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Myomectomy best for avoiding reintervention after fibroid procedures
Reintervention rates after uterus-preserving surgery for leiomyomata were lowest after vaginal myomectomy, the most frequent among four therapeutic approaches, a large cohort study reported.
Accounting for censoring, the 7-year reintervention risk for vaginal myomectomy was 20.6%, followed by uterine artery embolization (26%), endometrial ablation (35.5%), and hysteroscopic myomectomy (37%).
Hysterectomies accounted for 63.2% of reinterventions according to lead author Susanna D. Mitro, PhD, a research scientist in the Division of Research and Department of Obstetrics and Gynecology at Kaiser Permanente Northern California, Oakland, and colleagues.
Risk did not vary by body mass index, race/ethnicity, or Neighborhood Deprivation Index, but did vary for some procedures by age and parity,
These findings generally align with earlier research and “illustrate clinically meaningful long-term differences in reintervention rates after a first uterus-preserving treatment for leiomyomas,” the researchers wrote in Obstetrics & Gynecology.
The Study
In a cohort of 10,324 patients ages 18-50, 19.9% were Asian, 21.2% Black, 21.3% Hispanic, and 32.5% White, with 5.2% of other races and ethnicities. The most affected age groups were 41-45 and 46-50 years. All participants underwent a first uterus-preserving procedure after leiomyoma diagnosis according to 2009-2021 electronic health records at Kaiser Permanente Northern California.
Reintervention referred to a second uterus-preserving procedure or hysterectomy. Median follow-up was 3.8 years (interquartile range, 1.8-7.4 years), and the proportions of index procedures were as follows: 18% (1857) for hysteroscopic myomectomy; 16.2% (1669) for uterine artery embolization; 21.4% (2211) for endometrial ablations; and 44.4% (4,587) for myomectomy.
Reintervention rates were higher in younger patients after uterine artery embolization, with patients ages 18-35 at the index procedure having 1.4-3.7 times greater reintervention rates than patients ages 46-50 years. Reintervention rates for hysteroscopic myomectomy varied by parity, with multiparous patients at 35% greater risk than their nulliparous counterparts.
On the age issue, the authors note that symptom recurrence may be less common in older patients, perhaps because of the onset of menopause. “Alternatively, findings may be explained by age-specific care strategies: Older patients experiencing symptom recurrence may prefer to wait until the onset of menopause rather than pursuing another surgical treatment,” they wrote.
A recent study with 7 years’ follow-up reported a 2.4 times greater risk of hysterectomy after uterine artery embolization versus myomectomy. Reintervention rates may be lower after myomectomy because otherwise asymptomatic patients pursue myomectomy to treat infertility, the authors wrote. Alternatively, myomectomy may more completely remove leiomyomas.
These common benign tumors take a toll on healthcare resources, in 2012 costing up to $9.4 billion annually (in 2010 dollars) for related surgeries, medications, and procedures. Leiomyomas are reportedly the most frequent reason for hysterectomy.
Robust data on the optimal therapeutic approach to fibroids have been sparse, however, with a 2017 comparative-effectiveness review from the Agency for Healthcare Research and Quality reporting that evidence on leiomyoma treatments was insufficient to guide clinical care. Few well-conducted trials of leiomyoma treatment have directly compared different treatment options, the authors noted.
The rate of myomectomy is reported to be 9.2 per 10,000 woman-years in Black women and 1.3 per 10,000 woman years in White women, and the recurrence rate after myomectomy can be as great as 60% when patients are followed up to 5 years.
The authors said their findings “may be a reference to discuss expectations for treatment outcomes when choosing initial uterus-preserving treatment for leiomyomas, especially for patients receiving treatment years before the likely onset of menopause.”
This research was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. Coauthor Dr. Lauren Wise is a paid consultant for AbbVie and has received in-kind donations from Swiss Precision Diagnostics and Kindara.com; she has also received payment from the Gates Foundation.
Reintervention rates after uterus-preserving surgery for leiomyomata were lowest after vaginal myomectomy, the most frequent among four therapeutic approaches, a large cohort study reported.
Accounting for censoring, the 7-year reintervention risk for vaginal myomectomy was 20.6%, followed by uterine artery embolization (26%), endometrial ablation (35.5%), and hysteroscopic myomectomy (37%).
Hysterectomies accounted for 63.2% of reinterventions according to lead author Susanna D. Mitro, PhD, a research scientist in the Division of Research and Department of Obstetrics and Gynecology at Kaiser Permanente Northern California, Oakland, and colleagues.
Risk did not vary by body mass index, race/ethnicity, or Neighborhood Deprivation Index, but did vary for some procedures by age and parity,
These findings generally align with earlier research and “illustrate clinically meaningful long-term differences in reintervention rates after a first uterus-preserving treatment for leiomyomas,” the researchers wrote in Obstetrics & Gynecology.
The Study
In a cohort of 10,324 patients ages 18-50, 19.9% were Asian, 21.2% Black, 21.3% Hispanic, and 32.5% White, with 5.2% of other races and ethnicities. The most affected age groups were 41-45 and 46-50 years. All participants underwent a first uterus-preserving procedure after leiomyoma diagnosis according to 2009-2021 electronic health records at Kaiser Permanente Northern California.
Reintervention referred to a second uterus-preserving procedure or hysterectomy. Median follow-up was 3.8 years (interquartile range, 1.8-7.4 years), and the proportions of index procedures were as follows: 18% (1857) for hysteroscopic myomectomy; 16.2% (1669) for uterine artery embolization; 21.4% (2211) for endometrial ablations; and 44.4% (4,587) for myomectomy.
Reintervention rates were higher in younger patients after uterine artery embolization, with patients ages 18-35 at the index procedure having 1.4-3.7 times greater reintervention rates than patients ages 46-50 years. Reintervention rates for hysteroscopic myomectomy varied by parity, with multiparous patients at 35% greater risk than their nulliparous counterparts.
On the age issue, the authors note that symptom recurrence may be less common in older patients, perhaps because of the onset of menopause. “Alternatively, findings may be explained by age-specific care strategies: Older patients experiencing symptom recurrence may prefer to wait until the onset of menopause rather than pursuing another surgical treatment,” they wrote.
A recent study with 7 years’ follow-up reported a 2.4 times greater risk of hysterectomy after uterine artery embolization versus myomectomy. Reintervention rates may be lower after myomectomy because otherwise asymptomatic patients pursue myomectomy to treat infertility, the authors wrote. Alternatively, myomectomy may more completely remove leiomyomas.
These common benign tumors take a toll on healthcare resources, in 2012 costing up to $9.4 billion annually (in 2010 dollars) for related surgeries, medications, and procedures. Leiomyomas are reportedly the most frequent reason for hysterectomy.
Robust data on the optimal therapeutic approach to fibroids have been sparse, however, with a 2017 comparative-effectiveness review from the Agency for Healthcare Research and Quality reporting that evidence on leiomyoma treatments was insufficient to guide clinical care. Few well-conducted trials of leiomyoma treatment have directly compared different treatment options, the authors noted.
The rate of myomectomy is reported to be 9.2 per 10,000 woman-years in Black women and 1.3 per 10,000 woman years in White women, and the recurrence rate after myomectomy can be as great as 60% when patients are followed up to 5 years.
The authors said their findings “may be a reference to discuss expectations for treatment outcomes when choosing initial uterus-preserving treatment for leiomyomas, especially for patients receiving treatment years before the likely onset of menopause.”
This research was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. Coauthor Dr. Lauren Wise is a paid consultant for AbbVie and has received in-kind donations from Swiss Precision Diagnostics and Kindara.com; she has also received payment from the Gates Foundation.
Reintervention rates after uterus-preserving surgery for leiomyomata were lowest after vaginal myomectomy, the most frequent among four therapeutic approaches, a large cohort study reported.
Accounting for censoring, the 7-year reintervention risk for vaginal myomectomy was 20.6%, followed by uterine artery embolization (26%), endometrial ablation (35.5%), and hysteroscopic myomectomy (37%).
Hysterectomies accounted for 63.2% of reinterventions according to lead author Susanna D. Mitro, PhD, a research scientist in the Division of Research and Department of Obstetrics and Gynecology at Kaiser Permanente Northern California, Oakland, and colleagues.
Risk did not vary by body mass index, race/ethnicity, or Neighborhood Deprivation Index, but did vary for some procedures by age and parity,
These findings generally align with earlier research and “illustrate clinically meaningful long-term differences in reintervention rates after a first uterus-preserving treatment for leiomyomas,” the researchers wrote in Obstetrics & Gynecology.
The Study
In a cohort of 10,324 patients ages 18-50, 19.9% were Asian, 21.2% Black, 21.3% Hispanic, and 32.5% White, with 5.2% of other races and ethnicities. The most affected age groups were 41-45 and 46-50 years. All participants underwent a first uterus-preserving procedure after leiomyoma diagnosis according to 2009-2021 electronic health records at Kaiser Permanente Northern California.
Reintervention referred to a second uterus-preserving procedure or hysterectomy. Median follow-up was 3.8 years (interquartile range, 1.8-7.4 years), and the proportions of index procedures were as follows: 18% (1857) for hysteroscopic myomectomy; 16.2% (1669) for uterine artery embolization; 21.4% (2211) for endometrial ablations; and 44.4% (4,587) for myomectomy.
Reintervention rates were higher in younger patients after uterine artery embolization, with patients ages 18-35 at the index procedure having 1.4-3.7 times greater reintervention rates than patients ages 46-50 years. Reintervention rates for hysteroscopic myomectomy varied by parity, with multiparous patients at 35% greater risk than their nulliparous counterparts.
On the age issue, the authors note that symptom recurrence may be less common in older patients, perhaps because of the onset of menopause. “Alternatively, findings may be explained by age-specific care strategies: Older patients experiencing symptom recurrence may prefer to wait until the onset of menopause rather than pursuing another surgical treatment,” they wrote.
A recent study with 7 years’ follow-up reported a 2.4 times greater risk of hysterectomy after uterine artery embolization versus myomectomy. Reintervention rates may be lower after myomectomy because otherwise asymptomatic patients pursue myomectomy to treat infertility, the authors wrote. Alternatively, myomectomy may more completely remove leiomyomas.
These common benign tumors take a toll on healthcare resources, in 2012 costing up to $9.4 billion annually (in 2010 dollars) for related surgeries, medications, and procedures. Leiomyomas are reportedly the most frequent reason for hysterectomy.
Robust data on the optimal therapeutic approach to fibroids have been sparse, however, with a 2017 comparative-effectiveness review from the Agency for Healthcare Research and Quality reporting that evidence on leiomyoma treatments was insufficient to guide clinical care. Few well-conducted trials of leiomyoma treatment have directly compared different treatment options, the authors noted.
The rate of myomectomy is reported to be 9.2 per 10,000 woman-years in Black women and 1.3 per 10,000 woman years in White women, and the recurrence rate after myomectomy can be as great as 60% when patients are followed up to 5 years.
The authors said their findings “may be a reference to discuss expectations for treatment outcomes when choosing initial uterus-preserving treatment for leiomyomas, especially for patients receiving treatment years before the likely onset of menopause.”
This research was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. Coauthor Dr. Lauren Wise is a paid consultant for AbbVie and has received in-kind donations from Swiss Precision Diagnostics and Kindara.com; she has also received payment from the Gates Foundation.
FROM OBSTETRICS & GYNECOLOGY
New CRC stool test beats FIT for sensitivity but not specificity
, according to the large prospective BLUE-C study.
The multi-target assay by Exact Sciences Corporation, the makers of Cologuard, includes new biomarkers designed to increase specificity without decreasing sensitivity. It showed a sensitivity for CRC of almost 94%, with more than 43% sensitivity for advanced precancerous lesions and nearly 91% specificity for advanced neoplasia, according to the study results, which were published in The New England Journal of Medicine.
Adherence to CRC screening in the United States is well below the 80% national target, and the quest continues for noninvasive screening assays that might improve screening adherence, noted lead author Thomas F. Imperiale, MD, AGAF, a professor of medicine at Indiana University School of medicine in Indianapolis, and colleagues.
“The test’s manufacturer developed a new version of its existing Cologuard FIT/DNA test because it took to heart the feedback from primary care providers and gastroenterologists about the test’s low specificity,” Dr. Imperiale said in an interview. “The goal of the new test was to improve specificity without losing, and perhaps even gaining, some sensitivity — a goal that is not easily accomplished when you’re trying to improve on a sensitivity for colorectal cancer that was already 92.3% in the current version of Cologuard.”
Compared with the earlier version of Cologuard, he added, the new generation retained sensitivity for CRC and advanced precancerous lesions or polyps while improving specificity by 30% (90.6% vs 86.6%) for advanced neoplasia — a combination of CRC and advanced precancerous lesions, he said. “This with the caveat, however, that the two versions were not compared head-to-head in this new study,” Dr. Imperiale said.
The higher specificity for advanced lesions is expected to translate to a lower false positive rate. Lowering false positive rates is crucial because that reduces the need for costly, invasive, and unnecessary colonoscopies, said Aasma Shaukat, MD, MPH, AGAF, director of outcomes research in NYU Langone Health’s division of gastroenterology and hepatology in New York City.
“Many physicians felt there were too many false positives with the existing version, and that is anxiety-provoking in patients and providers,” said Dr. Shaukat, who was not involved in the study.
In her view, however, the test’s moderate improvements in detecting certain lesions does not make it demonstrably superior to its predecessor, and there is always the possibility of higher cost to consider.
While acknowledging that a higher sensitivity for all advanced precancerous lesions would have been welcome, Dr. Imperiale said the test detected 75% of the most worrisome of such lesions — “the ones containing high-grade dysplastic cells and suggesting near-term conversion to cancer. And its ability to detect other advanced lesions improved as the size of the lesions increased.”
Testing details
Almost 21,000 asymptomatic participants age 40 years and older undergoing screening colonoscopy were evaluated at 186 US sites during the period 2019 to 2023. Of the cohort, 98 had CRC, 2144 had advanced precancerous lesions, 6973 had nonadvanced adenomas, and 10,961 had nonneoplastic findings or negative colonoscopy.
Advanced precancerous lesions included one or more adenomas or sessile serrated lesions measuring at least 1 cm in the longest dimension, lesions with villous histologic features, and high-grade dysplasia. The new DNA test identified 92 of 98 participants with CRC and 76 of 82 participants with screening-relevant cancers. Among the findings for the new assay:
- Sensitivity for any-stage CRC was 93.9% (95% confidence interval [CI], 87.1- 97.7)
- Sensitivity for advanced precancerous lesions was 43.4% (95% CI, 41.3-45.6)
- Sensitivity for high-grade dysplasia was 74.6% (95% CI, 65.6-82.3)
- Specificity for advanced neoplasia was 90.6% (95% CI, 90.1- 91.0).
- Specificity for nonneoplastic findings or negative colonoscopy was 92.7% (95% CI, 92.2-93.1)
- Specificity for negative colonoscopy was 93.3 (95% CI, 92.8-93.9)
- No adverse events occurred.
In the comparator assay, OC-AUTO FIT by Polymedco, sensitivity was 67.3% (95% CI, 57.1-76.5) for CRC, 23.3% (95% CI, 21.5-25.2) for advanced precancerous lesions, and 47.4% (95% CI, 37.9-56.9) for high-grade dysplasia. In the comparator FIT, however, specificity was better across all age groups — at 94.8% (95% CI, 94.4-95.1) for advanced neoplasia, 95.7% (95% CI, 95.3- 96.1) for nonneoplastic findings, and 96.0% (95% CI, 95.5-96.4) for negative colonoscopy.
In another article in the same issue of NEJM, Guardant Health’s cell-free DNA blood-based test had 83% sensitivity for CRC, 90% specificity for advanced neoplasia, and 13% sensitivity for advanced precancerous lesions in an average-risk population.
An age-related decrease in specificity was observed with the new Cologuard test, but that did not concern Dr. Imperiale because the same observation was made with the current version. “In fact, the next-gen version appears to have less of an age-related decrease in specificity than the current version, although, again, the two versions were not tested head-to-head,” he noted.
The effect of age-related background methylation of DNA is well known, he explained. “Clinicians and older patients in the screening age range do need to be aware of this effect on specificity before ordering or agreeing to do the test. I do not see this as a stumbling block to implementation, but it does require discussion between patient and ordering provider.”
The new version of the DNA test is expected to be available in about a year.
According to Dr. Imperiale, further research is needed to ascertain the test’s acceptability and adherence rates and to quantify its yield in population-based screening. Determining its cost-effectiveness and making it easier to use are other goals. “And most importantly, the degree of reduction in the incidence and mortality from colorectal cancer,” he said.
Cost-effectiveness and the selection of the testing interval may play roles in adherence, particularly in populations with lower rates of screening adherence than the general population, John M. Carethers, MD, AGAF, of the University of California, San Diego, noted in a related editorial.
“Adherence to screening varies according to age group, including persons in the 45- to 49-year age group who are now eligible for average-risk screening,” he wrote. “It is hoped that these newer tests will increase use and adherence and elevate the percentage of the population undergoing screening in order to reduce deaths from colorectal cancer.”
This study was sponsored by Exact Sciences Corporation, which conducted the stool testing at its laboratories.
Dr. Imperiale had no competing interests to disclose. Several study co-authors reported employment with Exact Sciences, or stock and intellectual property ownership. Dr. Shaukat disclosed consulting for Freenome. Dr. Carethers reported ties to Avantor Inc. and Geneoscopy.
, according to the large prospective BLUE-C study.
The multi-target assay by Exact Sciences Corporation, the makers of Cologuard, includes new biomarkers designed to increase specificity without decreasing sensitivity. It showed a sensitivity for CRC of almost 94%, with more than 43% sensitivity for advanced precancerous lesions and nearly 91% specificity for advanced neoplasia, according to the study results, which were published in The New England Journal of Medicine.
Adherence to CRC screening in the United States is well below the 80% national target, and the quest continues for noninvasive screening assays that might improve screening adherence, noted lead author Thomas F. Imperiale, MD, AGAF, a professor of medicine at Indiana University School of medicine in Indianapolis, and colleagues.
“The test’s manufacturer developed a new version of its existing Cologuard FIT/DNA test because it took to heart the feedback from primary care providers and gastroenterologists about the test’s low specificity,” Dr. Imperiale said in an interview. “The goal of the new test was to improve specificity without losing, and perhaps even gaining, some sensitivity — a goal that is not easily accomplished when you’re trying to improve on a sensitivity for colorectal cancer that was already 92.3% in the current version of Cologuard.”
Compared with the earlier version of Cologuard, he added, the new generation retained sensitivity for CRC and advanced precancerous lesions or polyps while improving specificity by 30% (90.6% vs 86.6%) for advanced neoplasia — a combination of CRC and advanced precancerous lesions, he said. “This with the caveat, however, that the two versions were not compared head-to-head in this new study,” Dr. Imperiale said.
The higher specificity for advanced lesions is expected to translate to a lower false positive rate. Lowering false positive rates is crucial because that reduces the need for costly, invasive, and unnecessary colonoscopies, said Aasma Shaukat, MD, MPH, AGAF, director of outcomes research in NYU Langone Health’s division of gastroenterology and hepatology in New York City.
“Many physicians felt there were too many false positives with the existing version, and that is anxiety-provoking in patients and providers,” said Dr. Shaukat, who was not involved in the study.
In her view, however, the test’s moderate improvements in detecting certain lesions does not make it demonstrably superior to its predecessor, and there is always the possibility of higher cost to consider.
While acknowledging that a higher sensitivity for all advanced precancerous lesions would have been welcome, Dr. Imperiale said the test detected 75% of the most worrisome of such lesions — “the ones containing high-grade dysplastic cells and suggesting near-term conversion to cancer. And its ability to detect other advanced lesions improved as the size of the lesions increased.”
Testing details
Almost 21,000 asymptomatic participants age 40 years and older undergoing screening colonoscopy were evaluated at 186 US sites during the period 2019 to 2023. Of the cohort, 98 had CRC, 2144 had advanced precancerous lesions, 6973 had nonadvanced adenomas, and 10,961 had nonneoplastic findings or negative colonoscopy.
Advanced precancerous lesions included one or more adenomas or sessile serrated lesions measuring at least 1 cm in the longest dimension, lesions with villous histologic features, and high-grade dysplasia. The new DNA test identified 92 of 98 participants with CRC and 76 of 82 participants with screening-relevant cancers. Among the findings for the new assay:
- Sensitivity for any-stage CRC was 93.9% (95% confidence interval [CI], 87.1- 97.7)
- Sensitivity for advanced precancerous lesions was 43.4% (95% CI, 41.3-45.6)
- Sensitivity for high-grade dysplasia was 74.6% (95% CI, 65.6-82.3)
- Specificity for advanced neoplasia was 90.6% (95% CI, 90.1- 91.0).
- Specificity for nonneoplastic findings or negative colonoscopy was 92.7% (95% CI, 92.2-93.1)
- Specificity for negative colonoscopy was 93.3 (95% CI, 92.8-93.9)
- No adverse events occurred.
In the comparator assay, OC-AUTO FIT by Polymedco, sensitivity was 67.3% (95% CI, 57.1-76.5) for CRC, 23.3% (95% CI, 21.5-25.2) for advanced precancerous lesions, and 47.4% (95% CI, 37.9-56.9) for high-grade dysplasia. In the comparator FIT, however, specificity was better across all age groups — at 94.8% (95% CI, 94.4-95.1) for advanced neoplasia, 95.7% (95% CI, 95.3- 96.1) for nonneoplastic findings, and 96.0% (95% CI, 95.5-96.4) for negative colonoscopy.
In another article in the same issue of NEJM, Guardant Health’s cell-free DNA blood-based test had 83% sensitivity for CRC, 90% specificity for advanced neoplasia, and 13% sensitivity for advanced precancerous lesions in an average-risk population.
An age-related decrease in specificity was observed with the new Cologuard test, but that did not concern Dr. Imperiale because the same observation was made with the current version. “In fact, the next-gen version appears to have less of an age-related decrease in specificity than the current version, although, again, the two versions were not tested head-to-head,” he noted.
The effect of age-related background methylation of DNA is well known, he explained. “Clinicians and older patients in the screening age range do need to be aware of this effect on specificity before ordering or agreeing to do the test. I do not see this as a stumbling block to implementation, but it does require discussion between patient and ordering provider.”
The new version of the DNA test is expected to be available in about a year.
According to Dr. Imperiale, further research is needed to ascertain the test’s acceptability and adherence rates and to quantify its yield in population-based screening. Determining its cost-effectiveness and making it easier to use are other goals. “And most importantly, the degree of reduction in the incidence and mortality from colorectal cancer,” he said.
Cost-effectiveness and the selection of the testing interval may play roles in adherence, particularly in populations with lower rates of screening adherence than the general population, John M. Carethers, MD, AGAF, of the University of California, San Diego, noted in a related editorial.
“Adherence to screening varies according to age group, including persons in the 45- to 49-year age group who are now eligible for average-risk screening,” he wrote. “It is hoped that these newer tests will increase use and adherence and elevate the percentage of the population undergoing screening in order to reduce deaths from colorectal cancer.”
This study was sponsored by Exact Sciences Corporation, which conducted the stool testing at its laboratories.
Dr. Imperiale had no competing interests to disclose. Several study co-authors reported employment with Exact Sciences, or stock and intellectual property ownership. Dr. Shaukat disclosed consulting for Freenome. Dr. Carethers reported ties to Avantor Inc. and Geneoscopy.
, according to the large prospective BLUE-C study.
The multi-target assay by Exact Sciences Corporation, the makers of Cologuard, includes new biomarkers designed to increase specificity without decreasing sensitivity. It showed a sensitivity for CRC of almost 94%, with more than 43% sensitivity for advanced precancerous lesions and nearly 91% specificity for advanced neoplasia, according to the study results, which were published in The New England Journal of Medicine.
Adherence to CRC screening in the United States is well below the 80% national target, and the quest continues for noninvasive screening assays that might improve screening adherence, noted lead author Thomas F. Imperiale, MD, AGAF, a professor of medicine at Indiana University School of medicine in Indianapolis, and colleagues.
“The test’s manufacturer developed a new version of its existing Cologuard FIT/DNA test because it took to heart the feedback from primary care providers and gastroenterologists about the test’s low specificity,” Dr. Imperiale said in an interview. “The goal of the new test was to improve specificity without losing, and perhaps even gaining, some sensitivity — a goal that is not easily accomplished when you’re trying to improve on a sensitivity for colorectal cancer that was already 92.3% in the current version of Cologuard.”
Compared with the earlier version of Cologuard, he added, the new generation retained sensitivity for CRC and advanced precancerous lesions or polyps while improving specificity by 30% (90.6% vs 86.6%) for advanced neoplasia — a combination of CRC and advanced precancerous lesions, he said. “This with the caveat, however, that the two versions were not compared head-to-head in this new study,” Dr. Imperiale said.
The higher specificity for advanced lesions is expected to translate to a lower false positive rate. Lowering false positive rates is crucial because that reduces the need for costly, invasive, and unnecessary colonoscopies, said Aasma Shaukat, MD, MPH, AGAF, director of outcomes research in NYU Langone Health’s division of gastroenterology and hepatology in New York City.
“Many physicians felt there were too many false positives with the existing version, and that is anxiety-provoking in patients and providers,” said Dr. Shaukat, who was not involved in the study.
In her view, however, the test’s moderate improvements in detecting certain lesions does not make it demonstrably superior to its predecessor, and there is always the possibility of higher cost to consider.
While acknowledging that a higher sensitivity for all advanced precancerous lesions would have been welcome, Dr. Imperiale said the test detected 75% of the most worrisome of such lesions — “the ones containing high-grade dysplastic cells and suggesting near-term conversion to cancer. And its ability to detect other advanced lesions improved as the size of the lesions increased.”
Testing details
Almost 21,000 asymptomatic participants age 40 years and older undergoing screening colonoscopy were evaluated at 186 US sites during the period 2019 to 2023. Of the cohort, 98 had CRC, 2144 had advanced precancerous lesions, 6973 had nonadvanced adenomas, and 10,961 had nonneoplastic findings or negative colonoscopy.
Advanced precancerous lesions included one or more adenomas or sessile serrated lesions measuring at least 1 cm in the longest dimension, lesions with villous histologic features, and high-grade dysplasia. The new DNA test identified 92 of 98 participants with CRC and 76 of 82 participants with screening-relevant cancers. Among the findings for the new assay:
- Sensitivity for any-stage CRC was 93.9% (95% confidence interval [CI], 87.1- 97.7)
- Sensitivity for advanced precancerous lesions was 43.4% (95% CI, 41.3-45.6)
- Sensitivity for high-grade dysplasia was 74.6% (95% CI, 65.6-82.3)
- Specificity for advanced neoplasia was 90.6% (95% CI, 90.1- 91.0).
- Specificity for nonneoplastic findings or negative colonoscopy was 92.7% (95% CI, 92.2-93.1)
- Specificity for negative colonoscopy was 93.3 (95% CI, 92.8-93.9)
- No adverse events occurred.
In the comparator assay, OC-AUTO FIT by Polymedco, sensitivity was 67.3% (95% CI, 57.1-76.5) for CRC, 23.3% (95% CI, 21.5-25.2) for advanced precancerous lesions, and 47.4% (95% CI, 37.9-56.9) for high-grade dysplasia. In the comparator FIT, however, specificity was better across all age groups — at 94.8% (95% CI, 94.4-95.1) for advanced neoplasia, 95.7% (95% CI, 95.3- 96.1) for nonneoplastic findings, and 96.0% (95% CI, 95.5-96.4) for negative colonoscopy.
In another article in the same issue of NEJM, Guardant Health’s cell-free DNA blood-based test had 83% sensitivity for CRC, 90% specificity for advanced neoplasia, and 13% sensitivity for advanced precancerous lesions in an average-risk population.
An age-related decrease in specificity was observed with the new Cologuard test, but that did not concern Dr. Imperiale because the same observation was made with the current version. “In fact, the next-gen version appears to have less of an age-related decrease in specificity than the current version, although, again, the two versions were not tested head-to-head,” he noted.
The effect of age-related background methylation of DNA is well known, he explained. “Clinicians and older patients in the screening age range do need to be aware of this effect on specificity before ordering or agreeing to do the test. I do not see this as a stumbling block to implementation, but it does require discussion between patient and ordering provider.”
The new version of the DNA test is expected to be available in about a year.
According to Dr. Imperiale, further research is needed to ascertain the test’s acceptability and adherence rates and to quantify its yield in population-based screening. Determining its cost-effectiveness and making it easier to use are other goals. “And most importantly, the degree of reduction in the incidence and mortality from colorectal cancer,” he said.
Cost-effectiveness and the selection of the testing interval may play roles in adherence, particularly in populations with lower rates of screening adherence than the general population, John M. Carethers, MD, AGAF, of the University of California, San Diego, noted in a related editorial.
“Adherence to screening varies according to age group, including persons in the 45- to 49-year age group who are now eligible for average-risk screening,” he wrote. “It is hoped that these newer tests will increase use and adherence and elevate the percentage of the population undergoing screening in order to reduce deaths from colorectal cancer.”
This study was sponsored by Exact Sciences Corporation, which conducted the stool testing at its laboratories.
Dr. Imperiale had no competing interests to disclose. Several study co-authors reported employment with Exact Sciences, or stock and intellectual property ownership. Dr. Shaukat disclosed consulting for Freenome. Dr. Carethers reported ties to Avantor Inc. and Geneoscopy.
FROM NEW ENGLAND JOURNAL OF MEDICINE
USPSTF: Insufficient Evidence for Primary Care Interventions to Prevent Child Maltreatment
While primary care physicians are uniquely positioned to identify mistreated minors, there is insufficient evidence of benefits and harms to support primary care interventions to prevent maltreatment in children who have no indicative signs or symptoms. That is the conclusion of the US Preventive Services Task Force (USPSTF) in an update of its 2018 statement published in JAMA Network Open.
This gap, however, might be partially filled by addressing in young patients the known social determinants of health such as economic stability, food, shelter, and healthcare access. The USPSTF statement is based on a simultaneously published evidence review and synthesis compiled by Meera Viswanathan, PhD, of the RTI International-University of North Carolina at Chapel Hill Evidence-Based Practice Center in Triangle Park, NC, and colleagues.
The review included 14,355 participants in 25 trials, of which 23 included home visits. It measured such things as direct reports to Child Protective Services or removal of children from the home and proxy measures of abuse or neglect such as injury, emergency department visits, and hospitalizations. In addition, it looked at behavioral, developmental, emotional, mental or physical health and well-being, mortality, and harms.
More than 50% of the studies analyzed consisted of children with no prior reports of maltreatment. In addition to limited and inconsistent findings, the researchers noted wide variance in screening, identifying, and reporting child maltreatment to authorities, including variations by race or ethnicity, as well as wide variance in the accuracy of screening instruments.
“Contextual evidence pointed to the potential for bias or inaccuracy in screening, identification, and reporting of child maltreatment but also highlighted the importance of addressing social determinants when intervening to prevent child maltreatment,” Dr. Viswanathan’s group wrote.
The USPSTF panel, chaired by Michael J. Barry, MD, of Harvard Medical School, Boston, Massachusetts (now immediate past chair of the Task Force), stressed that the current statement applies only to children with no signs of maltreatment: Those with direct signs should be assessed and appropriately reported.
A Common and Costly Problem
Child abuse or neglect is widespread and has long-lasting adverse effects. In 2021, the statement noted, Child Protective Services identified 600,000 children as abused or neglected, with 1821 related deaths. Most (76%) experienced neglect, but many were subjected to physical abuse (16%), sexual abuse (10%), and sex trafficking (0.2%). Of the 1820 who died, 78% experienced neglect and 43% experienced physical abuse alone or combined with maltreatment such as neglect and psychological abuse.
Benefits aside, among the potential harms of intervention, the USPSTF noted, is family stigma and bias toward non-White and low-income groups. There may be a greater probability of clinicians’ disproportionately reporting abuse for the children of Black, Hispanic, indigenous, and one-parent households. Some studies indicate that more cases of maltreatment are missed in White children, the review authors noted.
“Additional evidence is needed to clarify potential linkages between improvements in social determinants of health and child maltreatment prevention,” the USPSTF panelists concluded. They acknowledged that their recommendation does not address the effectiveness of interventions such as home visits to improve family well-being.
In an accompanying editorial Samantha Schilling, MD, MSHP, of the Department of Pediatrics at the University of North Carolina at Chapel Hill, and colleagues from the Children’s Hospital of Philadelphia in Pennsylvania admitted they were “disheartened, but not surprised” at the USPSTF’s conclusions and urged that prevention measures be continued. “It is not yet time to wave the white flag of surrender and abandon primary care–based efforts to mitigate risks for child abuse and neglect.
They sent a heartfelt message to primary care doctors: “Know this: while additional evidence is amassed, do not stop your ongoing efforts to protect vulnerable children. You are an important component of child maltreatment prevention, although your actions and support cannot be delivered (or measured) in isolation.”
Dr. Schilling and associates argued that insufficient evidence does not mean that primary care prevention efforts are ineffective, only that evidence is lacking. They pointed out that proximal outcomes along a causal pathway have been used to assess the effectiveness of preventive measures and should be considered in this context. “For example, based on evidence that counseling about minimizing exposure to UV radiation is associated with a moderate increase in use of sunscreen protection, the USPSTF recommends that counseling be provided to certain populations,” they wrote. “The USPSTF did not require direct evidence that counseling decreases skin cancer.”
More high-quality research is needed, as the USPSTF recognized. “Given the inadequacy of the current gold standard measures of child maltreatment, proximal outcomes on the complex, multifactorial, causal pathway to child abuse and neglect should be considered,” the commentators wrote.
The commentators also acknowledged that patients’ caregivers often struggle to do their best with sparse resources and that resources such as food and housing, treatment for substance use and mental health disorders, appropriate strategies to manage typical child behavior, and affordable child care too often fall short.
They argued, therefore, that consequential prevention is not possible without sustained investment in policies and programs that provide tangible support to families, reduce childhood poverty, and target relevant risk factors.
The Agency for Healthcare Research and Quality of the US Department of Health and Human Services supports the operations of the USPSTF. Dr. Barry reported grants from Healthwise, a nonprofit organization, outside of the submitted work. Dr. Silverstein reported receiving a research grant on approaches to child maltreatment prevention. Dr. Lee reported grants from the National Institute on Aging. The evidence review was supported by a grant from the Agency for Healthcare Research. Dr. Viswanathan and colleagues disclosed no conflicts of interest. Dr. Wood reported grants from the Annie E. Casey Foundation outside of the submitted work. Dr. Christian reported personal fees from multiple government agencies and legal firms and provides medical-legal expert work in child abuse cases outside of the submitted work.
While primary care physicians are uniquely positioned to identify mistreated minors, there is insufficient evidence of benefits and harms to support primary care interventions to prevent maltreatment in children who have no indicative signs or symptoms. That is the conclusion of the US Preventive Services Task Force (USPSTF) in an update of its 2018 statement published in JAMA Network Open.
This gap, however, might be partially filled by addressing in young patients the known social determinants of health such as economic stability, food, shelter, and healthcare access. The USPSTF statement is based on a simultaneously published evidence review and synthesis compiled by Meera Viswanathan, PhD, of the RTI International-University of North Carolina at Chapel Hill Evidence-Based Practice Center in Triangle Park, NC, and colleagues.
The review included 14,355 participants in 25 trials, of which 23 included home visits. It measured such things as direct reports to Child Protective Services or removal of children from the home and proxy measures of abuse or neglect such as injury, emergency department visits, and hospitalizations. In addition, it looked at behavioral, developmental, emotional, mental or physical health and well-being, mortality, and harms.
More than 50% of the studies analyzed consisted of children with no prior reports of maltreatment. In addition to limited and inconsistent findings, the researchers noted wide variance in screening, identifying, and reporting child maltreatment to authorities, including variations by race or ethnicity, as well as wide variance in the accuracy of screening instruments.
“Contextual evidence pointed to the potential for bias or inaccuracy in screening, identification, and reporting of child maltreatment but also highlighted the importance of addressing social determinants when intervening to prevent child maltreatment,” Dr. Viswanathan’s group wrote.
The USPSTF panel, chaired by Michael J. Barry, MD, of Harvard Medical School, Boston, Massachusetts (now immediate past chair of the Task Force), stressed that the current statement applies only to children with no signs of maltreatment: Those with direct signs should be assessed and appropriately reported.
A Common and Costly Problem
Child abuse or neglect is widespread and has long-lasting adverse effects. In 2021, the statement noted, Child Protective Services identified 600,000 children as abused or neglected, with 1821 related deaths. Most (76%) experienced neglect, but many were subjected to physical abuse (16%), sexual abuse (10%), and sex trafficking (0.2%). Of the 1820 who died, 78% experienced neglect and 43% experienced physical abuse alone or combined with maltreatment such as neglect and psychological abuse.
Benefits aside, among the potential harms of intervention, the USPSTF noted, is family stigma and bias toward non-White and low-income groups. There may be a greater probability of clinicians’ disproportionately reporting abuse for the children of Black, Hispanic, indigenous, and one-parent households. Some studies indicate that more cases of maltreatment are missed in White children, the review authors noted.
“Additional evidence is needed to clarify potential linkages between improvements in social determinants of health and child maltreatment prevention,” the USPSTF panelists concluded. They acknowledged that their recommendation does not address the effectiveness of interventions such as home visits to improve family well-being.
In an accompanying editorial Samantha Schilling, MD, MSHP, of the Department of Pediatrics at the University of North Carolina at Chapel Hill, and colleagues from the Children’s Hospital of Philadelphia in Pennsylvania admitted they were “disheartened, but not surprised” at the USPSTF’s conclusions and urged that prevention measures be continued. “It is not yet time to wave the white flag of surrender and abandon primary care–based efforts to mitigate risks for child abuse and neglect.
They sent a heartfelt message to primary care doctors: “Know this: while additional evidence is amassed, do not stop your ongoing efforts to protect vulnerable children. You are an important component of child maltreatment prevention, although your actions and support cannot be delivered (or measured) in isolation.”
Dr. Schilling and associates argued that insufficient evidence does not mean that primary care prevention efforts are ineffective, only that evidence is lacking. They pointed out that proximal outcomes along a causal pathway have been used to assess the effectiveness of preventive measures and should be considered in this context. “For example, based on evidence that counseling about minimizing exposure to UV radiation is associated with a moderate increase in use of sunscreen protection, the USPSTF recommends that counseling be provided to certain populations,” they wrote. “The USPSTF did not require direct evidence that counseling decreases skin cancer.”
More high-quality research is needed, as the USPSTF recognized. “Given the inadequacy of the current gold standard measures of child maltreatment, proximal outcomes on the complex, multifactorial, causal pathway to child abuse and neglect should be considered,” the commentators wrote.
The commentators also acknowledged that patients’ caregivers often struggle to do their best with sparse resources and that resources such as food and housing, treatment for substance use and mental health disorders, appropriate strategies to manage typical child behavior, and affordable child care too often fall short.
They argued, therefore, that consequential prevention is not possible without sustained investment in policies and programs that provide tangible support to families, reduce childhood poverty, and target relevant risk factors.
The Agency for Healthcare Research and Quality of the US Department of Health and Human Services supports the operations of the USPSTF. Dr. Barry reported grants from Healthwise, a nonprofit organization, outside of the submitted work. Dr. Silverstein reported receiving a research grant on approaches to child maltreatment prevention. Dr. Lee reported grants from the National Institute on Aging. The evidence review was supported by a grant from the Agency for Healthcare Research. Dr. Viswanathan and colleagues disclosed no conflicts of interest. Dr. Wood reported grants from the Annie E. Casey Foundation outside of the submitted work. Dr. Christian reported personal fees from multiple government agencies and legal firms and provides medical-legal expert work in child abuse cases outside of the submitted work.
While primary care physicians are uniquely positioned to identify mistreated minors, there is insufficient evidence of benefits and harms to support primary care interventions to prevent maltreatment in children who have no indicative signs or symptoms. That is the conclusion of the US Preventive Services Task Force (USPSTF) in an update of its 2018 statement published in JAMA Network Open.
This gap, however, might be partially filled by addressing in young patients the known social determinants of health such as economic stability, food, shelter, and healthcare access. The USPSTF statement is based on a simultaneously published evidence review and synthesis compiled by Meera Viswanathan, PhD, of the RTI International-University of North Carolina at Chapel Hill Evidence-Based Practice Center in Triangle Park, NC, and colleagues.
The review included 14,355 participants in 25 trials, of which 23 included home visits. It measured such things as direct reports to Child Protective Services or removal of children from the home and proxy measures of abuse or neglect such as injury, emergency department visits, and hospitalizations. In addition, it looked at behavioral, developmental, emotional, mental or physical health and well-being, mortality, and harms.
More than 50% of the studies analyzed consisted of children with no prior reports of maltreatment. In addition to limited and inconsistent findings, the researchers noted wide variance in screening, identifying, and reporting child maltreatment to authorities, including variations by race or ethnicity, as well as wide variance in the accuracy of screening instruments.
“Contextual evidence pointed to the potential for bias or inaccuracy in screening, identification, and reporting of child maltreatment but also highlighted the importance of addressing social determinants when intervening to prevent child maltreatment,” Dr. Viswanathan’s group wrote.
The USPSTF panel, chaired by Michael J. Barry, MD, of Harvard Medical School, Boston, Massachusetts (now immediate past chair of the Task Force), stressed that the current statement applies only to children with no signs of maltreatment: Those with direct signs should be assessed and appropriately reported.
A Common and Costly Problem
Child abuse or neglect is widespread and has long-lasting adverse effects. In 2021, the statement noted, Child Protective Services identified 600,000 children as abused or neglected, with 1821 related deaths. Most (76%) experienced neglect, but many were subjected to physical abuse (16%), sexual abuse (10%), and sex trafficking (0.2%). Of the 1820 who died, 78% experienced neglect and 43% experienced physical abuse alone or combined with maltreatment such as neglect and psychological abuse.
Benefits aside, among the potential harms of intervention, the USPSTF noted, is family stigma and bias toward non-White and low-income groups. There may be a greater probability of clinicians’ disproportionately reporting abuse for the children of Black, Hispanic, indigenous, and one-parent households. Some studies indicate that more cases of maltreatment are missed in White children, the review authors noted.
“Additional evidence is needed to clarify potential linkages between improvements in social determinants of health and child maltreatment prevention,” the USPSTF panelists concluded. They acknowledged that their recommendation does not address the effectiveness of interventions such as home visits to improve family well-being.
In an accompanying editorial Samantha Schilling, MD, MSHP, of the Department of Pediatrics at the University of North Carolina at Chapel Hill, and colleagues from the Children’s Hospital of Philadelphia in Pennsylvania admitted they were “disheartened, but not surprised” at the USPSTF’s conclusions and urged that prevention measures be continued. “It is not yet time to wave the white flag of surrender and abandon primary care–based efforts to mitigate risks for child abuse and neglect.
They sent a heartfelt message to primary care doctors: “Know this: while additional evidence is amassed, do not stop your ongoing efforts to protect vulnerable children. You are an important component of child maltreatment prevention, although your actions and support cannot be delivered (or measured) in isolation.”
Dr. Schilling and associates argued that insufficient evidence does not mean that primary care prevention efforts are ineffective, only that evidence is lacking. They pointed out that proximal outcomes along a causal pathway have been used to assess the effectiveness of preventive measures and should be considered in this context. “For example, based on evidence that counseling about minimizing exposure to UV radiation is associated with a moderate increase in use of sunscreen protection, the USPSTF recommends that counseling be provided to certain populations,” they wrote. “The USPSTF did not require direct evidence that counseling decreases skin cancer.”
More high-quality research is needed, as the USPSTF recognized. “Given the inadequacy of the current gold standard measures of child maltreatment, proximal outcomes on the complex, multifactorial, causal pathway to child abuse and neglect should be considered,” the commentators wrote.
The commentators also acknowledged that patients’ caregivers often struggle to do their best with sparse resources and that resources such as food and housing, treatment for substance use and mental health disorders, appropriate strategies to manage typical child behavior, and affordable child care too often fall short.
They argued, therefore, that consequential prevention is not possible without sustained investment in policies and programs that provide tangible support to families, reduce childhood poverty, and target relevant risk factors.
The Agency for Healthcare Research and Quality of the US Department of Health and Human Services supports the operations of the USPSTF. Dr. Barry reported grants from Healthwise, a nonprofit organization, outside of the submitted work. Dr. Silverstein reported receiving a research grant on approaches to child maltreatment prevention. Dr. Lee reported grants from the National Institute on Aging. The evidence review was supported by a grant from the Agency for Healthcare Research. Dr. Viswanathan and colleagues disclosed no conflicts of interest. Dr. Wood reported grants from the Annie E. Casey Foundation outside of the submitted work. Dr. Christian reported personal fees from multiple government agencies and legal firms and provides medical-legal expert work in child abuse cases outside of the submitted work.
FROM JAMA NETWORK OPEN
Long-Term Calcium and Vitamin D: Cancer Deaths Down, CVD Deaths Up in Older Women?
Some doctors may be scratching their heads over a new analysis reporting that combined calcium and vitamin D (CaD) supplements appear to be associated with a slight 6% increase in cardiovascular (CVD) mortality, a slight 7% decrease in cancer risk, and no effect on osteoporotic fracture in postmenopausal women.
The study, in Annals of Internal Medicine, found no effect of supplementation on all-cause mortality.
The findings emerged from an analysis of more than 20 years’ follow-up data on a randomized trial in postmenopausal women conducted as part of the Women’s Health Initiative (WHI).
Cynthia A. Thomson, PhD, RD, first author and cancer prevention scientist at the Arizona Cancer Center and a professor of health promotion sciences at the University of Arizona in Tucson said the findings recommend individualized assessment of the need for supplements for older women as they consider them in hopes of preventing fractures.
“Evaluate your patients individually and understand that there are some who may benefit from supplementation, for example, in terms of reducing colorectal cancer mortality,” Dr. Thomson said in an interview. The approach should be nuanced. “If you check the adequacy of vitamin D and calcium in their diets, supplementation may not be needed.” She added that supplementation is best considered in the context of a woman’s overall health profile, including risk factors for fracture, heart disease, and cancer, especially colorectal cancer (CRC).
Study Details
The investigators conducted postintervention follow-up of the WHI’s 7-year multicenter randomized intervention trial of CaD vs placebo.
Since existing evidence of long-term health outcomes was limited, the trial, begun in 1999 and closed in 2005, enrolled 36,282 postmenopausal women (mean age 62) with no history of breast or colorectal cancer. They were randomly assigned 1:1 to supplementation with 1000 mg of calcium carbonate (400 mg elemental calcium) plus 400 IU of vitamin D3 daily or placebo, taken twice daily in half doses.
Study outcomes were incidence of CRC, total and invasive breast cancer; disease-specific and all-cause mortality; total CVD; and hip fracture measured through December 2020, with analyses stratified by personal supplement usage.
Cancer. CaD was associated with reduced incident total cancer, CRC, and invasive breast cancer — notably among participants not taking CaD before randomization. Cancer incidence estimates varied widely, the authors noted, when stratified by supplement use before randomization. Noting that CaD seemed to have more cancer-related impact in those without prior supplementation, the authors suggested supplementation may affect cancer biology primarily by augmenting nutrient insufficiency.
An estimated 7% reduction in cancer mortality was observed after a median cumulative follow-up of 22.3 years: 1817 vs 1943 deaths (hazard ratio, 0.93; 95% CI, 0.87-0.99).
CVD. An estimated 6% increase in CVD mortality was seen in the CaD group: 2621 vs 2420 deaths (HR, 1.06; 95% CI, 1.01-1.12). Pretrial supplement users were found to be at higher CVD risk.
Hip fracture. No effect on hip fracture risk was measured, but the authors cautioned that hip fracture and CVD outcomes were available only for a subset of participants, and the effects of calcium alone vs vitamin D alone vs the combination could not be disentangled.
In a small subgroup analysis, some CaD users were seen to respond in terms of bone mineral density but since only 4 of the study’s 40 sites collected such information, the study was underpowered to examine the effect. ”Many other studies, however, show a response to supplementation in women who already have bone mineral deficits,” Dr. Thomson said.
The Calcification Question
One of the possible mechanisms of harm is that high-dose calcium supplements can increase the rate of blood coagulation and promote vascular calcification, said Emma Laing, PhD, RD, director of dietetics at the University of Georgia in Athens and a spokesperson for the Chicago-based Academy of Nutrition and Dietetics.
“Other factors that should be considered when determining a patient’s CVD risk are race, genetic predisposition, medical and social history, response to stress, and lifestyle behaviors, as well as the length of time supplements have been consumed,” added Dr. Laing, who was not involved in the WHI analysis.
“We asked ourselves if CaD supplements might contribute to calcification of the coronary arteries, since some believe this to be the case, although the literature is mixed,” said Dr. Thomson.
“So we did a shorter ancillary study in a small sample of several hundred [women] to see if there was any increase in calcification” and no difference was seen on imaging across the two arms. “However, women who were already on supplements before entering the study seemed to be at higher CVD risk,” she said.
Added study coauthor JoAnn E. Manson, MD, DrPH, chief of the division of preventive medicine at Brigham and Women’s Hospital and professor of women’s health at Harvard Medical School, both in Boston: “With no increase or decrease in coronary artery calcium at the end of the trial, we don’t believe starting or continuing calcium/vitamin D supplements should require screening for coronary artery disease.”
Some randomized trials and systematic reviews, however, have observed an increased risk of CVD in healthy patients on calcium supplements, with one Korean meta-analysis reporting a 15% increase in CVD risk in healthy postmenopausal women taking calcium supplements. Another meta-analysis found a link between calcium supplements and a greater risk of various cardiovascular outcomes, especially myocardial infarction.
Vitamin D Supplementation
As for vitamin D only supplementation, an updated meta-analysis including more than 83,000 individuals showed that it confers no cardiovascular protection and is therefore not indicated for this purpose.
Practice Considerations
Offering an outsider’s perspective, Sarah G. Candler, MD, MPH, an internist in Houston specializing in primary care for older high-risk adults, said: “Unfortunately, this latest study continues the trend of creating more questions than answers. If the adverse outcome of CVD death is a result of supplementation, it is unclear if this is due to the vitamin D, the calcium, or both. And it is unclear if this is dose dependent, time dependent, or due to concurrent risk factors unique to certain populations.
“It is recommended that patients at risk of osteoporosis based on age, sex, medications, and lifestyle be screened for osteoporosis and treated accordingly, including supplementation with CaD,” Dr. Candler said. “It remains unclear whether supplementation with CaD in the absence of osteoporosis and osteopenia is net beneficial or harmful, and at this time I would not recommend it to my patients.”
Added Dr. Manson: “The very small increase seen in cardiovascular mortality wouldn’t be a reason to discontinue supplementation among women who have been advised by their healthcare providers to take these supplements for bone health or other purposes.
“Among those at usual risk of fracture, we recommend trying to obtain adequate calcium and vitamin D from food sources first and to use supplements only for the purpose of filling gaps in intake,” Dr. Manson continued. Overall, the findings support the national recommended dietary allowances for daily calcium intake of 1200 mg and daily vitamin D intake of 600-800 IU among postmenopausal women for maintenance of bone health, she said.
While a 2022 study found that vitamin D supplementation alone did not prevent fractures in healthy adults, other research has shown that a calcium/vitamin D combination is more likely to protect the skeleton.
“Patients at risk for fractures will probably benefit from calcium and/or vitamin D supplementation if they do not meet dietary intake requirements, have malabsorption syndromes, are taking medications that affect nutrient absorption, or if they are older and not regularly exposed to sunlight,” said Dr. Laing. “A combination of biochemical, imaging, functional, and dietary intake data can help determine if a supplement is warranted.”
She stressed that additional research is needed in more diverse populations before changing practice guidelines. “However, doctors should continue to weigh the risks and benefits of prescribing supplements for each patient.”
The WHI program is funded by the National Heart, Lung, and Blood Institute. Dr. Thomson disclosed no competing interests. Dr. Manson reported a relationship with Mars Edge. Multiple authors reported grant support from government funding agencies. The outside commentators had no relevant competing interests to disclose.
Some doctors may be scratching their heads over a new analysis reporting that combined calcium and vitamin D (CaD) supplements appear to be associated with a slight 6% increase in cardiovascular (CVD) mortality, a slight 7% decrease in cancer risk, and no effect on osteoporotic fracture in postmenopausal women.
The study, in Annals of Internal Medicine, found no effect of supplementation on all-cause mortality.
The findings emerged from an analysis of more than 20 years’ follow-up data on a randomized trial in postmenopausal women conducted as part of the Women’s Health Initiative (WHI).
Cynthia A. Thomson, PhD, RD, first author and cancer prevention scientist at the Arizona Cancer Center and a professor of health promotion sciences at the University of Arizona in Tucson said the findings recommend individualized assessment of the need for supplements for older women as they consider them in hopes of preventing fractures.
“Evaluate your patients individually and understand that there are some who may benefit from supplementation, for example, in terms of reducing colorectal cancer mortality,” Dr. Thomson said in an interview. The approach should be nuanced. “If you check the adequacy of vitamin D and calcium in their diets, supplementation may not be needed.” She added that supplementation is best considered in the context of a woman’s overall health profile, including risk factors for fracture, heart disease, and cancer, especially colorectal cancer (CRC).
Study Details
The investigators conducted postintervention follow-up of the WHI’s 7-year multicenter randomized intervention trial of CaD vs placebo.
Since existing evidence of long-term health outcomes was limited, the trial, begun in 1999 and closed in 2005, enrolled 36,282 postmenopausal women (mean age 62) with no history of breast or colorectal cancer. They were randomly assigned 1:1 to supplementation with 1000 mg of calcium carbonate (400 mg elemental calcium) plus 400 IU of vitamin D3 daily or placebo, taken twice daily in half doses.
Study outcomes were incidence of CRC, total and invasive breast cancer; disease-specific and all-cause mortality; total CVD; and hip fracture measured through December 2020, with analyses stratified by personal supplement usage.
Cancer. CaD was associated with reduced incident total cancer, CRC, and invasive breast cancer — notably among participants not taking CaD before randomization. Cancer incidence estimates varied widely, the authors noted, when stratified by supplement use before randomization. Noting that CaD seemed to have more cancer-related impact in those without prior supplementation, the authors suggested supplementation may affect cancer biology primarily by augmenting nutrient insufficiency.
An estimated 7% reduction in cancer mortality was observed after a median cumulative follow-up of 22.3 years: 1817 vs 1943 deaths (hazard ratio, 0.93; 95% CI, 0.87-0.99).
CVD. An estimated 6% increase in CVD mortality was seen in the CaD group: 2621 vs 2420 deaths (HR, 1.06; 95% CI, 1.01-1.12). Pretrial supplement users were found to be at higher CVD risk.
Hip fracture. No effect on hip fracture risk was measured, but the authors cautioned that hip fracture and CVD outcomes were available only for a subset of participants, and the effects of calcium alone vs vitamin D alone vs the combination could not be disentangled.
In a small subgroup analysis, some CaD users were seen to respond in terms of bone mineral density but since only 4 of the study’s 40 sites collected such information, the study was underpowered to examine the effect. ”Many other studies, however, show a response to supplementation in women who already have bone mineral deficits,” Dr. Thomson said.
The Calcification Question
One of the possible mechanisms of harm is that high-dose calcium supplements can increase the rate of blood coagulation and promote vascular calcification, said Emma Laing, PhD, RD, director of dietetics at the University of Georgia in Athens and a spokesperson for the Chicago-based Academy of Nutrition and Dietetics.
“Other factors that should be considered when determining a patient’s CVD risk are race, genetic predisposition, medical and social history, response to stress, and lifestyle behaviors, as well as the length of time supplements have been consumed,” added Dr. Laing, who was not involved in the WHI analysis.
“We asked ourselves if CaD supplements might contribute to calcification of the coronary arteries, since some believe this to be the case, although the literature is mixed,” said Dr. Thomson.
“So we did a shorter ancillary study in a small sample of several hundred [women] to see if there was any increase in calcification” and no difference was seen on imaging across the two arms. “However, women who were already on supplements before entering the study seemed to be at higher CVD risk,” she said.
Added study coauthor JoAnn E. Manson, MD, DrPH, chief of the division of preventive medicine at Brigham and Women’s Hospital and professor of women’s health at Harvard Medical School, both in Boston: “With no increase or decrease in coronary artery calcium at the end of the trial, we don’t believe starting or continuing calcium/vitamin D supplements should require screening for coronary artery disease.”
Some randomized trials and systematic reviews, however, have observed an increased risk of CVD in healthy patients on calcium supplements, with one Korean meta-analysis reporting a 15% increase in CVD risk in healthy postmenopausal women taking calcium supplements. Another meta-analysis found a link between calcium supplements and a greater risk of various cardiovascular outcomes, especially myocardial infarction.
Vitamin D Supplementation
As for vitamin D only supplementation, an updated meta-analysis including more than 83,000 individuals showed that it confers no cardiovascular protection and is therefore not indicated for this purpose.
Practice Considerations
Offering an outsider’s perspective, Sarah G. Candler, MD, MPH, an internist in Houston specializing in primary care for older high-risk adults, said: “Unfortunately, this latest study continues the trend of creating more questions than answers. If the adverse outcome of CVD death is a result of supplementation, it is unclear if this is due to the vitamin D, the calcium, or both. And it is unclear if this is dose dependent, time dependent, or due to concurrent risk factors unique to certain populations.
“It is recommended that patients at risk of osteoporosis based on age, sex, medications, and lifestyle be screened for osteoporosis and treated accordingly, including supplementation with CaD,” Dr. Candler said. “It remains unclear whether supplementation with CaD in the absence of osteoporosis and osteopenia is net beneficial or harmful, and at this time I would not recommend it to my patients.”
Added Dr. Manson: “The very small increase seen in cardiovascular mortality wouldn’t be a reason to discontinue supplementation among women who have been advised by their healthcare providers to take these supplements for bone health or other purposes.
“Among those at usual risk of fracture, we recommend trying to obtain adequate calcium and vitamin D from food sources first and to use supplements only for the purpose of filling gaps in intake,” Dr. Manson continued. Overall, the findings support the national recommended dietary allowances for daily calcium intake of 1200 mg and daily vitamin D intake of 600-800 IU among postmenopausal women for maintenance of bone health, she said.
While a 2022 study found that vitamin D supplementation alone did not prevent fractures in healthy adults, other research has shown that a calcium/vitamin D combination is more likely to protect the skeleton.
“Patients at risk for fractures will probably benefit from calcium and/or vitamin D supplementation if they do not meet dietary intake requirements, have malabsorption syndromes, are taking medications that affect nutrient absorption, or if they are older and not regularly exposed to sunlight,” said Dr. Laing. “A combination of biochemical, imaging, functional, and dietary intake data can help determine if a supplement is warranted.”
She stressed that additional research is needed in more diverse populations before changing practice guidelines. “However, doctors should continue to weigh the risks and benefits of prescribing supplements for each patient.”
The WHI program is funded by the National Heart, Lung, and Blood Institute. Dr. Thomson disclosed no competing interests. Dr. Manson reported a relationship with Mars Edge. Multiple authors reported grant support from government funding agencies. The outside commentators had no relevant competing interests to disclose.
Some doctors may be scratching their heads over a new analysis reporting that combined calcium and vitamin D (CaD) supplements appear to be associated with a slight 6% increase in cardiovascular (CVD) mortality, a slight 7% decrease in cancer risk, and no effect on osteoporotic fracture in postmenopausal women.
The study, in Annals of Internal Medicine, found no effect of supplementation on all-cause mortality.
The findings emerged from an analysis of more than 20 years’ follow-up data on a randomized trial in postmenopausal women conducted as part of the Women’s Health Initiative (WHI).
Cynthia A. Thomson, PhD, RD, first author and cancer prevention scientist at the Arizona Cancer Center and a professor of health promotion sciences at the University of Arizona in Tucson said the findings recommend individualized assessment of the need for supplements for older women as they consider them in hopes of preventing fractures.
“Evaluate your patients individually and understand that there are some who may benefit from supplementation, for example, in terms of reducing colorectal cancer mortality,” Dr. Thomson said in an interview. The approach should be nuanced. “If you check the adequacy of vitamin D and calcium in their diets, supplementation may not be needed.” She added that supplementation is best considered in the context of a woman’s overall health profile, including risk factors for fracture, heart disease, and cancer, especially colorectal cancer (CRC).
Study Details
The investigators conducted postintervention follow-up of the WHI’s 7-year multicenter randomized intervention trial of CaD vs placebo.
Since existing evidence of long-term health outcomes was limited, the trial, begun in 1999 and closed in 2005, enrolled 36,282 postmenopausal women (mean age 62) with no history of breast or colorectal cancer. They were randomly assigned 1:1 to supplementation with 1000 mg of calcium carbonate (400 mg elemental calcium) plus 400 IU of vitamin D3 daily or placebo, taken twice daily in half doses.
Study outcomes were incidence of CRC, total and invasive breast cancer; disease-specific and all-cause mortality; total CVD; and hip fracture measured through December 2020, with analyses stratified by personal supplement usage.
Cancer. CaD was associated with reduced incident total cancer, CRC, and invasive breast cancer — notably among participants not taking CaD before randomization. Cancer incidence estimates varied widely, the authors noted, when stratified by supplement use before randomization. Noting that CaD seemed to have more cancer-related impact in those without prior supplementation, the authors suggested supplementation may affect cancer biology primarily by augmenting nutrient insufficiency.
An estimated 7% reduction in cancer mortality was observed after a median cumulative follow-up of 22.3 years: 1817 vs 1943 deaths (hazard ratio, 0.93; 95% CI, 0.87-0.99).
CVD. An estimated 6% increase in CVD mortality was seen in the CaD group: 2621 vs 2420 deaths (HR, 1.06; 95% CI, 1.01-1.12). Pretrial supplement users were found to be at higher CVD risk.
Hip fracture. No effect on hip fracture risk was measured, but the authors cautioned that hip fracture and CVD outcomes were available only for a subset of participants, and the effects of calcium alone vs vitamin D alone vs the combination could not be disentangled.
In a small subgroup analysis, some CaD users were seen to respond in terms of bone mineral density but since only 4 of the study’s 40 sites collected such information, the study was underpowered to examine the effect. ”Many other studies, however, show a response to supplementation in women who already have bone mineral deficits,” Dr. Thomson said.
The Calcification Question
One of the possible mechanisms of harm is that high-dose calcium supplements can increase the rate of blood coagulation and promote vascular calcification, said Emma Laing, PhD, RD, director of dietetics at the University of Georgia in Athens and a spokesperson for the Chicago-based Academy of Nutrition and Dietetics.
“Other factors that should be considered when determining a patient’s CVD risk are race, genetic predisposition, medical and social history, response to stress, and lifestyle behaviors, as well as the length of time supplements have been consumed,” added Dr. Laing, who was not involved in the WHI analysis.
“We asked ourselves if CaD supplements might contribute to calcification of the coronary arteries, since some believe this to be the case, although the literature is mixed,” said Dr. Thomson.
“So we did a shorter ancillary study in a small sample of several hundred [women] to see if there was any increase in calcification” and no difference was seen on imaging across the two arms. “However, women who were already on supplements before entering the study seemed to be at higher CVD risk,” she said.
Added study coauthor JoAnn E. Manson, MD, DrPH, chief of the division of preventive medicine at Brigham and Women’s Hospital and professor of women’s health at Harvard Medical School, both in Boston: “With no increase or decrease in coronary artery calcium at the end of the trial, we don’t believe starting or continuing calcium/vitamin D supplements should require screening for coronary artery disease.”
Some randomized trials and systematic reviews, however, have observed an increased risk of CVD in healthy patients on calcium supplements, with one Korean meta-analysis reporting a 15% increase in CVD risk in healthy postmenopausal women taking calcium supplements. Another meta-analysis found a link between calcium supplements and a greater risk of various cardiovascular outcomes, especially myocardial infarction.
Vitamin D Supplementation
As for vitamin D only supplementation, an updated meta-analysis including more than 83,000 individuals showed that it confers no cardiovascular protection and is therefore not indicated for this purpose.
Practice Considerations
Offering an outsider’s perspective, Sarah G. Candler, MD, MPH, an internist in Houston specializing in primary care for older high-risk adults, said: “Unfortunately, this latest study continues the trend of creating more questions than answers. If the adverse outcome of CVD death is a result of supplementation, it is unclear if this is due to the vitamin D, the calcium, or both. And it is unclear if this is dose dependent, time dependent, or due to concurrent risk factors unique to certain populations.
“It is recommended that patients at risk of osteoporosis based on age, sex, medications, and lifestyle be screened for osteoporosis and treated accordingly, including supplementation with CaD,” Dr. Candler said. “It remains unclear whether supplementation with CaD in the absence of osteoporosis and osteopenia is net beneficial or harmful, and at this time I would not recommend it to my patients.”
Added Dr. Manson: “The very small increase seen in cardiovascular mortality wouldn’t be a reason to discontinue supplementation among women who have been advised by their healthcare providers to take these supplements for bone health or other purposes.
“Among those at usual risk of fracture, we recommend trying to obtain adequate calcium and vitamin D from food sources first and to use supplements only for the purpose of filling gaps in intake,” Dr. Manson continued. Overall, the findings support the national recommended dietary allowances for daily calcium intake of 1200 mg and daily vitamin D intake of 600-800 IU among postmenopausal women for maintenance of bone health, she said.
While a 2022 study found that vitamin D supplementation alone did not prevent fractures in healthy adults, other research has shown that a calcium/vitamin D combination is more likely to protect the skeleton.
“Patients at risk for fractures will probably benefit from calcium and/or vitamin D supplementation if they do not meet dietary intake requirements, have malabsorption syndromes, are taking medications that affect nutrient absorption, or if they are older and not regularly exposed to sunlight,” said Dr. Laing. “A combination of biochemical, imaging, functional, and dietary intake data can help determine if a supplement is warranted.”
She stressed that additional research is needed in more diverse populations before changing practice guidelines. “However, doctors should continue to weigh the risks and benefits of prescribing supplements for each patient.”
The WHI program is funded by the National Heart, Lung, and Blood Institute. Dr. Thomson disclosed no competing interests. Dr. Manson reported a relationship with Mars Edge. Multiple authors reported grant support from government funding agencies. The outside commentators had no relevant competing interests to disclose.
FROM ANNALS OF INTERNAL MEDICINE
AGA Supports Fecal Microbiota Therapies for CDI but Not IBD or IBS
Addressing Clostridium difficile infection (CDI), Crohn’s disease (CD) ulcerative colitis (UC), pouchitis, and irritable bowel syndrome (IBS), the guidance supports FMT for the prevention of recurrent CDI but not for inflammatory bowel disease (IBD) or IBS — outside of clinical trials.
The AGA’s recommendations were published in Gastroenterology.
“Fecal microbiota–based therapies are effective therapy to prevent recurrent C. difficile in select patients,” the AGA guideline states. “Conventional fecal microbiota transplant is an adjuvant treatment for select adults hospitalized with severe or fulminant C. difficile infection not responding to standard of care antibiotics. Fecal microbiota transplant cannot yet be recommended in other gastrointestinal conditions.”
“We thought it was important to write this guideline because of the growing number of trials of FMT in IBD and IBS populations. It was also important with the new FDA-approved treatments on the market,” the guideline’s first author, Anne F. Peery, MD, MSCR, AGAF, told this news organization, noting that the recently approved products did not yield better results than those of conventional rectal FMT. “The guidelines will help clinicians understand the available therapies and how to use these treatments,” added Dr. Peery, associate professor in the Division of Gastroenterology and Hepatology at the University of North Carolina School of Medicine in Chapel Hill.
Although the existing evidence is of low or very low certainty, Dr. Peery acknowledged, gastroenterologists “should be comfortable with conventional FMT and also the new FDA-approved products. We spent a considerable amount of time developing implementation considerations, which is practical advice to help clinicians use the guideline recommendations.”
Designed to counteract intestinal dysbiosis and restore protective gut flora, the FMT approach includes conventional, colonoscopically delivered donor stool transplants as well as two newly approved options: rectally given fecal microbiota (live-jslm/ Rebyota) and most recently, orally delivered fecal microbiota spores (live-brpk/ Vowst).
The AGA urges careful pretreatment consideration for patients who require frequent antibiotics or long-term antibiotic prophylaxis since ongoing antibiotics may diminish the efficacy of FMT.
The guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis, followed by the Evidence-to-Decision framework to develop recommendations for these therapies and algorithms for their implementation into clinical practice.
Recommendations
The eight-member panel suggested the following practices on behalf of the AGA Clinical Guidelines Committee:
- In immunocompetent adults with recurrent CDI, select use of FMT can be used after completion of standard-of-care antibiotics to prevent recurrence. It can be considered after the second recurrence (episode 3) of CDI or in select patients at high risk for either recurrent CDI or a morbid CDI recurrence. Recurrent CDI is defined as clinically significant diarrhea ≥ 3 unformed stools in 24 hours with a confirmatory positive test within 8 weeks of completing antibiotics. Select use includes patients who have recovered from severe, fulminant, or particularly treatment-refractory CDI and patients with significant comorbidities. Severe CDI involves a leukocyte count of ≥15 × 109 cells/L and/or creatinine ≥1.5 mg/dL, while fulminant CDI involves shock, ileus, or megacolon and can be fatal.
- In mildly or moderately immunocompromised adults with recurrent CDI, the guidance recommends select use of conventional fecal microbiota transplant.
- In severely immunocompromised adults or those undergoing cytotoxic treatment, the AGA advises against the use of any fecal microbiota-based therapies to prevent recurrent CDI.
- Conventional FMT is not advised in patients who have bowel perforation or obstruction or are severely immunocompromised.
- For CDI patients not interested in FMT, reasonable alternatives to prevent recurrence are a vancomycin taper, tapered-pulsed fidaxomicin, or bezlotoxumab.
- In adults hospitalized with severe or fulminant CDI not responding to standard-of-care antibiotics, the AGA recommends select use of conventional FM transplant.
- In the current absence of evidence, the guidance advises against the use of conventional fecal microbiota transplant as treatment for IBD or IBS except in the context of clinical trials.
“We felt the data for using FMT in the treatment of UC was promising, but there is still a lot more work to be done in IBD and IBS,” Dr. Peery said. For each disease section the guideline outlined directions for future research. It will be updated in 3-5 years as more evidence becomes available.
This guideline was fully funded by the AGA Institute. Dr. Peery and fellow panel member Dr. Benjamin Lebwohl are supported by grants the National Institute of Diabetes and Digestive and Kidney Diseases. Panel member Colleen R. Kelly, MD, is supported by the National Institute of Allergy and Infectious Diseases.
None of the panel members had any conflicts of interest to report.
Addressing Clostridium difficile infection (CDI), Crohn’s disease (CD) ulcerative colitis (UC), pouchitis, and irritable bowel syndrome (IBS), the guidance supports FMT for the prevention of recurrent CDI but not for inflammatory bowel disease (IBD) or IBS — outside of clinical trials.
The AGA’s recommendations were published in Gastroenterology.
“Fecal microbiota–based therapies are effective therapy to prevent recurrent C. difficile in select patients,” the AGA guideline states. “Conventional fecal microbiota transplant is an adjuvant treatment for select adults hospitalized with severe or fulminant C. difficile infection not responding to standard of care antibiotics. Fecal microbiota transplant cannot yet be recommended in other gastrointestinal conditions.”
“We thought it was important to write this guideline because of the growing number of trials of FMT in IBD and IBS populations. It was also important with the new FDA-approved treatments on the market,” the guideline’s first author, Anne F. Peery, MD, MSCR, AGAF, told this news organization, noting that the recently approved products did not yield better results than those of conventional rectal FMT. “The guidelines will help clinicians understand the available therapies and how to use these treatments,” added Dr. Peery, associate professor in the Division of Gastroenterology and Hepatology at the University of North Carolina School of Medicine in Chapel Hill.
Although the existing evidence is of low or very low certainty, Dr. Peery acknowledged, gastroenterologists “should be comfortable with conventional FMT and also the new FDA-approved products. We spent a considerable amount of time developing implementation considerations, which is practical advice to help clinicians use the guideline recommendations.”
Designed to counteract intestinal dysbiosis and restore protective gut flora, the FMT approach includes conventional, colonoscopically delivered donor stool transplants as well as two newly approved options: rectally given fecal microbiota (live-jslm/ Rebyota) and most recently, orally delivered fecal microbiota spores (live-brpk/ Vowst).
The AGA urges careful pretreatment consideration for patients who require frequent antibiotics or long-term antibiotic prophylaxis since ongoing antibiotics may diminish the efficacy of FMT.
The guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis, followed by the Evidence-to-Decision framework to develop recommendations for these therapies and algorithms for their implementation into clinical practice.
Recommendations
The eight-member panel suggested the following practices on behalf of the AGA Clinical Guidelines Committee:
- In immunocompetent adults with recurrent CDI, select use of FMT can be used after completion of standard-of-care antibiotics to prevent recurrence. It can be considered after the second recurrence (episode 3) of CDI or in select patients at high risk for either recurrent CDI or a morbid CDI recurrence. Recurrent CDI is defined as clinically significant diarrhea ≥ 3 unformed stools in 24 hours with a confirmatory positive test within 8 weeks of completing antibiotics. Select use includes patients who have recovered from severe, fulminant, or particularly treatment-refractory CDI and patients with significant comorbidities. Severe CDI involves a leukocyte count of ≥15 × 109 cells/L and/or creatinine ≥1.5 mg/dL, while fulminant CDI involves shock, ileus, or megacolon and can be fatal.
- In mildly or moderately immunocompromised adults with recurrent CDI, the guidance recommends select use of conventional fecal microbiota transplant.
- In severely immunocompromised adults or those undergoing cytotoxic treatment, the AGA advises against the use of any fecal microbiota-based therapies to prevent recurrent CDI.
- Conventional FMT is not advised in patients who have bowel perforation or obstruction or are severely immunocompromised.
- For CDI patients not interested in FMT, reasonable alternatives to prevent recurrence are a vancomycin taper, tapered-pulsed fidaxomicin, or bezlotoxumab.
- In adults hospitalized with severe or fulminant CDI not responding to standard-of-care antibiotics, the AGA recommends select use of conventional FM transplant.
- In the current absence of evidence, the guidance advises against the use of conventional fecal microbiota transplant as treatment for IBD or IBS except in the context of clinical trials.
“We felt the data for using FMT in the treatment of UC was promising, but there is still a lot more work to be done in IBD and IBS,” Dr. Peery said. For each disease section the guideline outlined directions for future research. It will be updated in 3-5 years as more evidence becomes available.
This guideline was fully funded by the AGA Institute. Dr. Peery and fellow panel member Dr. Benjamin Lebwohl are supported by grants the National Institute of Diabetes and Digestive and Kidney Diseases. Panel member Colleen R. Kelly, MD, is supported by the National Institute of Allergy and Infectious Diseases.
None of the panel members had any conflicts of interest to report.
Addressing Clostridium difficile infection (CDI), Crohn’s disease (CD) ulcerative colitis (UC), pouchitis, and irritable bowel syndrome (IBS), the guidance supports FMT for the prevention of recurrent CDI but not for inflammatory bowel disease (IBD) or IBS — outside of clinical trials.
The AGA’s recommendations were published in Gastroenterology.
“Fecal microbiota–based therapies are effective therapy to prevent recurrent C. difficile in select patients,” the AGA guideline states. “Conventional fecal microbiota transplant is an adjuvant treatment for select adults hospitalized with severe or fulminant C. difficile infection not responding to standard of care antibiotics. Fecal microbiota transplant cannot yet be recommended in other gastrointestinal conditions.”
“We thought it was important to write this guideline because of the growing number of trials of FMT in IBD and IBS populations. It was also important with the new FDA-approved treatments on the market,” the guideline’s first author, Anne F. Peery, MD, MSCR, AGAF, told this news organization, noting that the recently approved products did not yield better results than those of conventional rectal FMT. “The guidelines will help clinicians understand the available therapies and how to use these treatments,” added Dr. Peery, associate professor in the Division of Gastroenterology and Hepatology at the University of North Carolina School of Medicine in Chapel Hill.
Although the existing evidence is of low or very low certainty, Dr. Peery acknowledged, gastroenterologists “should be comfortable with conventional FMT and also the new FDA-approved products. We spent a considerable amount of time developing implementation considerations, which is practical advice to help clinicians use the guideline recommendations.”
Designed to counteract intestinal dysbiosis and restore protective gut flora, the FMT approach includes conventional, colonoscopically delivered donor stool transplants as well as two newly approved options: rectally given fecal microbiota (live-jslm/ Rebyota) and most recently, orally delivered fecal microbiota spores (live-brpk/ Vowst).
The AGA urges careful pretreatment consideration for patients who require frequent antibiotics or long-term antibiotic prophylaxis since ongoing antibiotics may diminish the efficacy of FMT.
The guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis, followed by the Evidence-to-Decision framework to develop recommendations for these therapies and algorithms for their implementation into clinical practice.
Recommendations
The eight-member panel suggested the following practices on behalf of the AGA Clinical Guidelines Committee:
- In immunocompetent adults with recurrent CDI, select use of FMT can be used after completion of standard-of-care antibiotics to prevent recurrence. It can be considered after the second recurrence (episode 3) of CDI or in select patients at high risk for either recurrent CDI or a morbid CDI recurrence. Recurrent CDI is defined as clinically significant diarrhea ≥ 3 unformed stools in 24 hours with a confirmatory positive test within 8 weeks of completing antibiotics. Select use includes patients who have recovered from severe, fulminant, or particularly treatment-refractory CDI and patients with significant comorbidities. Severe CDI involves a leukocyte count of ≥15 × 109 cells/L and/or creatinine ≥1.5 mg/dL, while fulminant CDI involves shock, ileus, or megacolon and can be fatal.
- In mildly or moderately immunocompromised adults with recurrent CDI, the guidance recommends select use of conventional fecal microbiota transplant.
- In severely immunocompromised adults or those undergoing cytotoxic treatment, the AGA advises against the use of any fecal microbiota-based therapies to prevent recurrent CDI.
- Conventional FMT is not advised in patients who have bowel perforation or obstruction or are severely immunocompromised.
- For CDI patients not interested in FMT, reasonable alternatives to prevent recurrence are a vancomycin taper, tapered-pulsed fidaxomicin, or bezlotoxumab.
- In adults hospitalized with severe or fulminant CDI not responding to standard-of-care antibiotics, the AGA recommends select use of conventional FM transplant.
- In the current absence of evidence, the guidance advises against the use of conventional fecal microbiota transplant as treatment for IBD or IBS except in the context of clinical trials.
“We felt the data for using FMT in the treatment of UC was promising, but there is still a lot more work to be done in IBD and IBS,” Dr. Peery said. For each disease section the guideline outlined directions for future research. It will be updated in 3-5 years as more evidence becomes available.
This guideline was fully funded by the AGA Institute. Dr. Peery and fellow panel member Dr. Benjamin Lebwohl are supported by grants the National Institute of Diabetes and Digestive and Kidney Diseases. Panel member Colleen R. Kelly, MD, is supported by the National Institute of Allergy and Infectious Diseases.
None of the panel members had any conflicts of interest to report.
FROM GASTROENTEROLOGY
Study: Healthy Plant-Based Diets Do Not Raise Hip Fracture Risk
Long-term adherence to a plant-based diet was not tied to a greater risk of hip fracture and some plant-based regimens may actually reduce the risk, a large cohort study of postmenopausal women in the United States suggested.
Not all plant-centered regimens are healthful, however, and this study factored dietary quality into risk.
Writing in JAMA Network Open, the study authors compared the lowest to highest quintiles of Plant-Based Diet Index scores. They found the most recent intake of a healthy plant-based diet (hPDI) to be associated with a somewhat lower (21%) risk of fracture while the most recent intake of its unhealthy counterpart (uPDI) was linked to a somewhat higher (28%) risk.
“In addition, higher baseline scores in the uPDI were associated with higher risk of hip fracture,” wrote the researchers, led by Mercedes Sotos Prieto, PhD, a nutritional epidemiologist in the Department of Preventive Medicine and Public Health at the Autonomous University of Madrid.
Plant-based diets, characterized by higher consumption of plant foods and lower or no intake of animal foods, have raised concerns about their potential harm to bone health. In a recent meta-analysis, vegetarians, but particularly vegans with no consumption of any animal food, had a higher fracture risk and lower bone mineral density compared with omnivores.
Another study found that compared with meat eaters, fish eaters and vegetarians had a higher risk of hip fractures. These analyses, however, did not assess the quality of the plant-based diets.
“We hypothesized that the differences in the quality of the plant-based diets — whole grains, fruits, and vegetables vs refined carbohydrates or snacks, which are both plant-based but very different, would be important in the association for the risk of hip fracture,” Dr. Sotos Prieto said in an interview.
Study details
Her study drew on data from 70,285 postmenopausal White women who were in the US Nurses’ Health Study from 1984 through 2014; data were analyzed from Jan. 1 to July 31, 2023.
The mean age of the nurses was 54.92 years, and 2038 cases of hip fracture were reported during the study over as long as 30 years of follow-up.
Healthy plant foods included whole grains, fruits, vegetables, nuts, legumes, vegetable oils, and tea or coffee and received positive scores, whereas less healthy plant foods such as fruit juices, sweetened beverages, refined grains, potatoes, sweets, or desserts and animal foods received reversed scores. Dietary and lifestyle information was collected by self-reported questionnaires.
Individuals with higher hPDI scores were leaner, more physically active, less likely to be smokers, and more likely to use vitamin and calcium supplements. Not surprisingly, they also had higher intakes of dietary calcium and healthy plant foods and had lower intake of less healthy plant foods. “It’s plausible that reverse causation may account for the risk associations, as individuals with underlying health conditions that predisposed them to higher fracture risk may have changed their diet,” Dr. Sotos Prieto said. “In addition, baseline diet may reflect diet early on, which could be an important predictor of bone mineral density when there was more active bone turnover.”
Lack of information precluded adjustment for the use of anti-osteoporotic medication.
Neither the hPDI, with a hazard ratio (HR) for highest vs lowest quintile of 0.97 (95% confidence interval, 0.83-1.14) nor the uPDI, with an HR for highest vs lowest quintile of 1.02 (95% CI, 0.87-1.20) for diet adherence over the long term was associated with hip fracture risk.
For recent dietary intake in the highest vs lowest quintiles, however, the hPDI was associated with a 21% lower risk of hip fracture: HR, 0.79 (95% CI, 0.68-0.92; P = .02 for trend). In contrast, the uPDI was associated with a 28% higher risk: HR, 1.28 (95% CI, 1.09-1.51; P = .008 for trend).
Future studies in other populations are needed to confirm the results and enhance their generalizability, Dr. Sotos Prieto said. “Investigating the temporal dynamics of dietary patterns and their effects by examining how recent dietary changes may impact health outcomes over different timeframes is important.” In the meantime, people wishing to follow a plant-based diet should make sure it features high-quality foods.
This work was supported by Instituto de Salud Carlos III, State Secretary of Research, Development and Innovation of Spain, and the European Research Funds and European Social Fund, the Agencia Estatal de Investigación, the National Institutes of Health, and a Ramón y Cajal contract from the Ministry of Science, Innovation, and Universities. A coauthor reported a patent pending. No other disclosures were reported.
Long-term adherence to a plant-based diet was not tied to a greater risk of hip fracture and some plant-based regimens may actually reduce the risk, a large cohort study of postmenopausal women in the United States suggested.
Not all plant-centered regimens are healthful, however, and this study factored dietary quality into risk.
Writing in JAMA Network Open, the study authors compared the lowest to highest quintiles of Plant-Based Diet Index scores. They found the most recent intake of a healthy plant-based diet (hPDI) to be associated with a somewhat lower (21%) risk of fracture while the most recent intake of its unhealthy counterpart (uPDI) was linked to a somewhat higher (28%) risk.
“In addition, higher baseline scores in the uPDI were associated with higher risk of hip fracture,” wrote the researchers, led by Mercedes Sotos Prieto, PhD, a nutritional epidemiologist in the Department of Preventive Medicine and Public Health at the Autonomous University of Madrid.
Plant-based diets, characterized by higher consumption of plant foods and lower or no intake of animal foods, have raised concerns about their potential harm to bone health. In a recent meta-analysis, vegetarians, but particularly vegans with no consumption of any animal food, had a higher fracture risk and lower bone mineral density compared with omnivores.
Another study found that compared with meat eaters, fish eaters and vegetarians had a higher risk of hip fractures. These analyses, however, did not assess the quality of the plant-based diets.
“We hypothesized that the differences in the quality of the plant-based diets — whole grains, fruits, and vegetables vs refined carbohydrates or snacks, which are both plant-based but very different, would be important in the association for the risk of hip fracture,” Dr. Sotos Prieto said in an interview.
Study details
Her study drew on data from 70,285 postmenopausal White women who were in the US Nurses’ Health Study from 1984 through 2014; data were analyzed from Jan. 1 to July 31, 2023.
The mean age of the nurses was 54.92 years, and 2038 cases of hip fracture were reported during the study over as long as 30 years of follow-up.
Healthy plant foods included whole grains, fruits, vegetables, nuts, legumes, vegetable oils, and tea or coffee and received positive scores, whereas less healthy plant foods such as fruit juices, sweetened beverages, refined grains, potatoes, sweets, or desserts and animal foods received reversed scores. Dietary and lifestyle information was collected by self-reported questionnaires.
Individuals with higher hPDI scores were leaner, more physically active, less likely to be smokers, and more likely to use vitamin and calcium supplements. Not surprisingly, they also had higher intakes of dietary calcium and healthy plant foods and had lower intake of less healthy plant foods. “It’s plausible that reverse causation may account for the risk associations, as individuals with underlying health conditions that predisposed them to higher fracture risk may have changed their diet,” Dr. Sotos Prieto said. “In addition, baseline diet may reflect diet early on, which could be an important predictor of bone mineral density when there was more active bone turnover.”
Lack of information precluded adjustment for the use of anti-osteoporotic medication.
Neither the hPDI, with a hazard ratio (HR) for highest vs lowest quintile of 0.97 (95% confidence interval, 0.83-1.14) nor the uPDI, with an HR for highest vs lowest quintile of 1.02 (95% CI, 0.87-1.20) for diet adherence over the long term was associated with hip fracture risk.
For recent dietary intake in the highest vs lowest quintiles, however, the hPDI was associated with a 21% lower risk of hip fracture: HR, 0.79 (95% CI, 0.68-0.92; P = .02 for trend). In contrast, the uPDI was associated with a 28% higher risk: HR, 1.28 (95% CI, 1.09-1.51; P = .008 for trend).
Future studies in other populations are needed to confirm the results and enhance their generalizability, Dr. Sotos Prieto said. “Investigating the temporal dynamics of dietary patterns and their effects by examining how recent dietary changes may impact health outcomes over different timeframes is important.” In the meantime, people wishing to follow a plant-based diet should make sure it features high-quality foods.
This work was supported by Instituto de Salud Carlos III, State Secretary of Research, Development and Innovation of Spain, and the European Research Funds and European Social Fund, the Agencia Estatal de Investigación, the National Institutes of Health, and a Ramón y Cajal contract from the Ministry of Science, Innovation, and Universities. A coauthor reported a patent pending. No other disclosures were reported.
Long-term adherence to a plant-based diet was not tied to a greater risk of hip fracture and some plant-based regimens may actually reduce the risk, a large cohort study of postmenopausal women in the United States suggested.
Not all plant-centered regimens are healthful, however, and this study factored dietary quality into risk.
Writing in JAMA Network Open, the study authors compared the lowest to highest quintiles of Plant-Based Diet Index scores. They found the most recent intake of a healthy plant-based diet (hPDI) to be associated with a somewhat lower (21%) risk of fracture while the most recent intake of its unhealthy counterpart (uPDI) was linked to a somewhat higher (28%) risk.
“In addition, higher baseline scores in the uPDI were associated with higher risk of hip fracture,” wrote the researchers, led by Mercedes Sotos Prieto, PhD, a nutritional epidemiologist in the Department of Preventive Medicine and Public Health at the Autonomous University of Madrid.
Plant-based diets, characterized by higher consumption of plant foods and lower or no intake of animal foods, have raised concerns about their potential harm to bone health. In a recent meta-analysis, vegetarians, but particularly vegans with no consumption of any animal food, had a higher fracture risk and lower bone mineral density compared with omnivores.
Another study found that compared with meat eaters, fish eaters and vegetarians had a higher risk of hip fractures. These analyses, however, did not assess the quality of the plant-based diets.
“We hypothesized that the differences in the quality of the plant-based diets — whole grains, fruits, and vegetables vs refined carbohydrates or snacks, which are both plant-based but very different, would be important in the association for the risk of hip fracture,” Dr. Sotos Prieto said in an interview.
Study details
Her study drew on data from 70,285 postmenopausal White women who were in the US Nurses’ Health Study from 1984 through 2014; data were analyzed from Jan. 1 to July 31, 2023.
The mean age of the nurses was 54.92 years, and 2038 cases of hip fracture were reported during the study over as long as 30 years of follow-up.
Healthy plant foods included whole grains, fruits, vegetables, nuts, legumes, vegetable oils, and tea or coffee and received positive scores, whereas less healthy plant foods such as fruit juices, sweetened beverages, refined grains, potatoes, sweets, or desserts and animal foods received reversed scores. Dietary and lifestyle information was collected by self-reported questionnaires.
Individuals with higher hPDI scores were leaner, more physically active, less likely to be smokers, and more likely to use vitamin and calcium supplements. Not surprisingly, they also had higher intakes of dietary calcium and healthy plant foods and had lower intake of less healthy plant foods. “It’s plausible that reverse causation may account for the risk associations, as individuals with underlying health conditions that predisposed them to higher fracture risk may have changed their diet,” Dr. Sotos Prieto said. “In addition, baseline diet may reflect diet early on, which could be an important predictor of bone mineral density when there was more active bone turnover.”
Lack of information precluded adjustment for the use of anti-osteoporotic medication.
Neither the hPDI, with a hazard ratio (HR) for highest vs lowest quintile of 0.97 (95% confidence interval, 0.83-1.14) nor the uPDI, with an HR for highest vs lowest quintile of 1.02 (95% CI, 0.87-1.20) for diet adherence over the long term was associated with hip fracture risk.
For recent dietary intake in the highest vs lowest quintiles, however, the hPDI was associated with a 21% lower risk of hip fracture: HR, 0.79 (95% CI, 0.68-0.92; P = .02 for trend). In contrast, the uPDI was associated with a 28% higher risk: HR, 1.28 (95% CI, 1.09-1.51; P = .008 for trend).
Future studies in other populations are needed to confirm the results and enhance their generalizability, Dr. Sotos Prieto said. “Investigating the temporal dynamics of dietary patterns and their effects by examining how recent dietary changes may impact health outcomes over different timeframes is important.” In the meantime, people wishing to follow a plant-based diet should make sure it features high-quality foods.
This work was supported by Instituto de Salud Carlos III, State Secretary of Research, Development and Innovation of Spain, and the European Research Funds and European Social Fund, the Agencia Estatal de Investigación, the National Institutes of Health, and a Ramón y Cajal contract from the Ministry of Science, Innovation, and Universities. A coauthor reported a patent pending. No other disclosures were reported.
FROM JAMA NETWORK OPEN
Real-World Dupilumab Wins in Treating Refractory EoE
Most patients achieved histologic, endoscopic, and symptom improvement with a median of 6 months’ treatment with the interleukin 4 and 13 blocker, and esophageal stricture diameter improved as well, according to a single-center retrospective study in Clinical Gastroenterology and Hepatology.
“Dupilumab has real-world efficacy for a severe EoE population, most of whom would not have qualified for prior clinical trials,” concluded gastroenterologists Christopher J. Lee, MD (lead author), and Evan S. Dellon, MD, MPH, AGAF, of the Center for Esophageal Diseases and Swallowing, at the University of North Carolina School of Medicine in Chapel Hill.
These real-world findings aligned with data from the group’s phase 3 clinical trial.
In addition, several case reports or series have highlighted the real-world efficacy of dupilumab, with a particular focus on pediatric patients and those with other atopic diseases.
“Despite nonresponse to prior treatments, these patients can likely expect to see results similar to what was seen in the clinical trial,” Dr. Dellon said in an interview. “However, it would be good to have similar confirmatory data from other centers, and I’m sure those data will be forthcoming as more EoE patients are treated with dupilumab.”
The placement of dupilumab in the EoE treatment algorithm is still actively being investigated. “While the phase 3 study led to [Food and Drug Administration] approval, it had strict inclusion and exclusion criteria, and some populations were ineligible,” he added. “In particular, the very severe EoE patients who either had a very narrow esophagus where the scope wouldn’t pass, or who had severe strictures and symptoms requiring esophageal dilation and who couldn’t go 6 to 12 months without dilation, couldn’t be enrolled. So the efficacy of dupilumab in this more severe group was not known.”
The group hypothesized that dupilumab would be effective in this population but did not know if the efficacy would be similar to that in the clinical trial. “The overall response rates, which were very similar to what were seen in the phase 3 trial, were surprising,“ Dr. Dellon said.”The other surprising finding was the increase in esophageal caliber, as measured by the size achieved with esophageal dilation.”
The study
The investigators identified 46 patients treated with dupilumab for refractory fibrostenotic EoE at the university’s medical center. All had failed or lost response to one or more standard therapies such as proton pump inhibitors, topical glucocorticosteroids, and a food elimination diet.
Previous treatments also included systemic steroids, cromolyn, ketotifen, montelukast, and 6-mercaptopurine, all with minimal response. Some 85% of patients had undergone an average of 9.0+ 7.0 pre-dupilumab dilations.
The biologic was initially prescribed off-label before FDA approval. Patients received it at a dose of 300 mg subcutaneously either fortnightly (n = 16) or weekly (n = 30), depending on insurance approval and timing of prescription. Length of treatment varied based on the time from prescription to first post-treatment evaluative endoscopy.
Patients showed endoscopic, histologic, and symptomatic improvement on dupilumab compared with both the worst and the pre-dupilumab esophagogastroduodenoscopies.
Among the specific findings:
- Peak eosinophil counts significantly decreased.
- Post-dupilumab histologic response rates were 80% and 57% for fewer than 15 eosinophils per high-power field, and 6 or fewer eosinophils per high-power field, respectively.
- The Endoscopic Reference Score decreased from 5.01 to 1.89 (P < .001 for all).
- Pre-dilation esophageal diameter increased from 13.9 to 16.0 mm (P < .001), although the proportion of strictures was stable.
- Global symptom improvement was reported in 91% of patients (P < .001).
Commenting on the study but not involved in it, David A. Katzka, MD, professor of medicine at Columbia University in New York City, said the findings would be of immediate use to practicing gastroenterologists.
“It’s necessary to do clinical trials, but real-world data make the clinician feel more comfortable in prescribing. Interestingly, I am seeing dupilumab being recommended not just for refractory disease but also as first-line therapy,” he said.
Dr. Dellon noted that the incidence and prevalence of EoE are rising rapidly in the US and around the world. “This increase is outpacing growing recognition of the disease,” he said. “Most likely, environmental factors are driving this change.” He called for studies to determine the long-term efficacy of dupilumab for this severe subgroup — and the potential benefit of moving dupilumab earlier into the treatment algorithm.
The latter is a controversial question, noted Dr. Katzka. “For patients with other indications such as asthma or eczema, dupilumab is the ideal medication,” he said. And it can be a first-line therapy if there are contraindications to alternatives or if compliance will be better with a once-weekly injection as opposed to a twice-daily medication or a food elimination diet. But overall, our more established therapies should be considered first.”
Dr. Katzka emphasized the need to further define EoE phenotypes in order to personalize therapy. “There’s likely a group of patients who should go straight to dupilumab, perhaps those marked by factors such as severity, progression, young age, or other atopic disorders. But we have yet to definitively identify this group.”
The authors reported no specific funding for this analysis. Dr. Dellon reported research funding and/or consulting fees from multiple pharmaceutical companies, including Regeneron/Sanofi, the developers of dupilumab. Dr. Lee had no competing interests to disclose. Dr. Katzka reported consulting for Medtronic, and is an associate editor for GI & Hepatology News.
Most patients achieved histologic, endoscopic, and symptom improvement with a median of 6 months’ treatment with the interleukin 4 and 13 blocker, and esophageal stricture diameter improved as well, according to a single-center retrospective study in Clinical Gastroenterology and Hepatology.
“Dupilumab has real-world efficacy for a severe EoE population, most of whom would not have qualified for prior clinical trials,” concluded gastroenterologists Christopher J. Lee, MD (lead author), and Evan S. Dellon, MD, MPH, AGAF, of the Center for Esophageal Diseases and Swallowing, at the University of North Carolina School of Medicine in Chapel Hill.
These real-world findings aligned with data from the group’s phase 3 clinical trial.
In addition, several case reports or series have highlighted the real-world efficacy of dupilumab, with a particular focus on pediatric patients and those with other atopic diseases.
“Despite nonresponse to prior treatments, these patients can likely expect to see results similar to what was seen in the clinical trial,” Dr. Dellon said in an interview. “However, it would be good to have similar confirmatory data from other centers, and I’m sure those data will be forthcoming as more EoE patients are treated with dupilumab.”
The placement of dupilumab in the EoE treatment algorithm is still actively being investigated. “While the phase 3 study led to [Food and Drug Administration] approval, it had strict inclusion and exclusion criteria, and some populations were ineligible,” he added. “In particular, the very severe EoE patients who either had a very narrow esophagus where the scope wouldn’t pass, or who had severe strictures and symptoms requiring esophageal dilation and who couldn’t go 6 to 12 months without dilation, couldn’t be enrolled. So the efficacy of dupilumab in this more severe group was not known.”
The group hypothesized that dupilumab would be effective in this population but did not know if the efficacy would be similar to that in the clinical trial. “The overall response rates, which were very similar to what were seen in the phase 3 trial, were surprising,“ Dr. Dellon said.”The other surprising finding was the increase in esophageal caliber, as measured by the size achieved with esophageal dilation.”
The study
The investigators identified 46 patients treated with dupilumab for refractory fibrostenotic EoE at the university’s medical center. All had failed or lost response to one or more standard therapies such as proton pump inhibitors, topical glucocorticosteroids, and a food elimination diet.
Previous treatments also included systemic steroids, cromolyn, ketotifen, montelukast, and 6-mercaptopurine, all with minimal response. Some 85% of patients had undergone an average of 9.0+ 7.0 pre-dupilumab dilations.
The biologic was initially prescribed off-label before FDA approval. Patients received it at a dose of 300 mg subcutaneously either fortnightly (n = 16) or weekly (n = 30), depending on insurance approval and timing of prescription. Length of treatment varied based on the time from prescription to first post-treatment evaluative endoscopy.
Patients showed endoscopic, histologic, and symptomatic improvement on dupilumab compared with both the worst and the pre-dupilumab esophagogastroduodenoscopies.
Among the specific findings:
- Peak eosinophil counts significantly decreased.
- Post-dupilumab histologic response rates were 80% and 57% for fewer than 15 eosinophils per high-power field, and 6 or fewer eosinophils per high-power field, respectively.
- The Endoscopic Reference Score decreased from 5.01 to 1.89 (P < .001 for all).
- Pre-dilation esophageal diameter increased from 13.9 to 16.0 mm (P < .001), although the proportion of strictures was stable.
- Global symptom improvement was reported in 91% of patients (P < .001).
Commenting on the study but not involved in it, David A. Katzka, MD, professor of medicine at Columbia University in New York City, said the findings would be of immediate use to practicing gastroenterologists.
“It’s necessary to do clinical trials, but real-world data make the clinician feel more comfortable in prescribing. Interestingly, I am seeing dupilumab being recommended not just for refractory disease but also as first-line therapy,” he said.
Dr. Dellon noted that the incidence and prevalence of EoE are rising rapidly in the US and around the world. “This increase is outpacing growing recognition of the disease,” he said. “Most likely, environmental factors are driving this change.” He called for studies to determine the long-term efficacy of dupilumab for this severe subgroup — and the potential benefit of moving dupilumab earlier into the treatment algorithm.
The latter is a controversial question, noted Dr. Katzka. “For patients with other indications such as asthma or eczema, dupilumab is the ideal medication,” he said. And it can be a first-line therapy if there are contraindications to alternatives or if compliance will be better with a once-weekly injection as opposed to a twice-daily medication or a food elimination diet. But overall, our more established therapies should be considered first.”
Dr. Katzka emphasized the need to further define EoE phenotypes in order to personalize therapy. “There’s likely a group of patients who should go straight to dupilumab, perhaps those marked by factors such as severity, progression, young age, or other atopic disorders. But we have yet to definitively identify this group.”
The authors reported no specific funding for this analysis. Dr. Dellon reported research funding and/or consulting fees from multiple pharmaceutical companies, including Regeneron/Sanofi, the developers of dupilumab. Dr. Lee had no competing interests to disclose. Dr. Katzka reported consulting for Medtronic, and is an associate editor for GI & Hepatology News.
Most patients achieved histologic, endoscopic, and symptom improvement with a median of 6 months’ treatment with the interleukin 4 and 13 blocker, and esophageal stricture diameter improved as well, according to a single-center retrospective study in Clinical Gastroenterology and Hepatology.
“Dupilumab has real-world efficacy for a severe EoE population, most of whom would not have qualified for prior clinical trials,” concluded gastroenterologists Christopher J. Lee, MD (lead author), and Evan S. Dellon, MD, MPH, AGAF, of the Center for Esophageal Diseases and Swallowing, at the University of North Carolina School of Medicine in Chapel Hill.
These real-world findings aligned with data from the group’s phase 3 clinical trial.
In addition, several case reports or series have highlighted the real-world efficacy of dupilumab, with a particular focus on pediatric patients and those with other atopic diseases.
“Despite nonresponse to prior treatments, these patients can likely expect to see results similar to what was seen in the clinical trial,” Dr. Dellon said in an interview. “However, it would be good to have similar confirmatory data from other centers, and I’m sure those data will be forthcoming as more EoE patients are treated with dupilumab.”
The placement of dupilumab in the EoE treatment algorithm is still actively being investigated. “While the phase 3 study led to [Food and Drug Administration] approval, it had strict inclusion and exclusion criteria, and some populations were ineligible,” he added. “In particular, the very severe EoE patients who either had a very narrow esophagus where the scope wouldn’t pass, or who had severe strictures and symptoms requiring esophageal dilation and who couldn’t go 6 to 12 months without dilation, couldn’t be enrolled. So the efficacy of dupilumab in this more severe group was not known.”
The group hypothesized that dupilumab would be effective in this population but did not know if the efficacy would be similar to that in the clinical trial. “The overall response rates, which were very similar to what were seen in the phase 3 trial, were surprising,“ Dr. Dellon said.”The other surprising finding was the increase in esophageal caliber, as measured by the size achieved with esophageal dilation.”
The study
The investigators identified 46 patients treated with dupilumab for refractory fibrostenotic EoE at the university’s medical center. All had failed or lost response to one or more standard therapies such as proton pump inhibitors, topical glucocorticosteroids, and a food elimination diet.
Previous treatments also included systemic steroids, cromolyn, ketotifen, montelukast, and 6-mercaptopurine, all with minimal response. Some 85% of patients had undergone an average of 9.0+ 7.0 pre-dupilumab dilations.
The biologic was initially prescribed off-label before FDA approval. Patients received it at a dose of 300 mg subcutaneously either fortnightly (n = 16) or weekly (n = 30), depending on insurance approval and timing of prescription. Length of treatment varied based on the time from prescription to first post-treatment evaluative endoscopy.
Patients showed endoscopic, histologic, and symptomatic improvement on dupilumab compared with both the worst and the pre-dupilumab esophagogastroduodenoscopies.
Among the specific findings:
- Peak eosinophil counts significantly decreased.
- Post-dupilumab histologic response rates were 80% and 57% for fewer than 15 eosinophils per high-power field, and 6 or fewer eosinophils per high-power field, respectively.
- The Endoscopic Reference Score decreased from 5.01 to 1.89 (P < .001 for all).
- Pre-dilation esophageal diameter increased from 13.9 to 16.0 mm (P < .001), although the proportion of strictures was stable.
- Global symptom improvement was reported in 91% of patients (P < .001).
Commenting on the study but not involved in it, David A. Katzka, MD, professor of medicine at Columbia University in New York City, said the findings would be of immediate use to practicing gastroenterologists.
“It’s necessary to do clinical trials, but real-world data make the clinician feel more comfortable in prescribing. Interestingly, I am seeing dupilumab being recommended not just for refractory disease but also as first-line therapy,” he said.
Dr. Dellon noted that the incidence and prevalence of EoE are rising rapidly in the US and around the world. “This increase is outpacing growing recognition of the disease,” he said. “Most likely, environmental factors are driving this change.” He called for studies to determine the long-term efficacy of dupilumab for this severe subgroup — and the potential benefit of moving dupilumab earlier into the treatment algorithm.
The latter is a controversial question, noted Dr. Katzka. “For patients with other indications such as asthma or eczema, dupilumab is the ideal medication,” he said. And it can be a first-line therapy if there are contraindications to alternatives or if compliance will be better with a once-weekly injection as opposed to a twice-daily medication or a food elimination diet. But overall, our more established therapies should be considered first.”
Dr. Katzka emphasized the need to further define EoE phenotypes in order to personalize therapy. “There’s likely a group of patients who should go straight to dupilumab, perhaps those marked by factors such as severity, progression, young age, or other atopic disorders. But we have yet to definitively identify this group.”
The authors reported no specific funding for this analysis. Dr. Dellon reported research funding and/or consulting fees from multiple pharmaceutical companies, including Regeneron/Sanofi, the developers of dupilumab. Dr. Lee had no competing interests to disclose. Dr. Katzka reported consulting for Medtronic, and is an associate editor for GI & Hepatology News.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
AHA: Urgent Need To Reduce Maternal Postpartum CVD Risk
Complications during pregnancy may be a wake-up call pointing to a higher risk for cardiovascular (CVD) and other diseases later in life. Therefore, the postpartum and interpregnancy periods are opportune windows for reducing CVD susceptibility and providing preventive care, especially for mothers with a history of adverse pregnancy outcomes (APOs). To that end, the American Heart Association recently released a scientific statement in Circulation outlining pregnancy-related CVD risks and reviewing evidence for preventive lifestyle strategies based on the AHA’s Life’s Essential 8 recommendations.
The Life’s Essential 8 encompass healthy eating, sleeping, and activity patterns; controlling weight, blood pressure, cholesterol, and blood sugar; and avoiding tobacco use.
“The motivation behind this statement was that complications in pregnancy are becoming more common and we now have more understanding that these serve as important risk factors for heart disease later in life,” said Jennifer Lewey, MD, MPH, director of the Penn Women’s Cardiovascular Health Program and an assistant professor of medicine at the University of Pennsylvania Perelman School of Medicine in Philadelphia.
“These risk factors are underrecognized and underappreciated. Clinicians don’t feel comfortable counseling their patients about how to reduce their cardiovascular disease risk,” Dr. Lewey, chair of the AHA writing group, said in an interview.
“So we thought this was the perfect time to highlight what we know and don’t know about how to care for this population,” she said.
APOs predispose mothers to heart disease and other long-term complications, including heart failure, stroke, chronic kidney disease, and vascular dementia. “Pregnancy is a significant stress on the body, and APOs such as preeclampsia can lead to vascular changes in the blood vessels and structural changes to the heart that can persist long term,” Dr. Lewey explained. Reduced maternal physical activity and unshed weight can compound the problem.
Varying by race and ethnicity, the proportion of mothers experiencing pregnancy complications, such as high blood pressure, gestational diabetes, and/or preterm birth is estimated at 10%-20%, the statement authors noted. These complications may serve as a wake-up call to young mothers.
The AHA panel believes that identifying at-risk women at younger ages will enable prevention through lifestyle changes and timely treatment. Little is known, however about what specific care may best reduce long-term CVD risk in women who had pregnancy complications, Dr. Lewey said. While randomized clinical trials have yet to evaluate the effects of postpartum interventions on CVD outcomes, the need for strategies supported by rigorous evidence is clear. “In particular, the fourth trimester, defined as the 12 weeks after delivery, is an optimal time to engage postpartum individuals in care to reduce maternal morbidity and improve care transitions,” the AHA group wrote.
An earlier AHA statement in 2021 recommended frequent cardiac risk factor screening in the first year postpartum at 6 and 12 weeks and again at 6 and 12 months, with appropriate transition from postpartum to longitudinal primary care around the 8- to 12-week mark.
Among the current statement’s findings: High blood pressure is the most prevalent cardiovascular condition during pregnancy, and the last two decades have seen a 25% increase in preeclampsia.
Hypertension during pregnancy carries a two- to fourfold higher risk of chronic hypertension within 2-7 years.
Women with one or more APOs experience heart attack and stroke at younger ages. Commenting on the statement but not involved in it, internist Natalie A. Cameron, MD, a primary and preventive care physician at Northwestern Medicine in Chicago, said, “This statement will be very helpful for physicians from a primary care perspective, especially since in internal medicine we don’t standardly receive education in cardiovascular health in the context of pregnancy and the first year postpartum.”
Dr. Cameron also noted that new research suggests the mother’s cardiovascular health during pregnancy can affect the child’s health through adolescence. “There’s a potential intergenerational effect and there may even be some programming and changes to the offspring in utero related to maternal lifestyle factors.”
While the postpartum period would seem like an opportune time to piggyback postpartum visits with infant wellness checkups, “the fact is that, in the U.S., many mothers are lost to care after delivery,” Dr. Lewey said. “But it’s essential to ensure transition to postpartum care.”
According to Dr. Cameron, physicians should be aware of the risk factor data and educate their pregnant and postpartum patients about reducing risk factors. “As I like to say, ‘If you’re going to take care of others, you need to take care of yourself first.’ ” While this statement may be a good starting point, future trials are needed to improve screening for subclinical CVD in individuals with APOs before symptom onset, the statement authors wrote.
This scientific statement was prepared on behalf of the American Heart Association. Dr. Lewey and several coauthors reported research funding from various agencies within the National Institutes of Health. Dr. Brown reported research funding from a cy-près court settlement with Wyeth. Dr. Cameron had no competing interests relevant to her comments.
Complications during pregnancy may be a wake-up call pointing to a higher risk for cardiovascular (CVD) and other diseases later in life. Therefore, the postpartum and interpregnancy periods are opportune windows for reducing CVD susceptibility and providing preventive care, especially for mothers with a history of adverse pregnancy outcomes (APOs). To that end, the American Heart Association recently released a scientific statement in Circulation outlining pregnancy-related CVD risks and reviewing evidence for preventive lifestyle strategies based on the AHA’s Life’s Essential 8 recommendations.
The Life’s Essential 8 encompass healthy eating, sleeping, and activity patterns; controlling weight, blood pressure, cholesterol, and blood sugar; and avoiding tobacco use.
“The motivation behind this statement was that complications in pregnancy are becoming more common and we now have more understanding that these serve as important risk factors for heart disease later in life,” said Jennifer Lewey, MD, MPH, director of the Penn Women’s Cardiovascular Health Program and an assistant professor of medicine at the University of Pennsylvania Perelman School of Medicine in Philadelphia.
“These risk factors are underrecognized and underappreciated. Clinicians don’t feel comfortable counseling their patients about how to reduce their cardiovascular disease risk,” Dr. Lewey, chair of the AHA writing group, said in an interview.
“So we thought this was the perfect time to highlight what we know and don’t know about how to care for this population,” she said.
APOs predispose mothers to heart disease and other long-term complications, including heart failure, stroke, chronic kidney disease, and vascular dementia. “Pregnancy is a significant stress on the body, and APOs such as preeclampsia can lead to vascular changes in the blood vessels and structural changes to the heart that can persist long term,” Dr. Lewey explained. Reduced maternal physical activity and unshed weight can compound the problem.
Varying by race and ethnicity, the proportion of mothers experiencing pregnancy complications, such as high blood pressure, gestational diabetes, and/or preterm birth is estimated at 10%-20%, the statement authors noted. These complications may serve as a wake-up call to young mothers.
The AHA panel believes that identifying at-risk women at younger ages will enable prevention through lifestyle changes and timely treatment. Little is known, however about what specific care may best reduce long-term CVD risk in women who had pregnancy complications, Dr. Lewey said. While randomized clinical trials have yet to evaluate the effects of postpartum interventions on CVD outcomes, the need for strategies supported by rigorous evidence is clear. “In particular, the fourth trimester, defined as the 12 weeks after delivery, is an optimal time to engage postpartum individuals in care to reduce maternal morbidity and improve care transitions,” the AHA group wrote.
An earlier AHA statement in 2021 recommended frequent cardiac risk factor screening in the first year postpartum at 6 and 12 weeks and again at 6 and 12 months, with appropriate transition from postpartum to longitudinal primary care around the 8- to 12-week mark.
Among the current statement’s findings: High blood pressure is the most prevalent cardiovascular condition during pregnancy, and the last two decades have seen a 25% increase in preeclampsia.
Hypertension during pregnancy carries a two- to fourfold higher risk of chronic hypertension within 2-7 years.
Women with one or more APOs experience heart attack and stroke at younger ages. Commenting on the statement but not involved in it, internist Natalie A. Cameron, MD, a primary and preventive care physician at Northwestern Medicine in Chicago, said, “This statement will be very helpful for physicians from a primary care perspective, especially since in internal medicine we don’t standardly receive education in cardiovascular health in the context of pregnancy and the first year postpartum.”
Dr. Cameron also noted that new research suggests the mother’s cardiovascular health during pregnancy can affect the child’s health through adolescence. “There’s a potential intergenerational effect and there may even be some programming and changes to the offspring in utero related to maternal lifestyle factors.”
While the postpartum period would seem like an opportune time to piggyback postpartum visits with infant wellness checkups, “the fact is that, in the U.S., many mothers are lost to care after delivery,” Dr. Lewey said. “But it’s essential to ensure transition to postpartum care.”
According to Dr. Cameron, physicians should be aware of the risk factor data and educate their pregnant and postpartum patients about reducing risk factors. “As I like to say, ‘If you’re going to take care of others, you need to take care of yourself first.’ ” While this statement may be a good starting point, future trials are needed to improve screening for subclinical CVD in individuals with APOs before symptom onset, the statement authors wrote.
This scientific statement was prepared on behalf of the American Heart Association. Dr. Lewey and several coauthors reported research funding from various agencies within the National Institutes of Health. Dr. Brown reported research funding from a cy-près court settlement with Wyeth. Dr. Cameron had no competing interests relevant to her comments.
Complications during pregnancy may be a wake-up call pointing to a higher risk for cardiovascular (CVD) and other diseases later in life. Therefore, the postpartum and interpregnancy periods are opportune windows for reducing CVD susceptibility and providing preventive care, especially for mothers with a history of adverse pregnancy outcomes (APOs). To that end, the American Heart Association recently released a scientific statement in Circulation outlining pregnancy-related CVD risks and reviewing evidence for preventive lifestyle strategies based on the AHA’s Life’s Essential 8 recommendations.
The Life’s Essential 8 encompass healthy eating, sleeping, and activity patterns; controlling weight, blood pressure, cholesterol, and blood sugar; and avoiding tobacco use.
“The motivation behind this statement was that complications in pregnancy are becoming more common and we now have more understanding that these serve as important risk factors for heart disease later in life,” said Jennifer Lewey, MD, MPH, director of the Penn Women’s Cardiovascular Health Program and an assistant professor of medicine at the University of Pennsylvania Perelman School of Medicine in Philadelphia.
“These risk factors are underrecognized and underappreciated. Clinicians don’t feel comfortable counseling their patients about how to reduce their cardiovascular disease risk,” Dr. Lewey, chair of the AHA writing group, said in an interview.
“So we thought this was the perfect time to highlight what we know and don’t know about how to care for this population,” she said.
APOs predispose mothers to heart disease and other long-term complications, including heart failure, stroke, chronic kidney disease, and vascular dementia. “Pregnancy is a significant stress on the body, and APOs such as preeclampsia can lead to vascular changes in the blood vessels and structural changes to the heart that can persist long term,” Dr. Lewey explained. Reduced maternal physical activity and unshed weight can compound the problem.
Varying by race and ethnicity, the proportion of mothers experiencing pregnancy complications, such as high blood pressure, gestational diabetes, and/or preterm birth is estimated at 10%-20%, the statement authors noted. These complications may serve as a wake-up call to young mothers.
The AHA panel believes that identifying at-risk women at younger ages will enable prevention through lifestyle changes and timely treatment. Little is known, however about what specific care may best reduce long-term CVD risk in women who had pregnancy complications, Dr. Lewey said. While randomized clinical trials have yet to evaluate the effects of postpartum interventions on CVD outcomes, the need for strategies supported by rigorous evidence is clear. “In particular, the fourth trimester, defined as the 12 weeks after delivery, is an optimal time to engage postpartum individuals in care to reduce maternal morbidity and improve care transitions,” the AHA group wrote.
An earlier AHA statement in 2021 recommended frequent cardiac risk factor screening in the first year postpartum at 6 and 12 weeks and again at 6 and 12 months, with appropriate transition from postpartum to longitudinal primary care around the 8- to 12-week mark.
Among the current statement’s findings: High blood pressure is the most prevalent cardiovascular condition during pregnancy, and the last two decades have seen a 25% increase in preeclampsia.
Hypertension during pregnancy carries a two- to fourfold higher risk of chronic hypertension within 2-7 years.
Women with one or more APOs experience heart attack and stroke at younger ages. Commenting on the statement but not involved in it, internist Natalie A. Cameron, MD, a primary and preventive care physician at Northwestern Medicine in Chicago, said, “This statement will be very helpful for physicians from a primary care perspective, especially since in internal medicine we don’t standardly receive education in cardiovascular health in the context of pregnancy and the first year postpartum.”
Dr. Cameron also noted that new research suggests the mother’s cardiovascular health during pregnancy can affect the child’s health through adolescence. “There’s a potential intergenerational effect and there may even be some programming and changes to the offspring in utero related to maternal lifestyle factors.”
While the postpartum period would seem like an opportune time to piggyback postpartum visits with infant wellness checkups, “the fact is that, in the U.S., many mothers are lost to care after delivery,” Dr. Lewey said. “But it’s essential to ensure transition to postpartum care.”
According to Dr. Cameron, physicians should be aware of the risk factor data and educate their pregnant and postpartum patients about reducing risk factors. “As I like to say, ‘If you’re going to take care of others, you need to take care of yourself first.’ ” While this statement may be a good starting point, future trials are needed to improve screening for subclinical CVD in individuals with APOs before symptom onset, the statement authors wrote.
This scientific statement was prepared on behalf of the American Heart Association. Dr. Lewey and several coauthors reported research funding from various agencies within the National Institutes of Health. Dr. Brown reported research funding from a cy-près court settlement with Wyeth. Dr. Cameron had no competing interests relevant to her comments.
FROM CIRCULATION
Telephone Best for Switching Patients to New Colonoscopy Intervals
In an article published in Clinical Gastroenterology and Hepatology, a group led by Jeffrey K. Lee, MD, MPH, a gastroenterologist at Kaiser Permanente Medical Center in San Francisco, reported the following 60-day response rates for the three contact methods in potentially transitioning more than 600 post-polypectomy patients to the new interval:
- Telephone: 64.5%
- Secure messaging: 51.7%
- Mailed letter: 31.3%
Compared with letter outreach, overall rate differences were significant for telephone (18.1%) and secure message outreach (13.1%).
Such interventions are widely used, the authors noted , but have not been compared for efficacy terms of communicating updated colonoscopy intervals.
The trial’s aim was to inform low-risk patients of the recommended interval update from 5 years — used since the 1990s — to 7-10 years. Given a choice, more patients opted to transition to the 10-year surveillance interval in the telephone (37%) and secure messaging arms (32.%) compared with mailed-letter arm (18.9%).
In addition to telephone and secure messaging outreach, factors positively associated with adoption of the 10-year interval were a positive fecal immunochemical test–based index colonoscopy and increasing age. Patients with these characteristics may be biased toward avoiding colonoscopy if not medically necessary, the authors conjectured.
Inversely associated factors included Asian or Pacific Islander race (odds ratio .58), Hispanic ethnicity (OR .40), and a higher Charlson comorbidity score of 2 vs 0 (OR .43).
Possible explanations for the race and ethnicity associations include gaps in culturally component care, lack of engagement with the English-based outreach approaches, and medical mistrust, the authors said.
“In this study, we gave all our patients an option to either extend their surveillance interval to current guideline recommendations or continue with their old interval, and some chose to do that,” Dr. Lee said in an interview. “Patients really appreciated having a choice and to be informed about the latest guideline changes.”
“A critical challenge to health systems is how to effectively de-implement outdated surveillance recommendations for low-risk patients who have a 5-year follow-up interval and potentially transition them to the recommended 7- to 10-year interval,” Dr. Lee and colleagues wrote.
More than 5 million surveillance colonoscopies are performed annually in US patients with a history of adenomas, the main precursor lesion for colorectal cancer, the authors noted.
With the recent guidelines issued in 2020 by the US Multi-Society Task Force on Colorectal Cancer lengthening the follow-up interval to 7-10 years , physicians are being advised to reevaluate low-risk patients previously scheduled with 5-year surveillance and provide an updated recommendation for follow-up.
Study Details
The three-arm pragmatic randomized trial was conducted in low-risk patients 54-70 years of age with one or two small (< 10 mm) tubular adenomas at baseline colonoscopy. Participants due for 5-year surveillance in 2022 were randomly assigned to one of three outreach arms: telephone (n = 200], secure messaging (n = 203), and mailed letter (n = 201). Stratified by age, sex, race, and ethnicity, participants could change their assigned interval to 10 years or continue with their previously scheduled 5-year interval.
As to economic considerations, the authors said that telephone may be the costliest form of outreach in terms of staffing resources. “We don’t know because we did not conduct a formal cost-effectiveness analysis,” Dr. Lee said. “However, we do know phone outreach requires a lot of personnel effort, which is why we also explored the less costly option of secure messaging/email.”
But based on the findings, telephone outreach would be a reasonable approach to update patients on post-polypectomy surveillance guideline changes if secure messaging or text messaging isn’t available, he added.
Downsides to Retroactive Changes?
Commenting on the study but not involved in it, Nabil M. Mansour, MD, an assistant professor and director of the McNair General GI Clinic at Baylor College of Medicine in Houston, noted that unlike Kaiser Permanente, his center decided against an overall effort to switch patients colonoscopied before the release of the new guidelines over to the new interval.
“Several of our physicians may have chosen to recommend a 5-year interval specifically for a variety of reasons and we felt going back, and making a blanket change to everyone’s interval retrospectively might create confusion and frustration and might actually delay the colonoscopies of some patients for which their doctors had a very good, legitimate reason to recommend a 5-year interval,” he said in an interview.
Dr. Mansour added that no difficulties were encountered in getting patients to agree to a 10-year interval. In his view telephone communication or in-person clinic visits are likely the most effective ways but both are more labor-intensive than automated patient portal messages. “I do not think traditional snail mail is effective.” His clinic uses automatic EMR reminders.
Offering another perspective on the study, Aditya Sreenivasan, MD, a gastroenterologist at Northwell Health in New York City, said his center has not reached out to correct the old intervals. “When I see a patient who previously had a colonoscopy with another physician, I always follow the previous recommendation for when the next colonoscopy should be, regardless of whether or not it technically meets guideline recommendations,” he told this news organization. “I do this because I was not there during the procedure and am not aware of any circumstances that would require a shorter interval that may not be apparent from the report.”
While he agrees with the new guidelines, Dr. Sreenivasan is “not sure if retroactively changing intervals is beneficial to patients, as the presence of guidelines may subconsciously influence the behavior of the endoscopist at the time of the procedure. For example, if a patient has a technically challenging colonoscopy and the endoscopist is running late, the endoscopist may drop their guard once they find a polyp and miss 1-2 additional small polyps that they would have spent more time looking for if they knew their next one would be in 10 years instead of 5.”
As for notification method, despite the logistical downside of taking dedicated staff time to make telephone calls, Dr. Sreenivasan said, “I think having a conversation with the patient directly is a much better way to communicate this information as it allows the patient to ask and answer questions. Things like tone of voice can provide reassurance that one cannot get via email.” Looking to the future, the study authors acknowledged that combinations of initial and reminder outreach approaches — for example, a mailed letter followed by secure message or telephone call — could potentially yield higher response rates and/or adoption rates than they observed. And a longer follow-up period with additional reminders may have produced higher yields. Additional studies are needed to optimize outreach approaches and to understand patient barriers to adopting the new guideline recommendations in different healthcare settings.
The study was supported by a Delivery Science grant from the Kaiser Permanente Northern California.
The authors disclosed no conflicts of interest. Dr. Mansour and Dr. Sreenivasan disclosed no conflicts of interest relevant to their comments.
In an article published in Clinical Gastroenterology and Hepatology, a group led by Jeffrey K. Lee, MD, MPH, a gastroenterologist at Kaiser Permanente Medical Center in San Francisco, reported the following 60-day response rates for the three contact methods in potentially transitioning more than 600 post-polypectomy patients to the new interval:
- Telephone: 64.5%
- Secure messaging: 51.7%
- Mailed letter: 31.3%
Compared with letter outreach, overall rate differences were significant for telephone (18.1%) and secure message outreach (13.1%).
Such interventions are widely used, the authors noted , but have not been compared for efficacy terms of communicating updated colonoscopy intervals.
The trial’s aim was to inform low-risk patients of the recommended interval update from 5 years — used since the 1990s — to 7-10 years. Given a choice, more patients opted to transition to the 10-year surveillance interval in the telephone (37%) and secure messaging arms (32.%) compared with mailed-letter arm (18.9%).
In addition to telephone and secure messaging outreach, factors positively associated with adoption of the 10-year interval were a positive fecal immunochemical test–based index colonoscopy and increasing age. Patients with these characteristics may be biased toward avoiding colonoscopy if not medically necessary, the authors conjectured.
Inversely associated factors included Asian or Pacific Islander race (odds ratio .58), Hispanic ethnicity (OR .40), and a higher Charlson comorbidity score of 2 vs 0 (OR .43).
Possible explanations for the race and ethnicity associations include gaps in culturally component care, lack of engagement with the English-based outreach approaches, and medical mistrust, the authors said.
“In this study, we gave all our patients an option to either extend their surveillance interval to current guideline recommendations or continue with their old interval, and some chose to do that,” Dr. Lee said in an interview. “Patients really appreciated having a choice and to be informed about the latest guideline changes.”
“A critical challenge to health systems is how to effectively de-implement outdated surveillance recommendations for low-risk patients who have a 5-year follow-up interval and potentially transition them to the recommended 7- to 10-year interval,” Dr. Lee and colleagues wrote.
More than 5 million surveillance colonoscopies are performed annually in US patients with a history of adenomas, the main precursor lesion for colorectal cancer, the authors noted.
With the recent guidelines issued in 2020 by the US Multi-Society Task Force on Colorectal Cancer lengthening the follow-up interval to 7-10 years , physicians are being advised to reevaluate low-risk patients previously scheduled with 5-year surveillance and provide an updated recommendation for follow-up.
Study Details
The three-arm pragmatic randomized trial was conducted in low-risk patients 54-70 years of age with one or two small (< 10 mm) tubular adenomas at baseline colonoscopy. Participants due for 5-year surveillance in 2022 were randomly assigned to one of three outreach arms: telephone (n = 200], secure messaging (n = 203), and mailed letter (n = 201). Stratified by age, sex, race, and ethnicity, participants could change their assigned interval to 10 years or continue with their previously scheduled 5-year interval.
As to economic considerations, the authors said that telephone may be the costliest form of outreach in terms of staffing resources. “We don’t know because we did not conduct a formal cost-effectiveness analysis,” Dr. Lee said. “However, we do know phone outreach requires a lot of personnel effort, which is why we also explored the less costly option of secure messaging/email.”
But based on the findings, telephone outreach would be a reasonable approach to update patients on post-polypectomy surveillance guideline changes if secure messaging or text messaging isn’t available, he added.
Downsides to Retroactive Changes?
Commenting on the study but not involved in it, Nabil M. Mansour, MD, an assistant professor and director of the McNair General GI Clinic at Baylor College of Medicine in Houston, noted that unlike Kaiser Permanente, his center decided against an overall effort to switch patients colonoscopied before the release of the new guidelines over to the new interval.
“Several of our physicians may have chosen to recommend a 5-year interval specifically for a variety of reasons and we felt going back, and making a blanket change to everyone’s interval retrospectively might create confusion and frustration and might actually delay the colonoscopies of some patients for which their doctors had a very good, legitimate reason to recommend a 5-year interval,” he said in an interview.
Dr. Mansour added that no difficulties were encountered in getting patients to agree to a 10-year interval. In his view telephone communication or in-person clinic visits are likely the most effective ways but both are more labor-intensive than automated patient portal messages. “I do not think traditional snail mail is effective.” His clinic uses automatic EMR reminders.
Offering another perspective on the study, Aditya Sreenivasan, MD, a gastroenterologist at Northwell Health in New York City, said his center has not reached out to correct the old intervals. “When I see a patient who previously had a colonoscopy with another physician, I always follow the previous recommendation for when the next colonoscopy should be, regardless of whether or not it technically meets guideline recommendations,” he told this news organization. “I do this because I was not there during the procedure and am not aware of any circumstances that would require a shorter interval that may not be apparent from the report.”
While he agrees with the new guidelines, Dr. Sreenivasan is “not sure if retroactively changing intervals is beneficial to patients, as the presence of guidelines may subconsciously influence the behavior of the endoscopist at the time of the procedure. For example, if a patient has a technically challenging colonoscopy and the endoscopist is running late, the endoscopist may drop their guard once they find a polyp and miss 1-2 additional small polyps that they would have spent more time looking for if they knew their next one would be in 10 years instead of 5.”
As for notification method, despite the logistical downside of taking dedicated staff time to make telephone calls, Dr. Sreenivasan said, “I think having a conversation with the patient directly is a much better way to communicate this information as it allows the patient to ask and answer questions. Things like tone of voice can provide reassurance that one cannot get via email.” Looking to the future, the study authors acknowledged that combinations of initial and reminder outreach approaches — for example, a mailed letter followed by secure message or telephone call — could potentially yield higher response rates and/or adoption rates than they observed. And a longer follow-up period with additional reminders may have produced higher yields. Additional studies are needed to optimize outreach approaches and to understand patient barriers to adopting the new guideline recommendations in different healthcare settings.
The study was supported by a Delivery Science grant from the Kaiser Permanente Northern California.
The authors disclosed no conflicts of interest. Dr. Mansour and Dr. Sreenivasan disclosed no conflicts of interest relevant to their comments.
In an article published in Clinical Gastroenterology and Hepatology, a group led by Jeffrey K. Lee, MD, MPH, a gastroenterologist at Kaiser Permanente Medical Center in San Francisco, reported the following 60-day response rates for the three contact methods in potentially transitioning more than 600 post-polypectomy patients to the new interval:
- Telephone: 64.5%
- Secure messaging: 51.7%
- Mailed letter: 31.3%
Compared with letter outreach, overall rate differences were significant for telephone (18.1%) and secure message outreach (13.1%).
Such interventions are widely used, the authors noted , but have not been compared for efficacy terms of communicating updated colonoscopy intervals.
The trial’s aim was to inform low-risk patients of the recommended interval update from 5 years — used since the 1990s — to 7-10 years. Given a choice, more patients opted to transition to the 10-year surveillance interval in the telephone (37%) and secure messaging arms (32.%) compared with mailed-letter arm (18.9%).
In addition to telephone and secure messaging outreach, factors positively associated with adoption of the 10-year interval were a positive fecal immunochemical test–based index colonoscopy and increasing age. Patients with these characteristics may be biased toward avoiding colonoscopy if not medically necessary, the authors conjectured.
Inversely associated factors included Asian or Pacific Islander race (odds ratio .58), Hispanic ethnicity (OR .40), and a higher Charlson comorbidity score of 2 vs 0 (OR .43).
Possible explanations for the race and ethnicity associations include gaps in culturally component care, lack of engagement with the English-based outreach approaches, and medical mistrust, the authors said.
“In this study, we gave all our patients an option to either extend their surveillance interval to current guideline recommendations or continue with their old interval, and some chose to do that,” Dr. Lee said in an interview. “Patients really appreciated having a choice and to be informed about the latest guideline changes.”
“A critical challenge to health systems is how to effectively de-implement outdated surveillance recommendations for low-risk patients who have a 5-year follow-up interval and potentially transition them to the recommended 7- to 10-year interval,” Dr. Lee and colleagues wrote.
More than 5 million surveillance colonoscopies are performed annually in US patients with a history of adenomas, the main precursor lesion for colorectal cancer, the authors noted.
With the recent guidelines issued in 2020 by the US Multi-Society Task Force on Colorectal Cancer lengthening the follow-up interval to 7-10 years , physicians are being advised to reevaluate low-risk patients previously scheduled with 5-year surveillance and provide an updated recommendation for follow-up.
Study Details
The three-arm pragmatic randomized trial was conducted in low-risk patients 54-70 years of age with one or two small (< 10 mm) tubular adenomas at baseline colonoscopy. Participants due for 5-year surveillance in 2022 were randomly assigned to one of three outreach arms: telephone (n = 200], secure messaging (n = 203), and mailed letter (n = 201). Stratified by age, sex, race, and ethnicity, participants could change their assigned interval to 10 years or continue with their previously scheduled 5-year interval.
As to economic considerations, the authors said that telephone may be the costliest form of outreach in terms of staffing resources. “We don’t know because we did not conduct a formal cost-effectiveness analysis,” Dr. Lee said. “However, we do know phone outreach requires a lot of personnel effort, which is why we also explored the less costly option of secure messaging/email.”
But based on the findings, telephone outreach would be a reasonable approach to update patients on post-polypectomy surveillance guideline changes if secure messaging or text messaging isn’t available, he added.
Downsides to Retroactive Changes?
Commenting on the study but not involved in it, Nabil M. Mansour, MD, an assistant professor and director of the McNair General GI Clinic at Baylor College of Medicine in Houston, noted that unlike Kaiser Permanente, his center decided against an overall effort to switch patients colonoscopied before the release of the new guidelines over to the new interval.
“Several of our physicians may have chosen to recommend a 5-year interval specifically for a variety of reasons and we felt going back, and making a blanket change to everyone’s interval retrospectively might create confusion and frustration and might actually delay the colonoscopies of some patients for which their doctors had a very good, legitimate reason to recommend a 5-year interval,” he said in an interview.
Dr. Mansour added that no difficulties were encountered in getting patients to agree to a 10-year interval. In his view telephone communication or in-person clinic visits are likely the most effective ways but both are more labor-intensive than automated patient portal messages. “I do not think traditional snail mail is effective.” His clinic uses automatic EMR reminders.
Offering another perspective on the study, Aditya Sreenivasan, MD, a gastroenterologist at Northwell Health in New York City, said his center has not reached out to correct the old intervals. “When I see a patient who previously had a colonoscopy with another physician, I always follow the previous recommendation for when the next colonoscopy should be, regardless of whether or not it technically meets guideline recommendations,” he told this news organization. “I do this because I was not there during the procedure and am not aware of any circumstances that would require a shorter interval that may not be apparent from the report.”
While he agrees with the new guidelines, Dr. Sreenivasan is “not sure if retroactively changing intervals is beneficial to patients, as the presence of guidelines may subconsciously influence the behavior of the endoscopist at the time of the procedure. For example, if a patient has a technically challenging colonoscopy and the endoscopist is running late, the endoscopist may drop their guard once they find a polyp and miss 1-2 additional small polyps that they would have spent more time looking for if they knew their next one would be in 10 years instead of 5.”
As for notification method, despite the logistical downside of taking dedicated staff time to make telephone calls, Dr. Sreenivasan said, “I think having a conversation with the patient directly is a much better way to communicate this information as it allows the patient to ask and answer questions. Things like tone of voice can provide reassurance that one cannot get via email.” Looking to the future, the study authors acknowledged that combinations of initial and reminder outreach approaches — for example, a mailed letter followed by secure message or telephone call — could potentially yield higher response rates and/or adoption rates than they observed. And a longer follow-up period with additional reminders may have produced higher yields. Additional studies are needed to optimize outreach approaches and to understand patient barriers to adopting the new guideline recommendations in different healthcare settings.
The study was supported by a Delivery Science grant from the Kaiser Permanente Northern California.
The authors disclosed no conflicts of interest. Dr. Mansour and Dr. Sreenivasan disclosed no conflicts of interest relevant to their comments.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Cardiorespiratory Fitness May Cut Prostate Cancer Risk
Men with cardiorespiratory fitness (CRF) who increased their CRF by more than 3% had a significantly lower risk of prostate cancer incidence, a large Swedish study found.
The prospective analysis, published in the British Journal of Sports Medicine, done in a cohort of nearly 58,000, was conducted by Kate A. Bolam, PhD, a clinical exercise physiologist at the Swedish School of Sport and Health Sciences in Stockholm.
“The findings suggest that physicians could work toward supporting patients to understand what types of activities could improve their fitness and ways they can incorporate these activities into their lives in an enjoyable way, or at the very least refer patients on to an exercise specialist,” Dr. Bolam said in an interview.
Grouped by baseline CRF, the association between change in absolute CRF and prostate cancer incidence was significant only for participants with a moderate baseline CRF. Moreover, changes in both absolute and relative CRF were not associated with prostate cancer mortality.
The lack of mortality significance may be due to the relatively few deaths from prostate cancer in the cohort, Dr. Bolam said. “It may be we weren’t powered to detect anything with such low numbers. And it’s not likely men will die from prostate cancer but more likely from more common chronic diseases such as heart disease.” The authors noted that unlike the case with other common cancers, there are relatively few preventable risk factors with strong evidence for reducing overall prostate cancer risk. “Aside from developmental factors, being diagnosed with overweight or obesity are the main risk factors for developing advanced prostate cancer, but insufficient evidence exists to extend this conclusion to non-advanced prostate cancer,” they wrote.
There is evidence, however, that exercise reduces all-cause mortality risk across many cancer types, including prostate.
Study details
The cohort was drawn from Swedish national health-profile database figures from 1982 to 2019. Participants completed an occupational health profile assessment including at least two valid CRF tests on a cycle ergometer. During a mean follow-up of 6.7 years, 592 (1%) of 57,652 men (mean age 41.3 years, standard deviation 10.55) were diagnosed with prostate cancer, and in 46 (.08%) prostate cancer was the primary cause of death.
An increase in absolute CRF (as a percentage of liters per minute of cardiac output) was associated with a reduced incidence risk, with a hazard ratio of 0.98 (95% CI, 0.96-0.99). Grouping participants as having increased (+3%), stable (±3%), or decreased (−3%) CRF, the investigators found increased fitness was associated with an HR for prostate cancer incidence of 0.65 (95% CI, 0.49-0.86), vs decreased fitness.
According to the authors, this and similar investigations of mechanisms behind physical activity benefits will lead to more targeted prevention recommendations. The results highlight the importance of encouraging the general public to increase CRF or reach moderate fitness levels, Dr. Bolam’s group wrote. The group is planning a similar study in breast cancer.
This study was funded by the Swedish Cancer Society. The authors declared no competing interests.
Men with cardiorespiratory fitness (CRF) who increased their CRF by more than 3% had a significantly lower risk of prostate cancer incidence, a large Swedish study found.
The prospective analysis, published in the British Journal of Sports Medicine, done in a cohort of nearly 58,000, was conducted by Kate A. Bolam, PhD, a clinical exercise physiologist at the Swedish School of Sport and Health Sciences in Stockholm.
“The findings suggest that physicians could work toward supporting patients to understand what types of activities could improve their fitness and ways they can incorporate these activities into their lives in an enjoyable way, or at the very least refer patients on to an exercise specialist,” Dr. Bolam said in an interview.
Grouped by baseline CRF, the association between change in absolute CRF and prostate cancer incidence was significant only for participants with a moderate baseline CRF. Moreover, changes in both absolute and relative CRF were not associated with prostate cancer mortality.
The lack of mortality significance may be due to the relatively few deaths from prostate cancer in the cohort, Dr. Bolam said. “It may be we weren’t powered to detect anything with such low numbers. And it’s not likely men will die from prostate cancer but more likely from more common chronic diseases such as heart disease.” The authors noted that unlike the case with other common cancers, there are relatively few preventable risk factors with strong evidence for reducing overall prostate cancer risk. “Aside from developmental factors, being diagnosed with overweight or obesity are the main risk factors for developing advanced prostate cancer, but insufficient evidence exists to extend this conclusion to non-advanced prostate cancer,” they wrote.
There is evidence, however, that exercise reduces all-cause mortality risk across many cancer types, including prostate.
Study details
The cohort was drawn from Swedish national health-profile database figures from 1982 to 2019. Participants completed an occupational health profile assessment including at least two valid CRF tests on a cycle ergometer. During a mean follow-up of 6.7 years, 592 (1%) of 57,652 men (mean age 41.3 years, standard deviation 10.55) were diagnosed with prostate cancer, and in 46 (.08%) prostate cancer was the primary cause of death.
An increase in absolute CRF (as a percentage of liters per minute of cardiac output) was associated with a reduced incidence risk, with a hazard ratio of 0.98 (95% CI, 0.96-0.99). Grouping participants as having increased (+3%), stable (±3%), or decreased (−3%) CRF, the investigators found increased fitness was associated with an HR for prostate cancer incidence of 0.65 (95% CI, 0.49-0.86), vs decreased fitness.
According to the authors, this and similar investigations of mechanisms behind physical activity benefits will lead to more targeted prevention recommendations. The results highlight the importance of encouraging the general public to increase CRF or reach moderate fitness levels, Dr. Bolam’s group wrote. The group is planning a similar study in breast cancer.
This study was funded by the Swedish Cancer Society. The authors declared no competing interests.
Men with cardiorespiratory fitness (CRF) who increased their CRF by more than 3% had a significantly lower risk of prostate cancer incidence, a large Swedish study found.
The prospective analysis, published in the British Journal of Sports Medicine, done in a cohort of nearly 58,000, was conducted by Kate A. Bolam, PhD, a clinical exercise physiologist at the Swedish School of Sport and Health Sciences in Stockholm.
“The findings suggest that physicians could work toward supporting patients to understand what types of activities could improve their fitness and ways they can incorporate these activities into their lives in an enjoyable way, or at the very least refer patients on to an exercise specialist,” Dr. Bolam said in an interview.
Grouped by baseline CRF, the association between change in absolute CRF and prostate cancer incidence was significant only for participants with a moderate baseline CRF. Moreover, changes in both absolute and relative CRF were not associated with prostate cancer mortality.
The lack of mortality significance may be due to the relatively few deaths from prostate cancer in the cohort, Dr. Bolam said. “It may be we weren’t powered to detect anything with such low numbers. And it’s not likely men will die from prostate cancer but more likely from more common chronic diseases such as heart disease.” The authors noted that unlike the case with other common cancers, there are relatively few preventable risk factors with strong evidence for reducing overall prostate cancer risk. “Aside from developmental factors, being diagnosed with overweight or obesity are the main risk factors for developing advanced prostate cancer, but insufficient evidence exists to extend this conclusion to non-advanced prostate cancer,” they wrote.
There is evidence, however, that exercise reduces all-cause mortality risk across many cancer types, including prostate.
Study details
The cohort was drawn from Swedish national health-profile database figures from 1982 to 2019. Participants completed an occupational health profile assessment including at least two valid CRF tests on a cycle ergometer. During a mean follow-up of 6.7 years, 592 (1%) of 57,652 men (mean age 41.3 years, standard deviation 10.55) were diagnosed with prostate cancer, and in 46 (.08%) prostate cancer was the primary cause of death.
An increase in absolute CRF (as a percentage of liters per minute of cardiac output) was associated with a reduced incidence risk, with a hazard ratio of 0.98 (95% CI, 0.96-0.99). Grouping participants as having increased (+3%), stable (±3%), or decreased (−3%) CRF, the investigators found increased fitness was associated with an HR for prostate cancer incidence of 0.65 (95% CI, 0.49-0.86), vs decreased fitness.
According to the authors, this and similar investigations of mechanisms behind physical activity benefits will lead to more targeted prevention recommendations. The results highlight the importance of encouraging the general public to increase CRF or reach moderate fitness levels, Dr. Bolam’s group wrote. The group is planning a similar study in breast cancer.
This study was funded by the Swedish Cancer Society. The authors declared no competing interests.
FROM BRITISH JOURNAL OF SPORTS MEDICINE