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Bone risk: Is time since menopause a better predictor than age?
Although early menopause is linked to increased risks in bone loss and fracture, new research indicates that, even among the majority of women who have menopause after age 45, the time since the final menstrual period can be a stronger predictor than chronological age for key risks in bone health and fracture.
In a large longitudinal cohort, the number of years since a woman’s final menstrual period specifically showed a stronger association with femoral neck bone mineral density (BMD) than chronological age, while an earlier age at menopause – even among those over 45 years, was linked to an increased risk of fracture.
“Most of our clinical tools to predict osteoporosis-related outcomes use chronological age,” first author Albert Shieh, MD, told this news organization.
“Our findings suggest that more research should be done to examine whether ovarian age (time since final menstrual period) should be used in these tools as well.”
An increased focus on the significance of age at the time of the final menstrual period, compared with chronological age, has gained interest in risk assessment because of the known acceleration in the decline of BMD that occurs 1 year prior to the final menstrual period and continues at a rapid pace for 3 years afterwards before slowing.
To further investigate the association with BMD, Dr. Shieh, an endocrinologist specializing in osteoporosis at the University of California, Los Angeles, and his colleagues turned to data from the Study of Women’s Health Across the Nation (SWAN), a longitudinal cohort study of ambulatory women with pre- or early perimenopausal baseline data and 15 annual follow-up assessments.
Outcomes regarding postmenopausal lumbar spine (LS) or femoral neck (FN) BMD were evaluated in 1,038 women, while the time to fracture in relation to the final menstrual period was separately evaluated in 1,554 women.
In both cohorts, the women had a known final menstrual period at age 45 or older, and on average, their final menstrual period occurred at age 52.
After a multivariate adjustment for age, body mass index, and various other factors, they found that each additional year after a woman’s final menstrual period was associated with a significant (0.006 g/cm2) reduction in postmenopausal lumbar spine BMD and a 0.004 g/cm2 reduction femoral neck BMD (both P < .0001).
Conversely, chronological age was not associated with a change in femoral neck BMD when evaluated independently of years since the final menstrual period, the researchers reported in the Journal of Clinical Endocrinology and Metabolism.
Regarding lumbar spine BMD, chronological age was unexpectedly associated not just with change, but in fact with increases in lumbar spine BMD (P < .0001 per year). However, the authors speculate the change “is likely a reflection of age-associated degenerative changes causing false elevations in BMD measured by dual-energy x-ray absorptiometry.”
Fracture risk with earlier menopause
In terms of the fracture risk analysis, despite the women all being aged 45 or older, earlier age at menopause was still tied to an increased risk of incident fracture, with a 5% increase in risk for each earlier year in age at the time of the final menstrual period (P = .02).
Compared with women who had their final menstrual period at age 55, for instance, those who finished menstruating at age 47 had a 6.3% greater 20-year cumulative fracture risk, the authors note.
While previous findings from the Malmo Perimenopausal Study showed menopause prior to the age of 47 to be associated with an 83% and 59% greater risk of densitometric osteoporosis and fracture, respectively, by age 77, the authors note that the new study is unique in including only women who had a final menstrual period over the age of 45, therefore reducing the potential confounding of data on women under 45.
The new results “add to a growing body of literature suggesting that the endocrine changes that occur during the menopause transition trigger a pathophysiologic cascade that leads to organ dysfunction,” the authors note.
In terms of implications in risk assessment, “future studies should examine whether years since the final menstrual period predicts major osteoporotic fractures and hip fractures, specifically, and, if so, whether replacing chronological age with years since the final menstrual period improves the performance of clinical prediction tools, such as FRAX [Fracture Risk Assessment Tool],” they add.
Addition to guidelines?
Commenting on the findings, Peter Ebeling, MD, the current president of the American Society of Bone and Mineral Research, noted that the study importantly “confirms what we had previously anticipated, that in women with menopause who are 45 years of age or older a lower age of final menstrual period is associated with lower spine and hip BMD and more fractures.”
“We had already known this for women with premature ovarian insufficiency or an early menopause, and this extends the observation to the vast majority of women – more than 90% – with a normal menopause age,” said Dr. Ebeling, professor of medicine at Monash Health, Monash University, in Melbourne.
Despite the known importance of the time since final menstrual period, guidelines still focus on age in terms of chronology, rather than biology, emphasizing the risk among women over 50, in general, rather than the time since the last menstrual period, he noted.
“There is an important difference [between those two], as shown by this study,” he said. “Guidelines could be easily adapted to reflect this.”
Specifically, the association between lower age of final menstrual period and lower spine and hip BMD and more fractures requires “more formal assessment to determine whether adding age of final menstrual period to existing fracture risk calculator tools, like FRAX, can improve absolute fracture risk prediction,” Dr. Ebeling noted.
The authors and Dr. Ebeling had no disclosures to report.
Although early menopause is linked to increased risks in bone loss and fracture, new research indicates that, even among the majority of women who have menopause after age 45, the time since the final menstrual period can be a stronger predictor than chronological age for key risks in bone health and fracture.
In a large longitudinal cohort, the number of years since a woman’s final menstrual period specifically showed a stronger association with femoral neck bone mineral density (BMD) than chronological age, while an earlier age at menopause – even among those over 45 years, was linked to an increased risk of fracture.
“Most of our clinical tools to predict osteoporosis-related outcomes use chronological age,” first author Albert Shieh, MD, told this news organization.
“Our findings suggest that more research should be done to examine whether ovarian age (time since final menstrual period) should be used in these tools as well.”
An increased focus on the significance of age at the time of the final menstrual period, compared with chronological age, has gained interest in risk assessment because of the known acceleration in the decline of BMD that occurs 1 year prior to the final menstrual period and continues at a rapid pace for 3 years afterwards before slowing.
To further investigate the association with BMD, Dr. Shieh, an endocrinologist specializing in osteoporosis at the University of California, Los Angeles, and his colleagues turned to data from the Study of Women’s Health Across the Nation (SWAN), a longitudinal cohort study of ambulatory women with pre- or early perimenopausal baseline data and 15 annual follow-up assessments.
Outcomes regarding postmenopausal lumbar spine (LS) or femoral neck (FN) BMD were evaluated in 1,038 women, while the time to fracture in relation to the final menstrual period was separately evaluated in 1,554 women.
In both cohorts, the women had a known final menstrual period at age 45 or older, and on average, their final menstrual period occurred at age 52.
After a multivariate adjustment for age, body mass index, and various other factors, they found that each additional year after a woman’s final menstrual period was associated with a significant (0.006 g/cm2) reduction in postmenopausal lumbar spine BMD and a 0.004 g/cm2 reduction femoral neck BMD (both P < .0001).
Conversely, chronological age was not associated with a change in femoral neck BMD when evaluated independently of years since the final menstrual period, the researchers reported in the Journal of Clinical Endocrinology and Metabolism.
Regarding lumbar spine BMD, chronological age was unexpectedly associated not just with change, but in fact with increases in lumbar spine BMD (P < .0001 per year). However, the authors speculate the change “is likely a reflection of age-associated degenerative changes causing false elevations in BMD measured by dual-energy x-ray absorptiometry.”
Fracture risk with earlier menopause
In terms of the fracture risk analysis, despite the women all being aged 45 or older, earlier age at menopause was still tied to an increased risk of incident fracture, with a 5% increase in risk for each earlier year in age at the time of the final menstrual period (P = .02).
Compared with women who had their final menstrual period at age 55, for instance, those who finished menstruating at age 47 had a 6.3% greater 20-year cumulative fracture risk, the authors note.
While previous findings from the Malmo Perimenopausal Study showed menopause prior to the age of 47 to be associated with an 83% and 59% greater risk of densitometric osteoporosis and fracture, respectively, by age 77, the authors note that the new study is unique in including only women who had a final menstrual period over the age of 45, therefore reducing the potential confounding of data on women under 45.
The new results “add to a growing body of literature suggesting that the endocrine changes that occur during the menopause transition trigger a pathophysiologic cascade that leads to organ dysfunction,” the authors note.
In terms of implications in risk assessment, “future studies should examine whether years since the final menstrual period predicts major osteoporotic fractures and hip fractures, specifically, and, if so, whether replacing chronological age with years since the final menstrual period improves the performance of clinical prediction tools, such as FRAX [Fracture Risk Assessment Tool],” they add.
Addition to guidelines?
Commenting on the findings, Peter Ebeling, MD, the current president of the American Society of Bone and Mineral Research, noted that the study importantly “confirms what we had previously anticipated, that in women with menopause who are 45 years of age or older a lower age of final menstrual period is associated with lower spine and hip BMD and more fractures.”
“We had already known this for women with premature ovarian insufficiency or an early menopause, and this extends the observation to the vast majority of women – more than 90% – with a normal menopause age,” said Dr. Ebeling, professor of medicine at Monash Health, Monash University, in Melbourne.
Despite the known importance of the time since final menstrual period, guidelines still focus on age in terms of chronology, rather than biology, emphasizing the risk among women over 50, in general, rather than the time since the last menstrual period, he noted.
“There is an important difference [between those two], as shown by this study,” he said. “Guidelines could be easily adapted to reflect this.”
Specifically, the association between lower age of final menstrual period and lower spine and hip BMD and more fractures requires “more formal assessment to determine whether adding age of final menstrual period to existing fracture risk calculator tools, like FRAX, can improve absolute fracture risk prediction,” Dr. Ebeling noted.
The authors and Dr. Ebeling had no disclosures to report.
Although early menopause is linked to increased risks in bone loss and fracture, new research indicates that, even among the majority of women who have menopause after age 45, the time since the final menstrual period can be a stronger predictor than chronological age for key risks in bone health and fracture.
In a large longitudinal cohort, the number of years since a woman’s final menstrual period specifically showed a stronger association with femoral neck bone mineral density (BMD) than chronological age, while an earlier age at menopause – even among those over 45 years, was linked to an increased risk of fracture.
“Most of our clinical tools to predict osteoporosis-related outcomes use chronological age,” first author Albert Shieh, MD, told this news organization.
“Our findings suggest that more research should be done to examine whether ovarian age (time since final menstrual period) should be used in these tools as well.”
An increased focus on the significance of age at the time of the final menstrual period, compared with chronological age, has gained interest in risk assessment because of the known acceleration in the decline of BMD that occurs 1 year prior to the final menstrual period and continues at a rapid pace for 3 years afterwards before slowing.
To further investigate the association with BMD, Dr. Shieh, an endocrinologist specializing in osteoporosis at the University of California, Los Angeles, and his colleagues turned to data from the Study of Women’s Health Across the Nation (SWAN), a longitudinal cohort study of ambulatory women with pre- or early perimenopausal baseline data and 15 annual follow-up assessments.
Outcomes regarding postmenopausal lumbar spine (LS) or femoral neck (FN) BMD were evaluated in 1,038 women, while the time to fracture in relation to the final menstrual period was separately evaluated in 1,554 women.
In both cohorts, the women had a known final menstrual period at age 45 or older, and on average, their final menstrual period occurred at age 52.
After a multivariate adjustment for age, body mass index, and various other factors, they found that each additional year after a woman’s final menstrual period was associated with a significant (0.006 g/cm2) reduction in postmenopausal lumbar spine BMD and a 0.004 g/cm2 reduction femoral neck BMD (both P < .0001).
Conversely, chronological age was not associated with a change in femoral neck BMD when evaluated independently of years since the final menstrual period, the researchers reported in the Journal of Clinical Endocrinology and Metabolism.
Regarding lumbar spine BMD, chronological age was unexpectedly associated not just with change, but in fact with increases in lumbar spine BMD (P < .0001 per year). However, the authors speculate the change “is likely a reflection of age-associated degenerative changes causing false elevations in BMD measured by dual-energy x-ray absorptiometry.”
Fracture risk with earlier menopause
In terms of the fracture risk analysis, despite the women all being aged 45 or older, earlier age at menopause was still tied to an increased risk of incident fracture, with a 5% increase in risk for each earlier year in age at the time of the final menstrual period (P = .02).
Compared with women who had their final menstrual period at age 55, for instance, those who finished menstruating at age 47 had a 6.3% greater 20-year cumulative fracture risk, the authors note.
While previous findings from the Malmo Perimenopausal Study showed menopause prior to the age of 47 to be associated with an 83% and 59% greater risk of densitometric osteoporosis and fracture, respectively, by age 77, the authors note that the new study is unique in including only women who had a final menstrual period over the age of 45, therefore reducing the potential confounding of data on women under 45.
The new results “add to a growing body of literature suggesting that the endocrine changes that occur during the menopause transition trigger a pathophysiologic cascade that leads to organ dysfunction,” the authors note.
In terms of implications in risk assessment, “future studies should examine whether years since the final menstrual period predicts major osteoporotic fractures and hip fractures, specifically, and, if so, whether replacing chronological age with years since the final menstrual period improves the performance of clinical prediction tools, such as FRAX [Fracture Risk Assessment Tool],” they add.
Addition to guidelines?
Commenting on the findings, Peter Ebeling, MD, the current president of the American Society of Bone and Mineral Research, noted that the study importantly “confirms what we had previously anticipated, that in women with menopause who are 45 years of age or older a lower age of final menstrual period is associated with lower spine and hip BMD and more fractures.”
“We had already known this for women with premature ovarian insufficiency or an early menopause, and this extends the observation to the vast majority of women – more than 90% – with a normal menopause age,” said Dr. Ebeling, professor of medicine at Monash Health, Monash University, in Melbourne.
Despite the known importance of the time since final menstrual period, guidelines still focus on age in terms of chronology, rather than biology, emphasizing the risk among women over 50, in general, rather than the time since the last menstrual period, he noted.
“There is an important difference [between those two], as shown by this study,” he said. “Guidelines could be easily adapted to reflect this.”
Specifically, the association between lower age of final menstrual period and lower spine and hip BMD and more fractures requires “more formal assessment to determine whether adding age of final menstrual period to existing fracture risk calculator tools, like FRAX, can improve absolute fracture risk prediction,” Dr. Ebeling noted.
The authors and Dr. Ebeling had no disclosures to report.
FROM JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
Use live donors for liver transplants for HCC patients, say experts
A new study shows that outcomes with liver transplants from live donors are better than outcomes with transplants from deceased donors, leading to calls for increasing the availability of live donation.
“Transplant programs worldwide should be encouraged to expand their live donor programs to manage patients with HCC,” suggest authors of the new study, published in September in JAMA Surgery.
The findings are important in light of the fact that among patients with HCC, liver transplants are restricted to those patients who have the highest chances of survival, owing to long donor organ waiting lists, say the authors. Use of transplants from living donors could increase the availability of organs for patients on the deceased donor waiting list.
“One could even argue that a living donor gives two organs back to the organ pool,” the authors comment.
“Efforts to expand the donor pool through living donor liver transplant for patients with HCC will ultimately increase the number of available deceased donor liver transplants to help all patients in need of liver transplant,” David A. Gerber, MD, of the University of North Carolina at Chapel Hill, and colleagues write in an accompanying commentary.
“It is very important that donors aren’t recruited or solicited, but with the growth of transplant programs, more potential donors will become aware of this opportunity and will step forward seeking to help someone else,” Dr. Gerber commented.
Live liver donor = lower death risk
The new study was conducted by first author Quirino Laid, MD, PhD, of the Department of General Surgery and Organ Transplantation, Sapienza University, Rome, and colleagues. They explain that the need to better understand the potential benefits of living donor organs is pressing. Liver cancer rates continue to rise, and the demand for organs outpaces the supply. Although various smaller studies have shown survival benefits of live donor liver transplant for people with HCC, debate continues. Previous evidence has suggested higher cancer recurrence rates and unfavorable outcomes.
The multicenter study is thought to be the largest to date on this issue. The investigators evaluated data from patients who were on liver donation waiting lists for a first transplant between January 2000 and December 2017. The study included two cohorts of patients on waiting lists: an international cohort, consisting of 3,052 patients at 12 collaborative transplant centers in Europe, Asia, and the United States; and a Canadian cohort, consisting of 906 patients.
The majority of patients were men (80.2%). The median age at the time of first referral was 58 years.
About a third of patients (33.1%) in the international cohort and slightly fewer than a third (27%) in the Canadian cohort received live donor liver transplants; the reminder received liver transplants from deceased donors.
The median follow-up period was 3.3 years. Receiving a live donor liver transplant was independently associated with a 49% reduction in the overall risk for death (hazard ratio, 0.51) in the international cohort and a 43% reduction in the Canadian cohort (HR, 0.57; both P < .001).
After adjustment for potential confounders, living donor liver transplantation remained independently associated with a reduced the risk for overall death. There was a reduction of 33% in the international cohort (P = .001) and a reduction of 48% in the Canadian cohort (P < .001).
“Divergent experiences all converged to a similar 40% to 50% reduction in intention-to-treat death risk,” the authors write.
Importantly, there were no increases in post-transplant cancer recurrence rates in the live donor groups in either cohort. Rates ranged from 13% to 16% over 5 years and from 17% to 22% after 10 years in both groups.
The median amount of time on the waiting list was significantly shorter for patients in the live donor group than for those in the deceased donor group (1 month vs. 6 months in the international cohort [P < .001]; 5 months vs. 6 months in the Canadian cohort [P = .006]).
Notably, in the deceased donor groups, there were 295 dropouts, compared with no dropouts among the live donor patients in the international cohort (P < .001). In the Canadian cohort, the corresponding rates were 32.2% and 13.9% (P < .001).
Diverse transplant centers, larger cohorts set study apart
Although these latest results are consistent with those of recent studies conducted in France, Hong Kong, and elsewhere, in the current study, the cohorts were larger, say the authors.
“Compared with previous studies, all of which were based on relatively small case series, the present study examined the data of almost 4,000 patients who were on a waiting list for a transplant; therefore, this study may be the largest cohort study on this topic,” they point out.
In addition to improved timing of a transplant, other factors, such as patient selection, help explain the better survival, editorialist Dr. Gerber commented.
“Survival improvement [with live donor liver transplants] is a combination of [surgeon] experience in this transplant procedure and an appropriate selection bias, meaning taking patients who aren’t too sick while waiting on the transplant but who would benefit from the operation,” he said.
Gaining that experience may be particularly challenging in the United States, owing to regulatory barriers to expanding the programs, but efforts to overcome that are moving ahead, Dr. Gerber added.
“This issue of where an individual gains the experience or expertise is being discussed as transplantation has grown worldwide,” he notes.
As programs expand, the availability of live liver donors should improve, he suggested.
In a related story, this news organization recently reported on the controversial issue of liver transplant as an option for the treatment of liver metastases resulting from colorectal cancer.
Study coauthor Gonzalo Sapisochin, MD, has received grants from Bayer and Roche outside the submitted work as well as personal fees from Integra, Novartis, and AstraZeneca. No other relevant financial relationships were reported.
A version of this article first appeared on Medscape.com.
A new study shows that outcomes with liver transplants from live donors are better than outcomes with transplants from deceased donors, leading to calls for increasing the availability of live donation.
“Transplant programs worldwide should be encouraged to expand their live donor programs to manage patients with HCC,” suggest authors of the new study, published in September in JAMA Surgery.
The findings are important in light of the fact that among patients with HCC, liver transplants are restricted to those patients who have the highest chances of survival, owing to long donor organ waiting lists, say the authors. Use of transplants from living donors could increase the availability of organs for patients on the deceased donor waiting list.
“One could even argue that a living donor gives two organs back to the organ pool,” the authors comment.
“Efforts to expand the donor pool through living donor liver transplant for patients with HCC will ultimately increase the number of available deceased donor liver transplants to help all patients in need of liver transplant,” David A. Gerber, MD, of the University of North Carolina at Chapel Hill, and colleagues write in an accompanying commentary.
“It is very important that donors aren’t recruited or solicited, but with the growth of transplant programs, more potential donors will become aware of this opportunity and will step forward seeking to help someone else,” Dr. Gerber commented.
Live liver donor = lower death risk
The new study was conducted by first author Quirino Laid, MD, PhD, of the Department of General Surgery and Organ Transplantation, Sapienza University, Rome, and colleagues. They explain that the need to better understand the potential benefits of living donor organs is pressing. Liver cancer rates continue to rise, and the demand for organs outpaces the supply. Although various smaller studies have shown survival benefits of live donor liver transplant for people with HCC, debate continues. Previous evidence has suggested higher cancer recurrence rates and unfavorable outcomes.
The multicenter study is thought to be the largest to date on this issue. The investigators evaluated data from patients who were on liver donation waiting lists for a first transplant between January 2000 and December 2017. The study included two cohorts of patients on waiting lists: an international cohort, consisting of 3,052 patients at 12 collaborative transplant centers in Europe, Asia, and the United States; and a Canadian cohort, consisting of 906 patients.
The majority of patients were men (80.2%). The median age at the time of first referral was 58 years.
About a third of patients (33.1%) in the international cohort and slightly fewer than a third (27%) in the Canadian cohort received live donor liver transplants; the reminder received liver transplants from deceased donors.
The median follow-up period was 3.3 years. Receiving a live donor liver transplant was independently associated with a 49% reduction in the overall risk for death (hazard ratio, 0.51) in the international cohort and a 43% reduction in the Canadian cohort (HR, 0.57; both P < .001).
After adjustment for potential confounders, living donor liver transplantation remained independently associated with a reduced the risk for overall death. There was a reduction of 33% in the international cohort (P = .001) and a reduction of 48% in the Canadian cohort (P < .001).
“Divergent experiences all converged to a similar 40% to 50% reduction in intention-to-treat death risk,” the authors write.
Importantly, there were no increases in post-transplant cancer recurrence rates in the live donor groups in either cohort. Rates ranged from 13% to 16% over 5 years and from 17% to 22% after 10 years in both groups.
The median amount of time on the waiting list was significantly shorter for patients in the live donor group than for those in the deceased donor group (1 month vs. 6 months in the international cohort [P < .001]; 5 months vs. 6 months in the Canadian cohort [P = .006]).
Notably, in the deceased donor groups, there were 295 dropouts, compared with no dropouts among the live donor patients in the international cohort (P < .001). In the Canadian cohort, the corresponding rates were 32.2% and 13.9% (P < .001).
Diverse transplant centers, larger cohorts set study apart
Although these latest results are consistent with those of recent studies conducted in France, Hong Kong, and elsewhere, in the current study, the cohorts were larger, say the authors.
“Compared with previous studies, all of which were based on relatively small case series, the present study examined the data of almost 4,000 patients who were on a waiting list for a transplant; therefore, this study may be the largest cohort study on this topic,” they point out.
In addition to improved timing of a transplant, other factors, such as patient selection, help explain the better survival, editorialist Dr. Gerber commented.
“Survival improvement [with live donor liver transplants] is a combination of [surgeon] experience in this transplant procedure and an appropriate selection bias, meaning taking patients who aren’t too sick while waiting on the transplant but who would benefit from the operation,” he said.
Gaining that experience may be particularly challenging in the United States, owing to regulatory barriers to expanding the programs, but efforts to overcome that are moving ahead, Dr. Gerber added.
“This issue of where an individual gains the experience or expertise is being discussed as transplantation has grown worldwide,” he notes.
As programs expand, the availability of live liver donors should improve, he suggested.
In a related story, this news organization recently reported on the controversial issue of liver transplant as an option for the treatment of liver metastases resulting from colorectal cancer.
Study coauthor Gonzalo Sapisochin, MD, has received grants from Bayer and Roche outside the submitted work as well as personal fees from Integra, Novartis, and AstraZeneca. No other relevant financial relationships were reported.
A version of this article first appeared on Medscape.com.
A new study shows that outcomes with liver transplants from live donors are better than outcomes with transplants from deceased donors, leading to calls for increasing the availability of live donation.
“Transplant programs worldwide should be encouraged to expand their live donor programs to manage patients with HCC,” suggest authors of the new study, published in September in JAMA Surgery.
The findings are important in light of the fact that among patients with HCC, liver transplants are restricted to those patients who have the highest chances of survival, owing to long donor organ waiting lists, say the authors. Use of transplants from living donors could increase the availability of organs for patients on the deceased donor waiting list.
“One could even argue that a living donor gives two organs back to the organ pool,” the authors comment.
“Efforts to expand the donor pool through living donor liver transplant for patients with HCC will ultimately increase the number of available deceased donor liver transplants to help all patients in need of liver transplant,” David A. Gerber, MD, of the University of North Carolina at Chapel Hill, and colleagues write in an accompanying commentary.
“It is very important that donors aren’t recruited or solicited, but with the growth of transplant programs, more potential donors will become aware of this opportunity and will step forward seeking to help someone else,” Dr. Gerber commented.
Live liver donor = lower death risk
The new study was conducted by first author Quirino Laid, MD, PhD, of the Department of General Surgery and Organ Transplantation, Sapienza University, Rome, and colleagues. They explain that the need to better understand the potential benefits of living donor organs is pressing. Liver cancer rates continue to rise, and the demand for organs outpaces the supply. Although various smaller studies have shown survival benefits of live donor liver transplant for people with HCC, debate continues. Previous evidence has suggested higher cancer recurrence rates and unfavorable outcomes.
The multicenter study is thought to be the largest to date on this issue. The investigators evaluated data from patients who were on liver donation waiting lists for a first transplant between January 2000 and December 2017. The study included two cohorts of patients on waiting lists: an international cohort, consisting of 3,052 patients at 12 collaborative transplant centers in Europe, Asia, and the United States; and a Canadian cohort, consisting of 906 patients.
The majority of patients were men (80.2%). The median age at the time of first referral was 58 years.
About a third of patients (33.1%) in the international cohort and slightly fewer than a third (27%) in the Canadian cohort received live donor liver transplants; the reminder received liver transplants from deceased donors.
The median follow-up period was 3.3 years. Receiving a live donor liver transplant was independently associated with a 49% reduction in the overall risk for death (hazard ratio, 0.51) in the international cohort and a 43% reduction in the Canadian cohort (HR, 0.57; both P < .001).
After adjustment for potential confounders, living donor liver transplantation remained independently associated with a reduced the risk for overall death. There was a reduction of 33% in the international cohort (P = .001) and a reduction of 48% in the Canadian cohort (P < .001).
“Divergent experiences all converged to a similar 40% to 50% reduction in intention-to-treat death risk,” the authors write.
Importantly, there were no increases in post-transplant cancer recurrence rates in the live donor groups in either cohort. Rates ranged from 13% to 16% over 5 years and from 17% to 22% after 10 years in both groups.
The median amount of time on the waiting list was significantly shorter for patients in the live donor group than for those in the deceased donor group (1 month vs. 6 months in the international cohort [P < .001]; 5 months vs. 6 months in the Canadian cohort [P = .006]).
Notably, in the deceased donor groups, there were 295 dropouts, compared with no dropouts among the live donor patients in the international cohort (P < .001). In the Canadian cohort, the corresponding rates were 32.2% and 13.9% (P < .001).
Diverse transplant centers, larger cohorts set study apart
Although these latest results are consistent with those of recent studies conducted in France, Hong Kong, and elsewhere, in the current study, the cohorts were larger, say the authors.
“Compared with previous studies, all of which were based on relatively small case series, the present study examined the data of almost 4,000 patients who were on a waiting list for a transplant; therefore, this study may be the largest cohort study on this topic,” they point out.
In addition to improved timing of a transplant, other factors, such as patient selection, help explain the better survival, editorialist Dr. Gerber commented.
“Survival improvement [with live donor liver transplants] is a combination of [surgeon] experience in this transplant procedure and an appropriate selection bias, meaning taking patients who aren’t too sick while waiting on the transplant but who would benefit from the operation,” he said.
Gaining that experience may be particularly challenging in the United States, owing to regulatory barriers to expanding the programs, but efforts to overcome that are moving ahead, Dr. Gerber added.
“This issue of where an individual gains the experience or expertise is being discussed as transplantation has grown worldwide,” he notes.
As programs expand, the availability of live liver donors should improve, he suggested.
In a related story, this news organization recently reported on the controversial issue of liver transplant as an option for the treatment of liver metastases resulting from colorectal cancer.
Study coauthor Gonzalo Sapisochin, MD, has received grants from Bayer and Roche outside the submitted work as well as personal fees from Integra, Novartis, and AstraZeneca. No other relevant financial relationships were reported.
A version of this article first appeared on Medscape.com.
Radiofrequency ablation gains favor for thyroid nodules in U.S.
And in one case, a hospital has taken the unique step of forming a multidisciplinary thyroid nodule RFA tumor board, which helps in the often tricky decision-making process that is involved.
“Our multidisciplinary RFA tumor board has been invaluable in this process, and it is the only one of its kind in the nation that I’m aware of,” James Lim, MD, of the Division of Surgical Oncology, Thyroid, and Parathyroid Center at Oregon Health Sciences University (OHSU), told this news organization.
Dr. Lim reports receiving referrals from “all avenues, some from thyroid specialists and others from nonthyroid specialists such as primary care practitioners or patient self-referrals.”
“Because of this, our centralized process of multidisciplinary review ensures that each patient is evaluated thoroughly through each thyroid specialists’ lens to optimize patient outcomes,” noted Dr. Lim, an assistant professor of endocrine surgery.
The RFA tumor board consists of experts in all specialties involved in thyroid nodule assessment and treatment, including surgeons, interventional radiologists, and endocrinologists.
Just because you can, doesn’t mean you should
However, there should be some caution that although there is enthusiasm regarding this noninvasive alternative to surgery, there is another option, that of mere observation, which is appropriate in many cases of thyroid nodules and should not be overlooked.
“For a number of reasons, the key to keep in mind is that, just because we can do something doesn’t mean we should,” Michael Singer, MD, director of the Division of Thyroid & Parathyroid Surgery, Department of Otolaryngology – Head and Neck Surgery, at the Henry Ford Health System, Detroit, said in an interview.
While emphasizing that he believes RFA to be a promising technology that will likely benefit patients in the future, Dr. Singer voiced concern about the approach becoming an easy choice – particularly if profit is to be had – when observation is a clear alternative. “If RFA becomes seen as an opportunity to create revenue, potential conflicts of interest may arise,” he said.
“As it is not a major procedure with a dramatic risk profile, my concern is that some clinicians [could] adopt the attitude of ‘Why not do it?’ even when the indication is minimal or nonexistent,” he added.
Dr. Lim said he agrees that “any new medical technology requires thoughtful evaluation and appropriate patient selection in order to ensure optimal patient outcomes.”
That’s where the tumor board has been especially beneficial.
“We have found great benefit in reviewing potential RFA cases in a multidisciplinary fashion within our tumor board and would recommend other institutions to consider it,” he noted. In the absence of a tumor board, “at a minimum, a thyroid specialist should be involved in the evaluation of a potential thyroid RFA patient prior to ablation treatment,” he advised.
Tumor board was able to identify a small subset of patients for surgery
In his research presented at the 90th Annual Meeting of the American Thyroid Association (ATA), Dr. Lim and colleagues evaluated the tumor board’s efficacy in altering diagnosis and treatment plans in a retrospective review of cases presented to the board for RFA consideration since its inception in July 2020 through June 2021.
Over the study period, 65 patients with biopsy-proven benign thyroid nodules were newly referred for RFA, with 58 referred for mass effect symptoms and seven for autonomous function.
After the multidisciplinary review, about half of the cases, 37 (56.9%), were approved for RFA.
Of the remainder, 22 (33.8%) were determined to need additional studies, just two (3.0%) were recommended for surgery, and four (6.2%) were recommended to not receive any intervention.
Of the 22 cases recommended for additional studies, 15 were subsequently recommended for RFA and four were recommended to receive surgery due to suspicious clinical findings.
Of those that underwent surgery, two showed thyroid cancer on final pathology.
Among the nodules recommended to RFA, the average nodule volume was 15.1 mL, whereas the average volume for those recommended for surgery was 40.9 mL (P = .08).
No significant complications occurred among patients that underwent RFA or those who had surgery.
“The tumor board’s multidisciplinary review was able to identify high-risk features in some patients with benign biopsies. This led to a change in recommendation from RFA to surgery for possible malignancy in a small subset of patients,” Dr. Lim noted.
In a separate analysis, Dr. Lim and colleagues reported that, among patients treated with RFA (with a mean baseline nodule volume of 11.9 mL), mean nodule volume was 6.4 mL after 1 month, 4.5 mL after 3 months, and 3.8 mL at 6 months, which were all significantly reduced versus baseline (P < .001). Similar improvements were also reported in symptom and cosmetic scores at each timepoint (all P < .001).
There were no cases of postprocedural hypothyroidism or symptomatic thyrotoxicosis.
Underlining that patients can expect noticeable improvement in symptom scores by their 30-day visit, Dr. Lim noted that patients should be warned of some early swelling.
“It is important to inform patients that they may have swelling of their treated nodule immediately after the procedure, but this should subside within a few days,” he said.
Outpatient RFA safe and efficacious
In a separate study also presented at the meeting, three practitioners described their experiences with RFA in their outpatient thyroid practices in San Antonio; Santa Monica, California; and Gettysburg, Pennsylvania.
Overall, there were 68 cases involving benign, class II thyroid nodules, and the authors reported average procedure times of under an hour, with actual RFA time varying from 7 to 22 minutes.
Of note, for nodules larger than 4.5 cm, two procedures were necessary to achieve desired results.
Excluding the larger nodules requiring more than one procedure, there was an average decrease in nodule size of 48% at 1 month and a decrease of 82% after 3 months in more than 80% of cases.
None of the cases required surgery. There were no major complications, and all patients had preserved baseline thyroid function.
“This preliminary study of 68 patients shows how thyroid RFA is safe and efficacious when performed in an endocrine outpatient office practice,” Kathleen Hands, MD, of the Thyroid Center of South Texas, and coauthors concluded.
Insurance coverage an issue in U.S.
Among much larger studies demonstrating the safety and efficacy of RFA for benign nodules, a study of 450 Chinese patients published in January showed RFA to be superior to conventional thyroidectomy in terms of patient satisfaction, postoperative quality of life, and shorter hospital stay, although the caveat was it took longer to achieve nodule volume reduction.
But if RFA use is to become more widespread in the United States, a key obstacle is that insurance companies generally do not cover the procedure. Although patients in Dr. Lim’s analyses did have coverage, it didn’t come easily, he said.
“Thankfully, all of our patients have been approved by insurance, and no one has had to pay by themselves, but this has sometimes required multiple appeals to the insurance company,” Dr. Lim said.
“The American Association of Endocrine Surgeons and Society of Interventional Radiology are both working towards getting this valuable treatment more readily accepted by more insurance companies,” he said.
Dr. Lim and Dr. Singer have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
And in one case, a hospital has taken the unique step of forming a multidisciplinary thyroid nodule RFA tumor board, which helps in the often tricky decision-making process that is involved.
“Our multidisciplinary RFA tumor board has been invaluable in this process, and it is the only one of its kind in the nation that I’m aware of,” James Lim, MD, of the Division of Surgical Oncology, Thyroid, and Parathyroid Center at Oregon Health Sciences University (OHSU), told this news organization.
Dr. Lim reports receiving referrals from “all avenues, some from thyroid specialists and others from nonthyroid specialists such as primary care practitioners or patient self-referrals.”
“Because of this, our centralized process of multidisciplinary review ensures that each patient is evaluated thoroughly through each thyroid specialists’ lens to optimize patient outcomes,” noted Dr. Lim, an assistant professor of endocrine surgery.
The RFA tumor board consists of experts in all specialties involved in thyroid nodule assessment and treatment, including surgeons, interventional radiologists, and endocrinologists.
Just because you can, doesn’t mean you should
However, there should be some caution that although there is enthusiasm regarding this noninvasive alternative to surgery, there is another option, that of mere observation, which is appropriate in many cases of thyroid nodules and should not be overlooked.
“For a number of reasons, the key to keep in mind is that, just because we can do something doesn’t mean we should,” Michael Singer, MD, director of the Division of Thyroid & Parathyroid Surgery, Department of Otolaryngology – Head and Neck Surgery, at the Henry Ford Health System, Detroit, said in an interview.
While emphasizing that he believes RFA to be a promising technology that will likely benefit patients in the future, Dr. Singer voiced concern about the approach becoming an easy choice – particularly if profit is to be had – when observation is a clear alternative. “If RFA becomes seen as an opportunity to create revenue, potential conflicts of interest may arise,” he said.
“As it is not a major procedure with a dramatic risk profile, my concern is that some clinicians [could] adopt the attitude of ‘Why not do it?’ even when the indication is minimal or nonexistent,” he added.
Dr. Lim said he agrees that “any new medical technology requires thoughtful evaluation and appropriate patient selection in order to ensure optimal patient outcomes.”
That’s where the tumor board has been especially beneficial.
“We have found great benefit in reviewing potential RFA cases in a multidisciplinary fashion within our tumor board and would recommend other institutions to consider it,” he noted. In the absence of a tumor board, “at a minimum, a thyroid specialist should be involved in the evaluation of a potential thyroid RFA patient prior to ablation treatment,” he advised.
Tumor board was able to identify a small subset of patients for surgery
In his research presented at the 90th Annual Meeting of the American Thyroid Association (ATA), Dr. Lim and colleagues evaluated the tumor board’s efficacy in altering diagnosis and treatment plans in a retrospective review of cases presented to the board for RFA consideration since its inception in July 2020 through June 2021.
Over the study period, 65 patients with biopsy-proven benign thyroid nodules were newly referred for RFA, with 58 referred for mass effect symptoms and seven for autonomous function.
After the multidisciplinary review, about half of the cases, 37 (56.9%), were approved for RFA.
Of the remainder, 22 (33.8%) were determined to need additional studies, just two (3.0%) were recommended for surgery, and four (6.2%) were recommended to not receive any intervention.
Of the 22 cases recommended for additional studies, 15 were subsequently recommended for RFA and four were recommended to receive surgery due to suspicious clinical findings.
Of those that underwent surgery, two showed thyroid cancer on final pathology.
Among the nodules recommended to RFA, the average nodule volume was 15.1 mL, whereas the average volume for those recommended for surgery was 40.9 mL (P = .08).
No significant complications occurred among patients that underwent RFA or those who had surgery.
“The tumor board’s multidisciplinary review was able to identify high-risk features in some patients with benign biopsies. This led to a change in recommendation from RFA to surgery for possible malignancy in a small subset of patients,” Dr. Lim noted.
In a separate analysis, Dr. Lim and colleagues reported that, among patients treated with RFA (with a mean baseline nodule volume of 11.9 mL), mean nodule volume was 6.4 mL after 1 month, 4.5 mL after 3 months, and 3.8 mL at 6 months, which were all significantly reduced versus baseline (P < .001). Similar improvements were also reported in symptom and cosmetic scores at each timepoint (all P < .001).
There were no cases of postprocedural hypothyroidism or symptomatic thyrotoxicosis.
Underlining that patients can expect noticeable improvement in symptom scores by their 30-day visit, Dr. Lim noted that patients should be warned of some early swelling.
“It is important to inform patients that they may have swelling of their treated nodule immediately after the procedure, but this should subside within a few days,” he said.
Outpatient RFA safe and efficacious
In a separate study also presented at the meeting, three practitioners described their experiences with RFA in their outpatient thyroid practices in San Antonio; Santa Monica, California; and Gettysburg, Pennsylvania.
Overall, there were 68 cases involving benign, class II thyroid nodules, and the authors reported average procedure times of under an hour, with actual RFA time varying from 7 to 22 minutes.
Of note, for nodules larger than 4.5 cm, two procedures were necessary to achieve desired results.
Excluding the larger nodules requiring more than one procedure, there was an average decrease in nodule size of 48% at 1 month and a decrease of 82% after 3 months in more than 80% of cases.
None of the cases required surgery. There were no major complications, and all patients had preserved baseline thyroid function.
“This preliminary study of 68 patients shows how thyroid RFA is safe and efficacious when performed in an endocrine outpatient office practice,” Kathleen Hands, MD, of the Thyroid Center of South Texas, and coauthors concluded.
Insurance coverage an issue in U.S.
Among much larger studies demonstrating the safety and efficacy of RFA for benign nodules, a study of 450 Chinese patients published in January showed RFA to be superior to conventional thyroidectomy in terms of patient satisfaction, postoperative quality of life, and shorter hospital stay, although the caveat was it took longer to achieve nodule volume reduction.
But if RFA use is to become more widespread in the United States, a key obstacle is that insurance companies generally do not cover the procedure. Although patients in Dr. Lim’s analyses did have coverage, it didn’t come easily, he said.
“Thankfully, all of our patients have been approved by insurance, and no one has had to pay by themselves, but this has sometimes required multiple appeals to the insurance company,” Dr. Lim said.
“The American Association of Endocrine Surgeons and Society of Interventional Radiology are both working towards getting this valuable treatment more readily accepted by more insurance companies,” he said.
Dr. Lim and Dr. Singer have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
And in one case, a hospital has taken the unique step of forming a multidisciplinary thyroid nodule RFA tumor board, which helps in the often tricky decision-making process that is involved.
“Our multidisciplinary RFA tumor board has been invaluable in this process, and it is the only one of its kind in the nation that I’m aware of,” James Lim, MD, of the Division of Surgical Oncology, Thyroid, and Parathyroid Center at Oregon Health Sciences University (OHSU), told this news organization.
Dr. Lim reports receiving referrals from “all avenues, some from thyroid specialists and others from nonthyroid specialists such as primary care practitioners or patient self-referrals.”
“Because of this, our centralized process of multidisciplinary review ensures that each patient is evaluated thoroughly through each thyroid specialists’ lens to optimize patient outcomes,” noted Dr. Lim, an assistant professor of endocrine surgery.
The RFA tumor board consists of experts in all specialties involved in thyroid nodule assessment and treatment, including surgeons, interventional radiologists, and endocrinologists.
Just because you can, doesn’t mean you should
However, there should be some caution that although there is enthusiasm regarding this noninvasive alternative to surgery, there is another option, that of mere observation, which is appropriate in many cases of thyroid nodules and should not be overlooked.
“For a number of reasons, the key to keep in mind is that, just because we can do something doesn’t mean we should,” Michael Singer, MD, director of the Division of Thyroid & Parathyroid Surgery, Department of Otolaryngology – Head and Neck Surgery, at the Henry Ford Health System, Detroit, said in an interview.
While emphasizing that he believes RFA to be a promising technology that will likely benefit patients in the future, Dr. Singer voiced concern about the approach becoming an easy choice – particularly if profit is to be had – when observation is a clear alternative. “If RFA becomes seen as an opportunity to create revenue, potential conflicts of interest may arise,” he said.
“As it is not a major procedure with a dramatic risk profile, my concern is that some clinicians [could] adopt the attitude of ‘Why not do it?’ even when the indication is minimal or nonexistent,” he added.
Dr. Lim said he agrees that “any new medical technology requires thoughtful evaluation and appropriate patient selection in order to ensure optimal patient outcomes.”
That’s where the tumor board has been especially beneficial.
“We have found great benefit in reviewing potential RFA cases in a multidisciplinary fashion within our tumor board and would recommend other institutions to consider it,” he noted. In the absence of a tumor board, “at a minimum, a thyroid specialist should be involved in the evaluation of a potential thyroid RFA patient prior to ablation treatment,” he advised.
Tumor board was able to identify a small subset of patients for surgery
In his research presented at the 90th Annual Meeting of the American Thyroid Association (ATA), Dr. Lim and colleagues evaluated the tumor board’s efficacy in altering diagnosis and treatment plans in a retrospective review of cases presented to the board for RFA consideration since its inception in July 2020 through June 2021.
Over the study period, 65 patients with biopsy-proven benign thyroid nodules were newly referred for RFA, with 58 referred for mass effect symptoms and seven for autonomous function.
After the multidisciplinary review, about half of the cases, 37 (56.9%), were approved for RFA.
Of the remainder, 22 (33.8%) were determined to need additional studies, just two (3.0%) were recommended for surgery, and four (6.2%) were recommended to not receive any intervention.
Of the 22 cases recommended for additional studies, 15 were subsequently recommended for RFA and four were recommended to receive surgery due to suspicious clinical findings.
Of those that underwent surgery, two showed thyroid cancer on final pathology.
Among the nodules recommended to RFA, the average nodule volume was 15.1 mL, whereas the average volume for those recommended for surgery was 40.9 mL (P = .08).
No significant complications occurred among patients that underwent RFA or those who had surgery.
“The tumor board’s multidisciplinary review was able to identify high-risk features in some patients with benign biopsies. This led to a change in recommendation from RFA to surgery for possible malignancy in a small subset of patients,” Dr. Lim noted.
In a separate analysis, Dr. Lim and colleagues reported that, among patients treated with RFA (with a mean baseline nodule volume of 11.9 mL), mean nodule volume was 6.4 mL after 1 month, 4.5 mL after 3 months, and 3.8 mL at 6 months, which were all significantly reduced versus baseline (P < .001). Similar improvements were also reported in symptom and cosmetic scores at each timepoint (all P < .001).
There were no cases of postprocedural hypothyroidism or symptomatic thyrotoxicosis.
Underlining that patients can expect noticeable improvement in symptom scores by their 30-day visit, Dr. Lim noted that patients should be warned of some early swelling.
“It is important to inform patients that they may have swelling of their treated nodule immediately after the procedure, but this should subside within a few days,” he said.
Outpatient RFA safe and efficacious
In a separate study also presented at the meeting, three practitioners described their experiences with RFA in their outpatient thyroid practices in San Antonio; Santa Monica, California; and Gettysburg, Pennsylvania.
Overall, there were 68 cases involving benign, class II thyroid nodules, and the authors reported average procedure times of under an hour, with actual RFA time varying from 7 to 22 minutes.
Of note, for nodules larger than 4.5 cm, two procedures were necessary to achieve desired results.
Excluding the larger nodules requiring more than one procedure, there was an average decrease in nodule size of 48% at 1 month and a decrease of 82% after 3 months in more than 80% of cases.
None of the cases required surgery. There were no major complications, and all patients had preserved baseline thyroid function.
“This preliminary study of 68 patients shows how thyroid RFA is safe and efficacious when performed in an endocrine outpatient office practice,” Kathleen Hands, MD, of the Thyroid Center of South Texas, and coauthors concluded.
Insurance coverage an issue in U.S.
Among much larger studies demonstrating the safety and efficacy of RFA for benign nodules, a study of 450 Chinese patients published in January showed RFA to be superior to conventional thyroidectomy in terms of patient satisfaction, postoperative quality of life, and shorter hospital stay, although the caveat was it took longer to achieve nodule volume reduction.
But if RFA use is to become more widespread in the United States, a key obstacle is that insurance companies generally do not cover the procedure. Although patients in Dr. Lim’s analyses did have coverage, it didn’t come easily, he said.
“Thankfully, all of our patients have been approved by insurance, and no one has had to pay by themselves, but this has sometimes required multiple appeals to the insurance company,” Dr. Lim said.
“The American Association of Endocrine Surgeons and Society of Interventional Radiology are both working towards getting this valuable treatment more readily accepted by more insurance companies,” he said.
Dr. Lim and Dr. Singer have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Adding statins to steroids in thyroid eye disease improves outcomes
Treatment of Graves’ orbitopathy with statins in combination with glucocorticoids shows benefits among people with – and even without – high cholesterol, results from a new randomized clinical trial show.
“Our results [indicate] that adding atorvastatin to intravenous glucocorticoids seems to potentiate the effects of glucocorticoids,” senior author Michelle Marino, MD, associate professor of endocrinology in the department of clinical and experimental medicine at the University of Pisa, Italy, told this news organization.
“At least in hypercholesterolemic patients with moderate to severe and active Graves’ orbitopathy, atorvastatin should be considered in addition to intravenous glucocorticoids,” Dr. Marino said.
The study was presented by first author Giulia Lanzolla, MD, also of the University of Pisa and University Hospital of Pisa, at the virtual annual meeting of the American Thyroid Association.
Hypercholesterolemia, well known to promote systemic inflammation, has been previously linked to Graves’ orbitopathy, and the use of statins has also been shown to possibly provide a protective effect in the risk of developing the thyroid eye disease.
Furthermore, patients with Graves’ orbitopathy and high cholesterol levels, compared with those with normal cholesterol, have been shown to have poorer responses to treatment with glucocorticoids, which have long been the first line of treatment.
Asked for comment on the findings, Marius Stan, MD, a consultant in the division of endocrinology, diabetes, metabolism, and nutrition, Mayo Clinic, Rochester, Minn., said he didn’t think the outcome measure used – a composite of a variety of measures of thyroid eye disease – was best to truly understand the benefits.
Statins for Graves’ orbitopathy (STAGO) study details
For a better understanding of the effects with and without the addition of statins in a randomized trial, Dr. Lanzolla and colleagues enrolled 88 patients with high cholesterol and moderate to severe active Graves’ orbitopathy in the phase 2 STAGO trial.
Patients were randomized to two groups of 44 patients each to receive treatment either with intravenous (IV) methylprednisolone at 500 mg per week for 6 weeks, followed by 250 mg per week for another 6 weeks, in combination with atorvastatin 20 mg daily for 12 weeks, or methylprednisolone alone for 12 weeks.
The primary endpoint was a composite of Graves orbitopathy outcomes and included measures of exophthalmos, clinical activity score, eyelid aperture, diplopia, and visual acuity, as assessed in the modified intention-to-treat population.
The trial met the primary composite endpoint, with 51.2% of those treated with statins achieving the outcome (21 of 41) versus 28.2% (11 of 39) of those treated with glucocorticoids alone (odds ratio, 2.76; P = .03).
The study also achieved secondary outcomes, with 43.9% in the statin group having a response to treatment at 12 weeks versus 23% in the glucocorticoid group (OR 2.60; P = .05). The statin group also had a greater improvement in quality of life measures (P = .03).
The glucocorticoid-only group meanwhile had a significantly greater rate of Graves orbitopathy relapse at 24 weeks, with six relapses versus none in the statin group (15.3% vs. 0.0%; OR 0.06; P = .01).
There were no significant differences in low-density lipoprotein (LDL) cholesterol between those who did and did not respond to treatment in the statin group.
The most likely explanation for those findings is that “atorvastatin acts through its pleiotropic action, resulting in an anti-inflammatory effect,” Dr. Marino said.
“In addition, the effect may be related to the capability of statins to inhibit fibroblast proliferation,” Dr. Marino added.
“Total cholesterol had a behavior similar to LDL cholesterol, [while] HDL cholesterol did not change across the study.”
There were no major adverse events related to atorvastatin, with one patient in each group requiring treatment discontinuation.
In the rapidly evolving landscape of treatments for Graves’ orbitopathy, including the recent Food and Drug Administration approval for teprotumumab in thyroid eye disease, the potential role of statins remains to be seen, Dr. Marino noted.
“Graves’ orbitopathy is a rather complex disease, and in its mild to moderate forms it is very rare for a patient to require only a single treatment,” Dr. Marino explained. “Rehabilitative surgery is needed quite often once the disease is inactive.”
The authors noted that a composite overall Graves’ orbitopathy outcome was used as the primary endpoint because the alternative of a change in single eye features may not reflect a true modification of Graves’ orbitopathy and could be affected by a number of unrelated factors.
“By contrast, the composite evaluation offers a more realistic picture,” the authors wrote in the article, which was published in The Lancet Diabetes and Endocrinology.
Composite outcome not best way of assessing effects of statins
Dr. Stan extrapolated on his criticism of the trial.
“The study has interesting results but fails to show that any particular eye feature is benefited by the combination therapy, showing only the composite outcome to be improved,” he told this news organization.
“Unfortunately, that is hard to extrapolate to patient care, where one or another of Graves’ orbitopathy features are present and are the intended target of therapy,” he said.
Dr. Stan added that IV glucocorticoids are meanwhile also changing the landscape of treatment of thyroid eye disease.
“This ... current plan is to recommend a more individualized approach, depending on what is the main problem for that thyroid eye disease case,” he explained.
Dr. Marino noted that the authors are planning a double-blind, placebo-controlled phase 3 clinical trial of the statin/glucocorticoid combination to include patients regardless of their cholesterol levels.
The study received funding from Associazione Allievi Endocrinologia Pisana. The authors have reported no relevant financial relationships. Dr. Stan is on the advisory board for Horizon Pharma/Immunovant and provides general consulting for VasaraGen/Septerna and ValenzaBio/Medicxi.
A version of this article first appeared on Medscape.com.
Treatment of Graves’ orbitopathy with statins in combination with glucocorticoids shows benefits among people with – and even without – high cholesterol, results from a new randomized clinical trial show.
“Our results [indicate] that adding atorvastatin to intravenous glucocorticoids seems to potentiate the effects of glucocorticoids,” senior author Michelle Marino, MD, associate professor of endocrinology in the department of clinical and experimental medicine at the University of Pisa, Italy, told this news organization.
“At least in hypercholesterolemic patients with moderate to severe and active Graves’ orbitopathy, atorvastatin should be considered in addition to intravenous glucocorticoids,” Dr. Marino said.
The study was presented by first author Giulia Lanzolla, MD, also of the University of Pisa and University Hospital of Pisa, at the virtual annual meeting of the American Thyroid Association.
Hypercholesterolemia, well known to promote systemic inflammation, has been previously linked to Graves’ orbitopathy, and the use of statins has also been shown to possibly provide a protective effect in the risk of developing the thyroid eye disease.
Furthermore, patients with Graves’ orbitopathy and high cholesterol levels, compared with those with normal cholesterol, have been shown to have poorer responses to treatment with glucocorticoids, which have long been the first line of treatment.
Asked for comment on the findings, Marius Stan, MD, a consultant in the division of endocrinology, diabetes, metabolism, and nutrition, Mayo Clinic, Rochester, Minn., said he didn’t think the outcome measure used – a composite of a variety of measures of thyroid eye disease – was best to truly understand the benefits.
Statins for Graves’ orbitopathy (STAGO) study details
For a better understanding of the effects with and without the addition of statins in a randomized trial, Dr. Lanzolla and colleagues enrolled 88 patients with high cholesterol and moderate to severe active Graves’ orbitopathy in the phase 2 STAGO trial.
Patients were randomized to two groups of 44 patients each to receive treatment either with intravenous (IV) methylprednisolone at 500 mg per week for 6 weeks, followed by 250 mg per week for another 6 weeks, in combination with atorvastatin 20 mg daily for 12 weeks, or methylprednisolone alone for 12 weeks.
The primary endpoint was a composite of Graves orbitopathy outcomes and included measures of exophthalmos, clinical activity score, eyelid aperture, diplopia, and visual acuity, as assessed in the modified intention-to-treat population.
The trial met the primary composite endpoint, with 51.2% of those treated with statins achieving the outcome (21 of 41) versus 28.2% (11 of 39) of those treated with glucocorticoids alone (odds ratio, 2.76; P = .03).
The study also achieved secondary outcomes, with 43.9% in the statin group having a response to treatment at 12 weeks versus 23% in the glucocorticoid group (OR 2.60; P = .05). The statin group also had a greater improvement in quality of life measures (P = .03).
The glucocorticoid-only group meanwhile had a significantly greater rate of Graves orbitopathy relapse at 24 weeks, with six relapses versus none in the statin group (15.3% vs. 0.0%; OR 0.06; P = .01).
There were no significant differences in low-density lipoprotein (LDL) cholesterol between those who did and did not respond to treatment in the statin group.
The most likely explanation for those findings is that “atorvastatin acts through its pleiotropic action, resulting in an anti-inflammatory effect,” Dr. Marino said.
“In addition, the effect may be related to the capability of statins to inhibit fibroblast proliferation,” Dr. Marino added.
“Total cholesterol had a behavior similar to LDL cholesterol, [while] HDL cholesterol did not change across the study.”
There were no major adverse events related to atorvastatin, with one patient in each group requiring treatment discontinuation.
In the rapidly evolving landscape of treatments for Graves’ orbitopathy, including the recent Food and Drug Administration approval for teprotumumab in thyroid eye disease, the potential role of statins remains to be seen, Dr. Marino noted.
“Graves’ orbitopathy is a rather complex disease, and in its mild to moderate forms it is very rare for a patient to require only a single treatment,” Dr. Marino explained. “Rehabilitative surgery is needed quite often once the disease is inactive.”
The authors noted that a composite overall Graves’ orbitopathy outcome was used as the primary endpoint because the alternative of a change in single eye features may not reflect a true modification of Graves’ orbitopathy and could be affected by a number of unrelated factors.
“By contrast, the composite evaluation offers a more realistic picture,” the authors wrote in the article, which was published in The Lancet Diabetes and Endocrinology.
Composite outcome not best way of assessing effects of statins
Dr. Stan extrapolated on his criticism of the trial.
“The study has interesting results but fails to show that any particular eye feature is benefited by the combination therapy, showing only the composite outcome to be improved,” he told this news organization.
“Unfortunately, that is hard to extrapolate to patient care, where one or another of Graves’ orbitopathy features are present and are the intended target of therapy,” he said.
Dr. Stan added that IV glucocorticoids are meanwhile also changing the landscape of treatment of thyroid eye disease.
“This ... current plan is to recommend a more individualized approach, depending on what is the main problem for that thyroid eye disease case,” he explained.
Dr. Marino noted that the authors are planning a double-blind, placebo-controlled phase 3 clinical trial of the statin/glucocorticoid combination to include patients regardless of their cholesterol levels.
The study received funding from Associazione Allievi Endocrinologia Pisana. The authors have reported no relevant financial relationships. Dr. Stan is on the advisory board for Horizon Pharma/Immunovant and provides general consulting for VasaraGen/Septerna and ValenzaBio/Medicxi.
A version of this article first appeared on Medscape.com.
Treatment of Graves’ orbitopathy with statins in combination with glucocorticoids shows benefits among people with – and even without – high cholesterol, results from a new randomized clinical trial show.
“Our results [indicate] that adding atorvastatin to intravenous glucocorticoids seems to potentiate the effects of glucocorticoids,” senior author Michelle Marino, MD, associate professor of endocrinology in the department of clinical and experimental medicine at the University of Pisa, Italy, told this news organization.
“At least in hypercholesterolemic patients with moderate to severe and active Graves’ orbitopathy, atorvastatin should be considered in addition to intravenous glucocorticoids,” Dr. Marino said.
The study was presented by first author Giulia Lanzolla, MD, also of the University of Pisa and University Hospital of Pisa, at the virtual annual meeting of the American Thyroid Association.
Hypercholesterolemia, well known to promote systemic inflammation, has been previously linked to Graves’ orbitopathy, and the use of statins has also been shown to possibly provide a protective effect in the risk of developing the thyroid eye disease.
Furthermore, patients with Graves’ orbitopathy and high cholesterol levels, compared with those with normal cholesterol, have been shown to have poorer responses to treatment with glucocorticoids, which have long been the first line of treatment.
Asked for comment on the findings, Marius Stan, MD, a consultant in the division of endocrinology, diabetes, metabolism, and nutrition, Mayo Clinic, Rochester, Minn., said he didn’t think the outcome measure used – a composite of a variety of measures of thyroid eye disease – was best to truly understand the benefits.
Statins for Graves’ orbitopathy (STAGO) study details
For a better understanding of the effects with and without the addition of statins in a randomized trial, Dr. Lanzolla and colleagues enrolled 88 patients with high cholesterol and moderate to severe active Graves’ orbitopathy in the phase 2 STAGO trial.
Patients were randomized to two groups of 44 patients each to receive treatment either with intravenous (IV) methylprednisolone at 500 mg per week for 6 weeks, followed by 250 mg per week for another 6 weeks, in combination with atorvastatin 20 mg daily for 12 weeks, or methylprednisolone alone for 12 weeks.
The primary endpoint was a composite of Graves orbitopathy outcomes and included measures of exophthalmos, clinical activity score, eyelid aperture, diplopia, and visual acuity, as assessed in the modified intention-to-treat population.
The trial met the primary composite endpoint, with 51.2% of those treated with statins achieving the outcome (21 of 41) versus 28.2% (11 of 39) of those treated with glucocorticoids alone (odds ratio, 2.76; P = .03).
The study also achieved secondary outcomes, with 43.9% in the statin group having a response to treatment at 12 weeks versus 23% in the glucocorticoid group (OR 2.60; P = .05). The statin group also had a greater improvement in quality of life measures (P = .03).
The glucocorticoid-only group meanwhile had a significantly greater rate of Graves orbitopathy relapse at 24 weeks, with six relapses versus none in the statin group (15.3% vs. 0.0%; OR 0.06; P = .01).
There were no significant differences in low-density lipoprotein (LDL) cholesterol between those who did and did not respond to treatment in the statin group.
The most likely explanation for those findings is that “atorvastatin acts through its pleiotropic action, resulting in an anti-inflammatory effect,” Dr. Marino said.
“In addition, the effect may be related to the capability of statins to inhibit fibroblast proliferation,” Dr. Marino added.
“Total cholesterol had a behavior similar to LDL cholesterol, [while] HDL cholesterol did not change across the study.”
There were no major adverse events related to atorvastatin, with one patient in each group requiring treatment discontinuation.
In the rapidly evolving landscape of treatments for Graves’ orbitopathy, including the recent Food and Drug Administration approval for teprotumumab in thyroid eye disease, the potential role of statins remains to be seen, Dr. Marino noted.
“Graves’ orbitopathy is a rather complex disease, and in its mild to moderate forms it is very rare for a patient to require only a single treatment,” Dr. Marino explained. “Rehabilitative surgery is needed quite often once the disease is inactive.”
The authors noted that a composite overall Graves’ orbitopathy outcome was used as the primary endpoint because the alternative of a change in single eye features may not reflect a true modification of Graves’ orbitopathy and could be affected by a number of unrelated factors.
“By contrast, the composite evaluation offers a more realistic picture,” the authors wrote in the article, which was published in The Lancet Diabetes and Endocrinology.
Composite outcome not best way of assessing effects of statins
Dr. Stan extrapolated on his criticism of the trial.
“The study has interesting results but fails to show that any particular eye feature is benefited by the combination therapy, showing only the composite outcome to be improved,” he told this news organization.
“Unfortunately, that is hard to extrapolate to patient care, where one or another of Graves’ orbitopathy features are present and are the intended target of therapy,” he said.
Dr. Stan added that IV glucocorticoids are meanwhile also changing the landscape of treatment of thyroid eye disease.
“This ... current plan is to recommend a more individualized approach, depending on what is the main problem for that thyroid eye disease case,” he explained.
Dr. Marino noted that the authors are planning a double-blind, placebo-controlled phase 3 clinical trial of the statin/glucocorticoid combination to include patients regardless of their cholesterol levels.
The study received funding from Associazione Allievi Endocrinologia Pisana. The authors have reported no relevant financial relationships. Dr. Stan is on the advisory board for Horizon Pharma/Immunovant and provides general consulting for VasaraGen/Septerna and ValenzaBio/Medicxi.
A version of this article first appeared on Medscape.com.
FROM ATA 2021
Pelvic floor dysfunction imaging: New guidelines provide recommendations
New consensus guidelines from a multispecialty working group of the Pelvic Floor Disorders Consortium (PFDC) clear up inconsistencies in the use of magnetic resonance defecography (MRD) and provide universal recommendations on MRD technique, interpretation, reporting, and other factors.
“The consensus language used to describe pelvic floor disorders is critical, so as to allow the various experts who treat these patients [to] communicate and collaborate effectively with each other,” coauthor Liliana Bordeianou, MD, MPH, an associate professor of surgery at Harvard Medical School and chair of the Massachusetts General Hospital Colorectal and Pelvic Floor Centers, told this news organization.
“These diseases do not choose an arbitrary side in the pelvis,” she noted. “Instead, these diseases affect the entire pelvis and require a multidisciplinary and collaborative solution.”
MRD is a key component in that solution, providing dynamic evaluation of pelvic floor function and visualization of the complex interaction in pelvic compartments among patients with defecatory pelvic floor disorders, such as vaginal or uterine prolapse, constipation, incontinence, or other pelvic floor dysfunctions.
However, a key shortcoming has been a lack of consistency in nomenclature and the reporting of MRD findings among institutions and subspecialties.
Clinicians may wind up using different definitions for the same condition and different thresholds for grading severity, resulting in inconsistent communication not only between clinicians across institutions but even within the same institution, the report notes.
To address the situation, radiologists with the Pelvic Floor Dysfunction Disease Focused Panel of the Society of Abdominal Radiology (SAR) published recommendations on MRD protocol and technique in April.
However, even with that guidance, there has been significant variability in the interpretation and utilization of MRD findings among specialties outside of radiology.
The new report was therefore developed to include input from the broad variety of specialists involved in the treatment of patients with pelvic floor disorders, including colorectal surgeons, urogynecologists, urologists, gynecologists, gastroenterologists, radiologists, physiotherapists, and other advanced care practitioners.
“The goal of this effort was to create a universal set of recommendations and language for MRD technique, interpretation, and reporting that can be utilized and carry the same significance across disciplines,” write the authors of the report, published in the American Journal of Roentgenology.
One key area addressed in the report is a recommendation that MRD can be performed in either the upright or supine position, which has been a topic of inconsistency, said Brooke Gurland, MD, medical director of the Pelvic Health Center at Stanford University, California, a co-author on the consensus statement.
“Supine versus upright position was a source of debate, but ultimately there was a consensus that supine position was acceptable,” she told said in an interview.
Regarding positioning, the recommendations conclude that “given the variable results from different studies, consortium members agreed that it is acceptable to perform MRD in the supine position when upright MRD is not available.”
“Importantly, consortium experts stressed that it is very important that this imaging be performed after proper patient education on the purpose of the examination,” they note.
Other recommendations delve into contrast medium considerations, such as the recommendation that MRD does not require the routine use of vaginal contrast medium for adequate imaging of pathology.
And guidance on the technique and grading of relevant pathology include a recommendation to use the pubococcygeal line (PCL) as a point of reference to quantify the prolapse of organs in all compartments of the pelvic floor.
“There is an increasing appreciation that most patients with pelvic organ prolapse experience dual or even triple compartment pathology, making it important to describe the observations in all three compartments to ensure the mobilization of the appropriate team of experts to treat the patient,” the authors note.
The consensus report features an interpretative template providing synopses of the recommendations, which can be adjusted and modified according to additional radiologic information, as well as individualized patient information or clinician preferences.
However, “the suggested verbiage and steps should be advocated as the minimum requirements when performing and interpreting MRD in patients with evacuation disorders of the pelvic floor,” the authors note.
Dr. Gurland added that, in addition to providing benefits in the present utilization of MRD, the clearer guidelines should help advance its use to improve patient care in the future.
“Standardizing imaging techniques, reporting, and language is critical to improving our understanding and then developing therapies for pelvic floor disorders,” she said.
“In the future, correlating MRD with surgical outcomes and identifying modifiable risk factors will improve patient care.”
In addition to being published in the AJR, the report was published concurrently in the journals Diseases of the Colon & Rectum, International Urogynecology Journal, and Female Pelvic Medicine and Reconstructive Surgery.
The authors of the guidelines have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
New consensus guidelines from a multispecialty working group of the Pelvic Floor Disorders Consortium (PFDC) clear up inconsistencies in the use of magnetic resonance defecography (MRD) and provide universal recommendations on MRD technique, interpretation, reporting, and other factors.
“The consensus language used to describe pelvic floor disorders is critical, so as to allow the various experts who treat these patients [to] communicate and collaborate effectively with each other,” coauthor Liliana Bordeianou, MD, MPH, an associate professor of surgery at Harvard Medical School and chair of the Massachusetts General Hospital Colorectal and Pelvic Floor Centers, told this news organization.
“These diseases do not choose an arbitrary side in the pelvis,” she noted. “Instead, these diseases affect the entire pelvis and require a multidisciplinary and collaborative solution.”
MRD is a key component in that solution, providing dynamic evaluation of pelvic floor function and visualization of the complex interaction in pelvic compartments among patients with defecatory pelvic floor disorders, such as vaginal or uterine prolapse, constipation, incontinence, or other pelvic floor dysfunctions.
However, a key shortcoming has been a lack of consistency in nomenclature and the reporting of MRD findings among institutions and subspecialties.
Clinicians may wind up using different definitions for the same condition and different thresholds for grading severity, resulting in inconsistent communication not only between clinicians across institutions but even within the same institution, the report notes.
To address the situation, radiologists with the Pelvic Floor Dysfunction Disease Focused Panel of the Society of Abdominal Radiology (SAR) published recommendations on MRD protocol and technique in April.
However, even with that guidance, there has been significant variability in the interpretation and utilization of MRD findings among specialties outside of radiology.
The new report was therefore developed to include input from the broad variety of specialists involved in the treatment of patients with pelvic floor disorders, including colorectal surgeons, urogynecologists, urologists, gynecologists, gastroenterologists, radiologists, physiotherapists, and other advanced care practitioners.
“The goal of this effort was to create a universal set of recommendations and language for MRD technique, interpretation, and reporting that can be utilized and carry the same significance across disciplines,” write the authors of the report, published in the American Journal of Roentgenology.
One key area addressed in the report is a recommendation that MRD can be performed in either the upright or supine position, which has been a topic of inconsistency, said Brooke Gurland, MD, medical director of the Pelvic Health Center at Stanford University, California, a co-author on the consensus statement.
“Supine versus upright position was a source of debate, but ultimately there was a consensus that supine position was acceptable,” she told said in an interview.
Regarding positioning, the recommendations conclude that “given the variable results from different studies, consortium members agreed that it is acceptable to perform MRD in the supine position when upright MRD is not available.”
“Importantly, consortium experts stressed that it is very important that this imaging be performed after proper patient education on the purpose of the examination,” they note.
Other recommendations delve into contrast medium considerations, such as the recommendation that MRD does not require the routine use of vaginal contrast medium for adequate imaging of pathology.
And guidance on the technique and grading of relevant pathology include a recommendation to use the pubococcygeal line (PCL) as a point of reference to quantify the prolapse of organs in all compartments of the pelvic floor.
“There is an increasing appreciation that most patients with pelvic organ prolapse experience dual or even triple compartment pathology, making it important to describe the observations in all three compartments to ensure the mobilization of the appropriate team of experts to treat the patient,” the authors note.
The consensus report features an interpretative template providing synopses of the recommendations, which can be adjusted and modified according to additional radiologic information, as well as individualized patient information or clinician preferences.
However, “the suggested verbiage and steps should be advocated as the minimum requirements when performing and interpreting MRD in patients with evacuation disorders of the pelvic floor,” the authors note.
Dr. Gurland added that, in addition to providing benefits in the present utilization of MRD, the clearer guidelines should help advance its use to improve patient care in the future.
“Standardizing imaging techniques, reporting, and language is critical to improving our understanding and then developing therapies for pelvic floor disorders,” she said.
“In the future, correlating MRD with surgical outcomes and identifying modifiable risk factors will improve patient care.”
In addition to being published in the AJR, the report was published concurrently in the journals Diseases of the Colon & Rectum, International Urogynecology Journal, and Female Pelvic Medicine and Reconstructive Surgery.
The authors of the guidelines have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
New consensus guidelines from a multispecialty working group of the Pelvic Floor Disorders Consortium (PFDC) clear up inconsistencies in the use of magnetic resonance defecography (MRD) and provide universal recommendations on MRD technique, interpretation, reporting, and other factors.
“The consensus language used to describe pelvic floor disorders is critical, so as to allow the various experts who treat these patients [to] communicate and collaborate effectively with each other,” coauthor Liliana Bordeianou, MD, MPH, an associate professor of surgery at Harvard Medical School and chair of the Massachusetts General Hospital Colorectal and Pelvic Floor Centers, told this news organization.
“These diseases do not choose an arbitrary side in the pelvis,” she noted. “Instead, these diseases affect the entire pelvis and require a multidisciplinary and collaborative solution.”
MRD is a key component in that solution, providing dynamic evaluation of pelvic floor function and visualization of the complex interaction in pelvic compartments among patients with defecatory pelvic floor disorders, such as vaginal or uterine prolapse, constipation, incontinence, or other pelvic floor dysfunctions.
However, a key shortcoming has been a lack of consistency in nomenclature and the reporting of MRD findings among institutions and subspecialties.
Clinicians may wind up using different definitions for the same condition and different thresholds for grading severity, resulting in inconsistent communication not only between clinicians across institutions but even within the same institution, the report notes.
To address the situation, radiologists with the Pelvic Floor Dysfunction Disease Focused Panel of the Society of Abdominal Radiology (SAR) published recommendations on MRD protocol and technique in April.
However, even with that guidance, there has been significant variability in the interpretation and utilization of MRD findings among specialties outside of radiology.
The new report was therefore developed to include input from the broad variety of specialists involved in the treatment of patients with pelvic floor disorders, including colorectal surgeons, urogynecologists, urologists, gynecologists, gastroenterologists, radiologists, physiotherapists, and other advanced care practitioners.
“The goal of this effort was to create a universal set of recommendations and language for MRD technique, interpretation, and reporting that can be utilized and carry the same significance across disciplines,” write the authors of the report, published in the American Journal of Roentgenology.
One key area addressed in the report is a recommendation that MRD can be performed in either the upright or supine position, which has been a topic of inconsistency, said Brooke Gurland, MD, medical director of the Pelvic Health Center at Stanford University, California, a co-author on the consensus statement.
“Supine versus upright position was a source of debate, but ultimately there was a consensus that supine position was acceptable,” she told said in an interview.
Regarding positioning, the recommendations conclude that “given the variable results from different studies, consortium members agreed that it is acceptable to perform MRD in the supine position when upright MRD is not available.”
“Importantly, consortium experts stressed that it is very important that this imaging be performed after proper patient education on the purpose of the examination,” they note.
Other recommendations delve into contrast medium considerations, such as the recommendation that MRD does not require the routine use of vaginal contrast medium for adequate imaging of pathology.
And guidance on the technique and grading of relevant pathology include a recommendation to use the pubococcygeal line (PCL) as a point of reference to quantify the prolapse of organs in all compartments of the pelvic floor.
“There is an increasing appreciation that most patients with pelvic organ prolapse experience dual or even triple compartment pathology, making it important to describe the observations in all three compartments to ensure the mobilization of the appropriate team of experts to treat the patient,” the authors note.
The consensus report features an interpretative template providing synopses of the recommendations, which can be adjusted and modified according to additional radiologic information, as well as individualized patient information or clinician preferences.
However, “the suggested verbiage and steps should be advocated as the minimum requirements when performing and interpreting MRD in patients with evacuation disorders of the pelvic floor,” the authors note.
Dr. Gurland added that, in addition to providing benefits in the present utilization of MRD, the clearer guidelines should help advance its use to improve patient care in the future.
“Standardizing imaging techniques, reporting, and language is critical to improving our understanding and then developing therapies for pelvic floor disorders,” she said.
“In the future, correlating MRD with surgical outcomes and identifying modifiable risk factors will improve patient care.”
In addition to being published in the AJR, the report was published concurrently in the journals Diseases of the Colon & Rectum, International Urogynecology Journal, and Female Pelvic Medicine and Reconstructive Surgery.
The authors of the guidelines have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Cancer risk after radioiodine for hyperthyroidism ‘small’: Meta-analysis
Amid ongoing debate over potential adverse effects of radioactive iodine (RAI) in the treatment of hyperthyroidism, a new meta-analysis shows no significant increase in the risk of cancer or cancer mortality in the vast majority of cases, with an increased dose-response risk with higher doses shown in some studies.
“These findings suggest that radiation-induced cancer risks following RAI therapy for hyperthyroidism are small and, in observational studies, may only be detectable at higher levels of administered dose,” report the authors of the analysis, published Sept. 27 in JAMA Network Open.
In a commentary published along with the study, Bernadette Biondi, MD, noted that, despite some limitations, “the current analysis from recent literature studies is reassuring on the potential negative effects of RAI”.
“These data can help reduce anxiety in both patients and clinicians as to the risk of cancer after RAI.”
Martin A. Walter, MD, agreed. “When including nearly a half-million patients into the analysis, there is no significant increase of risk for secondary cancers after radioiodine therapy for hyperthyroidism,” Dr. Walter, who was a coauthor on the American Thyroid Association’s guidelines for the diagnosis and management of hyperthyroidism (Thyroid. 2016 Oct;26:1343-421), told this news organization.
“For me, this paper is rather reassuring of the safety of the therapy,” he added.
Though used in the treatment of hyperthyroidism for more than 7 decades, the frequent use of RAI continues to generate concern of potential carcinogenic effects, with some previous studies linking the treatment with subsequent malignant neoplasms, while others have shown no risk.
However, the potential role of a dose-response effect on the cancer risk has not been well explored, the authors note.
For their meta-analysis, Sung Ryul Shim, PhD, of the department of preventive medicine, Korea University, Seoul, South Korea, and colleagues identified 12 studies including 479,452 participants that involved evaluation of cancer incidence and mortality with exposure versus nonexposure to RAI therapy for hyperthyroidism.
Overall, the results showed no significant difference in the pooled cancer incidence ratio between those who were and were not exposed to RAI therapy (incidence ratio, 1.02), and there also were no significant differences in mortality (IR, 0.98).
There were no increases in the risk of any specific cancers with the exception of thyroid cancer, which had a higher incidence among those with RAI treatment (1.86), and more than twice the risk of mortality (2.22).
Two studies did report a linear dose-response association between RAI for hyperthyroidism and breast cancer mortality (1.35 per 370 MBq; P = .03) and solid cancer mortality (1.14 per 370 MBq; P = .01).
Among them was a 2019 study, using data on nearly 19,000 patients from the multicenter Cooperative Thyrotoxicosis Therapy Follow-up Study, showing a dose-response effect on solid-cancer mortality that the study authors described as “modest.”
“For every 1,000 patients with hyperthyroidism receiving typical doses to the stomach (150-250 mGy), an estimated lifetime excess of 19-32 solid cancer deaths could occur,” the study concluded.
Caveats surrounding the issue include that hyperthyroidism itself has been associated with an increased risk of cancer, suggesting a potential role of an excess of thyroid hormone excess on cancer risk.
“The underlying conditions of the thyroid gland could be another possible reason for the increased risk of malignant thyroid tumor after RAI for hyperthyroidism,” the investigators of the current study write.
“Thyroid-stimulating hormone and thyroid-stimulating antibodies, present in Graves disease, may play a role in carcinogenesis and tumoral growth, and hyperthyroidism is associated with a high incidence of thyroid carcinoma,” they add.
Tumors developing from hyperthyroid tissue show aggressive behavior, they add, and note that an increased overall risk of cancer and greater cancer mortality has been also reported with the alternative of antithyroid drug therapy when compared with RAI.
Nevertheless, considering the dose-response risk observed in the two studies, the authors and Dr. Bondi agree that more rigorous studies are needed to investigate the issue.
“The limited quality of the evidence in the literature on the adverse effects of RAI underlines the need for future randomized clinical trials in this area,” writes Dr. Bondi, of the department of clinical medicine and surgery, University of Naples (Italy) Federico II, in her editorial.
In further commenting, Dr. Walter, of the department of nuclear medicine, University Hospital, University of Geneva, agreed that the benefits of treatment need to be weighed against the risks.
“There is always caution used when deciding for a medical therapy, including radioiodine therapy,” he added. “It has to be emphasized though, that poorly controlled hyperthyroidism is a serious condition that, for instance, can lead to arrhythmia, and that in elderly patients is associated with increased mortality,” Dr, Walter cautioned.
“Statistically significant does not always mean clinically relevant, and the benefits clearly outweigh the risks.”
The authors, Dr. Bondi, and Dr. Walter had no disclosures to report.
Amid ongoing debate over potential adverse effects of radioactive iodine (RAI) in the treatment of hyperthyroidism, a new meta-analysis shows no significant increase in the risk of cancer or cancer mortality in the vast majority of cases, with an increased dose-response risk with higher doses shown in some studies.
“These findings suggest that radiation-induced cancer risks following RAI therapy for hyperthyroidism are small and, in observational studies, may only be detectable at higher levels of administered dose,” report the authors of the analysis, published Sept. 27 in JAMA Network Open.
In a commentary published along with the study, Bernadette Biondi, MD, noted that, despite some limitations, “the current analysis from recent literature studies is reassuring on the potential negative effects of RAI”.
“These data can help reduce anxiety in both patients and clinicians as to the risk of cancer after RAI.”
Martin A. Walter, MD, agreed. “When including nearly a half-million patients into the analysis, there is no significant increase of risk for secondary cancers after radioiodine therapy for hyperthyroidism,” Dr. Walter, who was a coauthor on the American Thyroid Association’s guidelines for the diagnosis and management of hyperthyroidism (Thyroid. 2016 Oct;26:1343-421), told this news organization.
“For me, this paper is rather reassuring of the safety of the therapy,” he added.
Though used in the treatment of hyperthyroidism for more than 7 decades, the frequent use of RAI continues to generate concern of potential carcinogenic effects, with some previous studies linking the treatment with subsequent malignant neoplasms, while others have shown no risk.
However, the potential role of a dose-response effect on the cancer risk has not been well explored, the authors note.
For their meta-analysis, Sung Ryul Shim, PhD, of the department of preventive medicine, Korea University, Seoul, South Korea, and colleagues identified 12 studies including 479,452 participants that involved evaluation of cancer incidence and mortality with exposure versus nonexposure to RAI therapy for hyperthyroidism.
Overall, the results showed no significant difference in the pooled cancer incidence ratio between those who were and were not exposed to RAI therapy (incidence ratio, 1.02), and there also were no significant differences in mortality (IR, 0.98).
There were no increases in the risk of any specific cancers with the exception of thyroid cancer, which had a higher incidence among those with RAI treatment (1.86), and more than twice the risk of mortality (2.22).
Two studies did report a linear dose-response association between RAI for hyperthyroidism and breast cancer mortality (1.35 per 370 MBq; P = .03) and solid cancer mortality (1.14 per 370 MBq; P = .01).
Among them was a 2019 study, using data on nearly 19,000 patients from the multicenter Cooperative Thyrotoxicosis Therapy Follow-up Study, showing a dose-response effect on solid-cancer mortality that the study authors described as “modest.”
“For every 1,000 patients with hyperthyroidism receiving typical doses to the stomach (150-250 mGy), an estimated lifetime excess of 19-32 solid cancer deaths could occur,” the study concluded.
Caveats surrounding the issue include that hyperthyroidism itself has been associated with an increased risk of cancer, suggesting a potential role of an excess of thyroid hormone excess on cancer risk.
“The underlying conditions of the thyroid gland could be another possible reason for the increased risk of malignant thyroid tumor after RAI for hyperthyroidism,” the investigators of the current study write.
“Thyroid-stimulating hormone and thyroid-stimulating antibodies, present in Graves disease, may play a role in carcinogenesis and tumoral growth, and hyperthyroidism is associated with a high incidence of thyroid carcinoma,” they add.
Tumors developing from hyperthyroid tissue show aggressive behavior, they add, and note that an increased overall risk of cancer and greater cancer mortality has been also reported with the alternative of antithyroid drug therapy when compared with RAI.
Nevertheless, considering the dose-response risk observed in the two studies, the authors and Dr. Bondi agree that more rigorous studies are needed to investigate the issue.
“The limited quality of the evidence in the literature on the adverse effects of RAI underlines the need for future randomized clinical trials in this area,” writes Dr. Bondi, of the department of clinical medicine and surgery, University of Naples (Italy) Federico II, in her editorial.
In further commenting, Dr. Walter, of the department of nuclear medicine, University Hospital, University of Geneva, agreed that the benefits of treatment need to be weighed against the risks.
“There is always caution used when deciding for a medical therapy, including radioiodine therapy,” he added. “It has to be emphasized though, that poorly controlled hyperthyroidism is a serious condition that, for instance, can lead to arrhythmia, and that in elderly patients is associated with increased mortality,” Dr, Walter cautioned.
“Statistically significant does not always mean clinically relevant, and the benefits clearly outweigh the risks.”
The authors, Dr. Bondi, and Dr. Walter had no disclosures to report.
Amid ongoing debate over potential adverse effects of radioactive iodine (RAI) in the treatment of hyperthyroidism, a new meta-analysis shows no significant increase in the risk of cancer or cancer mortality in the vast majority of cases, with an increased dose-response risk with higher doses shown in some studies.
“These findings suggest that radiation-induced cancer risks following RAI therapy for hyperthyroidism are small and, in observational studies, may only be detectable at higher levels of administered dose,” report the authors of the analysis, published Sept. 27 in JAMA Network Open.
In a commentary published along with the study, Bernadette Biondi, MD, noted that, despite some limitations, “the current analysis from recent literature studies is reassuring on the potential negative effects of RAI”.
“These data can help reduce anxiety in both patients and clinicians as to the risk of cancer after RAI.”
Martin A. Walter, MD, agreed. “When including nearly a half-million patients into the analysis, there is no significant increase of risk for secondary cancers after radioiodine therapy for hyperthyroidism,” Dr. Walter, who was a coauthor on the American Thyroid Association’s guidelines for the diagnosis and management of hyperthyroidism (Thyroid. 2016 Oct;26:1343-421), told this news organization.
“For me, this paper is rather reassuring of the safety of the therapy,” he added.
Though used in the treatment of hyperthyroidism for more than 7 decades, the frequent use of RAI continues to generate concern of potential carcinogenic effects, with some previous studies linking the treatment with subsequent malignant neoplasms, while others have shown no risk.
However, the potential role of a dose-response effect on the cancer risk has not been well explored, the authors note.
For their meta-analysis, Sung Ryul Shim, PhD, of the department of preventive medicine, Korea University, Seoul, South Korea, and colleagues identified 12 studies including 479,452 participants that involved evaluation of cancer incidence and mortality with exposure versus nonexposure to RAI therapy for hyperthyroidism.
Overall, the results showed no significant difference in the pooled cancer incidence ratio between those who were and were not exposed to RAI therapy (incidence ratio, 1.02), and there also were no significant differences in mortality (IR, 0.98).
There were no increases in the risk of any specific cancers with the exception of thyroid cancer, which had a higher incidence among those with RAI treatment (1.86), and more than twice the risk of mortality (2.22).
Two studies did report a linear dose-response association between RAI for hyperthyroidism and breast cancer mortality (1.35 per 370 MBq; P = .03) and solid cancer mortality (1.14 per 370 MBq; P = .01).
Among them was a 2019 study, using data on nearly 19,000 patients from the multicenter Cooperative Thyrotoxicosis Therapy Follow-up Study, showing a dose-response effect on solid-cancer mortality that the study authors described as “modest.”
“For every 1,000 patients with hyperthyroidism receiving typical doses to the stomach (150-250 mGy), an estimated lifetime excess of 19-32 solid cancer deaths could occur,” the study concluded.
Caveats surrounding the issue include that hyperthyroidism itself has been associated with an increased risk of cancer, suggesting a potential role of an excess of thyroid hormone excess on cancer risk.
“The underlying conditions of the thyroid gland could be another possible reason for the increased risk of malignant thyroid tumor after RAI for hyperthyroidism,” the investigators of the current study write.
“Thyroid-stimulating hormone and thyroid-stimulating antibodies, present in Graves disease, may play a role in carcinogenesis and tumoral growth, and hyperthyroidism is associated with a high incidence of thyroid carcinoma,” they add.
Tumors developing from hyperthyroid tissue show aggressive behavior, they add, and note that an increased overall risk of cancer and greater cancer mortality has been also reported with the alternative of antithyroid drug therapy when compared with RAI.
Nevertheless, considering the dose-response risk observed in the two studies, the authors and Dr. Bondi agree that more rigorous studies are needed to investigate the issue.
“The limited quality of the evidence in the literature on the adverse effects of RAI underlines the need for future randomized clinical trials in this area,” writes Dr. Bondi, of the department of clinical medicine and surgery, University of Naples (Italy) Federico II, in her editorial.
In further commenting, Dr. Walter, of the department of nuclear medicine, University Hospital, University of Geneva, agreed that the benefits of treatment need to be weighed against the risks.
“There is always caution used when deciding for a medical therapy, including radioiodine therapy,” he added. “It has to be emphasized though, that poorly controlled hyperthyroidism is a serious condition that, for instance, can lead to arrhythmia, and that in elderly patients is associated with increased mortality,” Dr, Walter cautioned.
“Statistically significant does not always mean clinically relevant, and the benefits clearly outweigh the risks.”
The authors, Dr. Bondi, and Dr. Walter had no disclosures to report.
FROM JAMA OPEN NETWORK
Menopause society issues first osteoporosis advice in 10 years
In the first revision to its guidance on the management of osteoporosis in a decade, the North American Menopause Society has issued an updated position statement addressing evolving evidence on osteoporosis issues ranging from screening and risk assessment to appropriate use of preventive therapy in postmenopausal women.
“Since the 2010 statement, there have been important new developments in our field, including better delineation of risk factors for fracture, resulting in better strategies for assessing fracture risk,” Michael R. McClung, MD, who is a NAMS board member and colead of the editorial panel for the 2021 position statement, told this news organization. Dr. McClung is also director emeritus of the Oregon Osteoporosis Center in Portland.
“There is much more information about the long-term safety of therapies,” he added. Dr. McClung also noted “the availability of four new drugs for the prevention and treatment of osteoporosis and clinical experience informing us of the effects of using different treatments in various sequences.”
Osteoporosis is substantially underdiagnosed and undertreated
A basis for the update, recently published in Menopause: The Journal of the North American Menopause Society, is the need to tackle the troubling fact that approximately half of postmenopausal women will experience a fracture related to osteoporosis in their lifetime, yet the condition is “substantially underdiagnosed and undertreated,” NAMS underscores.
With that in mind, osteoporosis should be considered by practitioners treating menopausal and postmenopausal women at all levels of care.
“All physicians and advanced care providers caring for postmenopausal women should be comfortable assessing and managing their patients with, or at risk for, fractures,” Dr. McClung added.
Osteoporosis prevention in young menopausal women
The NAMS statement covers a broad range of issues, and while most recommendations generally follow those of other societies’ guidelines, a unique aspect is the emphasis on preventing osteoporosis in young menopausal women with estrogen or other drugs.
While underscoring that all menopausal women should be encouraged to adopt healthy lifestyles, with good diets and physical activity to reduce the risk of bone loss and fractures, pharmacologic interventions also have a role, NAMS says.
Though long an issue of debate, NAMS voices support for estrogen therapy as having an important role in osteoporosis prevention, as estrogen deficiency is the principal cause of bone loss in postmenopausal women.
“Hormone therapy is the most appropriate choice to prevent bone loss at the time of menopause for healthy women, particularly those who have menopause symptoms,” the group states. Drug interventions are specifically supported in women with premature menopause, at least until the average age of natural menopause, in addition to those with low bone mineral density (BMD) (T-score < –1.0) and those experiencing relatively rapid bone loss related to acute estrogen deficiency in the menopause transition or on discontinuing estrogen therapy.
“Although using drugs to prevent osteoporosis is not included in national osteoporosis guidelines, a strong clinical argument can be made for doing so, especially in women who come to menopause with low bone mass,” the report states.
And therapy is also recommended if patients have a low BMD and other risk factors for fracture, such as family history, but do not meet the criteria for osteoporosis treatment.
Ultimately, clinicians should work with patients when deciding the options, Dr. McClung said.
“After carefully weighing the small risks associated with hormone therapy or other therapies begun at the time of menopause, menopause practitioners and their patients can and should make informed decisions about the use of Food and Drug Administration–approved medications to prevent osteoporosis in women who are at risk for developing that condition,” he noted, adding that his view on the matter is his own and not necessarily that of NAMS.
New treatments endorsed for high-risk patients to avoid ‘bone attack’
While most patients are treated for osteoporosis with antiremodeling drugs such as bisphosphonates and denosumab, NAMS endorses “a new paradigm of beginning treatment with a bone-building agent followed by an antiremodeling agent” for women at very high risk of fracture.
“Consider osteoanabolic therapies for patients at very high risk of fracture, including older women with recent fractures, T-scores –3.0 and lower, or multiple other risk factors,” the statement suggests.
Among those at highest risk are women who have sustained a first fracture.
“A recent fracture in a postmenopausal woman is the strongest risk factor for another fracture,” Dr. McClung said.
In fact, “having a fracture should be thought of and assessed as a ‘bone attack,’ ” he asserted.
Therapy is recommended in such cases to rapidly increase bone density and reduce their subsequent fracture risk.
“For these patients, osteoanabolic or bone-building agents are more effective than bisphosphonates and are recommended as initial therapy,” Dr. McClung noted.
Treatment discontinuation?
On the issue of drug holidays and when or whether to stop therapy, as no therapies cure osteoporosis, medications should not be permanently stopped, even if bone density increases, NAMS recommends.
“By analogy, we do not stop diabetes therapy when A1c levels become normal,” Dr. McClung noted.
“Because the benefits of therapy on bone density and fracture protection wane, quickly for nonbisphosphonates and more slowly with bisphosphonates, short-term therapy, for instance 5 years, is not optimal treatment,” he said.
While the short-term interruption of bisphosphonate therapy may be considered in some patients, “the concept of ‘drug holidays’ does not pertain to nonbisphosphonate drugs,” Dr. McClung said.
NAMS adds that management of therapeutic choices should instead be ongoing.
“During therapy, reevaluate the treatment goals and the choice of medication on an ongoing basis through periodic medical examination and follow-up BMD testing,” NAMS recommends.
In terms of assessment, the measurement of bone mineral density while on treatment can gauge the current risk of fracture, and NAMS supports the use of the T-score at the hip as an appropriate clinical target in guiding choices of therapy.
Ultimately, “effective tools for diagnosing osteoporosis and assessing fracture risk are available, and well-studied strategies exist for managing bone health in women at both low and high risk of fracture,” NAMS concludes.
“By individualizing treatment approaches and monitoring and adjusting those approaches if the clinical picture changes, the consequences of osteoporosis on a menopausal woman’s activity and well-being can be minimized.”
Dr. McClung has reported receiving consulting fees from Amgen and Myovant, and honorarium for speaking from Amgen and Alexon. He serves on the boards of NAMS and the International Osteoporosis Foundation.
A version of this article first appeared on Medscape.com.
In the first revision to its guidance on the management of osteoporosis in a decade, the North American Menopause Society has issued an updated position statement addressing evolving evidence on osteoporosis issues ranging from screening and risk assessment to appropriate use of preventive therapy in postmenopausal women.
“Since the 2010 statement, there have been important new developments in our field, including better delineation of risk factors for fracture, resulting in better strategies for assessing fracture risk,” Michael R. McClung, MD, who is a NAMS board member and colead of the editorial panel for the 2021 position statement, told this news organization. Dr. McClung is also director emeritus of the Oregon Osteoporosis Center in Portland.
“There is much more information about the long-term safety of therapies,” he added. Dr. McClung also noted “the availability of four new drugs for the prevention and treatment of osteoporosis and clinical experience informing us of the effects of using different treatments in various sequences.”
Osteoporosis is substantially underdiagnosed and undertreated
A basis for the update, recently published in Menopause: The Journal of the North American Menopause Society, is the need to tackle the troubling fact that approximately half of postmenopausal women will experience a fracture related to osteoporosis in their lifetime, yet the condition is “substantially underdiagnosed and undertreated,” NAMS underscores.
With that in mind, osteoporosis should be considered by practitioners treating menopausal and postmenopausal women at all levels of care.
“All physicians and advanced care providers caring for postmenopausal women should be comfortable assessing and managing their patients with, or at risk for, fractures,” Dr. McClung added.
Osteoporosis prevention in young menopausal women
The NAMS statement covers a broad range of issues, and while most recommendations generally follow those of other societies’ guidelines, a unique aspect is the emphasis on preventing osteoporosis in young menopausal women with estrogen or other drugs.
While underscoring that all menopausal women should be encouraged to adopt healthy lifestyles, with good diets and physical activity to reduce the risk of bone loss and fractures, pharmacologic interventions also have a role, NAMS says.
Though long an issue of debate, NAMS voices support for estrogen therapy as having an important role in osteoporosis prevention, as estrogen deficiency is the principal cause of bone loss in postmenopausal women.
“Hormone therapy is the most appropriate choice to prevent bone loss at the time of menopause for healthy women, particularly those who have menopause symptoms,” the group states. Drug interventions are specifically supported in women with premature menopause, at least until the average age of natural menopause, in addition to those with low bone mineral density (BMD) (T-score < –1.0) and those experiencing relatively rapid bone loss related to acute estrogen deficiency in the menopause transition or on discontinuing estrogen therapy.
“Although using drugs to prevent osteoporosis is not included in national osteoporosis guidelines, a strong clinical argument can be made for doing so, especially in women who come to menopause with low bone mass,” the report states.
And therapy is also recommended if patients have a low BMD and other risk factors for fracture, such as family history, but do not meet the criteria for osteoporosis treatment.
Ultimately, clinicians should work with patients when deciding the options, Dr. McClung said.
“After carefully weighing the small risks associated with hormone therapy or other therapies begun at the time of menopause, menopause practitioners and their patients can and should make informed decisions about the use of Food and Drug Administration–approved medications to prevent osteoporosis in women who are at risk for developing that condition,” he noted, adding that his view on the matter is his own and not necessarily that of NAMS.
New treatments endorsed for high-risk patients to avoid ‘bone attack’
While most patients are treated for osteoporosis with antiremodeling drugs such as bisphosphonates and denosumab, NAMS endorses “a new paradigm of beginning treatment with a bone-building agent followed by an antiremodeling agent” for women at very high risk of fracture.
“Consider osteoanabolic therapies for patients at very high risk of fracture, including older women with recent fractures, T-scores –3.0 and lower, or multiple other risk factors,” the statement suggests.
Among those at highest risk are women who have sustained a first fracture.
“A recent fracture in a postmenopausal woman is the strongest risk factor for another fracture,” Dr. McClung said.
In fact, “having a fracture should be thought of and assessed as a ‘bone attack,’ ” he asserted.
Therapy is recommended in such cases to rapidly increase bone density and reduce their subsequent fracture risk.
“For these patients, osteoanabolic or bone-building agents are more effective than bisphosphonates and are recommended as initial therapy,” Dr. McClung noted.
Treatment discontinuation?
On the issue of drug holidays and when or whether to stop therapy, as no therapies cure osteoporosis, medications should not be permanently stopped, even if bone density increases, NAMS recommends.
“By analogy, we do not stop diabetes therapy when A1c levels become normal,” Dr. McClung noted.
“Because the benefits of therapy on bone density and fracture protection wane, quickly for nonbisphosphonates and more slowly with bisphosphonates, short-term therapy, for instance 5 years, is not optimal treatment,” he said.
While the short-term interruption of bisphosphonate therapy may be considered in some patients, “the concept of ‘drug holidays’ does not pertain to nonbisphosphonate drugs,” Dr. McClung said.
NAMS adds that management of therapeutic choices should instead be ongoing.
“During therapy, reevaluate the treatment goals and the choice of medication on an ongoing basis through periodic medical examination and follow-up BMD testing,” NAMS recommends.
In terms of assessment, the measurement of bone mineral density while on treatment can gauge the current risk of fracture, and NAMS supports the use of the T-score at the hip as an appropriate clinical target in guiding choices of therapy.
Ultimately, “effective tools for diagnosing osteoporosis and assessing fracture risk are available, and well-studied strategies exist for managing bone health in women at both low and high risk of fracture,” NAMS concludes.
“By individualizing treatment approaches and monitoring and adjusting those approaches if the clinical picture changes, the consequences of osteoporosis on a menopausal woman’s activity and well-being can be minimized.”
Dr. McClung has reported receiving consulting fees from Amgen and Myovant, and honorarium for speaking from Amgen and Alexon. He serves on the boards of NAMS and the International Osteoporosis Foundation.
A version of this article first appeared on Medscape.com.
In the first revision to its guidance on the management of osteoporosis in a decade, the North American Menopause Society has issued an updated position statement addressing evolving evidence on osteoporosis issues ranging from screening and risk assessment to appropriate use of preventive therapy in postmenopausal women.
“Since the 2010 statement, there have been important new developments in our field, including better delineation of risk factors for fracture, resulting in better strategies for assessing fracture risk,” Michael R. McClung, MD, who is a NAMS board member and colead of the editorial panel for the 2021 position statement, told this news organization. Dr. McClung is also director emeritus of the Oregon Osteoporosis Center in Portland.
“There is much more information about the long-term safety of therapies,” he added. Dr. McClung also noted “the availability of four new drugs for the prevention and treatment of osteoporosis and clinical experience informing us of the effects of using different treatments in various sequences.”
Osteoporosis is substantially underdiagnosed and undertreated
A basis for the update, recently published in Menopause: The Journal of the North American Menopause Society, is the need to tackle the troubling fact that approximately half of postmenopausal women will experience a fracture related to osteoporosis in their lifetime, yet the condition is “substantially underdiagnosed and undertreated,” NAMS underscores.
With that in mind, osteoporosis should be considered by practitioners treating menopausal and postmenopausal women at all levels of care.
“All physicians and advanced care providers caring for postmenopausal women should be comfortable assessing and managing their patients with, or at risk for, fractures,” Dr. McClung added.
Osteoporosis prevention in young menopausal women
The NAMS statement covers a broad range of issues, and while most recommendations generally follow those of other societies’ guidelines, a unique aspect is the emphasis on preventing osteoporosis in young menopausal women with estrogen or other drugs.
While underscoring that all menopausal women should be encouraged to adopt healthy lifestyles, with good diets and physical activity to reduce the risk of bone loss and fractures, pharmacologic interventions also have a role, NAMS says.
Though long an issue of debate, NAMS voices support for estrogen therapy as having an important role in osteoporosis prevention, as estrogen deficiency is the principal cause of bone loss in postmenopausal women.
“Hormone therapy is the most appropriate choice to prevent bone loss at the time of menopause for healthy women, particularly those who have menopause symptoms,” the group states. Drug interventions are specifically supported in women with premature menopause, at least until the average age of natural menopause, in addition to those with low bone mineral density (BMD) (T-score < –1.0) and those experiencing relatively rapid bone loss related to acute estrogen deficiency in the menopause transition or on discontinuing estrogen therapy.
“Although using drugs to prevent osteoporosis is not included in national osteoporosis guidelines, a strong clinical argument can be made for doing so, especially in women who come to menopause with low bone mass,” the report states.
And therapy is also recommended if patients have a low BMD and other risk factors for fracture, such as family history, but do not meet the criteria for osteoporosis treatment.
Ultimately, clinicians should work with patients when deciding the options, Dr. McClung said.
“After carefully weighing the small risks associated with hormone therapy or other therapies begun at the time of menopause, menopause practitioners and their patients can and should make informed decisions about the use of Food and Drug Administration–approved medications to prevent osteoporosis in women who are at risk for developing that condition,” he noted, adding that his view on the matter is his own and not necessarily that of NAMS.
New treatments endorsed for high-risk patients to avoid ‘bone attack’
While most patients are treated for osteoporosis with antiremodeling drugs such as bisphosphonates and denosumab, NAMS endorses “a new paradigm of beginning treatment with a bone-building agent followed by an antiremodeling agent” for women at very high risk of fracture.
“Consider osteoanabolic therapies for patients at very high risk of fracture, including older women with recent fractures, T-scores –3.0 and lower, or multiple other risk factors,” the statement suggests.
Among those at highest risk are women who have sustained a first fracture.
“A recent fracture in a postmenopausal woman is the strongest risk factor for another fracture,” Dr. McClung said.
In fact, “having a fracture should be thought of and assessed as a ‘bone attack,’ ” he asserted.
Therapy is recommended in such cases to rapidly increase bone density and reduce their subsequent fracture risk.
“For these patients, osteoanabolic or bone-building agents are more effective than bisphosphonates and are recommended as initial therapy,” Dr. McClung noted.
Treatment discontinuation?
On the issue of drug holidays and when or whether to stop therapy, as no therapies cure osteoporosis, medications should not be permanently stopped, even if bone density increases, NAMS recommends.
“By analogy, we do not stop diabetes therapy when A1c levels become normal,” Dr. McClung noted.
“Because the benefits of therapy on bone density and fracture protection wane, quickly for nonbisphosphonates and more slowly with bisphosphonates, short-term therapy, for instance 5 years, is not optimal treatment,” he said.
While the short-term interruption of bisphosphonate therapy may be considered in some patients, “the concept of ‘drug holidays’ does not pertain to nonbisphosphonate drugs,” Dr. McClung said.
NAMS adds that management of therapeutic choices should instead be ongoing.
“During therapy, reevaluate the treatment goals and the choice of medication on an ongoing basis through periodic medical examination and follow-up BMD testing,” NAMS recommends.
In terms of assessment, the measurement of bone mineral density while on treatment can gauge the current risk of fracture, and NAMS supports the use of the T-score at the hip as an appropriate clinical target in guiding choices of therapy.
Ultimately, “effective tools for diagnosing osteoporosis and assessing fracture risk are available, and well-studied strategies exist for managing bone health in women at both low and high risk of fracture,” NAMS concludes.
“By individualizing treatment approaches and monitoring and adjusting those approaches if the clinical picture changes, the consequences of osteoporosis on a menopausal woman’s activity and well-being can be minimized.”
Dr. McClung has reported receiving consulting fees from Amgen and Myovant, and honorarium for speaking from Amgen and Alexon. He serves on the boards of NAMS and the International Osteoporosis Foundation.
A version of this article first appeared on Medscape.com.
Molecular ‘theranostics’ could guide treatment in thyroid cancer
The statement was issued as ever more data on molecular markers help launch a “new paradigm” in the approach to thyroid cancer, while driving ongoing debate over how they will feed into the use of RAI, first author Seza A. Gulec, MD, of Herbert Wertheim College of Medicine, Florida International University, Miami, said in an interview.
“The controversy over the appropriate use of RAI in thyroid cancer goes back 70 years, as we’ve been long using it based on the assumption that the majority of high-risk tumors respond to RAI,” he explained.
“But the new paradigm calls for identifying, through molecular analysis, the cancers that have the ability to respond to RAI and/or those that could have the response to RAI enhanced through pretreatment.”
In the statement, published in Thyroid, the working group for the three societies describes their agreement on key issues in three broad areas of RAI use: RAI in perioperative risk stratification, the role of RAI imaging in initial staging, and the need to refine understanding of markers of response to RAI therapy.
Avoid unnecessary treatment
The working group underscores the value of the traditional risk stratification and staging models for thyroid cancer – the American Joint Committee on Cancer eighth edition staging rules and ATA risk stratification system – in the immediate perioperative period, which is well established.
The group supports the inclusion of secondary prognostic factors, specifically molecular markers, in risk stratification in the perioperative period, citing their therapeutic and diagnostic (or theranostic) value in improving individualized treatment decisions.
Molecular theranostics comprise molecular cytology, molecular pathology, and molecular imaging.
“Traditional risk stratification systems can be further refined by ... judicious incorporation of molecular theranostics in the primary framework to guide initial patient management decisions,” the authors wrote.
Dr. Gulec said the inclusion of molecular analysis in risk stratification in particular offers the potential to avoid unnecessary treatment in people who can be identified as likely nonresponders.
“The bottom line is that we need to know more about the cancer before we make decisions on how to tackle it,” he said in an interview.
“For the thyroid cancer to respond to RAI, it has to have an intact system to handle the treatment, and the fact is that most high-risk patients have a molecular profile that does not allow them to respond to RAI or to benefit from total thyroidectomy,” Dr. Gulec explained.
However, the ability to perform a complete genomic analysis with advanced molecular sequencing and identify those patients is radically changing things, he concluded.
Dr. Gulec has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The statement was issued as ever more data on molecular markers help launch a “new paradigm” in the approach to thyroid cancer, while driving ongoing debate over how they will feed into the use of RAI, first author Seza A. Gulec, MD, of Herbert Wertheim College of Medicine, Florida International University, Miami, said in an interview.
“The controversy over the appropriate use of RAI in thyroid cancer goes back 70 years, as we’ve been long using it based on the assumption that the majority of high-risk tumors respond to RAI,” he explained.
“But the new paradigm calls for identifying, through molecular analysis, the cancers that have the ability to respond to RAI and/or those that could have the response to RAI enhanced through pretreatment.”
In the statement, published in Thyroid, the working group for the three societies describes their agreement on key issues in three broad areas of RAI use: RAI in perioperative risk stratification, the role of RAI imaging in initial staging, and the need to refine understanding of markers of response to RAI therapy.
Avoid unnecessary treatment
The working group underscores the value of the traditional risk stratification and staging models for thyroid cancer – the American Joint Committee on Cancer eighth edition staging rules and ATA risk stratification system – in the immediate perioperative period, which is well established.
The group supports the inclusion of secondary prognostic factors, specifically molecular markers, in risk stratification in the perioperative period, citing their therapeutic and diagnostic (or theranostic) value in improving individualized treatment decisions.
Molecular theranostics comprise molecular cytology, molecular pathology, and molecular imaging.
“Traditional risk stratification systems can be further refined by ... judicious incorporation of molecular theranostics in the primary framework to guide initial patient management decisions,” the authors wrote.
Dr. Gulec said the inclusion of molecular analysis in risk stratification in particular offers the potential to avoid unnecessary treatment in people who can be identified as likely nonresponders.
“The bottom line is that we need to know more about the cancer before we make decisions on how to tackle it,” he said in an interview.
“For the thyroid cancer to respond to RAI, it has to have an intact system to handle the treatment, and the fact is that most high-risk patients have a molecular profile that does not allow them to respond to RAI or to benefit from total thyroidectomy,” Dr. Gulec explained.
However, the ability to perform a complete genomic analysis with advanced molecular sequencing and identify those patients is radically changing things, he concluded.
Dr. Gulec has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The statement was issued as ever more data on molecular markers help launch a “new paradigm” in the approach to thyroid cancer, while driving ongoing debate over how they will feed into the use of RAI, first author Seza A. Gulec, MD, of Herbert Wertheim College of Medicine, Florida International University, Miami, said in an interview.
“The controversy over the appropriate use of RAI in thyroid cancer goes back 70 years, as we’ve been long using it based on the assumption that the majority of high-risk tumors respond to RAI,” he explained.
“But the new paradigm calls for identifying, through molecular analysis, the cancers that have the ability to respond to RAI and/or those that could have the response to RAI enhanced through pretreatment.”
In the statement, published in Thyroid, the working group for the three societies describes their agreement on key issues in three broad areas of RAI use: RAI in perioperative risk stratification, the role of RAI imaging in initial staging, and the need to refine understanding of markers of response to RAI therapy.
Avoid unnecessary treatment
The working group underscores the value of the traditional risk stratification and staging models for thyroid cancer – the American Joint Committee on Cancer eighth edition staging rules and ATA risk stratification system – in the immediate perioperative period, which is well established.
The group supports the inclusion of secondary prognostic factors, specifically molecular markers, in risk stratification in the perioperative period, citing their therapeutic and diagnostic (or theranostic) value in improving individualized treatment decisions.
Molecular theranostics comprise molecular cytology, molecular pathology, and molecular imaging.
“Traditional risk stratification systems can be further refined by ... judicious incorporation of molecular theranostics in the primary framework to guide initial patient management decisions,” the authors wrote.
Dr. Gulec said the inclusion of molecular analysis in risk stratification in particular offers the potential to avoid unnecessary treatment in people who can be identified as likely nonresponders.
“The bottom line is that we need to know more about the cancer before we make decisions on how to tackle it,” he said in an interview.
“For the thyroid cancer to respond to RAI, it has to have an intact system to handle the treatment, and the fact is that most high-risk patients have a molecular profile that does not allow them to respond to RAI or to benefit from total thyroidectomy,” Dr. Gulec explained.
However, the ability to perform a complete genomic analysis with advanced molecular sequencing and identify those patients is radically changing things, he concluded.
Dr. Gulec has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Better to binge drink than regularly tipple, suggests GI cancer study
When weekly levels are similar
Alcohol use is a known risk factor for gastrointestinal (GI) cancers. Now, new research indicates that this risk is more associated with frequent drinking – even in smaller amounts – compared with higher amounts or binge drinking, given similar weekly levels.
“The novel finding of the current study is that frequent drinking may be more dangerous than binge drinking with regard to GI cancers. Alcohol use is a known risk factor for gastrointestinal (GI) cancers. Now, new research indicates that this risk is more associated with frequent drinking – even in smaller amounts -- compared with higher amounts or binge drinking, given similar weekly levels.” first author Jung Eun Yook, MD, of Seoul (South Korea) National University Hospital, and colleagues reported in an article published Aug. 18, 2021, in JAMA Network Open (doi: 10.1001/jamanetworkopen.2021.20382).
“This finding suggests that repeated alcohol consumption events even at lower amounts of alcohol may have a greater carcinogenic effect on GI organs than the consumption of larger amounts of alcohol at a lower frequency,” the investigators wrote.
A possible reason behind the difference in risk may be that the chronic “carcinogenic insult” from regular alcohol use may promote cancer development, whereas less frequent, episodic alcohol exposures may allow physiologic recovery, said the authors.
The results are from a population-based study that involved 11,737,467 participants in the Korean National Health System database who did not have cancer and who took part in a national screening program between January 2009 and December 2010.
They were followed from the year after their screening until either they had received a diagnosis of a GI cancer, death occurred, or the end of December 2017.
During a median follow-up of 6.4 years, 319,202 (2.7%) of those in the study developed a GI cancer.
The increase in the risk associated with alcohol consumption was dose dependent.
Compared with those who did not consume alcohol, the risk of developing GI cancer was higher for mild drinkers (adjusted hazard ratio, 1.04; 95% confidence interval, 1.03-1.05), moderate drinkers (aHR, 1.14; 95% CI, 1.12-1.15), and heavy drinkers (aHR, 1.28; 95% CI, 1.26-1.29), after adjusting for age, sex, income, smoking status with intensity, regular exercise, body mass index, diabetes, hypertension, and dyslipidemia.
There was a linear association between the frequency of drinking and GI cancer risk, with an aHR of 1.39 for individuals who reported drinking every day (95% CI, 1.36-1.41). The risk for GI cancer increased with consumption of five to seven units per occasion (aHR, 1.15). Notably, there were no similar increases with higher intake, including intake of 8-14 units per occasion (aHR, 1.11; 95% CI, 1.09-1.12), and even up to more than 14 units per occasion (aHR, 1.11; 95%CI, 1.08-1.14), in comparison with an intake of 5-7 units per occasion.
“Given similar weekly alcohol consumption levels, the risk of GI cancer increased with a higher frequency of drinking and decreased with a higher amount per occasion,” the authors write.
“Most previous studies just assess alcohol consumption as a total amount, [such as] drinks per occasion times occasion per week equals drinks per week [and] grams per week,” coauthor Dong Wook Shin, MD, DrPH, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea, said in an interview.
“But it was not known whether frequent drinking with small amount is more harmful than binge drinking, given a similar level of total drinking,” Dr. Shin said.
The increased risk associated with frequent drinking was generally similar with respect to esophageal, gastric, colorectal, biliary, and pancreatic cancer.
An exception was liver cancer, which showed a slightly decreased risk among mild drinkers (aHR, 0.91; 95% CI, 0.89-0.93).
Of note, the association between alcohol intake and the incidence of GI cancer was lower among women than men in terms of weekly consumption, frequency, and amount of alcohol consumed per occasion.
The associations between drinking and cancer type in terms of esophageal and liver cancers were similar between men and women. However, the alcohol-related risk for colorectal, biliary, and pancreatic cancers was less prominent for women.
Possible mechanisms related to regular drinking
A factor that might account for the increase in GI cancer risk with frequent drinking is that regular alcohol consumption “promotes the accumulation of cell divisions in the stem cells that maintain tissues in homeostasis,” the authors explained.
Another possible explanation is that long-term alcohol exposure may promote carcinogenesis, whereas less frequent exposure might allow “physiological homeostasis,” the authors wrote, adding that in vivo experiments have shown that duration and dose of alcohol exposure have been linked to cancer development.
Importantly, the findings support the importance of reducing the frequency of alcohol use to prevent cancer, the authors noted.
“Alcohol users who have a glass of wine or beer during dinner every day may develop more cancer than people who occasionally consume several drinks,” they cautioned.
Genetics, self-reporting considerations
In a related commentary, John D. Potter, MBBS, PhD, of the Research Center for Hauora and Health, Massey University, Wellington, New Zealand, noted that, in addition to supporting the known link between alcohol and cancers of the esophagus, colorectum, and liver, the study “strengthens evidence for a role of alcohol in stomach, biliary tract, and pancreas cancers.”
In comparison with nondrinkers, those who reported heavy drinking were much more likely to be smokers (51.6% vs. 9.0%); however, the study adjusted for smoking.
“Because the researchers were able to control for tobacco, this last finding [regarding the association with cancers of the stomach, biliary tract, and pancreas] is particularly informative,” Dr. Potter noted.
An important caveat is that more than a quarter of the Korean population is known to have an inactive form of the aldehyde dehydrogenase gene (ALDH2), which could have effects on alcohol metabolism as well as the risk for cancer, Dr. Potter wrote.
“This common polymorphism in ALDH2 (ALDH2 rs671 [c.1510G>A (Glu504Lys)]) has paradoxical effects,” he wrote.
“It increases the level of acetaldehyde in the blood of drinkers, which in turn increases the risk of cancer because acetaldehyde is a key player in the carcinogenicity of alcoholic beverages,” Dr. Potter explained. “On the other hand, the accumulation of acetaldehyde and the resultant flushing response are sufficiently unpleasant that they tend to reduce alcohol consumption among those with the Lys allele.”
The study results may therefore not be generalizable to a population in which the distribution of the variation in the ALDH2 enzyme differs, Dr. Potter added.
The lower prevalence of the inactive form (in North America, for instance) would mean that this lower prevalence was not a constraint on individuals’ drinking behavior as it is for some in Korea, Dr. Potter explained.
He noted another consideration: the underreporting of alcohol use is a well-known limitation of studies involving the assessment of alcohol consumption.
Dr. Shin agreed that underreporting is a limitation.
“People tend to underestimate their alcohol use,” Dr. Shin said in an interview.
However, he noted that “our study participants are health-screening participants aged 40 years and older, [and] people who participate in health screening tend to have higher awareness and better health behavior than nonparticipants.”
The authors and Dr. Potter disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
When weekly levels are similar
When weekly levels are similar
Alcohol use is a known risk factor for gastrointestinal (GI) cancers. Now, new research indicates that this risk is more associated with frequent drinking – even in smaller amounts – compared with higher amounts or binge drinking, given similar weekly levels.
“The novel finding of the current study is that frequent drinking may be more dangerous than binge drinking with regard to GI cancers. Alcohol use is a known risk factor for gastrointestinal (GI) cancers. Now, new research indicates that this risk is more associated with frequent drinking – even in smaller amounts -- compared with higher amounts or binge drinking, given similar weekly levels.” first author Jung Eun Yook, MD, of Seoul (South Korea) National University Hospital, and colleagues reported in an article published Aug. 18, 2021, in JAMA Network Open (doi: 10.1001/jamanetworkopen.2021.20382).
“This finding suggests that repeated alcohol consumption events even at lower amounts of alcohol may have a greater carcinogenic effect on GI organs than the consumption of larger amounts of alcohol at a lower frequency,” the investigators wrote.
A possible reason behind the difference in risk may be that the chronic “carcinogenic insult” from regular alcohol use may promote cancer development, whereas less frequent, episodic alcohol exposures may allow physiologic recovery, said the authors.
The results are from a population-based study that involved 11,737,467 participants in the Korean National Health System database who did not have cancer and who took part in a national screening program between January 2009 and December 2010.
They were followed from the year after their screening until either they had received a diagnosis of a GI cancer, death occurred, or the end of December 2017.
During a median follow-up of 6.4 years, 319,202 (2.7%) of those in the study developed a GI cancer.
The increase in the risk associated with alcohol consumption was dose dependent.
Compared with those who did not consume alcohol, the risk of developing GI cancer was higher for mild drinkers (adjusted hazard ratio, 1.04; 95% confidence interval, 1.03-1.05), moderate drinkers (aHR, 1.14; 95% CI, 1.12-1.15), and heavy drinkers (aHR, 1.28; 95% CI, 1.26-1.29), after adjusting for age, sex, income, smoking status with intensity, regular exercise, body mass index, diabetes, hypertension, and dyslipidemia.
There was a linear association between the frequency of drinking and GI cancer risk, with an aHR of 1.39 for individuals who reported drinking every day (95% CI, 1.36-1.41). The risk for GI cancer increased with consumption of five to seven units per occasion (aHR, 1.15). Notably, there were no similar increases with higher intake, including intake of 8-14 units per occasion (aHR, 1.11; 95% CI, 1.09-1.12), and even up to more than 14 units per occasion (aHR, 1.11; 95%CI, 1.08-1.14), in comparison with an intake of 5-7 units per occasion.
“Given similar weekly alcohol consumption levels, the risk of GI cancer increased with a higher frequency of drinking and decreased with a higher amount per occasion,” the authors write.
“Most previous studies just assess alcohol consumption as a total amount, [such as] drinks per occasion times occasion per week equals drinks per week [and] grams per week,” coauthor Dong Wook Shin, MD, DrPH, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea, said in an interview.
“But it was not known whether frequent drinking with small amount is more harmful than binge drinking, given a similar level of total drinking,” Dr. Shin said.
The increased risk associated with frequent drinking was generally similar with respect to esophageal, gastric, colorectal, biliary, and pancreatic cancer.
An exception was liver cancer, which showed a slightly decreased risk among mild drinkers (aHR, 0.91; 95% CI, 0.89-0.93).
Of note, the association between alcohol intake and the incidence of GI cancer was lower among women than men in terms of weekly consumption, frequency, and amount of alcohol consumed per occasion.
The associations between drinking and cancer type in terms of esophageal and liver cancers were similar between men and women. However, the alcohol-related risk for colorectal, biliary, and pancreatic cancers was less prominent for women.
Possible mechanisms related to regular drinking
A factor that might account for the increase in GI cancer risk with frequent drinking is that regular alcohol consumption “promotes the accumulation of cell divisions in the stem cells that maintain tissues in homeostasis,” the authors explained.
Another possible explanation is that long-term alcohol exposure may promote carcinogenesis, whereas less frequent exposure might allow “physiological homeostasis,” the authors wrote, adding that in vivo experiments have shown that duration and dose of alcohol exposure have been linked to cancer development.
Importantly, the findings support the importance of reducing the frequency of alcohol use to prevent cancer, the authors noted.
“Alcohol users who have a glass of wine or beer during dinner every day may develop more cancer than people who occasionally consume several drinks,” they cautioned.
Genetics, self-reporting considerations
In a related commentary, John D. Potter, MBBS, PhD, of the Research Center for Hauora and Health, Massey University, Wellington, New Zealand, noted that, in addition to supporting the known link between alcohol and cancers of the esophagus, colorectum, and liver, the study “strengthens evidence for a role of alcohol in stomach, biliary tract, and pancreas cancers.”
In comparison with nondrinkers, those who reported heavy drinking were much more likely to be smokers (51.6% vs. 9.0%); however, the study adjusted for smoking.
“Because the researchers were able to control for tobacco, this last finding [regarding the association with cancers of the stomach, biliary tract, and pancreas] is particularly informative,” Dr. Potter noted.
An important caveat is that more than a quarter of the Korean population is known to have an inactive form of the aldehyde dehydrogenase gene (ALDH2), which could have effects on alcohol metabolism as well as the risk for cancer, Dr. Potter wrote.
“This common polymorphism in ALDH2 (ALDH2 rs671 [c.1510G>A (Glu504Lys)]) has paradoxical effects,” he wrote.
“It increases the level of acetaldehyde in the blood of drinkers, which in turn increases the risk of cancer because acetaldehyde is a key player in the carcinogenicity of alcoholic beverages,” Dr. Potter explained. “On the other hand, the accumulation of acetaldehyde and the resultant flushing response are sufficiently unpleasant that they tend to reduce alcohol consumption among those with the Lys allele.”
The study results may therefore not be generalizable to a population in which the distribution of the variation in the ALDH2 enzyme differs, Dr. Potter added.
The lower prevalence of the inactive form (in North America, for instance) would mean that this lower prevalence was not a constraint on individuals’ drinking behavior as it is for some in Korea, Dr. Potter explained.
He noted another consideration: the underreporting of alcohol use is a well-known limitation of studies involving the assessment of alcohol consumption.
Dr. Shin agreed that underreporting is a limitation.
“People tend to underestimate their alcohol use,” Dr. Shin said in an interview.
However, he noted that “our study participants are health-screening participants aged 40 years and older, [and] people who participate in health screening tend to have higher awareness and better health behavior than nonparticipants.”
The authors and Dr. Potter disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Alcohol use is a known risk factor for gastrointestinal (GI) cancers. Now, new research indicates that this risk is more associated with frequent drinking – even in smaller amounts – compared with higher amounts or binge drinking, given similar weekly levels.
“The novel finding of the current study is that frequent drinking may be more dangerous than binge drinking with regard to GI cancers. Alcohol use is a known risk factor for gastrointestinal (GI) cancers. Now, new research indicates that this risk is more associated with frequent drinking – even in smaller amounts -- compared with higher amounts or binge drinking, given similar weekly levels.” first author Jung Eun Yook, MD, of Seoul (South Korea) National University Hospital, and colleagues reported in an article published Aug. 18, 2021, in JAMA Network Open (doi: 10.1001/jamanetworkopen.2021.20382).
“This finding suggests that repeated alcohol consumption events even at lower amounts of alcohol may have a greater carcinogenic effect on GI organs than the consumption of larger amounts of alcohol at a lower frequency,” the investigators wrote.
A possible reason behind the difference in risk may be that the chronic “carcinogenic insult” from regular alcohol use may promote cancer development, whereas less frequent, episodic alcohol exposures may allow physiologic recovery, said the authors.
The results are from a population-based study that involved 11,737,467 participants in the Korean National Health System database who did not have cancer and who took part in a national screening program between January 2009 and December 2010.
They were followed from the year after their screening until either they had received a diagnosis of a GI cancer, death occurred, or the end of December 2017.
During a median follow-up of 6.4 years, 319,202 (2.7%) of those in the study developed a GI cancer.
The increase in the risk associated with alcohol consumption was dose dependent.
Compared with those who did not consume alcohol, the risk of developing GI cancer was higher for mild drinkers (adjusted hazard ratio, 1.04; 95% confidence interval, 1.03-1.05), moderate drinkers (aHR, 1.14; 95% CI, 1.12-1.15), and heavy drinkers (aHR, 1.28; 95% CI, 1.26-1.29), after adjusting for age, sex, income, smoking status with intensity, regular exercise, body mass index, diabetes, hypertension, and dyslipidemia.
There was a linear association between the frequency of drinking and GI cancer risk, with an aHR of 1.39 for individuals who reported drinking every day (95% CI, 1.36-1.41). The risk for GI cancer increased with consumption of five to seven units per occasion (aHR, 1.15). Notably, there were no similar increases with higher intake, including intake of 8-14 units per occasion (aHR, 1.11; 95% CI, 1.09-1.12), and even up to more than 14 units per occasion (aHR, 1.11; 95%CI, 1.08-1.14), in comparison with an intake of 5-7 units per occasion.
“Given similar weekly alcohol consumption levels, the risk of GI cancer increased with a higher frequency of drinking and decreased with a higher amount per occasion,” the authors write.
“Most previous studies just assess alcohol consumption as a total amount, [such as] drinks per occasion times occasion per week equals drinks per week [and] grams per week,” coauthor Dong Wook Shin, MD, DrPH, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea, said in an interview.
“But it was not known whether frequent drinking with small amount is more harmful than binge drinking, given a similar level of total drinking,” Dr. Shin said.
The increased risk associated with frequent drinking was generally similar with respect to esophageal, gastric, colorectal, biliary, and pancreatic cancer.
An exception was liver cancer, which showed a slightly decreased risk among mild drinkers (aHR, 0.91; 95% CI, 0.89-0.93).
Of note, the association between alcohol intake and the incidence of GI cancer was lower among women than men in terms of weekly consumption, frequency, and amount of alcohol consumed per occasion.
The associations between drinking and cancer type in terms of esophageal and liver cancers were similar between men and women. However, the alcohol-related risk for colorectal, biliary, and pancreatic cancers was less prominent for women.
Possible mechanisms related to regular drinking
A factor that might account for the increase in GI cancer risk with frequent drinking is that regular alcohol consumption “promotes the accumulation of cell divisions in the stem cells that maintain tissues in homeostasis,” the authors explained.
Another possible explanation is that long-term alcohol exposure may promote carcinogenesis, whereas less frequent exposure might allow “physiological homeostasis,” the authors wrote, adding that in vivo experiments have shown that duration and dose of alcohol exposure have been linked to cancer development.
Importantly, the findings support the importance of reducing the frequency of alcohol use to prevent cancer, the authors noted.
“Alcohol users who have a glass of wine or beer during dinner every day may develop more cancer than people who occasionally consume several drinks,” they cautioned.
Genetics, self-reporting considerations
In a related commentary, John D. Potter, MBBS, PhD, of the Research Center for Hauora and Health, Massey University, Wellington, New Zealand, noted that, in addition to supporting the known link between alcohol and cancers of the esophagus, colorectum, and liver, the study “strengthens evidence for a role of alcohol in stomach, biliary tract, and pancreas cancers.”
In comparison with nondrinkers, those who reported heavy drinking were much more likely to be smokers (51.6% vs. 9.0%); however, the study adjusted for smoking.
“Because the researchers were able to control for tobacco, this last finding [regarding the association with cancers of the stomach, biliary tract, and pancreas] is particularly informative,” Dr. Potter noted.
An important caveat is that more than a quarter of the Korean population is known to have an inactive form of the aldehyde dehydrogenase gene (ALDH2), which could have effects on alcohol metabolism as well as the risk for cancer, Dr. Potter wrote.
“This common polymorphism in ALDH2 (ALDH2 rs671 [c.1510G>A (Glu504Lys)]) has paradoxical effects,” he wrote.
“It increases the level of acetaldehyde in the blood of drinkers, which in turn increases the risk of cancer because acetaldehyde is a key player in the carcinogenicity of alcoholic beverages,” Dr. Potter explained. “On the other hand, the accumulation of acetaldehyde and the resultant flushing response are sufficiently unpleasant that they tend to reduce alcohol consumption among those with the Lys allele.”
The study results may therefore not be generalizable to a population in which the distribution of the variation in the ALDH2 enzyme differs, Dr. Potter added.
The lower prevalence of the inactive form (in North America, for instance) would mean that this lower prevalence was not a constraint on individuals’ drinking behavior as it is for some in Korea, Dr. Potter explained.
He noted another consideration: the underreporting of alcohol use is a well-known limitation of studies involving the assessment of alcohol consumption.
Dr. Shin agreed that underreporting is a limitation.
“People tend to underestimate their alcohol use,” Dr. Shin said in an interview.
However, he noted that “our study participants are health-screening participants aged 40 years and older, [and] people who participate in health screening tend to have higher awareness and better health behavior than nonparticipants.”
The authors and Dr. Potter disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
US Preventive Services Task Force lowers diabetes screening age for overweight
The United States Preventive Services Task Force has updated its recommendation on the age of screening for prediabetes and type 2 diabetes in the primary care setting – lowering the age from 40 to 35 years for asymptomatic patients who are overweight or obese and encouraging greater interventions when patients do show a risk.
“The USPSTF concludes with moderate certainty that screening for prediabetes and type 2 diabetes and offering or referring patients with prediabetes to effective preventive interventions has a moderate net benefit,” the task force concludes in its recommendation, published Aug. 24 in JAMA.
“Clinicians should offer or refer patients with prediabetes to effective preventive interventions,” they write.
Experts commenting on the issue strongly emphasize that it’s not just the screening, but the subsequent intervention that is needed to make a difference.
“If young adults newly identified with abnormal glucose metabolism do not receive the needed intensive behavioral change support, screening may provide no benefit,” write Richard W. Grant, MD, MPH, and colleagues in an editorial published with the recommendation.
“Given the role of our obesogenic and physically inactive society in the shift toward earlier onset of diabetes, efforts to increase screening and recognition of abnormal glucose metabolism must be coupled with robust public health measures to address the underlying contributors.”
BMI cutoff lower for at-risk ethnic populations
The recommendation, which updates the task force’s 2015 guideline, carries a “B” classification, meaning the USPSTF has high certainty that the net benefit is moderate. It now specifies screening from age 35to 70 for persons classified as overweight (body mass index at least 25) or obese (BMI at least 30) and recommends referral to preventive interventions when patients are found to have prediabetes.
In addition to recommendations of lifestyle changes, such as diet and physical activity, the task force also endorses the diabetes drug metformin as a beneficial intervention in the prevention or delay of diabetes, while noting fewer overall health benefits from metformin than from the lifestyle changes.
A lower BMI cutoff of at least 23 is recommended for diabetes screening of Asian Americans, and, importantly, screening for prediabetes and diabetes should be considered at an even earlier age if the patient is from a population with a disproportionately high prevalence of diabetes, including American Indian/Alaska Native, Black, Hawaiian/Pacific Islander, Hispanic/Latino, the task force recommends.
Screening tests should include fasting plasma glucose, hemoglobin A1c, or an oral glucose tolerance test. Although screening every 3 years “may be a reasonable approach for adults with normal blood glucose levels,” the task force adds that “the optimal screening interval for adults with an initial normal glucose test result is uncertain.”
Data review: Few with prediabetes know they have it
The need for the update was prompted by troubling data showing increasing diabetes rates despite early signs that can and should be identified and acted upon in the primary care setting to prevent disease progression.
Data from the Centers for Disease Control and Prevention, for instance, show that while 13% of all U.S. adults 18 years or older have diabetes and 35% meet criteria for prediabetes, as many as 21% of those with diabetes were not aware of or did not report having the disease. Furthermore, only a small fraction – 15% of those with prediabetes – said they had been told by a health professional that they had this condition, the task force notes.
The task force’s final recommendation was based on a systematic review of evidence regarding the screening of asymptomatic, nonpregnant adults and the harms and benefits of interventions, such as physical activity, behavioral counseling, or pharmacotherapy.
Among key evidence supporting the lower age was a 2014 study showing that the number of people necessary to obtain one positive test for diabetes with screening sharply drops from 80 among those aged 30-34 years to just 31 among those aged 36-39.
Opportunistic universal screening of eligible people aged 35 and older would yield a ratio of 1 out of just 15 to spot a positive test, the authors of that study reported.
In addition, a large cohort study in more than 77,000 people with prediabetes strongly links the risk of developing diabetes with increases in A1c level and with increasing BMI.
ADA recommendations differ
The new recommendations differ from American Diabetes Association guidelines, which call for diabetes screening at all ages for people who are overweight or obese and who have one or more risk factors, such as physical inactivity or a first-degree relative with diabetes. If results are normal, repeat screening at least every 3 years is recommended.
The ADA further recommends universal screening for all adults 45 years and older, regardless of their risk factors.
For the screening of adults over 45, the ADA recommends using a fasting plasma glucose level, 2-hour plasma glucose level during a 75-g oral glucose tolerance test, or A1c level, regardless of risk factors.
The American Association of Clinical Endocrinology also recommends universal screening for prediabetes and diabetes for all adults 45 years or older, regardless of risk factors, and also advises screening those who have risk factors for diabetes regardless of age.
Screening of little benefit without behavior change support
In an interview, Dr. Grant added that broad efforts are essential as those at the practice level have clearly not succeeded.
“The medical model of individual counseling and referral has not really been effective, and so we really need to think in terms of large-scale public health action,” said Dr. Grant, of the division of research, Kaiser Permanente Northern California, Oakland.
His editorial details the sweeping, multifactorial efforts that are needed.
“To turn this recommendation into action – that is, to translate screening activities into improved clinical outcomes – change is needed at the patient-clinician level (recognizing and encouraging eligible individuals to be screened), health care system level (reducing screening barriers and ensuring access to robust lifestyle programs), and societal level (applying effective public health interventions to reduce obesity and increase exercise),” they write.
A top priority has to be a focus on individuals of diverse backgrounds and issues such as access to healthy programs in minority communities, Dr. Grant noted.
“Newly diagnosed adults are more likely to be African-American and Latinx,” he said.
“We really need to invest in healthier communities for low-income, non-White communities to reverse the persistent health care disparities in these communities.”
While the challenges may appear daunting, history shows they are not necessarily insurmountable – as evidenced in the campaign to discourage tobacco smoking.
“National smoking cessation efforts are one example of a mostly successful public health campaign that has made a difference in health behaviors,” Grant noted.
The recommendation is also posted on the USPSTF web site .
Dr. Grant reports receiving grants from the National Institutes of Health and the Patient-Centered Outcomes Research Institute.
The United States Preventive Services Task Force has updated its recommendation on the age of screening for prediabetes and type 2 diabetes in the primary care setting – lowering the age from 40 to 35 years for asymptomatic patients who are overweight or obese and encouraging greater interventions when patients do show a risk.
“The USPSTF concludes with moderate certainty that screening for prediabetes and type 2 diabetes and offering or referring patients with prediabetes to effective preventive interventions has a moderate net benefit,” the task force concludes in its recommendation, published Aug. 24 in JAMA.
“Clinicians should offer or refer patients with prediabetes to effective preventive interventions,” they write.
Experts commenting on the issue strongly emphasize that it’s not just the screening, but the subsequent intervention that is needed to make a difference.
“If young adults newly identified with abnormal glucose metabolism do not receive the needed intensive behavioral change support, screening may provide no benefit,” write Richard W. Grant, MD, MPH, and colleagues in an editorial published with the recommendation.
“Given the role of our obesogenic and physically inactive society in the shift toward earlier onset of diabetes, efforts to increase screening and recognition of abnormal glucose metabolism must be coupled with robust public health measures to address the underlying contributors.”
BMI cutoff lower for at-risk ethnic populations
The recommendation, which updates the task force’s 2015 guideline, carries a “B” classification, meaning the USPSTF has high certainty that the net benefit is moderate. It now specifies screening from age 35to 70 for persons classified as overweight (body mass index at least 25) or obese (BMI at least 30) and recommends referral to preventive interventions when patients are found to have prediabetes.
In addition to recommendations of lifestyle changes, such as diet and physical activity, the task force also endorses the diabetes drug metformin as a beneficial intervention in the prevention or delay of diabetes, while noting fewer overall health benefits from metformin than from the lifestyle changes.
A lower BMI cutoff of at least 23 is recommended for diabetes screening of Asian Americans, and, importantly, screening for prediabetes and diabetes should be considered at an even earlier age if the patient is from a population with a disproportionately high prevalence of diabetes, including American Indian/Alaska Native, Black, Hawaiian/Pacific Islander, Hispanic/Latino, the task force recommends.
Screening tests should include fasting plasma glucose, hemoglobin A1c, or an oral glucose tolerance test. Although screening every 3 years “may be a reasonable approach for adults with normal blood glucose levels,” the task force adds that “the optimal screening interval for adults with an initial normal glucose test result is uncertain.”
Data review: Few with prediabetes know they have it
The need for the update was prompted by troubling data showing increasing diabetes rates despite early signs that can and should be identified and acted upon in the primary care setting to prevent disease progression.
Data from the Centers for Disease Control and Prevention, for instance, show that while 13% of all U.S. adults 18 years or older have diabetes and 35% meet criteria for prediabetes, as many as 21% of those with diabetes were not aware of or did not report having the disease. Furthermore, only a small fraction – 15% of those with prediabetes – said they had been told by a health professional that they had this condition, the task force notes.
The task force’s final recommendation was based on a systematic review of evidence regarding the screening of asymptomatic, nonpregnant adults and the harms and benefits of interventions, such as physical activity, behavioral counseling, or pharmacotherapy.
Among key evidence supporting the lower age was a 2014 study showing that the number of people necessary to obtain one positive test for diabetes with screening sharply drops from 80 among those aged 30-34 years to just 31 among those aged 36-39.
Opportunistic universal screening of eligible people aged 35 and older would yield a ratio of 1 out of just 15 to spot a positive test, the authors of that study reported.
In addition, a large cohort study in more than 77,000 people with prediabetes strongly links the risk of developing diabetes with increases in A1c level and with increasing BMI.
ADA recommendations differ
The new recommendations differ from American Diabetes Association guidelines, which call for diabetes screening at all ages for people who are overweight or obese and who have one or more risk factors, such as physical inactivity or a first-degree relative with diabetes. If results are normal, repeat screening at least every 3 years is recommended.
The ADA further recommends universal screening for all adults 45 years and older, regardless of their risk factors.
For the screening of adults over 45, the ADA recommends using a fasting plasma glucose level, 2-hour plasma glucose level during a 75-g oral glucose tolerance test, or A1c level, regardless of risk factors.
The American Association of Clinical Endocrinology also recommends universal screening for prediabetes and diabetes for all adults 45 years or older, regardless of risk factors, and also advises screening those who have risk factors for diabetes regardless of age.
Screening of little benefit without behavior change support
In an interview, Dr. Grant added that broad efforts are essential as those at the practice level have clearly not succeeded.
“The medical model of individual counseling and referral has not really been effective, and so we really need to think in terms of large-scale public health action,” said Dr. Grant, of the division of research, Kaiser Permanente Northern California, Oakland.
His editorial details the sweeping, multifactorial efforts that are needed.
“To turn this recommendation into action – that is, to translate screening activities into improved clinical outcomes – change is needed at the patient-clinician level (recognizing and encouraging eligible individuals to be screened), health care system level (reducing screening barriers and ensuring access to robust lifestyle programs), and societal level (applying effective public health interventions to reduce obesity and increase exercise),” they write.
A top priority has to be a focus on individuals of diverse backgrounds and issues such as access to healthy programs in minority communities, Dr. Grant noted.
“Newly diagnosed adults are more likely to be African-American and Latinx,” he said.
“We really need to invest in healthier communities for low-income, non-White communities to reverse the persistent health care disparities in these communities.”
While the challenges may appear daunting, history shows they are not necessarily insurmountable – as evidenced in the campaign to discourage tobacco smoking.
“National smoking cessation efforts are one example of a mostly successful public health campaign that has made a difference in health behaviors,” Grant noted.
The recommendation is also posted on the USPSTF web site .
Dr. Grant reports receiving grants from the National Institutes of Health and the Patient-Centered Outcomes Research Institute.
The United States Preventive Services Task Force has updated its recommendation on the age of screening for prediabetes and type 2 diabetes in the primary care setting – lowering the age from 40 to 35 years for asymptomatic patients who are overweight or obese and encouraging greater interventions when patients do show a risk.
“The USPSTF concludes with moderate certainty that screening for prediabetes and type 2 diabetes and offering or referring patients with prediabetes to effective preventive interventions has a moderate net benefit,” the task force concludes in its recommendation, published Aug. 24 in JAMA.
“Clinicians should offer or refer patients with prediabetes to effective preventive interventions,” they write.
Experts commenting on the issue strongly emphasize that it’s not just the screening, but the subsequent intervention that is needed to make a difference.
“If young adults newly identified with abnormal glucose metabolism do not receive the needed intensive behavioral change support, screening may provide no benefit,” write Richard W. Grant, MD, MPH, and colleagues in an editorial published with the recommendation.
“Given the role of our obesogenic and physically inactive society in the shift toward earlier onset of diabetes, efforts to increase screening and recognition of abnormal glucose metabolism must be coupled with robust public health measures to address the underlying contributors.”
BMI cutoff lower for at-risk ethnic populations
The recommendation, which updates the task force’s 2015 guideline, carries a “B” classification, meaning the USPSTF has high certainty that the net benefit is moderate. It now specifies screening from age 35to 70 for persons classified as overweight (body mass index at least 25) or obese (BMI at least 30) and recommends referral to preventive interventions when patients are found to have prediabetes.
In addition to recommendations of lifestyle changes, such as diet and physical activity, the task force also endorses the diabetes drug metformin as a beneficial intervention in the prevention or delay of diabetes, while noting fewer overall health benefits from metformin than from the lifestyle changes.
A lower BMI cutoff of at least 23 is recommended for diabetes screening of Asian Americans, and, importantly, screening for prediabetes and diabetes should be considered at an even earlier age if the patient is from a population with a disproportionately high prevalence of diabetes, including American Indian/Alaska Native, Black, Hawaiian/Pacific Islander, Hispanic/Latino, the task force recommends.
Screening tests should include fasting plasma glucose, hemoglobin A1c, or an oral glucose tolerance test. Although screening every 3 years “may be a reasonable approach for adults with normal blood glucose levels,” the task force adds that “the optimal screening interval for adults with an initial normal glucose test result is uncertain.”
Data review: Few with prediabetes know they have it
The need for the update was prompted by troubling data showing increasing diabetes rates despite early signs that can and should be identified and acted upon in the primary care setting to prevent disease progression.
Data from the Centers for Disease Control and Prevention, for instance, show that while 13% of all U.S. adults 18 years or older have diabetes and 35% meet criteria for prediabetes, as many as 21% of those with diabetes were not aware of or did not report having the disease. Furthermore, only a small fraction – 15% of those with prediabetes – said they had been told by a health professional that they had this condition, the task force notes.
The task force’s final recommendation was based on a systematic review of evidence regarding the screening of asymptomatic, nonpregnant adults and the harms and benefits of interventions, such as physical activity, behavioral counseling, or pharmacotherapy.
Among key evidence supporting the lower age was a 2014 study showing that the number of people necessary to obtain one positive test for diabetes with screening sharply drops from 80 among those aged 30-34 years to just 31 among those aged 36-39.
Opportunistic universal screening of eligible people aged 35 and older would yield a ratio of 1 out of just 15 to spot a positive test, the authors of that study reported.
In addition, a large cohort study in more than 77,000 people with prediabetes strongly links the risk of developing diabetes with increases in A1c level and with increasing BMI.
ADA recommendations differ
The new recommendations differ from American Diabetes Association guidelines, which call for diabetes screening at all ages for people who are overweight or obese and who have one or more risk factors, such as physical inactivity or a first-degree relative with diabetes. If results are normal, repeat screening at least every 3 years is recommended.
The ADA further recommends universal screening for all adults 45 years and older, regardless of their risk factors.
For the screening of adults over 45, the ADA recommends using a fasting plasma glucose level, 2-hour plasma glucose level during a 75-g oral glucose tolerance test, or A1c level, regardless of risk factors.
The American Association of Clinical Endocrinology also recommends universal screening for prediabetes and diabetes for all adults 45 years or older, regardless of risk factors, and also advises screening those who have risk factors for diabetes regardless of age.
Screening of little benefit without behavior change support
In an interview, Dr. Grant added that broad efforts are essential as those at the practice level have clearly not succeeded.
“The medical model of individual counseling and referral has not really been effective, and so we really need to think in terms of large-scale public health action,” said Dr. Grant, of the division of research, Kaiser Permanente Northern California, Oakland.
His editorial details the sweeping, multifactorial efforts that are needed.
“To turn this recommendation into action – that is, to translate screening activities into improved clinical outcomes – change is needed at the patient-clinician level (recognizing and encouraging eligible individuals to be screened), health care system level (reducing screening barriers and ensuring access to robust lifestyle programs), and societal level (applying effective public health interventions to reduce obesity and increase exercise),” they write.
A top priority has to be a focus on individuals of diverse backgrounds and issues such as access to healthy programs in minority communities, Dr. Grant noted.
“Newly diagnosed adults are more likely to be African-American and Latinx,” he said.
“We really need to invest in healthier communities for low-income, non-White communities to reverse the persistent health care disparities in these communities.”
While the challenges may appear daunting, history shows they are not necessarily insurmountable – as evidenced in the campaign to discourage tobacco smoking.
“National smoking cessation efforts are one example of a mostly successful public health campaign that has made a difference in health behaviors,” Grant noted.
The recommendation is also posted on the USPSTF web site .
Dr. Grant reports receiving grants from the National Institutes of Health and the Patient-Centered Outcomes Research Institute.
FROM JAMA