident atrial fibrillation (AF), myocardial infarction (MI), stroke, and heart failure (HF) over a median follow-up of 6.3 years at both weekly exercise thresholds, the group reported.

“The take-home [message] is that efforts to optimize activity, even if concentrated within just a day or 2 each week, should be expected to result in improved cardiovascular risk profiles,” lead author Shaan Khurshid, MD, MPH, Massachusetts General Hospital, Boston, said in an interview.

The study was published online in JAMA.

The research “provides novel data on patterns of physical activity accumulation and the risk of developing cardiovascular diseases,” observed Peter Katzmarzyk, PhD, Pennington Biomedical Research Center, Baton Rouge, La., in an interview. He was not involved with the research. Its “marked strengths,” he noted, include a large sample population and “use of accelerometers to measure physical activity levels and patterns.”

Moreover, Dr. Katzmarzyk said, its findings are “important” for showing that physical activity “can be accumulated throughout the week in different ways, which opens up more options for busy people to get their physical activity in.”

Current guidelines from the World Health Organization and the American Heart Association recommend at least 150 minutes of MVPA weekly to lower risk for cardiovascular disease and death, but do not specify an optimal exercise time frame. The U.K. National Health Service recommends MVPA daily or spread evenly over perhaps 4-5 days.

“The weekend warrior pattern has been studied previously, but typically relying on self-reported data, which may be biased, or [in studies] too small to look at specific cardiovascular outcomes,” Dr. Khurshid explained.

In the UK Biobank database, he said, “We saw the opportunity to leverage the largest sample of measured activity to date” to address the question of whether exercise time pattern “affects specific major cardiovascular diseases differently,” Dr. Khurshid said

The primary analysis assessed exercise amount in a week based on the guideline-recommended threshold of at least 2.5 hours; a 3-hour, 50-minutes threshold was used in a secondary analysis. The group assessed multiple thresholds because optimal MVPS levels derived from wrist-based accelerometers are “unclear,” he said.

The sample consisted of 89,573 participants with a mean age 62; slightly more than half (56%) were women. Based on the weekly MVPA threshold of 2.5 hours , the WW, active regular, and inactive groups made up 42.2%, 24%, and 33.7% of the population, respectively.

Compared with the inactive group, the two active groups both showed significant risk reductions for the four clinical outcomes, to similar degrees, in multivariate analysis. The results were similar at the 230-minute weekly exercise threshold for incident AF, MI, and HF but not for stroke.

A version of this article appeared on Medscape.com.

Moderate to vigorous physical activity (MVPA) is a familiar and established approach to reducing cardiovascular (CV) risk, but it’s often believed that the exercise should be spread out across the week rather than concentrated within a couple of days.

A challenge to that view comes from an observational study of accelerometer-confirmed exercise in almost 90,000 people in their 60s. It suggests, among those who exercised at least 2.5 hours per week, similar CV-risk reductions in “weekend warriors” (WW) who focused their workouts on 1 or 2 days per week and those who spread their weekly exercise over more days.

Researchers compared three patterns of MVPA in their subjects who wore accelerometers on their wrists for 1 week. Active WW subjects obtained at least 2.5 hours of exercise weekly, with at least half the amount completed over 1-2 days; “active regular” subjects achieved that exercise level but not mostly during 1 or 2 days; and those who were “inactive” fell short of 2.5 hours of exercise during the week. The group used a median exercise threshold of 3 hours, 50 minutes in a separate analysis.

The “active” groups, compared with inactive subjects, achieved similar and significant reductions in risk for incident atrial fibrillation (AF), myocardial infarction (MI), stroke, and heart failure (HF) over a median follow-up of 6.3 years at both weekly exercise thresholds, the group reported.

“The take-home [message] is that efforts to optimize activity, even if concentrated within just a day or 2 each week, should be expected to result in improved cardiovascular risk profiles,” lead author Shaan Khurshid, MD, MPH, Massachusetts General Hospital, Boston, said in an interview.

The study was published online in JAMA.

The research “provides novel data on patterns of physical activity accumulation and the risk of developing cardiovascular diseases,” observed Peter Katzmarzyk, PhD, Pennington Biomedical Research Center, Baton Rouge, La., in an interview. He was not involved with the research. Its “marked strengths,” he noted, include a large sample population and “use of accelerometers to measure physical activity levels and patterns.”

Moreover, Dr. Katzmarzyk said, its findings are “important” for showing that physical activity “can be accumulated throughout the week in different ways, which opens up more options for busy people to get their physical activity in.”

Current guidelines from the World Health Organization and the American Heart Association recommend at least 150 minutes of MVPA weekly to lower risk for cardiovascular disease and death, but do not specify an optimal exercise time frame. The U.K. National Health Service recommends MVPA daily or spread evenly over perhaps 4-5 days.

“The weekend warrior pattern has been studied previously, but typically relying on self-reported data, which may be biased, or [in studies] too small to look at specific cardiovascular outcomes,” Dr. Khurshid explained.

In the UK Biobank database, he said, “We saw the opportunity to leverage the largest sample of measured activity to date” to address the question of whether exercise time pattern “affects specific major cardiovascular diseases differently,” Dr. Khurshid said

The primary analysis assessed exercise amount in a week based on the guideline-recommended threshold of at least 2.5 hours; a 3-hour, 50-minutes threshold was used in a secondary analysis. The group assessed multiple thresholds because optimal MVPS levels derived from wrist-based accelerometers are “unclear,” he said.

The sample consisted of 89,573 participants with a mean age 62; slightly more than half (56%) were women. Based on the weekly MVPA threshold of 2.5 hours , the WW, active regular, and inactive groups made up 42.2%, 24%, and 33.7% of the population, respectively.

Compared with the inactive group, the two active groups both showed significant risk reductions for the four clinical outcomes, to similar degrees, in multivariate analysis. The results were similar at the 230-minute weekly exercise threshold for incident AF, MI, and HF but not for stroke.

A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved quizartinib (Vanflyta) for adults with acute myeloid leukemia (AML) that carries the FLT3-ITD genetic mutation.

On July 20 the FDA also approved the LeukoStrat CDx FLT3 Mutation Assay to determine whether patients have this mutation.

The agency granted quizartinib a first-line indication for use in combination with standard chemotherapy – cytarabine and anthracycline induction followed by cytarabine consolidation – and as maintenance monotherapy afterwards, in adults whose tumors express FLT3-ITD.

The FLT3 protein is a tyrosine kinase receptor found on hematopoietic stem cells. Wild-type FLT3 promotes cell survival, growth, and differentiation, but ITD (internal tandem duplication)-mutated FLT3, which quizartinib targets, is associated with a higher relapse risk and shorter survival. About a quarter of AML patients carry the mutation. 

Approval was based on the phase 3 QuANTUM-First trial in over 500 patients with the mutation. Median overall survival among patients on standard chemotherapy randomly assigned to quizartinib was 31.9 months versus 15.1 months in patients randomly assigned to placebo, a 22.4% reduction in the risk of death (P = .0324).

Quizartinib is not indicated as maintenance monotherapy after allogeneic hematopoietic stem cell transplantation.

In a company press release, the drug’s manufacturer Daiichi Sankyo said quizartinib will be available in the United States soon.

Company executive Ken Takeshita, MD, called the approval “an important milestone, as patients with the FLT3-ITD subtype of AML can now be treated with the first-ever FLT3 inhibitor approved across the three phases of treatment these patients typically receive.”

The FDA’s original decision date was April 24, but the agency pushed it back 3 months to review updates Daiichi Sankyo made to quizartinib’s Risk Evaluation and Mitigation Strategies (REMS) program in response to an agency request.

Quizartinib carries a boxed warning of QT prolongation, torsades de pointes, and cardiac arrest. Because of these risks, it’s only available through a new program, dubbed “Vanflyta REMS.”

In the trial, the most common adverse with quizartinib included lymphopenia (60%), hypokalemia (59%), hypoalbuminemia (53%), hypophosphatemia (52%), alkaline phosphatase increased (51%), hypomagnesemia (44%), febrile neutropenia (44%), diarrhea (42%), mucositis (38%), nausea (34%), and hypocalcemia (33%), among others.

The most common grade 3/4 adverse events were febrile neutropenia (43% with quizartinib vs. 41% with placebo), neutropenia (18% vs. 9%), hypokalemia (19% vs. 16%), and pneumonia (11% both). Adverse events were fatal in 11.3% of patients receiving quizartinib versus 9.7% of patients on placebo, mostly caused by infections.

In 2019, the FDA rejected quizartinib for FLT3-ITD mutated relapsed/refractory AML monotherapy in adults, after most of its oncology advisers thought the risk of treatment outweighed the benefits in an earlier trial.

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

The Food and Drug Administration has approved quizartinib (Vanflyta) for adults with acute myeloid leukemia (AML) that carries the FLT3-ITD genetic mutation.

On July 20 the FDA also approved the LeukoStrat CDx FLT3 Mutation Assay to determine whether patients have this mutation.

The agency granted quizartinib a first-line indication for use in combination with standard chemotherapy – cytarabine and anthracycline induction followed by cytarabine consolidation – and as maintenance monotherapy afterwards, in adults whose tumors express FLT3-ITD.

The FLT3 protein is a tyrosine kinase receptor found on hematopoietic stem cells. Wild-type FLT3 promotes cell survival, growth, and differentiation, but ITD (internal tandem duplication)-mutated FLT3, which quizartinib targets, is associated with a higher relapse risk and shorter survival. About a quarter of AML patients carry the mutation. 

Approval was based on the phase 3 QuANTUM-First trial in over 500 patients with the mutation. Median overall survival among patients on standard chemotherapy randomly assigned to quizartinib was 31.9 months versus 15.1 months in patients randomly assigned to placebo, a 22.4% reduction in the risk of death (P = .0324).

Quizartinib is not indicated as maintenance monotherapy after allogeneic hematopoietic stem cell transplantation.

In a company press release, the drug’s manufacturer Daiichi Sankyo said quizartinib will be available in the United States soon.

Company executive Ken Takeshita, MD, called the approval “an important milestone, as patients with the FLT3-ITD subtype of AML can now be treated with the first-ever FLT3 inhibitor approved across the three phases of treatment these patients typically receive.”

The FDA’s original decision date was April 24, but the agency pushed it back 3 months to review updates Daiichi Sankyo made to quizartinib’s Risk Evaluation and Mitigation Strategies (REMS) program in response to an agency request.

Quizartinib carries a boxed warning of QT prolongation, torsades de pointes, and cardiac arrest. Because of these risks, it’s only available through a new program, dubbed “Vanflyta REMS.”

In the trial, the most common adverse with quizartinib included lymphopenia (60%), hypokalemia (59%), hypoalbuminemia (53%), hypophosphatemia (52%), alkaline phosphatase increased (51%), hypomagnesemia (44%), febrile neutropenia (44%), diarrhea (42%), mucositis (38%), nausea (34%), and hypocalcemia (33%), among others.

The most common grade 3/4 adverse events were febrile neutropenia (43% with quizartinib vs. 41% with placebo), neutropenia (18% vs. 9%), hypokalemia (19% vs. 16%), and pneumonia (11% both). Adverse events were fatal in 11.3% of patients receiving quizartinib versus 9.7% of patients on placebo, mostly caused by infections.

In 2019, the FDA rejected quizartinib for FLT3-ITD mutated relapsed/refractory AML monotherapy in adults, after most of its oncology advisers thought the risk of treatment outweighed the benefits in an earlier trial.

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

The Food and Drug Administration has approved quizartinib (Vanflyta) for adults with acute myeloid leukemia (AML) that carries the FLT3-ITD genetic mutation.

On July 20 the FDA also approved the LeukoStrat CDx FLT3 Mutation Assay to determine whether patients have this mutation.

The agency granted quizartinib a first-line indication for use in combination with standard chemotherapy – cytarabine and anthracycline induction followed by cytarabine consolidation – and as maintenance monotherapy afterwards, in adults whose tumors express FLT3-ITD.

The FLT3 protein is a tyrosine kinase receptor found on hematopoietic stem cells. Wild-type FLT3 promotes cell survival, growth, and differentiation, but ITD (internal tandem duplication)-mutated FLT3, which quizartinib targets, is associated with a higher relapse risk and shorter survival. About a quarter of AML patients carry the mutation. 

Approval was based on the phase 3 QuANTUM-First trial in over 500 patients with the mutation. Median overall survival among patients on standard chemotherapy randomly assigned to quizartinib was 31.9 months versus 15.1 months in patients randomly assigned to placebo, a 22.4% reduction in the risk of death (P = .0324).

Quizartinib is not indicated as maintenance monotherapy after allogeneic hematopoietic stem cell transplantation.

In a company press release, the drug’s manufacturer Daiichi Sankyo said quizartinib will be available in the United States soon.

Company executive Ken Takeshita, MD, called the approval “an important milestone, as patients with the FLT3-ITD subtype of AML can now be treated with the first-ever FLT3 inhibitor approved across the three phases of treatment these patients typically receive.”

The FDA’s original decision date was April 24, but the agency pushed it back 3 months to review updates Daiichi Sankyo made to quizartinib’s Risk Evaluation and Mitigation Strategies (REMS) program in response to an agency request.

Quizartinib carries a boxed warning of QT prolongation, torsades de pointes, and cardiac arrest. Because of these risks, it’s only available through a new program, dubbed “Vanflyta REMS.”

In the trial, the most common adverse with quizartinib included lymphopenia (60%), hypokalemia (59%), hypoalbuminemia (53%), hypophosphatemia (52%), alkaline phosphatase increased (51%), hypomagnesemia (44%), febrile neutropenia (44%), diarrhea (42%), mucositis (38%), nausea (34%), and hypocalcemia (33%), among others.

The most common grade 3/4 adverse events were febrile neutropenia (43% with quizartinib vs. 41% with placebo), neutropenia (18% vs. 9%), hypokalemia (19% vs. 16%), and pneumonia (11% both). Adverse events were fatal in 11.3% of patients receiving quizartinib versus 9.7% of patients on placebo, mostly caused by infections.

In 2019, the FDA rejected quizartinib for FLT3-ITD mutated relapsed/refractory AML monotherapy in adults, after most of its oncology advisers thought the risk of treatment outweighed the benefits in an earlier trial.

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

The effect of the highly touted MIND diet with mild calorie restriction offered no greater protection against cognitive decline than a control diet with mild calorie restriction alone 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.

The effect of the highly touted MIND diet with mild calorie restriction offered no greater protection against cognitive decline than a control diet with mild calorie restriction alone 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.

The effect of the highly touted MIND diet with mild calorie restriction offered no greater protection against cognitive decline than a control diet with mild calorie restriction alone 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.

TOPLINE:

Researchers found that, prior to resection, performing a minimally invasive staging procedure on newly diagnosed patients with pancreatic cancer helped identify metastatic disease and cancer stage, and prompted a change in management in about one in five patients.

METHODOLOGY:

• The study included 1,004 patients who underwent staging laparoscopy at the Mayo Clinic, Rochester, Minn., from January 2017 to December 2021. 
• Patients’ median age was 66 years; 48% of the cohort were female. 
• Tumor location was proximal in 644 patients (64%) and distal in 360 patients (36%); median tumor size was 29 mm. 
• Upfront resectable disease was present in 351 patients (35%), and borderline resectable or locally advanced anatomy was present in 653 (65%).

TAKEAWAY:

• Overall, 180 patients had a positive staging laparoscopy because of gross metastatic disease (n = 140) and/or positive peritoneal cytology (n = 96); patients who underwent neoadjuvant chemotherapy before staging laparoscopy had lower rates of positive laparoscopy (14% vs. 22%; P = .002).
• When the analysis was restricted to chemo-naive patients who had concurrent peritoneal lavage performed, 95 of 419 patients (23%) had positive laparoscopy. 
• Among 721 patients who had a staged procedure with peritoneal washings, 151 (21%) had confirmed metastatic disease; cytology was positive in 96 (13%).
• Among patients with positive staging laparoscopy, median overall survival was 11 months in those with gross metastatic disease and 13 months in those with positive peritoneal cytology only (P = .40).

IN PRACTICE:

“Staging laparoscopy should be considered in the majority of patients prior to resection and/or initiation of neoadjuvant therapy, specifically in patients with high-risk features such as indeterminate extrapancreatic lesions on imaging, young age, large tumor size, distal tumor location, or elevated serum tumor markers,” the authors concluded. 

SOURCE:

The study, led by Hallbera Gudmundsdottir, MD, of the Mayo Clinic was published in the  Journal of the American College of Surgeons  in June. 

LIMITATIONS:

Staging laparoscopy may have been performed in higher-risk patients in earlier years of the study. The Mayo Clinic is a high-volume pancreatic surgery center that sees high-risk patients with advances lesions. This study population may not be generalizable to the those at other centers.

DISCLOSURES:

The authors did not disclose any financial interests.

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

TOPLINE:

Researchers found that, prior to resection, performing a minimally invasive staging procedure on newly diagnosed patients with pancreatic cancer helped identify metastatic disease and cancer stage, and prompted a change in management in about one in five patients.

METHODOLOGY:

• The study included 1,004 patients who underwent staging laparoscopy at the Mayo Clinic, Rochester, Minn., from January 2017 to December 2021. 
• Patients’ median age was 66 years; 48% of the cohort were female. 
• Tumor location was proximal in 644 patients (64%) and distal in 360 patients (36%); median tumor size was 29 mm. 
• Upfront resectable disease was present in 351 patients (35%), and borderline resectable or locally advanced anatomy was present in 653 (65%).

TAKEAWAY:

• Overall, 180 patients had a positive staging laparoscopy because of gross metastatic disease (n = 140) and/or positive peritoneal cytology (n = 96); patients who underwent neoadjuvant chemotherapy before staging laparoscopy had lower rates of positive laparoscopy (14% vs. 22%; P = .002).
• When the analysis was restricted to chemo-naive patients who had concurrent peritoneal lavage performed, 95 of 419 patients (23%) had positive laparoscopy. 
• Among 721 patients who had a staged procedure with peritoneal washings, 151 (21%) had confirmed metastatic disease; cytology was positive in 96 (13%).
• Among patients with positive staging laparoscopy, median overall survival was 11 months in those with gross metastatic disease and 13 months in those with positive peritoneal cytology only (P = .40).

IN PRACTICE:

“Staging laparoscopy should be considered in the majority of patients prior to resection and/or initiation of neoadjuvant therapy, specifically in patients with high-risk features such as indeterminate extrapancreatic lesions on imaging, young age, large tumor size, distal tumor location, or elevated serum tumor markers,” the authors concluded. 

SOURCE:

The study, led by Hallbera Gudmundsdottir, MD, of the Mayo Clinic was published in the  Journal of the American College of Surgeons  in June. 

LIMITATIONS:

Staging laparoscopy may have been performed in higher-risk patients in earlier years of the study. The Mayo Clinic is a high-volume pancreatic surgery center that sees high-risk patients with advances lesions. This study population may not be generalizable to the those at other centers.

DISCLOSURES:

The authors did not disclose any financial interests.

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

TOPLINE:

Researchers found that, prior to resection, performing a minimally invasive staging procedure on newly diagnosed patients with pancreatic cancer helped identify metastatic disease and cancer stage, and prompted a change in management in about one in five patients.

METHODOLOGY:

• The study included 1,004 patients who underwent staging laparoscopy at the Mayo Clinic, Rochester, Minn., from January 2017 to December 2021. 
• Patients’ median age was 66 years; 48% of the cohort were female. 
• Tumor location was proximal in 644 patients (64%) and distal in 360 patients (36%); median tumor size was 29 mm. 
• Upfront resectable disease was present in 351 patients (35%), and borderline resectable or locally advanced anatomy was present in 653 (65%).

TAKEAWAY:

• Overall, 180 patients had a positive staging laparoscopy because of gross metastatic disease (n = 140) and/or positive peritoneal cytology (n = 96); patients who underwent neoadjuvant chemotherapy before staging laparoscopy had lower rates of positive laparoscopy (14% vs. 22%; P = .002).
• When the analysis was restricted to chemo-naive patients who had concurrent peritoneal lavage performed, 95 of 419 patients (23%) had positive laparoscopy. 
• Among 721 patients who had a staged procedure with peritoneal washings, 151 (21%) had confirmed metastatic disease; cytology was positive in 96 (13%).
• Among patients with positive staging laparoscopy, median overall survival was 11 months in those with gross metastatic disease and 13 months in those with positive peritoneal cytology only (P = .40).

IN PRACTICE:

“Staging laparoscopy should be considered in the majority of patients prior to resection and/or initiation of neoadjuvant therapy, specifically in patients with high-risk features such as indeterminate extrapancreatic lesions on imaging, young age, large tumor size, distal tumor location, or elevated serum tumor markers,” the authors concluded. 

SOURCE:

The study, led by Hallbera Gudmundsdottir, MD, of the Mayo Clinic was published in the  Journal of the American College of Surgeons  in June. 

LIMITATIONS:

Staging laparoscopy may have been performed in higher-risk patients in earlier years of the study. The Mayo Clinic is a high-volume pancreatic surgery center that sees high-risk patients with advances lesions. This study population may not be generalizable to the those at other centers.

DISCLOSURES:

The authors did not disclose any financial interests.

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

Dysphagia is one of the most common side effects of radiation for head and neck cancer and can be so bad that patients require a permanent gastrostomy tube for feeding.

A team of British investigators are now reporting a new strategy to help lessen this problem.

In the trial, the approach – dubbed dysphagia-optimized intensity-modulated radiotherapy (DO-IMRT) – reduced incidental radiation to the pharyngeal constrictor muscles responsible for swallowing during IMRT for pharyngeal cancer. Patients randomized to DO-IMRT reported significant improvements in swallowing at 1 year, compared with those receiving standard IMRT, at no cost to oncologic outcomes.

Overall, the findings show “DO-IMRT improves patient-reported swallowing function, compared with standard IMRT,” said investigators led by Christopher Nutting, MD, PhD, a head and neck cancer specialist at the Royal Marsden Hospital, London. “DO-IMRT should be considered a new standard of care.”

The team reported the results of their phase 3 trial in The Lancet Oncology.

Swallowing issues affect most patients with head and neck cancer after radiation therapy but strategies to mitigate this long-term adverse effect remain limited.

Dr. Nutting and colleagues wanted to assess whether a novel approach to radiation therapy could reduce the swallowing problems patients often encounter.

In the trial, 112 subjects with T1-4, N0-3, M0 oropharyngeal (90%) or hypopharyngeal cancer (10%) were randomized to standard IMRT or DO-IMRT. Patients received care at 22 radiation therapy centers in Ireland and the UK from 2016 to 2018.

Patients got radiation in 30 fractions over 6 weeks; most also had chemotherapy. The standard IMRT group received 65 Gy to their primary and nodal tumors and 54 Gy to other pharyngeal and nodal areas. In the DO-IMRT group, radiation doses to pharyngeal constrictor muscles lying outside of the tumor target area were limited to 50 Gy.

At 1 year, 56 patients randomized to DO-IMRT scored, on average, 7.2 points higher than the 56 patients randomized to standard IMRT – 77.7 points vs. 70.6 (P = .037) – on the 100-point MD Anderson Dysphagia Inventory (MDADI). MDADI is a validated scale for tracking radiation-induced dysphagia, with higher scores indicating better swallowing function.

The difference grew to 9.8 points when adjusted for chemotherapy use and tumor location and stage.

DO-IMRT patients were also more likely to report eating their normal diet and dining in public. Speech and language therapists who, like patients, were blinded to treatment allocation, reported better outcomes among patients receiving DO-IMRT as well.

At just over 3 years, oncologic outcomes were essentially equivalent in both groups. Two local recurrences occurred in both arms; distant metastatic recurrences occurred in three patients in the DO-IMRT group and two in the standard IMRT group.

The most common grade 3-4 late adverse events were hearing impairment (16% with DO-IMRT vs. 13% with standard IMRT), dry mouth (5% vs. 15%), and dysphagia (5% vs. 15%).

Taken together, the findings indicate that reducing doses to the pharyngeal constrictor muscle translates to “a meaningful benefit for patients” in terms of improved swallowing function, the investigators said.

In an accompanying editorial, Sandra Nuyts, MD, PhD, noted, however, that the trial failed to meet the predefined threshold for clinical significance, a 10-point difference in MDADI scores.

Still, “several other patient-reported and physician-reported secondary endpoints favored DO-IMRT,” explained Dr. Nuyts, a radiation oncologist at the Leuven Cancer Institute, Belgium. Considered alongside positive reports from smaller, nonrandomized studies, “there is now compelling evidence that the risk of dysphagia after head and neck radiotherapy can be reduced with this technology, without increasing the risk of local recurrences.”

The study team and Dr. Nuyts both called for further refinement of the technique, particularly figuring out what specific sections of the constrictor muscles need to be spared to optimize outcomes.

For now, there is a limit on “how much organ sparing can be achieved with the current DO-IMRT technique” because “use of even narrower margins” around the tumor runs the risk of not treating it adequately, investigators said.

The study was funded by Cancer Research UK. Dr. Nutting reports stock options in Advanced Oncotherapy. Another investigator reports institutional grants from Varian, AstraZeneca, Roche, and other companies. Dr. Nuyts reports no relevant financial relationships.

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

Dysphagia is one of the most common side effects of radiation for head and neck cancer and can be so bad that patients require a permanent gastrostomy tube for feeding.

A team of British investigators are now reporting a new strategy to help lessen this problem.

In the trial, the approach – dubbed dysphagia-optimized intensity-modulated radiotherapy (DO-IMRT) – reduced incidental radiation to the pharyngeal constrictor muscles responsible for swallowing during IMRT for pharyngeal cancer. Patients randomized to DO-IMRT reported significant improvements in swallowing at 1 year, compared with those receiving standard IMRT, at no cost to oncologic outcomes.

Overall, the findings show “DO-IMRT improves patient-reported swallowing function, compared with standard IMRT,” said investigators led by Christopher Nutting, MD, PhD, a head and neck cancer specialist at the Royal Marsden Hospital, London. “DO-IMRT should be considered a new standard of care.”

The team reported the results of their phase 3 trial in The Lancet Oncology.

Swallowing issues affect most patients with head and neck cancer after radiation therapy but strategies to mitigate this long-term adverse effect remain limited.

Dr. Nutting and colleagues wanted to assess whether a novel approach to radiation therapy could reduce the swallowing problems patients often encounter.

In the trial, 112 subjects with T1-4, N0-3, M0 oropharyngeal (90%) or hypopharyngeal cancer (10%) were randomized to standard IMRT or DO-IMRT. Patients received care at 22 radiation therapy centers in Ireland and the UK from 2016 to 2018.

Patients got radiation in 30 fractions over 6 weeks; most also had chemotherapy. The standard IMRT group received 65 Gy to their primary and nodal tumors and 54 Gy to other pharyngeal and nodal areas. In the DO-IMRT group, radiation doses to pharyngeal constrictor muscles lying outside of the tumor target area were limited to 50 Gy.

At 1 year, 56 patients randomized to DO-IMRT scored, on average, 7.2 points higher than the 56 patients randomized to standard IMRT – 77.7 points vs. 70.6 (P = .037) – on the 100-point MD Anderson Dysphagia Inventory (MDADI). MDADI is a validated scale for tracking radiation-induced dysphagia, with higher scores indicating better swallowing function.

The difference grew to 9.8 points when adjusted for chemotherapy use and tumor location and stage.

DO-IMRT patients were also more likely to report eating their normal diet and dining in public. Speech and language therapists who, like patients, were blinded to treatment allocation, reported better outcomes among patients receiving DO-IMRT as well.

At just over 3 years, oncologic outcomes were essentially equivalent in both groups. Two local recurrences occurred in both arms; distant metastatic recurrences occurred in three patients in the DO-IMRT group and two in the standard IMRT group.

The most common grade 3-4 late adverse events were hearing impairment (16% with DO-IMRT vs. 13% with standard IMRT), dry mouth (5% vs. 15%), and dysphagia (5% vs. 15%).

Taken together, the findings indicate that reducing doses to the pharyngeal constrictor muscle translates to “a meaningful benefit for patients” in terms of improved swallowing function, the investigators said.

In an accompanying editorial, Sandra Nuyts, MD, PhD, noted, however, that the trial failed to meet the predefined threshold for clinical significance, a 10-point difference in MDADI scores.

Still, “several other patient-reported and physician-reported secondary endpoints favored DO-IMRT,” explained Dr. Nuyts, a radiation oncologist at the Leuven Cancer Institute, Belgium. Considered alongside positive reports from smaller, nonrandomized studies, “there is now compelling evidence that the risk of dysphagia after head and neck radiotherapy can be reduced with this technology, without increasing the risk of local recurrences.”

The study team and Dr. Nuyts both called for further refinement of the technique, particularly figuring out what specific sections of the constrictor muscles need to be spared to optimize outcomes.

For now, there is a limit on “how much organ sparing can be achieved with the current DO-IMRT technique” because “use of even narrower margins” around the tumor runs the risk of not treating it adequately, investigators said.

The study was funded by Cancer Research UK. Dr. Nutting reports stock options in Advanced Oncotherapy. Another investigator reports institutional grants from Varian, AstraZeneca, Roche, and other companies. Dr. Nuyts reports no relevant financial relationships.

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

Dysphagia is one of the most common side effects of radiation for head and neck cancer and can be so bad that patients require a permanent gastrostomy tube for feeding.

A team of British investigators are now reporting a new strategy to help lessen this problem.

In the trial, the approach – dubbed dysphagia-optimized intensity-modulated radiotherapy (DO-IMRT) – reduced incidental radiation to the pharyngeal constrictor muscles responsible for swallowing during IMRT for pharyngeal cancer. Patients randomized to DO-IMRT reported significant improvements in swallowing at 1 year, compared with those receiving standard IMRT, at no cost to oncologic outcomes.

Overall, the findings show “DO-IMRT improves patient-reported swallowing function, compared with standard IMRT,” said investigators led by Christopher Nutting, MD, PhD, a head and neck cancer specialist at the Royal Marsden Hospital, London. “DO-IMRT should be considered a new standard of care.”

The team reported the results of their phase 3 trial in The Lancet Oncology.

Swallowing issues affect most patients with head and neck cancer after radiation therapy but strategies to mitigate this long-term adverse effect remain limited.

Dr. Nutting and colleagues wanted to assess whether a novel approach to radiation therapy could reduce the swallowing problems patients often encounter.

In the trial, 112 subjects with T1-4, N0-3, M0 oropharyngeal (90%) or hypopharyngeal cancer (10%) were randomized to standard IMRT or DO-IMRT. Patients received care at 22 radiation therapy centers in Ireland and the UK from 2016 to 2018.

Patients got radiation in 30 fractions over 6 weeks; most also had chemotherapy. The standard IMRT group received 65 Gy to their primary and nodal tumors and 54 Gy to other pharyngeal and nodal areas. In the DO-IMRT group, radiation doses to pharyngeal constrictor muscles lying outside of the tumor target area were limited to 50 Gy.

At 1 year, 56 patients randomized to DO-IMRT scored, on average, 7.2 points higher than the 56 patients randomized to standard IMRT – 77.7 points vs. 70.6 (P = .037) – on the 100-point MD Anderson Dysphagia Inventory (MDADI). MDADI is a validated scale for tracking radiation-induced dysphagia, with higher scores indicating better swallowing function.

The difference grew to 9.8 points when adjusted for chemotherapy use and tumor location and stage.

DO-IMRT patients were also more likely to report eating their normal diet and dining in public. Speech and language therapists who, like patients, were blinded to treatment allocation, reported better outcomes among patients receiving DO-IMRT as well.

At just over 3 years, oncologic outcomes were essentially equivalent in both groups. Two local recurrences occurred in both arms; distant metastatic recurrences occurred in three patients in the DO-IMRT group and two in the standard IMRT group.

The most common grade 3-4 late adverse events were hearing impairment (16% with DO-IMRT vs. 13% with standard IMRT), dry mouth (5% vs. 15%), and dysphagia (5% vs. 15%).

Taken together, the findings indicate that reducing doses to the pharyngeal constrictor muscle translates to “a meaningful benefit for patients” in terms of improved swallowing function, the investigators said.

In an accompanying editorial, Sandra Nuyts, MD, PhD, noted, however, that the trial failed to meet the predefined threshold for clinical significance, a 10-point difference in MDADI scores.

Still, “several other patient-reported and physician-reported secondary endpoints favored DO-IMRT,” explained Dr. Nuyts, a radiation oncologist at the Leuven Cancer Institute, Belgium. Considered alongside positive reports from smaller, nonrandomized studies, “there is now compelling evidence that the risk of dysphagia after head and neck radiotherapy can be reduced with this technology, without increasing the risk of local recurrences.”

The study team and Dr. Nuyts both called for further refinement of the technique, particularly figuring out what specific sections of the constrictor muscles need to be spared to optimize outcomes.

For now, there is a limit on “how much organ sparing can be achieved with the current DO-IMRT technique” because “use of even narrower margins” around the tumor runs the risk of not treating it adequately, investigators said.

The study was funded by Cancer Research UK. Dr. Nutting reports stock options in Advanced Oncotherapy. Another investigator reports institutional grants from Varian, AstraZeneca, Roche, and other companies. Dr. Nuyts reports no relevant financial relationships.

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

The key to reducing problem drinking may just be an app away.

A brief intervention with web- and app-based components helped risky drinkers substantially reduce their alcohol intake to a level that is considered not to be hazardous, researchers in Australia have found.

Participants in the randomized controlled trial tracked information about their alcohol consumption, including the quantity and frequency. The intervention then generated an impulsivity score and implications for their risk for alcohol-related disorders and diseases, hospitalization, and death. The findings were published in Alcohol: Clinical & Experimental Research.

Worldwide each year, alcohol consumption accounts for 5.3% of all deaths. In the United States, an estimated 29.5 million people older than 12 years had alcohol use disorder in 2021.

More than 60% of people with alcohol use problems never seek out in-person treatment. Many are deterred from doing so by fear of judgment, stigma, and embarrassment, especially those at the low end of the alcohol use severity spectrum, according to the Australian researchers. Such fear-based barriers, however, may be overcome through the anonymity of a smartphone app.

The researchers tested whether hazardous drinkers who receive personalized feedback about their alcohol consumption and level of self-control would reduce their problem drinking more than hazardous drinkers who received only personalized information about their alcohol consumption or no feedback at all would.

“I knew from my previous research that just putting in the information is not enough to change someone’s drinking: It seems that putting in the information and then having someone tell you, ‘You drank x number of drinks, and that level of drinking is high according to Australian or WHO [World Health Organization] standards’ seems to be the critical point,” said Antoinette Poulton, PhD, of the University of Melbourne, who developed the app and led the study.

The study was conducted among first-year psychology students at the University of Melbourne between 2020 and 2022.

Each of the 313 participants in the study (average age 21.7 years; 74% women) provided estimates of alcohol intake over 14 days. A subset of 178 individuals utilized Alcohol Capture, the validated smartphone app, which records alcohol intake in real-time and includes an online cognitive task assessing impulsivity.

Participants were categorized as “hazardous” or “nonharmful” drinkers according to guidelines from the World Health Organization and were divided into three groups. Members in the alcohol intake feedback (Alc) group were given personalized feedback about their alcohol consumption, including whether their drinking exceeded Australian and/or WHO guidelines. Others were assigned to the Alc plus cognitive feedback (AlcCog) group and received the same feedback plus details about their level of self-control and information about the links between poor self-control and vulnerability for transition to alcohol use disorder. The control group did not receive personalized feedback. After 8 weeks, alcohol intake was again recorded over 14 days.

Relative to hazardous drinkers in the control group, total alcohol consumption among risky drinkers in the Alc group fell by 32% (or 3.8 standard drinks per week) and by 35% (or 4.2 standard drinks per week) in the AlcCog group, according to the researchers. That difference was not statistically significant.

“Our brief electronic intervention had clear impact on the drinking behavior of hazardous drinkers,” the researchers reported. “In fact, following the intervention, hazardous drinkers did not differ from non-harmful ones on total alcohol intake, quantity of intake per drinking day, or frequency of six or more drinking occasions.”

Drinks per drinking day also decreased by 31% (or 1.6 standard drinks) and 32% (or 2.1 standard drinks) in the Alc and AlcCog groups, respectively, compared with the control group.

Alcohol use did not appear to change among nonharmful drinkers in any of the study groups.

“This is a nice study, because it shows that a simple, small intervention can really have a profound effect on hazardous drinking,” said Akhil Anand, MD, an addiction psychiatrist and Medical Director of the Alcohol and Drug Recovery Center at Cleveland Clinic. “It’s hard to say if this intervention would work on very severe cases, but I like it because it’s anonymous, it’s quick, it’s easily accessible, and it doesn’t take too much health care personnel power to apply it,” Dr. Anand added.

This research was supported by an Early Career Researcher grant from the University of Melbourne. Dr. Poulton and Dr. Anand reported no financial conflicts of interest.

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

The key to reducing problem drinking may just be an app away.

A brief intervention with web- and app-based components helped risky drinkers substantially reduce their alcohol intake to a level that is considered not to be hazardous, researchers in Australia have found.

Participants in the randomized controlled trial tracked information about their alcohol consumption, including the quantity and frequency. The intervention then generated an impulsivity score and implications for their risk for alcohol-related disorders and diseases, hospitalization, and death. The findings were published in Alcohol: Clinical & Experimental Research.

Worldwide each year, alcohol consumption accounts for 5.3% of all deaths. In the United States, an estimated 29.5 million people older than 12 years had alcohol use disorder in 2021.

More than 60% of people with alcohol use problems never seek out in-person treatment. Many are deterred from doing so by fear of judgment, stigma, and embarrassment, especially those at the low end of the alcohol use severity spectrum, according to the Australian researchers. Such fear-based barriers, however, may be overcome through the anonymity of a smartphone app.

The researchers tested whether hazardous drinkers who receive personalized feedback about their alcohol consumption and level of self-control would reduce their problem drinking more than hazardous drinkers who received only personalized information about their alcohol consumption or no feedback at all would.

“I knew from my previous research that just putting in the information is not enough to change someone’s drinking: It seems that putting in the information and then having someone tell you, ‘You drank x number of drinks, and that level of drinking is high according to Australian or WHO [World Health Organization] standards’ seems to be the critical point,” said Antoinette Poulton, PhD, of the University of Melbourne, who developed the app and led the study.

The study was conducted among first-year psychology students at the University of Melbourne between 2020 and 2022.

Each of the 313 participants in the study (average age 21.7 years; 74% women) provided estimates of alcohol intake over 14 days. A subset of 178 individuals utilized Alcohol Capture, the validated smartphone app, which records alcohol intake in real-time and includes an online cognitive task assessing impulsivity.

Participants were categorized as “hazardous” or “nonharmful” drinkers according to guidelines from the World Health Organization and were divided into three groups. Members in the alcohol intake feedback (Alc) group were given personalized feedback about their alcohol consumption, including whether their drinking exceeded Australian and/or WHO guidelines. Others were assigned to the Alc plus cognitive feedback (AlcCog) group and received the same feedback plus details about their level of self-control and information about the links between poor self-control and vulnerability for transition to alcohol use disorder. The control group did not receive personalized feedback. After 8 weeks, alcohol intake was again recorded over 14 days.

Relative to hazardous drinkers in the control group, total alcohol consumption among risky drinkers in the Alc group fell by 32% (or 3.8 standard drinks per week) and by 35% (or 4.2 standard drinks per week) in the AlcCog group, according to the researchers. That difference was not statistically significant.

“Our brief electronic intervention had clear impact on the drinking behavior of hazardous drinkers,” the researchers reported. “In fact, following the intervention, hazardous drinkers did not differ from non-harmful ones on total alcohol intake, quantity of intake per drinking day, or frequency of six or more drinking occasions.”

Drinks per drinking day also decreased by 31% (or 1.6 standard drinks) and 32% (or 2.1 standard drinks) in the Alc and AlcCog groups, respectively, compared with the control group.

Alcohol use did not appear to change among nonharmful drinkers in any of the study groups.

“This is a nice study, because it shows that a simple, small intervention can really have a profound effect on hazardous drinking,” said Akhil Anand, MD, an addiction psychiatrist and Medical Director of the Alcohol and Drug Recovery Center at Cleveland Clinic. “It’s hard to say if this intervention would work on very severe cases, but I like it because it’s anonymous, it’s quick, it’s easily accessible, and it doesn’t take too much health care personnel power to apply it,” Dr. Anand added.

This research was supported by an Early Career Researcher grant from the University of Melbourne. Dr. Poulton and Dr. Anand reported no financial conflicts of interest.

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

The key to reducing problem drinking may just be an app away.

A brief intervention with web- and app-based components helped risky drinkers substantially reduce their alcohol intake to a level that is considered not to be hazardous, researchers in Australia have found.

Participants in the randomized controlled trial tracked information about their alcohol consumption, including the quantity and frequency. The intervention then generated an impulsivity score and implications for their risk for alcohol-related disorders and diseases, hospitalization, and death. The findings were published in Alcohol: Clinical & Experimental Research.

Worldwide each year, alcohol consumption accounts for 5.3% of all deaths. In the United States, an estimated 29.5 million people older than 12 years had alcohol use disorder in 2021.

More than 60% of people with alcohol use problems never seek out in-person treatment. Many are deterred from doing so by fear of judgment, stigma, and embarrassment, especially those at the low end of the alcohol use severity spectrum, according to the Australian researchers. Such fear-based barriers, however, may be overcome through the anonymity of a smartphone app.

The researchers tested whether hazardous drinkers who receive personalized feedback about their alcohol consumption and level of self-control would reduce their problem drinking more than hazardous drinkers who received only personalized information about their alcohol consumption or no feedback at all would.

“I knew from my previous research that just putting in the information is not enough to change someone’s drinking: It seems that putting in the information and then having someone tell you, ‘You drank x number of drinks, and that level of drinking is high according to Australian or WHO [World Health Organization] standards’ seems to be the critical point,” said Antoinette Poulton, PhD, of the University of Melbourne, who developed the app and led the study.

The study was conducted among first-year psychology students at the University of Melbourne between 2020 and 2022.

Each of the 313 participants in the study (average age 21.7 years; 74% women) provided estimates of alcohol intake over 14 days. A subset of 178 individuals utilized Alcohol Capture, the validated smartphone app, which records alcohol intake in real-time and includes an online cognitive task assessing impulsivity.

Participants were categorized as “hazardous” or “nonharmful” drinkers according to guidelines from the World Health Organization and were divided into three groups. Members in the alcohol intake feedback (Alc) group were given personalized feedback about their alcohol consumption, including whether their drinking exceeded Australian and/or WHO guidelines. Others were assigned to the Alc plus cognitive feedback (AlcCog) group and received the same feedback plus details about their level of self-control and information about the links between poor self-control and vulnerability for transition to alcohol use disorder. The control group did not receive personalized feedback. After 8 weeks, alcohol intake was again recorded over 14 days.

Relative to hazardous drinkers in the control group, total alcohol consumption among risky drinkers in the Alc group fell by 32% (or 3.8 standard drinks per week) and by 35% (or 4.2 standard drinks per week) in the AlcCog group, according to the researchers. That difference was not statistically significant.

“Our brief electronic intervention had clear impact on the drinking behavior of hazardous drinkers,” the researchers reported. “In fact, following the intervention, hazardous drinkers did not differ from non-harmful ones on total alcohol intake, quantity of intake per drinking day, or frequency of six or more drinking occasions.”

Drinks per drinking day also decreased by 31% (or 1.6 standard drinks) and 32% (or 2.1 standard drinks) in the Alc and AlcCog groups, respectively, compared with the control group.

Alcohol use did not appear to change among nonharmful drinkers in any of the study groups.

“This is a nice study, because it shows that a simple, small intervention can really have a profound effect on hazardous drinking,” said Akhil Anand, MD, an addiction psychiatrist and Medical Director of the Alcohol and Drug Recovery Center at Cleveland Clinic. “It’s hard to say if this intervention would work on very severe cases, but I like it because it’s anonymous, it’s quick, it’s easily accessible, and it doesn’t take too much health care personnel power to apply it,” Dr. Anand added.

This research was supported by an Early Career Researcher grant from the University of Melbourne. Dr. Poulton and Dr. Anand reported no financial conflicts of interest.

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.

Lynda Banzi/MDedge News

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.

Lynda Banzi/MDedge News

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.

Lynda Banzi/MDedge News

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.

Three California nurse practitioners with doctorates (DNP) have sued the state over its law that only physicians can call themselves doctors, saying it violates their first amendment right to use the honorific title without fear of regulatory repercussions.

The case highlights ongoing scope-creep battles as the American Medical Association tries to preserve the physician-led team model and nursing organizations and some lawmakers push for greater autonomy for allied professionals.

In the complaint filed in district court in June, plaintiffs Jacqueline Palmer, DNP, Heather Lewis, DNP, and Rodolfo Jaravata-Hanson, DNP, say they fear the state will sanction them. They note that “Doctor Sarah,” another DNP, was fined nearly $20,000 by the state last November for false advertising and fraud after using the moniker in her online advertising and social media accounts.

The fine was part of a settlement that the DNP, Sarah Erny, reached with the state to resolve allegations that she failed to identify her supervising physician and inform the public that she was not a medical doctor.

Under California’s Medical Practice Act, individuals cannot refer to themselves as “doctor, physician, or any other terms or letters indicating or implying that he or she is a physician and surgeon ... without having ... a certificate as a physician and surgeon.”

Instead, nurse practitioners certified by the California Board of Registered Nursing may use titles like “Certified Nurse Practitioner” and “Advanced Practice Registered Nurse,” corresponding letters such as APRN-CNP, RN, and NP, and phrases like pediatric nurse practitioner to identify specialization.

Individuals who misrepresent themselves are subject to misdemeanor charges and civil penalties.

The nonprofit Pacific Legal Foundation represents the plaintiffs. In court records, its attorneys argue that after “years earning their advanced degrees and qualifications ... they should be able to speak truthfully about them in their workplaces, on their business cards, the Internet, and social media, so long as they clarify that they are nurse practitioners.”

State lawmakers’ attempts to clarify the roles of physicians and nurse practitioners have seen mixed results. Florida legislators recently passed a bill to prevent advanced practice nurses from using the honorific title, reserving it only for MDs and DOs. Gov. Ron DeSantis vetoed it last month.

In May, Georgia lawmakers passed the Health Care Practitioners Truth and Transparency Act. It requires advanced practice nurses and physician assistants with doctoral degrees who refer to themselves as doctors in a clinical setting to state they are not medical doctors or physicians.

Still, some health professionals say that the designation should only be used in academic settings or among peers, and that all doctoral degree holders should ditch the moniker at the bedside to ease patient communications.

Named as defendants in the suit are three state officials: California Attorney General Rob Bonta, state Medical Board President Kristina Lawson, and California Board of Registered Nursing Executive Officer Loretta Melby.

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

Three California nurse practitioners with doctorates (DNP) have sued the state over its law that only physicians can call themselves doctors, saying it violates their first amendment right to use the honorific title without fear of regulatory repercussions.

The case highlights ongoing scope-creep battles as the American Medical Association tries to preserve the physician-led team model and nursing organizations and some lawmakers push for greater autonomy for allied professionals.

In the complaint filed in district court in June, plaintiffs Jacqueline Palmer, DNP, Heather Lewis, DNP, and Rodolfo Jaravata-Hanson, DNP, say they fear the state will sanction them. They note that “Doctor Sarah,” another DNP, was fined nearly $20,000 by the state last November for false advertising and fraud after using the moniker in her online advertising and social media accounts.

The fine was part of a settlement that the DNP, Sarah Erny, reached with the state to resolve allegations that she failed to identify her supervising physician and inform the public that she was not a medical doctor.

Under California’s Medical Practice Act, individuals cannot refer to themselves as “doctor, physician, or any other terms or letters indicating or implying that he or she is a physician and surgeon ... without having ... a certificate as a physician and surgeon.”

Instead, nurse practitioners certified by the California Board of Registered Nursing may use titles like “Certified Nurse Practitioner” and “Advanced Practice Registered Nurse,” corresponding letters such as APRN-CNP, RN, and NP, and phrases like pediatric nurse practitioner to identify specialization.

Individuals who misrepresent themselves are subject to misdemeanor charges and civil penalties.

The nonprofit Pacific Legal Foundation represents the plaintiffs. In court records, its attorneys argue that after “years earning their advanced degrees and qualifications ... they should be able to speak truthfully about them in their workplaces, on their business cards, the Internet, and social media, so long as they clarify that they are nurse practitioners.”

State lawmakers’ attempts to clarify the roles of physicians and nurse practitioners have seen mixed results. Florida legislators recently passed a bill to prevent advanced practice nurses from using the honorific title, reserving it only for MDs and DOs. Gov. Ron DeSantis vetoed it last month.

In May, Georgia lawmakers passed the Health Care Practitioners Truth and Transparency Act. It requires advanced practice nurses and physician assistants with doctoral degrees who refer to themselves as doctors in a clinical setting to state they are not medical doctors or physicians.

Still, some health professionals say that the designation should only be used in academic settings or among peers, and that all doctoral degree holders should ditch the moniker at the bedside to ease patient communications.

Named as defendants in the suit are three state officials: California Attorney General Rob Bonta, state Medical Board President Kristina Lawson, and California Board of Registered Nursing Executive Officer Loretta Melby.

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

Three California nurse practitioners with doctorates (DNP) have sued the state over its law that only physicians can call themselves doctors, saying it violates their first amendment right to use the honorific title without fear of regulatory repercussions.

The case highlights ongoing scope-creep battles as the American Medical Association tries to preserve the physician-led team model and nursing organizations and some lawmakers push for greater autonomy for allied professionals.

In the complaint filed in district court in June, plaintiffs Jacqueline Palmer, DNP, Heather Lewis, DNP, and Rodolfo Jaravata-Hanson, DNP, say they fear the state will sanction them. They note that “Doctor Sarah,” another DNP, was fined nearly $20,000 by the state last November for false advertising and fraud after using the moniker in her online advertising and social media accounts.

The fine was part of a settlement that the DNP, Sarah Erny, reached with the state to resolve allegations that she failed to identify her supervising physician and inform the public that she was not a medical doctor.

Under California’s Medical Practice Act, individuals cannot refer to themselves as “doctor, physician, or any other terms or letters indicating or implying that he or she is a physician and surgeon ... without having ... a certificate as a physician and surgeon.”

Instead, nurse practitioners certified by the California Board of Registered Nursing may use titles like “Certified Nurse Practitioner” and “Advanced Practice Registered Nurse,” corresponding letters such as APRN-CNP, RN, and NP, and phrases like pediatric nurse practitioner to identify specialization.

Individuals who misrepresent themselves are subject to misdemeanor charges and civil penalties.

The nonprofit Pacific Legal Foundation represents the plaintiffs. In court records, its attorneys argue that after “years earning their advanced degrees and qualifications ... they should be able to speak truthfully about them in their workplaces, on their business cards, the Internet, and social media, so long as they clarify that they are nurse practitioners.”

State lawmakers’ attempts to clarify the roles of physicians and nurse practitioners have seen mixed results. Florida legislators recently passed a bill to prevent advanced practice nurses from using the honorific title, reserving it only for MDs and DOs. Gov. Ron DeSantis vetoed it last month.

In May, Georgia lawmakers passed the Health Care Practitioners Truth and Transparency Act. It requires advanced practice nurses and physician assistants with doctoral degrees who refer to themselves as doctors in a clinical setting to state they are not medical doctors or physicians.

Still, some health professionals say that the designation should only be used in academic settings or among peers, and that all doctoral degree holders should ditch the moniker at the bedside to ease patient communications.

Named as defendants in the suit are three state officials: California Attorney General Rob Bonta, state Medical Board President Kristina Lawson, and California Board of Registered Nursing Executive Officer Loretta Melby.

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

A recent update to the U.S. recommendations for breast cancer screening is raising concerns about the costs associated with potential follow-up tests, while also renewing debates about the timing of these tests and the screening approaches used.
 

The U.S. Preventive Services Task Force is currently finalizing an update to its recommendations on breast cancer screening. In May, the task force released a proposed update that dropped the initial age for routine mammogram screening from 50 to 40.

The task force intends to give a “B” rating to this recommendation, which covers screening every other year up to age 74 for women deemed average risk for breast cancer.

The task force’s rating carries clout, A. Mark Fendrick, MD, director of the Value-Based Insurance Design at the University of Michigan, Ann Arbor, said in an interview.

For one, the Affordable Care Act requires that private insurers cover services that get top A or B marks from USPSTF without charging copays.

However, Dr. Fendrick noted, such coverage does not necessarily apply to follow-up testing when a routine mammogram comes back with a positive finding. The expense of follow-up testing may deter some women from seeking follow-up diagnostic imaging or biopsies after an abnormal result on a screening mammogram.

A recent analysis in JAMA Network Open found that women facing higher anticipated out-of-pocket costs for breast cancer diagnostic tests, based on their health insurance plan, were less likely to get that follow-up screening. For instance, the use of breast MRI decreased by nearly 24% between patients undergoing subsequent diagnostic testing in plans with the lowest out-of-pocket costs vs. those with the highest.

“The study’s central finding that some women who have an abnormal result on a mammogram may not get appropriate follow-up because of cost is worrisome,” said Dr. Fendrick and Ilana B. Richman, MD, MHS, in an accompanying commentary to the JAMA analysis. “On an individual level, high out-of-pocket costs may directly contribute to worse health outcomes or require individuals to use scarce financial resources that may otherwise be used for critical items such as food or rent.”

For patients to fully benefit from early detection, the USPSTF would also need to make clear that follow-up diagnostic mammograms are covered, Dr. Fendrick said.
 

The ongoing debates

Concerns over the costs of potential follow-up tests are not the only issues experts have highlighted since USPSTF released its updated draft guidance on screening mammography.

The task force’s proposed update has also reignited questions and uncertainties surrounding when to screen, how often, and what types are best.

When it comes to frequency, the major organizations that provide screening guidance don’t see eye to eye. The USPSTF recommends breast cancer screening every other year, while the American College of Radiology recommends screening every year because that approach leads to saves “the most lives.”

At this time, the American College of Obstetricians and Gynecologists guidance currently teeters in the middle, suggesting either annual or biennial screening and highlighting the pros and cons of either approach. According to ACOG, “annual screening intervals appear to result in the least number of breast cancer deaths, particularly in younger women, but at the cost of additional callbacks and biopsies.”

When to begin screening represents another point of contention. While some experts, such as ACOG, agree with the task force’s decision to lower the screening start age to 40, others point to the need for greater nuance on setting the appropriate screening age. The main issue: the task force’s draft sets a uniform age to begin screening, but the risk for breast cancer and breast cancer mortality is not uniform across different racial and ethnic groups.

A recent study published in JAMA Network Open found that, among women aged 40-49, breast cancer mortality was highest among Black women (27 deaths per 100,000 person-years) followed by White women (15 deaths per 100,000 person-years). Based on a recommended screening age of 50, the authors suggested that Black women should start screening at age 42, whereas White women could start at 51.

“These findings suggest that health policy makers and clinicians could consider an alternative, race and ethnicity–adapted approach in which Black female patients start screening earlier,” writes Tianhui Chen, PhD, of China’s Zhejiang Cancer Hospital and coauthor of the study.

Weighing in on the guidance, the nonprofit National Center for Health Research urged the task force to consider suggesting different screening schedules based on race and ethnicity data. That would mean the recommendation to start at age 40 should only apply to Black women and other groups with higher-than-average risk for breast cancer at a younger age.

“Women are capable of understanding why the age to start mammography screening may be different for women with different risk factors,” the National Center for Health Research wrote in a comment to USPSTF, provided to this news organization by request. “What is confusing is when some physician groups recommend annual mammograms for all women starting at age 40, even though the data do not support that recommendation.”

While the ACR agreed with the task force’s recommendation to lower the screening age, the organization suggested starting risk assessments based on racial variations in breast cancer incidence and death even earlier. Specifically, the ACR recommended that high-risk groups, such as Black women, get risk assessments by age 25 to determine whether mammography before age 40 is needed.

Screening options for women with dense breasts may be some of the most challenging to weigh. Having dense breasts increases an individual’s risk for breast cancer, and mammography alone is not as effective at identifying breast cancer among these women. However, the evidence on the benefits vs. harms of additional screening beyond mammography remains mixed.

As a result, the task force decided to maintain its “I” grade on additional screening beyond mammography for these women – a grade that indicates insufficient evidence to determine the benefits and harms for a service.

The task force largely based its decision on the findings of two key reports. One report from the Cancer Intervention and Surveillance Modeling Network, which modeled potential outcomes of different screening strategies, indicated that extra screening might reduce breast cancer mortality in those with dense breasts, but at a cost of more false-positive reports.

The second report, a review from the Kaiser Permanente Evidence-based Practice Center, reaffirmed the benefits of routine mammography for reducing deaths from breast cancer, but found no solid evidence that different strategies – including supplemental screening in women with denser breasts – lowered breast cancer mortality or the risk of progression to advanced cancer. Further studies may show which approaches work best to reduce breast cancer deaths, the report said.

In this instance, ACOG agreed with USPSTF: “Based on the lack of data, ACOG does not recommend routine use of alternative or adjunctive tests to screening mammography in women with dense breasts who are asymptomatic and have no additional risk factors.”

Women with dense breasts should still be encouraged to receive regular screening mammography, even if the results they get may not be as accurate as those for women with less dense breasts, said Diana L. Miglioretti, PhD, of the University of California, Davis, who worked on a report for the USPSTF guidelines.
 

What’s next?

Despite ongoing debate and uncertainties surrounding some breast screening guidance, support for ending copay requirements for follow-up tests after a positive mammogram finding is widespread.

According to Dr. Fendrick, the USPSTF should expand coverage of follow-up testing after a positive mammogram to ensure people receive routine screening and any necessary diagnostic tests, as it did with colon cancer.

Before 2021, patients could face high costs for a colonoscopy following a positive stool-based Cologuard test. But in 2021, the USPSTF said that positive results on stool-based tests would require follow-up with colonoscopy, defining this follow-up as part of the screening benefit. In 2022, Medicare followed by setting a policy that ended the copay for these follow-up colonoscopies.

For breast screening, there are efforts underway in Congress to end copays for breast screening. In May, Rep. Rosa DeLauro (D-Conn.) introduced a bill, the Find It Early Act, that would require both private and government insurers to cover the out-of-pocket costs for many women receiving screening with ultrasound and MRI.

When the USPSTF finalizes its breast screening guidelines, the recommendations will be woven into discussions between primary care physicians and patients about breast cancer screening.

As guidelines and evidence evolve, “we’re learning to adjust” and communicate these changes to patients, said Tochi Iroku-Malize, MD, president of the American Academy of Family Physicians.

However, gaps in the guidance will leave some open-ended questions about optimal screening practices and how much screening may cost.

Given that, Dr. Iroku-Malize takes many factors into account when discussing screening options with her patients. Based on the new information and the patient’s information, she said she will tell her patients, “We’re going to adjust our guidance as to what you need.”

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

A recent update to the U.S. recommendations for breast cancer screening is raising concerns about the costs associated with potential follow-up tests, while also renewing debates about the timing of these tests and the screening approaches used.
 

The U.S. Preventive Services Task Force is currently finalizing an update to its recommendations on breast cancer screening. In May, the task force released a proposed update that dropped the initial age for routine mammogram screening from 50 to 40.

The task force intends to give a “B” rating to this recommendation, which covers screening every other year up to age 74 for women deemed average risk for breast cancer.

The task force’s rating carries clout, A. Mark Fendrick, MD, director of the Value-Based Insurance Design at the University of Michigan, Ann Arbor, said in an interview.

For one, the Affordable Care Act requires that private insurers cover services that get top A or B marks from USPSTF without charging copays.

However, Dr. Fendrick noted, such coverage does not necessarily apply to follow-up testing when a routine mammogram comes back with a positive finding. The expense of follow-up testing may deter some women from seeking follow-up diagnostic imaging or biopsies after an abnormal result on a screening mammogram.

A recent analysis in JAMA Network Open found that women facing higher anticipated out-of-pocket costs for breast cancer diagnostic tests, based on their health insurance plan, were less likely to get that follow-up screening. For instance, the use of breast MRI decreased by nearly 24% between patients undergoing subsequent diagnostic testing in plans with the lowest out-of-pocket costs vs. those with the highest.

“The study’s central finding that some women who have an abnormal result on a mammogram may not get appropriate follow-up because of cost is worrisome,” said Dr. Fendrick and Ilana B. Richman, MD, MHS, in an accompanying commentary to the JAMA analysis. “On an individual level, high out-of-pocket costs may directly contribute to worse health outcomes or require individuals to use scarce financial resources that may otherwise be used for critical items such as food or rent.”

For patients to fully benefit from early detection, the USPSTF would also need to make clear that follow-up diagnostic mammograms are covered, Dr. Fendrick said.
 

The ongoing debates

Concerns over the costs of potential follow-up tests are not the only issues experts have highlighted since USPSTF released its updated draft guidance on screening mammography.

The task force’s proposed update has also reignited questions and uncertainties surrounding when to screen, how often, and what types are best.

When it comes to frequency, the major organizations that provide screening guidance don’t see eye to eye. The USPSTF recommends breast cancer screening every other year, while the American College of Radiology recommends screening every year because that approach leads to saves “the most lives.”

At this time, the American College of Obstetricians and Gynecologists guidance currently teeters in the middle, suggesting either annual or biennial screening and highlighting the pros and cons of either approach. According to ACOG, “annual screening intervals appear to result in the least number of breast cancer deaths, particularly in younger women, but at the cost of additional callbacks and biopsies.”

When to begin screening represents another point of contention. While some experts, such as ACOG, agree with the task force’s decision to lower the screening start age to 40, others point to the need for greater nuance on setting the appropriate screening age. The main issue: the task force’s draft sets a uniform age to begin screening, but the risk for breast cancer and breast cancer mortality is not uniform across different racial and ethnic groups.

A recent study published in JAMA Network Open found that, among women aged 40-49, breast cancer mortality was highest among Black women (27 deaths per 100,000 person-years) followed by White women (15 deaths per 100,000 person-years). Based on a recommended screening age of 50, the authors suggested that Black women should start screening at age 42, whereas White women could start at 51.

“These findings suggest that health policy makers and clinicians could consider an alternative, race and ethnicity–adapted approach in which Black female patients start screening earlier,” writes Tianhui Chen, PhD, of China’s Zhejiang Cancer Hospital and coauthor of the study.

Weighing in on the guidance, the nonprofit National Center for Health Research urged the task force to consider suggesting different screening schedules based on race and ethnicity data. That would mean the recommendation to start at age 40 should only apply to Black women and other groups with higher-than-average risk for breast cancer at a younger age.

“Women are capable of understanding why the age to start mammography screening may be different for women with different risk factors,” the National Center for Health Research wrote in a comment to USPSTF, provided to this news organization by request. “What is confusing is when some physician groups recommend annual mammograms for all women starting at age 40, even though the data do not support that recommendation.”

While the ACR agreed with the task force’s recommendation to lower the screening age, the organization suggested starting risk assessments based on racial variations in breast cancer incidence and death even earlier. Specifically, the ACR recommended that high-risk groups, such as Black women, get risk assessments by age 25 to determine whether mammography before age 40 is needed.

Screening options for women with dense breasts may be some of the most challenging to weigh. Having dense breasts increases an individual’s risk for breast cancer, and mammography alone is not as effective at identifying breast cancer among these women. However, the evidence on the benefits vs. harms of additional screening beyond mammography remains mixed.

As a result, the task force decided to maintain its “I” grade on additional screening beyond mammography for these women – a grade that indicates insufficient evidence to determine the benefits and harms for a service.

The task force largely based its decision on the findings of two key reports. One report from the Cancer Intervention and Surveillance Modeling Network, which modeled potential outcomes of different screening strategies, indicated that extra screening might reduce breast cancer mortality in those with dense breasts, but at a cost of more false-positive reports.

The second report, a review from the Kaiser Permanente Evidence-based Practice Center, reaffirmed the benefits of routine mammography for reducing deaths from breast cancer, but found no solid evidence that different strategies – including supplemental screening in women with denser breasts – lowered breast cancer mortality or the risk of progression to advanced cancer. Further studies may show which approaches work best to reduce breast cancer deaths, the report said.

In this instance, ACOG agreed with USPSTF: “Based on the lack of data, ACOG does not recommend routine use of alternative or adjunctive tests to screening mammography in women with dense breasts who are asymptomatic and have no additional risk factors.”

Women with dense breasts should still be encouraged to receive regular screening mammography, even if the results they get may not be as accurate as those for women with less dense breasts, said Diana L. Miglioretti, PhD, of the University of California, Davis, who worked on a report for the USPSTF guidelines.
 

What’s next?

Despite ongoing debate and uncertainties surrounding some breast screening guidance, support for ending copay requirements for follow-up tests after a positive mammogram finding is widespread.

According to Dr. Fendrick, the USPSTF should expand coverage of follow-up testing after a positive mammogram to ensure people receive routine screening and any necessary diagnostic tests, as it did with colon cancer.

Before 2021, patients could face high costs for a colonoscopy following a positive stool-based Cologuard test. But in 2021, the USPSTF said that positive results on stool-based tests would require follow-up with colonoscopy, defining this follow-up as part of the screening benefit. In 2022, Medicare followed by setting a policy that ended the copay for these follow-up colonoscopies.

For breast screening, there are efforts underway in Congress to end copays for breast screening. In May, Rep. Rosa DeLauro (D-Conn.) introduced a bill, the Find It Early Act, that would require both private and government insurers to cover the out-of-pocket costs for many women receiving screening with ultrasound and MRI.

When the USPSTF finalizes its breast screening guidelines, the recommendations will be woven into discussions between primary care physicians and patients about breast cancer screening.

As guidelines and evidence evolve, “we’re learning to adjust” and communicate these changes to patients, said Tochi Iroku-Malize, MD, president of the American Academy of Family Physicians.

However, gaps in the guidance will leave some open-ended questions about optimal screening practices and how much screening may cost.

Given that, Dr. Iroku-Malize takes many factors into account when discussing screening options with her patients. Based on the new information and the patient’s information, she said she will tell her patients, “We’re going to adjust our guidance as to what you need.”

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

A recent update to the U.S. recommendations for breast cancer screening is raising concerns about the costs associated with potential follow-up tests, while also renewing debates about the timing of these tests and the screening approaches used.
 

The U.S. Preventive Services Task Force is currently finalizing an update to its recommendations on breast cancer screening. In May, the task force released a proposed update that dropped the initial age for routine mammogram screening from 50 to 40.

The task force intends to give a “B” rating to this recommendation, which covers screening every other year up to age 74 for women deemed average risk for breast cancer.

The task force’s rating carries clout, A. Mark Fendrick, MD, director of the Value-Based Insurance Design at the University of Michigan, Ann Arbor, said in an interview.

For one, the Affordable Care Act requires that private insurers cover services that get top A or B marks from USPSTF without charging copays.

However, Dr. Fendrick noted, such coverage does not necessarily apply to follow-up testing when a routine mammogram comes back with a positive finding. The expense of follow-up testing may deter some women from seeking follow-up diagnostic imaging or biopsies after an abnormal result on a screening mammogram.

A recent analysis in JAMA Network Open found that women facing higher anticipated out-of-pocket costs for breast cancer diagnostic tests, based on their health insurance plan, were less likely to get that follow-up screening. For instance, the use of breast MRI decreased by nearly 24% between patients undergoing subsequent diagnostic testing in plans with the lowest out-of-pocket costs vs. those with the highest.

“The study’s central finding that some women who have an abnormal result on a mammogram may not get appropriate follow-up because of cost is worrisome,” said Dr. Fendrick and Ilana B. Richman, MD, MHS, in an accompanying commentary to the JAMA analysis. “On an individual level, high out-of-pocket costs may directly contribute to worse health outcomes or require individuals to use scarce financial resources that may otherwise be used for critical items such as food or rent.”

For patients to fully benefit from early detection, the USPSTF would also need to make clear that follow-up diagnostic mammograms are covered, Dr. Fendrick said.
 

The ongoing debates

Concerns over the costs of potential follow-up tests are not the only issues experts have highlighted since USPSTF released its updated draft guidance on screening mammography.

The task force’s proposed update has also reignited questions and uncertainties surrounding when to screen, how often, and what types are best.

When it comes to frequency, the major organizations that provide screening guidance don’t see eye to eye. The USPSTF recommends breast cancer screening every other year, while the American College of Radiology recommends screening every year because that approach leads to saves “the most lives.”

At this time, the American College of Obstetricians and Gynecologists guidance currently teeters in the middle, suggesting either annual or biennial screening and highlighting the pros and cons of either approach. According to ACOG, “annual screening intervals appear to result in the least number of breast cancer deaths, particularly in younger women, but at the cost of additional callbacks and biopsies.”

When to begin screening represents another point of contention. While some experts, such as ACOG, agree with the task force’s decision to lower the screening start age to 40, others point to the need for greater nuance on setting the appropriate screening age. The main issue: the task force’s draft sets a uniform age to begin screening, but the risk for breast cancer and breast cancer mortality is not uniform across different racial and ethnic groups.

A recent study published in JAMA Network Open found that, among women aged 40-49, breast cancer mortality was highest among Black women (27 deaths per 100,000 person-years) followed by White women (15 deaths per 100,000 person-years). Based on a recommended screening age of 50, the authors suggested that Black women should start screening at age 42, whereas White women could start at 51.

“These findings suggest that health policy makers and clinicians could consider an alternative, race and ethnicity–adapted approach in which Black female patients start screening earlier,” writes Tianhui Chen, PhD, of China’s Zhejiang Cancer Hospital and coauthor of the study.

Weighing in on the guidance, the nonprofit National Center for Health Research urged the task force to consider suggesting different screening schedules based on race and ethnicity data. That would mean the recommendation to start at age 40 should only apply to Black women and other groups with higher-than-average risk for breast cancer at a younger age.

“Women are capable of understanding why the age to start mammography screening may be different for women with different risk factors,” the National Center for Health Research wrote in a comment to USPSTF, provided to this news organization by request. “What is confusing is when some physician groups recommend annual mammograms for all women starting at age 40, even though the data do not support that recommendation.”

While the ACR agreed with the task force’s recommendation to lower the screening age, the organization suggested starting risk assessments based on racial variations in breast cancer incidence and death even earlier. Specifically, the ACR recommended that high-risk groups, such as Black women, get risk assessments by age 25 to determine whether mammography before age 40 is needed.

Screening options for women with dense breasts may be some of the most challenging to weigh. Having dense breasts increases an individual’s risk for breast cancer, and mammography alone is not as effective at identifying breast cancer among these women. However, the evidence on the benefits vs. harms of additional screening beyond mammography remains mixed.

As a result, the task force decided to maintain its “I” grade on additional screening beyond mammography for these women – a grade that indicates insufficient evidence to determine the benefits and harms for a service.

The task force largely based its decision on the findings of two key reports. One report from the Cancer Intervention and Surveillance Modeling Network, which modeled potential outcomes of different screening strategies, indicated that extra screening might reduce breast cancer mortality in those with dense breasts, but at a cost of more false-positive reports.

The second report, a review from the Kaiser Permanente Evidence-based Practice Center, reaffirmed the benefits of routine mammography for reducing deaths from breast cancer, but found no solid evidence that different strategies – including supplemental screening in women with denser breasts – lowered breast cancer mortality or the risk of progression to advanced cancer. Further studies may show which approaches work best to reduce breast cancer deaths, the report said.

In this instance, ACOG agreed with USPSTF: “Based on the lack of data, ACOG does not recommend routine use of alternative or adjunctive tests to screening mammography in women with dense breasts who are asymptomatic and have no additional risk factors.”

Women with dense breasts should still be encouraged to receive regular screening mammography, even if the results they get may not be as accurate as those for women with less dense breasts, said Diana L. Miglioretti, PhD, of the University of California, Davis, who worked on a report for the USPSTF guidelines.
 

What’s next?

Despite ongoing debate and uncertainties surrounding some breast screening guidance, support for ending copay requirements for follow-up tests after a positive mammogram finding is widespread.

According to Dr. Fendrick, the USPSTF should expand coverage of follow-up testing after a positive mammogram to ensure people receive routine screening and any necessary diagnostic tests, as it did with colon cancer.

Before 2021, patients could face high costs for a colonoscopy following a positive stool-based Cologuard test. But in 2021, the USPSTF said that positive results on stool-based tests would require follow-up with colonoscopy, defining this follow-up as part of the screening benefit. In 2022, Medicare followed by setting a policy that ended the copay for these follow-up colonoscopies.

For breast screening, there are efforts underway in Congress to end copays for breast screening. In May, Rep. Rosa DeLauro (D-Conn.) introduced a bill, the Find It Early Act, that would require both private and government insurers to cover the out-of-pocket costs for many women receiving screening with ultrasound and MRI.

When the USPSTF finalizes its breast screening guidelines, the recommendations will be woven into discussions between primary care physicians and patients about breast cancer screening.

As guidelines and evidence evolve, “we’re learning to adjust” and communicate these changes to patients, said Tochi Iroku-Malize, MD, president of the American Academy of Family Physicians.

However, gaps in the guidance will leave some open-ended questions about optimal screening practices and how much screening may cost.

Given that, Dr. Iroku-Malize takes many factors into account when discussing screening options with her patients. Based on the new information and the patient’s information, she said she will tell her patients, “We’re going to adjust our guidance as to what you need.”

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

A U.S. Food and Drug Administration investigation of injection-site necrosis in some people who received the 23-valent pneumococcal vaccine has concluded that the benefits of the vaccine outweigh the risks.

No similar safety signal has been detected for the more recently approved 15-valent and 20-valent pneumococcal conjugate vaccines, explain the investigators, led by Brendan Day, MD, MPH, from the FDA’s Center for Biologics Evaluation and Research, in their report published online in JAMA Internal Medicine.

Reports of injection-site necrosis emerged after the vaccine (Pneumovax 23, Merck) had been approved by the FDA and was administered to a large, diverse, real-world population.

Rare safety events can emerge after FDA approval, as clinical trials may not be able to detect them in a study-group population.

Therefore, “postmarketing safety surveillance is critical to further characterize the safety profile of licensed vaccines,” the investigators point out.

The FDA and the Centers for Disease Control and Prevention monitor the postmarketing safety of licensed vaccines using the Vaccine Adverse Event Reporting System (VAERS), which relies on people who get the vaccines to report adverse events.
 

Real-world finding

After reports indicated a safety signal in 2020, the researchers conducted a case-series review, calculated the reporting rate, and did a PubMed search for similar reports.

They found that the reporting rate for injection-site necrosis was less than 0.2 cases per 1 million vaccine doses administered. The PubMed search yielded two cases of injection-site necrosis after the vaccine.

The 23-valent vaccine helps protect people from pneumococcus bacterial infection. The manufacturer reports that it is for people at least 50 years of age and for children who are at least 2 years of age with medical conditions that put them at elevated risk for infection.

The U.S. package insert has been updated, in the Post-Marketing Experience section, to include injection-site necrosis.

Of the 104 VAERS reports identified by the researchers, 48 met the case definition. Of those cases, most were for skin necrosis (n = 43), five of which also included fat necrosis. The remaining five cases of necrosis affected fascia (n = 2); fat and fascia (n = 1); fat, fascia, and muscle (n = 1); and muscle (n = 1).

In 23 of the 48 cases (47.9%), the reactions were serious and included one death (unrelated to vaccination).

Seventeen patients (35.4%) were hospitalized and 26 (54.2%) required surgery, most commonly debridement. Eight patients (16.7%) underwent multiple surgical procedures and three (6.3%) required a skin graft.

For patients with skin necrosis (n = 43), the median age was 67 years, and most patients were female (n = 36). Twelve patients were immunocompromised.

Concomitant vaccinations were reported in 10 patients, five of whom got the shot in the same arm as the 23-valent pneumococcal vaccine. A concurrent diagnosis of cellulitis was reported in 16 patients and an abscess was reported in three patients. There were too few cases of fat, fascia, or muscle necrosis to draw conclusions, the researchers report.

Often, skin necrosis was seen after a progression of symptoms, such as redness, pain, or swelling.

“These reports are consistent with published descriptions of injection-site necrosis, which has been reported as a rare complication for many vaccines and injectable drugs,” the investigators report.

Although the researchers couldn’t conclude from the VAERS reports alone that the vaccine injection caused the necrosis, “the timing and the location of reactions at the injection site suggest a possible causal association with the vaccine,” they explain. However, they add, patient comorbidities and poor injection technique may also be contributors.

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

A U.S. Food and Drug Administration investigation of injection-site necrosis in some people who received the 23-valent pneumococcal vaccine has concluded that the benefits of the vaccine outweigh the risks.

No similar safety signal has been detected for the more recently approved 15-valent and 20-valent pneumococcal conjugate vaccines, explain the investigators, led by Brendan Day, MD, MPH, from the FDA’s Center for Biologics Evaluation and Research, in their report published online in JAMA Internal Medicine.

Reports of injection-site necrosis emerged after the vaccine (Pneumovax 23, Merck) had been approved by the FDA and was administered to a large, diverse, real-world population.

Rare safety events can emerge after FDA approval, as clinical trials may not be able to detect them in a study-group population.

Therefore, “postmarketing safety surveillance is critical to further characterize the safety profile of licensed vaccines,” the investigators point out.

The FDA and the Centers for Disease Control and Prevention monitor the postmarketing safety of licensed vaccines using the Vaccine Adverse Event Reporting System (VAERS), which relies on people who get the vaccines to report adverse events.
 

Real-world finding

After reports indicated a safety signal in 2020, the researchers conducted a case-series review, calculated the reporting rate, and did a PubMed search for similar reports.

They found that the reporting rate for injection-site necrosis was less than 0.2 cases per 1 million vaccine doses administered. The PubMed search yielded two cases of injection-site necrosis after the vaccine.

The 23-valent vaccine helps protect people from pneumococcus bacterial infection. The manufacturer reports that it is for people at least 50 years of age and for children who are at least 2 years of age with medical conditions that put them at elevated risk for infection.

The U.S. package insert has been updated, in the Post-Marketing Experience section, to include injection-site necrosis.

Of the 104 VAERS reports identified by the researchers, 48 met the case definition. Of those cases, most were for skin necrosis (n = 43), five of which also included fat necrosis. The remaining five cases of necrosis affected fascia (n = 2); fat and fascia (n = 1); fat, fascia, and muscle (n = 1); and muscle (n = 1).

In 23 of the 48 cases (47.9%), the reactions were serious and included one death (unrelated to vaccination).

Seventeen patients (35.4%) were hospitalized and 26 (54.2%) required surgery, most commonly debridement. Eight patients (16.7%) underwent multiple surgical procedures and three (6.3%) required a skin graft.

For patients with skin necrosis (n = 43), the median age was 67 years, and most patients were female (n = 36). Twelve patients were immunocompromised.

Concomitant vaccinations were reported in 10 patients, five of whom got the shot in the same arm as the 23-valent pneumococcal vaccine. A concurrent diagnosis of cellulitis was reported in 16 patients and an abscess was reported in three patients. There were too few cases of fat, fascia, or muscle necrosis to draw conclusions, the researchers report.

Often, skin necrosis was seen after a progression of symptoms, such as redness, pain, or swelling.

“These reports are consistent with published descriptions of injection-site necrosis, which has been reported as a rare complication for many vaccines and injectable drugs,” the investigators report.

Although the researchers couldn’t conclude from the VAERS reports alone that the vaccine injection caused the necrosis, “the timing and the location of reactions at the injection site suggest a possible causal association with the vaccine,” they explain. However, they add, patient comorbidities and poor injection technique may also be contributors.