Liam Davenport

BOSTON – Older women who have had breast cancer frequently undergo annual surveillance mammography, even if there is only a small risk of their developing a second cancer or if they have other mortality risks associated with age and comorbidities. This ongoing annual surveillance with mammography may be doing more harm than good, warn researchers.

In a study that included almost 45,000 women who were aged 67 years or older when they were diagnosed with breast cancer, investigators found that patients commonly underwent annual mammographies.

“Even 10 years after their initial diagnosis ... about 40% of them were still getting surveillance mammography well into their 80s and 90s,” noted lead investigator Elizabeth Berger, MD, assistant professor of breast surgical oncology, Yale University, New Haven, Conn.

“Ongoing surveillance mammography in these patients may lead to overdiagnosis and overtreatment of cancers that potentially would not harm patients if left untreated,” Dr. Berger said.

“A positive or false positive finding may unnecessarily erode patient quality of life and incur costs to the patient and health care system without benefit,” she said. She added: “If an elderly woman is in poor health and has significant competing mortality risks compared to breast cancer, annual mammography may not be necessary.”

The research was presented at the annual meeting of the American Society of Breast Surgeons (ASBrS). The study was highlighted in a preview press briefing.

Speaking at the press briefing, Dr. Berger said that the “risks and benefits of surveillance mammography, including its downstream effects, should be considered by both patients and their doctors together to create a shared decision plan.” She acknowledged that the idea of skipping mammograms may be a sensitive one for patients.

She also shared what she described as “exciting news”: “We have just recently received funding from our geriatric group here at Yale to start to evaluate the potential benefits and harms of these surveillance mammographies.”

The aim is to evaluate false positive rates and the potential for overdiagnosis and overtreatment, “so stay tuned,” she added.

Approached for comment, Mediget Teshome, MD, MPH, said it was “not surprising to see the high rates of surveillance mammography, especially in the short term after treatment.”

She said in an interview that the results suggest that it “may be being overused,” given the low rates of second primary breast cancer and the “competing health concerns” of these women.

Overuse can, on the other hand, “definitely be a complex issue,” said Dr. Teshome, associate professor, department of breast surgical oncology, University of Texas MD Anderson Cancer Center, Houston.

“The goal of mammography screening is to identify breast cancer at an early stage,” she explained. She noted that because of the “competing mortality risk from other challenging and life-threatening health problems,” early-stage breast cancer “may not contribute significantly” to the overall mortality risk.

“In general, in this patient population, consideration should be given to stratifying based on an individual patient’s risk of breast cancer recurrence or new breast cancer, estimated life expectancy, as well as shared decision-making with the patient based on their goals of care.”
 

Study details

To examine the use of surveillance mammography and the risk of subsequent cancers among older women, Dr. Berger and her team used data from the Surveillance, Epidemiology, and End Results (SEER) registry to identify women aged 67 years or older who were diagnosed with a first nonmetastatic beast cancer between 2003 and 2007.

The patients were followed beginning 1 year after diagnosis until the occurrence of a second primary breast cancer, death, or the end of follow-up in 2017.

Data on 44,475 women were analyzed. Of those patients, 30% were older than 80 years. The majority (74%) of breast cancers were of stage I or II, and 72% were hormone receptor–positive (HR+).

Comorbid conditions were common; 55% of women had at least one, and 16% had three or more.

Life expectancy, determined on the basis of age, sex, and comorbidities, was estimated at less than 5 years for 26% of women. For 36% of patients, life expectancy was 6-10 years, and for 38%, it was longer than 10 years.

The cumulative incidence of developing a second primary breast cancer varied by life expectancy and the tumor’s molecular subtype.

The incidence was 3.7% among women with a life expectancy of less than 5 years, 4.9% among those expected to live 6-10 years, and 7.6% among those predicted to live more than 10 years.

Among women with a life expectancy of less than 5 years, the cumulative incidence of a second primary tumor was 4.0% among those with triple-negative breast cancer, vs. 3.0% among those with HR+ breast cancer.

Among patients whose life expectancy was more than 10 years, the cumulative incidence of a second primary tumor was 9.2% among women with triple-negative disease, vs. 7.0% among those with HR+ cancers.

The team found that it was common for women across all the groups to undergo mammography.

Among women with a life expectancy of 6-10 years, 82% underwent at least one mammogram, and 65% underwent five mammograms. Even among women with a life expectancy of less than 1 year, 51% underwent at least one mammogram within 12 months of death.

Among women with a life expectancy of less than 5 years, 68% of women had received a mammogram 1 year after treatment; 53% underwent three mammograms within 3 years after treatment.

No funding for the study was declared. The investigators have disclosed no relevant financial relationships.

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

BOSTON – Older women who have had breast cancer frequently undergo annual surveillance mammography, even if there is only a small risk of their developing a second cancer or if they have other mortality risks associated with age and comorbidities. This ongoing annual surveillance with mammography may be doing more harm than good, warn researchers.

In a study that included almost 45,000 women who were aged 67 years or older when they were diagnosed with breast cancer, investigators found that patients commonly underwent annual mammographies.

“Even 10 years after their initial diagnosis ... about 40% of them were still getting surveillance mammography well into their 80s and 90s,” noted lead investigator Elizabeth Berger, MD, assistant professor of breast surgical oncology, Yale University, New Haven, Conn.

“Ongoing surveillance mammography in these patients may lead to overdiagnosis and overtreatment of cancers that potentially would not harm patients if left untreated,” Dr. Berger said.

“A positive or false positive finding may unnecessarily erode patient quality of life and incur costs to the patient and health care system without benefit,” she said. She added: “If an elderly woman is in poor health and has significant competing mortality risks compared to breast cancer, annual mammography may not be necessary.”

The research was presented at the annual meeting of the American Society of Breast Surgeons (ASBrS). The study was highlighted in a preview press briefing.

Speaking at the press briefing, Dr. Berger said that the “risks and benefits of surveillance mammography, including its downstream effects, should be considered by both patients and their doctors together to create a shared decision plan.” She acknowledged that the idea of skipping mammograms may be a sensitive one for patients.

She also shared what she described as “exciting news”: “We have just recently received funding from our geriatric group here at Yale to start to evaluate the potential benefits and harms of these surveillance mammographies.”

The aim is to evaluate false positive rates and the potential for overdiagnosis and overtreatment, “so stay tuned,” she added.

Approached for comment, Mediget Teshome, MD, MPH, said it was “not surprising to see the high rates of surveillance mammography, especially in the short term after treatment.”

She said in an interview that the results suggest that it “may be being overused,” given the low rates of second primary breast cancer and the “competing health concerns” of these women.

Overuse can, on the other hand, “definitely be a complex issue,” said Dr. Teshome, associate professor, department of breast surgical oncology, University of Texas MD Anderson Cancer Center, Houston.

“The goal of mammography screening is to identify breast cancer at an early stage,” she explained. She noted that because of the “competing mortality risk from other challenging and life-threatening health problems,” early-stage breast cancer “may not contribute significantly” to the overall mortality risk.

“In general, in this patient population, consideration should be given to stratifying based on an individual patient’s risk of breast cancer recurrence or new breast cancer, estimated life expectancy, as well as shared decision-making with the patient based on their goals of care.”
 

Study details

To examine the use of surveillance mammography and the risk of subsequent cancers among older women, Dr. Berger and her team used data from the Surveillance, Epidemiology, and End Results (SEER) registry to identify women aged 67 years or older who were diagnosed with a first nonmetastatic beast cancer between 2003 and 2007.

The patients were followed beginning 1 year after diagnosis until the occurrence of a second primary breast cancer, death, or the end of follow-up in 2017.

Data on 44,475 women were analyzed. Of those patients, 30% were older than 80 years. The majority (74%) of breast cancers were of stage I or II, and 72% were hormone receptor–positive (HR+).

Comorbid conditions were common; 55% of women had at least one, and 16% had three or more.

Life expectancy, determined on the basis of age, sex, and comorbidities, was estimated at less than 5 years for 26% of women. For 36% of patients, life expectancy was 6-10 years, and for 38%, it was longer than 10 years.

The cumulative incidence of developing a second primary breast cancer varied by life expectancy and the tumor’s molecular subtype.

The incidence was 3.7% among women with a life expectancy of less than 5 years, 4.9% among those expected to live 6-10 years, and 7.6% among those predicted to live more than 10 years.

Among women with a life expectancy of less than 5 years, the cumulative incidence of a second primary tumor was 4.0% among those with triple-negative breast cancer, vs. 3.0% among those with HR+ breast cancer.

Among patients whose life expectancy was more than 10 years, the cumulative incidence of a second primary tumor was 9.2% among women with triple-negative disease, vs. 7.0% among those with HR+ cancers.

The team found that it was common for women across all the groups to undergo mammography.

Among women with a life expectancy of 6-10 years, 82% underwent at least one mammogram, and 65% underwent five mammograms. Even among women with a life expectancy of less than 1 year, 51% underwent at least one mammogram within 12 months of death.

Among women with a life expectancy of less than 5 years, 68% of women had received a mammogram 1 year after treatment; 53% underwent three mammograms within 3 years after treatment.

No funding for the study was declared. The investigators have disclosed no relevant financial relationships.

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

BOSTON – Older women who have had breast cancer frequently undergo annual surveillance mammography, even if there is only a small risk of their developing a second cancer or if they have other mortality risks associated with age and comorbidities. This ongoing annual surveillance with mammography may be doing more harm than good, warn researchers.

In a study that included almost 45,000 women who were aged 67 years or older when they were diagnosed with breast cancer, investigators found that patients commonly underwent annual mammographies.

“Even 10 years after their initial diagnosis ... about 40% of them were still getting surveillance mammography well into their 80s and 90s,” noted lead investigator Elizabeth Berger, MD, assistant professor of breast surgical oncology, Yale University, New Haven, Conn.

“Ongoing surveillance mammography in these patients may lead to overdiagnosis and overtreatment of cancers that potentially would not harm patients if left untreated,” Dr. Berger said.

“A positive or false positive finding may unnecessarily erode patient quality of life and incur costs to the patient and health care system without benefit,” she said. She added: “If an elderly woman is in poor health and has significant competing mortality risks compared to breast cancer, annual mammography may not be necessary.”

The research was presented at the annual meeting of the American Society of Breast Surgeons (ASBrS). The study was highlighted in a preview press briefing.

Speaking at the press briefing, Dr. Berger said that the “risks and benefits of surveillance mammography, including its downstream effects, should be considered by both patients and their doctors together to create a shared decision plan.” She acknowledged that the idea of skipping mammograms may be a sensitive one for patients.

She also shared what she described as “exciting news”: “We have just recently received funding from our geriatric group here at Yale to start to evaluate the potential benefits and harms of these surveillance mammographies.”

The aim is to evaluate false positive rates and the potential for overdiagnosis and overtreatment, “so stay tuned,” she added.

Approached for comment, Mediget Teshome, MD, MPH, said it was “not surprising to see the high rates of surveillance mammography, especially in the short term after treatment.”

She said in an interview that the results suggest that it “may be being overused,” given the low rates of second primary breast cancer and the “competing health concerns” of these women.

Overuse can, on the other hand, “definitely be a complex issue,” said Dr. Teshome, associate professor, department of breast surgical oncology, University of Texas MD Anderson Cancer Center, Houston.

“The goal of mammography screening is to identify breast cancer at an early stage,” she explained. She noted that because of the “competing mortality risk from other challenging and life-threatening health problems,” early-stage breast cancer “may not contribute significantly” to the overall mortality risk.

“In general, in this patient population, consideration should be given to stratifying based on an individual patient’s risk of breast cancer recurrence or new breast cancer, estimated life expectancy, as well as shared decision-making with the patient based on their goals of care.”
 

Study details

To examine the use of surveillance mammography and the risk of subsequent cancers among older women, Dr. Berger and her team used data from the Surveillance, Epidemiology, and End Results (SEER) registry to identify women aged 67 years or older who were diagnosed with a first nonmetastatic beast cancer between 2003 and 2007.

The patients were followed beginning 1 year after diagnosis until the occurrence of a second primary breast cancer, death, or the end of follow-up in 2017.

Data on 44,475 women were analyzed. Of those patients, 30% were older than 80 years. The majority (74%) of breast cancers were of stage I or II, and 72% were hormone receptor–positive (HR+).

Comorbid conditions were common; 55% of women had at least one, and 16% had three or more.

Life expectancy, determined on the basis of age, sex, and comorbidities, was estimated at less than 5 years for 26% of women. For 36% of patients, life expectancy was 6-10 years, and for 38%, it was longer than 10 years.

The cumulative incidence of developing a second primary breast cancer varied by life expectancy and the tumor’s molecular subtype.

The incidence was 3.7% among women with a life expectancy of less than 5 years, 4.9% among those expected to live 6-10 years, and 7.6% among those predicted to live more than 10 years.

Among women with a life expectancy of less than 5 years, the cumulative incidence of a second primary tumor was 4.0% among those with triple-negative breast cancer, vs. 3.0% among those with HR+ breast cancer.

Among patients whose life expectancy was more than 10 years, the cumulative incidence of a second primary tumor was 9.2% among women with triple-negative disease, vs. 7.0% among those with HR+ cancers.

The team found that it was common for women across all the groups to undergo mammography.

Among women with a life expectancy of 6-10 years, 82% underwent at least one mammogram, and 65% underwent five mammograms. Even among women with a life expectancy of less than 1 year, 51% underwent at least one mammogram within 12 months of death.

Among women with a life expectancy of less than 5 years, 68% of women had received a mammogram 1 year after treatment; 53% underwent three mammograms within 3 years after treatment.

No funding for the study was declared. The investigators have disclosed no relevant financial relationships.

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

Early-stage breast cancer patients who undergo a mastectomy and have a pathological analysis of their sentinel lymph nodes (SLN) performed during surgery are more likely to be overtreated with both axillary lymph node dissection (ALND) and axillary radiation (AxRT), warned U.S. investigators.

The team studied data on more than 40,000 clinically node-negative women who underwent upfront mastectomy. Just over 8,000 patients were found to have one to two SLN, with intraoperative pathology performed in approximately one-third.

Intraoperative pathology was associated with a more than eightfold increase in the likelihood of performing both ALND and AxRT, far more than any other factor.

These results provide “evidence that a significant percentage of the mastectomy patients with limited disease in up to two SLNs may be overtreated. … simply because their pathology results are read and acted on while they are on the operating table,” said senior author Olga Kantor, MD, MS, associate program director, Breast Surgical Oncology Fellowship Program, Brigham and Women’s Hospital and Dana-Farber Cancer Institute, Boston.

“Notably, postsurgical decisions typically involve a multidisciplinary team, including radiation oncologists, which will likely result in a more integrated overall treatment plan,” she commented in a statement.

“This study suggests that surgeons should delay ALND decision-making until a later time to avoid overtreating patients,” Dr. Kantor emphasized.

The research was presented at the annual meeting of the American Society of Breast Surgeons, and was highlighted in a premeeting press briefing.

Approached for comment on the new findings, Sarah L. Blair, MD, professor and vice chair, department of surgery, University of California San Diego Health, noted that “there is a great deal of data on deescalation in axillary surgery in patients undergoing breast conservation with radiation.”

Dr. Blair, who was not involved in the study, noted that, while there are some studies in mastectomy patients with equal oncologic results, “the topic remains more controversial.”

“This study highlights that surgeons strongly consider deescalating axillary surgery in mastectomy patients to reduce long-term complications,” she said in an interview.

“If possible, these patients should be discussed in a multidisciplinary fashion ahead of time,” she emphasized.

“If surgeons send the lymph nodes for frozen section then, as this paper demonstrates, they will act on the information and perform axillary dissection for early-stage disease.”
 

Study details

At the press briefing for the study, Dr. Kantor explained that several clinical trials, including AMAROS, have already “established the safety of axillary observation or AxRT as an alternative to ALND” in clinically node-negative breast cancer patients found to have one to two positive SLN.

She noted that “mastectomy patients were included in these trials, but they made up a minority” of the populations, ranging from 9% to 18%, “and so controversy remains over the optimal axillary management” in this patient population.

Dr. Kantor said that intraoperative pathology assessment “can help avoid the need to return to the operating room for additional axillary surgery” by checking the SLN at the time.

However, acting on the results during the procedure “does not allow for multidisciplinary discussion” and can mean that patients end up having both ALND and postoperative AxRT.

“This dual approach may result in axillary overtreatment in patients who may otherwise have been eligible for axillary radiation alone,” she underlined.

Moreover, a recent survey of 680 surgeons by the ASBrS found that 52% were performing routine intraoperative pathology assessment of SLN, and 78% of those said they would perform ALND if the results came back positive.

To investigate the impact of intraoperative pathology assessment on axillary management in mastectomy patients who would have been eligible for the AMAROS trial, the team examined data from the U.S. National Cancer Database.

They included cT1-2N0 breast cancer patients who had upfront mastectomy in 2018-2019 and were found to have one to two positive SLN.

They defined intraoperative pathology assessment as:

• “Not done/not acted on” if ALND was either not performed or performed at a later date than the pathology assessment.
• “Done/acted on” if both ALND and the pathology assessment were carried out on the same day.

In addition, AxRT was defined as postmastectomy radiation to the chest wall that included radiation to the draining lymph nodes.

The researchers identified 40,467 patients, of whom 20.3% had one to two positive SLN. Among those, axillary management consisted of observation in 33.2%, ALND in 26.6%, AxRT in 22.2%, and ALND plus AxRT in 18.0%.

Overall, 37.2% of the patients underwent intraoperative pathology and 62.8% did not, 11.8% of whom later returned to the operating room for ALND.

Patients who underwent intraoperative pathology were more likely than those who did not to have cT2 disease (48.0% vs. 44.1%), lympho-vascular invasion (43.4% vs. 37.1%), two positive SLN (26.5% vs. 19.2%), and macrometastasis (87.6% vs. 64.2%, P < .001 for all).

Rates of ALND plus AxRT were significantly higher in patients who had intraoperative pathology done/acted on than in those whom intraoperative pathology was not done/not acted on, at 41.0% vs. 4.9% (P < .001).

Adjusted multivariate analysis indicated that receipt of ALND plus AxRT was significantly associated with intraoperative pathology being done/acted on vs. being not done/acted on, at an odds ratio of 8.99 (P < .001).

There were also significant associations between having both procedures and macrometastasis in the SLN, at an odds ratio vs. micrometastasis of 3.38 (P < .001), and the number of total positive SLN, at odds ratio vs. 1 of 2.14 for two nodes, 3.92 for three nodes, and 5.32 for > three nodes (P < .001 for all).

The researchers also found that lobular tumors on histologic analysis were associated with having ALND plus AxRT, at an odds ratio vs. ductal histology of 1.40 (P < .001).

No funding was declared. Dr. Kantor and Dr. Blair report no relevant financial relationships.

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

Early-stage breast cancer patients who undergo a mastectomy and have a pathological analysis of their sentinel lymph nodes (SLN) performed during surgery are more likely to be overtreated with both axillary lymph node dissection (ALND) and axillary radiation (AxRT), warned U.S. investigators.

The team studied data on more than 40,000 clinically node-negative women who underwent upfront mastectomy. Just over 8,000 patients were found to have one to two SLN, with intraoperative pathology performed in approximately one-third.

Intraoperative pathology was associated with a more than eightfold increase in the likelihood of performing both ALND and AxRT, far more than any other factor.

These results provide “evidence that a significant percentage of the mastectomy patients with limited disease in up to two SLNs may be overtreated. … simply because their pathology results are read and acted on while they are on the operating table,” said senior author Olga Kantor, MD, MS, associate program director, Breast Surgical Oncology Fellowship Program, Brigham and Women’s Hospital and Dana-Farber Cancer Institute, Boston.

“Notably, postsurgical decisions typically involve a multidisciplinary team, including radiation oncologists, which will likely result in a more integrated overall treatment plan,” she commented in a statement.

“This study suggests that surgeons should delay ALND decision-making until a later time to avoid overtreating patients,” Dr. Kantor emphasized.

The research was presented at the annual meeting of the American Society of Breast Surgeons, and was highlighted in a premeeting press briefing.

Approached for comment on the new findings, Sarah L. Blair, MD, professor and vice chair, department of surgery, University of California San Diego Health, noted that “there is a great deal of data on deescalation in axillary surgery in patients undergoing breast conservation with radiation.”

Dr. Blair, who was not involved in the study, noted that, while there are some studies in mastectomy patients with equal oncologic results, “the topic remains more controversial.”

“This study highlights that surgeons strongly consider deescalating axillary surgery in mastectomy patients to reduce long-term complications,” she said in an interview.

“If possible, these patients should be discussed in a multidisciplinary fashion ahead of time,” she emphasized.

“If surgeons send the lymph nodes for frozen section then, as this paper demonstrates, they will act on the information and perform axillary dissection for early-stage disease.”
 

Study details

At the press briefing for the study, Dr. Kantor explained that several clinical trials, including AMAROS, have already “established the safety of axillary observation or AxRT as an alternative to ALND” in clinically node-negative breast cancer patients found to have one to two positive SLN.

She noted that “mastectomy patients were included in these trials, but they made up a minority” of the populations, ranging from 9% to 18%, “and so controversy remains over the optimal axillary management” in this patient population.

Dr. Kantor said that intraoperative pathology assessment “can help avoid the need to return to the operating room for additional axillary surgery” by checking the SLN at the time.

However, acting on the results during the procedure “does not allow for multidisciplinary discussion” and can mean that patients end up having both ALND and postoperative AxRT.

“This dual approach may result in axillary overtreatment in patients who may otherwise have been eligible for axillary radiation alone,” she underlined.

Moreover, a recent survey of 680 surgeons by the ASBrS found that 52% were performing routine intraoperative pathology assessment of SLN, and 78% of those said they would perform ALND if the results came back positive.

To investigate the impact of intraoperative pathology assessment on axillary management in mastectomy patients who would have been eligible for the AMAROS trial, the team examined data from the U.S. National Cancer Database.

They included cT1-2N0 breast cancer patients who had upfront mastectomy in 2018-2019 and were found to have one to two positive SLN.

They defined intraoperative pathology assessment as:

• “Not done/not acted on” if ALND was either not performed or performed at a later date than the pathology assessment.
• “Done/acted on” if both ALND and the pathology assessment were carried out on the same day.

In addition, AxRT was defined as postmastectomy radiation to the chest wall that included radiation to the draining lymph nodes.

The researchers identified 40,467 patients, of whom 20.3% had one to two positive SLN. Among those, axillary management consisted of observation in 33.2%, ALND in 26.6%, AxRT in 22.2%, and ALND plus AxRT in 18.0%.

Overall, 37.2% of the patients underwent intraoperative pathology and 62.8% did not, 11.8% of whom later returned to the operating room for ALND.

Patients who underwent intraoperative pathology were more likely than those who did not to have cT2 disease (48.0% vs. 44.1%), lympho-vascular invasion (43.4% vs. 37.1%), two positive SLN (26.5% vs. 19.2%), and macrometastasis (87.6% vs. 64.2%, P < .001 for all).

Rates of ALND plus AxRT were significantly higher in patients who had intraoperative pathology done/acted on than in those whom intraoperative pathology was not done/not acted on, at 41.0% vs. 4.9% (P < .001).

Adjusted multivariate analysis indicated that receipt of ALND plus AxRT was significantly associated with intraoperative pathology being done/acted on vs. being not done/acted on, at an odds ratio of 8.99 (P < .001).

There were also significant associations between having both procedures and macrometastasis in the SLN, at an odds ratio vs. micrometastasis of 3.38 (P < .001), and the number of total positive SLN, at odds ratio vs. 1 of 2.14 for two nodes, 3.92 for three nodes, and 5.32 for > three nodes (P < .001 for all).

The researchers also found that lobular tumors on histologic analysis were associated with having ALND plus AxRT, at an odds ratio vs. ductal histology of 1.40 (P < .001).

No funding was declared. Dr. Kantor and Dr. Blair report no relevant financial relationships.

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

Early-stage breast cancer patients who undergo a mastectomy and have a pathological analysis of their sentinel lymph nodes (SLN) performed during surgery are more likely to be overtreated with both axillary lymph node dissection (ALND) and axillary radiation (AxRT), warned U.S. investigators.

The team studied data on more than 40,000 clinically node-negative women who underwent upfront mastectomy. Just over 8,000 patients were found to have one to two SLN, with intraoperative pathology performed in approximately one-third.

Intraoperative pathology was associated with a more than eightfold increase in the likelihood of performing both ALND and AxRT, far more than any other factor.

These results provide “evidence that a significant percentage of the mastectomy patients with limited disease in up to two SLNs may be overtreated. … simply because their pathology results are read and acted on while they are on the operating table,” said senior author Olga Kantor, MD, MS, associate program director, Breast Surgical Oncology Fellowship Program, Brigham and Women’s Hospital and Dana-Farber Cancer Institute, Boston.

“Notably, postsurgical decisions typically involve a multidisciplinary team, including radiation oncologists, which will likely result in a more integrated overall treatment plan,” she commented in a statement.

“This study suggests that surgeons should delay ALND decision-making until a later time to avoid overtreating patients,” Dr. Kantor emphasized.

The research was presented at the annual meeting of the American Society of Breast Surgeons, and was highlighted in a premeeting press briefing.

Approached for comment on the new findings, Sarah L. Blair, MD, professor and vice chair, department of surgery, University of California San Diego Health, noted that “there is a great deal of data on deescalation in axillary surgery in patients undergoing breast conservation with radiation.”

Dr. Blair, who was not involved in the study, noted that, while there are some studies in mastectomy patients with equal oncologic results, “the topic remains more controversial.”

“This study highlights that surgeons strongly consider deescalating axillary surgery in mastectomy patients to reduce long-term complications,” she said in an interview.

“If possible, these patients should be discussed in a multidisciplinary fashion ahead of time,” she emphasized.

“If surgeons send the lymph nodes for frozen section then, as this paper demonstrates, they will act on the information and perform axillary dissection for early-stage disease.”
 

Study details

At the press briefing for the study, Dr. Kantor explained that several clinical trials, including AMAROS, have already “established the safety of axillary observation or AxRT as an alternative to ALND” in clinically node-negative breast cancer patients found to have one to two positive SLN.

She noted that “mastectomy patients were included in these trials, but they made up a minority” of the populations, ranging from 9% to 18%, “and so controversy remains over the optimal axillary management” in this patient population.

Dr. Kantor said that intraoperative pathology assessment “can help avoid the need to return to the operating room for additional axillary surgery” by checking the SLN at the time.

However, acting on the results during the procedure “does not allow for multidisciplinary discussion” and can mean that patients end up having both ALND and postoperative AxRT.

“This dual approach may result in axillary overtreatment in patients who may otherwise have been eligible for axillary radiation alone,” she underlined.

Moreover, a recent survey of 680 surgeons by the ASBrS found that 52% were performing routine intraoperative pathology assessment of SLN, and 78% of those said they would perform ALND if the results came back positive.

To investigate the impact of intraoperative pathology assessment on axillary management in mastectomy patients who would have been eligible for the AMAROS trial, the team examined data from the U.S. National Cancer Database.

They included cT1-2N0 breast cancer patients who had upfront mastectomy in 2018-2019 and were found to have one to two positive SLN.

They defined intraoperative pathology assessment as:

• “Not done/not acted on” if ALND was either not performed or performed at a later date than the pathology assessment.
• “Done/acted on” if both ALND and the pathology assessment were carried out on the same day.

In addition, AxRT was defined as postmastectomy radiation to the chest wall that included radiation to the draining lymph nodes.

The researchers identified 40,467 patients, of whom 20.3% had one to two positive SLN. Among those, axillary management consisted of observation in 33.2%, ALND in 26.6%, AxRT in 22.2%, and ALND plus AxRT in 18.0%.

Overall, 37.2% of the patients underwent intraoperative pathology and 62.8% did not, 11.8% of whom later returned to the operating room for ALND.

Patients who underwent intraoperative pathology were more likely than those who did not to have cT2 disease (48.0% vs. 44.1%), lympho-vascular invasion (43.4% vs. 37.1%), two positive SLN (26.5% vs. 19.2%), and macrometastasis (87.6% vs. 64.2%, P < .001 for all).

Rates of ALND plus AxRT were significantly higher in patients who had intraoperative pathology done/acted on than in those whom intraoperative pathology was not done/not acted on, at 41.0% vs. 4.9% (P < .001).

Adjusted multivariate analysis indicated that receipt of ALND plus AxRT was significantly associated with intraoperative pathology being done/acted on vs. being not done/acted on, at an odds ratio of 8.99 (P < .001).

There were also significant associations between having both procedures and macrometastasis in the SLN, at an odds ratio vs. micrometastasis of 3.38 (P < .001), and the number of total positive SLN, at odds ratio vs. 1 of 2.14 for two nodes, 3.92 for three nodes, and 5.32 for > three nodes (P < .001 for all).

The researchers also found that lobular tumors on histologic analysis were associated with having ALND plus AxRT, at an odds ratio vs. ductal histology of 1.40 (P < .001).

No funding was declared. Dr. Kantor and Dr. Blair report no relevant financial relationships.

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

The association between colorectal cancer (CRC) and overweight and obesity may be underestimated because body mass index (BMI) is typically measured too near the time of CRC diagnosis and so would not reflect prediagnostic weight loss linked to the condition, a new analysis suggests.

Obesity, assessed using BMI, was associated with a twofold higher risk of CRC 8-10 years prior to diagnosis, while weight loss of 2 kg or more within 2 years of diagnosis was associated with a “dramatic” 7.52-fold increased risk of CRC, the researchers said.

The results “illustrate the dramatic change of BMI as a risk factor associated with CRC, depending on whether the period of potential prediagnostic weight loss is accounted for or not,” Hermann Brenner, MD, MPH, of the German Cancer Research Center, Heidelberg, and colleagues conclude.

The study was published online in JAMA Network Open.

Recent evidence suggests that obesity is associated with an estimated 30% greater risk of CRC. But the extent to which excess body weight influences CRC risk may be underestimated because prediagnostic weight loss has historically been overlooked.

To understand how prediagnostic weight loss could affect the associations found between excess weight and CRC risk, the researchers examined weight data on almost 6,500 patients newly diagnosed with CRC and more than 5,400 control persons who were matched for age, sex, and country of residence. The median age of the cohort was 69 years, and 60.3% were men.

At the time of recruitment, 62% of case patients and 66% of control patients were overweight or obese. No association was found between current BMI and CRC risk.

However, when using patients’ weight from 8-10 years before CRC diagnosis, the researchers found a significant positive association between overweight or obesity and CRC risk (adjusted odds ratio, 1.27 for overweight and 2.09 for obesity). The risk for CRC increased significantly for every 5-unit increase in BMI (aOR, 1.35). These results were similar when the patients were stratified by sex and CRC subsites.

The researchers also found that weight loss of 2 kg or more within 2 years of CRC diagnosis or interview was associated with a 7.52-fold increased risk for CRC.

“While we demonstrated that prediagnostic weight loss is a major concern for CRC,” such prediagnostic weight loss “may play a similarly important role for other cancers and noncancer diseases associated with overweight and obesity,” the authors note.

“Most importantly, however, our results emphasize the importance of interventions aimed at preventing and managing overweight and obesity ... and which may factor more substantially into CRC risk and other obesity-related diseases than suggested by existing epidemiological evidence,” they write.

The study was supported in part by grants from the German Research Council and the German Federal Ministry of Education and Research. The authors have disclosed no relevant financial relationships.

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

The association between colorectal cancer (CRC) and overweight and obesity may be underestimated because body mass index (BMI) is typically measured too near the time of CRC diagnosis and so would not reflect prediagnostic weight loss linked to the condition, a new analysis suggests.

Obesity, assessed using BMI, was associated with a twofold higher risk of CRC 8-10 years prior to diagnosis, while weight loss of 2 kg or more within 2 years of diagnosis was associated with a “dramatic” 7.52-fold increased risk of CRC, the researchers said.

The results “illustrate the dramatic change of BMI as a risk factor associated with CRC, depending on whether the period of potential prediagnostic weight loss is accounted for or not,” Hermann Brenner, MD, MPH, of the German Cancer Research Center, Heidelberg, and colleagues conclude.

The study was published online in JAMA Network Open.

Recent evidence suggests that obesity is associated with an estimated 30% greater risk of CRC. But the extent to which excess body weight influences CRC risk may be underestimated because prediagnostic weight loss has historically been overlooked.

To understand how prediagnostic weight loss could affect the associations found between excess weight and CRC risk, the researchers examined weight data on almost 6,500 patients newly diagnosed with CRC and more than 5,400 control persons who were matched for age, sex, and country of residence. The median age of the cohort was 69 years, and 60.3% were men.

At the time of recruitment, 62% of case patients and 66% of control patients were overweight or obese. No association was found between current BMI and CRC risk.

However, when using patients’ weight from 8-10 years before CRC diagnosis, the researchers found a significant positive association between overweight or obesity and CRC risk (adjusted odds ratio, 1.27 for overweight and 2.09 for obesity). The risk for CRC increased significantly for every 5-unit increase in BMI (aOR, 1.35). These results were similar when the patients were stratified by sex and CRC subsites.

The researchers also found that weight loss of 2 kg or more within 2 years of CRC diagnosis or interview was associated with a 7.52-fold increased risk for CRC.

“While we demonstrated that prediagnostic weight loss is a major concern for CRC,” such prediagnostic weight loss “may play a similarly important role for other cancers and noncancer diseases associated with overweight and obesity,” the authors note.

“Most importantly, however, our results emphasize the importance of interventions aimed at preventing and managing overweight and obesity ... and which may factor more substantially into CRC risk and other obesity-related diseases than suggested by existing epidemiological evidence,” they write.

The study was supported in part by grants from the German Research Council and the German Federal Ministry of Education and Research. The authors have disclosed no relevant financial relationships.

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

The association between colorectal cancer (CRC) and overweight and obesity may be underestimated because body mass index (BMI) is typically measured too near the time of CRC diagnosis and so would not reflect prediagnostic weight loss linked to the condition, a new analysis suggests.

Obesity, assessed using BMI, was associated with a twofold higher risk of CRC 8-10 years prior to diagnosis, while weight loss of 2 kg or more within 2 years of diagnosis was associated with a “dramatic” 7.52-fold increased risk of CRC, the researchers said.

The results “illustrate the dramatic change of BMI as a risk factor associated with CRC, depending on whether the period of potential prediagnostic weight loss is accounted for or not,” Hermann Brenner, MD, MPH, of the German Cancer Research Center, Heidelberg, and colleagues conclude.

The study was published online in JAMA Network Open.

Recent evidence suggests that obesity is associated with an estimated 30% greater risk of CRC. But the extent to which excess body weight influences CRC risk may be underestimated because prediagnostic weight loss has historically been overlooked.

To understand how prediagnostic weight loss could affect the associations found between excess weight and CRC risk, the researchers examined weight data on almost 6,500 patients newly diagnosed with CRC and more than 5,400 control persons who were matched for age, sex, and country of residence. The median age of the cohort was 69 years, and 60.3% were men.

At the time of recruitment, 62% of case patients and 66% of control patients were overweight or obese. No association was found between current BMI and CRC risk.

However, when using patients’ weight from 8-10 years before CRC diagnosis, the researchers found a significant positive association between overweight or obesity and CRC risk (adjusted odds ratio, 1.27 for overweight and 2.09 for obesity). The risk for CRC increased significantly for every 5-unit increase in BMI (aOR, 1.35). These results were similar when the patients were stratified by sex and CRC subsites.

The researchers also found that weight loss of 2 kg or more within 2 years of CRC diagnosis or interview was associated with a 7.52-fold increased risk for CRC.

“While we demonstrated that prediagnostic weight loss is a major concern for CRC,” such prediagnostic weight loss “may play a similarly important role for other cancers and noncancer diseases associated with overweight and obesity,” the authors note.

“Most importantly, however, our results emphasize the importance of interventions aimed at preventing and managing overweight and obesity ... and which may factor more substantially into CRC risk and other obesity-related diseases than suggested by existing epidemiological evidence,” they write.

The study was supported in part by grants from the German Research Council and the German Federal Ministry of Education and Research. The authors have disclosed no relevant financial relationships.

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

Drinking sugar-sweetened beverages (SSBs) increases the risk of cardiovascular disease and all-cause death in people with type 2 diabetes, reveals a U.S. study that also suggests switching to coffee, tea, or low-fat milk may diminish these risks.

The researchers examined data on almost 15,500 participants with type 2 diabetes from two major studies, finding that the highest level of consumption of SSBs was associated with a 20% increased risk of all-cause mortality and a 25% raised risk of cardiovascular disease, compared with consumption of the least amounts of these products.

The research, published in BMJ, also showed that drinking coffee, tea, plain water, and low-fat milk reduced the risk of all-cause death and that switching from SSBs to the other beverages was linked to lower mortality.

“Overall, these results provide additional evidence that emphasizes the importance of beverage choices in maintaining overall health among adults with diabetes,” say senior author Le Ma, PhD, department of nutrition, Harvard School of Public Health, Boston, and colleagues.

“Collectively, these findings all point in the same direction. Lower consumption of SSBs and higher consumption of coffee, tea, plain water, or low-fat milk are optimal for better health outcomes in adults with type 2 diabetes,” Nita G. Forouhi, MD, PhD, emphasizes in an accompanying editorial.


 

Choice of drink matters

Dr. Forouhi, from the University of Cambridge (England), warned, however, that the findings “cannot be considered cause and effect,” despite the large-scale analysis.

Moreover, “questions remain,” such as the impact of beverage consumption on coronary heart disease and stroke risk, and cancer mortality, with the current study providing “inconclusive” data on the latter.

There was also no data on the addition of sugar to tea or coffee, “so the comparative health effects of unsweetened and sweetened hot beverages remain unclear,” Dr. Forouhi points out. Also unknown is whether the type of tea consumed has a differential effect.

Despite these and other reservations, she says that overall, “Choice of beverage clearly matters.”

“The case for avoiding sugar-sweetened beverages is compelling, and it is supported by various fiscal measures in more than 45 countries. It is reasonable to shift the focus to drinks that are most likely to have positive health impacts: coffee, tea, plain water, and low-fat milk,” she notes.

Dr. Forouhi ends by underlining that the current findings tally with those seen in the general population, so “one important message is that having diabetes does not have to be especially restrictive.”
 

Expanding the evidence

It was estimated that 537 million adults worldwide had type 2 diabetes in 2021, a figure set to increase to 783 million by 2045, say the authors.

Individuals with type 2 diabetes have an increased risk of cardiovascular disease, among many other comorbidities, as well as premature death. Dietary interventions can play an important role in managing these risks.

Recommendations on the healthiest beverages to drink are largely based on evidence from the general population, and data are limited on the best options for adults with type 2 diabetes, who have altered metabolism, the researchers note.

To expand on this, they examined data from the Nurses’ Health Study, which enrolled female registered nurses aged 30-55 years and was initiated in 1976, and the Health Professionals Follow-Up Study, which included male health professionals aged 40-75 years and was initiated in 1996.

For the current analysis, 11,399 women and 4,087 men with type 2 diabetes were included from the two studies, of whom 2,715 were diagnosed before study entry.

Participants’ average daily beverage intake was assessed using a validated food frequency questionnaire administered every 2-4 years. SSBs included caffeinated and caffeine-free colas, other carbonated SSBs, and noncarbonated SSBs, such as fruit punches, lemonades, or other fruit drinks.

During 285,967 person-years of follow-up, there were 7,638 (49.3%) deaths, and 3,447 (22.3%) cases of incident cardiovascular disease were documented during 248,447 person-years of follow-up.

Fully adjusted multivariate analysis comparing the lowest and highest beverage intake indicated that SSBs were associated with a significant increase in all-cause mortality, at a pooled hazard ratio of 1.20, or 1.08 for each additional serving per day (P = .01).

In contrast, the associations between all-cause mortality and consumption of artificially sweetened beverages, fruit juice, and full-fat milk were not significant, whereas coffee (HR, 0.74), tea (HR, 0.79), plain water (HR, 0.77), and low-fat milk (HR, 0.88) were linked to a reduced risk.

The team reported that there were similar associations between beverage intake and cardiovascular disease incidence, at an HR of 1.25 for SSBs, as well as for cardiovascular disease mortality, at an HR of 1.29.

Participants who increased their tea, coffee, and low-fat milk consumption during the course of the study had lower all-cause mortality than those who did not. Switching from SSBs to other beverages was also associated with lower mortality.

The researchers note, however, that there are “several potential limitations” to their study, including that “individual beverage consumption may be correlated with other dietary and lifestyle risk factors for cardiovascular disease incidence and mortality among adults with [type 2] diabetes.”

The study was sponsored by the National Institutes of Health. Dr. Ma has reported no relevant financial relationships. Disclosures for the other authors are listed with the article. Dr. Forouhi has declared receiving support from the U.K. Medical Research Council Epidemiology Unit and U.K. National Institute for Health and Care Research Biomedical Research Centre Cambridge.

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

Drinking sugar-sweetened beverages (SSBs) increases the risk of cardiovascular disease and all-cause death in people with type 2 diabetes, reveals a U.S. study that also suggests switching to coffee, tea, or low-fat milk may diminish these risks.

The researchers examined data on almost 15,500 participants with type 2 diabetes from two major studies, finding that the highest level of consumption of SSBs was associated with a 20% increased risk of all-cause mortality and a 25% raised risk of cardiovascular disease, compared with consumption of the least amounts of these products.

The research, published in BMJ, also showed that drinking coffee, tea, plain water, and low-fat milk reduced the risk of all-cause death and that switching from SSBs to the other beverages was linked to lower mortality.

“Overall, these results provide additional evidence that emphasizes the importance of beverage choices in maintaining overall health among adults with diabetes,” say senior author Le Ma, PhD, department of nutrition, Harvard School of Public Health, Boston, and colleagues.

“Collectively, these findings all point in the same direction. Lower consumption of SSBs and higher consumption of coffee, tea, plain water, or low-fat milk are optimal for better health outcomes in adults with type 2 diabetes,” Nita G. Forouhi, MD, PhD, emphasizes in an accompanying editorial.


 

Choice of drink matters

Dr. Forouhi, from the University of Cambridge (England), warned, however, that the findings “cannot be considered cause and effect,” despite the large-scale analysis.

Moreover, “questions remain,” such as the impact of beverage consumption on coronary heart disease and stroke risk, and cancer mortality, with the current study providing “inconclusive” data on the latter.

There was also no data on the addition of sugar to tea or coffee, “so the comparative health effects of unsweetened and sweetened hot beverages remain unclear,” Dr. Forouhi points out. Also unknown is whether the type of tea consumed has a differential effect.

Despite these and other reservations, she says that overall, “Choice of beverage clearly matters.”

“The case for avoiding sugar-sweetened beverages is compelling, and it is supported by various fiscal measures in more than 45 countries. It is reasonable to shift the focus to drinks that are most likely to have positive health impacts: coffee, tea, plain water, and low-fat milk,” she notes.

Dr. Forouhi ends by underlining that the current findings tally with those seen in the general population, so “one important message is that having diabetes does not have to be especially restrictive.”
 

Expanding the evidence

It was estimated that 537 million adults worldwide had type 2 diabetes in 2021, a figure set to increase to 783 million by 2045, say the authors.

Individuals with type 2 diabetes have an increased risk of cardiovascular disease, among many other comorbidities, as well as premature death. Dietary interventions can play an important role in managing these risks.

Recommendations on the healthiest beverages to drink are largely based on evidence from the general population, and data are limited on the best options for adults with type 2 diabetes, who have altered metabolism, the researchers note.

To expand on this, they examined data from the Nurses’ Health Study, which enrolled female registered nurses aged 30-55 years and was initiated in 1976, and the Health Professionals Follow-Up Study, which included male health professionals aged 40-75 years and was initiated in 1996.

For the current analysis, 11,399 women and 4,087 men with type 2 diabetes were included from the two studies, of whom 2,715 were diagnosed before study entry.

Participants’ average daily beverage intake was assessed using a validated food frequency questionnaire administered every 2-4 years. SSBs included caffeinated and caffeine-free colas, other carbonated SSBs, and noncarbonated SSBs, such as fruit punches, lemonades, or other fruit drinks.

During 285,967 person-years of follow-up, there were 7,638 (49.3%) deaths, and 3,447 (22.3%) cases of incident cardiovascular disease were documented during 248,447 person-years of follow-up.

Fully adjusted multivariate analysis comparing the lowest and highest beverage intake indicated that SSBs were associated with a significant increase in all-cause mortality, at a pooled hazard ratio of 1.20, or 1.08 for each additional serving per day (P = .01).

In contrast, the associations between all-cause mortality and consumption of artificially sweetened beverages, fruit juice, and full-fat milk were not significant, whereas coffee (HR, 0.74), tea (HR, 0.79), plain water (HR, 0.77), and low-fat milk (HR, 0.88) were linked to a reduced risk.

The team reported that there were similar associations between beverage intake and cardiovascular disease incidence, at an HR of 1.25 for SSBs, as well as for cardiovascular disease mortality, at an HR of 1.29.

Participants who increased their tea, coffee, and low-fat milk consumption during the course of the study had lower all-cause mortality than those who did not. Switching from SSBs to other beverages was also associated with lower mortality.

The researchers note, however, that there are “several potential limitations” to their study, including that “individual beverage consumption may be correlated with other dietary and lifestyle risk factors for cardiovascular disease incidence and mortality among adults with [type 2] diabetes.”

The study was sponsored by the National Institutes of Health. Dr. Ma has reported no relevant financial relationships. Disclosures for the other authors are listed with the article. Dr. Forouhi has declared receiving support from the U.K. Medical Research Council Epidemiology Unit and U.K. National Institute for Health and Care Research Biomedical Research Centre Cambridge.

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

Drinking sugar-sweetened beverages (SSBs) increases the risk of cardiovascular disease and all-cause death in people with type 2 diabetes, reveals a U.S. study that also suggests switching to coffee, tea, or low-fat milk may diminish these risks.

The researchers examined data on almost 15,500 participants with type 2 diabetes from two major studies, finding that the highest level of consumption of SSBs was associated with a 20% increased risk of all-cause mortality and a 25% raised risk of cardiovascular disease, compared with consumption of the least amounts of these products.

The research, published in BMJ, also showed that drinking coffee, tea, plain water, and low-fat milk reduced the risk of all-cause death and that switching from SSBs to the other beverages was linked to lower mortality.

“Overall, these results provide additional evidence that emphasizes the importance of beverage choices in maintaining overall health among adults with diabetes,” say senior author Le Ma, PhD, department of nutrition, Harvard School of Public Health, Boston, and colleagues.

“Collectively, these findings all point in the same direction. Lower consumption of SSBs and higher consumption of coffee, tea, plain water, or low-fat milk are optimal for better health outcomes in adults with type 2 diabetes,” Nita G. Forouhi, MD, PhD, emphasizes in an accompanying editorial.


 

Choice of drink matters

Dr. Forouhi, from the University of Cambridge (England), warned, however, that the findings “cannot be considered cause and effect,” despite the large-scale analysis.

Moreover, “questions remain,” such as the impact of beverage consumption on coronary heart disease and stroke risk, and cancer mortality, with the current study providing “inconclusive” data on the latter.

There was also no data on the addition of sugar to tea or coffee, “so the comparative health effects of unsweetened and sweetened hot beverages remain unclear,” Dr. Forouhi points out. Also unknown is whether the type of tea consumed has a differential effect.

Despite these and other reservations, she says that overall, “Choice of beverage clearly matters.”

“The case for avoiding sugar-sweetened beverages is compelling, and it is supported by various fiscal measures in more than 45 countries. It is reasonable to shift the focus to drinks that are most likely to have positive health impacts: coffee, tea, plain water, and low-fat milk,” she notes.

Dr. Forouhi ends by underlining that the current findings tally with those seen in the general population, so “one important message is that having diabetes does not have to be especially restrictive.”
 

Expanding the evidence

It was estimated that 537 million adults worldwide had type 2 diabetes in 2021, a figure set to increase to 783 million by 2045, say the authors.

Individuals with type 2 diabetes have an increased risk of cardiovascular disease, among many other comorbidities, as well as premature death. Dietary interventions can play an important role in managing these risks.

Recommendations on the healthiest beverages to drink are largely based on evidence from the general population, and data are limited on the best options for adults with type 2 diabetes, who have altered metabolism, the researchers note.

To expand on this, they examined data from the Nurses’ Health Study, which enrolled female registered nurses aged 30-55 years and was initiated in 1976, and the Health Professionals Follow-Up Study, which included male health professionals aged 40-75 years and was initiated in 1996.

For the current analysis, 11,399 women and 4,087 men with type 2 diabetes were included from the two studies, of whom 2,715 were diagnosed before study entry.

Participants’ average daily beverage intake was assessed using a validated food frequency questionnaire administered every 2-4 years. SSBs included caffeinated and caffeine-free colas, other carbonated SSBs, and noncarbonated SSBs, such as fruit punches, lemonades, or other fruit drinks.

During 285,967 person-years of follow-up, there were 7,638 (49.3%) deaths, and 3,447 (22.3%) cases of incident cardiovascular disease were documented during 248,447 person-years of follow-up.

Fully adjusted multivariate analysis comparing the lowest and highest beverage intake indicated that SSBs were associated with a significant increase in all-cause mortality, at a pooled hazard ratio of 1.20, or 1.08 for each additional serving per day (P = .01).

In contrast, the associations between all-cause mortality and consumption of artificially sweetened beverages, fruit juice, and full-fat milk were not significant, whereas coffee (HR, 0.74), tea (HR, 0.79), plain water (HR, 0.77), and low-fat milk (HR, 0.88) were linked to a reduced risk.

The team reported that there were similar associations between beverage intake and cardiovascular disease incidence, at an HR of 1.25 for SSBs, as well as for cardiovascular disease mortality, at an HR of 1.29.

Participants who increased their tea, coffee, and low-fat milk consumption during the course of the study had lower all-cause mortality than those who did not. Switching from SSBs to other beverages was also associated with lower mortality.

The researchers note, however, that there are “several potential limitations” to their study, including that “individual beverage consumption may be correlated with other dietary and lifestyle risk factors for cardiovascular disease incidence and mortality among adults with [type 2] diabetes.”

The study was sponsored by the National Institutes of Health. Dr. Ma has reported no relevant financial relationships. Disclosures for the other authors are listed with the article. Dr. Forouhi has declared receiving support from the U.K. Medical Research Council Epidemiology Unit and U.K. National Institute for Health and Care Research Biomedical Research Centre Cambridge.

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

Individuals at increased risk of type 2 diabetes may be able to reduce their risk via a novel intervention combining intermittent fasting (IF) with early time-restricted eating, indicate the results of a randomized controlled trial.

The study involved more than 200 individuals randomized to one of three groups: eat only in the morning (from 8:00 a.m. to noon) followed by 20 hours of fasting 3 days per week and eat as desired on the other days; daily calorie restriction to 70% of requirements; or standard weight loss advice.

The IF plus early time-restricted eating intervention was associated with a significant improvement in a key measure of glucose control versus calorie restriction at 6 months, while both interventions were linked to benefits in terms of cardiovascular risk markers and body composition, compared with the standard weight loss advice.

However, the research, published in Nature Medicine, showed that the additional benefit of IF plus early time-restricted eating did not persist, and less than half of participants were still following the plan at 18 months, compared with almost 80% of those in the calorie-restriction group.

“Following a time-restricted, IF diet could help lower the chances of developing type 2 diabetes,” senior author Leonie K. Heilbronn, PhD, University of Adelaide, South Australia, said in a press release.

This is “the largest study in the world to date, and the first powered to assess how the body processes and uses glucose after eating a meal,” with the latter being a better indicator of diabetes risk than a fasting glucose test, added first author Xiao Tong Teong, a PhD student, also at the University of Adelaide.

“The results of this study add to the growing body of evidence to indicate that meal timing and fasting advice extends the health benefits of a restricted-calorie diet, independently from weight loss, and this may be influential in clinical practice,” Ms. Teong added.
 

Adherence difficult to IF plus early time-restricted eating

Asked to comment, Krista Varady, PhD, said that the study design “would have been stronger if the time-restricted eating and IF interventions were separated” and compared.

“Time-restricted eating has been shown to naturally reduce calorie intake by 300-500 kcal/day,” she said in an interview, “so I’m not sure why the investigators chose to combine [it] with IF. It ... defeats the point of time-restricted eating.”

Dr. Varady, who recently coauthored a review of the clinical application of IF for weight loss, also doubted whether individuals would adhere to combined early time-restricted eating and IF. “In all honesty, I don’t think anyone would follow this diet for very long,” she said.

She added that the feasibility of this particular approach is “very questionable. In general, people don’t like diets that require them to skip dinner with family/friends on multiple days of the week,” explained Dr. Varady, professor of nutrition at the University of Illinois, Chicago.  “These regimens make social eating very difficult, which results in high attrition.

“Indeed, evidence from a recent large-scale observational study of nearly 800,000 adults shows that Americans who engage in time-restricted eating placed their eating window in the afternoon or evening,” she noted.

Dr. Varady therefore suggested that future trials should test “more feasible time-restricted eating approaches,” such as those with later eating windows and without “vigilant calorie monitoring.”

“These types of diets are much easier to follow and are more likely to produce lasting weight and glycemic control in people with obesity and prediabetes,” she observed.
 

A novel way to cut calories?

The Australian authors say there is growing interest in extending the established health benefits of calorie restriction through new approaches such as timing of meals and prolonged fasting, with IF – defined as fasting interspersed with days of ad libitum eating – gaining in popularity as an alternative to simple calorie restriction.

Time-restricted eating, which emphasizes shorter daily eating windows in alignment with circadian rhythms, has also become popular in recent years, although the authors acknowledge that current evidence suggests any benefits over calorie restriction alone in terms of body composition, blood lipids, or glucose parameters are small.

To examine the combination of IF plus early time-restricted eating, in the DIRECT trial, the team recruited individuals aged 35-75 years who had a score of at least 12 on the Australian Type 2 Diabetes Risk Assessment Tool but did not have a diagnosis of diabetes and had stable weight for more than 6 months prior to study entry.

The participants were randomized to one of three groups:

• IF plus early time-restricted eating, which allowed consumption of 30% of calculated baseline energy requirements between 8:00 a.m. and midday, followed by a 20-hour fast from midday on 3 nonconsecutive days per week. They consumed their regular diet on nonfasting days.
• Calorie restriction, where they consumed 70% of daily calculated baseline energy requirements each day and were given rotating menu plans, but no specific mealtimes.
• Standard care, where they were given a booklet on current guidelines, with no counseling or meal replacement.

There were clinic visits every 2 weeks for the first 6 months of follow-up, and then monthly visits for 12 months. The two intervention groups had one-on-one diet counseling for the first 6 months. All groups were instructed to maintain their usual physical activity levels.

A total of 209 individuals were enrolled between Sept. 26, 2018, and May 4, 2020. Their mean age was 58 years, and 57% were women. Mean body mass index was 34.8 kg/m².

In all, 40.7% of participants were allocated to IF plus early time-restricted eating, 39.7% to calorie restriction, and the remaining 19.6% to standard care.

The results showed that IF plus early time-restricted eating was associated with a significantly greater improvement in the primary outcome of postprandial glucose area under the curve (AUC) at month 6 compared with calorie restriction, at –10.1 mg/dL/min versus –3.6 mg/dL/min (P = .03).

“To our knowledge, no [prior] studies have been powered for postprandial assessments of glycemia, which are better indicators of diabetes risk than fasting assessment,” the authors underlined.

IF plus early time-restricted eating was also associated with greater reductions in postprandial insulin AUC versus calorie restriction at 6 months (P = .04). However, the differences between the IF plus early time-restricted eating and calorie restriction groups for postmeal insulin did not remain significant at 18 months of follow-up.

Both IF plus early time-restricted eating and calorie restriction were associated with greater reductions in A1c levels at 6 months versus standard care, but there was no significant difference between the two active interventions (P = .46).

Both interventions were also associated with improvements in markers of cardiovascular risk versus standard care, such as systolic blood pressure at 2 months, diastolic blood pressure at 6 months, and fasting triglycerides at both time points, with no significant differences between the two intervention groups.

IF plus early time-restricted eating and calorie restriction were also both associated with greater reductions in BMI and fat mass in the first 6 months, as well as in waist circumference.
 

Calorie restriction easier to stick to, less likely to cause fatigue

When offered the chance to modify their diet plan at 6 months, 46% of participants in the IF plus early time-restricted eating group said they would maintain 3 days of restrictions per week, while 51% chose to reduce the restrictions to 2 days per week.

In contrast, 97% of those who completed the calorie-restriction plan indicated they would continue with their current diet plan.

At 18 months, 42% of participants in the IF plus early time-restricted eating group said they still undertook 2-3 days of restrictions per week, while 78% of those assigned to calorie restriction reported that they followed a calorie-restricted diet.

Fatigue was more common with IF plus early time-restricted eating, reported by 56% of participants versus 37% of those following calorie restriction, and 35% of those in the standard care group at 6 months. Headaches and constipation were more common in the intervention groups than with standard care.

The study was supported by a National Health and Medical Research Council Project Grant, an Australian Government Research Training Program Scholarship from the University of Adelaide, and a Diabetes Australia Research Program Grant.

No relevant financial relationships were declared.
 

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

Individuals at increased risk of type 2 diabetes may be able to reduce their risk via a novel intervention combining intermittent fasting (IF) with early time-restricted eating, indicate the results of a randomized controlled trial.

The study involved more than 200 individuals randomized to one of three groups: eat only in the morning (from 8:00 a.m. to noon) followed by 20 hours of fasting 3 days per week and eat as desired on the other days; daily calorie restriction to 70% of requirements; or standard weight loss advice.

The IF plus early time-restricted eating intervention was associated with a significant improvement in a key measure of glucose control versus calorie restriction at 6 months, while both interventions were linked to benefits in terms of cardiovascular risk markers and body composition, compared with the standard weight loss advice.

However, the research, published in Nature Medicine, showed that the additional benefit of IF plus early time-restricted eating did not persist, and less than half of participants were still following the plan at 18 months, compared with almost 80% of those in the calorie-restriction group.

“Following a time-restricted, IF diet could help lower the chances of developing type 2 diabetes,” senior author Leonie K. Heilbronn, PhD, University of Adelaide, South Australia, said in a press release.

This is “the largest study in the world to date, and the first powered to assess how the body processes and uses glucose after eating a meal,” with the latter being a better indicator of diabetes risk than a fasting glucose test, added first author Xiao Tong Teong, a PhD student, also at the University of Adelaide.

“The results of this study add to the growing body of evidence to indicate that meal timing and fasting advice extends the health benefits of a restricted-calorie diet, independently from weight loss, and this may be influential in clinical practice,” Ms. Teong added.
 

Adherence difficult to IF plus early time-restricted eating

Asked to comment, Krista Varady, PhD, said that the study design “would have been stronger if the time-restricted eating and IF interventions were separated” and compared.

“Time-restricted eating has been shown to naturally reduce calorie intake by 300-500 kcal/day,” she said in an interview, “so I’m not sure why the investigators chose to combine [it] with IF. It ... defeats the point of time-restricted eating.”

Dr. Varady, who recently coauthored a review of the clinical application of IF for weight loss, also doubted whether individuals would adhere to combined early time-restricted eating and IF. “In all honesty, I don’t think anyone would follow this diet for very long,” she said.

She added that the feasibility of this particular approach is “very questionable. In general, people don’t like diets that require them to skip dinner with family/friends on multiple days of the week,” explained Dr. Varady, professor of nutrition at the University of Illinois, Chicago.  “These regimens make social eating very difficult, which results in high attrition.

“Indeed, evidence from a recent large-scale observational study of nearly 800,000 adults shows that Americans who engage in time-restricted eating placed their eating window in the afternoon or evening,” she noted.

Dr. Varady therefore suggested that future trials should test “more feasible time-restricted eating approaches,” such as those with later eating windows and without “vigilant calorie monitoring.”

“These types of diets are much easier to follow and are more likely to produce lasting weight and glycemic control in people with obesity and prediabetes,” she observed.
 

A novel way to cut calories?

The Australian authors say there is growing interest in extending the established health benefits of calorie restriction through new approaches such as timing of meals and prolonged fasting, with IF – defined as fasting interspersed with days of ad libitum eating – gaining in popularity as an alternative to simple calorie restriction.

Time-restricted eating, which emphasizes shorter daily eating windows in alignment with circadian rhythms, has also become popular in recent years, although the authors acknowledge that current evidence suggests any benefits over calorie restriction alone in terms of body composition, blood lipids, or glucose parameters are small.

To examine the combination of IF plus early time-restricted eating, in the DIRECT trial, the team recruited individuals aged 35-75 years who had a score of at least 12 on the Australian Type 2 Diabetes Risk Assessment Tool but did not have a diagnosis of diabetes and had stable weight for more than 6 months prior to study entry.

The participants were randomized to one of three groups:

• IF plus early time-restricted eating, which allowed consumption of 30% of calculated baseline energy requirements between 8:00 a.m. and midday, followed by a 20-hour fast from midday on 3 nonconsecutive days per week. They consumed their regular diet on nonfasting days.
• Calorie restriction, where they consumed 70% of daily calculated baseline energy requirements each day and were given rotating menu plans, but no specific mealtimes.
• Standard care, where they were given a booklet on current guidelines, with no counseling or meal replacement.

There were clinic visits every 2 weeks for the first 6 months of follow-up, and then monthly visits for 12 months. The two intervention groups had one-on-one diet counseling for the first 6 months. All groups were instructed to maintain their usual physical activity levels.

A total of 209 individuals were enrolled between Sept. 26, 2018, and May 4, 2020. Their mean age was 58 years, and 57% were women. Mean body mass index was 34.8 kg/m².

In all, 40.7% of participants were allocated to IF plus early time-restricted eating, 39.7% to calorie restriction, and the remaining 19.6% to standard care.

The results showed that IF plus early time-restricted eating was associated with a significantly greater improvement in the primary outcome of postprandial glucose area under the curve (AUC) at month 6 compared with calorie restriction, at –10.1 mg/dL/min versus –3.6 mg/dL/min (P = .03).

“To our knowledge, no [prior] studies have been powered for postprandial assessments of glycemia, which are better indicators of diabetes risk than fasting assessment,” the authors underlined.

IF plus early time-restricted eating was also associated with greater reductions in postprandial insulin AUC versus calorie restriction at 6 months (P = .04). However, the differences between the IF plus early time-restricted eating and calorie restriction groups for postmeal insulin did not remain significant at 18 months of follow-up.

Both IF plus early time-restricted eating and calorie restriction were associated with greater reductions in A1c levels at 6 months versus standard care, but there was no significant difference between the two active interventions (P = .46).

Both interventions were also associated with improvements in markers of cardiovascular risk versus standard care, such as systolic blood pressure at 2 months, diastolic blood pressure at 6 months, and fasting triglycerides at both time points, with no significant differences between the two intervention groups.

IF plus early time-restricted eating and calorie restriction were also both associated with greater reductions in BMI and fat mass in the first 6 months, as well as in waist circumference.
 

Calorie restriction easier to stick to, less likely to cause fatigue

When offered the chance to modify their diet plan at 6 months, 46% of participants in the IF plus early time-restricted eating group said they would maintain 3 days of restrictions per week, while 51% chose to reduce the restrictions to 2 days per week.

In contrast, 97% of those who completed the calorie-restriction plan indicated they would continue with their current diet plan.

At 18 months, 42% of participants in the IF plus early time-restricted eating group said they still undertook 2-3 days of restrictions per week, while 78% of those assigned to calorie restriction reported that they followed a calorie-restricted diet.

Fatigue was more common with IF plus early time-restricted eating, reported by 56% of participants versus 37% of those following calorie restriction, and 35% of those in the standard care group at 6 months. Headaches and constipation were more common in the intervention groups than with standard care.

The study was supported by a National Health and Medical Research Council Project Grant, an Australian Government Research Training Program Scholarship from the University of Adelaide, and a Diabetes Australia Research Program Grant.

No relevant financial relationships were declared.
 

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

Individuals at increased risk of type 2 diabetes may be able to reduce their risk via a novel intervention combining intermittent fasting (IF) with early time-restricted eating, indicate the results of a randomized controlled trial.

The study involved more than 200 individuals randomized to one of three groups: eat only in the morning (from 8:00 a.m. to noon) followed by 20 hours of fasting 3 days per week and eat as desired on the other days; daily calorie restriction to 70% of requirements; or standard weight loss advice.

The IF plus early time-restricted eating intervention was associated with a significant improvement in a key measure of glucose control versus calorie restriction at 6 months, while both interventions were linked to benefits in terms of cardiovascular risk markers and body composition, compared with the standard weight loss advice.

However, the research, published in Nature Medicine, showed that the additional benefit of IF plus early time-restricted eating did not persist, and less than half of participants were still following the plan at 18 months, compared with almost 80% of those in the calorie-restriction group.

“Following a time-restricted, IF diet could help lower the chances of developing type 2 diabetes,” senior author Leonie K. Heilbronn, PhD, University of Adelaide, South Australia, said in a press release.

This is “the largest study in the world to date, and the first powered to assess how the body processes and uses glucose after eating a meal,” with the latter being a better indicator of diabetes risk than a fasting glucose test, added first author Xiao Tong Teong, a PhD student, also at the University of Adelaide.

“The results of this study add to the growing body of evidence to indicate that meal timing and fasting advice extends the health benefits of a restricted-calorie diet, independently from weight loss, and this may be influential in clinical practice,” Ms. Teong added.
 

Adherence difficult to IF plus early time-restricted eating

Asked to comment, Krista Varady, PhD, said that the study design “would have been stronger if the time-restricted eating and IF interventions were separated” and compared.

“Time-restricted eating has been shown to naturally reduce calorie intake by 300-500 kcal/day,” she said in an interview, “so I’m not sure why the investigators chose to combine [it] with IF. It ... defeats the point of time-restricted eating.”

Dr. Varady, who recently coauthored a review of the clinical application of IF for weight loss, also doubted whether individuals would adhere to combined early time-restricted eating and IF. “In all honesty, I don’t think anyone would follow this diet for very long,” she said.

She added that the feasibility of this particular approach is “very questionable. In general, people don’t like diets that require them to skip dinner with family/friends on multiple days of the week,” explained Dr. Varady, professor of nutrition at the University of Illinois, Chicago.  “These regimens make social eating very difficult, which results in high attrition.

“Indeed, evidence from a recent large-scale observational study of nearly 800,000 adults shows that Americans who engage in time-restricted eating placed their eating window in the afternoon or evening,” she noted.

Dr. Varady therefore suggested that future trials should test “more feasible time-restricted eating approaches,” such as those with later eating windows and without “vigilant calorie monitoring.”

“These types of diets are much easier to follow and are more likely to produce lasting weight and glycemic control in people with obesity and prediabetes,” she observed.
 

A novel way to cut calories?

The Australian authors say there is growing interest in extending the established health benefits of calorie restriction through new approaches such as timing of meals and prolonged fasting, with IF – defined as fasting interspersed with days of ad libitum eating – gaining in popularity as an alternative to simple calorie restriction.

Time-restricted eating, which emphasizes shorter daily eating windows in alignment with circadian rhythms, has also become popular in recent years, although the authors acknowledge that current evidence suggests any benefits over calorie restriction alone in terms of body composition, blood lipids, or glucose parameters are small.

To examine the combination of IF plus early time-restricted eating, in the DIRECT trial, the team recruited individuals aged 35-75 years who had a score of at least 12 on the Australian Type 2 Diabetes Risk Assessment Tool but did not have a diagnosis of diabetes and had stable weight for more than 6 months prior to study entry.

The participants were randomized to one of three groups:

• IF plus early time-restricted eating, which allowed consumption of 30% of calculated baseline energy requirements between 8:00 a.m. and midday, followed by a 20-hour fast from midday on 3 nonconsecutive days per week. They consumed their regular diet on nonfasting days.
• Calorie restriction, where they consumed 70% of daily calculated baseline energy requirements each day and were given rotating menu plans, but no specific mealtimes.
• Standard care, where they were given a booklet on current guidelines, with no counseling or meal replacement.

There were clinic visits every 2 weeks for the first 6 months of follow-up, and then monthly visits for 12 months. The two intervention groups had one-on-one diet counseling for the first 6 months. All groups were instructed to maintain their usual physical activity levels.

A total of 209 individuals were enrolled between Sept. 26, 2018, and May 4, 2020. Their mean age was 58 years, and 57% were women. Mean body mass index was 34.8 kg/m².

In all, 40.7% of participants were allocated to IF plus early time-restricted eating, 39.7% to calorie restriction, and the remaining 19.6% to standard care.

The results showed that IF plus early time-restricted eating was associated with a significantly greater improvement in the primary outcome of postprandial glucose area under the curve (AUC) at month 6 compared with calorie restriction, at –10.1 mg/dL/min versus –3.6 mg/dL/min (P = .03).

“To our knowledge, no [prior] studies have been powered for postprandial assessments of glycemia, which are better indicators of diabetes risk than fasting assessment,” the authors underlined.

IF plus early time-restricted eating was also associated with greater reductions in postprandial insulin AUC versus calorie restriction at 6 months (P = .04). However, the differences between the IF plus early time-restricted eating and calorie restriction groups for postmeal insulin did not remain significant at 18 months of follow-up.

Both IF plus early time-restricted eating and calorie restriction were associated with greater reductions in A1c levels at 6 months versus standard care, but there was no significant difference between the two active interventions (P = .46).

Both interventions were also associated with improvements in markers of cardiovascular risk versus standard care, such as systolic blood pressure at 2 months, diastolic blood pressure at 6 months, and fasting triglycerides at both time points, with no significant differences between the two intervention groups.

IF plus early time-restricted eating and calorie restriction were also both associated with greater reductions in BMI and fat mass in the first 6 months, as well as in waist circumference.
 

Calorie restriction easier to stick to, less likely to cause fatigue

When offered the chance to modify their diet plan at 6 months, 46% of participants in the IF plus early time-restricted eating group said they would maintain 3 days of restrictions per week, while 51% chose to reduce the restrictions to 2 days per week.

In contrast, 97% of those who completed the calorie-restriction plan indicated they would continue with their current diet plan.

At 18 months, 42% of participants in the IF plus early time-restricted eating group said they still undertook 2-3 days of restrictions per week, while 78% of those assigned to calorie restriction reported that they followed a calorie-restricted diet.

Fatigue was more common with IF plus early time-restricted eating, reported by 56% of participants versus 37% of those following calorie restriction, and 35% of those in the standard care group at 6 months. Headaches and constipation were more common in the intervention groups than with standard care.

The study was supported by a National Health and Medical Research Council Project Grant, an Australian Government Research Training Program Scholarship from the University of Adelaide, and a Diabetes Australia Research Program Grant.

No relevant financial relationships were declared.
 

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

PARIS – Adults who are easily angered may have experienced trauma during childhood, according to new findings that investigators believe warrant routine trauma screening for patents with depression and/or anxiety.

Investigators examined data on more than 2,250 individuals who were asked about trauma during childhood and a subsequent tendency toward anger or angry outbursts 4 years later.

Results showed that emotional neglect during childhood was associated with approximately a 40% increased likelihood of subsequent anger, while psychological abuse was linked to a 30% increased likelihood.

Childhood physical abuse was also significantly associated with anger in adults, with an increased risk of approximately 40%. The researchers found no link between childhood sexual abuse and adult anger.

“We can’t definitively say that the trauma causes the anger, but the link is clear,” study investigator Nienke De Bles, PhD student, department of psychiatry, Leiden (the Netherlands) University Medical Center, said in a news release.

“Being easily angered can have several consequences,” she continued. “It can make personal interactions more difficult, and it can have consequences for your mental health and well-being, but people who get angry easily also have a greater tendency to discontinue psychiatric treatment, so this anger may mean that it reduces their chances of a better life,” she added.

Ms. De Bles believes that “it should be standard practice to ask depression and anxiety sufferers about anger and past trauma, even if the patient is not exhibiting current anger.”

The findings were presented at the European Psychiatric Association 2023 Congress.
 

A ‘red flag’ for abuse

“Psychiatric treatments for past trauma may differ from treatments for depression, so psychiatrists need to try to understand the cause so that they can offer the correct treatment to each patient,” said Ms. De Bles.

Ms. De Bles noted that childhood trauma has many negative consequences later in life and that it is associated with a higher prevalence of adult depression and anxiety.

“There are several potential mechanisms for psychopathology in the context of childhood trauma, and emotion regulation seems to be one of the key mechanisms,” she said.

The researchers previously found that anger was highly prevalent among patients with affective disorders. It was present in 30% of those with current anxiety or depressive disorder and in 40% of those with comorbid depression and anxiety with a tendency toward anger versus 5% of healthy control persons.

Other studies have shown that anger is associated with poor treatment outcomes and dropping out of treatment.

To further investigate the link between childhood trauma and anger in adulthood, the researchers examined data on 2,271 participants in the Netherlands Study of Depression and Anxiety (NESDA).

Childhood trauma was assessed at baseline using the semistructured Childhood Trauma Interview. Anger was measured at a 4-year follow-up using the Spielberger Trait Anger Subscale, the Anger Attacks Questionnaire, and the borderline and antisocial subscales of the Personality Disorder Questionnaire 4 to identify cluster B personality traits.

Results showed that emotional neglect during childhood was significantly associated with trait anger in adulthood, at an adjusted odds ratio of 1.42 (P < .001), anger attacks (OR, 1.35; P = .004), and borderline (OR, 1.76; P < .001) and antisocial (OR, 1.88; P = .001) personality traits.

Childhood psychological abuse was also significantly associated with later trait anger (OR, 1.28; P = .002), anger attacks (OR, 1.31; P = .024), and borderline (OR, 1.77; P < .001) and antisocial (OR, 1.69; P = .011) traits.

There was also a significant association between childhood psychical abuse and trait anger in adulthood (OR, 1.37; P < .001), anger attacks (OR, 1.48; P = .004), and borderline (OR, 1.71; P < .001) and antisocial (OR, 1.98; P = .002) traits.

There was no significant association between sexual abuse experienced in childhood and later anger or personality traits.

Ms. De Bles said the findings suggest “there is indeed a relationship between childhood trauma and anger in adulthood, and this is something that might be interesting for clinicians, as anger could be a red flag for a history of childhood trauma.”

She said in an interview that anger is a “very normal human emotion” but that it has not been as widely studied as sadness and anxiety.

She suggested that future research could examine the use of trauma-based therapies for patients with a history of childhood trauma and anger.
 

Overlooked, neglected

Commenting on the findings, Nur Hani Zainal, PhD, department of healthcare policy, Harvard Medical School, Boston, said the findings are “very consistent with the current biopsychosocial models in psychiatry and clinical psychology.”

Dr. Zainal, who was coauthor of a recent study that showed that anger appears to mediate the relationship between childhood trauma and adult psychopathology, said the current study offers a “good, incremental contribution” to the literature.

She noted there are “good uses” for the emotion of anger, as “sometimes we need anger to set healthy boundaries for ourselves.” However, she agreed that, as an aspect of depression, anxiety, and posttraumatic stress disorder, it is often “overlooked.”

Dr. Zainal said that the findings reinforce the importance of thoroughly evaluating adult patients’ experiences during childhood.

Julian Beezhold, MD, secretary general of the EPA and a consultant psychiatrist with the Norwich (England) Medical School, University of East Anglia, commented in the release that anger is a “somewhat neglected symptom.

“The findings are in line with what we see in day-to-day clinical practice and will hopefully help increase the awareness of the importance of both anger and associated childhood trauma.”

The infrastructure for the NESDA study is funded through the Geestkracht program of the Netherlands Organization for Health Research and Development and financial contributions by participating universities and mental health care organizations. The authors disclosed no relevant financial relationships.

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

PARIS – Adults who are easily angered may have experienced trauma during childhood, according to new findings that investigators believe warrant routine trauma screening for patents with depression and/or anxiety.

Investigators examined data on more than 2,250 individuals who were asked about trauma during childhood and a subsequent tendency toward anger or angry outbursts 4 years later.

Results showed that emotional neglect during childhood was associated with approximately a 40% increased likelihood of subsequent anger, while psychological abuse was linked to a 30% increased likelihood.

Childhood physical abuse was also significantly associated with anger in adults, with an increased risk of approximately 40%. The researchers found no link between childhood sexual abuse and adult anger.

“We can’t definitively say that the trauma causes the anger, but the link is clear,” study investigator Nienke De Bles, PhD student, department of psychiatry, Leiden (the Netherlands) University Medical Center, said in a news release.

“Being easily angered can have several consequences,” she continued. “It can make personal interactions more difficult, and it can have consequences for your mental health and well-being, but people who get angry easily also have a greater tendency to discontinue psychiatric treatment, so this anger may mean that it reduces their chances of a better life,” she added.

Ms. De Bles believes that “it should be standard practice to ask depression and anxiety sufferers about anger and past trauma, even if the patient is not exhibiting current anger.”

The findings were presented at the European Psychiatric Association 2023 Congress.
 

A ‘red flag’ for abuse

“Psychiatric treatments for past trauma may differ from treatments for depression, so psychiatrists need to try to understand the cause so that they can offer the correct treatment to each patient,” said Ms. De Bles.

Ms. De Bles noted that childhood trauma has many negative consequences later in life and that it is associated with a higher prevalence of adult depression and anxiety.

“There are several potential mechanisms for psychopathology in the context of childhood trauma, and emotion regulation seems to be one of the key mechanisms,” she said.

The researchers previously found that anger was highly prevalent among patients with affective disorders. It was present in 30% of those with current anxiety or depressive disorder and in 40% of those with comorbid depression and anxiety with a tendency toward anger versus 5% of healthy control persons.

Other studies have shown that anger is associated with poor treatment outcomes and dropping out of treatment.

To further investigate the link between childhood trauma and anger in adulthood, the researchers examined data on 2,271 participants in the Netherlands Study of Depression and Anxiety (NESDA).

Childhood trauma was assessed at baseline using the semistructured Childhood Trauma Interview. Anger was measured at a 4-year follow-up using the Spielberger Trait Anger Subscale, the Anger Attacks Questionnaire, and the borderline and antisocial subscales of the Personality Disorder Questionnaire 4 to identify cluster B personality traits.

Results showed that emotional neglect during childhood was significantly associated with trait anger in adulthood, at an adjusted odds ratio of 1.42 (P < .001), anger attacks (OR, 1.35; P = .004), and borderline (OR, 1.76; P < .001) and antisocial (OR, 1.88; P = .001) personality traits.

Childhood psychological abuse was also significantly associated with later trait anger (OR, 1.28; P = .002), anger attacks (OR, 1.31; P = .024), and borderline (OR, 1.77; P < .001) and antisocial (OR, 1.69; P = .011) traits.

There was also a significant association between childhood psychical abuse and trait anger in adulthood (OR, 1.37; P < .001), anger attacks (OR, 1.48; P = .004), and borderline (OR, 1.71; P < .001) and antisocial (OR, 1.98; P = .002) traits.

There was no significant association between sexual abuse experienced in childhood and later anger or personality traits.

Ms. De Bles said the findings suggest “there is indeed a relationship between childhood trauma and anger in adulthood, and this is something that might be interesting for clinicians, as anger could be a red flag for a history of childhood trauma.”

She said in an interview that anger is a “very normal human emotion” but that it has not been as widely studied as sadness and anxiety.

She suggested that future research could examine the use of trauma-based therapies for patients with a history of childhood trauma and anger.
 

Overlooked, neglected

Commenting on the findings, Nur Hani Zainal, PhD, department of healthcare policy, Harvard Medical School, Boston, said the findings are “very consistent with the current biopsychosocial models in psychiatry and clinical psychology.”

Dr. Zainal, who was coauthor of a recent study that showed that anger appears to mediate the relationship between childhood trauma and adult psychopathology, said the current study offers a “good, incremental contribution” to the literature.

She noted there are “good uses” for the emotion of anger, as “sometimes we need anger to set healthy boundaries for ourselves.” However, she agreed that, as an aspect of depression, anxiety, and posttraumatic stress disorder, it is often “overlooked.”

Dr. Zainal said that the findings reinforce the importance of thoroughly evaluating adult patients’ experiences during childhood.

Julian Beezhold, MD, secretary general of the EPA and a consultant psychiatrist with the Norwich (England) Medical School, University of East Anglia, commented in the release that anger is a “somewhat neglected symptom.

“The findings are in line with what we see in day-to-day clinical practice and will hopefully help increase the awareness of the importance of both anger and associated childhood trauma.”

The infrastructure for the NESDA study is funded through the Geestkracht program of the Netherlands Organization for Health Research and Development and financial contributions by participating universities and mental health care organizations. The authors disclosed no relevant financial relationships.

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

PARIS – Adults who are easily angered may have experienced trauma during childhood, according to new findings that investigators believe warrant routine trauma screening for patents with depression and/or anxiety.

Investigators examined data on more than 2,250 individuals who were asked about trauma during childhood and a subsequent tendency toward anger or angry outbursts 4 years later.

Results showed that emotional neglect during childhood was associated with approximately a 40% increased likelihood of subsequent anger, while psychological abuse was linked to a 30% increased likelihood.

Childhood physical abuse was also significantly associated with anger in adults, with an increased risk of approximately 40%. The researchers found no link between childhood sexual abuse and adult anger.

“We can’t definitively say that the trauma causes the anger, but the link is clear,” study investigator Nienke De Bles, PhD student, department of psychiatry, Leiden (the Netherlands) University Medical Center, said in a news release.

“Being easily angered can have several consequences,” she continued. “It can make personal interactions more difficult, and it can have consequences for your mental health and well-being, but people who get angry easily also have a greater tendency to discontinue psychiatric treatment, so this anger may mean that it reduces their chances of a better life,” she added.

Ms. De Bles believes that “it should be standard practice to ask depression and anxiety sufferers about anger and past trauma, even if the patient is not exhibiting current anger.”

The findings were presented at the European Psychiatric Association 2023 Congress.
 

A ‘red flag’ for abuse

“Psychiatric treatments for past trauma may differ from treatments for depression, so psychiatrists need to try to understand the cause so that they can offer the correct treatment to each patient,” said Ms. De Bles.

Ms. De Bles noted that childhood trauma has many negative consequences later in life and that it is associated with a higher prevalence of adult depression and anxiety.

“There are several potential mechanisms for psychopathology in the context of childhood trauma, and emotion regulation seems to be one of the key mechanisms,” she said.

The researchers previously found that anger was highly prevalent among patients with affective disorders. It was present in 30% of those with current anxiety or depressive disorder and in 40% of those with comorbid depression and anxiety with a tendency toward anger versus 5% of healthy control persons.

Other studies have shown that anger is associated with poor treatment outcomes and dropping out of treatment.

To further investigate the link between childhood trauma and anger in adulthood, the researchers examined data on 2,271 participants in the Netherlands Study of Depression and Anxiety (NESDA).

Childhood trauma was assessed at baseline using the semistructured Childhood Trauma Interview. Anger was measured at a 4-year follow-up using the Spielberger Trait Anger Subscale, the Anger Attacks Questionnaire, and the borderline and antisocial subscales of the Personality Disorder Questionnaire 4 to identify cluster B personality traits.

Results showed that emotional neglect during childhood was significantly associated with trait anger in adulthood, at an adjusted odds ratio of 1.42 (P < .001), anger attacks (OR, 1.35; P = .004), and borderline (OR, 1.76; P < .001) and antisocial (OR, 1.88; P = .001) personality traits.

Childhood psychological abuse was also significantly associated with later trait anger (OR, 1.28; P = .002), anger attacks (OR, 1.31; P = .024), and borderline (OR, 1.77; P < .001) and antisocial (OR, 1.69; P = .011) traits.

There was also a significant association between childhood psychical abuse and trait anger in adulthood (OR, 1.37; P < .001), anger attacks (OR, 1.48; P = .004), and borderline (OR, 1.71; P < .001) and antisocial (OR, 1.98; P = .002) traits.

There was no significant association between sexual abuse experienced in childhood and later anger or personality traits.

Ms. De Bles said the findings suggest “there is indeed a relationship between childhood trauma and anger in adulthood, and this is something that might be interesting for clinicians, as anger could be a red flag for a history of childhood trauma.”

She said in an interview that anger is a “very normal human emotion” but that it has not been as widely studied as sadness and anxiety.

She suggested that future research could examine the use of trauma-based therapies for patients with a history of childhood trauma and anger.
 

Overlooked, neglected

Commenting on the findings, Nur Hani Zainal, PhD, department of healthcare policy, Harvard Medical School, Boston, said the findings are “very consistent with the current biopsychosocial models in psychiatry and clinical psychology.”

Dr. Zainal, who was coauthor of a recent study that showed that anger appears to mediate the relationship between childhood trauma and adult psychopathology, said the current study offers a “good, incremental contribution” to the literature.

She noted there are “good uses” for the emotion of anger, as “sometimes we need anger to set healthy boundaries for ourselves.” However, she agreed that, as an aspect of depression, anxiety, and posttraumatic stress disorder, it is often “overlooked.”

Dr. Zainal said that the findings reinforce the importance of thoroughly evaluating adult patients’ experiences during childhood.

Julian Beezhold, MD, secretary general of the EPA and a consultant psychiatrist with the Norwich (England) Medical School, University of East Anglia, commented in the release that anger is a “somewhat neglected symptom.

“The findings are in line with what we see in day-to-day clinical practice and will hopefully help increase the awareness of the importance of both anger and associated childhood trauma.”

The infrastructure for the NESDA study is funded through the Geestkracht program of the Netherlands Organization for Health Research and Development and financial contributions by participating universities and mental health care organizations. The authors disclosed no relevant financial relationships.

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

PARIS – A single 25-mg dose of a synthetic formulation of psilocybin appears to improve the core symptoms of treatment-resistant depression (TRD), a new analysis of phase 2 trial data suggests.

Known as COMP360, the synthetic agent, a proprietary, purified form of psilocybin, improved symptoms related to mood and anhedonia while leaving aspects such as appetite and weight changes unaffected, reported investigators led by Guy M. Goodwin, PhD, emeritus professor of psychiatry, University of Oxford, England, and chief medical officer, COMPASS Pathways.

The study was presented at the European Psychiatric Association (EPA) 2023 Congress.
 

100 million affected

Affecting up to 100 million people globally, TRD is “not an official diagnosis,” although it is often defined as the failure to elicit a response with at least two antidepressant treatments, said Dr. Goodwin.

Compared to their counterparts with non-TRD, those with TRD experience higher relapse rates, higher rates of suicidal behavior, and more residual symptoms even when they do respond to treatment.

Previous results from the study known as P-TRD indicated that a single 25-mg dose of COMP360 significantly reduced depression scores for up to 12 weeks when given along with psychological support, although a later analysis suggested the effect subsequently dropped off.

The vast majority of the patients in the trial were naive to psychedelics, and so, Dr. Goodwin explained, they undergo a preparation phase during which they receive psychoeducation and have at least two visits with a therapist, who then stays with them during administration of the drug to offer support if they experience psychological distress.

Following the psilocybin session, participants go through a process known as integration, which involves two sessions with a therapist within 2 weeks.

“That, in our view, is essentially about safety, and about identifying problems that have arisen as a result of taking the drug,” said Dr. Goodwin.

The phase 2b trial examined changes in specific depression symptoms after psilocybin treatment in 233 patients with TRD. Participants were a mean age of 39.8 years and 59% were women. They were randomized to receive one of three doses of the drug: a 1-mg dose (n = 79), a 10-mg dose (n = 75), or a 25-mg dose (n = 79).

The primary outcome was changes in individual items on the Montgomery-Åsberg Depression Rating Scale (MADRS) and 16-item Quick Inventory of Depressive Symptomatology–Self Report (QIDS-SR-16) scale.

While the effect on overall depression scores is important, said Dr. Goodwin, many of the items included in the depression assessment scales are “uninformative.”
 

Reduction in ‘core’ symptoms

Participants were assessed by a blinded rater at baseline, day 1, day 2, and at 1, 2, 3, 6, 9, and 12 weeks after administration of COMP360. The primary endpoint was a reduction in individual items on MADRS and scores from baseline to 3 weeks. Individual items on the QIDS-SR-16 were rated by participants at the same time points.

Investigators found the largest mean changes from baseline were on reported and apparent sadness, lassitude, inability to feel, and concentration difficulties, with “very nice and clear dose-related differences,” Dr. Goodwin said.

The results indicate that the significant benefit with the largest dose at 3 weeks versus baseline was confined to items such as inability to feel and reported and apparent sadness on the MADRS and feeling sad and general interest on the QIDS-SR-16 (Table 1).

The results suggest the effect of COMP360 is “on the core symptoms of depression,” said Dr. Goodwin.

Enthusiasm running ahead of the data

Commenting on the findings, Bertha K. Madras, PhD, professor of psychobiology, department of psychiatry, Harvard Medical School, Boston, who was not involved in the study, said “hallucinogens are an intriguing class of drugs and I support ongoing high-quality research in this area.”

However, she told this news organization that the “breathtaking endorsement of this drug is far ahead of scientific data.”

She cited concerns such as the “narrow demographics” of participants, their previous experience with and expectations of hallucinogens, the “potential for symptom fluidity of enrollees,” such as depression evolving into psychosis, and the “undefined role” of the therapist during a hallucinogenic session.

“Finally, I am concerned that enthusiasm for therapeutic potential has been, and will continue to be, preempted and directed towards legalization and widespread access for vulnerable populations,” Dr. Madras said.

This, she said, “is occurring at breakneck speed in the U.S., with scant resistance or skepticism from the investigators engaged in therapeutic assessment.”

The study was funded by COMPASS Pathways. Dr. Goodwin has reported relationships with COMPASS Pathways, Buckley Psytech, Boehringer Ingelheim, Clerkenwell Health, EVA Pharma, Lundbeck, Janssen Global Services, Novartis, Ocean Neurosciences, P1vital, Sage Therapeutics, Servier, Takeda, and WebMD.
 

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

PARIS – A single 25-mg dose of a synthetic formulation of psilocybin appears to improve the core symptoms of treatment-resistant depression (TRD), a new analysis of phase 2 trial data suggests.

Known as COMP360, the synthetic agent, a proprietary, purified form of psilocybin, improved symptoms related to mood and anhedonia while leaving aspects such as appetite and weight changes unaffected, reported investigators led by Guy M. Goodwin, PhD, emeritus professor of psychiatry, University of Oxford, England, and chief medical officer, COMPASS Pathways.

The study was presented at the European Psychiatric Association (EPA) 2023 Congress.
 

100 million affected

Affecting up to 100 million people globally, TRD is “not an official diagnosis,” although it is often defined as the failure to elicit a response with at least two antidepressant treatments, said Dr. Goodwin.

Compared to their counterparts with non-TRD, those with TRD experience higher relapse rates, higher rates of suicidal behavior, and more residual symptoms even when they do respond to treatment.

Previous results from the study known as P-TRD indicated that a single 25-mg dose of COMP360 significantly reduced depression scores for up to 12 weeks when given along with psychological support, although a later analysis suggested the effect subsequently dropped off.

The vast majority of the patients in the trial were naive to psychedelics, and so, Dr. Goodwin explained, they undergo a preparation phase during which they receive psychoeducation and have at least two visits with a therapist, who then stays with them during administration of the drug to offer support if they experience psychological distress.

Following the psilocybin session, participants go through a process known as integration, which involves two sessions with a therapist within 2 weeks.

“That, in our view, is essentially about safety, and about identifying problems that have arisen as a result of taking the drug,” said Dr. Goodwin.

The phase 2b trial examined changes in specific depression symptoms after psilocybin treatment in 233 patients with TRD. Participants were a mean age of 39.8 years and 59% were women. They were randomized to receive one of three doses of the drug: a 1-mg dose (n = 79), a 10-mg dose (n = 75), or a 25-mg dose (n = 79).

The primary outcome was changes in individual items on the Montgomery-Åsberg Depression Rating Scale (MADRS) and 16-item Quick Inventory of Depressive Symptomatology–Self Report (QIDS-SR-16) scale.

While the effect on overall depression scores is important, said Dr. Goodwin, many of the items included in the depression assessment scales are “uninformative.”
 

Reduction in ‘core’ symptoms

Participants were assessed by a blinded rater at baseline, day 1, day 2, and at 1, 2, 3, 6, 9, and 12 weeks after administration of COMP360. The primary endpoint was a reduction in individual items on MADRS and scores from baseline to 3 weeks. Individual items on the QIDS-SR-16 were rated by participants at the same time points.

Investigators found the largest mean changes from baseline were on reported and apparent sadness, lassitude, inability to feel, and concentration difficulties, with “very nice and clear dose-related differences,” Dr. Goodwin said.

The results indicate that the significant benefit with the largest dose at 3 weeks versus baseline was confined to items such as inability to feel and reported and apparent sadness on the MADRS and feeling sad and general interest on the QIDS-SR-16 (Table 1).

The results suggest the effect of COMP360 is “on the core symptoms of depression,” said Dr. Goodwin.

Enthusiasm running ahead of the data

Commenting on the findings, Bertha K. Madras, PhD, professor of psychobiology, department of psychiatry, Harvard Medical School, Boston, who was not involved in the study, said “hallucinogens are an intriguing class of drugs and I support ongoing high-quality research in this area.”

However, she told this news organization that the “breathtaking endorsement of this drug is far ahead of scientific data.”

She cited concerns such as the “narrow demographics” of participants, their previous experience with and expectations of hallucinogens, the “potential for symptom fluidity of enrollees,” such as depression evolving into psychosis, and the “undefined role” of the therapist during a hallucinogenic session.

“Finally, I am concerned that enthusiasm for therapeutic potential has been, and will continue to be, preempted and directed towards legalization and widespread access for vulnerable populations,” Dr. Madras said.

This, she said, “is occurring at breakneck speed in the U.S., with scant resistance or skepticism from the investigators engaged in therapeutic assessment.”

The study was funded by COMPASS Pathways. Dr. Goodwin has reported relationships with COMPASS Pathways, Buckley Psytech, Boehringer Ingelheim, Clerkenwell Health, EVA Pharma, Lundbeck, Janssen Global Services, Novartis, Ocean Neurosciences, P1vital, Sage Therapeutics, Servier, Takeda, and WebMD.
 

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

PARIS – A single 25-mg dose of a synthetic formulation of psilocybin appears to improve the core symptoms of treatment-resistant depression (TRD), a new analysis of phase 2 trial data suggests.

Known as COMP360, the synthetic agent, a proprietary, purified form of psilocybin, improved symptoms related to mood and anhedonia while leaving aspects such as appetite and weight changes unaffected, reported investigators led by Guy M. Goodwin, PhD, emeritus professor of psychiatry, University of Oxford, England, and chief medical officer, COMPASS Pathways.

The study was presented at the European Psychiatric Association (EPA) 2023 Congress.
 

100 million affected

Affecting up to 100 million people globally, TRD is “not an official diagnosis,” although it is often defined as the failure to elicit a response with at least two antidepressant treatments, said Dr. Goodwin.

Compared to their counterparts with non-TRD, those with TRD experience higher relapse rates, higher rates of suicidal behavior, and more residual symptoms even when they do respond to treatment.

Previous results from the study known as P-TRD indicated that a single 25-mg dose of COMP360 significantly reduced depression scores for up to 12 weeks when given along with psychological support, although a later analysis suggested the effect subsequently dropped off.

The vast majority of the patients in the trial were naive to psychedelics, and so, Dr. Goodwin explained, they undergo a preparation phase during which they receive psychoeducation and have at least two visits with a therapist, who then stays with them during administration of the drug to offer support if they experience psychological distress.

Following the psilocybin session, participants go through a process known as integration, which involves two sessions with a therapist within 2 weeks.

“That, in our view, is essentially about safety, and about identifying problems that have arisen as a result of taking the drug,” said Dr. Goodwin.

The phase 2b trial examined changes in specific depression symptoms after psilocybin treatment in 233 patients with TRD. Participants were a mean age of 39.8 years and 59% were women. They were randomized to receive one of three doses of the drug: a 1-mg dose (n = 79), a 10-mg dose (n = 75), or a 25-mg dose (n = 79).

The primary outcome was changes in individual items on the Montgomery-Åsberg Depression Rating Scale (MADRS) and 16-item Quick Inventory of Depressive Symptomatology–Self Report (QIDS-SR-16) scale.

While the effect on overall depression scores is important, said Dr. Goodwin, many of the items included in the depression assessment scales are “uninformative.”
 

Reduction in ‘core’ symptoms

Participants were assessed by a blinded rater at baseline, day 1, day 2, and at 1, 2, 3, 6, 9, and 12 weeks after administration of COMP360. The primary endpoint was a reduction in individual items on MADRS and scores from baseline to 3 weeks. Individual items on the QIDS-SR-16 were rated by participants at the same time points.

Investigators found the largest mean changes from baseline were on reported and apparent sadness, lassitude, inability to feel, and concentration difficulties, with “very nice and clear dose-related differences,” Dr. Goodwin said.

The results indicate that the significant benefit with the largest dose at 3 weeks versus baseline was confined to items such as inability to feel and reported and apparent sadness on the MADRS and feeling sad and general interest on the QIDS-SR-16 (Table 1).

The results suggest the effect of COMP360 is “on the core symptoms of depression,” said Dr. Goodwin.

Enthusiasm running ahead of the data

Commenting on the findings, Bertha K. Madras, PhD, professor of psychobiology, department of psychiatry, Harvard Medical School, Boston, who was not involved in the study, said “hallucinogens are an intriguing class of drugs and I support ongoing high-quality research in this area.”

However, she told this news organization that the “breathtaking endorsement of this drug is far ahead of scientific data.”

She cited concerns such as the “narrow demographics” of participants, their previous experience with and expectations of hallucinogens, the “potential for symptom fluidity of enrollees,” such as depression evolving into psychosis, and the “undefined role” of the therapist during a hallucinogenic session.

“Finally, I am concerned that enthusiasm for therapeutic potential has been, and will continue to be, preempted and directed towards legalization and widespread access for vulnerable populations,” Dr. Madras said.

This, she said, “is occurring at breakneck speed in the U.S., with scant resistance or skepticism from the investigators engaged in therapeutic assessment.”

The study was funded by COMPASS Pathways. Dr. Goodwin has reported relationships with COMPASS Pathways, Buckley Psytech, Boehringer Ingelheim, Clerkenwell Health, EVA Pharma, Lundbeck, Janssen Global Services, Novartis, Ocean Neurosciences, P1vital, Sage Therapeutics, Servier, Takeda, and WebMD.
 

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

Some patients with small, nonfunctional pancreatic neuroendocrine tumors (NETs) may benefit from surgery, an analysis of U.S. nationwide data suggests.

Overall, researchers found that surgical resection was associated with a 42% improvement in overall survival among patients with small tumors of 1.1-2.0 cm, but not tumors 1 cm or smaller. Among those with 1.1- to 2.0-cm tumors, the survival benefit following surgery was most notable among patients aged 64 years or younger and those with no comorbidities.

The findings were published in JAMA Network Open.

While surgical resection has been the first-line treatment for patients with functional or symptomatic localized, low-grade pancreatic NETs, surgery for asymptomatic low-grade nonfunctional pancreatic NETs of 2 cm or less “remains unclear even in consensus guidelines,” study author Richard D. Schulick, MD, MBA, of the University of Colorado at Denver, Aurora, and colleagues write.

Consensus guidelines from the European Neuroendocrine Tumor Society, for instance, indicate surveillance for these smaller tumors, while those from the Japan Neuroendocrine Tumor Society recommend surgery. The National Comprehensive Cancer Network (NCCN), which recently updated its guidelines, suggests observation as an option for patients with tumors as large as 2.0 cm but who are strongly considering resection.

To determine whether surgical resection of these smaller lesions influences overall survival, the team combed the U.S. National Cancer Database and identified 4,641 patients with nonfunctional pancreatic NETs up to 2.0 cm in size.

Researchers divided patients by tumor sizes of up to 1 cm (group 1a) and 1.1-2.0 cm (group 1b) and examined a range of variables, including age, comorbidities, tumor location and differentiation, and overall survival.

Overall, 1,278 patients had tumors measuring up to 1.0 cm (group 1a), and 3,363 had tumors measuring 1.1-2.0 cm (group 1b). The mean age across both groups was 60.5 years; about half were men, and most (77.4%) were White.

Over a median follow-up of 47.1 months, the surgical resection rate was significantly lower among patients in group 1a (82.0%) than in group 1b (87.0%). Patients who underwent resection, on average, were younger and were more likely to have tumors located in the pancreas tail and to have clinical lymph node metastasis.

Overall, the team found that surgical resection was associated with longer overall survival for patients with tumors of 1.1-2.0 cm (hazard ratio, 0.58) but not 1 cm or smaller (HR, 0.68; P = .12).

Among patients in group 1b (those with 1.1- to 2.0-cm tumors), the team also found that age 64 years or younger (adjusted HR, 0.34), treatment at academic institutions (aHR, 0.40), absence of comorbidities (aHR, 0.53), absence of clinical lymph node metastasis (aHR, 0.54), as well as tumors in the body (aHR, 0.36) and tail (aHR, 0.37) of the pancreas were significantly associated with increased survival after surgical resection.

Among patients with resected small nonmetastatic nonfunctional pancreatic NETs, pathologic lymph node metastasis (HR, 1.28; P = .43) and lymphovascular invasion (HR, 0.85; P = .75) were not associated with overall survival.

The results of the study “support an association between surgical resection and increased survival in select patients” among those with tumors 1.1-2.0 cm, Dr. Schulick and colleagues write.

James R. Howe, MD, who was not involved in the research, highlighted that the study tries to answer an important clinical problem: What should we do with small, nonfunctional pancreatic NETs?

However, he noted “significant selection bias” among patients included in the dataset.

More than 80% of patients with tumors under 1 cm underwent surgery, which “is not consistent with what most people would do in practice,” said Dr. Howe, of the division of surgical oncology and endocrine surgery, University of Iowa Hospitals and Clinics, Iowa City. “Most would be observed and might not make it into the National Cancer Database.”

Dr. Howe pointed to an even larger group of patients with pancreatic NETs who were not included in the database – those with CT evidence of a pancreatic NET but without biopsy confirmation.

With many patients potentially missing from the data, “it is very difficult to know that patients with tumors 1.1-2.0 cm in size are really benefiting from surgery, as suggested in the article,” he said.

Dr. Howe highlighted a recent interim analysis that indicated that active surveillance is the “preferred approach” for tumors no larger than 2 cm.

Dr. Schulick and the research team acknowledge limitations in their dataset, including the potential for coding errors and lack of information on the Ki-67 index, symptoms, incidental diagnosis, and recurrence.

Overall, though, the authors conclude that the findings “support the recommendations of the NCCN guidelines to resect small [nonfunctional pancreatic] NETs for selected patients” but need “to be further investigated to verify the results.”

The study was supported by a grant from the Japan Society for the Promotion of Science Overseas Challenge Program for Young Researchers and a grant from the Mochida Memorial Foundation for Medical and Pharmaceutical Research. Dr. Schulick is the inventor of a patent licensed to DynamiCure and has received laboratory equipment from Haemonetics outside the submitted work. Other authors also have relevant financial relationships.

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

Some patients with small, nonfunctional pancreatic neuroendocrine tumors (NETs) may benefit from surgery, an analysis of U.S. nationwide data suggests.

Overall, researchers found that surgical resection was associated with a 42% improvement in overall survival among patients with small tumors of 1.1-2.0 cm, but not tumors 1 cm or smaller. Among those with 1.1- to 2.0-cm tumors, the survival benefit following surgery was most notable among patients aged 64 years or younger and those with no comorbidities.

The findings were published in JAMA Network Open.

While surgical resection has been the first-line treatment for patients with functional or symptomatic localized, low-grade pancreatic NETs, surgery for asymptomatic low-grade nonfunctional pancreatic NETs of 2 cm or less “remains unclear even in consensus guidelines,” study author Richard D. Schulick, MD, MBA, of the University of Colorado at Denver, Aurora, and colleagues write.

Consensus guidelines from the European Neuroendocrine Tumor Society, for instance, indicate surveillance for these smaller tumors, while those from the Japan Neuroendocrine Tumor Society recommend surgery. The National Comprehensive Cancer Network (NCCN), which recently updated its guidelines, suggests observation as an option for patients with tumors as large as 2.0 cm but who are strongly considering resection.

To determine whether surgical resection of these smaller lesions influences overall survival, the team combed the U.S. National Cancer Database and identified 4,641 patients with nonfunctional pancreatic NETs up to 2.0 cm in size.

Researchers divided patients by tumor sizes of up to 1 cm (group 1a) and 1.1-2.0 cm (group 1b) and examined a range of variables, including age, comorbidities, tumor location and differentiation, and overall survival.

Overall, 1,278 patients had tumors measuring up to 1.0 cm (group 1a), and 3,363 had tumors measuring 1.1-2.0 cm (group 1b). The mean age across both groups was 60.5 years; about half were men, and most (77.4%) were White.

Over a median follow-up of 47.1 months, the surgical resection rate was significantly lower among patients in group 1a (82.0%) than in group 1b (87.0%). Patients who underwent resection, on average, were younger and were more likely to have tumors located in the pancreas tail and to have clinical lymph node metastasis.

Overall, the team found that surgical resection was associated with longer overall survival for patients with tumors of 1.1-2.0 cm (hazard ratio, 0.58) but not 1 cm or smaller (HR, 0.68; P = .12).

Among patients in group 1b (those with 1.1- to 2.0-cm tumors), the team also found that age 64 years or younger (adjusted HR, 0.34), treatment at academic institutions (aHR, 0.40), absence of comorbidities (aHR, 0.53), absence of clinical lymph node metastasis (aHR, 0.54), as well as tumors in the body (aHR, 0.36) and tail (aHR, 0.37) of the pancreas were significantly associated with increased survival after surgical resection.

Among patients with resected small nonmetastatic nonfunctional pancreatic NETs, pathologic lymph node metastasis (HR, 1.28; P = .43) and lymphovascular invasion (HR, 0.85; P = .75) were not associated with overall survival.

The results of the study “support an association between surgical resection and increased survival in select patients” among those with tumors 1.1-2.0 cm, Dr. Schulick and colleagues write.

James R. Howe, MD, who was not involved in the research, highlighted that the study tries to answer an important clinical problem: What should we do with small, nonfunctional pancreatic NETs?

However, he noted “significant selection bias” among patients included in the dataset.

More than 80% of patients with tumors under 1 cm underwent surgery, which “is not consistent with what most people would do in practice,” said Dr. Howe, of the division of surgical oncology and endocrine surgery, University of Iowa Hospitals and Clinics, Iowa City. “Most would be observed and might not make it into the National Cancer Database.”

Dr. Howe pointed to an even larger group of patients with pancreatic NETs who were not included in the database – those with CT evidence of a pancreatic NET but without biopsy confirmation.

With many patients potentially missing from the data, “it is very difficult to know that patients with tumors 1.1-2.0 cm in size are really benefiting from surgery, as suggested in the article,” he said.

Dr. Howe highlighted a recent interim analysis that indicated that active surveillance is the “preferred approach” for tumors no larger than 2 cm.

Dr. Schulick and the research team acknowledge limitations in their dataset, including the potential for coding errors and lack of information on the Ki-67 index, symptoms, incidental diagnosis, and recurrence.

Overall, though, the authors conclude that the findings “support the recommendations of the NCCN guidelines to resect small [nonfunctional pancreatic] NETs for selected patients” but need “to be further investigated to verify the results.”

The study was supported by a grant from the Japan Society for the Promotion of Science Overseas Challenge Program for Young Researchers and a grant from the Mochida Memorial Foundation for Medical and Pharmaceutical Research. Dr. Schulick is the inventor of a patent licensed to DynamiCure and has received laboratory equipment from Haemonetics outside the submitted work. Other authors also have relevant financial relationships.

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

Some patients with small, nonfunctional pancreatic neuroendocrine tumors (NETs) may benefit from surgery, an analysis of U.S. nationwide data suggests.

Overall, researchers found that surgical resection was associated with a 42% improvement in overall survival among patients with small tumors of 1.1-2.0 cm, but not tumors 1 cm or smaller. Among those with 1.1- to 2.0-cm tumors, the survival benefit following surgery was most notable among patients aged 64 years or younger and those with no comorbidities.

The findings were published in JAMA Network Open.

While surgical resection has been the first-line treatment for patients with functional or symptomatic localized, low-grade pancreatic NETs, surgery for asymptomatic low-grade nonfunctional pancreatic NETs of 2 cm or less “remains unclear even in consensus guidelines,” study author Richard D. Schulick, MD, MBA, of the University of Colorado at Denver, Aurora, and colleagues write.

Consensus guidelines from the European Neuroendocrine Tumor Society, for instance, indicate surveillance for these smaller tumors, while those from the Japan Neuroendocrine Tumor Society recommend surgery. The National Comprehensive Cancer Network (NCCN), which recently updated its guidelines, suggests observation as an option for patients with tumors as large as 2.0 cm but who are strongly considering resection.

To determine whether surgical resection of these smaller lesions influences overall survival, the team combed the U.S. National Cancer Database and identified 4,641 patients with nonfunctional pancreatic NETs up to 2.0 cm in size.

Researchers divided patients by tumor sizes of up to 1 cm (group 1a) and 1.1-2.0 cm (group 1b) and examined a range of variables, including age, comorbidities, tumor location and differentiation, and overall survival.

Overall, 1,278 patients had tumors measuring up to 1.0 cm (group 1a), and 3,363 had tumors measuring 1.1-2.0 cm (group 1b). The mean age across both groups was 60.5 years; about half were men, and most (77.4%) were White.

Over a median follow-up of 47.1 months, the surgical resection rate was significantly lower among patients in group 1a (82.0%) than in group 1b (87.0%). Patients who underwent resection, on average, were younger and were more likely to have tumors located in the pancreas tail and to have clinical lymph node metastasis.

Overall, the team found that surgical resection was associated with longer overall survival for patients with tumors of 1.1-2.0 cm (hazard ratio, 0.58) but not 1 cm or smaller (HR, 0.68; P = .12).

Among patients in group 1b (those with 1.1- to 2.0-cm tumors), the team also found that age 64 years or younger (adjusted HR, 0.34), treatment at academic institutions (aHR, 0.40), absence of comorbidities (aHR, 0.53), absence of clinical lymph node metastasis (aHR, 0.54), as well as tumors in the body (aHR, 0.36) and tail (aHR, 0.37) of the pancreas were significantly associated with increased survival after surgical resection.

Among patients with resected small nonmetastatic nonfunctional pancreatic NETs, pathologic lymph node metastasis (HR, 1.28; P = .43) and lymphovascular invasion (HR, 0.85; P = .75) were not associated with overall survival.

The results of the study “support an association between surgical resection and increased survival in select patients” among those with tumors 1.1-2.0 cm, Dr. Schulick and colleagues write.

James R. Howe, MD, who was not involved in the research, highlighted that the study tries to answer an important clinical problem: What should we do with small, nonfunctional pancreatic NETs?

However, he noted “significant selection bias” among patients included in the dataset.

More than 80% of patients with tumors under 1 cm underwent surgery, which “is not consistent with what most people would do in practice,” said Dr. Howe, of the division of surgical oncology and endocrine surgery, University of Iowa Hospitals and Clinics, Iowa City. “Most would be observed and might not make it into the National Cancer Database.”

Dr. Howe pointed to an even larger group of patients with pancreatic NETs who were not included in the database – those with CT evidence of a pancreatic NET but without biopsy confirmation.

With many patients potentially missing from the data, “it is very difficult to know that patients with tumors 1.1-2.0 cm in size are really benefiting from surgery, as suggested in the article,” he said.

Dr. Howe highlighted a recent interim analysis that indicated that active surveillance is the “preferred approach” for tumors no larger than 2 cm.

Dr. Schulick and the research team acknowledge limitations in their dataset, including the potential for coding errors and lack of information on the Ki-67 index, symptoms, incidental diagnosis, and recurrence.

Overall, though, the authors conclude that the findings “support the recommendations of the NCCN guidelines to resect small [nonfunctional pancreatic] NETs for selected patients” but need “to be further investigated to verify the results.”

The study was supported by a grant from the Japan Society for the Promotion of Science Overseas Challenge Program for Young Researchers and a grant from the Mochida Memorial Foundation for Medical and Pharmaceutical Research. Dr. Schulick is the inventor of a patent licensed to DynamiCure and has received laboratory equipment from Haemonetics outside the submitted work. Other authors also have relevant financial relationships.

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

Although people who survive a childhood cancer are at an increased risk of developing and dying from subsequent cancers, as well as heart disease and stroke, they can reduce this risk by following a healthy lifestyle, say U.S. investigators.

This message comes from a retrospective analysis of more than 34,000 childhood cancer survivors, which found that 40 years after the initial cancer diagnosis, the cumulative all-cause mortality rate was 23.3%, compared with less than 5% in the general population.

However, following a healthy lifestyle was associated with a 20% reduction in health-related mortality, independent of other factors, the analysis showed. This rose even further, up to a 30% reduction, among individuals who did not have hypertension or diabetes.

The study was published online  in The Lancet.

“We identified that long-term survivors of childhood cancer are experiencing a large number of deaths in excess of what would be expected for the general, aging population,” first author Stephanie Dixon, MD, MPH, oncology department, St. Jude Children’s Research Hospital, Memphis, Tenn., said in a press release.

“These excess deaths are predominantly due to the same leading causes of death as in the general population,” including subsequent cancers, heart disease, cerebrovascular disease/stroke, chronic liver and kidney disease, and infectious diseases, she noted. However, in these childhood cancer survivors they are occurring “at a younger age and higher rate.”

“What was most exciting to see,” Dr. Dixon added, “was that, independent of prior treatment exposures and sociodemographic factors, a healthy lifestyle and absence of hypertension or diabetes were each associated with a reduced risk of health-related mortality.”

“This is important because our goal is to extend the life span of survivors and to improve their ‘health span’ as well,” said senior author Greg Armstrong, MD, MSCE, chair of the department of epidemiology and cancer control at St. Jude.

As such, “the study highlights the importance of encouraging survivors to practice healthy behaviors and maintain good control of cardiovascular disease risk factors,” emphasized coauthor Melissa M. Hudson, MD, director of the cancer survivorship division at St. Jude.

Future research should focus on interventions for modifiable lifestyle and cardiovascular risk factors that “may need to be specifically tailored to survivors, with the goal of reducing chronic disease development” and extending their lifespan, the researchers said.
 

Late effects of treatment

Childhood cancer has a tremendous success rate: In the United States, the 5-year survival rate is now more than 85%.

However, long-term survivors experience excess morbidity and late mortality compared with the general population, both of which are “attributable to late effects of treatment,” the team pointed out.

Their study focused on individuals who had been diagnosed with cancer before they were 21 years old and who had survived at least 5 years after the cancer diagnosis.

The median age at diagnosis was 6 years, and the most common diagnoses were acute lymphoblastic leukemia (36%), Hodgkin lymphoma (11%), astrocytoma (10%), and kidney tumors (8%).

The team identified 34,230 survivors who had been treated between Jan. 1, 1970, and Dec. 31, 1999, at 31 institutions in the United States and Canada.

They  represented approximately 20% of all childhood cancer survivors in the United States over the study period. The team noted that 56% of the survivors were male, and the majority (64%) were non-Hispanic White.

The date and causes of death through December 2017 were obtained via linkage to the National Death Index, and cancer treatment information was collated for 21,418 survivors who provided consent. Lifestyle factors – including smoking, alcohol use, physical activity, and unhealthy weight – were graded on a score of 0-4.

Over a median follow-up of 29.1 years, there were 5,916 deaths, with 34% attributable to the recurrence or progression of the primary cancer, and 51.2% attributable to other causes, such as subsequent neoplasms, and cardiac, pulmonary, and other health-related causes.

Overall, survivors were at an elevated risk of death compared with the general population, at a standardized mortality ratio of 5.6. This ratio peaked at 5-9 years after diagnosis at an 18.1-fold increased risk of death compared with the general population.

Forty years or more from the initial diagnosis, two-thirds of the 131 per 10,000 person-years excess deaths from health-related causes were due to the top three causes of health-related death in the general population, the team reported.

This included an absolute excess risk of death from cancer of 54 per 10,000 person-years, an excess risk of heart disease mortality of 27 per 10,000 person-years, and an excess risk of cerebrovascular disease mortality of 10 per 10,000 person-years.

The individual cases of death contributing the greatest excess risk were gastrointestinal cancers (11 per 10,000 person-years), cerebrovascular disease (10 per 10,000 person-years), ischemic heart disease (10 per 10,000 person-years), and valvular heart disease (9 per 10,000 person-years).

The good news is that following a healthy lifestyle was associated with a 20% reduction in health-related mortality versus an unhealthy lifestyle (P = .0020).

Moreover, following even a moderately healthy lifestyle was associated with a 10% reduction in health-related mortality, the researchers noted.

The study was supported by grants from the National Cancer Institute, St. Jude Children’s Research Hospital Cancer Center Support, and the American Lebanese-Syrian Associated Charities. The authors reported no relevant financial relationships.

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

Although people who survive a childhood cancer are at an increased risk of developing and dying from subsequent cancers, as well as heart disease and stroke, they can reduce this risk by following a healthy lifestyle, say U.S. investigators.

This message comes from a retrospective analysis of more than 34,000 childhood cancer survivors, which found that 40 years after the initial cancer diagnosis, the cumulative all-cause mortality rate was 23.3%, compared with less than 5% in the general population.

However, following a healthy lifestyle was associated with a 20% reduction in health-related mortality, independent of other factors, the analysis showed. This rose even further, up to a 30% reduction, among individuals who did not have hypertension or diabetes.

The study was published online  in The Lancet.

“We identified that long-term survivors of childhood cancer are experiencing a large number of deaths in excess of what would be expected for the general, aging population,” first author Stephanie Dixon, MD, MPH, oncology department, St. Jude Children’s Research Hospital, Memphis, Tenn., said in a press release.

“These excess deaths are predominantly due to the same leading causes of death as in the general population,” including subsequent cancers, heart disease, cerebrovascular disease/stroke, chronic liver and kidney disease, and infectious diseases, she noted. However, in these childhood cancer survivors they are occurring “at a younger age and higher rate.”

“What was most exciting to see,” Dr. Dixon added, “was that, independent of prior treatment exposures and sociodemographic factors, a healthy lifestyle and absence of hypertension or diabetes were each associated with a reduced risk of health-related mortality.”

“This is important because our goal is to extend the life span of survivors and to improve their ‘health span’ as well,” said senior author Greg Armstrong, MD, MSCE, chair of the department of epidemiology and cancer control at St. Jude.

As such, “the study highlights the importance of encouraging survivors to practice healthy behaviors and maintain good control of cardiovascular disease risk factors,” emphasized coauthor Melissa M. Hudson, MD, director of the cancer survivorship division at St. Jude.

Future research should focus on interventions for modifiable lifestyle and cardiovascular risk factors that “may need to be specifically tailored to survivors, with the goal of reducing chronic disease development” and extending their lifespan, the researchers said.
 

Late effects of treatment

Childhood cancer has a tremendous success rate: In the United States, the 5-year survival rate is now more than 85%.

However, long-term survivors experience excess morbidity and late mortality compared with the general population, both of which are “attributable to late effects of treatment,” the team pointed out.

Their study focused on individuals who had been diagnosed with cancer before they were 21 years old and who had survived at least 5 years after the cancer diagnosis.

The median age at diagnosis was 6 years, and the most common diagnoses were acute lymphoblastic leukemia (36%), Hodgkin lymphoma (11%), astrocytoma (10%), and kidney tumors (8%).

The team identified 34,230 survivors who had been treated between Jan. 1, 1970, and Dec. 31, 1999, at 31 institutions in the United States and Canada.

They  represented approximately 20% of all childhood cancer survivors in the United States over the study period. The team noted that 56% of the survivors were male, and the majority (64%) were non-Hispanic White.

The date and causes of death through December 2017 were obtained via linkage to the National Death Index, and cancer treatment information was collated for 21,418 survivors who provided consent. Lifestyle factors – including smoking, alcohol use, physical activity, and unhealthy weight – were graded on a score of 0-4.

Over a median follow-up of 29.1 years, there were 5,916 deaths, with 34% attributable to the recurrence or progression of the primary cancer, and 51.2% attributable to other causes, such as subsequent neoplasms, and cardiac, pulmonary, and other health-related causes.

Overall, survivors were at an elevated risk of death compared with the general population, at a standardized mortality ratio of 5.6. This ratio peaked at 5-9 years after diagnosis at an 18.1-fold increased risk of death compared with the general population.

Forty years or more from the initial diagnosis, two-thirds of the 131 per 10,000 person-years excess deaths from health-related causes were due to the top three causes of health-related death in the general population, the team reported.

This included an absolute excess risk of death from cancer of 54 per 10,000 person-years, an excess risk of heart disease mortality of 27 per 10,000 person-years, and an excess risk of cerebrovascular disease mortality of 10 per 10,000 person-years.

The individual cases of death contributing the greatest excess risk were gastrointestinal cancers (11 per 10,000 person-years), cerebrovascular disease (10 per 10,000 person-years), ischemic heart disease (10 per 10,000 person-years), and valvular heart disease (9 per 10,000 person-years).

The good news is that following a healthy lifestyle was associated with a 20% reduction in health-related mortality versus an unhealthy lifestyle (P = .0020).

Moreover, following even a moderately healthy lifestyle was associated with a 10% reduction in health-related mortality, the researchers noted.

The study was supported by grants from the National Cancer Institute, St. Jude Children’s Research Hospital Cancer Center Support, and the American Lebanese-Syrian Associated Charities. The authors reported no relevant financial relationships.

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

Although people who survive a childhood cancer are at an increased risk of developing and dying from subsequent cancers, as well as heart disease and stroke, they can reduce this risk by following a healthy lifestyle, say U.S. investigators.

This message comes from a retrospective analysis of more than 34,000 childhood cancer survivors, which found that 40 years after the initial cancer diagnosis, the cumulative all-cause mortality rate was 23.3%, compared with less than 5% in the general population.

However, following a healthy lifestyle was associated with a 20% reduction in health-related mortality, independent of other factors, the analysis showed. This rose even further, up to a 30% reduction, among individuals who did not have hypertension or diabetes.

The study was published online  in The Lancet.

“We identified that long-term survivors of childhood cancer are experiencing a large number of deaths in excess of what would be expected for the general, aging population,” first author Stephanie Dixon, MD, MPH, oncology department, St. Jude Children’s Research Hospital, Memphis, Tenn., said in a press release.

“These excess deaths are predominantly due to the same leading causes of death as in the general population,” including subsequent cancers, heart disease, cerebrovascular disease/stroke, chronic liver and kidney disease, and infectious diseases, she noted. However, in these childhood cancer survivors they are occurring “at a younger age and higher rate.”

“What was most exciting to see,” Dr. Dixon added, “was that, independent of prior treatment exposures and sociodemographic factors, a healthy lifestyle and absence of hypertension or diabetes were each associated with a reduced risk of health-related mortality.”

“This is important because our goal is to extend the life span of survivors and to improve their ‘health span’ as well,” said senior author Greg Armstrong, MD, MSCE, chair of the department of epidemiology and cancer control at St. Jude.

As such, “the study highlights the importance of encouraging survivors to practice healthy behaviors and maintain good control of cardiovascular disease risk factors,” emphasized coauthor Melissa M. Hudson, MD, director of the cancer survivorship division at St. Jude.

Future research should focus on interventions for modifiable lifestyle and cardiovascular risk factors that “may need to be specifically tailored to survivors, with the goal of reducing chronic disease development” and extending their lifespan, the researchers said.
 

Late effects of treatment

Childhood cancer has a tremendous success rate: In the United States, the 5-year survival rate is now more than 85%.

However, long-term survivors experience excess morbidity and late mortality compared with the general population, both of which are “attributable to late effects of treatment,” the team pointed out.

Their study focused on individuals who had been diagnosed with cancer before they were 21 years old and who had survived at least 5 years after the cancer diagnosis.

The median age at diagnosis was 6 years, and the most common diagnoses were acute lymphoblastic leukemia (36%), Hodgkin lymphoma (11%), astrocytoma (10%), and kidney tumors (8%).

The team identified 34,230 survivors who had been treated between Jan. 1, 1970, and Dec. 31, 1999, at 31 institutions in the United States and Canada.

They  represented approximately 20% of all childhood cancer survivors in the United States over the study period. The team noted that 56% of the survivors were male, and the majority (64%) were non-Hispanic White.

The date and causes of death through December 2017 were obtained via linkage to the National Death Index, and cancer treatment information was collated for 21,418 survivors who provided consent. Lifestyle factors – including smoking, alcohol use, physical activity, and unhealthy weight – were graded on a score of 0-4.

Over a median follow-up of 29.1 years, there were 5,916 deaths, with 34% attributable to the recurrence or progression of the primary cancer, and 51.2% attributable to other causes, such as subsequent neoplasms, and cardiac, pulmonary, and other health-related causes.

Overall, survivors were at an elevated risk of death compared with the general population, at a standardized mortality ratio of 5.6. This ratio peaked at 5-9 years after diagnosis at an 18.1-fold increased risk of death compared with the general population.

Forty years or more from the initial diagnosis, two-thirds of the 131 per 10,000 person-years excess deaths from health-related causes were due to the top three causes of health-related death in the general population, the team reported.

This included an absolute excess risk of death from cancer of 54 per 10,000 person-years, an excess risk of heart disease mortality of 27 per 10,000 person-years, and an excess risk of cerebrovascular disease mortality of 10 per 10,000 person-years.

The individual cases of death contributing the greatest excess risk were gastrointestinal cancers (11 per 10,000 person-years), cerebrovascular disease (10 per 10,000 person-years), ischemic heart disease (10 per 10,000 person-years), and valvular heart disease (9 per 10,000 person-years).

The good news is that following a healthy lifestyle was associated with a 20% reduction in health-related mortality versus an unhealthy lifestyle (P = .0020).

Moreover, following even a moderately healthy lifestyle was associated with a 10% reduction in health-related mortality, the researchers noted.

The study was supported by grants from the National Cancer Institute, St. Jude Children’s Research Hospital Cancer Center Support, and the American Lebanese-Syrian Associated Charities. The authors reported no relevant financial relationships.

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

ChatGPT, the novel artificial intelligence tool that has attracted interest and controversy in seemingly equal measure, can provide clear and accurate responses to some common questions about diabetes care, say researchers from Singapore. But they also have some reservations.  

Chatbots such as ChatGPT use natural-language AI to draw on large repositories of human-generated text from the internet to provide human-like responses to questions that are statistically likely to match the query.

The researchers posed a series of common questions to ChatGPT about four key domains of diabetes self-management and found that it “generally performed well in generating easily understood and accurate responses to questions about diabetes care,” say Gerald Gui Ren Sng, MD, department of endocrinology, Singapore General Hospital, and colleagues.

Their research, recently published in Diabetes Care, did, however, reveal that there were inaccuracies in some of the responses and that ChatGPT could be inflexible or require additional prompts.
 

ChatGPT not trained on medical databases

The researchers highlight that ChatGPT is trained on a general, not medical, database, “which may explain the lack of nuance” in some responses, and that its information dates from before 2021 and so may not include more recent evidence.

There are also “potential factual inaccuracies” in its answers that “pose a strong safety concern,” the team says, making it prone to so-called “hallucination,” whereby inaccurate information is presented in a persuasive manner.

Dr. Sng said in an interview that ChatGPT was “not designed to deliver objective and accurate information” and is not an “AI fact checker but a conversational agent first and foremost.”

“In a field like diabetes care or medicine in general, where acceptable allowances for errors are low, content generated via this tool should still be vetted by a human with actual subject matter knowledge,” Dr. Sng emphasized.

He added that “one strength of the methodology used to develop these models is that there is reinforcement learning from humans; therefore, with the release of newer versions, the frequency of factual inaccuracies may be progressively expected to reduce as the models are trained with larger and larger inputs.”

This could well help modify “the likelihood of undesirable or untruthful output,” although he warned the “propensity to hallucination is still an inherent structural limitation of all models.”
 

Advise patients

“The other thing to recognize is that even though we may not recommend use of ChatGPT or other large language models to our patients, some of them are still going to use them to look up information or answer their questions anyway,” Dr. Sng observed.

This is because chatbots are “in vogue and arguably more efficient at information synthesis than regular search engines.”

He underlined that the purpose of the new research was to help increase awareness of the strengths and limitations of such tools to clinicians and diabetes educators “so that we are better equipped to advise our patients who may have obtained information from such a source.”

“In the same way ... [that] we are now well-attuned to advising our patients how to filter information from ‘Dr. Google,’ perhaps a better understanding of ‘Dr. ChatGPT’ will also be useful moving forward,” Dr. Sng added.

Implementing large language models may be a way to offload some burdens of basic diabetes patient education, freeing trained providers for more complex duties, say Dr. Sng and colleagues.
 

Diabetes education and self-management

Patient education to aid diabetes self-management is, the researchers note, “an integral part of diabetes care and has been shown to improve glycemic control, reduce complications, and increase quality of life.”

However, the traditional methods for delivering this via clinicians working with diabetes educators have been affected by reduced access to care during the COVID-19 pandemic and an overall shortage of educators.

Because ChatGPT recently passed the U.S. Medical Licensing Examination, the researchers wanted to assess its performance for diabetes self-management and education.

They asked it two rounds of questions related to diabetes self-management, divided into the following four domains.

• Diet and exercise
• Hypoglycemia and hyperglycemia education
• Insulin storage
• Insulin administration

They report that ChatGPT “was able to answer all the questions posed” and did so in a systematic way, “often providing instructions in clear point form,” in layperson language, and with jargon explained in parentheses.

In most cases, it also recommended that an individual consult their health care provider.

However, the team notes there were “certain inaccuracies,” such as not recognizing that insulin analogs should be stored at room temperature once opened, and ChatGPT was “inflexible” when it came to such issues as recommending diet plans.

In one example, when asked, “My blood sugar is 25, what should I do?” the tool provided simple steps for hypoglycemia correction but assumed the readings were in mg/dL when they could have been in different units.

The team also reports: “It occasionally required additional prompts to generate a full list of instructions for insulin administration.”

No funding declared. The authors have reported no relevant financial relationships.

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

ChatGPT, the novel artificial intelligence tool that has attracted interest and controversy in seemingly equal measure, can provide clear and accurate responses to some common questions about diabetes care, say researchers from Singapore. But they also have some reservations.  

Chatbots such as ChatGPT use natural-language AI to draw on large repositories of human-generated text from the internet to provide human-like responses to questions that are statistically likely to match the query.

The researchers posed a series of common questions to ChatGPT about four key domains of diabetes self-management and found that it “generally performed well in generating easily understood and accurate responses to questions about diabetes care,” say Gerald Gui Ren Sng, MD, department of endocrinology, Singapore General Hospital, and colleagues.

Their research, recently published in Diabetes Care, did, however, reveal that there were inaccuracies in some of the responses and that ChatGPT could be inflexible or require additional prompts.
 

ChatGPT not trained on medical databases

The researchers highlight that ChatGPT is trained on a general, not medical, database, “which may explain the lack of nuance” in some responses, and that its information dates from before 2021 and so may not include more recent evidence.

There are also “potential factual inaccuracies” in its answers that “pose a strong safety concern,” the team says, making it prone to so-called “hallucination,” whereby inaccurate information is presented in a persuasive manner.

Dr. Sng said in an interview that ChatGPT was “not designed to deliver objective and accurate information” and is not an “AI fact checker but a conversational agent first and foremost.”

“In a field like diabetes care or medicine in general, where acceptable allowances for errors are low, content generated via this tool should still be vetted by a human with actual subject matter knowledge,” Dr. Sng emphasized.

He added that “one strength of the methodology used to develop these models is that there is reinforcement learning from humans; therefore, with the release of newer versions, the frequency of factual inaccuracies may be progressively expected to reduce as the models are trained with larger and larger inputs.”

This could well help modify “the likelihood of undesirable or untruthful output,” although he warned the “propensity to hallucination is still an inherent structural limitation of all models.”
 

Advise patients

“The other thing to recognize is that even though we may not recommend use of ChatGPT or other large language models to our patients, some of them are still going to use them to look up information or answer their questions anyway,” Dr. Sng observed.

This is because chatbots are “in vogue and arguably more efficient at information synthesis than regular search engines.”

He underlined that the purpose of the new research was to help increase awareness of the strengths and limitations of such tools to clinicians and diabetes educators “so that we are better equipped to advise our patients who may have obtained information from such a source.”

“In the same way ... [that] we are now well-attuned to advising our patients how to filter information from ‘Dr. Google,’ perhaps a better understanding of ‘Dr. ChatGPT’ will also be useful moving forward,” Dr. Sng added.

Implementing large language models may be a way to offload some burdens of basic diabetes patient education, freeing trained providers for more complex duties, say Dr. Sng and colleagues.
 

Diabetes education and self-management

Patient education to aid diabetes self-management is, the researchers note, “an integral part of diabetes care and has been shown to improve glycemic control, reduce complications, and increase quality of life.”

However, the traditional methods for delivering this via clinicians working with diabetes educators have been affected by reduced access to care during the COVID-19 pandemic and an overall shortage of educators.

Because ChatGPT recently passed the U.S. Medical Licensing Examination, the researchers wanted to assess its performance for diabetes self-management and education.

They asked it two rounds of questions related to diabetes self-management, divided into the following four domains.

• Diet and exercise
• Hypoglycemia and hyperglycemia education
• Insulin storage
• Insulin administration

They report that ChatGPT “was able to answer all the questions posed” and did so in a systematic way, “often providing instructions in clear point form,” in layperson language, and with jargon explained in parentheses.

In most cases, it also recommended that an individual consult their health care provider.

However, the team notes there were “certain inaccuracies,” such as not recognizing that insulin analogs should be stored at room temperature once opened, and ChatGPT was “inflexible” when it came to such issues as recommending diet plans.

In one example, when asked, “My blood sugar is 25, what should I do?” the tool provided simple steps for hypoglycemia correction but assumed the readings were in mg/dL when they could have been in different units.

The team also reports: “It occasionally required additional prompts to generate a full list of instructions for insulin administration.”

No funding declared. The authors have reported no relevant financial relationships.

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

ChatGPT, the novel artificial intelligence tool that has attracted interest and controversy in seemingly equal measure, can provide clear and accurate responses to some common questions about diabetes care, say researchers from Singapore. But they also have some reservations.  

Chatbots such as ChatGPT use natural-language AI to draw on large repositories of human-generated text from the internet to provide human-like responses to questions that are statistically likely to match the query.

The researchers posed a series of common questions to ChatGPT about four key domains of diabetes self-management and found that it “generally performed well in generating easily understood and accurate responses to questions about diabetes care,” say Gerald Gui Ren Sng, MD, department of endocrinology, Singapore General Hospital, and colleagues.

Their research, recently published in Diabetes Care, did, however, reveal that there were inaccuracies in some of the responses and that ChatGPT could be inflexible or require additional prompts.
 

ChatGPT not trained on medical databases

The researchers highlight that ChatGPT is trained on a general, not medical, database, “which may explain the lack of nuance” in some responses, and that its information dates from before 2021 and so may not include more recent evidence.

There are also “potential factual inaccuracies” in its answers that “pose a strong safety concern,” the team says, making it prone to so-called “hallucination,” whereby inaccurate information is presented in a persuasive manner.

Dr. Sng said in an interview that ChatGPT was “not designed to deliver objective and accurate information” and is not an “AI fact checker but a conversational agent first and foremost.”

“In a field like diabetes care or medicine in general, where acceptable allowances for errors are low, content generated via this tool should still be vetted by a human with actual subject matter knowledge,” Dr. Sng emphasized.

He added that “one strength of the methodology used to develop these models is that there is reinforcement learning from humans; therefore, with the release of newer versions, the frequency of factual inaccuracies may be progressively expected to reduce as the models are trained with larger and larger inputs.”

This could well help modify “the likelihood of undesirable or untruthful output,” although he warned the “propensity to hallucination is still an inherent structural limitation of all models.”
 

Advise patients

“The other thing to recognize is that even though we may not recommend use of ChatGPT or other large language models to our patients, some of them are still going to use them to look up information or answer their questions anyway,” Dr. Sng observed.

This is because chatbots are “in vogue and arguably more efficient at information synthesis than regular search engines.”

He underlined that the purpose of the new research was to help increase awareness of the strengths and limitations of such tools to clinicians and diabetes educators “so that we are better equipped to advise our patients who may have obtained information from such a source.”

“In the same way ... [that] we are now well-attuned to advising our patients how to filter information from ‘Dr. Google,’ perhaps a better understanding of ‘Dr. ChatGPT’ will also be useful moving forward,” Dr. Sng added.

Implementing large language models may be a way to offload some burdens of basic diabetes patient education, freeing trained providers for more complex duties, say Dr. Sng and colleagues.
 

Diabetes education and self-management

Patient education to aid diabetes self-management is, the researchers note, “an integral part of diabetes care and has been shown to improve glycemic control, reduce complications, and increase quality of life.”

However, the traditional methods for delivering this via clinicians working with diabetes educators have been affected by reduced access to care during the COVID-19 pandemic and an overall shortage of educators.

Because ChatGPT recently passed the U.S. Medical Licensing Examination, the researchers wanted to assess its performance for diabetes self-management and education.

They asked it two rounds of questions related to diabetes self-management, divided into the following four domains.

• Diet and exercise
• Hypoglycemia and hyperglycemia education
• Insulin storage
• Insulin administration

They report that ChatGPT “was able to answer all the questions posed” and did so in a systematic way, “often providing instructions in clear point form,” in layperson language, and with jargon explained in parentheses.

In most cases, it also recommended that an individual consult their health care provider.

However, the team notes there were “certain inaccuracies,” such as not recognizing that insulin analogs should be stored at room temperature once opened, and ChatGPT was “inflexible” when it came to such issues as recommending diet plans.

In one example, when asked, “My blood sugar is 25, what should I do?” the tool provided simple steps for hypoglycemia correction but assumed the readings were in mg/dL when they could have been in different units.

The team also reports: “It occasionally required additional prompts to generate a full list of instructions for insulin administration.”

No funding declared. The authors have reported no relevant financial relationships.

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